US2778769A - Heparin-aminobenzoate compositions - Google Patents
Heparin-aminobenzoate compositions Download PDFInfo
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- US2778769A US2778769A US254809A US25480951A US2778769A US 2778769 A US2778769 A US 2778769A US 254809 A US254809 A US 254809A US 25480951 A US25480951 A US 25480951A US 2778769 A US2778769 A US 2778769A
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- heparin
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- solution
- water
- aminobenzoate
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- 239000000203 mixture Substances 0.000 title claims description 8
- 229940064734 aminobenzoate Drugs 0.000 title claims description 5
- 229920000669 heparin Polymers 0.000 claims description 14
- 229960002897 heparin Drugs 0.000 claims description 11
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 10
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 claims description 3
- 239000003589 local anesthetic agent Substances 0.000 claims description 3
- 239000012265 solid product Substances 0.000 claims description 2
- 239000000243 solution Substances 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 239000007787 solid Substances 0.000 description 13
- 239000003146 anticoagulant agent Substances 0.000 description 7
- 229940127219 anticoagulant drug Drugs 0.000 description 7
- 238000005119 centrifugation Methods 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- VWZAGCZUPZKTET-UHFFFAOYSA-N 3-(dibutylamino)propyl 4-aminobenzoate;sulfuric acid Chemical compound OS(O)(=O)=O.CCCCN(CCCC)CCCOC(=O)C1=CC=C(N)C=C1.CCCCN(CCCC)CCCOC(=O)C1=CC=C(N)C=C1 VWZAGCZUPZKTET-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 229960004598 butacaine sulfate Drugs 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 102000004895 Lipoproteins Human genes 0.000 description 3
- 108090001030 Lipoproteins Proteins 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 150000004676 glycans Chemical class 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 229920001282 polysaccharide Polymers 0.000 description 3
- 239000005017 polysaccharide Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000023555 blood coagulation Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 239000004570 mortar (masonry) Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- -1 sulfuric acid ester Chemical class 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000007330 LDL Lipoproteins Human genes 0.000 description 1
- 108010007622 LDL Lipoproteins Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 229910021607 Silver chloride Inorganic materials 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- XXXHSQBVHSJQKS-UHFFFAOYSA-N amino benzoate Chemical class NOC(=O)C1=CC=CC=C1 XXXHSQBVHSJQKS-UHFFFAOYSA-N 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 229960003369 butacaine Drugs 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- JLYIJXURSRVSOT-UHFFFAOYSA-N methyl 3,4-dihydroxy-6-methoxy-5-sulfooxyoxane-2-carboxylate Chemical compound COC1OC(C(=O)OC)C(O)C(O)C1OS(O)(=O)=O JLYIJXURSRVSOT-UHFFFAOYSA-N 0.000 description 1
- 230000014508 negative regulation of coagulation Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000010414 supernatant solution Substances 0.000 description 1
- GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
- C08B37/0075—Heparin; Heparan sulfate; Derivatives thereof, e.g. heparosan; Purification or extraction methods thereof
Definitions
- This invention relates to new compositions of matter which have useful therapeutic efiects.
- the invention includes the new substances, preparations containing the same, their use and methods by which they are prepared.
- sulfated polysaccharides notably heparin
- these substances have been known for some time to be anti-coagulants and when injected into an animal increase the blood clotting time. It has also been found that heparin and related anti-coagulants have an effect on the lipoproteins in the bloodstream; in pathological conditions low density lipo-proteins are thus converted to higher density molecules, which reduces the tendency to form deposits of these materials in the vascular system. For this latter purpose, it is desirable that relatively low levels of the anti-coagulants be present in the bloodstream over a considerable period of time.
- the anti-coagulant action of heparin and related anticoagulants is found to be of comparatively short duration and in injection of 50 to 100 mg.
- heparin for example, in an adult patient may lose its effect on bloodclotting in 5 or 6 hours due to the fact that it is rapidly excreted or broken down in the body.
- some progress in prolonging the action of heparin following injection has been made by incorporating it in a menstruum which delays the absorption, yet it is found that these are only partially successful and unduly painful to the patient. As a result, many patients are reluctant to continue medication with the drug and the full advantages of such therapy cannot be generally realized.
- compositions of the present invention to maintain in the patient satisfactory levels of the drugs with a single relatively painless injection the effects of which last for several days. This enables the clotting time of the blood to be prolonged for a protracted period and also enables the efiect of the heparin on the lipoproteins to be maintained.
- anti-coagulant sulfated polysaccharides which may be reacted in accordance with the present invention to provide new compositions of matter are generally of high molecular weight. Several of these are commercially available and their use in the process of the present invention is shown in specific examples which follow.
- amino benzoates which may be reacted with the sulfated anti-coagulants have the following general formula:
- Example 2 To a solution of 5 parts sodium heparinate in 200 volumes of water at 45 C. was slowly added a solution of 15 parts Butacaine sulfate in 400 volumes of water; a cream colored finely divided solid precipitated immediately. This solid was separated from the supernatant by centrifugation for 15 minutes at 1850 R. P. M. The deep cream colored residue was washed three times with 150 volumes of water, each time removing the supernatant by centrifugation for 15 minutes at 1850 R. P. M. Weight of the wet residue of Butacaine-heparin was 30.6 parts.
- Example 3 To a solution of 1 part of the sulfuric acid ester of polyanhydromannuronic acid, sold under the name Paritol- A, in 25 volumes of water at 25 C. was slowly added with stirring a solution of 3 parts Butacaine sulfate in 25 volumes of water. A heavy white finely divided precipitate formed immediately and settled quickly.
- This white Butacaine-Paritol-A salt was filtered on a sintered glass funnel, washed with 50 volumes of water, and dried in a vacuum desiccator over anhydrous magnesium sulfate to give 2.61 parts of a hard vitreous solid, which was readily pulverized in a mortar and pestle to a fine white powder. The product melted to a viscous oil between 124-140" C. with decomposition.
- Example 4 To 0.05 part of the sodium salt of sulfated polygalacturonic acid methyl ester methyl glycoside, sold under the name Treburon, in 2 volumes of 0.9 sodium chloride solution was slowly added 3.08 volumes of 0.1 N silver nitrate solution in order to remove chloride ions. The precipitate of silver chloride was removed by centrifugation. To the supernatant solution of-Treburon at 25 C. was slowly added 0.15 part of Butacaine sulfate in 5 volumes -of Water. A white, finely divided solid precipitated.
- This Butacaine-Treburon salt was filtered on a sintered glass funnel, washed with "20 volumes of water and dried in a vacuum desiccator over anhydrous magnesium sulfate to give 0.110 part of :a hard vitreous solid, which was readily pulverized in a mortar and pestle to a fine 'w'hite powder. The product melted to a viscous oi l between 155-165 C. with slight decomposition.
- Example 5 To a 2 volume portion of a 30% aqueous solution of sodium heparinate was slowly added 2 volumes of a 30% aqueous solution of 2-.dimethylaminoethyl p-butylaminobenzoate hydrochloride. .An oily collodial solution was formed which changed slowly to a gummy very finely divided solid after standing at room temperature. The solids were separated by centrifugation, washed twice with volumes of water and dried in :a vacuum desiccator over anhydrous magnesium sulfate to a gummy vitreous solid.
- Example 6 To .a 2 volume portion of va 30% aqueous solution .of sodium heparinate is slowly :added 2 volumes of a 30% aqueous solution of .S-dimethylamino-LZ-dipropyl paminobenzoate hydrochloride. .An oily collodial :solution was formed which .changed to a gummy very timely divided solid aliter standing .at room temperature. The solid was separated by centrifugation, washed twice with '10 volumes of water and dried .in a vacuum desiccator over anhydrous magnesium sulfate "to .a gummy vitreous solid.
- a new composition of matter comprising the solid product obtained by reacting substantially equivalent amounts of heparin and an aminobenzoate local anesthetic having the following formula References Cited in the file of this patent UNITED STATES PATENTS 2,100,054 .Hopkinson Nov. 23, 1937 2,487,975 .Koree Nov. 15, 1949 2,508,433 Snyder May 23, 1950 2,561,384 Lee July 24, 1951 FOREIGN PATENTS 653,368 Great Britain May 16, 1951 OTHER REFERENCES Loomis: I. Pharmacol. and Exptl. Therap., vol. 104,
- Vorzimer J. A. M. A., vol. 138, No. 10, pp. 747-8. Clinical Medicine, August 1948, p. 197.
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- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
United States Patent HEP-AMINOBENZOATE COMPOSITIONS Marvin Jay Fahrenbach, Pearl River, and Kenneth Austen Burke, Nanuet, N. Y., assignors to American Cg'ltc lnamid Company, New York, N. Y., a corporation 0 alne No Drawing. Application November 3, 1951, Serial No. 254,809
4 Claims. (Cl. 167-74) This invention relates to new compositions of matter which have useful therapeutic efiects. The invention includes the new substances, preparations containing the same, their use and methods by which they are prepared.
In recent years certain sulfated polysaccharides, notably heparin, have had an increased use in medicine in the treatment of diseases of the vascular system. These substances have been known for some time to be anti-coagulants and when injected into an animal increase the blood clotting time. It has also been found that heparin and related anti-coagulants have an effect on the lipoproteins in the bloodstream; in pathological conditions low density lipo-proteins are thus converted to higher density molecules, which reduces the tendency to form deposits of these materials in the vascular system. For this latter purpose, it is desirable that relatively low levels of the anti-coagulants be present in the bloodstream over a considerable period of time.
The anti-coagulant action of heparin and related anticoagulants is found to be of comparatively short duration and in injection of 50 to 100 mg. of heparin, for example, in an adult patient may lose its effect on bloodclotting in 5 or 6 hours due to the fact that it is rapidly excreted or broken down in the body. Although some progress in prolonging the action of heparin following injection has been made by incorporating it in a menstruum which delays the absorption, yet it is found that these are only partially successful and unduly painful to the patient. As a result, many patients are reluctant to continue medication with the drug and the full advantages of such therapy cannot be generally realized.
We have discovered that heparin and other sulfated polysaccharides having anti-coagulant activity can be reacted with certain local anesthetics of the amino-benzoate type to form insoluble compounds which can be injected in the patient with less pain. Of perhaps greater importance is thesurprising discovery that these compounds maintain a therapeutic level of the anti-coagulant in the bloodstream of sufficient eflect to allow the lipoproteins to reach their normal density, and this effect is maintained for a matter of days. Accordingly, it is possible by the use of the compositions of the present invention to maintain in the patient satisfactory levels of the drugs with a single relatively painless injection the effects of which last for several days. This enables the clotting time of the blood to be prolonged for a protracted period and also enables the efiect of the heparin on the lipoproteins to be maintained.
The anti-coagulant sulfated polysaccharides which may be reacted in accordance with the present invention to provide new compositions of matter are generally of high molecular weight. Several of these are commercially available and their use in the process of the present invention is shown in specific examples which follow.
The amino benzoates which may be reacted with the sulfated anti-coagulants have the following general formula:
"ice
To a solution of 1 part sodium hepalinate in 25 volumes of water at 25 C. was slowly added a solution of 3 parts S-dibutylaminopropyl p-aminobenzoate sulfate, sold un der the name Butacaine sulfate, in volumes of water. A white, finely divided precipitate formed immediately. The pH of this slurry was about 5.0. After stirring for 10 minutes at 25 C., the white solid was filtered on a sintered glass funnel, washed with 50 volumes of water, them redissolved in 200 volumes of 50% alcohol. This solution had a colloidal appearance. After filtration of the solution, the filtrate and wash (250 volumes) still remained slightly colloidal in appearance. By drying an aliquot, it was shown that there were 3 parts of the Butacaine-heparin salt present.
Dilution of one part of the above solution to 18 and 180 parts by volume with water resalted in a solution which contained 0.00067 and 0.000067 part respectively of heparin-butacaine per volume. Injection of 0.5 volume of these two solutions into white rats once a day for 3 days resulted in no gross toxicity. By the virtue of the high molecular weight and variable composition of heparin, the products that are obtained in accordance with the above procedure and in other examples are not sharply characteristic in physical properties such as melting point or crystalline structure.
Example 2 To a solution of 5 parts sodium heparinate in 200 volumes of water at 45 C. was slowly added a solution of 15 parts Butacaine sulfate in 400 volumes of water; a cream colored finely divided solid precipitated immediately. This solid was separated from the supernatant by centrifugation for 15 minutes at 1850 R. P. M. The deep cream colored residue was washed three times with 150 volumes of water, each time removing the supernatant by centrifugation for 15 minutes at 1850 R. P. M. Weight of the wet residue of Butacaine-heparin was 30.6 parts. A 5.2 part aliquot of this residue was dried in a vacuum desiccator over concentrated sulfuric acid to give 1.6 parts of a light tan colored solid which pulverized easily to a fine particle size. The product melted to a viscous oil between -125 C.
Example 3 To a solution of 1 part of the sulfuric acid ester of polyanhydromannuronic acid, sold under the name Paritol- A, in 25 volumes of water at 25 C. was slowly added with stirring a solution of 3 parts Butacaine sulfate in 25 volumes of water. A heavy white finely divided precipitate formed immediately and settled quickly. This white Butacaine-Paritol-A salt was filtered on a sintered glass funnel, washed with 50 volumes of water, and dried in a vacuum desiccator over anhydrous magnesium sulfate to give 2.61 parts of a hard vitreous solid, which was readily pulverized in a mortar and pestle to a fine white powder. The product melted to a viscous oil between 124-140" C. with decomposition.
. Example 4 To 0.05 part of the sodium salt of sulfated polygalacturonic acid methyl ester methyl glycoside, sold under the name Treburon, in 2 volumes of 0.9 sodium chloride solution was slowly added 3.08 volumes of 0.1 N silver nitrate solution in order to remove chloride ions. The precipitate of silver chloride was removed by centrifugation. To the supernatant solution of-Treburon at 25 C. was slowly added 0.15 part of Butacaine sulfate in 5 volumes -of Water. A white, finely divided solid precipitated. This Butacaine-Treburon salt was filtered on a sintered glass funnel, washed with "20 volumes of water and dried in a vacuum desiccator over anhydrous magnesium sulfate to give 0.110 part of :a hard vitreous solid, which was readily pulverized in a mortar and pestle to a fine 'w'hite powder. The product melted to a viscous oi l between 155-165 C. with slight decomposition.
Example 5 To a 2 volume portion of a 30% aqueous solution of sodium heparinate was slowly added 2 volumes of a 30% aqueous solution of 2-.dimethylaminoethyl p-butylaminobenzoate hydrochloride. .An oily collodial solution was formed which changed slowly to a gummy very finely divided solid after standing at room temperature. The solids were separated by centrifugation, washed twice with volumes of water and dried in :a vacuum desiccator over anhydrous magnesium sulfate to a gummy vitreous solid.
Example 6 To .a 2 volume portion of va 30% aqueous solution .of sodium heparinate is slowly :added 2 volumes of a 30% aqueous solution of .S-dimethylamino-LZ-dipropyl paminobenzoate hydrochloride. .An oily collodial :solution was formed which .changed to a gummy very timely divided solid aliter standing .at room temperature. The solid was separated by centrifugation, washed twice with '10 volumes of water and dried .in a vacuum desiccator over anhydrous magnesium sulfate "to .a gummy vitreous solid.
What we claimis:
1. A new composition of matter comprising the solid product obtained by reacting substantially equivalent amounts of heparin and an aminobenzoate local anesthetic having the following formula References Cited in the file of this patent UNITED STATES PATENTS 2,100,054 .Hopkinson Nov. 23, 1937 2,487,975 .Koree Nov. 15, 1949 2,508,433 Snyder May 23, 1950 2,561,384 Lee July 24, 1951 FOREIGN PATENTS 653,368 Great Britain May 16, 1951 OTHER REFERENCES Loomis: I. Pharmacol. and Exptl. Therap., vol. 104,
No. 1, pp. 87-92, January 1952. (Recdfor publication Oct. 8., 1951.) (Copy in POSL 167-65.5A').
Vorzimer: J. A. M. A., vol. 138, No. 10, pp. 747-8. Clinical Medicine, August 1948, p. 197.
'Punde'l: Presse Med, vol. 57 ('Dec. 3, 1949), pp. 1120-1.
I. A. M. A., vol. 139., No. 13, p. 883, March 26, 1949.
Scott: Royal Soc. Canada, 3rd series, sect. V, 1942, pp. 49-51.
.Proc. Stall Meetings Mayo Clinic, Dec. 10, 1947, pp. 567-570.
Claims (1)
1. A NEW COMPOSITION OF MATTER COMPRISING THE SOLID PRODUCT OBTAINED BY REACTING SUBSTANTIALLY EQUIVALENT AMOUNTS OF HEPARIN AND AN AMINOBENZOATE LOCAL ANESTHETIC HAVING THE FOLLOWING FORMULA
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US254809A US2778769A (en) | 1951-11-03 | 1951-11-03 | Heparin-aminobenzoate compositions |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US254809A US2778769A (en) | 1951-11-03 | 1951-11-03 | Heparin-aminobenzoate compositions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US2778769A true US2778769A (en) | 1957-01-22 |
Family
ID=22965672
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US254809A Expired - Lifetime US2778769A (en) | 1951-11-03 | 1951-11-03 | Heparin-aminobenzoate compositions |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US2778769A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3062716A (en) * | 1960-02-08 | 1962-11-06 | Applic Chimiques D Etudes Et D | Method of treating hemorrhoids |
| US3244594A (en) * | 1962-01-12 | 1966-04-05 | Egyt Gyogyszervegyeszeti Gyar | 1, 6-bis-(beta-chloro-ethyl-amino)-1, 6-deoxy-d-mannitol heparinate |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2100054A (en) * | 1933-10-27 | 1937-11-23 | Ostro Res Lab Inc | Anesthetic tannate |
| US2487975A (en) * | 1947-02-14 | 1949-11-15 | Jacques Loewe Res Foundation I | Therapeutic preparations for intramuscular or subcutaneous injection and methods of making the same |
| US2508433A (en) * | 1946-10-16 | 1950-05-23 | Wyeth Corp | Alginic acid sulfate anticoagulant |
| GB653368A (en) * | 1948-11-24 | 1951-05-16 | Hoffmann La Roche | Salts of heparinic acid with organic bases and process for manufacture of same |
| US2561384A (en) * | 1949-06-04 | 1951-07-24 | Hoffmann La Roche | Decamethylenediamine salt of heparin |
-
1951
- 1951-11-03 US US254809A patent/US2778769A/en not_active Expired - Lifetime
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2100054A (en) * | 1933-10-27 | 1937-11-23 | Ostro Res Lab Inc | Anesthetic tannate |
| US2508433A (en) * | 1946-10-16 | 1950-05-23 | Wyeth Corp | Alginic acid sulfate anticoagulant |
| US2487975A (en) * | 1947-02-14 | 1949-11-15 | Jacques Loewe Res Foundation I | Therapeutic preparations for intramuscular or subcutaneous injection and methods of making the same |
| GB653368A (en) * | 1948-11-24 | 1951-05-16 | Hoffmann La Roche | Salts of heparinic acid with organic bases and process for manufacture of same |
| US2561384A (en) * | 1949-06-04 | 1951-07-24 | Hoffmann La Roche | Decamethylenediamine salt of heparin |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3062716A (en) * | 1960-02-08 | 1962-11-06 | Applic Chimiques D Etudes Et D | Method of treating hemorrhoids |
| US3244594A (en) * | 1962-01-12 | 1966-04-05 | Egyt Gyogyszervegyeszeti Gyar | 1, 6-bis-(beta-chloro-ethyl-amino)-1, 6-deoxy-d-mannitol heparinate |
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