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Publication numberUS3924000 A
Publication typeGrant
Publication dateDec 2, 1975
Filing dateJun 12, 1973
Priority dateFeb 8, 1971
Also published asCA1014474A1, DE2332221A1, US3982017
Publication numberUS 3924000 A, US 3924000A, US-A-3924000, US3924000 A, US3924000A
InventorsGeraldine H Thiele
Original AssigneeGeraldine H Thiele
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Injectable solution
US 3924000 A
Abstract
Fractures, breaks and nonunions of bones are more readily healed without muscle atrophy, etc., by injecting a liquefied composition containing a non-necrotic vascular sclerosing agent into the site of the fracture or nonunion. No cast is used. The preferred non-necrotic vascular sclerosing agent is sodium oleate.
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Description  (OCR text may contain errors)

United States Patent Thiele [451 *Dec.2, 1975 I INJECTABLE SOLUTION {76] Inventor: Geraldine H. Thiele, Glen-Haven Farms, Rte. 1, Box 12, Windber, Pa. 15963 Notice: The portion of the term of this patent subsequent to June 26, 1990, has been disclaimed.

22 Filed: June 12, 1973 [21] Appl. No.: 369,236

Related US. Application Data [63] Continuation-impart of Ser. No. 113,362, Feb. 8,

1971, Pat. No. 3,741,204, and Ser. No. 123,830, March 12, 1971, Pat. No. 3,767,812, and Ser. No. 283,663, Aug. 25, 1972, and Ser. No. 283,662, Aug. 25, 1972, Pat. No. 3,805,776, said Ser. No. 123,830, and Ser. No. 283,663, and Ser. No. 283,662, each is a continuation-in-part of Ser. No. 113,362, said Ser. No. 283,662, and Ser. No. 283,663, each is a continuation-in-part of Ser. No. 123,830.

[52] US. Cl. 424/318 [51] Int. Cl A6lk 31/20 [58] Field of Search 424/318 [56] References Cited OTHER PUBLICATIONS Renaud-Chem. Abst., Vol. 25 (1931), p. 30787. Rabbeno--Chem. Abst., Vol. 23 (1929), p. 206. Fewell et al.,--Chem. Abst., Vol. 66 (1967), p. 640485.

Crespin et al.,--Chem. Abst., Vol. 71 (1969), p. 110518Y.

GutmanModern Drug Encyclopedia2nd Edit. (1941) pp. 538, 539, 568 and 961.

Primary ExaminerStanley J. Friedman Attorney, Agent, or Firm-Christen & Sabol [57] ABSTRACT Fractures, breaks and nonunions of bones are more readily healed without muscle atrophy, etc., by injecting a liquefied composition containing a non-necrotic vascular sclerosing agent into the site of the fracture or nonunion. No cast is used. The preferred nonnecrotic vascular sclerosing agent is sodium oleate.

Bones can be fused together by injecting a liquefied composition containing a non-necrotic vascular sclerosing agent into the interface region between the bones. Normally a cast or brace is not used. The preferred non-necrotic vascular sclerosing agent is sodium oleate. Splints and diffused splints can be prepared using the bone fusing technique.

Splints, ringbone, bucked shins and osslets can be treated according to this invention.

Before, during and after the above treatment is completed, the fractures and nonunions of bones can more readily be healed without muscle atrophy, etc, by injecting a liquefied composition containing a non-necrotic vascular sclerosing agent (e.g., sodium oleate) into the site of the fracture or nonunion.

20 Claims, 4 Drawing Figures US. Patent Dec. 2, 1975 3,924,000

FIG]

INJECTABLE SOLUTION This application is a continuation-in-part application of applicants copending application Ser. No. 1 13,362, titled Method of Treating Bone Fractures and Nonunions, which was filed on Feb. 8, 1971 now US. Pat. No. 3,741,204; this application is a continuation-inpart application of applicants copending application Ser. No. 123,830, entitled Non-Surgical Removal of Abnormal New Bone Proliferation, which was filed on Mar. 12, 1971, now US. Pat. No. 3,767,812 and which is a continuation-in-part application of applicants copending application Ser. No. 113,362 (filed February 8, 1971); this application is a continuation-in-part application of applicants copending application Ser. No. 283,663, entitled Method of Fusing Bones, which was filed on August 25, 1972, and is a continuation-inpart application of applicants copending application Ser. No. 113,362 (filed on February 8, 1971) and is a continuation-in-part application of applicants copending application Ser. No. 123,830 (filed on March 12, 1971 and this application is a continuation-in-part application of applicants copending application Serial No. 283,662, entitled Treatment of Non-Surgical Osteolysis of Bone, which was filed on August 25, 1972, now US. Patent No. 3,805,776 and is a continuationin-part of applicants copending application serial no. 113,362 (filed on February 8, 1971) and is a continuation-in-part of applicants copending application serial no. 123,830 (filed on March 12, 1971).

BACKGROUND OF THIS INVENTION 1. Field of this Invention This invention relates to the fusion of bones, to the treatment of bone fractures, breaks and nonunions, and to the treatment of osteolysis of the region of bone around a metal object in or contacting the bone using a non-necrotic vascular sclerosing agent.

BROAD DESCRIPTION OF THIS INVENTION This invention involves an injectable liquefied composition comprised of a non-necrotic vascular sclerosing agent which is a fatty acid compound and a liquid carrier, which is useful, for example, for the treatment of bone fractures, breaks and nonunions, for the fusing of bones, having surfaces in juxtaposition, and for the treatment of osteolysis of the region of bone around a metal object in or contacting said bone.

Preferably the fatty acid compound is a fatty acid salt, and preferably the fatty acid salt is prepared from an alkali metal or basic alkali metal compound,. and a fatty acid. More preferably the non-necrotic vascular sclerosing agent is sodium olete. The preferred liquid carrier is water. Preferably a buffering agent is present in the injectable liquefied composition and the preferred buffering agent is sodium dihydrogen phosphate. The injectable liquefied composition is preferably in a dosage form and preferably the dosage contains between 0.1 and cc. More preferably the dosage contains between 0.5 and 5 cc Preferably the injectable liquefied composition has a pH between 8 and l1,'and more preferably has a pH between 9 and 10. Preferably the injectable liquefied composition contains a minor amount of ethanol. More preferably the injectable liquefied composition contains 0.1 to 5 percent ethanol. A preferred composition contains sodium oleate, water, ethyl alcohol and sodium dihydrogen phosphate.

2 Another preferred injectable liquefied composition contains 1 to 10 percent of the non-necrotic vascular sclerosing agent, enough buffering agent to adjust the pH to the stated preferred range and the remainder water.

The most preferred injectable liquefied composition is comprised of5 percent of sodium oleate, 1.5 percent of ethyl alcohol, enough disodium hydrogen phosphate to adjust the pH to 9.8, and the remainder water.

The injectable liquefied composition of this invention can be used in a process of treating bone fractures breaks and nonunions of man and animal. The process includes: aligning (only when necessary) the bone parts to position for setting; and then injecting at least one dosage of the injectable liquefied composition comprised of a non-necrotic vascular sclerosing agent and a liquid carrier into the site of the fracture, break or nonunion area of the bone until there is a substantially complete bone union. Preferably another dosage is injected a week or two after the first dosage and then every week or two thereafter, as needed, until there is a substantially complete bone union. Preferably each dosage of the injectable liquefied composition is injected into the site of the fracture, break or nonunion at its axis.

Reduction of a fracture, heretofore, must be complimented by immobilization of a cast as compression is put into effect. Compression, per se, can only increase the mass, it cannot align. My theory is that a cast leading to compression and atrophy of muscle is not only undesirable, but in the case of the equine reduction in many bones is impossible. I have proven that by injecting a non-necrotic vascular sclerosing agent at the axis of the fracture, l chemically introduce struts giving rise to sheer, and thus alignment. The lack of the cast not only eliminates atrophy of muscles, the complication of lipping but the movement of bone against the tension of muscle insertion helps to promote the flow blood to and from the damaged area.

The injectable liquefied compositions of this invention can be used to heal (treat) simple, compound, comminuted, linear, green-stick, multiple, distracted and partial fractures as well as non-unions which have been in existance as long as one year. This invention can also be used for splints, diffused splints, and fusion of meta-carpals and/or meta-torsals in regards to the three bone weight bearing complex or any boney material.

The use of the liquefied composition of this invention allows the healing of bone fractures, breaks and nonunions to be reduced from as long as 18 months to 8 to 10 weeks, sometimes less.

More broadly, this invention involves an injectable liquefied composition comprised of a non-necrotic agent which is a fatty acid compound and a liquid carrier. The injectable composition is useful for the treatment of bone surfaces in juxtaposition in order to achieve substantially complete bone union, and for the treatment of osteolysis of the region of bone around a metal object in or contacting said bone. This invention also more broadly involves a process of treating bone surfaces in juxtaposition. The process includes injecting at least one dosage in an effective amount of a liquefied composition comprised of a nonnecrotic agent which is a fatty acid compound and a liquid carrier into the site of the bone surfaces which are in juxtaposition. The process is repeated until there is a substantially complete bone union.

This invention also involves an injectable liquefied composition comprised of a non-necrotic vascular sclerosing agent which is a fatty acid compound and a liquid carrier. The injectable liquefied composition is useful for the treatment of bone surfaces in juxtaposition in order to achieve a substantially complete bone union, and for the treatment of osteolysis of the region of bone around a metal object in or contacting said bone. This invention further involves a process of treating bone surfaces in juxtaposition, the process involving the injecting at least one dosage in an effective amount of a liquefied composition comprised of a non-necrotic vascular sclerosing agent which is a fatty acid compound and a liquid carrier into the site of the bone surfaces which are in juxtaposition. The process being repeated until there is a substantially complete bone union.

The accepted four stages of the healing of fractures (including mosaic fractures) to date are: (1) Stage of haematoma formation, (2) Stage of Callus formation, (3) Stage of Consolidation, and (4) Remodeling of Callus.

This invention involves the use of the injectable liquefied composition of this invention to treat and heal and the process of using the injectable liquefied composition of this invention to treat and heal mosaic fractures of the bone and periosteum, which are commonly called bucked shins in horses and other minute fractures of the bone periosteum (such as, splints, osselets and ringbone). The injection is normally made at a number of points around the site of the mosaic fracture. The injection is made right into the mosaic bone fracture site, going through the tissue and the coagulated tissue. The mosaic fracture in a bucked shin is normally quite long and extends down most of the bone. Each set of injections normally takes 6 to 8 c.c. of the injectable liquefied composition. One set of injections in that manner is normally all that is required to effect healing and curing. The use of the most preferred injectable liquefied composition is the preferred form of this method.

The injectable liquefied composition of this invention can be used in a process of fusing the bones of man and animal. The process includes: aligning (only when necessary) the bones to position, so that the interfaces of the bones are in juxtaposition, for fusing; and the injecting at least one dosage of the injectable liquefied composition comprised of a non-necrotic vascular sclerosing agent and a liquid carrier into the interface region between the bones. The injection is repeated, if necessary, until there is a substantially complete fusion of the bones. Preferably another dosage is injected a week or two after the first dosage and then every week or two thereafter, as needed, until there is a substantially complete fusion of the bones.

The injectable liquefied composition of this invention can be used to fuse bones to prevent the occurrence of trauma of bones and possible fracture, break or nonunion of such bones. For example, the injectable liquefied composition of this invention can be used in the fusion of the meta-carpals and/or meta-tarsals in regards to the three bone weight bearing complex in horses. More specifically, the medial and lateral meta-carpal and/or meta-tarsal is fused to the main shaft of the leg in horses, particularly in race horses which suffer a great deal of trauma in the affected region. The injectable liquefied composition of this invention can also be to fuse bones together whenever needed for medical reasons, for example, when vertebra in the spinal column need to be fused together. Broadly, the injectable liquefied composition of this invention can be used to fuse any boney materials, such as, tendons and bone cartilages.

The fusion usually is completed in 8 to 10 weeks, sometimes less.

A cast or brace should not normally be used around the bone areas to be fused. A cast leads to compression and atrophy of muscle, which of course is undesirable. In the case of equines, the use of a cast in the case of certain bones is impossible. The injection of a nonnecrotic vascular sclerosing agent at the interface region of the bones to be fused quickly chemically introduces struts, which aligns and fixes the bones in relationship to each other which means braces and casts usually do not have to be used. The lack of the cast only eliminates atrophy of muscles.

Bone is almost incompressible under normal loads. Trauma to the bone results from excessive loads to the bone, which is compressed during those periods, for example, in the legs of show and race horses. Fusion of certain bones in the legs of show and race horses prevents the occurence of such trauma and helps prevent leg fractures, breaks and non-unions.

When a non-necrotic vascular sclerosing agent is injected into the interface region between bones a nonvascular environment, which is controlled by an electrical field, the appropriate ionic concentration charges the area and the fantastic selectivity of the osteogenic cells can, therefore, put down cartilage. (In a non-vascular environment bone is formed.) Struts of callus are laid down between the bone surfaces. Callus is comprised almost entirely of cartilage, and nature converts it into bone so that a permanent union can be established.

The injectable liquefied composition of this invention can also be used to fuse pieces of bone to other bones in order to form a splint in order to strengthen or protect the other bone from excessive force, pressure, compressive trauma, etc. The bones to which such splints are applied can be those which have been weakened to some reason or which nature has not made strong enough for the task to which man or animal has put it. A splint can also be applied to prevent movement of a joint (as it would involve fusing a piece of bone to two or more other bones). This invention can also be used to prepare diffused splints.

Bone is composed of living cells and an intercellular matrix that is impregnated with calcium salts. Calcium phosphate makes up about percent of the mineral matter, with the remainder composed largely of calcium carbonate and magnesium phosphate. One hundred cc. of bone contain 10,000 mg. of calcium, as compared with 6 mg. of calcium per cc. of blood. Thus, bone serves as a mineral reservoir which is either constantly being replenished or constantly being depleted.

Adult bone cells are found in the lacunae within the matrix of the bone. Throughout life, osteoblasts are found in the deep layer of periosteum surrounding the bone, in Haversian canals, and in the endosteum. These cells function in bone growth and in fracture and bone repair.

Ossification is the formation of true bone by the deposition of calcium salts in a matrix of osteoid tissue Bone (even in a fresh carcass) appears hard, dense, inelastic, and almost lifeless. Actually bone as a tissue is extremely responsive to environmental changes in blood supply and to changes in nutrition. Bone can decrease in size (atrophy), increase in size (hypertrophy), repair breaks, and rearrange its internal structure to best resist stresses and strains. Under both normal and pathological conditions, bone can normally reshape itself according to good engineering principles to sustain a maximum of stress with a minimum of bone tissue.

Osteolysis is the softening, absorption and destruction of bony tissue. It is also commonly termed demineralization. When metal screws, pins and the like are used in bone, osteolysis often occurs, i.e., the bone rejects the metal screws, etc. Calcium, which is the major component of bone, migrates from the includes of the bone around the screws and deposits on the screws. The, region from which the migration occurs becomes soft and spongy. The ossifluent regions are returned to normal bone by treatment using the injectable liquefied composition of this invention.

This invention involves injectable liquefied composition for the treatment of osteolysis of the region of bone around a metal object in or contacting the bone. The metal object is usually a screw or pin which has been inserted in bone to hold a fracture, non-union or break together. Treatment inclludes injecting at least one dosage of the injectable liquefied composition of this invention, which comprises a non-necrotic vascular sclerosing agent and a liquid carrier, into the ossifluent region around the metal object. The result is a substantially complete curing (return to normal, healthy bone) of the ossifluent region.

After, before or along with the treatment of the demineralized region around the screwsfpins, etc., with the vascular sclerosing anionic agent, the bone fracture, break or nonunions of the man or the animal can be treated. Preferably this additional treatment is conducted only after the screws, etc., have been removed. This additional treatment includes: aligning (only when necessary) the bone parts for setting; and then injecting at least one dosage of the injectable liquefied composition of this invention, which is comprised of a nonnecrotic vascular sclerosing agent and a liquid carrier, into the site of the fracture, break or nonunion area of the bone until there is a substantially complete bone union. This additional treatment is described in detail elsewhere herein. Preferably another dosage is injected a week or two after the first dosage and then every week or two thereafter, as needed, until there is a substantially complete bone union. Preferably each dosage of the injectable liquefied composition is injected into the site of the fracture, break or nonunion at its axis. By injecting a non-necrotic vascular sclerosing agent at the axis of the fracture struts are chemically introduced, giving rise to sheer and thus alignment. The lack of the cast not only eliminates atrophy of muscles and the complication of lipping, but the movement of bone against the tension of muscle insertion helps to promote the flow of blood to andfrom the damaged area.

This invention can be used to treat man and/or animal. This invention is particularly useful in the treatment of racing and troting horses; can be used to treat, for example, all equine, e.g., horses and mules, donkeys, sheep, goats, swine, bovines, e.g., oxen andcows, dogs, poultry, cats, etc.

Ater treatment using the injectable liquefied composition of this invention and healing of bone breaks, fractures and nonunions of racing horses, no lameness due to re-fracturing, etc., has been noted even after a large number of races.

DETAILED DESCRIPTION OF THIS INVENTION In FIG. 1, the bone is located at 10, the locus of the fracture-being indicated at 1 1. Screw 12 holds the fracture together. The demineralized or ossifluent region around screw 12 is indicated by l3. 14 is an exploratory hypodermic needle which is inserted into the demineralized region 13. The injection is made through needle 14.

In FIG. 2, demineralized region 13 is absent around screw 13.

In FIG. 3, the bone is illustrated at l 10, the locus of the fracture being indicated at l l l and a blood clot l 12 (hematoma in periosteum). l 13 is an exploratory hypodermic needle which is inserted through the axis of fracture site 1 l l. The injection is made through needle 1 13.

In FIG. 4, the main bone is illustrated at 210, the minor bone is illustrated at 211, and the interface region of bones 210 and 21 l is illustrated at 212. 213 is an exploratory hypodermic needle which is inserted into interface region 212. The injection is made through needle 213.

As used herein the phrase alien material means metals or other substances which cause the osteolysis demineralization of the bone. Examples of such metals are iron, steel, ferrous alloys, copper alloys, aluminum, aluminum alloys, etc. The phrase metal object" includes any object such as a screw which is metallic, and is in or contacts the bone. The metal object can be clad or coated with other substances such as chrome or stainless steels. Examples of other substances are rigid resinous materials.

The alien materials can be in the form of screws, pins,

and so forth inserted in the bone in order to hold together a fractured bone or merelyinserted in the bone for some other purpose (for example as electrodes). The alien material can also be in any other form, such as, a plate attached to or in contact with the bone (for example, as a plate screwed to two vertbra where an intermediate vertebra has been removed).

As used herein the term mosaic fracture includes minute apophysis fractures, minute smear fractures and micro-stress fractures or lesions.

The term liquefied composition includes slurries, suspensions, solutions, etc.

All of the components of the liquefied composition must be and are substantially non-toxic in the amounts under the conditions of use.

The pH of the liquefied composition should be between about 8 and about 11, and preferably between about 9 and about 10. Each non-necrotic vascular sclerosing agent will produce a different pH at a different concentration levels, so non-toxic agents may be added to adjust the pH level, e.g., sodium dihydrogen phosphate or sodium hydroxide, can be used when sodium oleate or other non-necrotic vascular sclerosing agent is used.

It should be noted that alkali metal salts of fatty acids in general have an alkaline or neutral pH. Examples are: sodium oleate, alkaline pH; potassium acetate, pH of 9.7 (0.1 M); potassium stearate, strongly alkaline pH; sodium stearate, strongly alkaline pH; lithium formate, practically neutral pH; potassium formate, practically neutral pH; sodium acetate, pH of 8.9 (0.1 M); sodium propionate, slightly alkaline pH; sodium morrhuate, alkaline pH; lithium acetate, neutral pH; sodium formate, neutral pH; soidum phylliate, pH of 8.7 to 9.2; and sodium ricinoleate, alkaline pH. The above is usually due to hydrolysis in the aqueous solution.

The preferred non-necrotic vascular sclerosing agent is sodium oleate.

Natural or synthetic fatty acids can be used to form the fatty acid compound. Mixtures of fatty acids can be used to form the fatty acid compound. Mixtures of fatty acids can be used.

Useful fatty acids for forming the fatty acid compounds may be saturated or unsaturated. The useful standard fatty acids are represented by the general formula: RCOOH, where R can be H, an alkyl group, branched or straight chain. Such alkyl groups should contain between 1 and 50 carbon atoms and preferably between 14 and 22 carbon atoms. Examples of useful saturated fatty acids are formic acid, acetic acid, propionic acid, n-butyric acid, isobutyric acid, n-valeric acid, n-caproic acid, n-heptoic acid, caprylic acid, nnonylic acid, capric acid, undecylic acid, lauric acid, tridecyl acid, myristic acid, pentadecylic acid, palmitic acid, margaric acid, stearic acid, nonadecanoic acid, heneiscosanoic acid, triosanic acid, lignoceric acid, pentacosanoic acid, cerotic acid, arachidic acid and behenic acid. Examples of useful unsaturated fatty acids are oleic acid, linoleic acid, licanic acid, eleostearic acid, ricinoleic acid, clupanodonic acid and palmitoleic acid. The useful unsaturated fatty acids can be those containing one double bone, e.g., oleic acid, two double bonds, e.g., linoleic acid, three double bonds, e.g., eleostearic acid, etc.

Useful fatty acids for forming the fatty acid salts which contain one or more hydroxyl groups are, e.g., dihydroxystearic acid. Useful hydrogenated fatty acids are cod liver oil fatty acids, tallow fat fatty acids, castor oil fatty acids, rape oil fatty acids, peanut oil fatty acids, linseed oil fatty acids, tung oil fatty acids, oiticia oil fatty acids, lard oil fatty acids, neats foot oil fatty acids, whale oil fatty acids, olive oil fatty acids, coconut fat fatty acids, palm fat fatty acids, butter fat fatty acids, lard fat fatty acids and fish oil fatty acids. The useful hydrogenated fatty acids can be obtained from vegetable oils and fats, and animal oils and fats. Polymeric fatty acids can be used.

The fatty acid compound can be a fatty acid salt. The fatty acid salts can be those prepared from metals, such as, aluminum and alkaline earth metals, e.g., calcium, but are preferably those prepared by alkali metals, e.g., sodium (preferred), lithium, potassium, caesium and rubidium. (Ionic fatty acid compounds of sodium, such as, sodium oleate, are preferred, even though the potassium salts are usually more soluble.) The metals are used as hydroxides, carbonates, etc. The fatty acid salts can be prepared from ammonia and similar non-metallic inorganic bases. The fatty acid compounds can be esterified fatty acids, e.g., methyl formate, ethyl propionate and n-amyl acetate. The fatty acid compounds can be soaps such as the reaction product of fatty acids and organic bases, e.g., methylamine, triethanolamine, monoethanolamine, diethanolamine, phenyl ethanol amine, ephedrine and pseudoephedrine. Fatty acid soaps of mono diand tri-alkyl amines and aryl amines can be used.

US. Pat No. 2,1 15,491, teaches a method of preparing the sodium salts or soaps of the fatty acids of psyllium seed oil. Amine soaps of the fatty acids can be prepared by the method taught by U.s. Pat. No. 2,090,456.

US. Pat. No. 1,767,041 discloses a method of making the product of alkali metals and fatty acids. The other fatty acid compounds can be made by method readily known by those ordinarily skilled in the art.

The liquefied solution should contain between about 0.5 and about 10 percent by weight of the fatty acid compound, and preferably contain between about 1 and about 5 percent by weight of the fatty acid compound.

Examples of specific useful compounds of fatty acids which can be used as non-necrotic vascular sclerosing agents are: sodium oleate (preferred); sodium psylliate (a mixture of the sodium salts of psyllium oil liquid fatty acids); sodium ricinoleate; ethylamine oleate; monoethanolamine oleate; sodium formate; sodium acetate; and calcium propionate. Salts of fatty acids are preferred, particularly those formed from alkali metals, and the preferred fatty acid salt is sodium oleate. Examples of other useful non-necrotic sclerosing agents are dextrose and invert sugar. (Invert sugar is a mixture of dextrose and levulose obtained by the inversion of sucrose.) Solutions containing, for example, dextrose (25 wt. percent) and sodium chloride (15 wt. percent) or invert sugar 30 wt. percent) and sodium chloride (10 wt. percent) can be used. Solutions containing about 50 percent by weight of dextrose are preferred. Solutions containing about 60 to about percent by weight of invert sugar are preferred.

The fatty acid compounds (preparations) are preferred over the other useful non-necrotic vascular sclerosing agents because, for among several reasons, less of the liquefied composition (dosage) is needed. This means the less concentrated fatty acid compound preparations are needed than the more concentrated preparation such as those containing dextrose or invert sugar.

Any non-necrotic fatty acid compound can be used, but preferably a non-necrotic fatty acid compound is used.

Solutions of dextrose or invert sugar or salts of fatty acids are not very irritating and do not produce necro- SIS.

Examples of the liquid carrier for the non-necrotic vascular sclerosing agent are water (preferred); monoglycerides; diglycerides; etc. Water is the preferred liquid carrier, and salt (NaCl) can be added to make an isotonic aqueous solution as the liquid carrier.

The useful vascular sclerosing agents must be nonnecrotic in effect or operation. Sclerosing agents to be useful must not cause the pathologic death of one or more cells, or a portion of tissue or organ, resulting from irreversible damage to the nucleus.'

Anodynes in amounts of up to and including about 5 percent by weight may be added. An anodyne is an agent which has the power to relieve pain. An example of a useful anodyne is benzyl alcohol. In general small amount of antiseptics or anaesthetics can be used.

Suitable preservations can be added in an amount not to exceed 0.5 percent by weight. Up to about 5 weight percent, based on the weight of the total composition, of mild local anesthetics and/or antiseptics can be added. Examples of such materials are chlorobutanol and benzyl alcohol.

The injectable liquefied composition preferably contains a buffering agent, such as, sodium phosphate such as secondary sodium phosphate, sodium carbonate, or the salt of a weak organic acid with a strong base of which sodium citrate is an example. Examples of useful buffers are disodium hydrogen phosphate and sodium dihydrogen phosphate (preferred).

Each dosage preferably contains between 0.1 and c.c., depending on the size, etc., of the man or animal and the bone being treated. More preferably, the dosage usually contains between 0.2 and 5 c.c. When a horse is being treated, the best results are obtained when the dosage is between 0.5 and 3 c.c.

The dosage used in treating bucked shins preferably ranges from 1 to 25 c.c., most preferably 5 to 12 c.c. Treatment of other types of mosaic fractures use amounts that are relative to the size of the fracture area, using the data herein for bucked shins. A series of one-eighth to one-fourth cc are made around the periphery and in the middle regions of the bucked shins or splints. This means that about 30 to 40 small injections are made, preferably in three lines running the length of the afflicted region (one on each side and one down the middle). A large injection of 1 cc or more is not as effective as a number of smaller injections due to the fact that a large mosaic fracture area has to be covered. Such a large injection also forms a lump that takes awhile to dissipate since most of such an injection has not actually been placed at the fracture site and a fatty acid compound is usually not very soluble in body fluid (materials such as ethanol are often used in small amounts to aid in the solubility factor in formulating the dosage).

The following four seats of unsoundness on the equine plus in other animals and man, namely, ringbone, splints, bucked shins and osselets can be successfully treated in much the same manner as a fracture or non-union of a fracture is treated according to this invention. l-leretofore these four sets of unsoundness have been erroneously treated. Each of the four unsoundness have been often classified as a form of periostitis and applicant and others skilled in the art know that this is incorrect. These unsoundnesses are in fact examples of periostostetis.

Periostitis is the inflammation of the periosteum. Periostostetis is the inflammation involving both bone and its connective tissue covering (periosteum), or a mosaic fracture of the bone and periosteum.

Ringbone or (phalangeal exostosis) is new bone growth which occurs on the first, second or third phalanges. It is a result of a periostetis and may lead to an osteoarthritis or ankylosis of the pastern or coffin joints. Splints is a disturbance of the fibrous interosseous ligament, between the second and third metacarpal bones, or between the third and fourth metacarpal bones, causes splints. This irritation to the periosteum and underlying bone causes periostetis and new bone growth. Bucked shins is a periostetis of the dorsal (anterior) surface of the third metacarpal or third metatarsal bone. Bucked shins result from a tearing of the periosteum along the front of the metacarpal bone. Osselets occur at the fetlocks along the anterior margin of the articular cartilage of the large metacarpal bone. When they appear they are hot, painful, and comparatively soft swellings. Radiographs will show a rarefaction of the bone where the joint capsule is attached. Later, calcium will be deposited and an exostosis will form in this area.

Because of the close connection between the periosteum and the bone itself, it is very difficult to determine whether an ostitis is present, however, the applicant feels it is evident and is displayed clinically through the 10 recurrance of lameness and the continued proliferations which lead to ankylosing.

All four of these ailments are created by a traumatic pulling or tearing of the periosteum.

The applicant has invented a cure for splints and bucked shins. If treated properly the boney union enhances the structures. Perhaps it is better explained to say that a healed splint (one that cannot diffuse) is an expediency in fusing the small metacarpal to the large (3rd) metacarpal which would occur in the normal ossification of maturity. Bucked shins if treated to heal properly, produce a more solid union of the periosteum and bone and is an aid to the young horse lacking such maturity. Microstress-fractures must be treated in the same manner as any fracture as the stages of healing are the same, namely, (1) haematoma formation, (2) callus formation, (3) consolidation and (4) remodelling.

In the case of osselets and ringbone, the applicant is disclosing a treatment by which micro-stress-fractures are healed. however not a cure'because mechanical stress involved in faulty conformation would not be corrected and therefore the healing of the micro-stressfractures would retard but could not necessarily prevent the traumatic reoccurence.

To date, 92 horses have been treated successfully for one or more of these four seats of unsoundness using applicants invention.

Unless otherwise stated or indicated, in the following examples, all percentages and proportions are expressed on a weight basis.

The following examples further illustrate, but do not limit this invention.

EXAMPLE 1 An injectable liquefied composition containing 5 weight percent of sodium oleate, 1.5 weight percent of ethanol, enough sodium dihydrogen phosphate to obtain a pH of 9.8 and 50 ml. of sterile distilled water (q.s.). The liquefied composition was placed in several 2 c.c. ampoules. One of the ampoules was used to fill a conventional hypodermic needle syringe. The liquefied solution was injected into the axis or plane of a fresh break of the coffin bone of a horse, the ends being held mutually in alignment during the injection. No cast was used and the horse was not suspended. The treatment was not painful. X-rays indicated that struts were produced, giving rise to sheer and thus alignment. The horse was able to test out the leg and successfully put minor weight on the foot after about ten days. Another injection was made on the tenth day, and about every ten days thereafter until the fracture was substantially cured after about three months.

EXAMPLE 2 Example 1 was repeated, except that the injectable liquefied composition containing the non-necrotic vascular sclerosing agent of Example 1 was replaced with an injectable liquefied composition comprising an aqueous solution (5 c.c. vial) containing 5 percent of sodium psylliate and 2 percent by weight of benzyl alcohol. That aqueous solution had a pH of 8.9 (enough 10% NaOH solution was added to achieve that level). The fracture was substantially cured in about three months after repeated injections.

EXAMPLE 3 Example 1 was repeated, except that the injectable liquefied composition containing the non-necrotic vascular sclerosing agent of Example 1 was replaced with an injectable liquefied composition comprising an aqueous solution aqueous solution (2 c.c. vial) containing percent of sodium psylliate. A NaOH solution was added to obtain a pH level of 8.7. The fracture was substantially cured in about three months after repeated injections.

EXAMPLE 4 Example 1 was repeated, except that the injectable liquefied composition containing the non-necrotic vascular sclerosing agent of Example 1 was replaced with. an injectable liquefied composition comprising an aqueous solution (2 c.c. ampul) containing 5 percent ethylamine oleate and 2 percent benzyl alcohol. The fracture was substantially cured in about three months after repeated injections.

EXAMPLE 5 Example 1 was repeated, except that the injectable liquefied composition containing the non-necrotic vascular sclerosing agent of Example 1 was replaced with an injectable liquefied composition comrising an aqueous solution (2 c.c. ampul) containing 5 percent ethylamine oleate. The fracture was substantially cured in about three months after repeated injections.

EXAMPLE 6 Example 1 was repeated, except that the injectable liquefied composition containing the non-necrotic vascular sclerosing agent of Example 1 was replaced with an injectable liquefied composition containing an aqueous solution (2 c.c. ampul) containing 5 percent of potassium oleate, 3 percent of benzyl alcohol, and enough KOH to bring the pH up to 9.5. The fracture was substantially cured in about three months after repeated injections.

EXAMPLE 7 Example 1 was repeated, except that the injectable liquefied composition containing the non-necrotic vascular sclerosing agent of Example 1 was replaced with an injectable liquefied composition comprising an aqueous solution (2 c.c. vial) containing 2 percent of sodium ricinoleate. That solution has a pH between 8.2 and 8.5. The fracture was substantially cured in about three months after repeated injections.

EXAMPLE 8 Example 1 was repeated, except that the injectable liquefied composition containing the non-necrotic vascular sclerosing agent of Example 1 was replaced with an injectable liquefied composition comprising an aqueous solution (2 c.c.) containing 3 percent sodium oleate. The fracture was substantially cured in about three months after repeated injections.

EXAMPLE 9 Example 1 was repeated, except that the injectable liquefied composition containing the non-necrotic vascular sclerosing agent of Example 1 was replaced with an injectable liquefied composition comprising an aqueous solution (2 c.c. ampul) containing 7 percent of 12 lithium oleate. The fracture was substantially cured in about three months after repeated injections.

EXAMPLE 10 Example 1 was repeated except that the treatment was done to an apex sesamoid fracture of a horse. The fracture was substantially cured in about three months after repeated injections.

EXAMPLE 1 1 Example 1 was repeated except that the treatment was done to a distal sesamoid fracture of a horse. The fracture was substantially cured in about three months after repeated injections.

EXAMPLE 12 Example 1 was repeated except that the treatment was done to a chip fracture in the carpus of a horse. The fracture was substantially cured in about three months after repeated injections.

EXAMPLE 13 A horse was purchased at the Belmont sale and shipped to West Virginia. X-rays showed a complete transverse fracture of the sesamoid. The horse was shipped to Pennsylvania and confined to a stall for eight months. Then a Stineman pin was inserted to hold the fracture. The Stineman pin was removed after two weeks and a screw was inserted. After 3% months, healing was occuring at the fracture sight, however, demineralization (osteolysis) had begun around the screw. After six months the horse was sent to a track and put in light training. The horse remained sound for about 25 days and then pulled up lame. An X-ray showed that demineralization had increased (2 months after pulling up lame). The horse was shipped to the applicants stable and X-rayed; the X-rays showed extensive demineralization around the screw. See FIG. 1. 2 c.c. of an injectable liquefied composition comprising a sterile aqueous solution, containing 5 percent of sodium oleate, 1.5 percent of ethyl alcohol enough sodium dihydrogen phosphate to adjust the pH to 9.8 and 50 ml. of sterile distilled water (q.s.), were injected the same day at one site of the demineralized region around the screw. Seventeen days later 2 c.c. of the sodium oleate solution was injected at one site of the demineralized region. Seven days later 1.5 c.c. of the sodium oleate solution was injected into each of two sites of the demineralized region. Thirty days later, an X-ray was taken of the subject region and the X-ray showed that essentially complete restoration of the demineralization (ossifluent) region to healthy bone had occurred. See FIG. 2.

EXAMPLE 14 Example 13 was repeated, except that the injectable liquefied composition containing the non-necrotic vascular sclerosing agent of Example 13 was replaced with an injectable liquefied composition comprising an aqueous solution (2 c.c. ampoule) containing 5 percent ethylamine oleate and 2 percent benzyl alcohol. The ossifluent region was substantially cured in about two months after repeated injections.

EXAMPLE 15 Example 13 was repeated, except that the injectable liquefied composition containing the non-necrotic vascular sclerosing agent of Example 13 was replaced with an injectable liquefied composition comprising an aqueous solution (5 c.c. vial) containing 5 percent of sodium psylliate and 2 percent of benzyl alcohol. That aqueous solution had a pH of 8.9 (enough NaOH solution was added to achieve that level). The ossifluent region was substantially cured in about two months after repeated injections.

EXAMPLE 16 Example 13 was repeated on a horse having a broken coffin bone. The following procedure was followed to treat the break itself. An injectable liquefied compositioncomprising a sterile aqueous solution containing 5 weight percentof sodium oleate, 1.5 percent of ethanol and enough sodium dihydrogen phosphate to obtain a pH of 9.8 and the remainder water was placed in several 2 c.c..ampoules. One of the ampoules was used to fill a hypodermic needle syringe. The liquefied solution was injected into the axis or plane of the break of the coffin bone of the horse, the ends being held manually in alignment during the injection. See FIG. 3. No cast was used and the horse was not suspended. The treatment was not painful. X-rays indicated that struts (of callus along the line of stress) were produced, giving rise to sheer and thus alignment. The horse was able to test out the leg and successfully put minor weight in a very short time. Another injection was made on the tenth day, and about every ten days thereafter until the fracture was substantially cured.

EXAMPLE 1? Example 16 was repeated, except that the injectable liquefied composition containing the non-necrotic vascular sclerosing agent of Example 16 was replaced with an injectable liquefied composition comprising an aqueous solution (2 c.c. ampoule) containing 5 percent ethylamine oleate and 2 percent benzyl alcohol. The fracture was substantially cured in about three months after repeated injections.

EXAMPLE 18 Example 16 was repeated, except that the injectable liquefied composition containing the non-necrotic vascular sclerosing agent of Example 16 was replaced with an injectable liquefied composition comprising an aqueous solution (5 c.c. vial) containing 5 percent of sodium psylliate and 2 percent by weight of benzyl alcohol. That aqueous solution had a pH of 8.9 (enough NaOH solution was added to achieve that level). The fracture was substantially cured in about three months after repeated injections.

EXAMPLE 19 An injectable liquefied composition containing 5 weight percent of sodium oleate, 1.5 weight percent of ethanol, enough sodium dihydrogen phosphate to obtain a pH of 9.8 and 50 ml. of sterile distilled water (q.s.). The liquefied composition was placed in several 2 c.c. ampoules. One of the ampoules was used to fill a hypodermic needle syringe of the type shown in FIG. 4. The liquefied solution was injected into the interface region between two bones in a leg of a horse to be fused. The treatment was not painful. X-rays indicated that struts were produced, giving rise to fixation and then complete fusion of the bones. The horse used the leg during the entire period of time. Another injection was made on the tenth day, and abotii: every ten days 14 thereafter until the surfaces of the bones were substantially fused after about two months.

EXAMPLE 20 Example 19 was repeated, except that the injectable liquefied composition containing the non-necrotic vascular sclerosing agent of Example l9 was replaced with an injectable liquefied composition comprising an aqueous solution (5 c.c. vial) containing 5 percent of sodium psylliate and 2 percent by weight of benzyl alcohol. That aqueous solution had a pH of 8.9 (enough 10% NaOH solution was added to achieve that level). The surfaces of the bones were substantially fused in about two months after repeated injections.

EXAMPLE 21 EXAMPLE 22 Example 19 was repeated, except that the injectable liquefied composition containing the non-necrotic vascular sclerosing agent of Example 19 was replaced with an injectable liquefied composition comprising an aqueous solution (2 c.c. ampul) containing 5 percent ethylamine oleate and 2 percent benzyl alcohol. The surfaces of the bones were substantially fused in about two months after repeated injections.

EXAMPLE 23 Example 19 was repeated, except that the injectable liquefied composition containing the non-necrotic vascular sclerosing agent of Example 19 was replaced with an injectable liquefied composition comprising an aqueous solution (2 c.c. ampoule) of 1 percent of sodium oleate and enough NaOH to bring the pH up to 9.1. The surfaces of the bones were substantially fused in about two months after repeated injections.

EXAMPLE 24 Example 19 was repeated, except that the injectable liquefied composition containing the non-necrotic vascular sclerosing agent of Example 19 was replaced with an injectable liquefied composition comprising an aqueous solution (2 c.c. ampoule) of a 3 percent solution of sodium oleate and enough KOH to bring the pH up to 9.3. The surfaces of the bones were substantially fused in about two months after repeated injections.

EXAMPLE 25 Using the same injection technique and injectable liquefied composition of Example 19, a piece of bone was fused on both ends to another bone, thereby creating a splint.

EXAMPLE 26 A two-year old thoroughbred (colt) race horse had metacarpal periostetis (bucked shins) on the left and right fore legs. An injection was made into the site of each bucked shin using the injectable liquefied composition of Example 1 (in 10 cc. ampoules). The injection was rnade following the profile of proliferation, distributing 6 c.c. in each leg. There was no reaction to the injection and there was no follow up injection. The accepted healing time for bucked shins is 12 weeks (when not injected using the injectable liquid of this invention). The cold was exercised in 2 days, was pasture sound in 2 days, was returned to training in days, was worked out on a track in 11 days and raced in 18 days. The colt was sound following the work out and race. This establishes the marked acceleration of healing using the injectable liquefied composition of this invention.

EXAMPLE 27 A two-year old thoroughbred (colt) race horse had metacarpal periostetis (bucked shins) on the left and right fore legs. (The bucked shins had been blistered and the colt rested for six weeks; after re-bucking, the bucked shins had been blistered again and then rested; but then the shins re-bucked again.) An injection was made into the site of each bucked shin using the injectable liquefied composition of Example 1 (in 10 c.c. ampoules). The injection was made following the profile of proliferation, distributing 8 c.c. in each leg. There was no reaction fo the injection and there was no follow up injection. The accepted healing time for bucked shins is 12 weeks (when not injected using the injectable liquid of this invention). The cold was exercised in 1 day, was pasture sound in 2 days, was returned to training in 10 days and was worked out on a track in 10 days. The colt was sound following the work out. This establishes the marked acceleration of healing using the injectable liquefied composition of this invention.

EXAMPLE 28 A three-year old thoroughbred race horse (male) had (left fore leg third metacarpal periostetis (bucked shin). The affected area was swollen. (The bucked shin had been previously fired and blistered.) An injection was made into the site of the bucked shin using the injectable liquefied composition of Example 1 (in 10 cc. ampoules). The injection was made following the profile of proliferation, distributing 6 c.c. in the leg. There was some heat and swelling following the injection. There was no follow up injection. The accepted healing time for bucked shins is 12 weeks (when not injected using the injectable liquid of this invention). The colt was exercised in 10 days, and was returned to training in IQ days. The colt was sound following a work out. This establishes the marked acceleration of healing using the injectable liquefied composition of this invention.

EXAMPLE 29 A three-year old thoroughbred race horse (female) left fore leg third metacarpal periostetis (bucked shin), specifically, the anterior surface one half way between the carpus and the first phalax. (The bucked shin had been previously blistered). An injection was made into the site of each bucked shins using the injectable liquefied composition of Example 1 (in 10 cc. ampoules). The injection was made following the profile of proliferation, distributing 6 c.c. in the leg. There was some heat and swelling over the area after the injection. There was no follow up injection. The accepted healing time for bucked shins is 12 weeks (when not injected using the injectable liquid of this invention). The colt was exercised in 12 days, and was returned to training 16 in 12 days. The colt was sound following a work out. This establishes the marked acceleration of healing using the injectable liquefied composition of this invention.

EXAMPLE 30 A two-year old thoroughbred race horse (filly) had metacarpal periostetis (bucked shins) on the left and right fore legs. (The buckes shins had been previously fired.) An injection was made into the site of each bucked shin using the injectable liquefied composition of Example 1 (in 10 cc. ampoules). The injection was made following the profile of proliferation, distributing 6 c.c. in each leg. There was no reaction to the injection and there was no follow up injection. The accepted healing time for bucked shins is 12 weeks (when not injected using the injectable liquid of this invention). The colt was exercised in 2 days, was pastur'e'sound in 2 days, was returned to training in 10 days and was worked out on a track in 18 days. The colt was sound following the work out, and has raced, won and remained sound. This establishes the marked acceleration of healing using the injectable liquefied composition of this invention.

EXAMPLE 31 using the injectable liquid of this invention). The colt was exercised in 2 days, was pasture sound in 2 days, was returned to training in 10 days and was worked out on a track in l 1 days. The colt was sound following the work out, has raced, won and remained sound. This establishes the marked acceleration of healing using the injectable liquefied composition of this invention.

EXAMPLE 32 2 cc of an injectable liquefied composition, the same as the one of Example 1, was injected into the site of ringbone of a horse. The ringbone was healed.

EXAMPLE 33 2 cc. of an injectable liquefied composition, the same as the one of Example 1, was injected into the site of osselets of a horse. The osselets healed.

This invention still further involves another embodiment which includes process of accelerating the death and destruction of bony cells producing unwanted new bone proliferation, say, both without and within joint capsules. This is not a surgical procedure but it is accomplished by injecting a dosage of a liquefied composition comprised of a vascular sclerosing anionic agent and a liquid carrier into and around abnormal new bone proliferations. Subsequent dosages are preferably administered approximately every five days, but the injection interval depends on the density and location of the calcium deposits. This injection method is also used to remove unwanted new bone proliferation which occur immediately around the region of or in the perimeter of a broken bone (or fractured bone or nonunion). This embodiment can be used to treat both man and animal. In a sense, this embodiment involves the absorption of abnormal new bone proliferation. The pertinent portions of applicants copending application serial no. 123,830 are incorporated herein by reference.

Each dosage contains between about 0.1 and about 10 c.c., although a 2 c.c. dosage is normally used. The liquefied composition should contain about 0.5 and about 5 weight percent of a vascular sclerosing anionic agent, and preferably between about 1 and about 3 percent of a vascular sclerosing anionic agent. The liquefied composition should have a pH between 6 and 10, and preferably between about 7 and about 8.1, and most preferably about 7.2.

The preferred liquefied composition is comprised of an aqueous solution of 3 weight percent of sodium tetradecyl sulfate. The preferred liquefied composition contains 2 percent of benzyl alcohol, is buffered with disodium phosphate and is adjusted with sodium dihydrogen phosphate or sodium hydroxide to a pH of about 7 to about 8.1.

This embodiment is often used before a fracture, break or non-union is treated using the injectable liquefied composition of this invention (described above).

The process of this embodiment can also be used to remove arthritic spurs or deposits or growth which result from certain types of arthritis, and can further be used to perform what is commonly known as cosmetic surgery.

What is claimed is:

l. The process of treating a mosaic fracture of the bone and periosteum of man or animal which comprises injecting at least one dosage in an effective amount of a liquefied composition comprised of (a) a non-necrotic fatty acid compound, sclerosing agent and (b) a liquid carrier into the site of the fracture of the periosteum until there is a substantially complete bone union.

2. The process of claim 1 wherein said dosage is between 1 and 25 c.c.

3. The process of claim 1 wherein said dosage is between 0.1 and 10 c.c.

4. The process of claim 1 wherein the carrier is water, and wherein said liquefied composition which has a pH between 8 and 11.

5. The process of claim 1 wherein a buffering agent is present in said liquefied composition.

6. A process as described in claim 1 wherein said liquid carrier is water, wherein said fatty acid compound is present in an amount between about 0.5 and about 10 percent, and wherein said liquefied composition has a pH between about 8 and about 11.

7. The process of claim 2 wherein each of said injections comprises making a number of injections, using a portion of said dosage, in the middle region of and around the periphery of the site of the fracture of the periosteum.

8. The process described in claim 7 wherein said nonnecrotic fatty acid compound is sodium oleate.

9. The process described in claim 2 wherein said liquefied composition is comprised of sodium oleate, up to about 5 percent of ethanol, enough disodium hydrogen phosphate to obtain a pH between about 9 and 10, and water.

10. The process described in claim 2 wherein said fatty acid compound is a fatty acid salt.

11. The process described in claim 10 wherein said fatty acid compound is a salt of an alkali metal and a fatty acid.

12. The process described in claim 11 wherein said liquid carrier is water.

13. The process of treating a mosaic fracture of the bone and periosteum of man or animal which comprises injecting at least one dosage in an effective amount of a liquefied composition comprised of (a) a non-necrotic fatty acid compound, and (b) a liquid carrier into the site of the fracture of the periosteum until there is a substantially complete bone union.

14. The process of claim 13 wherein said dosage is between 1 and 25 c.c.

15. The process of claim 14 wherein each of said injections comprises making a number of injections, using a portion of said dosage, in the middle region of and around the periphery of the site of the fracture of the periosteum.

16. The process described in claim 15 wherein said non-necrotic fatty acid compound is sodium oleate.

17. The process described in claim 14 wherein said liquefied composition is comprised of sodium oleate, up to about 5 percent of ethanol, enough disodium hydrogen phosphate to obtain a pH between about 9 and 10, and water.

18. The process described in claim 14 wherein said fatty acid compound is a fatty acid salt.

19. The process described in claim 18 wherein said fatty acid compound is a salt of an alkali metal and a fatty acid.

20. The process described in claim 19 wherein said liquid carrier is water.

Non-Patent Citations
Reference
1 *Crespin et al., Chem. Abst., Vol. 71 (1969), p. 110518Y
2 *Fewell et al., Chem. Abst., Vol. 66 (1967), p. 64048S
3 *Gutman, Modern Drug Encyclopedia--2nd Edit. (1941) pp. 538, 539, 568 and 961
4 *Rabbeno, Chem. Abst., Vol. 23 (1929), p. 206
5 *Renaud, Chem. Abst., Vol. 25 (1931), p. 30787
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US4224028 *Nov 20, 1978Sep 23, 1980Thiele Geraldine HRetardation of the putrefaction of hides and skins
US7399742 *Dec 21, 2004Jul 15, 2008Depuy Spine, Inc.Anti-osteolytic therapy involving adiponectin
US7955616Sep 12, 2005Jun 7, 2011Orthocon, Inc.Absorbable implants and methods for their use in hemostasis and in the treatment of osseous defects
US7989000Sep 16, 2004Aug 2, 2011Orthocon, Inc.Absorbable putty-like implants and methods for their use for mechanical hemostasis of bone and for the treatment of osseous defects
US8105628Sep 16, 2004Jan 31, 2012Orthocon, Inc.Absorbable implants and methods for their use in hemostasis and in the treatment of osseous defects
US8309131Jun 30, 2011Nov 13, 2012Orthocon, Inc.Absorbable putty-like implants and methods for their use for mechanical hemostasis of bone and for the treatment of osseous defects
US8337879Apr 15, 2011Dec 25, 2012Orthocon, Inc.Absorbable implants and methods for their use in hemostasis and in the treatment of osseous defects
US8603528Jul 25, 2006Dec 10, 2013Abyrx, Inc.Compositions and method for the reduction of post-operative pain
DE3410850A1 *Mar 23, 1984Oct 4, 1984Otsuka Pharma Co LtdArzneimittel zum verstaerken von blutgefaessen und dessen verwendung
Classifications
U.S. Classification514/560, 514/557, 514/558
International ClassificationA61K31/20, A61B17/88
Cooperative ClassificationA61B17/7061, A61K31/20
European ClassificationA61B17/70L, A61K31/20