CA2061196C - Acetylsalicyloyl l-carnitine and process for its preparation - Google Patents
Acetylsalicyloyl l-carnitine and process for its preparation Download PDFInfo
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- CA2061196C CA2061196C CA 2061196 CA2061196A CA2061196C CA 2061196 C CA2061196 C CA 2061196C CA 2061196 CA2061196 CA 2061196 CA 2061196 A CA2061196 A CA 2061196A CA 2061196 C CA2061196 C CA 2061196C
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- Prior art keywords
- trimethylammonio
- acetoxybenzoyloxy
- pharmaceutically acceptable
- butyric acid
- acid betaine
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- 238000000034 method Methods 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title claims description 3
- XOXKBVCLTJWGTD-BZSJEYESSA-N C(C)(=O)C([C@](O)(CC([O-])=O)C(C=1C(O)=CC=CC1)=O)[N+](C)(C)C Chemical compound C(C)(=O)C([C@](O)(CC([O-])=O)C(C=1C(O)=CC=CC1)=O)[N+](C)(C)C XOXKBVCLTJWGTD-BZSJEYESSA-N 0.000 title description 5
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 claims abstract description 34
- 229960003237 betaine Drugs 0.000 claims abstract description 17
- 150000003839 salts Chemical class 0.000 claims abstract description 13
- IHWNOPAHRHEFIE-UHFFFAOYSA-N CC(=O)OC1=CC=CC=C1C(=O)OC(CC([O-])=O)C[N+](C)(C)C Chemical compound CC(=O)OC1=CC=CC=C1C(=O)OC(CC([O-])=O)C[N+](C)(C)C IHWNOPAHRHEFIE-UHFFFAOYSA-N 0.000 claims abstract description 8
- 230000002496 gastric effect Effects 0.000 claims abstract description 8
- 230000000397 acetylating effect Effects 0.000 claims abstract description 3
- 230000000202 analgesic effect Effects 0.000 claims description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 6
- 210000004400 mucous membrane Anatomy 0.000 claims description 6
- 230000001225 therapeutic effect Effects 0.000 claims description 5
- IHWNOPAHRHEFIE-GFCCVEGCSA-N (3r)-3-(2-acetyloxybenzoyl)oxy-4-(trimethylazaniumyl)butanoate Chemical compound CC(=O)OC1=CC=CC=C1C(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C IHWNOPAHRHEFIE-GFCCVEGCSA-N 0.000 claims description 4
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 3
- 239000012346 acetyl chloride Substances 0.000 claims description 3
- 230000021736 acetylation Effects 0.000 claims description 3
- 238000006640 acetylation reaction Methods 0.000 claims description 3
- 230000003197 catalytic effect Effects 0.000 claims description 2
- IHWNOPAHRHEFIE-LBPRGKRZSA-N CC(=O)OC1=CC=CC=C1C(=O)O[C@@H](CC(=O)[O-])C[N+](C)(C)C Chemical compound CC(=O)OC1=CC=CC=C1C(=O)O[C@@H](CC(=O)[O-])C[N+](C)(C)C IHWNOPAHRHEFIE-LBPRGKRZSA-N 0.000 claims 3
- IVKTUTOOZFCEQC-UHFFFAOYSA-N C[N+](C)(C)CC(CC([O-])=O)OC(=O)C1=CC=CC=C1O Chemical compound C[N+](C)(C)CC(CC([O-])=O)OC(=O)C1=CC=CC=C1O IVKTUTOOZFCEQC-UHFFFAOYSA-N 0.000 claims 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 1
- 235000011149 sulphuric acid Nutrition 0.000 claims 1
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 abstract description 8
- 229960001138 acetylsalicylic acid Drugs 0.000 abstract description 8
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 abstract description 7
- 229960004203 carnitine Drugs 0.000 abstract description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 4
- 150000001875 compounds Chemical class 0.000 abstract description 2
- 231100000419 toxicity Toxicity 0.000 abstract description 2
- 230000001988 toxicity Effects 0.000 abstract description 2
- 150000003902 salicylic acid esters Chemical class 0.000 abstract 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- -1 acetylsalicyloyl carnitine Chemical compound 0.000 description 6
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- 208000025865 Ulcer Diseases 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 231100000397 ulcer Toxicity 0.000 description 3
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 235000019439 ethyl acetate Nutrition 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 210000003463 organelle Anatomy 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 230000009103 reabsorption Effects 0.000 description 2
- 229960004889 salicylic acid Drugs 0.000 description 2
- 150000003872 salicylic acid derivatives Chemical class 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 239000012345 acetylating agent Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000002337 anti-port Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/22—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated the carbon skeleton being further substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Novel 3-(2-acetoxybenzoyloxy)-4-(trimethylammonio)-butyric acid betaine and its pharmaceutically acceptable salts are disclosed. The compounds are distinguished by high water solubility, minimum toxicity and good gastric tolerance vis-a-vis acetylsalicylic acid and can be prepared by acetylating the corresponding salicylic acid ester of the carnitine.
Description
This invention relates to the novel 3-(2-acetoxybenzoyloxy)-4-(trimethylammonio)-butyric acid betaine acetylsalicyloyl L-carnitine of the general formula:
O
O
. C'3 I (z) C''~'.~ H o ~ / W
~'3 in racemic and optically active form, and pharmaceutically acceptable salts thereof, as well as to a new process for its preparation. As an ester of acetylsalicylic acid with carnitine (acetylsalicyloyl carnitine), 3-(2-acetoxybenzoyloxy)-4-(trimethylammonio)-butyric acid betaine is a salicylic acid derivative with promising therapeutic properties.
Salicylic acid is used to a great extent as an analgetic in the form of its acetyl derivative. Although this acetyl derivative (known, inter alia, as Aspirin*) was originally developed to reduce undesirable side-effects of the previously known salicylic acid, it is nevertheless burdened with some properties which limit its use. Among these disadvantageous properties is, above all, its low water solubility, especially in an acidic environment, such as in gastric juice. The low solubility can lead to precipitation of the active component in the stomach when aqueous solutions are orally administered. This effect is undesirable not only in persons having a sensitive or already damaged gastric mucous membrane, as it may lead to * Trade-mark 2~~I~~6 serious side-effects in these persons, but it also generally delays the reabsorption, and thus postpones the onset of the analgetic effect.
Moreover, acetylsalicylic acid can virtually only be administered orally, and not parenterally, (e. g.
intravenously intraperitoneally) or topically. It is for facilitating a quick response while protecting the gastrointestinal tract that a parenteral application would often be desirable.
Thus, the object of this invention is to provide a salicylic acid derivative which has good water solubility in an acidic environment, a high reabsorption rate and minimum toxicity, and which can be administered both orally and parenterally or topically and exhibits a quick analgetic effect in all forms of administration.
Accordingly, the invention provides 3-(2-acetoxybenzoyloxy)-4-(trimethylammonio)-butyric acid betaine of formula I above. This compound has an asymmetric carbon atom and can therefore occur in two mirror-inverted optically active forms and as a racemic mixture. All forms constitute a part of the invention, however, the enantiomer with (R) configuration, which is derived from the naturally occurring L-carnitine, is preferred.
The advantageous physical and chemical properties, such as high water solubility and a good pH
value of the solution, are, of course, also attained by the (S) enantiomer and the racemate. However, L-carnitine is known as an acyl-group transmitter in fat metabolism. It is actively absorbed in most of the organs of the body via high affinity transport systems and in cellular organelles (mitochondria etc.) via antiport transporters.
There is reason to assume that acetylsalicyloyl L-carnitine also reaches the cells and organelles via these transport systems and that the onset of the analgetic effect is thus accelerated.
O
O
. C'3 I (z) C''~'.~ H o ~ / W
~'3 in racemic and optically active form, and pharmaceutically acceptable salts thereof, as well as to a new process for its preparation. As an ester of acetylsalicylic acid with carnitine (acetylsalicyloyl carnitine), 3-(2-acetoxybenzoyloxy)-4-(trimethylammonio)-butyric acid betaine is a salicylic acid derivative with promising therapeutic properties.
Salicylic acid is used to a great extent as an analgetic in the form of its acetyl derivative. Although this acetyl derivative (known, inter alia, as Aspirin*) was originally developed to reduce undesirable side-effects of the previously known salicylic acid, it is nevertheless burdened with some properties which limit its use. Among these disadvantageous properties is, above all, its low water solubility, especially in an acidic environment, such as in gastric juice. The low solubility can lead to precipitation of the active component in the stomach when aqueous solutions are orally administered. This effect is undesirable not only in persons having a sensitive or already damaged gastric mucous membrane, as it may lead to * Trade-mark 2~~I~~6 serious side-effects in these persons, but it also generally delays the reabsorption, and thus postpones the onset of the analgetic effect.
Moreover, acetylsalicylic acid can virtually only be administered orally, and not parenterally, (e. g.
intravenously intraperitoneally) or topically. It is for facilitating a quick response while protecting the gastrointestinal tract that a parenteral application would often be desirable.
Thus, the object of this invention is to provide a salicylic acid derivative which has good water solubility in an acidic environment, a high reabsorption rate and minimum toxicity, and which can be administered both orally and parenterally or topically and exhibits a quick analgetic effect in all forms of administration.
Accordingly, the invention provides 3-(2-acetoxybenzoyloxy)-4-(trimethylammonio)-butyric acid betaine of formula I above. This compound has an asymmetric carbon atom and can therefore occur in two mirror-inverted optically active forms and as a racemic mixture. All forms constitute a part of the invention, however, the enantiomer with (R) configuration, which is derived from the naturally occurring L-carnitine, is preferred.
The advantageous physical and chemical properties, such as high water solubility and a good pH
value of the solution, are, of course, also attained by the (S) enantiomer and the racemate. However, L-carnitine is known as an acyl-group transmitter in fat metabolism. It is actively absorbed in most of the organs of the body via high affinity transport systems and in cellular organelles (mitochondria etc.) via antiport transporters.
There is reason to assume that acetylsalicyloyl L-carnitine also reaches the cells and organelles via these transport systems and that the onset of the analgetic effect is thus accelerated.
Acyl L-carnitines continue to be easily dissociated by enzymes of the individual cells, so that one can expect a quick release of the salicylate radical.
Studies on rats have already shown an extremely slight acute toxicity of acetylsalicyloyl L-carnitine.
However, dosages of up to 7.000 mg/kg body weight were easily tolerated orally. Furthermore, there were no harmful side-effects observed with intravenous and intraperitoneal administration of therapeutic amounts.
The invention also provides for the production of salts of the acetylsalicyloyl carnitine with pharmaceutically acceptable acids.
According to the invention acetylsalicyloxy carnitine is prepared by acetylating salicyloyl carnitine.
Acetyl chloride or acetic anhydride, in the presence of a catalytic amount of HZSO~, is especially suitable as acetylating agent.
Acetylation takes place advantageously in the presence of acetic acid as solvent and in a temperature range of from ~0°C to 100°C.
Previous experience has shown that, after a reaction time of about 5 hours and after conventional processing, acetylsalicylayl carnitine can be obtained in good yield and with high purity.
It is also within the scope of the process of the invention to subsequently convert the betaine into a corresponding salt by addition of a pharmaceutically acceptable acid.
The following Example illustrates the process according to the invention.
Example Acetylsalicyl~l L-carnitine HC1 0. 95 g of salicoyl L-carnitine HC1 ( [a D - -31.2° (c=l, HZO); melting point: 185-187°C) were mixed with 35 2.35 g of acetyl chloride and 5.0 ml of acetic acid and heated for 5 hours at 60°C. The reaction mixture was subsequently evaporated under vacuum and the residue was suspended with 10.0 ml acetic ester. The crystallized product was rinsed with 5.0 ml of acetic ester and dried under vacuum at 40°C. Thus, 0.95 g of white, crystalline acetylsalicyloyl L-carnitine-HC1 was obtained having a melting point of 154-158°C.
~H-NMR (DMSO-db, 300 MHz) d = 12.9 (br.s, 1H), 8.04 (d, 1H, J=1.9 Hz), 7.73 (t, 1H, J=7.5 Hz), 7.46 (t, 1H, J=7.6 Hz), 7.28 (d, 1H, J=8.0 Hz), 5.70 (m, 1H), 4.08-3.83 (m, 2H), 3.20 (s, 9H), 2.93-2.78 (m, 2H), 2.33 (s, 3H)p [a] D~ - -41.7° (c=1, H20).
Gastric Tolerance Test on Rats (Ulcer Index The (R)-(-)-3-(2-acetoxybenzoyloxy)-4 (trimethylammonio)-butyric acid betaine~HC1 (acetylsalicoyl L-carnitine = ASC) was tested on male rats in comparison to acetylsalicylic acid (ASA) by inducing gastric mucous membrane charges based on the method of Okabe et al., Japan. J. Pharmacol. 1974, 24, 3&3 ff.
The test substances were administered p.o. to the test rats in a 1% carboxymethyl cellulose suspension (1%
CMC ) .
The gastric mucous membrane changes were measured by the Ulcer Index according to Chaumontet et al., Arzneimittelforschung [Pharmacological Research] 1978, 28, 2047-2178.
The results are shown in Table 1.
Table 1 Substance Ulcer Index Number of (U. I.) Rats Tested Comparison1% CMC 1 ml/250 63.00 10 g Comparison ASA200 mgkg~ 300.00 20 Invention ASC200 mgkg~ 170.00 10 Invention ASC500 mgkg~~ 190.00 10 Invention 1000mgkg1 220.00 10 ASC
CMC - carboxymethyl cellulose ASA - acetylsalicylic acid ASC - acetylsalicoyl L-carnitine~HC1
Studies on rats have already shown an extremely slight acute toxicity of acetylsalicyloyl L-carnitine.
However, dosages of up to 7.000 mg/kg body weight were easily tolerated orally. Furthermore, there were no harmful side-effects observed with intravenous and intraperitoneal administration of therapeutic amounts.
The invention also provides for the production of salts of the acetylsalicyloyl carnitine with pharmaceutically acceptable acids.
According to the invention acetylsalicyloxy carnitine is prepared by acetylating salicyloyl carnitine.
Acetyl chloride or acetic anhydride, in the presence of a catalytic amount of HZSO~, is especially suitable as acetylating agent.
Acetylation takes place advantageously in the presence of acetic acid as solvent and in a temperature range of from ~0°C to 100°C.
Previous experience has shown that, after a reaction time of about 5 hours and after conventional processing, acetylsalicylayl carnitine can be obtained in good yield and with high purity.
It is also within the scope of the process of the invention to subsequently convert the betaine into a corresponding salt by addition of a pharmaceutically acceptable acid.
The following Example illustrates the process according to the invention.
Example Acetylsalicyl~l L-carnitine HC1 0. 95 g of salicoyl L-carnitine HC1 ( [a D - -31.2° (c=l, HZO); melting point: 185-187°C) were mixed with 35 2.35 g of acetyl chloride and 5.0 ml of acetic acid and heated for 5 hours at 60°C. The reaction mixture was subsequently evaporated under vacuum and the residue was suspended with 10.0 ml acetic ester. The crystallized product was rinsed with 5.0 ml of acetic ester and dried under vacuum at 40°C. Thus, 0.95 g of white, crystalline acetylsalicyloyl L-carnitine-HC1 was obtained having a melting point of 154-158°C.
~H-NMR (DMSO-db, 300 MHz) d = 12.9 (br.s, 1H), 8.04 (d, 1H, J=1.9 Hz), 7.73 (t, 1H, J=7.5 Hz), 7.46 (t, 1H, J=7.6 Hz), 7.28 (d, 1H, J=8.0 Hz), 5.70 (m, 1H), 4.08-3.83 (m, 2H), 3.20 (s, 9H), 2.93-2.78 (m, 2H), 2.33 (s, 3H)p [a] D~ - -41.7° (c=1, H20).
Gastric Tolerance Test on Rats (Ulcer Index The (R)-(-)-3-(2-acetoxybenzoyloxy)-4 (trimethylammonio)-butyric acid betaine~HC1 (acetylsalicoyl L-carnitine = ASC) was tested on male rats in comparison to acetylsalicylic acid (ASA) by inducing gastric mucous membrane charges based on the method of Okabe et al., Japan. J. Pharmacol. 1974, 24, 3&3 ff.
The test substances were administered p.o. to the test rats in a 1% carboxymethyl cellulose suspension (1%
CMC ) .
The gastric mucous membrane changes were measured by the Ulcer Index according to Chaumontet et al., Arzneimittelforschung [Pharmacological Research] 1978, 28, 2047-2178.
The results are shown in Table 1.
Table 1 Substance Ulcer Index Number of (U. I.) Rats Tested Comparison1% CMC 1 ml/250 63.00 10 g Comparison ASA200 mgkg~ 300.00 20 Invention ASC200 mgkg~ 170.00 10 Invention ASC500 mgkg~~ 190.00 10 Invention 1000mgkg1 220.00 10 ASC
CMC - carboxymethyl cellulose ASA - acetylsalicylic acid ASC - acetylsalicoyl L-carnitine~HC1
Claims (12)
1. 3-(2-Acetoxybenzoyloxy)-4-(trimethylammonio)-butyric acid betaine of the formula:
and pharmaceutically acceptable salts thereof.
and pharmaceutically acceptable salts thereof.
2. (R)-(-)-3-(2-Acetoxybenzoyloxy)-4-(trimethylammonio)-butyric-acid betaine of the formula:
and pharmaceutically acceptable salts thereof.
and pharmaceutically acceptable salts thereof.
3. (S)-(+)-3-(2-Acetoxybenzoyloxy)-4-(trimethylammonio)-butyric acid betaine of the formula:
and pharmaceutically acceptable salts thereof.
and pharmaceutically acceptable salts thereof.
4. 3-(2-Acetoxybenzoyloxy)-4-(trimethylammonio)-butyric acid betaine, or a pharmaceutically acceptable salt thereof, for use as an active therapeutic component.
5. (R)-(-)-3-(2-Acetoxybenzoyloxy)-4-(trimethylammonio) -butyric acid betaine, or a pharmaceutically acceptable salt thereof, for use as an active therapeutic component.
6. (S)-(+)-3-(2-Acetoxybenzoyloxy)-4-(trimethylammonio)-butyric acid betaine or a pharmaceutically acceptable salt thereof, for use as an active therapeutic component.
7. 3-(2-Acetoxybenzoyloxy)-4-(trimethylammonio)-butyric acid betaine, or a pharmaceutically acceptable salt thereof, for use as an analgetic for the protection of the gastric mucous membrane.
8. (R)-(-)-3-(2-Acetoxybenzoyloxy)-4-(trimethylammonio)-butyric acid betaine, or a pharmaceutically acceptable salt thereof, for use as an analgetic for the protection of the gastric mucous membrane.
9. (S)-(+)-3-(2-Acetoxybenzoyloxy)-4-(trimethylammonio) -butyric acid betaine, or a pharmaceutically acceptable salt thereof, for use as an analgetic for the protection of the gastric mucous membrane.
10. A process for the preparation of 3-(2-acetoxybenzoyloxy)-4-(trimethylammonio)-butyric acid betaine, which comprises acetylating 3-(2-hydroxybenzoyloxy)-4-(trimethylammonio)-butyric acid betaine.
11. A process according to claim 10, wherein the acetylation is carried out with acetyl chloride or acetic anhydride in the presence of a catalytic amount of H2SO4.
12. A process according to claim 10 or 11, wherein the acetylation is carried out at a temperature between 40°C and 100°C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2061196 CA2061196C (en) | 1992-02-13 | 1992-02-13 | Acetylsalicyloyl l-carnitine and process for its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2061196 CA2061196C (en) | 1992-02-13 | 1992-02-13 | Acetylsalicyloyl l-carnitine and process for its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2061196A1 CA2061196A1 (en) | 1993-08-14 |
| CA2061196C true CA2061196C (en) | 2002-05-14 |
Family
ID=4149252
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2061196 Expired - Fee Related CA2061196C (en) | 1992-02-13 | 1992-02-13 | Acetylsalicyloyl l-carnitine and process for its preparation |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2061196C (en) |
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1992
- 1992-02-13 CA CA 2061196 patent/CA2061196C/en not_active Expired - Fee Related
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| Publication number | Publication date |
|---|---|
| CA2061196A1 (en) | 1993-08-14 |
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