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Publication numberUS2115492 A
Publication typeGrant
Publication dateApr 26, 1938
Filing dateApr 27, 1936
Priority dateApr 27, 1936
Publication numberUS 2115492 A, US 2115492A, US-A-2115492, US2115492 A, US2115492A
InventorsKober Philip A
Original AssigneeSearle & Co
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Pharmaceutical products adapted for injection into the human body
US 2115492 A
Abstract  available in
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Claims  available in
Description  (OCR text may contain errors)

Patented Apr. 26, 1938 PATENT OFFICE PHARMACEUTICAL PRODUCTS ADAPTED roa'nwnc'rron m'ro 'rnannMAN BODY Philip A. Kober, Evanston, 'niniagm to G; D. I Sear-le k C0,, Chicago, Ill,- a corporation-of Illinois No Drawing. Application April 27, 1936,

, Serial N0.*f16,702 l l 9 Claims.

This invention relates to pharmaceutical prodnets, and more particularly to medicinal agents in the nature of irritants adapted for introduction, as byinjection, into various regions of the 5 human body for the purpose of correcting structural abnormalities through the production of changes in the tissues involved or in contiguous tissues. 7

Pharmaceutical preparations of this general m character have been known and used for some time past in the treatment of various physical defects. For example, they have been injected into, and into the neighborhood of, hernial defects for the purpose of closing the defects and strengthening contiguous structures by producing ,or'stimulating proliferation of connective and/or flbroustissue. Such injections'set up a mild tissue irritation in the margins of the ring or canal through which the herniaprotrudes and thuscause these tissuesto throw out young flbrous tissue'cells or fibroblasts which mature into tough adult fibrous tissue and ultimately close or obliterate the ring or canaLthereby pro hibiting the protrusion of the hernia. These medicinal agents are also commonly used for the obliteration of varicose veins'by injecting them into the lumen of the veins and thereby producing an inflammatory reaction resulting in occlusion of the vessel lumen, for the obliteration 3 vascular structures thereof, and for the shrinkage or obliteration of cavities such as hydrocele sacs, bursae, and various types of cysts, as well as soft tissue sinuses. Among the different agents which have been used for these purposes are phenol, alcohol, zinc sulphate, glucose, strong sodium chloride solution,-tannic acid and extracts containing tannins, urea, quinine, irritating resins and extracts 40 containing them, and irritating mineralacids.

tion. 7 These agents first exert upon the tissue injected a severe irritating action which causes the tissue to throw out a serous exudate or an accumulationof serum containing a large number of polymorphonuclear cells, and repair comes 5 only as a secondary reaction to the initial tissue of hemorrhoids and naevi by sclerosis of the (o1. ISL-G5) destruction. Another disadvantage of the preparations previously known resides in the fact that these agents are in general harmful if introduced into the blood stream, a result which is not unlikely to occur accidentally during their use. For 5 example, it is known that certain of these agents,

particularly the soaps vmadefrom castor oil and cod liver oil, are hemolytic in character and that their introduction into the circulation is therefore undesirable. It is also known that the acids 10 of castor oil are pharmacologically active and that their eifects may be deleterious should they ilndtheir way into the general circulation. Still another disadvantage of thehernlal solutions previously used is that serious complications may 15 result from their injection into the peritoneal cavity or into the hernial sac.

It is therefore one of the objects of the present invention to provide a novel pharmaceutical preparation particularly adapted for use in the 20 injection treatment of structural abnormalities 7 of the human body-which is both highly effective in its intended action and also free of the dis-k advantages of the various agents hitherto known and used forsimilar purposes. 2 Another object is'to provide a pharmaceutical product of novel composition which may be safe- 1y injected into the human body without; danger I of harmful reaction and which will serve in a remarkably effective manner as a means of 30 stimulating the repair of body abnormalities of the types previously mentioned. o

A further object is to provide a medicinal agent of new and unusual character which is especially well adapted for use in the injection'treatment 35- of hernia. l a

Still another object is to provide a new product of thecharacter described which may beeasily and economically prepared from readily obtainable materials. l These and otherobjects will ap ear more fully upon a consideration of the character, advantages and uses of the preferred form of the invention hereinafter described.

It has been discovered that a pharmaceutical 4 product of the character sought, possessing unusually -desirable features and free from the various disadvantages of the preparations previously known andused for similar purposes, can be produced from the oil of various seeds of the ,50

Plantago family, especially the blond psyllium seeds known as Plantago ovata or Plantago ispaghula. By setting free the fatty acids of this oil, purifying them, and then causing them to combine with an inorganic or organic basic ingredient to form salts or soaps of the acid and the basic ingredient, a product is obtained which, as has been thoroughly demonstrated by clinical tests, is particularly well adapted for the repair of those abnormalities of the human body which are treated by injecting into the body medicinal agents in the nature of irritants which serve as proliferative stimulants for connective and fibrous tissue, or as obliterative and sclerosing agents for vascular tissue. Although the exact chemical composition of this new productcannot be stated with certainty, it has been determined that its effectiveness as a pharmaceutical agent for the injection treatment of these various physical conditions is due to the presence therein of the salts or soaps oi the fatty acids of the oil derived from psyllium seeds.

In preparing this product, the oil is preferably obtained from the psyllium seeds by grinding and milling and then extracting the oil with suitable fat solvents in any desired manner. The oil may also be obtained from parts of the milled seeds such as the hulls which are an article of commerce. After clarification the oil is saponificd with an alcoholic alkali in the customary manner to produce salts of the fatty acids of the oil. These salts are then acidified, as with hydrochloric acid. Upon acidification the fatty acids are liberated in the form of an oily layer and, being insoluble in water, may be readily collected and purified by washing with water. The purified fatty acids are next converted to water soluble salts or soaps by combination with an inorganic as sodium, potassium, or ammonium hydroxides, or with an organic basic ingredient such as triethanolamine or methylamine. The salts may be treated with organic solvents to further remove impurities. The resultant purified salts or soaps are preferably prepared for commercial use in the form of aqueous solutions which may, if desired, also include a small amount of some antiseptic or anaesthetic, such as benzyl alcohol. The final solution is usually filtered with animal charcoal before being bottled.

Although it will be recognized by those skilled in the art that the specific steps in the preparation of the product of the present invention may be varied in certain respects, the following procedure has been found preferable in thepractice of the invention. 1200 grams of psyllium seed oil are placed in suspension in 2750 cc. of ethyl alcohol and the mixture is heated in a water bath until the internal temperature is about 50 C. During this operation, it is probable that some of the oil is dissolved. The psyllium seed oil used may be obtained in any suitable manner, as by extraction with fat solvents from milled psyllium seed'hulls as previously mentioned. 325 cc. of a cold 50% solution (by weight) of sodium hydroxide are then poured slowly into the heated oil and alcohol while the same is stirred. The resulting mixture is permitted to stand with occasional shaking for approximately fifteen minutes, at the end of which time distilled water is added until thetotab volume equals 6 liters. The soap solution thus produced is then poured into a solution of 2000 cc. of distilled water and centrated hydrochloric acid, accompanied by vigorous stirring. As a result of the acidification, the fatty acids which are insoluble in water rise to the surface and maybe readily siphoned off from the aqueous layer. The fatty acids are then washed with liters of hot distilled water, separated from the washing water, and filtered to remove impurities.

600 cc. of con-' 700 grams of the fatty acids thus obtained and 300 grams of benzyl alcohol are then placed in suspension in 13,000 cc. of distilled water, after which a 10% solution (by weight) of sodium hydroxide is added slowly, accompanied by stirring, until the pH of the resulting solution is 8.3 as determined with phenolphthalein as indicator. The solution thus produced is then diluted with distilled water to a volume of 15,000 cc. and finally filtered with animal charcoal to remove any remaining impurities. This final solution, which may be characterized as an approximately 5% aqueous solution of the sodium salts of the fatty acids of an oil of the type obtained from psyllium seeds, is then bottled in sterile containers or otherwise suitably prepared for marketing.

There is thus provided by the present invention a novel pharmaceutical product which is particularly well adapted for the treatment of various abnormalities of the human body. This product is different from and superior to those hitherto known and used for similar purposes in that it can be injected intravenously in massive doses without harm, as contrasted with the dangers attending intravenous injection of caustic or escharotic agents, tannins, resins, or metallic salts such as zinc sulphate. Consequently, accidental escape from the site of injection into the general circulation of the body cannot cause serious in- Jury as often results when these other agents are used. It has also been found that the product of the present invention is less prone to cause hemolysis than are salts prepared from the acids of other oils such as castor oil or cod liver oil, and hence is less likely to cause harm should some of the injected solution find its way into the blood stream. Another of the more important distinctions between the present product and those of the prior art resides in the fact that m iection into the body of a solution containing salts of the fatty acids of psyllium seed oil produces a primary proliferation and rapid maturation of connective tissue, whereas the injection of previously known agents produces first an exudative reaction accompanied by tissue necrosis, the proliferation of tissue coming only as a secondary reaction to the primary destruction caused by the injected agent. Clinical tests of this new product on human beings have proven that it is highly effective in its action, that it can be freely used without serious ill effects, and that its use causes little or no pain to the patient. These and other advantages including the fact that it can be readily prepared in a simple and economical manner, are indicative of the novelty, usefulness and superiority of the product herein disclosed.

Although only one specific embodiment of the product of the present invention has been described in detail, together with a preferred method of preparing that product; it will be understood that the invention is not limited to either a product of the precise composition or the meth- 0d ,of preparation described, but is capable of variation in a number of respects. For example, although it has been found preferable to utilize as the startingmaterial the oil extracted from blond psyllium seeds, the oils obtained from various other seeds of the Plantago family may also be used. It is also contemplated that an'oil possessing the same characteristics as psyllium seed oil may be produced synthetically or artificially and used instead of the natural oil. Furthermore, while in its preferred form the present product comprises an approximately 5% aqueous sohrtion'of: the sodium salts of the fatty acids of psyllium seed oil containing a small amount of benzyl alcohol as an anaesthetic, it will be obvious to those skilled in the art that other salts or soaps of the acids may be used, that the benzyl alcohol may be either omitted or replaced by other anaesthetics or antiseptics, and that the concentration of the solution may be varied as desired within those limits which are satisfactory to the medical profession. Moreover, the disclosed method bywhich the product of the present invention may be made, which is the subject matter of application Serial No. 76,701, filed April 27, 1936, is not to be considered as the only method by which the product can be obtained or as limitative of the scope of the invention represented by the product. Reference is therefore to be had to the appended claims for a definition of the limits of the invention.

What is claimed is:

l. A pharmaceutical product adapted for injeetion into the human body for the treatment of hernial and other physical defects comprising salts of the fatty acids obtained from psyllium seed oil.

2. A pharmaceutical product adapted for injection into the human body for the treatment of hernial and other physical defects comprising the sodium salts of the fatty acids obtained from psyllium seed oil.

3. A pharmaceutical product adapted for injection into the human body for the treatment of hernial and other physical defects comprising a solution of the soaps of the fatty acids obtained from psyllium seed oil.

4. A pharmaceutical product adapted for injection into the human body for the treatment of hernial and other physical defects comprising salts of the fatty acids obtained from psyllium seed oil, and an anaesthetic.

5. A pharmaceutical product adapted for injection into the human body for the treatment of hernial and other physical defects comprising a solution of the soaps of the fatty acids obtained from psyllium seed oil and including a small amount of benzyl alcohol.

6. A pharmaceutical product adapted for injection into the human body for the treatment of hernial and other physical defects comprising an approximately 5% aqueous solution of the sodium salts of the fatty acids obtained from psyllium seed oil.

7. A pharmaceutical product adapted for injection into the human body for the treatment of hernial and other physical defects comprising an approximately 5% aqueous solution of the sodium salts of the fatty acids obtained from psyllium seed oil and including about 2% of henzyl alcohol.

8. A proliferative stimulant for connective and fibrous tissue containing saponified psyllium seed oil.

9. A medicinal agent for use in the injection treatment of hernia comprising an aqueous solution of saponified psyllium seed oil.

PHILIP A. KOBER.

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EP0030444A2 *Dec 2, 1980Jun 17, 1981Kitasato KenkyushoA process for preparing substances having interferon inducing activity
Classifications
U.S. Classification424/738, 606/213, 514/558
International ClassificationA61K36/68, A61K36/185
Cooperative ClassificationA61K36/68
European ClassificationA61K36/68