diff options
| author | nfenwick <nfenwick@pglaf.org> | 2025-01-22 01:26:39 -0800 |
|---|---|---|
| committer | nfenwick <nfenwick@pglaf.org> | 2025-01-22 01:26:39 -0800 |
| commit | 09607ec5dc63ef137d27f3cd31cbba856170bb0a (patch) | |
| tree | 104bb359c402363cc62572b9a3b475833cd12a6b | |
| parent | 37b1ae72bde88383a715ca676e6e991d160b567b (diff) | |
| -rw-r--r-- | .gitattributes | 4 | ||||
| -rw-r--r-- | LICENSE.txt | 11 | ||||
| -rw-r--r-- | README.md | 2 | ||||
| -rw-r--r-- | old/67736-0.txt | 1434 | ||||
| -rw-r--r-- | old/67736-0.zip | bin | 23126 -> 0 bytes | |||
| -rw-r--r-- | old/67736-h.zip | bin | 106668 -> 0 bytes | |||
| -rw-r--r-- | old/67736-h/67736-h.htm | 2453 | ||||
| -rw-r--r-- | old/67736-h/images/cover.jpg | bin | 30517 -> 0 bytes | |||
| -rw-r--r-- | old/67736-h/images/i_002-signature.jpg | bin | 2883 -> 0 bytes | |||
| -rw-r--r-- | old/67736-h/images/i_012.jpg | bin | 63266 -> 0 bytes |
10 files changed, 17 insertions, 3887 deletions
diff --git a/.gitattributes b/.gitattributes new file mode 100644 index 0000000..d7b82bc --- /dev/null +++ b/.gitattributes @@ -0,0 +1,4 @@ +*.txt text eol=lf +*.htm text eol=lf +*.html text eol=lf +*.md text eol=lf diff --git a/LICENSE.txt b/LICENSE.txt new file mode 100644 index 0000000..6312041 --- /dev/null +++ b/LICENSE.txt @@ -0,0 +1,11 @@ +This eBook, including all associated images, markup, improvements, +metadata, and any other content or labor, has been confirmed to be +in the PUBLIC DOMAIN IN THE UNITED STATES. + +Procedures for determining public domain status are described in +the "Copyright How-To" at https://www.gutenberg.org. + +No investigation has been made concerning possible copyrights in +jurisdictions other than the United States. Anyone seeking to utilize +this eBook outside of the United States should confirm copyright +status under the laws that apply to them. diff --git a/README.md b/README.md new file mode 100644 index 0000000..e3c8761 --- /dev/null +++ b/README.md @@ -0,0 +1,2 @@ +Project Gutenberg (https://www.gutenberg.org) public repository for +eBook #67736 (https://www.gutenberg.org/ebooks/67736) diff --git a/old/67736-0.txt b/old/67736-0.txt deleted file mode 100644 index decea6e..0000000 --- a/old/67736-0.txt +++ /dev/null @@ -1,1434 +0,0 @@ -The Project Gutenberg eBook of The Chemical Constituents of Piper -Methysticum; The Chemical Constituents of the Active Principle of the -Ava Root, by Alice Augusta Ball - -This eBook is for the use of anyone anywhere in the United States and -most other parts of the world at no cost and with almost no restrictions -whatsoever. You may copy it, give it away or re-use it under the terms -of the Project Gutenberg License included with this eBook or online at -www.gutenberg.org. If you are not located in the United States, you -will have to check the laws of the country where you are located before -using this eBook. - -Title: The Chemical Constituents of Piper Methysticum; The Chemical - Constituents of the Active Principle of the Ava Root - -Author: Alice Augusta Ball - -Release Date: March 29, 2022 [eBook #67736] - -Language: English - -Produced by: Mary Glenn Krause, Les Galloway and the Online Distributed - Proofreading Team at https://www.pgdp.net (The University - of Hawaiʻi at Mānoa) - -*** START OF THE PROJECT GUTENBERG EBOOK THE CHEMICAL CONSTITUENTS OF -PIPER METHYSTICUM; THE CHEMICAL CONSTITUENTS OF THE ACTIVE PRINCIPLE OF -THE AVA ROOT *** - - Transcriber’s Notes - -Obvious typographical errors have been silently corrected. All other -spelling and punctuation remains unchanged. In particular the author -uses Kavahin for what is now normally referred to as Kavain. - -Italics are represented thus _italic_. - - - - - THESIS - - presented for the degree of - - MASTER OF SCIENCE - - at - - THE COLLEGE OF HAWAII - - JUNE 1915 - - by - - ALICE A. BALL. - - - - -The Thesis, herewith, on “The Chemical Constituents of the Active -Principle of the Ava Root” by Alice A. Ball, clearly demonstrates her -ability to do original work and to present her results in logical form. -Approved. - -[Illustration: J. F. Illingworth] - - Chair of the Committee on - Advanced Degrees. - - College of Hawaii, - May 14, 1915. - - - - - THE CHEMICAL CONSTITUENTS - - OF - - PIPER METHYSTICUM - - OR - - THE CHEMICAL CONSTITUENTS - - OF THE ACTIVE PRINCIPLE - - OF THE AVA ROOT. - - - - - _INDEX._ - - - Page - - 1. Historical 1 - - 2. Method of Extraction 7 - - 3. Method of Separation of the Resins 9 - - 4. Various Metallic Salts of the Resinous Acids 12 - - 5. The Total Resins 13 - - 6. The Barium Acid 15 - - 7. Oxidation Products of the Barium Acids 21 - - 8. The Iron Acids 28 - - 9. Oxidation of the Iron Acids and - the Free Acids 33 - - 10. Alcohol Radicals 34 - - 11. Methysticin and Methysticinic Acid 36 - - 12. Physiological Action 38 - - 13. Conclusion 43 - - - - - _HISTORICAL._ - - -“Among the customs peculiar to the inhabitants of the South Pacific -Islands, perhaps the most noted is that of the preparation and drinking -of a narcotic beverage called _ava_, _kava_, or _yakona_. Much of -its notoriety arises from the repulsive way in which it is sometimes -made. Aside from this, it is characteristic of a certain oceanic -area, and seems to be as strikingly limited to this area as is the -stick-and-groove method of making fire. The custom, is not confined -to one ethnic stock, many notices in literature showing that both -Papuans and Polynesians practise it. In many of the islands the Liquor -is concocted by chewing the root of the Macropiper methysticum, or -long pepper, ejecting the comminuted mass into a bowl, adding water, -straining out the pulp, and drinking the fluid. In other localities it -is made by simply grating the root and adding water. - -“The plant from which kava is made is a shrub of the natural order -Piperaceae. It is about six feet high with stems ranging from an inch -to an inch and a half in thickness; the leaves are cordate and from -four to eight inches long. This family is the source of the pepper -of commerce and contains several species that are of medicinal and -commercial importance. - -In making kava, the root and base of the stem is used. The roots -usually weigh from two to four pounds, though sometimes as much as -22 pounds. Several varieties are distinguished by the natives; for -instance, in Tahiti there is a yellow variety called _Marea_; another, -which becomes pink on exposure to the air, is called _avini-ute_. - -“Chewed when freshly gathered, the root first tastes sweet and -aromatic, then bitter, acrid and pungent. It provokes abundant -secretion of saliva and in a few seconds occasions a sensation of -burning on the tongue. The root contains about fifty percent of starch, -a little pale-yellow essential oil, two percent of an acrid resin, and -one percent of the neutral crystalline principle methysticin, called -kavahin. To the latter principle we must attribute the toxic qualities -of the kava preparation. The resin and the kavahin are insoluble in -water, but are soluble in saliva and the gastric juices. - -“In Samoa, the ava root is grated or chewed, then soaked, the woody -pulp strained off, and the fluid drunk. The root is used either dry or -green. The flavor of the liquid is at first like that of soapsuds, but -immediately afterward a pleasant aromatic taste is imparted, faintly -bitter, as in quinine. In Samoa, ava drinking is the accompaniment of -all meetings of the men. - -“Kava is at first stimulating, but the effect of an excess resembles -that of opium, producing a drowsy drunkenness, lasting for two hours. -The inebriate is usually peaceable, but sometimes is irritated by -noises, which is attributed by natives to the use of kava grown in -moist ground. The results of excess are skin disease, emaciation, and -general decrepitude. The peculiar whiteness of the skin caused by kava -drinking is said to be sought after in some islands as a sign that its -possessor is wealthy enough to devote his time to its acquirement. - -“There is some misapprehension in regard to whether the liquid -undergoes fermentation before it is consumed, but it is positively -known that there can be no fermentation, for the liquor is drunk -immediately after the addition of water to the macerated root. Kava -that is prepared by chewing is said to be more palatable, which -is perhaps due to the conversion of the starch into a fermentable -substance by the ptyalin of the saliva.”[1] - - [1]—By Walter Hough—Reprinted from Smithsonian Miscellaneous - Collections—No. 1472—August 1904. “Kava Drinking as Practised by the - Papuans and Polynesians.” - -“In 1779 Captain King, R. N., who followed Captain Cook to the Islands, -describes the case of a priest as follows ‘a little old man of an -emaciated figure, his eyes exceedingly sore and red, and his body -covered with a white leprous scurf, the effects of an immoderate use -of ava.’ He also says, ‘The chiefs suffer dreadful effects from the -immoderate use of ava. Those who are most affected by it had their -bodies covered with a white scurf, their eyes red and inflamed, their -limbs emaciated, their whole frame trembling and accompanied with a -disability to raise the head.’”[2] - -[2] “Leprosy Prize Essays,” 2nd series by Thompson and Cantile, 1897. - -F. A. Griel, makes the following statement in a foot note. “The mixture -is a subnarcotic, and if drunk by European sailors produces highly -nauseous effects. If frequently taken a dry burning heat is produced -all over the body, the eyes become red, skin peels off in flakes -and then degenerates into leprous ulcers or the whole body becomes -emaciated and wastes away.”[3] - -[3] Miquel, Systema Piperacearum. - -Numerous attempts have been made to isolate the active chemical -constituent or constituents. As early as 1844 Morson discovered an -active principal _Kawine_. This is a greenish-yellow, strongly aromatic -and acrid resin. This was again studied by Cuzant in 1860. - -Gobley isolated from kava root a crystalline principle (analogous to -piperin), _methysticin_, or _kavahin_, which is without odor and taste -and is probably inert.[4] In 1886 Lewin separated the resin into two -resins, of which the Beta resin is greasy and of a reddish-brown color, -appearing in mass almost black. This is less active than the alpha -resin which is yellowish brown, has the characteristic odor of the -drug, is freely soluble in alcohol, and placed upon the tongue produces -a burning sensation followed by local anaesthesia.[5] - - [4] J. P. C. Jan. 1860. - - [5] A. J. P. 1886, 450. - -A volatile oil has been found in the root.[6] - - [6] J. P. C. March 1862. - -Lavialle claimed to have obtained an alkaloid, _Kavaine_.[7] - - [7] L’Union Pharm. Jan. 1889. - -The following statement was found in “Watts Chemical Dictionary”, -“Kawain—a crystalline resin occurring along with methysticin in -kawa-kawa, It is not a glucoside. On oxidation it yields benzoic -acid.[8] - - [8] Gobley, J. Ph. (3) 37, 19. - -The following statement appears in the Encyclopedia Britannica. -“There appears to be little doubt that the active principle in this -beverage is a poison of an alkaloidal nature. It seems likely that -this substance is not present as such (i.e. as a free alkaloid) in the -plant, but that it exists in the form of a glucoside, and that by the -process of chewing, this glucoside is split up by one of the ferments -in the saliva and the free alkaloid and sugar is formed”. - -Arthur Bossingham[9] communicates the results of a chemical examination -of Kava-kava. Besides the crystalline body, methysticin, which has -already been described by others, he was able to isolate and identify -three resins, one soluble in 5% solution of potassium carbonate, the -second insoluble in this, but soluble in 5% solution of caustic potash, -while the third was insoluble in both of these alkaline solvents, The -ash amounts to 2.495% of the air dried root, and contained besides mere -traces of Fe, Mn, mainly Calcium, Sodium and Potassium.[10] - - [9] Proc. A. Ph. A. 1898, 564. - - [10] Proc. Wisc. Pharm. Assos. 1898, 53, 55. - - - - - _METHOD OF EXTRACTION._ - - -The fresh rhizome was chopped up and then ground up by means of a -meat chopper. In the preliminary work the material was dried in a -vacuum oven at a temperature not exceeding forty degrees Centigrade. -In the later work the material was rapidly dried in the sun. This -operation required about two days time. After being thoroughly dried, -the material was finely powdered, and then extracted with ether. The -following continuous extraction apparatus was used. Due to the extreme -rapidity with which the ether evaporated, it was necessary to surround -the coils with ice so as to keep the condensers cold. - -[Illustration: Diagram of apparatus] - - - - - _METHOD OF SEPARATION OF THE RESINS._ - - -After the removal of the crystalline methysticin from the extract, the -following method of separation of the resinous products was used. - -The free acids were removed by shaking the total resins successively -with solutions of one percent ammonium carbonate, one percent -sodium carbonate and one percent sodium hydroxide. The acids thus -removed were recovered by treating the alkaline solution with dilute -hydrochloric acid and shaking out with ether. The three acids were not -markedly different in their physical properties. They possessed the -characteristic odor of the crude drug, were viscous, brown in color -and did not solidify at minus ten degrees Centigrade. These free acids -constitute about five percent of the total resins. - -The remainder of the extract was treated with alcoholic potassium -hydroxide and saponified by heating the solution to about eighty -degrees for fifteen minutes. After the alcohol was removed by -distillation a small quantity of water was added. This resulting -solution was then extracted with ether to remove the alcohol radical or -radicals and the unsaponifiable material from the saponified product. -The ether extract was saved to be used in the work on the alcohol -radicals. The aqueous portion was evaporated to a semi-solid mass. -Carbon dioxide was passed over this mass for about fifteen minutes -to change any excess of potassium hydroxide to potassium carbonate. -Alcohol (95%) was then added to precipitate the carbonate. The -carbonate was then filtered off and water added to the filtrate. - -To the clear filtrate a solution of barium chloride was added. -Immediately a dense thick cream yellow precipitate formed. Barium -chloride was added in excess. The barium salt was filtered off by -means of a suction pump and the precipitate washed with water. The -filtrate was treated with a few drops more of barium chloride so as to -be sure that an excess had been added, which was proven if no further -precipitate formed. To this clear filtrate an excess of a solution of -ferric chloride was added. Immediately a thick heavy precipitate of the -iron salt came down, which was filtered off by means of a suction pump -and the precipitate washed with water. - -The barium precipitate was treated with dilute hydrochloric acid and -heated to boiling to decompose the barium resinate, and to liberate -the free resin acid. The liberated acid was a brown resin of a thin -consistency and had a characteristic odor. This acid was removed by -shaking out with ether. The ethereal solution was dried with anhydrous -sodium sulphate, filtered, and the ether removed by distillation. The -last traces of ether were removed by heating the resin acids in a -vacuum oven at sixty five degrees Centigrade. This resinous acid is the -acid spoken hereafter in this paper as the BARIUM ACID. - -The iron precipitate was treated with dilute sulphuric acid (ferric -chloride is soluble in ether and ferric sulphate is not) and heated to -boiling to decompose the iron resinate. The acid when liberated had a -strong characteristic aromatic odor. It was extracted with ether in the -same manner as the barium acid. This resinous acid is the acid spoken -of in this paper as the IRON ACID. - -The resinous extract left after the removal of the crystalline -methysticin is spoken of as the TOTAL RESINS. - -The resin acids removed by the preliminary shaking out with the various -aqueous alkalies are spoken of as the TOTAL FREE ACIDS. - - - - - _THE VARIOUS METALLIC SALTS OF THE RESINOUS ACIDS._ - - -After obtaining the potassium salts of the acids and having freed -the same from the excess of the potassium hydroxide and potassium -carbonate, the possibilities of the formation of different metallic -salts were tried. - -The soluble salts of the following metals yielded precipitates:— - - Manganese - Barium - Cobalt - Silver - Mercury - Iron - Zinc - Copper - Calcium - Lead - -The following metallic salts gave a complete precipitation:— - - Silver - Iron (ferric) - Manganese - -Since the barium and iron (ferric) salts gave the best means of -separation, they were used to separate the resins. - - - - - _THE TOTAL RESINS._ - - -The total resins were brown in color, thick syrupy consistency and -possessed the characteristic odor of the drug. - -A molecular weight determination was made in the same manner as with -the Barium acids, and the following data obtained. - - - Wt. of pipette before 18.7660 - Wt. of pipette after 14.7160 - Wt. of resin used 4.0500 - Temperature before 3.52 - Temperature after 3.71 - Change in temperature .18 - Volume 37 cc. - Constant for solvent 3280 - Approximate molecular weight 2000 - -Combustions were made and the following data obtained. - - Wt. of boat 3.4722 3.4720 - Wt. of boat and resin 3.6355 3.6220 - Wt. of resin .1633 .1500 - - Sulphuric acid tube 79.1051 79.3865 - Tube plus water 79.2073 79.4770 - Water .1022 .0905 - Hydrogen equivalent .01136 .01006 - - KOH bulb 49.4316 50.8720 - Bulb plus carbon dioxide 49.8350 51.2430 - Carbon dioxide .4034 .3710 - Carbon equivalent .12102 .1010 - - Percent Carbon 67.31% 67.3 - Percent Hydrogen 6.9 % 6.7 - Percent Oxygen 26.8 % 27.0 - -The total resins when placed on the end of the tongue produced a marked -stinging sensation followed by a local anaesthesia. After the first -stinging was produced the sensation was rather pleasant. The local -anaesthesia persisted a long time, giving a sensation much the same as -that produced by cocaine. The barium and iron acids also produced this -local anaesthesia, but the initial stinging sensation was much more -pronounced, which was probably due to the acid nature of the substance. - - - - - _THE BARIUM ACID._ - - -The resinous material used and spoken of as the “Barium Acid” is -the material prepared and so named as given under the “Method of -Separation”. - -PHYSICAL PROPERTIES:—Dark reddish brown in color, syrupy in consistency -and has a characteristic odor; heavier than water; soluble in benzol, -ether, alcohol and acetone, but insoluble in petroleum ether and water. - -This resin constitutes about sixty percent of the total ester resins; -i.e. the resins left after the free acids have been removed with -aqueous potassium hydroxide. - -An analysis of the barium salt obtained by precipitation from the -potassium soap was made and the following data obtained:— - - Wt. of substance used 1.1715 .5860 - Wt. of barium sulphate .4430 .2205 - Barium equivalent .2606 .1298 - Percent barium 22.2% 22.1% - -The following method was used in making the above analysis. The weighed -material was ignited in a platinum crucible by gently heating until the -combustible gases formed were given off. The crucible was then more -strongly heated to completely burn off the carbonaceous material left. -The residue was extracted with nitric acid and the barium precipitated -as the sulphate with dilute sulphuric acid, and the weight of the -barium sulphate determined. - -Expressed as the ACID NUMBER, or the number of milligrams of potassium -hydroxide required to neutralize the free acids in one gram of the -substance, the following data was obtained:— - - Barium equivalent .2606 .1298 - Barium expressed as KOH equiv. .2131 .1062 - Wt. of material used 1.1715 .5860 - Milligrams of KOH per gram 181.9 181.3 - ACID NUMBER 181.9 181.3 - -The following gives the ACID NUMBER obtained by direct titration of -the barium acid; in “A”, barium hydroxide was used and in “B”, sodium -hydroxide was used. - -A small quantity of the material was dissolved in a sufficient quantity -of neutralized alcohol to give a liquid of a light yellow color, -Phenolphthalein was used as the indicator, and the alkali was added -until a red color was produced. - - “A” “B” - - Wt. of substance .6160 .2345 - Cc. of alkalie 4.54 1.75 - KOH equiv. per gram 41.40 41.90 - Acid number 41.40 41.90 - -On evaporating a portion of the alcohol from the material left after -titrating with the sodium hydroxide, and adding water to obtain an -aqueous solution of the sodium salt, an emulsion was formed, and on -standing globules of the free resinous acid separated. From the data -thus obtained, it can readily be seen that the acid or acids which -constitute the BARIUM ACID must have a number of carboxyl groups and -form a different series of salts by precipitation than by direct -titration. The salt or salts formed by direct titration, although -neutral to phenolthalein may be acid in structure. This is further -shown by the fact that the potassium salts produced by direct titration -are readily hydrolyzed. The acid number obtained by the precipitation -of the barium salt may be called the COMBINING VALUE, and the acid -number obtained by titration the TITRATION VALUE. - -A number of molecular weight determinations were made on the free -barium acid. McCoy’s Boiling Point Apparatus was used and Merk’s benzol -(free from thiophene) was used as the solvent. A weighing pipette with -a bulb was used to introduce the material, the bulb being weighed -before the material was introduced into the apparatus, and afterwards, -the difference being the weight of the material used. - - Wt. of pipette (before) 16.3670 14.8895 - Wt. of pipette (after) 14.8895 12.4610 - Wt. of material used 1.5225 2.4285 - Original temperature 3.53 3.53 - Final temperature 3.60 3.62-3 - Change in temperature .07 .09 - Volume of solution 37 cc 43.5 cc - Constant for solvent 3280 3280 - Approx. Molecular Wt. 2000 2100 or 1800 - -Combustions were made using the barium acids. By qualitative tests it -was found that the acids contained only carbon, hydrogen and oxygen. -The following gives the results of the combustions. - - Wt. of boat 2.8402 2.8402 - Wt. of boat and resin 3.0500 3.0250 - Wt. of resin .2098 .1848 - Wt. of H2SO4 tube 78.0250 78.1415 - Wt. of tube plus water 78.1520 78.2550 - Wt. of water .1270 .1135 - Hydrogen equiv. .0143 .0126 - - Wt. of KOH bulb 48.8140 51.7095 - Wt. of bulb plus CO2 49.3800 52.2085 - Wt. of CO2 .5660 .4990 - Carbon equiv. .1543 .1361 - - Percent Hydrogen 78.5% 73.6% - Percent Carbon 6.8% 6.8% - Percent Oxygen 19.7% 19.6% - -An attempt was made to make the potassium salts of the barium acids by -saponification with alcoholic potash. A small quantity of the acid was -treated with an excess of ten percent alcoholic potash and heated to -eighty degrees Centigrade to complete the saponification. Instead of -the formation of the potassium salts, a thick dark brown solid, gummy -mass separated. On cooling it solidified to a brittle solid which had -all the physical properties of a true resin. This solid is soluble -in ether, chloroform and benzol, slightly soluble in alcohol and -insoluble in petroleum ether and water. It burns without the formation -of an ash. Evidently, this brittle material is a condensation product -of the original barium acid. - - - - - _OXIDATION PRODUCTS OF THE BARIUM ACIDS._ - - -A small amount of the Barium acids was sealed with concentrated nitric -acid in a hard glass tube and heated in a bomb furnace for an hour -and a half at 115 to 120 degrees Centigrade. On cooling a yellow -solid separated. Qualitative tests showed that this oxidation product -contained no nitrogen, combined with sodium hydroxide readily, is -soluble in hot water, slightly soluble in cold water, easily soluble in -ether, alcohol and benzol and slightly soluble in carbon tetrachloride. -It decolorizes alkaline permanganate but does not decolorize bromine -water. - -That there are a number of intermediate products formed and that -nitration also takes place during the formation of these intermediate -products is shown by the following. A small quantity of the acids were -placed in a test tube and covered with concentrated nitric acid. This -was suspended in an H2SO4 bath and a thermometer inserted so as to -observe the temperature. On being gently warmed the nitric acid and -the resin began to react with a rapid evolution of carbon dioxide and -oxides of nitrogen. As soon as the reaction had modified and before the -temperature rose above one hundred degrees Centigrade, a small amount -was removed and added to water. Some of the solid acid was formed and -also a number of globules of oil and there was a strong persistent odor -of nitrobenzene. The original test tube was heated to about one hundred -and twenty degrees centigrade and a small portion again removed. There -was more of the solid material formed and the odor was similar to -vanillin or coumarin or cinnamic aldehyde. The test tube was again -tested when the temperature had reached one hundred and thirty five -degrees Centigrade. There was no aromatic odor and a large amount of -the solid formed. When viewed under the microscope the substance had -the appearance of curled threads. - -When the barium acids were treated with the standard nitrating mixture, -a solid was obtained which showed the presence of nitrogen when the -standard test was applied. - -After the preliminary tests were made, the following method of -preparation was used. Two or three grams of the barium acids were -introduced into a hard glass tube of about thirty centimeters in length -and fifteen or twenty cubic centimeters of concentrated nitric acid -added. The reaction which is very vigorous at first was regulated by -keeping the tube under running water. After this vigorous action was -over the tube was placed in a sulphuric acid bath, and the temperature -gradually increased until it had reached one hundred and twenty five -degrees Centigrade, at which temperature it was kept for about five -hours. It was necessary to add a small quantities of nitric acid from -time to time to make up the loss by evaporation. When the oxidation -was completed the product was poured into water and then heated to -boiling. The resulting solution was filtered and the filtrate allowed -to cool. On standing a quantity of a pale yellow substance separated. -The following data gives the percent yield of this oxidation product. - - Wt. of container 6.7220 - Wt. of container and substance 7.5920 - Wt. of substance .8700 - Wt. of oxidation product .1240 - Percent yield 14% - -The oxidation product was dried by placing it in a vacuum over -sulphuric acid for several days. The neutralization equivalent of this -crude oxidation product was 157. - - Wt. of substance used .0502 - Number Cc. of NaOH N/10 3.2 cc. - Neutralization equivalent 157 - -The oxidation product was heated on a watch crystal and the sublimate -allowed to collect on a funnel. The first sublimate gave a melting -point of 109 degrees Centigrade. - -Combustions were made on this sublimate with the following results. - - (1) C 66% - H 4.7% - - (2) C 65.7% - H 4.8% - - (3) C 65.15% - H 4.8% - - (4) C 65.8% - H 4.85% - -The neutralization equivalent was obtained by titrating an alcoholic -solution of the sublimate with standard sodium hydroxide. The following -results were obtained on two different lots of the sublimed oxidation -product. - - Wt. of substance .09 .1006 - Cc. of alkali N/10 7 cc 7.9cc - Neutralization equiv. 128.6 127.3 - -Using a third sample the neutralization equivalent was obtained from -the analysis of the silver salt. The silver salt was formed by adding -silver nitrate solution to a carefully neutralized solution of the -sublimate. The insoluble silver salt was filtered off, washed with -water to remove the excess of silver nitrate, and dried in a vacuum -over sulphuric acid for several days. A weighed quantity of the silver -salt was ignited in a platinum crucible and the residue of metallic -silver was weighed. The following data were obtained using material -from the same sample for each analysis. - - Wt. of dish 12.8825 12.8826 - Wt. of dish and substance 13.0060 13.1310 - Wt. of substance .1235 .2484 - Wt. of dish and silver 12.9400 12.9980 - Wt. of silver .0575 .1154 - Neutralization equiv. 125 125.3 - -Using the same sample, a neutralization equivalent was obtained by -titration with standard NaOH. - - Wt. of substance .0912 - N/10 NaOH 7.25cc - Neutralization equiv. 125.8 - -The above data shows that the sublimate is a mixture. No empirical -formula can be calculated from the combustions, and different samples -give different neutralization equivalents although the duplicate -determinations on the same sample showed good agreement thus -demonstrating the reliability of the methods. - -By fractional sublimation it was possible to obtain fractions with -different melting points. The first sublimate melted sharply at 109 -degrees. From the last fraction it was possible to separate some -crystals that melt at 200 degrees Centigrade. These might possibly be -p-acetyl-benzoic acid, as its properties of solubility, crystalline -form, its melting point and power of sublimation agree with those of -p-acetyl-benzoic acid. - -Those crystals that appeared identical with benzoic acid were placed -in a melting point tube, and some known benzoic acid (from toluol) -was placed in another tube. These two tubes were placed in the same -sulphuric acid container and their melting points taken at the same -time. They melted at the same temperature. - -The sublimate had a very pleasant aromatic odor resembling benzoin. -It gave no coloration with ferric chloride, thus eliminating a large -group of aromatic compounds. Some of the crystals were found to be -identical with benzoic acid when examined under the microscope. -The characteristic odor of methyl benzoate was produced when a -small quantity of the crystals were heated with methyl alcohol and -concentrated sulphuric acid. On treating some of the carefully -neutralized product with ferric chloride solution, a flesh colored -precipitate was formed. It agreed closely in its analysis with the -precipitate formed with known benzoic acid. - -The filtrate left after the removal of the iron precipitate was -acidified and extracted with ether, and the ether removed by -evaporation. The resulting substance decolorized alkaline permanganate -solution, but did not decolorize bromine water. When the leaflet -needles that melt at 200 degrees were mechanically removed from the -original sublimate, the substance left after precipitating with ferric -chloride melted at 109 degrees. When these crystals were not removed, -the melting point of this material was not definite, but was over a -range of five degrees, from 110 to 115 degrees Centigrade. - -The oxidation product contains at least three distinct substances, -benzoic acid, a substance melting at 200 degrees and—which is probably -p-acetyl benzoic acid and a third substance melting at 110 degrees. - - - - - _THE IRON ACIDS._ - - -The resinous material used and spoken of as the IRON ACIDS is the -material prepared and so named under the “Method of Separation”. - -PHYSICAL PROPERTIES:—Transparent and reddish brown in color, oily in -consistency and has a characteristic tea like odor, heavier than water, -freely soluble in benzol, ether, alcohol and acetone, but insoluble in -petroleum ether and water. - -This resin constitutes about eighteen percent of the total ester resins. - -By qualitative tests it was shown that the acids contained only carbon, -hydrogen and oxygen. Combustions made on the iron acids gave the -following results. - - Wt. of boat 2.6950 2.6950 - Wt. of boat and substance 2.8470 2.8495 - Wt. of substance .1520 .1545 - - KOH bulb 50.9620 51.0805 - Bulb and CO2 51.3370 51.4610 - Wt. of CO2 .3750 .3805 - Carbon equivalent .1023 .10376 - Sulphuric acid tube 76.2448 76.3450 - Tube and water 76.3400 76.4453 - Wt. of water .0952 .1003 - Hydrogen equiv. .0106 .01114 - - Percent Carbon 67.3% 67.2% - Percent hydrogen 7.0% 7.2% - Percent Oxygen 25.7% 25.6% - -An analysis of the iron salt obtained by precipitation from the -potassium soap gave the following data. - - Wt. of substance used .2955 .3387 - Wt. of FeSO4 .0445 .0509 - Ferric equiv. .03208 .03676 - Percent Iron 10.85% 10.85% - -The following method was used in making the above analysis. The weighed -material was ignited in a platinum crucible by gently heating until the -combustible gases formed were given off. The crucible was then strongly -heated until the carbonaceous material was completely burned off. The -residue was weighed and the percentage of iron determined. - -Expressed as the ACID NUMBER, or the number of milligrams of KOH -required to neutralize the free acids in one gram of the substance, -the following data was obtained. - - Ferric equivalent .03208 .03676 - Fe expressed as KOH equiv. .0965 .1107 - Wt. of material used .2955 .3387 - Mg. of KOH per gram 326.6 326.7 - Acid number 326.6 326.7 - -The following gives the ACID NUMBER obtained by direct titration of the -Iron acid. The method is the same as that used in getting the titration -value of the Barium acid. - - Wt. of substance .2450 .2472 - Cc of alkalie 2.2 2.3 - KOH equiv. .01232 .01288 - KOH equiv. per gram 53.87 52. - -An attempt was made to saponify some of the iron acid, but it was -impossible. The alcohol was partially distilled off, and the acid -freed by making the mass acid with sulphuric acid, and shaking out -with ether. The ether was distilled off, but the remaining acid had -different physical properties from the acid with which the experiment -was started. It was lighter in color, and solidified at zero degrees. -At room temperature it was almost solid. On ignition it left no ash. -This probably is a polymerization product of the original acid. - -Since many organic acids whose salts cannot be prepared by the ordinary -methods can be prepared by passing dry ammonia gas through a solution -of the acid in anhydrous ether, this method was tried with the iron -acid. The iron acid was dissolved in anhydrous ether, and the dry -ammonia gas was bubbled through this ether solution. At first no change -was noted, but after several minutes there was a flocculent thready -precipitate formed which was light brown in color. The experiment was -repeated. At first the precipitate was a very light brown, but after -forming it quickly darkened. After standing a few hours the flocculent -precipitate changed to a sticky brown mass. This same change was -produced immediately if the precipitate was exposed to the air. The -resulting mass had no odor of ammonia. - -The flocculent precipitate formed at first was probably the ammonium -salt of the iron acid, which like most ammonium salts, it was -precipitated due to its insolubility in ether. Due to the ease of -hydrolysis this salt immediately decomposed to the acid and ammonia -when traces of moisture were present. - - - - - _OXIDATION OF THE IRON ACIDS AND THE FREE ACIDS._ - - -When the iron acids were oxidized in the same manner as the barium -acids the amount of the oxidation product formed was about one fourth -of that produced with an equal amount of the barium acids. The time -necessary to completely oxidize the iron acids was much less then -required for the barium acids. On sublimation the iron acid gave a -product melting at 110 degrees Centigrade and is probably identical -with the one formed from the barium acids. The iron acid also yielded a -sublimate melting at 208 degrees C. - -The free acids when oxidized in a like manner gave as one of the -products a low melting crystalline compound that contained nitrogen. - -The iron acid although related to the barium acid as shown by the -formation of a common oxidation product is different in structure as -shown by the difference in the amount of the oxidation product formed -and the time to complete the oxidation. - - - - - _THE ALCOHOL RADICALS AND UNSAPONIFIABLE MATERIAL._ - - -The material that was shaken out with ether after the saponification -consists of the unsaponifiable material and the alcohol radicals of the -acids produced by saponification. - -On allowing the ether to evaporate from this material, feathery -needles separated. These were removed by means of a suction pump and -recrystallized from hot acetone. The melting point of this product was -122-125 degrees Centigrade. The precipitate was dissolved in benzol and -allowed to slowly crystallize. It formed long prismatic needles with -melting point of 130 degrees Centigrade. When heated with concentrated -sulphuric acid, a brown green fluorescent solution was produced. - -The remaining material was steam distilled, and the distillate -extracted with ether to remove the oil. The ether was dried with -anhydrous sodium carbonate, the solution filtered and the ether removed -by distillation. The oil that remained was light yellow, specific -gravity less than that of water, and possessed a very characteristic -odor resembling that of musk. The material left after the steam -distillation was cooled and shaken out with ether. The ethereal -solution was dried with anhydrous sodium sulphate and the ether -removed by distillation. The resulting mass was a dark brown resin -without any characteristic odor, solidifying at zero degrees. - -The crystalline product with a melting point of 130 degrees and the -essential oil are evidently the alcohols formed through saponification -of the resin esters. The crystalline product could be readily separated -from the resinous material because of its slight solubility in -acetone. Since this product was not precipitated when the unsaponified -resin esters were treated with acetone and because it did not make -its appearance until after the process of saponification, it is -quite probable it is a product of saponification. The essential oil -can be detected in extremely small amounts due to its penetrating -characteristic odor. Before the process of saponification it could not -be detected, but as soon as saponification took place the odor was very -marked. From this it is quite evident that this oil is a product of -saponification. - -The dark brown resinous mass that remained may be either an alcoholic -resin formed through the hydrolysis of the ester resins or it may -be a resin belonging to the class known as resenes[11] which resist -saponification. - -[11] Com. Organic Analysis. Allen Vol. II, 146. - - - - - _METHYSTICIN AND METHYSTICINIC ACID._ - - -The crystalline product obtained from the ether extract was -recrystallized several times from absolute alcohol to remove all -traces of any resinous material. It had a melting point of 122-123. -It therefore was not pure methysticin, which has a melting point of -138-139 degrees. On examining this product under the microscope it -was found to contain two distinct forms of crystals, long needles and -prismatic plates. Some free methysticinic acid, melting point 180 -was examined under the microscope and found to consist entirely of -prismatic plates. Therefore the original crystalline body contains some -methysticinic acid. - -Some of the original precipitate was crystallized once from absolute -alcohol and thoroughly dried. This was used for the following data to -determine the percent of free methysticinic acid in the crystalline -product. A weighed amount of the crystalline product was dissolved in -carefully neutralized alcohol, and titrated with tenth normal NaOH, -using phenolthalein as the indicator. - - Wt. of substance used .2590 - NaOH N/10 .5 cc - % methysticinic acid. - -The potassium salts of the various resin acids formed by the -saponification of the ester resins should yield a resinous mass syrupy -or oily in consistency when acidified, if it consists entirely of the -two groups of acids spoken of as the iron acids and the barium acids. -Also the weight of the barium acids plus the weight of the iron acids -should nearly equal the weight of the ester resins, if these are the -only two acids, because the alcohol radicals constitute not more than -two percent of the ester resins. But when the total potassium salts -were acidified the product formed contained a crystalline substance -in addition to the resinous acids. This crystalline substance was -separated from the resinous acids by means of their difference in -solubility in ether. On recrystallization from absolute alcohol, -it had a melting point of 179 degrees Centigrade. It is therefore -methysticinic acid. This acid constitutes about twenty percent of the -total acids from the ester resins because the barium and iron acids -constitute only about seventy five percent. - -This methysticinic acid cannot be entirely formed by hydrolysis of -methysticin which was incompletely removed from the resinous material. -The methysticinic acid existed either combined with some other alcohol -than methyl alcohol or was combined with one of the resin alcohol -radicals. - - - - - _PHYSIOLOGICAL ACTION._ - - -Due to the impossibility of preparing the alkali salts of the barium -and iron acids so as to be positive that the resulting preparations -completely represented the barium and iron acids, and due to the -insolubility of the acids and the total resins in solvents from -which they would not again be precipitated when introduced into -the circulation, it was found necessary to make an emulsion. The -emulsifying agent used was acacia (gum arabic). It was possible by -careful preparation to make a permanent emulsion that was miscible -with water in all proportions to form a homogeneous mixture. The -animals used were rabbits of about six pounds weight. The injections -were made by Dr. Geo. McCoy, director of the Leprosy Investigation -Station at Kalihi. All the physiological experiments were made at the -bacteriological laboratory at the Leprosy Investigation Station. - -One cubic centimeter of the emulsion of the total resinous extract -(strength 1 in 5) was injected into the ear of a rabbit; the animal -died immediately. Another rabbit was injected in the same manner -with one half cubic centimeter of the same preparation. The animal -immediately stretched out and became rigid, or appeared to be -paralyzed, but after several minutes these symptoms lessened and after -about five minutes the rabbit appeared normal as far as activity was -concerned. As soon as the rabbit had recovered a second injection of -one quarter of a cubic centimeter of the same preparation was injected -in the same manner into the same animal. The same symptoms were -produced and with equal intensity, but ten minutes passed before the -animal again became conscious. For several minutes after recovery the -animal appeared somewhat drowsy and stupid but it soon regained its -former activity. - -One half cubic centimeter of the iron acid emulsion (strength 1 in 7) -was injected into the ear of a rabbit. Immediate paralysis and apparent -anaesthesia set in lasting very pronouncedly for eight minutes. The -rabbit’s head was drawn backwards and its legs stiffened giving -symptoms similar to strychnine poisoning but they did not persist. -When a second injection of one quarter cubic centimeter was given to -the same animal, the same symptoms were produced, the animal remaining -under the influence of the injection for about fifteen minutes. - -The iron acid injection was repeated on another rabbit with the same -pronounced symptoms of strychnine poisoning but the effect lasted only -about ten minutes. - -One half cubic centimeter of the barium acid emulsion (strength 1 in -7) was injected into the ear vein of a rabbit. The animal uttered -several loud cries and after moving several feet it became spastic and -went into a sort of a stupor, beginning to come out of it after ten -minutes. As soon as the animal recovered, a second injection of one -quarter cubic centimeter was made. The animal again uttered loud cries -and then it went into a stupor, but it was not spastic. This lasted -approximately ten minutes. The animal did not completely recover until -about twenty minutes. - -Thinking that the action might be largely mechanical and that the -symptoms produced were from the emulsion itself and not from the effect -of the material that was emulsified, an emulsion of olive oil was used -in a like manner. This olive oil emulsion was made in approximately the -same consistency as the resinous emulsions, and one cubic centimeter -was injected into the ear vein of a rabbit. No visible effects followed -this injection during the one hour’s time the rabbit was under -observation. - -One cubic centimeter intraperitoneal injections of the total resinous -extract emulsion and the same amount of the iron acid emulsion were -made into rabbits. During the three hours the animals were under -observation no symptoms were produced. This may have been due to the -extreme slowness of absorption as compared with the rate of elimination -from the circulation. - -Dr. J. F. Illingworth states as the result of his observations while -in the Fiji Islands that the kava beverage even when taken in large -amounts, does not apparently affect the brain to an extent as to cause -the drinker to appear as if under the influence of alcohol, but he -appears as if the muscles from the hips downward are paralyzed. These -symptoms last for about half an hour, at the end of which time the -person is perfectly able to walk home. - -In general the active constituent of any drug produces a more -pronounced but more fugitive effect than the crude drug itself, and one -might therefore expect more violent reactions from the isolated active -constituents of the Ava then from the crude infusion. Judging from the -negative results obtained from the injection of the olive oil emulsion, -it is probable that the physiological effects described above -following the intravenous injections of the various preparations were -not mechanical but must be ascribed to the action of the constituents -of the Ava. - - - - - _CONCLUSION._ - - -The crystalline product consists, largely of methysticin, the methyl -ester of methysticinic acid. In addition to this there is about five -percent of the free methysticinic acid present. - -The resinous product consists of about five percent of free resinous -acids, which acids can be separated into three different acids or -groups of acids according to their solubility in the different -alkalies. The remaining resinous product is composed of ester resins. -On hydrolysis these esters yield three distinct acids, two resinous -acids and methysticinic acid. The two resinous acids are distinctly -different, both in physical properties and in chemical properties. They -can be sharply separated by means of the difference in solubility of -their barium and iron salts. These acids may be separate individual -substances, or a group of related substances. The barium and iron acids -although different chemically, have some groups in common as shown by -the formation of a common oxidation product. There are at least three -alcohol radicals formed through hydrolysis, a resinous alcohol radical, -a crystalline substance with a melting point of 130 degrees, and a -volatile oil. - -The physiological action of the Ava is due to the ester resins. The two -resinous acids formed through the hydrolysis of these esters seem to be -the two active constituents of the resin ester. - -From the above outlined work it appears that the ava root does not -contain any alkaloidal substance, as none of the constituents were -found to contain nitrogen. - -That the aqueous infusion used by the ava drinkers contains the same -constituents as are extracted by the ether is shown by the following. -An infusion of the ava was made by allowing some of the powdered drug -to remain in contact with water for about twelve hours. The infusion -was then filtered and the filtrate extracted with ether. A resinous -mass remained which from all appearances was identical with the resins -obtained from the ether extract. It also gave the same action when -placed on the tongue as was produced by the resins from the ether -extract. - -*** END OF THE PROJECT GUTENBERG EBOOK THE CHEMICAL CONSTITUENTS OF -PIPER METHYSTICUM; THE CHEMICAL CONSTITUENTS OF THE ACTIVE PRINCIPLE OF -THE AVA ROOT *** - -Updated editions will replace the previous one--the old editions will -be renamed. - -Creating the works from print editions not protected by U.S. copyright -law means that no one owns a United States copyright in these works, -so the Foundation (and you!) can copy and distribute it in the -United States without permission and without paying copyright -royalties. Special rules, set forth in the General Terms of Use part -of this license, apply to copying and distributing Project -Gutenberg-tm electronic works to protect the PROJECT GUTENBERG-tm -concept and trademark. Project Gutenberg is a registered trademark, -and may not be used if you charge for an eBook, except by following -the terms of the trademark license, including paying royalties for use -of the Project Gutenberg trademark. If you do not charge anything for -copies of this eBook, complying with the trademark license is very -easy. You may use this eBook for nearly any purpose such as creation -of derivative works, reports, performances and research. Project -Gutenberg eBooks may be modified and printed and given away--you may -do practically ANYTHING in the United States with eBooks not protected -by U.S. copyright law. Redistribution is subject to the trademark -license, especially commercial redistribution. - -START: FULL LICENSE - -THE FULL PROJECT GUTENBERG LICENSE -PLEASE READ THIS BEFORE YOU DISTRIBUTE OR USE THIS WORK - -To protect the Project Gutenberg-tm mission of promoting the free -distribution of electronic works, by using or distributing this work -(or any other work associated in any way with the phrase "Project -Gutenberg"), you agree to comply with all the terms of the Full -Project Gutenberg-tm License available with this file or online at -www.gutenberg.org/license. - -Section 1. General Terms of Use and Redistributing Project -Gutenberg-tm electronic works - -1.A. By reading or using any part of this Project Gutenberg-tm -electronic work, you indicate that you have read, understand, agree to -and accept all the terms of this license and intellectual property -(trademark/copyright) agreement. If you do not agree to abide by all -the terms of this agreement, you must cease using and return or -destroy all copies of Project Gutenberg-tm electronic works in your -possession. If you paid a fee for obtaining a copy of or access to a -Project Gutenberg-tm electronic work and you do not agree to be bound -by the terms of this agreement, you may obtain a refund from the -person or entity to whom you paid the fee as set forth in paragraph -1.E.8. - -1.B. "Project Gutenberg" is a registered trademark. It may only be -used on or associated in any way with an electronic work by people who -agree to be bound by the terms of this agreement. There are a few -things that you can do with most Project Gutenberg-tm electronic works -even without complying with the full terms of this agreement. See -paragraph 1.C below. There are a lot of things you can do with Project -Gutenberg-tm electronic works if you follow the terms of this -agreement and help preserve free future access to Project Gutenberg-tm -electronic works. See paragraph 1.E below. - -1.C. The Project Gutenberg Literary Archive Foundation ("the -Foundation" or PGLAF), owns a compilation copyright in the collection -of Project Gutenberg-tm electronic works. Nearly all the individual -works in the collection are in the public domain in the United -States. If an individual work is unprotected by copyright law in the -United States and you are located in the United States, we do not -claim a right to prevent you from copying, distributing, performing, -displaying or creating derivative works based on the work as long as -all references to Project Gutenberg are removed. Of course, we hope -that you will support the Project Gutenberg-tm mission of promoting -free access to electronic works by freely sharing Project Gutenberg-tm -works in compliance with the terms of this agreement for keeping the -Project Gutenberg-tm name associated with the work. You can easily -comply with the terms of this agreement by keeping this work in the -same format with its attached full Project Gutenberg-tm License when -you share it without charge with others. - -1.D. The copyright laws of the place where you are located also govern -what you can do with this work. Copyright laws in most countries are -in a constant state of change. If you are outside the United States, -check the laws of your country in addition to the terms of this -agreement before downloading, copying, displaying, performing, -distributing or creating derivative works based on this work or any -other Project Gutenberg-tm work. The Foundation makes no -representations concerning the copyright status of any work in any -country other than the United States. - -1.E. Unless you have removed all references to Project Gutenberg: - -1.E.1. The following sentence, with active links to, or other -immediate access to, the full Project Gutenberg-tm License must appear -prominently whenever any copy of a Project Gutenberg-tm work (any work -on which the phrase "Project Gutenberg" appears, or with which the -phrase "Project Gutenberg" is associated) is accessed, displayed, -performed, viewed, copied or distributed: - - This eBook is for the use of anyone anywhere in the United States and - most other parts of the world at no cost and with almost no - restrictions whatsoever. You may copy it, give it away or re-use it - under the terms of the Project Gutenberg License included with this - eBook or online at www.gutenberg.org. If you are not located in the - United States, you will have to check the laws of the country where - you are located before using this eBook. - -1.E.2. If an individual Project Gutenberg-tm electronic work is -derived from texts not protected by U.S. copyright law (does not -contain a notice indicating that it is posted with permission of the -copyright holder), the work can be copied and distributed to anyone in -the United States without paying any fees or charges. If you are -redistributing or providing access to a work with the phrase "Project -Gutenberg" associated with or appearing on the work, you must comply -either with the requirements of paragraphs 1.E.1 through 1.E.7 or -obtain permission for the use of the work and the Project Gutenberg-tm -trademark as set forth in paragraphs 1.E.8 or 1.E.9. - -1.E.3. If an individual Project Gutenberg-tm electronic work is posted -with the permission of the copyright holder, your use and distribution -must comply with both paragraphs 1.E.1 through 1.E.7 and any -additional terms imposed by the copyright holder. Additional terms -will be linked to the Project Gutenberg-tm License for all works -posted with the permission of the copyright holder found at the -beginning of this work. - -1.E.4. Do not unlink or detach or remove the full Project Gutenberg-tm -License terms from this work, or any files containing a part of this -work or any other work associated with Project Gutenberg-tm. - -1.E.5. Do not copy, display, perform, distribute or redistribute this -electronic work, or any part of this electronic work, without -prominently displaying the sentence set forth in paragraph 1.E.1 with -active links or immediate access to the full terms of the Project -Gutenberg-tm License. - -1.E.6. You may convert to and distribute this work in any binary, -compressed, marked up, nonproprietary or proprietary form, including -any word processing or hypertext form. However, if you provide access -to or distribute copies of a Project Gutenberg-tm work in a format -other than "Plain Vanilla ASCII" or other format used in the official -version posted on the official Project Gutenberg-tm website -(www.gutenberg.org), you must, at no additional cost, fee or expense -to the user, provide a copy, a means of exporting a copy, or a means -of obtaining a copy upon request, of the work in its original "Plain -Vanilla ASCII" or other form. Any alternate format must include the -full Project Gutenberg-tm License as specified in paragraph 1.E.1. - -1.E.7. Do not charge a fee for access to, viewing, displaying, -performing, copying or distributing any Project Gutenberg-tm works -unless you comply with paragraph 1.E.8 or 1.E.9. - -1.E.8. You may charge a reasonable fee for copies of or providing -access to or distributing Project Gutenberg-tm electronic works -provided that: - -* You pay a royalty fee of 20% of the gross profits you derive from - the use of Project Gutenberg-tm works calculated using the method - you already use to calculate your applicable taxes. The fee is owed - to the owner of the Project Gutenberg-tm trademark, but he has - agreed to donate royalties under this paragraph to the Project - Gutenberg Literary Archive Foundation. Royalty payments must be paid - within 60 days following each date on which you prepare (or are - legally required to prepare) your periodic tax returns. Royalty - payments should be clearly marked as such and sent to the Project - Gutenberg Literary Archive Foundation at the address specified in - Section 4, "Information about donations to the Project Gutenberg - Literary Archive Foundation." - -* You provide a full refund of any money paid by a user who notifies - you in writing (or by e-mail) within 30 days of receipt that s/he - does not agree to the terms of the full Project Gutenberg-tm - License. You must require such a user to return or destroy all - copies of the works possessed in a physical medium and discontinue - all use of and all access to other copies of Project Gutenberg-tm - works. - -* You provide, in accordance with paragraph 1.F.3, a full refund of - any money paid for a work or a replacement copy, if a defect in the - electronic work is discovered and reported to you within 90 days of - receipt of the work. - -* You comply with all other terms of this agreement for free - distribution of Project Gutenberg-tm works. - -1.E.9. If you wish to charge a fee or distribute a Project -Gutenberg-tm electronic work or group of works on different terms than -are set forth in this agreement, you must obtain permission in writing -from the Project Gutenberg Literary Archive Foundation, the manager of -the Project Gutenberg-tm trademark. Contact the Foundation as set -forth in Section 3 below. - -1.F. - -1.F.1. Project Gutenberg volunteers and employees expend considerable -effort to identify, do copyright research on, transcribe and proofread -works not protected by U.S. copyright law in creating the Project -Gutenberg-tm collection. Despite these efforts, Project Gutenberg-tm -electronic works, and the medium on which they may be stored, may -contain "Defects," such as, but not limited to, incomplete, inaccurate -or corrupt data, transcription errors, a copyright or other -intellectual property infringement, a defective or damaged disk or -other medium, a computer virus, or computer codes that damage or -cannot be read by your equipment. - -1.F.2. LIMITED WARRANTY, DISCLAIMER OF DAMAGES - Except for the "Right -of Replacement or Refund" described in paragraph 1.F.3, the Project -Gutenberg Literary Archive Foundation, the owner of the Project -Gutenberg-tm trademark, and any other party distributing a Project -Gutenberg-tm electronic work under this agreement, disclaim all -liability to you for damages, costs and expenses, including legal -fees. YOU AGREE THAT YOU HAVE NO REMEDIES FOR NEGLIGENCE, STRICT -LIABILITY, BREACH OF WARRANTY OR BREACH OF CONTRACT EXCEPT THOSE -PROVIDED IN PARAGRAPH 1.F.3. YOU AGREE THAT THE FOUNDATION, THE -TRADEMARK OWNER, AND ANY DISTRIBUTOR UNDER THIS AGREEMENT WILL NOT BE -LIABLE TO YOU FOR ACTUAL, DIRECT, INDIRECT, CONSEQUENTIAL, PUNITIVE OR -INCIDENTAL DAMAGES EVEN IF YOU GIVE NOTICE OF THE POSSIBILITY OF SUCH -DAMAGE. - -1.F.3. LIMITED RIGHT OF REPLACEMENT OR REFUND - If you discover a -defect in this electronic work within 90 days of receiving it, you can -receive a refund of the money (if any) you paid for it by sending a -written explanation to the person you received the work from. If you -received the work on a physical medium, you must return the medium -with your written explanation. The person or entity that provided you -with the defective work may elect to provide a replacement copy in -lieu of a refund. If you received the work electronically, the person -or entity providing it to you may choose to give you a second -opportunity to receive the work electronically in lieu of a refund. If -the second copy is also defective, you may demand a refund in writing -without further opportunities to fix the problem. - -1.F.4. Except for the limited right of replacement or refund set forth -in paragraph 1.F.3, this work is provided to you 'AS-IS', WITH NO -OTHER WARRANTIES OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING BUT NOT -LIMITED TO WARRANTIES OF MERCHANTABILITY OR FITNESS FOR ANY PURPOSE. - -1.F.5. Some states do not allow disclaimers of certain implied -warranties or the exclusion or limitation of certain types of -damages. If any disclaimer or limitation set forth in this agreement -violates the law of the state applicable to this agreement, the -agreement shall be interpreted to make the maximum disclaimer or -limitation permitted by the applicable state law. The invalidity or -unenforceability of any provision of this agreement shall not void the -remaining provisions. - -1.F.6. INDEMNITY - You agree to indemnify and hold the Foundation, the -trademark owner, any agent or employee of the Foundation, anyone -providing copies of Project Gutenberg-tm electronic works in -accordance with this agreement, and any volunteers associated with the -production, promotion and distribution of Project Gutenberg-tm -electronic works, harmless from all liability, costs and expenses, -including legal fees, that arise directly or indirectly from any of -the following which you do or cause to occur: (a) distribution of this -or any Project Gutenberg-tm work, (b) alteration, modification, or -additions or deletions to any Project Gutenberg-tm work, and (c) any -Defect you cause. - -Section 2. Information about the Mission of Project Gutenberg-tm - -Project Gutenberg-tm is synonymous with the free distribution of -electronic works in formats readable by the widest variety of -computers including obsolete, old, middle-aged and new computers. It -exists because of the efforts of hundreds of volunteers and donations -from people in all walks of life. - -Volunteers and financial support to provide volunteers with the -assistance they need are critical to reaching Project Gutenberg-tm's -goals and ensuring that the Project Gutenberg-tm collection will -remain freely available for generations to come. In 2001, the Project -Gutenberg Literary Archive Foundation was created to provide a secure -and permanent future for Project Gutenberg-tm and future -generations. To learn more about the Project Gutenberg Literary -Archive Foundation and how your efforts and donations can help, see -Sections 3 and 4 and the Foundation information page at -www.gutenberg.org - -Section 3. Information about the Project Gutenberg Literary -Archive Foundation - -The Project Gutenberg Literary Archive Foundation is a non-profit -501(c)(3) educational corporation organized under the laws of the -state of Mississippi and granted tax exempt status by the Internal -Revenue Service. The Foundation's EIN or federal tax identification -number is 64-6221541. Contributions to the Project Gutenberg Literary -Archive Foundation are tax deductible to the full extent permitted by -U.S. federal laws and your state's laws. - -The Foundation's business office is located at 809 North 1500 West, -Salt Lake City, UT 84116, (801) 596-1887. Email contact links and up -to date contact information can be found at the Foundation's website -and official page at www.gutenberg.org/contact - -Section 4. Information about Donations to the Project Gutenberg -Literary Archive Foundation - -Project Gutenberg-tm depends upon and cannot survive without -widespread public support and donations to carry out its mission of -increasing the number of public domain and licensed works that can be -freely distributed in machine-readable form accessible by the widest -array of equipment including outdated equipment. Many small donations -($1 to $5,000) are particularly important to maintaining tax exempt -status with the IRS. - -The Foundation is committed to complying with the laws regulating -charities and charitable donations in all 50 states of the United -States. Compliance requirements are not uniform and it takes a -considerable effort, much paperwork and many fees to meet and keep up -with these requirements. We do not solicit donations in locations -where we have not received written confirmation of compliance. To SEND -DONATIONS or determine the status of compliance for any particular -state visit www.gutenberg.org/donate - -While we cannot and do not solicit contributions from states where we -have not met the solicitation requirements, we know of no prohibition -against accepting unsolicited donations from donors in such states who -approach us with offers to donate. - -International donations are gratefully accepted, but we cannot make -any statements concerning tax treatment of donations received from -outside the United States. U.S. laws alone swamp our small staff. - -Please check the Project Gutenberg web pages for current donation -methods and addresses. Donations are accepted in a number of other -ways including checks, online payments and credit card donations. To -donate, please visit: www.gutenberg.org/donate - -Section 5. General Information About Project Gutenberg-tm electronic works - -Professor Michael S. Hart was the originator of the Project -Gutenberg-tm concept of a library of electronic works that could be -freely shared with anyone. For forty years, he produced and -distributed Project Gutenberg-tm eBooks with only a loose network of -volunteer support. - -Project Gutenberg-tm eBooks are often created from several printed -editions, all of which are confirmed as not protected by copyright in -the U.S. unless a copyright notice is included. Thus, we do not -necessarily keep eBooks in compliance with any particular paper -edition. - -Most people start at our website which has the main PG search -facility: www.gutenberg.org - -This website includes information about Project Gutenberg-tm, -including how to make donations to the Project Gutenberg Literary -Archive Foundation, how to help produce our new eBooks, and how to -subscribe to our email newsletter to hear about new eBooks. diff --git a/old/67736-0.zip b/old/67736-0.zip Binary files differdeleted file mode 100644 index 2555ae8..0000000 --- a/old/67736-0.zip +++ /dev/null diff --git a/old/67736-h.zip b/old/67736-h.zip Binary files differdeleted file mode 100644 index 20c8599..0000000 --- a/old/67736-h.zip +++ /dev/null diff --git a/old/67736-h/67736-h.htm b/old/67736-h/67736-h.htm deleted file mode 100644 index 4a68709..0000000 --- a/old/67736-h/67736-h.htm +++ /dev/null @@ -1,2453 +0,0 @@ -<!DOCTYPE html PUBLIC "-//W3C//DTD XHTML 1.0 Strict//EN" - "http://www.w3.org/TR/xhtml1/DTD/xhtml1-strict.dtd"> -<html xmlns="http://www.w3.org/1999/xhtml" xml:lang="en" lang="en"> - <head> - <meta http-equiv="Content-Type" content="text/html;charset=utf-8" /> - <meta http-equiv="Content-Style-Type" content="text/css" /> - <title> - The Project Gutenberg eBook of The Chemical Constituents of Piper Methysticom, by Alice A. Ball.. - </title> - <link rel="coverpage" href="images/cover.jpg" /> - <style type="text/css"> - -body { - margin-left: 10%; - margin-right: 10%; -} - -h1 -{ - margin-top: 2em; margin-bottom: 2em; - text-align: center; - font-size: x-large; - font-weight: normal; - line-height: 1.6; -} - - h2,h3{ - text-align: center; - clear: both; - } - -.half-title { - margin-top: 2em; margin-bottom: 2em; - text-align: center; - font-size: x-large; - font-weight: normal; - line-height: 1.6; - } - -div.chapter {page-break-before: always;} -h2.nobreak {page-break-before: avoid;} - -/* Paragraphs */ - -p {text-indent: 1em; - margin-top: .75em; - text-align: justify; - margin-bottom: .75em; - } - -.hang {text-align: justify; padding-left: 1.75em; text-indent: -1.75em;} - - -hr { - width: 33%; - margin-top: 2em; - margin-bottom: 2em; - margin-left: 33.5%; - margin-right: 33.5%; - clear: both; -} - - -hr.chap {width: 65%; margin-left: 17.5%; margin-right: 17.5%;} -@media print { hr.chap {display: none; visibility: hidden;} } - -ul {font-size: .9em; list-style-type: none; } - -table { - margin-left: auto; - margin-right: auto; - } - -.standard { font-size: .9em; border-collapse: collapse; } -td {padding-left: 5px;} - -.tdl {text-align: left; padding-left: 2em;} - -.tdr {text-align: right;} - -.pagenum { /* uncomment the next line for invisible page numbers */ - /* visibility: hidden; */ - position: absolute; - left: 92%; - font-size: smaller; - text-align: right; -} /* page numbers */ - -.center {text-align: center;} - -/* Images */ - -img {border: none; max-width: 100%} - -.inline { - display: inline-block; - vertical-align: bottom; - max-width: 30%;} - -.figcenter { - margin: auto; - text-align: center; - page-break-inside: avoid; - max-width: 100%; -} - -/* Footnotes */ - - .footnotes {border: dashed 1px;} - - .footnote { - margin-left: 10%; - margin-right: 10%; - font-size: 0.9em; - } - -.footnote .label { - position: absolute; - right: 84%; - text-align: right; - } - -.fnanchor { - vertical-align: super; - font-size: .8em; - text-decoration: none; - white-space: nowrap - } - - - -/* Transcriber's notes */ - -.transnote { - background-color: #E6E6FA; - color: black; - font-size:smaller; - padding:0.5em; - margin-bottom:5em; - font-family:sans-serif, serif; - } - -/* Illustration classes */ -.illowp60 {width: 60%;} - - </style> - </head> -<body> -<p style='text-align:center; font-size:1.2em; font-weight:bold'>The Project Gutenberg eBook of The Chemical Constituents of Piper Methysticum; The Chemical Constituents of the Active Principle of the Ava Root, by Alice Augusta Ball</p> -<div style='display:block; margin:1em 0'> -This eBook is for the use of anyone anywhere in the United States and -most other parts of the world at no cost and with almost no restrictions -whatsoever. You may copy it, give it away or re-use it under the terms -of the Project Gutenberg License included with this eBook or online -at <a href="https://www.gutenberg.org">www.gutenberg.org</a>. If you -are not located in the United States, you will have to check the laws of the -country where you are located before using this eBook. -</div> - -<p style='display:block; margin-top:1em; margin-bottom:1em; margin-left:2em; text-indent:-2em'>Title: The Chemical Constituents of Piper Methysticum; The Chemical Constituents of the Active Principle of the Ava Root</p> -<p style='display:block; margin-top:1em; margin-bottom:0; margin-left:2em; text-indent:-2em'>Author: Alice Augusta Ball</p> -<p style='display:block; text-indent:0; margin:1em 0'>Release Date: March 29, 2022 [eBook #67736]</p> -<p style='display:block; text-indent:0; margin:1em 0'>Language: English</p> - <p style='display:block; margin-top:1em; margin-bottom:0; margin-left:2em; text-indent:-2em; text-align:left'>Produced by: Mary Glenn Krause, Les Galloway and the Online Distributed Proofreading Team at https://www.pgdp.net (The University of Hawaiʻi at Mānoa)</p> -<div style='margin-top:2em; margin-bottom:4em'>*** START OF THE PROJECT GUTENBERG EBOOK THE CHEMICAL CONSTITUENTS OF PIPER METHYSTICUM; THE CHEMICAL CONSTITUENTS OF THE ACTIVE PRINCIPLE OF THE AVA ROOT ***</div> - -<div class="transnote"> - -<h3>Transcriber’s Notes</h3> - -<p>Obvious typographical errors have been silently corrected. All other -spelling and punctuation remains unchanged. In particular the author -uses Kavahin for what is now normally referred to as Kavain.</p> - -</div> - - -<p class="half-title"> -THESIS<br /> - -<small>presented for the degree of</small><br /> - -MASTER OF SCIENCE<br /> - -<small>at</small><br /> - -THE COLLEGE OF HAWAII<br /> - -JUNE 1915<br /> - -<small>by</small><br /> - -ALICE A. BALL. -</p> - - -<hr class="chap x-ebookmaker-drop" /> - - -<p>The Thesis, herewith, on “The Chemical Constituents -of the Active Principle of the Ava Root” by Alice A. Ball, -clearly demonstrates her ability to do original work and to -present her results in logical form. Approved.</p> - -<div class="inline"> -<p class="center"> - <img src="images/i_002-signature.jpg" alt="" /><br /> -J. F. Illingworth<br /> -Chair of the Committee on<br /> -Advanced Degrees.</p> -</div> - - - -<p class="hang">College of Hawaii,<br /> -May 14, 1915.</p> - -<hr class="chap x-ebookmaker-drop" /> - -<div class="chapter"></div> - -<h1> -THE CHEMICAL CONSTITUENTS<br /> - -OF<br /> - -PIPER METHYSTICUM</h1> - -<p class="half-title">OR<br /> - -THE CHEMICAL CONSTITUENTS<br /> - -OF THE ACTIVE PRINCIPLE<br /> - -OF THE AVA ROOT.</p> - - -<hr class="chap x-ebookmaker-drop" /> - -<div class="chapter"> -<h2 class="nobreak" id="INDEX"><i>INDEX.</i></h2> -</div> - - -<table class="standard" summary=""> -<tr> -<td class="tdl" colspan="2"></td> -<td class="tdr">Page</td> -</tr> -<tr> -<td class="tdl">1. </td> -<td class="tdl"><a href="#HISTORICAL">Historical</a></td> -<td class="tdr">1</td> -</tr> -<tr> -<td class="tdl">2. </td> -<td class="tdl"><a href="#METHOD_OF_EXTRACTION"> Method of Extraction</a></td> -<td class="tdr">7</td> -</tr> -<tr> -<td class="tdl">3.</td> -<td class="tdl"><a href="#METHOD_OF_SEPARATION_OF_THE_RESINS">Method of Separation of the Resins</a></td> -<td class="tdr">9</td> -</tr> -<tr> -<td class="tdl">4.</td> -<td class="tdl"><a href="#THE_VARIOUS_METALLIC_SALTS">Various Metallic Salts of the Resinous Acids</a></td> -<td class="tdr">12</td> -</tr> -<tr> -<td class="tdl">5.</td> -<td class="tdl"><a href="#THE_TOTAL_RESINS">The Total Resins</a></td> -<td class="tdr">13</td> -</tr> -<tr> -<td class="tdl">6.</td> -<td class="tdl"><a href="#THE_BARIUM_ACID">The Barium Acid</a></td> -<td class="tdr">15</td> -</tr> -<tr> -<td class="tdl">7.</td> -<td class="tdl"><a href="#OXIDATION_PRODUCTS_OF_THE_BARIUM_ACIDS">Oxidation Products of the Barium Acids</a></td> -<td class="tdr">21</td> -</tr> -<tr> -<td class="tdl">8.</td> -<td class="tdl"><a href="#THE_IRON_ACIDS">The Iron Acids</a></td> -<td class="tdr">28</td> -</tr> -<tr> -<td class="tdl">9.</td> -<td class="tdl"><a href="#OXIDATION_OF_THE_IRON_ACIDS">Oxidation of the Iron Acids and the Free Acids</a></td> -<td class="tdr">33</td> -</tr> -<tr> -<td class="tdl">10.</td> -<td class="tdl"><a href="#THE_ALCOHOL_RADICALS_AND_UNSAPONIFIABLE_MATERIAL">Alcohol Radicals</a></td> -<td class="tdr">34</td> -</tr> -<tr> -<td class="tdl">11.</td> -<td class="tdl"><a href="#METHYSTICIN_AND_METHYSTICINIC_ACID">Methysticin and Methysticinic Acid</a></td> -<td class="tdr">36</td> -</tr> -<tr> -<td class="tdl">12.</td> -<td class="tdl"><a href="#PHYSIOLOGICAL_ACTION">Physiological Action</a></td> -<td class="tdr">38</td> -</tr> -<tr> -<td class="tdl">13.</td> -<td class="tdl"><a href="#CONCLUSION">Conclusion</a></td> -<td class="tdr">43</td> -</tr> -</table> - - -<hr class="chap x-ebookmaker-drop" /> - -<div class="chapter"> -<p><span class="pagenum" id="Page_1">[Pg 1]</span></p> - -<h2 class="nobreak" id="HISTORICAL"><i>HISTORICAL.</i></h2> -</div> - - -<p>“Among the customs peculiar to the inhabitants -of the South Pacific Islands, perhaps the most noted is that -of the preparation and drinking of a narcotic beverage -called <i>ava</i>, <i>kava</i>, or <i>yakona</i>. Much of its notoriety arises -from the repulsive way in which it is sometimes made. Aside -from this, it is characteristic of a certain oceanic area, -and seems to be as strikingly limited to this area as is the -stick-and-groove method of making fire. The custom, is not -confined to one ethnic stock, many notices in literature -showing that both Papuans and Polynesians practise it. In -many of the islands the Liquor is concocted by chewing the -root of the Macropiper methysticum, or long pepper, ejecting -the comminuted mass into a bowl, adding water, straining -out the pulp, and drinking the fluid. In other localities -it is made by simply grating the root and adding water.</p> - -<p>“The plant from which kava is made is a shrub -of the natural order Piperaceae. It is about six feet high -with stems ranging from an inch to an inch and a half in -thickness; the leaves are cordate and from four to eight -inches long. This family is the source of the pepper of -commerce and contains several species that are of medicinal -and commercial importance.</p> - -<p><span class="pagenum" id="Page_2">[Pg 2]</span></p> - -<p>In making kava, the root and base of the stem is -used. The roots usually weigh from two to four pounds, -though sometimes as much as 22 pounds. Several varieties -are distinguished by the natives; for instance, in Tahiti -there is a yellow variety called <i>Marea</i>; another, which becomes -pink on exposure to the air, is called <i>avini-ute</i>.</p> - -<p>“Chewed when freshly gathered, the root first -tastes sweet and aromatic, then bitter, acrid and pungent. -It provokes abundant secretion of saliva and in a few seconds -occasions a sensation of burning on the tongue. The root -contains about fifty percent of starch, a little pale-yellow -essential oil, two percent of an acrid resin, and one percent -of the neutral crystalline principle methysticin, called -kavahin. To the latter principle we must attribute the toxic -qualities of the kava preparation. The resin and the kavahin -are insoluble in water, but are soluble in saliva and the -gastric juices.</p> - -<p>“In Samoa, the ava root is grated or chewed, then -soaked, the woody pulp strained off, and the fluid drunk. -The root is used either dry or green. The flavor of the -liquid is at first like that of soapsuds, but immediately -afterward a pleasant aromatic taste is imparted, faintly -bitter, as in quinine. In Samoa, ava drinking is the accompaniment -of all meetings of the men.</p> - -<p><span class="pagenum" id="Page_3">[Pg 3]</span></p> - -<p>“Kava is at first stimulating, but the effect of -an excess resembles that of opium, producing a drowsy drunkenness, -lasting for two hours. The inebriate is usually -peaceable, but sometimes is irritated by noises, which is -attributed by natives to the use of kava grown in moist -ground. The results of excess are skin disease, emaciation, -and general decrepitude. The peculiar whiteness of the skin -caused by kava drinking is said to be sought after in some -islands as a sign that its possessor is wealthy enough to -devote his time to its acquirement.</p> - -<p>“There is some misapprehension in regard to whether -the liquid undergoes fermentation before it is consumed, but -it is positively known that there can be no fermentation, for -the liquor is drunk immediately after the addition of water -to the macerated root. Kava that is prepared by chewing -is said to be more palatable, which is perhaps due to the -conversion of the starch into a fermentable substance by the -ptyalin of the saliva.”<a id="FNanchor_1" href="#Footnote_1" class="fnanchor">[1]</a></p> - -<div class="footnotes"> -<div class="footnote"> - -<p><a id="Footnote_1" href="#FNanchor_1" class="label">[1]</a>—By Walter Hough—Reprinted from Smithsonian -Miscellaneous Collections—No. 1472—August 1904. -“Kava Drinking as Practised by the Papuans and Polynesians.”</p> - -</div></div> - -<p>“In 1779 Captain King, R. N., who followed Captain -Cook to the Islands, describes the case of a priest as follows -‘a little old man of an emaciated figure, his eyes exceedingly<span class="pagenum" id="Page_4">[Pg 4]</span> -sore and red, and his body covered with a white leprous -scurf, the effects of an immoderate use of ava.’ He also -says, ‘The chiefs suffer dreadful effects from the immoderate -use of ava. Those who are most affected by it had their -bodies covered with a white scurf, their eyes red and inflamed, -their limbs emaciated, their whole frame trembling -and accompanied with a disability to raise the head.’”<a id="FNanchor_2" href="#Footnote_2" class="fnanchor">[2]</a></p> - -<div class="footnotes"> -<div class="footnote"> - -<p><a id="Footnote_2" href="#FNanchor_2" class="label">[2]</a> “Leprosy Prize Essays,” 2nd series by Thompson -and Cantile, 1897.</p> - -</div></div> - -<p>F. A. Griel, makes the following statement in a -foot note. “The mixture is a subnarcotic, and if drunk by -European sailors produces highly nauseous effects. If frequently -taken a dry burning heat is produced all over the -body, the eyes become red, skin peels off in flakes and then -degenerates into leprous ulcers or the whole body becomes -emaciated and wastes away.”<a id="FNanchor_3" href="#Footnote_3" class="fnanchor">[3]</a></p> - -<div class="footnotes"> -<div class="footnote"> - -<p><a id="Footnote_3" href="#FNanchor_3" class="label">[3]</a> Miquel, Systema Piperacearum.</p> - -</div></div> - -<p>Numerous attempts have been made to isolate the -active chemical constituent or constituents. As early as -1844 Morson discovered an active principal <i>Kawine</i>. This is a -greenish-yellow, strongly aromatic and acrid resin. This -was again studied by Cuzant in 1860.</p> - -<p><span class="pagenum" id="Page_5">[Pg 5]</span></p> - -<p>Gobley isolated from kava root a crystalline -principle (analogous to piperin), <i>methysticin</i>, or <i>kavahin</i>, -which is without odor and taste and is probably inert.<a id="FNanchor_4" href="#Footnote_4" class="fnanchor">[4]</a> -In 1886 Lewin separated the resin into two resins, of which -the Beta resin is greasy and of a reddish-brown color, -appearing in mass almost black. This is less active than the -alpha resin which is yellowish brown, has the characteristic -odor of the drug, is freely soluble in alcohol, and placed -upon the tongue produces a burning sensation followed by -local anaesthesia.<a id="FNanchor_5" href="#Footnote_5" class="fnanchor">[5]</a></p> - -<div class="footnotes"> -<div class="footnote"> - -<p><a id="Footnote_4" href="#FNanchor_4" class="label">[4]</a> J. P. C. Jan. 1860.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_5" href="#FNanchor_5" class="label">[5]</a> A. J. P. 1886, 450.</p> - -</div> - -<p>A volatile oil has been found in the root.<a id="FNanchor_6" href="#Footnote_6" class="fnanchor">[6]</a></p> - -<div class="footnote"> - -<p><a id="Footnote_6" href="#FNanchor_6" class="label">[6]</a> J. P. C. March 1862.</p> - -</div></div> - -<p>Lavialle claimed to have obtained an alkaloid, -<i>Kavaine</i>.<a id="FNanchor_7" href="#Footnote_7" class="fnanchor">[7]</a></p> - -<div class="footnotes"> -<div class="footnote"> - -<p><a id="Footnote_7" href="#FNanchor_7" class="label">[7]</a> L’Union Pharm. Jan. 1889.</p> - -</div></div> - -<p>The following statement was found in “Watts -Chemical Dictionary”, “Kawain—a crystalline resin occurring -along with methysticin in kawa-kawa, It is not a glucoside. -On oxidation it yields benzoic acid.<a id="FNanchor_8" href="#Footnote_8" class="fnanchor">[8]</a></p> - -<div class="footnotes"> -<div class="footnote"> - -<p><a id="Footnote_8" href="#FNanchor_8" class="label">[8]</a> Gobley, J. Ph. (3) 37, 19.</p> - -</div></div> - -<p><span class="pagenum" id="Page_6">[Pg 6]</span></p> - -<p>The following statement appears in the Encyclopedia -Britannica. “There appears to be little doubt that the -active principle in this beverage is a poison of an alkaloidal -nature. It seems likely that this substance is not -present as such (i.e. as a free alkaloid) in the plant, but -that it exists in the form of a glucoside, and that by the -process of chewing, this glucoside is split up by one of the -ferments in the saliva and the free alkaloid and sugar is -formed”.</p> - -<p>Arthur Bossingham<a id="FNanchor_9" href="#Footnote_9" class="fnanchor">[9]</a> communicates the results -of a chemical examination of Kava-kava. Besides the -crystalline body, methysticin, which has already been -described by others, he was able to isolate and identify -three resins, one soluble in 5% solution of potassium carbonate, -the second insoluble in this, but soluble in 5% -solution of caustic potash, while the third was insoluble -in both of these alkaline solvents, The ash amounts to -2.495% of the air dried root, and contained besides mere -traces of Fe, Mn, mainly Calcium, Sodium and Potassium.<a id="FNanchor_10" href="#Footnote_10" class="fnanchor">[10]</a></p> - -<div class="footnotes"> -<div class="footnote"> - -<p><a id="Footnote_9" href="#FNanchor_9" class="label">[9]</a> Proc. A. Ph. A. 1898, 564.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_10" href="#FNanchor_10" class="label">[10]</a> Proc. Wisc. Pharm. Assos. 1898, 53, 55.</p> - -</div></div> -<hr class="chap x-ebookmaker-drop" /> - -<div class="chapter"> -<p><span class="pagenum" id="Page_7">[Pg 7]</span></p> - -<h2 class="nobreak" id="METHOD_OF_EXTRACTION"><i>METHOD OF EXTRACTION.</i></h2> -</div> - - -<p>The fresh rhizome was chopped up and then -ground up by means of a meat chopper. In the preliminary -work the material was dried in a vacuum oven at a -temperature not exceeding forty degrees Centigrade. -In the later work the material was rapidly dried in -the sun. This operation required about two days time. -After being thoroughly dried, the material was finely -powdered, and then extracted with ether. The following -continuous extraction apparatus was used. Due to the -extreme rapidity with which the ether evaporated, it -was necessary to surround the coils with ice so as to -keep the condensers cold.</p> - -<p><span class="pagenum" id="Page_8">[Pg 8]</span></p> - -<div class="figcenter illowp60" id="i_012" style="max-width: 50em;"> - <img class="w100" src="images/i_012.jpg" alt="Diagram of apparatus" /> -</div> - -<hr class="chap x-ebookmaker-drop" /> - -<div class="chapter"> -<p><span class="pagenum" id="Page_9">[Pg 9]</span></p> - -<h2 class="nobreak" id="METHOD_OF_SEPARATION_OF_THE_RESINS"><i>METHOD OF SEPARATION OF THE RESINS.</i></h2> -</div> - - -<p>After the removal of the crystalline methysticin -from the extract, the following method of separation of -the resinous products was used.</p> - -<p>The free acids were removed by shaking the total -resins successively with solutions of one percent ammonium -carbonate, one percent sodium carbonate and one percent -sodium hydroxide. The acids thus removed were recovered -by treating the alkaline solution with dilute hydrochloric -acid and shaking out with ether. The three acids were not -markedly different in their physical properties. They -possessed the characteristic odor of the crude drug, were -viscous, brown in color and did not solidify at minus ten -degrees Centigrade. These free acids constitute about five -percent of the total resins.</p> - -<p>The remainder of the extract was treated with -alcoholic potassium hydroxide and saponified by heating the -solution to about eighty degrees for fifteen minutes. After -the alcohol was removed by distillation a small quantity -of water was added. This resulting solution was then extracted -with ether to remove the alcohol radical or radicals and -the unsaponifiable material from the saponified product. -The ether extract was saved to be used in the work on the<span class="pagenum" id="Page_10">[Pg 10]</span> -alcohol radicals. The aqueous portion was evaporated to a -semi-solid mass. Carbon dioxide was passed over this mass -for about fifteen minutes to change any excess of potassium -hydroxide to potassium carbonate. Alcohol (95%) was then -added to precipitate the carbonate. The carbonate was then -filtered off and water added to the filtrate.</p> - -<p>To the clear filtrate a solution of barium -chloride was added. Immediately a dense thick cream yellow -precipitate formed. Barium chloride was added in excess. -The barium salt was filtered off by means of a suction pump -and the precipitate washed with water. The filtrate was -treated with a few drops more of barium chloride so as to -be sure that an excess had been added, which was proven if -no further precipitate formed. To this clear filtrate an -excess of a solution of ferric chloride was added. -Immediately a thick heavy precipitate of the iron salt came -down, which was filtered off by means of a suction pump and -the precipitate washed with water.</p> - -<p>The barium precipitate was treated with dilute -hydrochloric acid and heated to boiling to decompose the -barium resinate, and to liberate the free resin acid. The -liberated acid was a brown resin of a thin consistency and -had a characteristic odor. This acid was removed by<span class="pagenum" id="Page_11">[Pg 11]</span> -shaking out with ether. The ethereal solution was dried -with anhydrous sodium sulphate, filtered, and the ether -removed by distillation. The last traces of ether were -removed by heating the resin acids in a vacuum oven at sixty -five degrees Centigrade. This resinous acid is the acid -spoken hereafter in this paper as the BARIUM ACID.</p> - -<p>The iron precipitate was treated with dilute sulphuric -acid (ferric chloride is soluble in ether and -ferric sulphate is not) and heated to boiling to decompose -the iron resinate. The acid when liberated had a strong -characteristic aromatic odor. It was extracted with ether -in the same manner as the barium acid. This resinous acid -is the acid spoken of in this paper as the IRON ACID.</p> - -<p>The resinous extract left after the removal of the -crystalline methysticin is spoken of as the TOTAL RESINS.</p> - -<p>The resin acids removed by the preliminary shaking -out with the various aqueous alkalies are spoken of as the -TOTAL FREE ACIDS.</p> -<hr class="chap x-ebookmaker-drop" /> - -<div class="chapter"> -<p><span class="pagenum" id="Page_12">[Pg 12]</span></p> - -<h2 class="nobreak" id="THE_VARIOUS_METALLIC_SALTS"><i>THE VARIOUS METALLIC SALTS -OF THE RESINOUS ACIDS.</i></h2> -</div> - - -<p>After obtaining the potassium salts of the acids -and having freed the same from the excess of the potassium -hydroxide and potassium carbonate, the possibilities of the -formation of different metallic salts were tried.</p> - -<p>The soluble salts of the following metals yielded -precipitates:—</p> - - -<ul> -<li>Manganese</li> -<li>Barium</li> -<li>Cobalt</li> -<li>Silver</li> -<li>Mercury</li> -<li>Iron</li> -<li>Zinc</li> -<li>Copper</li> -<li>Calcium</li> -<li>Lead</li> -</ul> - - -<p>The following metallic salts gave a complete -precipitation:—</p> - - -<ul> -<li>Silver</li> -<li>Iron (ferric)</li> -<li>Manganese</li> -</ul> - -<p>Since the barium and iron (ferric) salts gave the -best means of separation, they were used to separate the -resins.</p> -<hr class="chap x-ebookmaker-drop" /> - -<div class="chapter"> -<p><span class="pagenum" id="Page_13">[Pg 13]</span></p> - -<h2 class="nobreak" id="THE_TOTAL_RESINS"><i>THE TOTAL RESINS.</i></h2> -</div> - - -<p>The total resins were brown in color, thick syrupy -consistency and possessed the characteristic odor of the drug.</p> - -<p>A molecular weight determination was made in the -same manner as with the Barium acids, and the following -data obtained.</p> - - - -<table class="standard" summary=""> -<tr> -<td class="tdl">Wt. of pipette before</td> -<td class="tdl">18.7660</td> -</tr> -<tr> -<td class="tdl">Wt. of pipette after</td> -<td class="tdl">14.7160</td> -</tr> -<tr> -<td class="tdl">Wt. of resin used</td> -<td class="tdl">4.0500</td> -</tr> -<tr> -<td class="tdl">Temperature before</td> -<td class="tdl">3.52</td> -</tr> -<tr> -<td class="tdl">Temperature after</td> -<td class="tdl">3.71</td> -</tr> -<tr> -<td class="tdl">Change in temperature</td> -<td class="tdl">.18</td> -</tr> -<tr> -<td class="tdl">Volume</td> -<td class="tdl">37 cc.</td> -</tr> -<tr> -<td class="tdl">Constant for solvent</td> -<td class="tdl">3280</td> -</tr> -<tr> -<td class="tdl">Approximate molecular weight</td> -<td class="tdl">2000</td> -</tr> -</table> - - -<p>Combustions were made and the following data -obtained.</p> - - -<table class="standard" summary=""> -<tr> -<td class="tdl">Wt. of boat</td> -<td class="tdl">3.4722</td> -<td class="tdl">3.4720</td> -</tr> -<tr> -<td class="tdl">Wt. of boat and resin</td> -<td class="tdl">3.6355</td> -<td class="tdl">3.6220</td> -</tr> -<tr> -<td class="tdl">Wt. of resin</td> -<td class="tdl">.1633</td> -<td class="tdl">.1500<span class="pagenum" id="Page_14">[Pg 14]</span></td> -</tr> -<tr> -<td class="tdl">Sulphuric acid tube</td> -<td class="tdl">79.1051</td> -<td class="tdl">79.3865</td> -</tr> -<tr> -<td class="tdl">Tube plus water</td> -<td class="tdl">79.2073</td> -<td class="tdl">79.4770</td> -</tr> -<tr> -<td class="tdl">Water</td> -<td class="tdl">.1022</td> -<td class="tdl">.0905</td> -</tr> -<tr> -<td class="tdl">Hydrogen equivalent</td> -<td class="tdl">.01136</td> -<td class="tdl">.01006</td> -</tr> -<tr> -<td class="tdl">KOH bulb</td> -<td class="tdl">49.4316</td> -<td class="tdl">50.8720</td> -</tr> -<tr> -<td class="tdl">Bulb plus carbon dioxide</td> -<td class="tdl">49.8350</td> -<td class="tdl">51.2430</td> -</tr> -<tr> -<td class="tdl">Carbon dioxide</td> -<td class="tdl">.4034</td> -<td class="tdl">.3710</td> -</tr> -<tr> -<td class="tdl">Carbon equivalent</td> -<td class="tdl">.12102</td> -<td class="tdl">.1010</td> -</tr> -<tr> -<td class="tdl">Percent Carbon</td> -<td class="tdl">67.31%</td> -<td class="tdl">67.3</td> -</tr> -<tr> -<td class="tdl">Percent Hydrogen</td> -<td class="tdl">6.9 %</td> -<td class="tdl">6.7</td> -</tr> -<tr> -<td class="tdl">Percent Oxygen</td> -<td class="tdl">26.8 %</td> -<td class="tdl">27.0</td> -</tr> -</table> - - -<p>The total resins when placed on the end of the -tongue produced a marked stinging sensation followed by a -local anaesthesia. After the first stinging was produced -the sensation was rather pleasant. The local anaesthesia -persisted a long time, giving a sensation much the same as -that produced by cocaine. The barium and iron acids also -produced this local anaesthesia, but the initial stinging -sensation was much more pronounced, which was probably due to -the acid nature of the substance.</p> -<hr class="chap x-ebookmaker-drop" /> - -<div class="chapter"> -<p><span class="pagenum" id="Page_15">[Pg 15]</span></p> - -<h2 class="nobreak" id="THE_BARIUM_ACID"><i>THE BARIUM ACID.</i></h2> -</div> - - -<p>The resinous material used and spoken of as the -“Barium Acid” is the material prepared and so named as given -under the “Method of Separation”.</p> - -<p>PHYSICAL PROPERTIES:—Dark reddish brown in -color, syrupy in consistency and has a characteristic odor; -heavier than water; soluble in benzol, ether, alcohol and -acetone, but insoluble in petroleum ether and water.</p> - -<p>This resin constitutes about sixty percent of the -total ester resins; i.e. the resins left after the free -acids have been removed with aqueous potassium hydroxide.</p> - -<p>An analysis of the barium salt obtained by precipitation -from the potassium soap was made and the following -data obtained:—</p> - - -<table class="standard" summary=""> -<tr> -<td class="tdl">Wt. of substance used</td> -<td class="tdl">1.1715</td> -<td class="tdl">.5860</td> -</tr> -<tr> -<td class="tdl">Wt. of barium sulphate</td> -<td class="tdl">.4430</td> -<td class="tdl">.2205</td> -</tr> -<tr> -<td class="tdl">Barium equivalent</td> -<td class="tdl">.2606</td> -<td class="tdl">.1298</td> -</tr> -<tr> -<td class="tdl">Percent barium</td> -<td class="tdl">22.2%</td> -<td class="tdl">22.1%</td> -</tr> -</table> - - -<p>The following method was used in making the -above analysis. The weighed material was ignited in a -platinum crucible by gently heating until the combustible -gases formed were given off. The crucible was then more<span class="pagenum" id="Page_16">[Pg 16]</span> -strongly heated to completely burn off the carbonaceous -material left. The residue was extracted with nitric acid -and the barium precipitated as the sulphate with dilute -sulphuric acid, and the weight of the barium sulphate -determined.</p> - -<p>Expressed as the ACID NUMBER, or the number of -milligrams of potassium hydroxide required to neutralize -the free acids in one gram of the substance, the following -data was obtained:—</p> - - -<table class="standard" summary=""> -<tr> -<td class="tdl">Barium equivalent</td> -<td class="tdl">.2606</td> -<td class="tdl">.1298</td> -</tr> -<tr> -<td class="tdl">Barium expressed as KOH equiv.</td> -<td class="tdl">.2131</td> -<td class="tdl">.1062</td> -</tr> -<tr> -<td class="tdl">Wt. of material used</td> -<td class="tdl">1.1715</td> -<td class="tdl">.5860</td> -</tr> -<tr> -<td class="tdl">Milligrams of KOH per gram</td> -<td class="tdl">181.9</td> -<td class="tdl">181.3</td> -</tr> -<tr> -<td class="tdl">ACID NUMBER</td> -<td class="tdl">181.9</td> -<td class="tdl">181.3</td> -</tr> -</table> - - -<p>The following gives the ACID NUMBER obtained by -direct titration of the barium acid; in “A”, barium -hydroxide was used and in “B”, sodium hydroxide was used.</p> - -<p>A small quantity of the material was dissolved -in a sufficient quantity of neutralized alcohol to give a -liquid of a light yellow color, Phenolphthalein was used as -the indicator, and the alkali was added until a red color -was produced.</p> - -<p><span class="pagenum" id="Page_17">[Pg 17]</span></p> - - -<table class="standard" summary=""> -<tr> -<td class="tdl"></td> -<td class="tdl">“A”</td> -<td class="tdl">“B”</td> -</tr> -<tr> -<td class="tdl">Wt. of substance</td> -<td class="tdl">.6160</td> -<td class="tdl">.2345</td> -</tr> -<tr> -<td class="tdl">Cc. of alkalie</td> -<td class="tdl">4.54</td> -<td class="tdl">1.75</td> -</tr> -<tr> -<td class="tdl">KOH equiv. per gram</td> -<td class="tdl">41.40</td> -<td class="tdl">41.90</td> -</tr> -<tr> -<td class="tdl">Acid number</td> -<td class="tdl">41.40</td> -<td class="tdl">41.90</td> -</tr> -</table> - - -<p>On evaporating a portion of the alcohol from the -material left after titrating with the sodium hydroxide, -and adding water to obtain an aqueous solution of the sodium -salt, an emulsion was formed, and on standing globules -of the free resinous acid separated. From the data thus -obtained, it can readily be seen that the acid or acids -which constitute the BARIUM ACID must have a number of -carboxyl groups and form a different series of salts by -precipitation than by direct titration. The salt or salts -formed by direct titration, although neutral to phenolthalein -may be acid in structure. This is further shown -by the fact that the potassium salts produced by direct -titration are readily hydrolyzed. The acid number obtained -by the precipitation of the barium salt may be called the -COMBINING VALUE, and the acid number obtained by titration -the TITRATION VALUE.</p> - -<p>A number of molecular weight determinations were<span class="pagenum" id="Page_18">[Pg 18]</span> -made on the free barium acid. McCoy’s Boiling Point Apparatus -was used and Merk’s benzol (free from thiophene) was used -as the solvent. A weighing pipette with a bulb was used -to introduce the material, the bulb being weighed before -the material was introduced into the apparatus, and afterwards, -the difference being the weight of the material used.</p> - - -<table class="standard" summary=""> -<tr> -<td class="tdl">Wt. of pipette (before)</td> -<td class="tdl">16.3670</td> -<td class="tdl">14.8895</td> -</tr> -<tr> -<td class="tdl">Wt. of pipette (after)</td> -<td class="tdl">14.8895</td> -<td class="tdl">12.4610</td> -</tr> -<tr> -<td class="tdl">Wt. of material used</td> -<td class="tdl">1.5225</td> -<td class="tdl">2.4285</td> -</tr> -<tr> -<td class="tdl">Original temperature</td> -<td class="tdl">3.53</td> -<td class="tdl">3.53</td> -</tr> -<tr> -<td class="tdl">Final temperature</td> -<td class="tdl">3.60</td> -<td class="tdl">3.62-3</td> -</tr> -<tr> -<td class="tdl">Change in temperature</td> -<td class="tdl">.07</td> -<td class="tdl">.09</td> -</tr> -<tr> -<td class="tdl">Volume of solution</td> -<td class="tdl">37 cc</td> -<td class="tdl">43.5 cc</td> -</tr> -<tr> -<td class="tdl">Constant for solvent</td> -<td class="tdl">3280</td> -<td class="tdl">3280</td> -</tr> -<tr> -<td class="tdl">Approx. Molecular Wt.</td> -<td class="tdl">2000</td> -<td class="tdl">2100 or 1800</td> -</tr> -</table> - - -<p>Combustions were made using the barium acids. By -qualitative tests it was found that the acids contained only -carbon, hydrogen and oxygen. The following gives the results -of the combustions.</p> - - -<table class="standard" summary=""> -<tr> -<td class="tdl">Wt. of boat</td> -<td class="tdl">2.8402</td> -<td class="tdl">2.8402</td> -</tr> -<tr> -<td class="tdl">Wt. of boat and resin</td> -<td class="tdl">3.0500</td> -<td class="tdl">3.0250</td> -</tr> -<tr> -<td class="tdl">Wt. of resin</td> -<td class="tdl">.2098</td> -<td class="tdl">.1848<span class="pagenum" id="Page_19">[Pg 19]</span></td> -</tr> -<tr> -<td class="tdl">Wt. of H2SO4 tube</td> -<td class="tdl">78.0250</td> -<td class="tdl">78.1415</td> -</tr> -<tr> -<td class="tdl">Wt. of tube plus water</td> -<td class="tdl">78.1520</td> -<td class="tdl">78.2550</td> -</tr> -<tr> -<td class="tdl">Wt. of water</td> -<td class="tdl">.1270</td> -<td class="tdl">.1135</td> -</tr> -<tr> -<td class="tdl">Hydrogen equiv.</td> -<td class="tdl">.0143</td> -<td class="tdl">.0126</td> -</tr> -<tr> -<td class="tdl">Wt. of KOH bulb</td> -<td class="tdl">48.8140</td> -<td class="tdl">51.7095</td> -</tr> -<tr> -<td class="tdl">Wt. of bulb plus CO2</td> -<td class="tdl">49.3800</td> -<td class="tdl">52.2085</td> -</tr> -<tr> -<td class="tdl">Wt. of CO2</td> -<td class="tdl">.5660</td> -<td class="tdl">.4990</td> -</tr> -<tr> -<td class="tdl">Carbon equiv.</td> -<td class="tdl">.1543</td> -<td class="tdl">.1361</td> -</tr> -<tr> -<td class="tdl">Percent Hydrogen</td> -<td class="tdl">78.5%</td> -<td class="tdl">73.6%</td> -</tr> -<tr> -<td class="tdl">Percent Carbon</td> -<td class="tdl">6.8%</td> -<td class="tdl">6.8%</td> -</tr> -<tr> -<td class="tdl">Percent Oxygen</td> -<td class="tdl">19.7%</td> -<td class="tdl">19.6%</td> -</tr> -</table> - - -<p>An attempt was made to make the potassium salts -of the barium acids by saponification with alcoholic potash. -A small quantity of the acid was treated with an excess of -ten percent alcoholic potash and heated to eighty degrees -Centigrade to complete the saponification. Instead of the -formation of the potassium salts, a thick dark brown solid, -gummy mass separated. On cooling it solidified to a brittle -solid which had all the physical properties of a true resin. -This solid is soluble in ether, chloroform and benzol,<span class="pagenum" id="Page_20">[Pg 20]</span> -slightly soluble in alcohol and insoluble in petroleum -ether and water. It burns without the formation of an ash. -Evidently, this brittle material is a condensation product -of the original barium acid.</p> -<hr class="chap x-ebookmaker-drop" /> - -<div class="chapter"> -<p><span class="pagenum" id="Page_21">[Pg 21]</span></p> - -<h2 class="nobreak" id="OXIDATION_PRODUCTS_OF_THE_BARIUM_ACIDS"><i>OXIDATION PRODUCTS OF THE BARIUM ACIDS.</i></h2> -</div> - - -<p>A small amount of the Barium acids was sealed -with concentrated nitric acid in a hard glass tube and -heated in a bomb furnace for an hour and a half at 115 to -120 degrees Centigrade. On cooling a yellow solid separated. -Qualitative tests showed that this oxidation product contained -no nitrogen, combined with sodium hydroxide readily, -is soluble in hot water, slightly soluble in cold water, -easily soluble in ether, alcohol and benzol and slightly -soluble in carbon tetrachloride. It decolorizes alkaline -permanganate but does not decolorize bromine water.</p> - -<p>That there are a number of intermediate products -formed and that nitration also takes place during the -formation of these intermediate products is shown by the -following. A small quantity of the acids were placed in -a test tube and covered with concentrated nitric acid. This -was suspended in an H2SO4 bath and a thermometer inserted -so as to observe the temperature. On being gently warmed -the nitric acid and the resin began to react with a rapid -evolution of carbon dioxide and oxides of nitrogen. As soon -as the reaction had modified and before the temperature rose -above one hundred degrees Centigrade, a small amount was removed -and added to water. Some of the solid acid was formed<span class="pagenum" id="Page_22">[Pg 22]</span> -and also a number of globules of oil and there was a strong -persistent odor of nitrobenzene. The original test tube was -heated to about one hundred and twenty degrees centigrade -and a small portion again removed. There was more of the -solid material formed and the odor was similar to vanillin -or coumarin or cinnamic aldehyde. The test tube was again -tested when the temperature had reached one hundred and -thirty five degrees Centigrade. There was no aromatic odor -and a large amount of the solid formed. When viewed under -the microscope the substance had the appearance of curled -threads.</p> - -<p>When the barium acids were treated with the standard -nitrating mixture, a solid was obtained which showed -the presence of nitrogen when the standard test was applied.</p> - -<p>After the preliminary tests were made, the following -method of preparation was used. Two or three grams of -the barium acids were introduced into a hard glass tube of -about thirty centimeters in length and fifteen or twenty -cubic centimeters of concentrated nitric acid added. -The reaction which is very vigorous at first was regulated -by keeping the tube under running water. After this vigorous -action was over the tube was placed in a sulphuric acid -bath, and the temperature gradually increased until it had<span class="pagenum" id="Page_23">[Pg 23]</span> -reached one hundred and twenty five degrees Centigrade, at -which temperature it was kept for about five hours. It was -necessary to add a small quantities of nitric acid from -time to time to make up the loss by evaporation. When the -oxidation was completed the product was poured into water -and then heated to boiling. The resulting solution was -filtered and the filtrate allowed to cool. On standing a -quantity of a pale yellow substance separated. The following -data gives the percent yield of this oxidation product.</p> - -<table class="standard" summary=""> -<tr> -<td class="tdl">Wt. of container</td> -<td class="tdl">6.7220</td> -</tr> -<tr> -<td class="tdl">Wt. of container and substance</td> -<td class="tdl">7.5920</td> -</tr> -<tr> -<td class="tdl">Wt. of substance</td> -<td class="tdl">.8700</td> -</tr> -<tr> -<td class="tdl">Wt. of oxidation product</td> -<td class="tdl">.1240</td> -</tr> -<tr> -<td class="tdl">Percent yield</td> -<td class="tdl">14%</td> -</tr> -</table> - - -<p>The oxidation product was dried by placing it in -a vacuum over sulphuric acid for several days. The neutralization -equivalent of this crude oxidation product was 157.</p> - -<table class="standard" summary=""> -<tr> -<td class="tdl">Wt. of substance used</td> -<td class="tdl">.0502</td> -</tr> -<tr> -<td class="tdl">Number Cc. of NaOH N/10</td> -<td class="tdl">3.2 cc.</td> -</tr> -<tr> -<td class="tdl">Neutralization equivalent</td> -<td class="tdl">157</td> -</tr> -</table> - - -<p>The oxidation product was heated on a watch crystal -and the sublimate allowed to collect on a funnel. The -first sublimate gave a melting point of 109 degrees Centigrade.</p> - -<p><span class="pagenum" id="Page_24">[Pg 24]</span></p> - -<p>Combustions were made on this sublimate with the -following results.</p> - -<table class="standard" summary=""> -<tr> -<td class="tdl">(1)</td> -<td class="tdl">C</td> -<td class="tdl">66%</td> -</tr> -<tr> -<td class="tdl"></td> -<td class="tdl">H</td> -<td class="tdl">4.7%</td> -</tr> -<tr> -<td class="tdl">(2)</td> -<td class="tdl">C</td> -<td class="tdl">65.7%</td> -</tr> -<tr> -<td class="tdl"></td> -<td class="tdl">H</td> -<td class="tdl">4.8%</td> -</tr> -<tr> -<td class="tdl">(3)</td> -<td class="tdl">C</td> -<td class="tdl">65.15%</td> -</tr> -<tr> -<td class="tdl"></td> -<td class="tdl">H</td> -<td class="tdl">4.8%</td> -</tr> -<tr> -<td class="tdl">(4)</td> -<td class="tdl">C</td> -<td class="tdl">65.8%</td> -</tr> -<tr> -<td class="tdl"></td> -<td class="tdl">H</td> -<td class="tdl">4.85%</td> -</tr> -</table> - - -<p>The neutralization equivalent was obtained by -titrating an alcoholic solution of the sublimate with standard -sodium hydroxide. The following results were obtained -on two different lots of the sublimed oxidation product.</p> - -<table class="standard" summary=""> -<tr> -<td class="tdl">Wt. of substance</td> -<td class="tdl">.09</td> -<td class="tdl">.1006</td> -</tr> -<tr> -<td class="tdl">Cc. of alkali N/10</td> -<td class="tdl">7 cc</td> -<td class="tdl">7.9cc</td> -</tr> -<tr> -<td class="tdl">Neutralization equiv.</td> -<td class="tdl">128.6</td> -<td class="tdl">127.3</td> -</tr> -</table> - - -<p>Using a third sample the neutralization equivalent -was obtained from the analysis of the silver salt. The -silver salt was formed by adding silver nitrate solution to a -carefully neutralized solution of the sublimate. The insoluble -silver salt was filtered off, washed with water to re<span class="pagenum" id="Page_25">[Pg 25]</span>move -the excess of silver nitrate, and dried in a vacuum over -sulphuric acid for several days. A weighed quantity of the -silver salt was ignited in a platinum crucible and the residue -of metallic silver was weighed. The following data were -obtained using material from the same sample for each -analysis.</p> - -<table class="standard" summary=""> -<tr> -<td class="tdl">Wt. of dish</td> -<td class="tdl">12.8825</td> -<td class="tdl">12.8826</td> -</tr> -<tr> -<td class="tdl">Wt. of dish and substance</td> -<td class="tdl">13.0060</td> -<td class="tdl">13.1310</td> -</tr> -<tr> -<td class="tdl">Wt. of substance</td> -<td class="tdl">.1235</td> -<td class="tdl">.2484</td> -</tr> -<tr> -<td class="tdl">Wt. of dish and silver</td> -<td class="tdl">12.9400</td> -<td class="tdl">12.9980</td> -</tr> -<tr> -<td class="tdl">Wt. of silver</td> -<td class="tdl">.0575</td> -<td class="tdl">.1154</td> -</tr> -<tr> -<td class="tdl">Neutralization equiv.</td> -<td class="tdl">125</td> -<td class="tdl">125.3</td> -</tr> -</table> - - -<p>Using the same sample, a neutralization equivalent -was obtained by titration with standard NaOH.</p> - -<table class="standard" summary=""> -<tr> -<td class="tdl">Wt. of substance</td> -<td class="tdl">.0912</td> -</tr> -<tr> -<td class="tdl">N/10 NaOH</td> -<td class="tdl">7.25cc</td> -</tr> -<tr> -<td class="tdl">Neutralization equiv.</td> -<td class="tdl">125.8</td> -</tr> -</table> - - -<p>The above data shows that the sublimate is a mixture. -No empirical formula can be calculated from the -combustions, and different samples give different neutralization -equivalents although the duplicate determinations on -the same sample showed good agreement thus demonstrating<span class="pagenum" id="Page_26">[Pg 26]</span> -the reliability of the methods.</p> - -<p>By fractional sublimation it was possible to obtain -fractions with different melting points. The first -sublimate melted sharply at 109 degrees. From the last -fraction it was possible to separate some crystals that melt -at 200 degrees Centigrade. These might possibly be p-acetyl-benzoic -acid, as its properties of solubility, crystalline -form, its melting point and power of sublimation agree with -those of p-acetyl-benzoic acid.</p> - -<p>Those crystals that appeared identical with benzoic -acid were placed in a melting point tube, and some -known benzoic acid (from toluol) was placed in another tube. -These two tubes were placed in the same sulphuric acid -container and their melting points taken at the same time. -They melted at the same temperature.</p> - -<p>The sublimate had a very pleasant aromatic odor -resembling benzoin. It gave no coloration with ferric -chloride, thus eliminating a large group of aromatic compounds. -Some of the crystals were found to be identical with benzoic -acid when examined under the microscope. The characteristic -odor of methyl benzoate was produced when a small quantity of -the crystals were heated with methyl alcohol and concentrated -sulphuric acid. On treating some of the carefully<span class="pagenum" id="Page_27">[Pg 27]</span> -neutralized product with ferric chloride solution, a flesh -colored precipitate was formed. It agreed closely in its -analysis with the precipitate formed with known benzoic acid.</p> - -<p>The filtrate left after the removal of the iron -precipitate was acidified and extracted with ether, and the -ether removed by evaporation. The resulting substance -decolorized alkaline permanganate solution, but did not decolorize -bromine water. When the leaflet needles that melt -at 200 degrees were mechanically removed from the original -sublimate, the substance left after precipitating with -ferric chloride melted at 109 degrees. When these crystals -were not removed, the melting point of this material was -not definite, but was over a range of five degrees, from 110 -to 115 degrees Centigrade.</p> - -<p>The oxidation product contains at least three -distinct substances, benzoic acid, a substance melting at -200 degrees and—which is probably p-acetyl benzoic acid -and a third substance melting at 110 degrees.</p> -<hr class="chap x-ebookmaker-drop" /> - -<div class="chapter"> -<p><span class="pagenum" id="Page_28">[Pg 28]</span></p> - -<h2 class="nobreak" id="THE_IRON_ACIDS"><i>THE IRON ACIDS.</i></h2> -</div> - - -<p>The resinous material used and spoken of as the -IRON ACIDS is the material prepared and so named under the -“Method of Separation”.</p> - -<p>PHYSICAL PROPERTIES:—Transparent and reddish -brown in color, oily in consistency and has a characteristic -tea like odor, heavier than water, freely soluble in benzol, -ether, alcohol and acetone, but insoluble in petroleum ether -and water.</p> - -<p>This resin constitutes about eighteen percent of -the total ester resins.</p> - -<p>By qualitative tests it was shown that the acids -contained only carbon, hydrogen and oxygen. Combustions -made on the iron acids gave the following results.</p> - -<table class="standard" summary=""> -<tr> -<td class="tdl">Wt. of boat</td> -<td class="tdl">2.6950</td> -<td class="tdl">2.6950</td> -</tr> -<tr> -<td class="tdl">Wt. of boat and substance</td> -<td class="tdl">2.8470</td> -<td class="tdl">2.8495</td> -</tr> -<tr> -<td class="tdl">Wt. of substance</td> -<td class="tdl">.1520</td> -<td class="tdl">.1545</td> -</tr> -<tr> -<td class="tdl">KOH bulb</td> -<td class="tdl">50.9620</td> -<td class="tdl">51.0805</td> -</tr> -<tr> -<td class="tdl">Bulb and CO2</td> -<td class="tdl">51.3370</td> -<td class="tdl">51.4610</td> -</tr> -<tr> -<td class="tdl">Wt. of CO2</td> -<td class="tdl">.3750</td> -<td class="tdl">.3805</td> -</tr> -<tr> -<td class="tdl">Carbon equivalent</td> -<td class="tdl">.1023</td> -<td class="tdl">.10376<span class="pagenum" id="Page_29">[Pg 29]</span></td> -</tr> -<tr> -<td class="tdl">Sulphuric acid tube</td> -<td class="tdl">76.2448</td> -<td class="tdl">76.3450</td> -</tr> -<tr> -<td class="tdl">Tube and water</td> -<td class="tdl">76.3400</td> -<td class="tdl">76.4453</td> -</tr> -<tr> -<td class="tdl">Wt. of water</td> -<td class="tdl">.0952</td> -<td class="tdl">.1003</td> -</tr> -<tr> -<td class="tdl">Hydrogen equiv.</td> -<td class="tdl">.0106</td> -<td class="tdl">.01114</td> -</tr> -<tr> -<td class="tdl">Percent Carbon</td> -<td class="tdl">67.3%</td> -<td class="tdl">67.2%</td> -</tr> -<tr> -<td class="tdl">Percent hydrogen</td> -<td class="tdl">7.0%</td> -<td class="tdl">7.2%</td> -</tr> -<tr> -<td class="tdl">Percent Oxygen</td> -<td class="tdl">25.7%</td> -<td class="tdl">25.6%</td> -</tr> -</table> - - -<p>An analysis of the iron salt obtained by precipitation -from the potassium soap gave the following data.</p> - -<table class="standard" summary=""> -<tr> -<td class="tdl">Wt. of substance used</td> -<td class="tdl">.2955</td> -<td class="tdl">.3387</td> -</tr> -<tr> -<td class="tdl">Wt. of FeSO4</td> -<td class="tdl">.0445</td> -<td class="tdl">.0509</td> -</tr> -<tr> -<td class="tdl">Ferric equiv.</td> -<td class="tdl">.03208</td> -<td class="tdl">.03676</td> -</tr> -<tr> -<td class="tdl">Percent Iron</td> -<td class="tdl">10.85%</td> -<td class="tdl">10.85%</td> -</tr> -</table> - - -<p>The following method was used in making the above -analysis. The weighed material was ignited in a platinum -crucible by gently heating until the combustible gases -formed were given off. The crucible was then strongly heated -until the carbonaceous material was completely burned off. -The residue was weighed and the percentage of iron determined.</p> - -<p>Expressed as the ACID NUMBER, or the number of -milligrams of KOH required to neutralize the free acids in<span class="pagenum" id="Page_30">[Pg 30]</span> -one gram of the substance, the following data was obtained.</p> - -<table class="standard" summary=""> -<tr> -<td class="tdl">Ferric equivalent</td> -<td class="tdl">.03208</td> -<td class="tdl">.03676</td> -</tr> -<tr> -<td class="tdl">Fe expressed as KOH equiv.</td> -<td class="tdl">.0965</td> -<td class="tdl">.1107</td> -</tr> -<tr> -<td class="tdl">Wt. of material used</td> -<td class="tdl">.2955</td> -<td class="tdl">.3387</td> -</tr> -<tr> -<td class="tdl">Mg. of KOH per gram</td> -<td class="tdl">326.6</td> -<td class="tdl">326.7</td> -</tr> -<tr> -<td class="tdl">Acid number</td> -<td class="tdl">326.6</td> -<td class="tdl">326.7</td> -</tr> -</table> - - -<p>The following gives the ACID NUMBER obtained by -direct titration of the Iron acid. The method is the same -as that used in getting the titration value of the Barium -acid.</p> - -<table class="standard" summary=""> -<tr> -<td class="tdl">Wt. of substance</td> -<td class="tdl">.2450</td> -<td class="tdl">.2472</td> -</tr> -<tr> -<td class="tdl">Cc of alkalie</td> -<td class="tdl">2.2</td> -<td class="tdl">2.3</td> -</tr> -<tr> -<td class="tdl">KOH equiv.</td> -<td class="tdl">.01232</td> -<td class="tdl">.01288</td> -</tr> -<tr> -<td class="tdl">KOH equiv. per gram</td> -<td class="tdl">53.87</td> -<td class="tdl">52.</td> -</tr> -</table> - - -<p><span class="pagenum" id="Page_31">[Pg 31]</span></p> - -<p>An attempt was made to saponify some of the iron -acid, but it was impossible. The alcohol was partially -distilled off, and the acid freed by making the mass acid -with sulphuric acid, and shaking out with ether. The ether -was distilled off, but the remaining acid had different -physical properties from the acid with which the experiment -was started. It was lighter in color, and solidified at -zero degrees. At room temperature it was almost solid. -On ignition it left no ash. This probably is a polymerization -product of the original acid.</p> - -<p>Since many organic acids whose salts cannot be -prepared by the ordinary methods can be prepared by passing -dry ammonia gas through a solution of the acid in anhydrous -ether, this method was tried with the iron acid. The iron -acid was dissolved in anhydrous ether, and the dry -ammonia gas was bubbled through this ether solution. At -first no change was noted, but after several minutes there -was a flocculent thready precipitate formed which was light -brown in color. The experiment was repeated. At first the -precipitate was a very light brown, but after forming it -quickly darkened. After standing a few hours the flocculent -precipitate changed to a sticky brown mass. This same change -was produced immediately if the precipitate was exposed to -the air. The resulting mass had no odor of ammonia.</p> - -<p><span class="pagenum" id="Page_32">[Pg 32]</span></p> - -<p>The flocculent precipitate formed at first was probably -the ammonium salt of the iron acid, which like most -ammonium salts, it was precipitated due to its insolubility -in ether. Due to the ease of hydrolysis this salt immediately -decomposed to the acid and ammonia when traces of moisture -were present.</p> -<hr class="chap x-ebookmaker-drop" /> - -<div class="chapter"> -<p><span class="pagenum" id="Page_33">[Pg 33]</span></p> - -<h2 class="nobreak" id="OXIDATION_OF_THE_IRON_ACIDS"><i>OXIDATION OF THE IRON ACIDS -AND THE FREE ACIDS.</i></h2> -</div> - - -<p>When the iron acids were oxidized in the same manner -as the barium acids the amount of the oxidation product -formed was about one fourth of that produced with an equal -amount of the barium acids. The time necessary to completely -oxidize the iron acids was much less then required for -the barium acids. On sublimation the iron acid gave a -product melting at 110 degrees Centigrade and is probably -identical with the one formed from the barium acids. The -iron acid also yielded a sublimate melting at 208 degrees C.</p> - -<p>The free acids when oxidized in a like manner -gave as one of the products a low melting crystalline -compound that contained nitrogen.</p> - -<p>The iron acid although related to the barium -acid as shown by the formation of a common oxidation product -is different in structure as shown by the difference in the -amount of the oxidation product formed and the time to -complete the oxidation.</p> -<hr class="chap x-ebookmaker-drop" /> - -<div class="chapter"> -<p><span class="pagenum" id="Page_34">[Pg 34]</span></p> - -<h2 class="nobreak" id="THE_ALCOHOL_RADICALS_AND_UNSAPONIFIABLE_MATERIAL"><i>THE ALCOHOL RADICALS AND UNSAPONIFIABLE MATERIAL.</i></h2> -</div> - - -<p>The material that was shaken out with ether after -the saponification consists of the unsaponifiable material -and the alcohol radicals of the acids produced by saponification.</p> - -<p>On allowing the ether to evaporate from this -material, feathery needles separated. These were removed -by means of a suction pump and recrystallized from hot -acetone. The melting point of this product was 122-125 -degrees Centigrade. The precipitate was dissolved in benzol -and allowed to slowly crystallize. It formed long prismatic -needles with melting point of 130 degrees Centigrade. -When heated with concentrated sulphuric acid, a brown green -fluorescent solution was produced.</p> - -<p>The remaining material was steam distilled, and -the distillate extracted with ether to remove the oil. The -ether was dried with anhydrous sodium carbonate, the solution -filtered and the ether removed by distillation. The oil that -remained was light yellow, specific gravity less than that of -water, and possessed a very characteristic odor resembling -that of musk. The material left after the steam distillation -was cooled and shaken out with ether. The ethereal solution<span class="pagenum" id="Page_35">[Pg 35]</span> -was dried with anhydrous sodium sulphate and the ether removed -by distillation. The resulting mass was a dark brown -resin without any characteristic odor, solidifying at zero -degrees.</p> - -<p>The crystalline product with a melting point of -130 degrees and the essential oil are evidently the alcohols -formed through saponification of the resin esters. The -crystalline product could be readily separated from the -resinous material because of its slight solubility in acetone. -Since this product was not precipitated when the unsaponified -resin esters were treated with acetone and because it did -not make its appearance until after the process of saponification, -it is quite probable it is a product of saponification. -The essential oil can be detected in extremely small -amounts due to its penetrating characteristic odor. Before -the process of saponification it could not be detected, but -as soon as saponification took place the odor was very marked. -From this it is quite evident that this oil is a product -of saponification.</p> - -<p>The dark brown resinous mass that remained may be -either an alcoholic resin formed through the hydrolysis of -the ester resins or it may be a resin belonging to the class -known as resenes<a id="FNanchor_11" href="#Footnote_11" class="fnanchor">[11]</a> which resist saponification.</p> - -<div class="footnote"> - -<p><a id="Footnote_11" href="#FNanchor_11" class="label">[11]</a> Com. Organic Analysis. Allen Vol. II, 146.</p> - -</div> -<hr class="chap x-ebookmaker-drop" /> - -<div class="chapter"> -<p><span class="pagenum" id="Page_36">[Pg 36]</span></p> - -<h2 class="nobreak" id="METHYSTICIN_AND_METHYSTICINIC_ACID"><i>METHYSTICIN AND METHYSTICINIC ACID.</i></h2> -</div> - - -<p>The crystalline product obtained from the ether -extract was recrystallized several times from absolute -alcohol to remove all traces of any resinous material. It had -a melting point of 122-123. It therefore was not pure -methysticin, which has a melting point of 138-139 degrees. -On examining this product under the microscope it was found -to contain two distinct forms of crystals, long needles and -prismatic plates. Some free methysticinic acid, melting -point 180 was examined under the microscope and found to -consist entirely of prismatic plates. Therefore the original -crystalline body contains some methysticinic acid.</p> - -<p>Some of the original precipitate was crystallized -once from absolute alcohol and thoroughly dried. This was -used for the following data to determine the percent of -free methysticinic acid in the crystalline product. -A weighed amount of the crystalline product was dissolved -in carefully neutralized alcohol, and titrated with tenth -normal NaOH, using phenolthalein as the indicator.</p> - -<table class="standard" summary=""> -<tr> -<td class="tdl">Wt. of substance used</td> -<td class="tdl">.2590</td> -</tr> -<tr> -<td class="tdl">NaOH N/10</td> -<td class="tdl">.5 cc</td> -</tr> -<tr> -<td class="tdl">% methysticinic acid.</td> -</tr> -</table> - - -<p><span class="pagenum" id="Page_37">[Pg 37]</span></p> - -<p>The potassium salts of the various resin acids -formed by the saponification of the ester resins should -yield a resinous mass syrupy or oily in consistency when -acidified, if it consists entirely of the two groups of acids -spoken of as the iron acids and the barium acids. Also the -weight of the barium acids plus the weight of the iron -acids should nearly equal the weight of the ester resins, if -these are the only two acids, because the alcohol radicals -constitute not more than two percent of the ester resins. -But when the total potassium salts were acidified the product -formed contained a crystalline substance in addition to the -resinous acids. This crystalline substance was separated -from the resinous acids by means of their difference in -solubility in ether. On recrystallization from absolute -alcohol, it had a melting point of 179 degrees Centigrade. -It is therefore methysticinic acid. This acid constitutes -about twenty percent of the total acids from the ester -resins because the barium and iron acids constitute only -about seventy five percent.</p> - -<p>This methysticinic acid cannot be entirely formed -by hydrolysis of methysticin which was incompletely removed -from the resinous material. The methysticinic acid existed -either combined with some other alcohol than methyl alcohol -or was combined with one of the resin alcohol radicals.</p> -<hr class="chap x-ebookmaker-drop" /> - -<div class="chapter"> -<p><span class="pagenum" id="Page_38">[Pg 38]</span></p> - -<h2 class="nobreak" id="PHYSIOLOGICAL_ACTION"><i>PHYSIOLOGICAL ACTION.</i></h2> -</div> - - -<p>Due to the impossibility of preparing the alkali -salts of the barium and iron acids so as to be positive -that the resulting preparations completely represented the -barium and iron acids, and due to the insolubility of the -acids and the total resins in solvents from which they -would not again be precipitated when introduced into the -circulation, it was found necessary to make an emulsion. -The emulsifying agent used was acacia (gum arabic). It -was possible by careful preparation to make a permanent -emulsion that was miscible with water in all proportions -to form a homogeneous mixture. The animals used were rabbits -of about six pounds weight. The injections were made by -Dr. Geo. McCoy, director of the Leprosy Investigation -Station at Kalihi. All the physiological experiments were -made at the bacteriological laboratory at the Leprosy -Investigation Station.</p> - -<p>One cubic centimeter of the emulsion of the total -resinous extract (strength 1 in 5) was injected into the ear -of a rabbit; the animal died immediately. Another rabbit -was injected in the same manner with one half cubic centimeter<span class="pagenum" id="Page_39">[Pg 39]</span> -of the same preparation. The animal immediately stretched -out and became rigid, or appeared to be paralyzed, but after -several minutes these symptoms lessened and after about five -minutes the rabbit appeared normal as far as activity was -concerned. As soon as the rabbit had recovered a second -injection of one quarter of a cubic centimeter of the same -preparation was injected in the same manner into the same -animal. The same symptoms were produced and with equal -intensity, but ten minutes passed before the animal again -became conscious. For several minutes after recovery the -animal appeared somewhat drowsy and stupid but it soon -regained its former activity.</p> - -<p>One half cubic centimeter of the iron acid emulsion -(strength 1 in 7) was injected into the ear of a rabbit. -Immediate paralysis and apparent anaesthesia set in lasting -very pronouncedly for eight minutes. The rabbit’s head -was drawn backwards and its legs stiffened giving symptoms -similar to strychnine poisoning but they did not persist. -When a second injection of one quarter cubic centimeter -was given to the same animal, the same symptoms were produced, -the animal remaining under the influence of the injection -for about fifteen minutes.</p> - -<p><span class="pagenum" id="Page_40">[Pg 40]</span></p> - -<p>The iron acid injection was repeated on another -rabbit with the same pronounced symptoms of strychnine -poisoning but the effect lasted only about ten minutes.</p> - -<p>One half cubic centimeter of the barium acid -emulsion (strength 1 in 7) was injected into the ear -vein of a rabbit. The animal uttered several loud cries -and after moving several feet it became spastic and went -into a sort of a stupor, beginning to come out of it after -ten minutes. As soon as the animal recovered, a second -injection of one quarter cubic centimeter was made. The -animal again uttered loud cries and then it went into a -stupor, but it was not spastic. This lasted approximately -ten minutes. The animal did not completely recover until -about twenty minutes.</p> - -<p>Thinking that the action might be largely mechanical -and that the symptoms produced were from the emulsion -itself and not from the effect of the material that was -emulsified, an emulsion of olive oil was used in a like manner. -This olive oil emulsion was made in approximately the -same consistency as the resinous emulsions, and one cubic -centimeter was injected into the ear vein of a rabbit. -No visible effects followed this injection during the one -hour’s time the rabbit was under observation.</p> - -<p><span class="pagenum" id="Page_41">[Pg 41]</span></p> - -<p>One cubic centimeter intraperitoneal injections -of the total resinous extract emulsion and the same amount -of the iron acid emulsion were made into rabbits. During -the three hours the animals were under observation no symptoms -were produced. This may have been due to the extreme -slowness of absorption as compared with the rate of elimination -from the circulation.</p> - -<p>Dr. J. F. Illingworth states as the result of his -observations while in the Fiji Islands that the kava beverage -even when taken in large amounts, does not apparently affect -the brain to an extent as to cause the drinker to appear -as if under the influence of alcohol, but he appears as if -the muscles from the hips downward are paralyzed. These -symptoms last for about half an hour, at the end of which -time the person is perfectly able to walk home.</p> - -<p>In general the active constituent of any drug -produces a more pronounced but more fugitive effect than -the crude drug itself, and one might therefore expect more -violent reactions from the isolated active constituents of -the Ava then from the crude infusion. Judging from the -negative results obtained from the injection of the olive -oil emulsion, it is probable that the physiological effects<span class="pagenum" id="Page_42">[Pg 42]</span> -described above following the intravenous injections of the -various preparations were not mechanical but must be -ascribed to the action of the constituents of the Ava.</p> -<hr class="chap x-ebookmaker-drop" /> - -<div class="chapter"> -<p><span class="pagenum" id="Page_43">[Pg 43]</span></p> - -<h2 class="nobreak" id="CONCLUSION"><i>CONCLUSION.</i></h2> -</div> - - -<p>The crystalline product consists, largely of -methysticin, the methyl ester of methysticinic acid. In -addition to this there is about five percent of the free -methysticinic acid present.</p> - -<p>The resinous product consists of about five percent -of free resinous acids, which acids can be separated into -three different acids or groups of acids according to their -solubility in the different alkalies. The remaining resinous -product is composed of ester resins. On hydrolysis these -esters yield three distinct acids, two resinous acids and -methysticinic acid. The two resinous acids are distinctly -different, both in physical properties and in chemical -properties. They can be sharply separated by means of the -difference in solubility of their barium and iron salts. -These acids may be separate individual substances, or a group -of related substances. The barium and iron acids although -different chemically, have some groups in common as shown -by the formation of a common oxidation product. There are -at least three alcohol radicals formed through hydrolysis, -a resinous alcohol radical, a crystalline substance with a -melting point of 130 degrees, and a volatile oil.</p> - -<p><span class="pagenum" id="Page_44">[Pg 44]</span></p> - -<p>The physiological action of the Ava is due to the -ester resins. The two resinous acids formed through the -hydrolysis of these esters seem to be the two active -constituents of the resin ester.</p> - -<p>From the above outlined work it appears that the -ava root does not contain any alkaloidal substance, as none -of the constituents were found to contain nitrogen.</p> - -<p>That the aqueous infusion used by the ava -drinkers contains the same constituents as are extracted -by the ether is shown by the following. An infusion of the -ava was made by allowing some of the powdered drug to -remain in contact with water for about twelve hours. The -infusion was then filtered and the filtrate extracted -with ether. A resinous mass remained which from all -appearances was identical with the resins obtained from the -ether extract. It also gave the same action when placed -on the tongue as was produced by the resins from the ether -extract.</p> - -<div style='display:block; margin-top:4em'>*** END OF THE PROJECT GUTENBERG EBOOK THE CHEMICAL CONSTITUENTS OF PIPER METHYSTICUM; THE CHEMICAL CONSTITUENTS OF THE ACTIVE PRINCIPLE OF THE AVA ROOT ***</div> -<div style='text-align:left'> - -<div style='display:block; margin:1em 0'> -Updated editions will replace the previous one—the old editions will -be renamed. -</div> - -<div style='display:block; margin:1em 0'> -Creating the works from print editions not protected by U.S. copyright -law means that no one owns a United States copyright in these works, -so the Foundation (and you!) can copy and distribute it in the United -States without permission and without paying copyright -royalties. Special rules, set forth in the General Terms of Use part -of this license, apply to copying and distributing Project -Gutenberg™ electronic works to protect the PROJECT GUTENBERG™ -concept and trademark. Project Gutenberg is a registered trademark, -and may not be used if you charge for an eBook, except by following -the terms of the trademark license, including paying royalties for use -of the Project Gutenberg trademark. If you do not charge anything for -copies of this eBook, complying with the trademark license is very -easy. You may use this eBook for nearly any purpose such as creation -of derivative works, reports, performances and research. Project -Gutenberg eBooks may be modified and printed and given away—you may -do practically ANYTHING in the United States with eBooks not protected -by U.S. copyright law. Redistribution is subject to the trademark -license, especially commercial redistribution. -</div> - -<div style='margin:0.83em 0; font-size:1.1em; text-align:center'>START: FULL LICENSE<br /> -<span style='font-size:smaller'>THE FULL PROJECT GUTENBERG LICENSE<br /> -PLEASE READ THIS BEFORE YOU DISTRIBUTE OR USE THIS WORK</span> -</div> - -<div style='display:block; margin:1em 0'> -To protect the Project Gutenberg™ mission of promoting the free -distribution of electronic works, by using or distributing this work -(or any other work associated in any way with the phrase “Project -Gutenberg”), you agree to comply with all the terms of the Full -Project Gutenberg™ License available with this file or online at -www.gutenberg.org/license. -</div> - -<div style='display:block; font-size:1.1em; margin:1em 0; font-weight:bold'> -Section 1. General Terms of Use and Redistributing Project Gutenberg™ electronic works -</div> - -<div style='display:block; margin:1em 0'> -1.A. By reading or using any part of this Project Gutenberg™ -electronic work, you indicate that you have read, understand, agree to -and accept all the terms of this license and intellectual property -(trademark/copyright) agreement. If you do not agree to abide by all -the terms of this agreement, you must cease using and return or -destroy all copies of Project Gutenberg™ electronic works in your -possession. If you paid a fee for obtaining a copy of or access to a -Project Gutenberg™ electronic work and you do not agree to be bound -by the terms of this agreement, you may obtain a refund from the person -or entity to whom you paid the fee as set forth in paragraph 1.E.8. -</div> - -<div style='display:block; margin:1em 0'> -1.B. “Project Gutenberg” is a registered trademark. It may only be -used on or associated in any way with an electronic work by people who -agree to be bound by the terms of this agreement. There are a few -things that you can do with most Project Gutenberg™ electronic works -even without complying with the full terms of this agreement. See -paragraph 1.C below. There are a lot of things you can do with Project -Gutenberg™ electronic works if you follow the terms of this -agreement and help preserve free future access to Project Gutenberg™ -electronic works. See paragraph 1.E below. -</div> - -<div style='display:block; margin:1em 0'> -1.C. The Project Gutenberg Literary Archive Foundation (“the -Foundation” or PGLAF), owns a compilation copyright in the collection -of Project Gutenberg™ electronic works. Nearly all the individual -works in the collection are in the public domain in the United -States. If an individual work is unprotected by copyright law in the -United States and you are located in the United States, we do not -claim a right to prevent you from copying, distributing, performing, -displaying or creating derivative works based on the work as long as -all references to Project Gutenberg are removed. Of course, we hope -that you will support the Project Gutenberg™ mission of promoting -free access to electronic works by freely sharing Project Gutenberg™ -works in compliance with the terms of this agreement for keeping the -Project Gutenberg™ name associated with the work. You can easily -comply with the terms of this agreement by keeping this work in the -same format with its attached full Project Gutenberg™ License when -you share it without charge with others. -</div> - -<div style='display:block; margin:1em 0'> -1.D. The copyright laws of the place where you are located also govern -what you can do with this work. Copyright laws in most countries are -in a constant state of change. If you are outside the United States, -check the laws of your country in addition to the terms of this -agreement before downloading, copying, displaying, performing, -distributing or creating derivative works based on this work or any -other Project Gutenberg™ work. The Foundation makes no -representations concerning the copyright status of any work in any -country other than the United States. -</div> - -<div style='display:block; margin:1em 0'> -1.E. Unless you have removed all references to Project Gutenberg: -</div> - -<div style='display:block; margin:1em 0'> -1.E.1. The following sentence, with active links to, or other -immediate access to, the full Project Gutenberg™ License must appear -prominently whenever any copy of a Project Gutenberg™ work (any work -on which the phrase “Project Gutenberg” appears, or with which the -phrase “Project Gutenberg” is associated) is accessed, displayed, -performed, viewed, copied or distributed: -</div> - -<blockquote> - <div style='display:block; margin:1em 0'> - This eBook is for the use of anyone anywhere in the United States and most - other parts of the world at no cost and with almost no restrictions - whatsoever. You may copy it, give it away or re-use it under the terms - of the Project Gutenberg License included with this eBook or online - at <a href="https://www.gutenberg.org">www.gutenberg.org</a>. If you - are not located in the United States, you will have to check the laws - of the country where you are located before using this eBook. - </div> -</blockquote> - -<div style='display:block; margin:1em 0'> -1.E.2. If an individual Project Gutenberg™ electronic work is -derived from texts not protected by U.S. copyright law (does not -contain a notice indicating that it is posted with permission of the -copyright holder), the work can be copied and distributed to anyone in -the United States without paying any fees or charges. If you are -redistributing or providing access to a work with the phrase “Project -Gutenberg” associated with or appearing on the work, you must comply -either with the requirements of paragraphs 1.E.1 through 1.E.7 or -obtain permission for the use of the work and the Project Gutenberg™ -trademark as set forth in paragraphs 1.E.8 or 1.E.9. -</div> - -<div style='display:block; margin:1em 0'> -1.E.3. If an individual Project Gutenberg™ electronic work is posted -with the permission of the copyright holder, your use and distribution -must comply with both paragraphs 1.E.1 through 1.E.7 and any -additional terms imposed by the copyright holder. Additional terms -will be linked to the Project Gutenberg™ License for all works -posted with the permission of the copyright holder found at the -beginning of this work. -</div> - -<div style='display:block; margin:1em 0'> -1.E.4. Do not unlink or detach or remove the full Project Gutenberg™ -License terms from this work, or any files containing a part of this -work or any other work associated with Project Gutenberg™. -</div> - -<div style='display:block; margin:1em 0'> -1.E.5. Do not copy, display, perform, distribute or redistribute this -electronic work, or any part of this electronic work, without -prominently displaying the sentence set forth in paragraph 1.E.1 with -active links or immediate access to the full terms of the Project -Gutenberg™ License. -</div> - -<div style='display:block; margin:1em 0'> -1.E.6. You may convert to and distribute this work in any binary, -compressed, marked up, nonproprietary or proprietary form, including -any word processing or hypertext form. However, if you provide access -to or distribute copies of a Project Gutenberg™ work in a format -other than “Plain Vanilla ASCII” or other format used in the official -version posted on the official Project Gutenberg™ website -(www.gutenberg.org), you must, at no additional cost, fee or expense -to the user, provide a copy, a means of exporting a copy, or a means -of obtaining a copy upon request, of the work in its original “Plain -Vanilla ASCII” or other form. Any alternate format must include the -full Project Gutenberg™ License as specified in paragraph 1.E.1. -</div> - -<div style='display:block; margin:1em 0'> -1.E.7. Do not charge a fee for access to, viewing, displaying, -performing, copying or distributing any Project Gutenberg™ works -unless you comply with paragraph 1.E.8 or 1.E.9. -</div> - -<div style='display:block; margin:1em 0'> -1.E.8. You may charge a reasonable fee for copies of or providing -access to or distributing Project Gutenberg™ electronic works -provided that: -</div> - -<div style='margin-left:0.7em;'> - <div style='text-indent:-0.7em'> - • You pay a royalty fee of 20% of the gross profits you derive from - the use of Project Gutenberg™ works calculated using the method - you already use to calculate your applicable taxes. The fee is owed - to the owner of the Project Gutenberg™ trademark, but he has - agreed to donate royalties under this paragraph to the Project - Gutenberg Literary Archive Foundation. Royalty payments must be paid - within 60 days following each date on which you prepare (or are - legally required to prepare) your periodic tax returns. Royalty - payments should be clearly marked as such and sent to the Project - Gutenberg Literary Archive Foundation at the address specified in - Section 4, “Information about donations to the Project Gutenberg - Literary Archive Foundation.” - </div> - - <div style='text-indent:-0.7em'> - • You provide a full refund of any money paid by a user who notifies - you in writing (or by e-mail) within 30 days of receipt that s/he - does not agree to the terms of the full Project Gutenberg™ - License. You must require such a user to return or destroy all - copies of the works possessed in a physical medium and discontinue - all use of and all access to other copies of Project Gutenberg™ - works. - </div> - - <div style='text-indent:-0.7em'> - • You provide, in accordance with paragraph 1.F.3, a full refund of - any money paid for a work or a replacement copy, if a defect in the - electronic work is discovered and reported to you within 90 days of - receipt of the work. - </div> - - <div style='text-indent:-0.7em'> - • You comply with all other terms of this agreement for free - distribution of Project Gutenberg™ works. - </div> -</div> - -<div style='display:block; margin:1em 0'> -1.E.9. If you wish to charge a fee or distribute a Project -Gutenberg™ electronic work or group of works on different terms than -are set forth in this agreement, you must obtain permission in writing -from the Project Gutenberg Literary Archive Foundation, the manager of -the Project Gutenberg™ trademark. Contact the Foundation as set -forth in Section 3 below. -</div> - -<div style='display:block; margin:1em 0'> -1.F. -</div> - -<div style='display:block; margin:1em 0'> -1.F.1. Project Gutenberg volunteers and employees expend considerable -effort to identify, do copyright research on, transcribe and proofread -works not protected by U.S. copyright law in creating the Project -Gutenberg™ collection. Despite these efforts, Project Gutenberg™ -electronic works, and the medium on which they may be stored, may -contain “Defects,” such as, but not limited to, incomplete, inaccurate -or corrupt data, transcription errors, a copyright or other -intellectual property infringement, a defective or damaged disk or -other medium, a computer virus, or computer codes that damage or -cannot be read by your equipment. -</div> - -<div style='display:block; margin:1em 0'> -1.F.2. LIMITED WARRANTY, DISCLAIMER OF DAMAGES - Except for the “Right -of Replacement or Refund” described in paragraph 1.F.3, the Project -Gutenberg Literary Archive Foundation, the owner of the Project -Gutenberg™ trademark, and any other party distributing a Project -Gutenberg™ electronic work under this agreement, disclaim all -liability to you for damages, costs and expenses, including legal -fees. YOU AGREE THAT YOU HAVE NO REMEDIES FOR NEGLIGENCE, STRICT -LIABILITY, BREACH OF WARRANTY OR BREACH OF CONTRACT EXCEPT THOSE -PROVIDED IN PARAGRAPH 1.F.3. YOU AGREE THAT THE FOUNDATION, THE -TRADEMARK OWNER, AND ANY DISTRIBUTOR UNDER THIS AGREEMENT WILL NOT BE -LIABLE TO YOU FOR ACTUAL, DIRECT, INDIRECT, CONSEQUENTIAL, PUNITIVE OR -INCIDENTAL DAMAGES EVEN IF YOU GIVE NOTICE OF THE POSSIBILITY OF SUCH -DAMAGE. -</div> - -<div style='display:block; margin:1em 0'> -1.F.3. LIMITED RIGHT OF REPLACEMENT OR REFUND - If you discover a -defect in this electronic work within 90 days of receiving it, you can -receive a refund of the money (if any) you paid for it by sending a -written explanation to the person you received the work from. If you -received the work on a physical medium, you must return the medium -with your written explanation. The person or entity that provided you -with the defective work may elect to provide a replacement copy in -lieu of a refund. If you received the work electronically, the person -or entity providing it to you may choose to give you a second -opportunity to receive the work electronically in lieu of a refund. If -the second copy is also defective, you may demand a refund in writing -without further opportunities to fix the problem. -</div> - -<div style='display:block; margin:1em 0'> -1.F.4. Except for the limited right of replacement or refund set forth -in paragraph 1.F.3, this work is provided to you ‘AS-IS’, WITH NO -OTHER WARRANTIES OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING BUT NOT -LIMITED TO WARRANTIES OF MERCHANTABILITY OR FITNESS FOR ANY PURPOSE. -</div> - -<div style='display:block; margin:1em 0'> -1.F.5. Some states do not allow disclaimers of certain implied -warranties or the exclusion or limitation of certain types of -damages. If any disclaimer or limitation set forth in this agreement -violates the law of the state applicable to this agreement, the -agreement shall be interpreted to make the maximum disclaimer or -limitation permitted by the applicable state law. The invalidity or -unenforceability of any provision of this agreement shall not void the -remaining provisions. -</div> - -<div style='display:block; margin:1em 0'> -1.F.6. INDEMNITY - You agree to indemnify and hold the Foundation, the -trademark owner, any agent or employee of the Foundation, anyone -providing copies of Project Gutenberg™ electronic works in -accordance with this agreement, and any volunteers associated with the -production, promotion and distribution of Project Gutenberg™ -electronic works, harmless from all liability, costs and expenses, -including legal fees, that arise directly or indirectly from any of -the following which you do or cause to occur: (a) distribution of this -or any Project Gutenberg™ work, (b) alteration, modification, or -additions or deletions to any Project Gutenberg™ work, and (c) any -Defect you cause. -</div> - -<div style='display:block; font-size:1.1em; margin:1em 0; font-weight:bold'> -Section 2. Information about the Mission of Project Gutenberg™ -</div> - -<div style='display:block; margin:1em 0'> -Project Gutenberg™ is synonymous with the free distribution of -electronic works in formats readable by the widest variety of -computers including obsolete, old, middle-aged and new computers. It -exists because of the efforts of hundreds of volunteers and donations -from people in all walks of life. -</div> - -<div style='display:block; margin:1em 0'> -Volunteers and financial support to provide volunteers with the -assistance they need are critical to reaching Project Gutenberg™’s -goals and ensuring that the Project Gutenberg™ collection will -remain freely available for generations to come. In 2001, the Project -Gutenberg Literary Archive Foundation was created to provide a secure -and permanent future for Project Gutenberg™ and future -generations. To learn more about the Project Gutenberg Literary -Archive Foundation and how your efforts and donations can help, see -Sections 3 and 4 and the Foundation information page at www.gutenberg.org. -</div> - -<div style='display:block; font-size:1.1em; margin:1em 0; font-weight:bold'> -Section 3. Information about the Project Gutenberg Literary Archive Foundation -</div> - -<div style='display:block; margin:1em 0'> -The Project Gutenberg Literary Archive Foundation is a non-profit -501(c)(3) educational corporation organized under the laws of the -state of Mississippi and granted tax exempt status by the Internal -Revenue Service. The Foundation’s EIN or federal tax identification -number is 64-6221541. Contributions to the Project Gutenberg Literary -Archive Foundation are tax deductible to the full extent permitted by -U.S. federal laws and your state’s laws. -</div> - -<div style='display:block; margin:1em 0'> -The Foundation’s business office is located at 809 North 1500 West, -Salt Lake City, UT 84116, (801) 596-1887. Email contact links and up -to date contact information can be found at the Foundation’s website -and official page at www.gutenberg.org/contact -</div> - -<div style='display:block; font-size:1.1em; margin:1em 0; font-weight:bold'> -Section 4. Information about Donations to the Project Gutenberg Literary Archive Foundation -</div> - -<div style='display:block; margin:1em 0'> -Project Gutenberg™ depends upon and cannot survive without widespread -public support and donations to carry out its mission of -increasing the number of public domain and licensed works that can be -freely distributed in machine-readable form accessible by the widest -array of equipment including outdated equipment. Many small donations -($1 to $5,000) are particularly important to maintaining tax exempt -status with the IRS. -</div> - -<div style='display:block; margin:1em 0'> -The Foundation is committed to complying with the laws regulating -charities and charitable donations in all 50 states of the United -States. Compliance requirements are not uniform and it takes a -considerable effort, much paperwork and many fees to meet and keep up -with these requirements. We do not solicit donations in locations -where we have not received written confirmation of compliance. To SEND -DONATIONS or determine the status of compliance for any particular state -visit <a href="https://www.gutenberg.org/donate/">www.gutenberg.org/donate</a>. -</div> - -<div style='display:block; margin:1em 0'> -While we cannot and do not solicit contributions from states where we -have not met the solicitation requirements, we know of no prohibition -against accepting unsolicited donations from donors in such states who -approach us with offers to donate. -</div> - -<div style='display:block; margin:1em 0'> -International donations are gratefully accepted, but we cannot make -any statements concerning tax treatment of donations received from -outside the United States. U.S. laws alone swamp our small staff. -</div> - -<div style='display:block; margin:1em 0'> -Please check the Project Gutenberg web pages for current donation -methods and addresses. Donations are accepted in a number of other -ways including checks, online payments and credit card donations. To -donate, please visit: www.gutenberg.org/donate -</div> - -<div style='display:block; font-size:1.1em; margin:1em 0; font-weight:bold'> -Section 5. General Information About Project Gutenberg™ electronic works -</div> - -<div style='display:block; margin:1em 0'> -Professor Michael S. Hart was the originator of the Project -Gutenberg™ concept of a library of electronic works that could be -freely shared with anyone. For forty years, he produced and -distributed Project Gutenberg™ eBooks with only a loose network of -volunteer support. -</div> - -<div style='display:block; margin:1em 0'> -Project Gutenberg™ eBooks are often created from several printed -editions, all of which are confirmed as not protected by copyright in -the U.S. unless a copyright notice is included. Thus, we do not -necessarily keep eBooks in compliance with any particular paper -edition. -</div> - -<div style='display:block; margin:1em 0'> -Most people start at our website which has the main PG search -facility: <a href="https://www.gutenberg.org">www.gutenberg.org</a>. -</div> - -<div style='display:block; margin:1em 0'> -This website includes information about Project Gutenberg™, -including how to make donations to the Project Gutenberg Literary -Archive Foundation, how to help produce our new eBooks, and how to -subscribe to our email newsletter to hear about new eBooks. -</div> - -</div> -</body> -</html> diff --git a/old/67736-h/images/cover.jpg b/old/67736-h/images/cover.jpg Binary files differdeleted file mode 100644 index 6204b92..0000000 --- a/old/67736-h/images/cover.jpg +++ /dev/null diff --git a/old/67736-h/images/i_002-signature.jpg b/old/67736-h/images/i_002-signature.jpg Binary files differdeleted file mode 100644 index 47ac083..0000000 --- a/old/67736-h/images/i_002-signature.jpg +++ /dev/null diff --git a/old/67736-h/images/i_012.jpg b/old/67736-h/images/i_012.jpg Binary files differdeleted file mode 100644 index aea365c..0000000 --- a/old/67736-h/images/i_012.jpg +++ /dev/null |
