CA1338907C - 2-hydroxy-n,n,n-trimethylethanaminium salts of 5 beta-cholanic-24 acid derivatives - Google Patents
2-hydroxy-n,n,n-trimethylethanaminium salts of 5 beta-cholanic-24 acid derivativesInfo
- Publication number
- CA1338907C CA1338907C CA000610954A CA610954A CA1338907C CA 1338907 C CA1338907 C CA 1338907C CA 000610954 A CA000610954 A CA 000610954A CA 610954 A CA610954 A CA 610954A CA 1338907 C CA1338907 C CA 1338907C
- Authority
- CA
- Canada
- Prior art keywords
- hydroxy
- beta
- cholanic
- alpha
- dihydroxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0055—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
- C07J41/0061—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives one of the carbon atoms being part of an amide group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
- C07J9/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton
Abstract
2-Hydroxy-N,N,N-trimethylethanaminium salts of 5beta-cholanic-24 acid derivatives, of formula I
Description
This invention provides 2-hy~lo~y-N,N,N-trimethylethanaminium salts (= choline salts) of formula \l O
~ C~I CNI ~ 3NCNzCNzO
/ .
~I), HO ~ 1 wherein R1 and R2, and R3 and R4, independently, together are an oxo group, or are two hydrogen atoms or a hydrogen atom and a hydroxy group, and X is a C-O bond (i.e., a single bond directly o connecting -C- and -O-) or an -NH-CH2-CO- or -NH-(CH2)2-S02- group, X' - 2 - l 338907 which are pharmacologically effective substances which can be used, for example, as active ingredients of cholagogue or biliary tract therapeutic agents, as well as pharmaceutical and cosmetic preparations containing them.
The production of 2-hydroxy-N,N,N-trimethylethanaminium salts (= choline salts) of formula I can be performed under conditions which are well known to one skilled in the art.
lo Thus, for example, the free carboxylic acids of formula II
~ ~ C
, \X-O-Y
/ ^\ ~ ~l~J, Ho ~ ~ 2 wherein R1 and R2, and R3 and R4, independently, together are an oxo group, or are two hydrogen atoms or a hydrogen atom and a hydroxy group, and X is a C-O bond or an -NH-CH2-C0- or -NH-(CH2)2-S02-group, and Y represents a hydrogen or an alkali metal atom, is reacted with a compound of general formula III
z I
(CH3)3-N-HC2-CH2-OH
~ C~I CNI ~ 3NCNzCNzO
/ .
~I), HO ~ 1 wherein R1 and R2, and R3 and R4, independently, together are an oxo group, or are two hydrogen atoms or a hydrogen atom and a hydroxy group, and X is a C-O bond (i.e., a single bond directly o connecting -C- and -O-) or an -NH-CH2-CO- or -NH-(CH2)2-S02- group, X' - 2 - l 338907 which are pharmacologically effective substances which can be used, for example, as active ingredients of cholagogue or biliary tract therapeutic agents, as well as pharmaceutical and cosmetic preparations containing them.
The production of 2-hydroxy-N,N,N-trimethylethanaminium salts (= choline salts) of formula I can be performed under conditions which are well known to one skilled in the art.
lo Thus, for example, the free carboxylic acids of formula II
~ ~ C
, \X-O-Y
/ ^\ ~ ~l~J, Ho ~ ~ 2 wherein R1 and R2, and R3 and R4, independently, together are an oxo group, or are two hydrogen atoms or a hydrogen atom and a hydroxy group, and X is a C-O bond or an -NH-CH2-C0- or -NH-(CH2)2-S02-group, and Y represents a hydrogen or an alkali metal atom, is reacted with a compound of general formula III
z I
(CH3)3-N-HC2-CH2-OH
- 3 - l 3~89~7 wherein Z represents a hydroxy group, if Y is a hydrogen atom, or means the radical of an inorganic acid, if Y is an alkali metal atom;
can be reacted in a polar inert solvent with choline.
Suitable solvents include, for example, lower alcohols (e.g., methanol, ethanol, propanol, isopropanol, etc.) or lower ketones (e.g., acetone, methyl ethyl ketone). On the other hand, dipolar aprotic solvents (e.g., dimethylformamide, hexamethylphosphoric acid triamide, etc.) are also suitable. But the latter generally do not produce any advantages. If lower alcohols and about 0.2 to 1 mol of acid per mol of choline are used, the salts can be isolated in a simple way, by the reaction mixture being concentrated by evaporation and/or the reaction products being precipitated by addition of nonpolar solvents, such as, for example, acetone.
On the other hand, the alkali metal salts of cholanic-24 acid derivatives of formula II (preferably the sodium and potassium salts) can also be reacted with choline salts of inorganic acids (preferably choline chloride or choline sulfate). This reaction can also be performed in inert polar solvents. If the reaction is performed in one of the above-named lower alcohols by use of approximately equimolar amounts of the two reactants, then the reaction product, after filtering off of the alkali metal salt of the inorganic acid, can be isolated in a simple way, by the filtrate being concentrated by evaporation and/or precipitated by addition of nonpolar solvents such as, for example, acetone.
These reaction variants can of course also be performed so that the free acids of formula II are reacted with a choline salt or an inorganic acid in an inert solvent, for example in the presence of alkali - 4 - l 3389~7 metal bicarbonates (e.g., sodium bicarbonate or potassium bicarbonate).
The 2-hydroxy-N,N,N-trimethylethanaminium salts of general formula I have the same pharmacological effect as the 5beta-cholanic-24 acid derivatives of general formula II, wherein R1 and R2 are oxo, and R3, R4 and Y are H.
Further, they exhibit a bactericidal or virucidal effectiveness.
Furthermore, the compounds according to the invention surprisingly exhibit, among other properties, good water solubility, good stability, relatively low basicity, and relatively good resorbability.
For production of pharmaceutical agent specialties the compounds according to the invention optionally are processed with the usual additives and flavorings into tablets, dragees and capsules, which normally contain 50 to 500 mg of active ingredient per dosage unit.
If the pharmaceutical agent specialty is to be used for medicinal dissolution of cholesterol gallstones, in animals, e.g., mammals, e.g., humans, as prophylaxis against gallstone formation or as bactericidal or virucidal agents, 5 to 20 mg of active ingredient per kg of body weight per day is generally administered to the patient, analogously to the known compound It will be appreciated that the actual preferred amounts of active compound in a specific case will vary according to the specific compound being utilized, the particular compositions formulated, the mode of application, and the particular situs and organism being treated. Dosages for a given host can be determined using conventional considerations, e.g., by customary comparison of the differential activities of the subject compounds and of a known agent, e.g., by means of an appropriate, conventional pharmacological protocol.
The great water solubility of the substances according to the invention further also make possible the production of aqueous solutions, which, for example, are suitable for infusion or injection, which can advantageously be used for treatment of primary biliary cirrhosis and primary sclerosing cholangitis as well as also for treatment of organ-caused acute disturbances of the bile flow or of intestinal absorption or which are suitable for irrigation of the bile duct or of the gallbladder by percutaneous transhepatic drainage.
Further, the substances according to the invention are also suitable for making into water/oil and/or oil/water emulsions. The lotions, creams or ointments are suitable as dermatological preparations, for example, for treatment of wounds or as cosmetics. Production of these lotions, creams or ointments takes place according to methods as they are well known to one skilled in the art (Dr. J. Stephen Jellinek "Kosmetologie" [Cosmetology]
2nd edition, 1967, Dr. Alfred Huethig Verlag, Heidelberg (West Germany) and European patent specification 0065 929).
The substances according to the invention are further suitable as galenical auxiliary agents for pharmaceutical preparations of active ingredients to improve their transdermal resorption.
Without further elaboration, it is believed that one ~killed in the art can, using the preceding description, utilize the present invention to its fullest extent. The following preferred specific embodiments are, therefore, to be construed as merely illustrative, and not 19 limitative of the remainder of the disclosure in any way whatsoever.
In the foregoing and in the following examples, all temperatures are set forth uncorrected in degrees Celsius and unless otherwise indicated, all parts and percentages are by weight.
Example 1 21.6 g of sodium salt of 3alpha,7beta-dihydroxy-Sbeta-cholanic-24 acid (= 0.052 mol) is dissolved in 250 ml of ethanol with warming, mixed with a solution of 7.0 g of choline chloride in 50 ml of ethanol and reacted for 2 hours. Then the reaction mixture is allowed to cool, the precipitated common salt is filtered out and the filtrate is largely concentrated by evaporation and the still flowable residue is instilled in 0.5 1 of acetone.
The mixture is stirred for two hours more, the product is suctioned off and dried in a vacuum. Thus, 17.9 g of 2-hydroxy-N,N,N-trimethylethanaminium salt of 3alpha,7beta-dihydroxy-Sbeta-cholanic-24 acid with a melting point of 185 to 190C is obtained.
Example 2 6.05 g of choline (=0.05 mol) is dissolved in S0 ml of ethanol, mixed with 19.6 g of 3alpha,7beta-dihydroxy-Sbeta-cholanic-24 acid (= 0.05 mol) and after dissolution is completed, is evaporated to dryness. The residue is taken up in acetone, the separated crystallizate is suctioned off and dried. 21.6 g of 2-hydroxy-N,N,N-trimethyleth~n~rinium salt of 3alpha,7beta-dihydroxy-Sbeta-cholanic-24 acid with a melting point of 186 to 190C is obtained.
Example 3 6.05 g of choline (0.05 mol) is dissolved in 50 ml of ethanol, mixed with 19.6 of 3alpha,7alpha-5beta-cholanic-24 acid (= 0.05 mol) and, after dissolution is completed, is instilled in 200 ml of acetone. It is stirred for another hour, the separated crystallizate is suctioned off and dried in a vacuum. Thus 20.0 g of 2-hydroxy-N,N,N-trimethylethanaminium salt of 3alpha,7alpha-dihydroxy-5beta-cholanic-24 acid with a melting point of 70 to 75C is obtained.
Example 4 11.7 g of 3alpha,12alpha-dihydroxy-5beta-cholanic-24 acid (= 0.030 mol) is dissolved in 30 ml of ethanol and mixed with 14.3 ml (= 0.030 mol) of a 2.1 molar solution of choline base in ethanol. Then the reaction mixture is instilled in 250 ml of acetone, the precipitate is suctioned off and dried in a vacuum. 12.8 g of 2-hydroxy-N,N,N-trimethylethanaminium salt of 3alpha,12alpha-dihydroxy-5beta-cholanic-24 acid with a melting point of 253 to 255C is obtained.
ExamPle 5 57 g of 3alpha,12beta-dihydroxy-5beta-cholanic-24 acid (= 0.145 mol) is dissolved in 100 ml of ethanol and mixed with a solution of 17.5 g of choline base (145 mmol) in ethanol. Then the ethanol is distilled off, the residue is mixed with 200 ml of acetone, the precipitate is suctioned off and dried in a vacuum.
60 g of 2-hydroxy-N,N,N-trimethylethanaminium salt of 3alpha,12beta-dihydroxy-5beta-cholanic-24 acid with a melting point of 170 to 174.5C is obtained.
Example 6 4.6 g of N-(3alpha,7alpha-dihydroxy-24-oxo-5beta-cholan-24-yl) glycine (= 0.00832 mol) is dissolved in 10 9 _ 1 3 3 8 9 0 7 ml of ethanol and mixed with a solution of 1.0 g of choline base (= 0.00832 mol) in 10 ml of ethanol. Then the mixture is instilled in 200 ml of acetone, stirred for some additional time, the crystals are suctioned off s and dried in a vacuum.
3.6 g of 2-hydroxy-N,N,N-trimethylethanaminium salt of N-(3alpha,7alpha-dihydroxy-24-oxo-5beta-cholan-24-yl) glycine with a melting point of 80 to 83C is obtained.
ExamPle 7 8.04 g of 2-[(3alpha,7beta-dihydroxy-24-oxo-5beta-24-yl)-amino]-ethane sulfonic acid (= 0.0133 mol) is dissolved in 30 ml of ethanol and mixed with a solution of 1.61 g of choline base (= 0.0133 mol) in 16 ml of ethanol. Then the mixture is instilled in 200 ml of acetone, stirred for some additional time, the crystals are suctioned off and dried in a vacuum.
Thus, 6.9 g of 2-hydroxy-N,N,N-trimethylethanaminium salt of 2-t(3alpha,7beta-dihydroxy-24-oxo-5beta-cholan-24-yl)-amino]-ethane sulfonic acid with a melting point of 80 to 85C is obtained.
- lo 1 338 90 7 Example 8 30 g of 3alpha-hydroxy-7-oxo-5beta-cholanic-24 acid (0.1 mol) is suspended in 200 ml of ethanol and mixed with a solution of 12.1 g of choline base (0.1 mol) in 100 ml of ethanol. Then the solvent is distilled off in a vacuum, the residue is mixed with 500 ml of acetone, the precipitate is filtered off and dried in a vacuum.
Thus 37.7 g of 2-hydroxy-N,N,N-trimethylethanaminium salt of 3alpha-hydroxy-7-oxo-5beta-cholanic-24 acid with an indefinite melting point is obtained.
t ~]20 = 11.2 (ethanol).
The preceding examples can be repeated with similar success by substituting the generically or specifically described reactants and/or operating conditions of this invention for those used in the preceding examples.
From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions.
can be reacted in a polar inert solvent with choline.
Suitable solvents include, for example, lower alcohols (e.g., methanol, ethanol, propanol, isopropanol, etc.) or lower ketones (e.g., acetone, methyl ethyl ketone). On the other hand, dipolar aprotic solvents (e.g., dimethylformamide, hexamethylphosphoric acid triamide, etc.) are also suitable. But the latter generally do not produce any advantages. If lower alcohols and about 0.2 to 1 mol of acid per mol of choline are used, the salts can be isolated in a simple way, by the reaction mixture being concentrated by evaporation and/or the reaction products being precipitated by addition of nonpolar solvents, such as, for example, acetone.
On the other hand, the alkali metal salts of cholanic-24 acid derivatives of formula II (preferably the sodium and potassium salts) can also be reacted with choline salts of inorganic acids (preferably choline chloride or choline sulfate). This reaction can also be performed in inert polar solvents. If the reaction is performed in one of the above-named lower alcohols by use of approximately equimolar amounts of the two reactants, then the reaction product, after filtering off of the alkali metal salt of the inorganic acid, can be isolated in a simple way, by the filtrate being concentrated by evaporation and/or precipitated by addition of nonpolar solvents such as, for example, acetone.
These reaction variants can of course also be performed so that the free acids of formula II are reacted with a choline salt or an inorganic acid in an inert solvent, for example in the presence of alkali - 4 - l 3389~7 metal bicarbonates (e.g., sodium bicarbonate or potassium bicarbonate).
The 2-hydroxy-N,N,N-trimethylethanaminium salts of general formula I have the same pharmacological effect as the 5beta-cholanic-24 acid derivatives of general formula II, wherein R1 and R2 are oxo, and R3, R4 and Y are H.
Further, they exhibit a bactericidal or virucidal effectiveness.
Furthermore, the compounds according to the invention surprisingly exhibit, among other properties, good water solubility, good stability, relatively low basicity, and relatively good resorbability.
For production of pharmaceutical agent specialties the compounds according to the invention optionally are processed with the usual additives and flavorings into tablets, dragees and capsules, which normally contain 50 to 500 mg of active ingredient per dosage unit.
If the pharmaceutical agent specialty is to be used for medicinal dissolution of cholesterol gallstones, in animals, e.g., mammals, e.g., humans, as prophylaxis against gallstone formation or as bactericidal or virucidal agents, 5 to 20 mg of active ingredient per kg of body weight per day is generally administered to the patient, analogously to the known compound It will be appreciated that the actual preferred amounts of active compound in a specific case will vary according to the specific compound being utilized, the particular compositions formulated, the mode of application, and the particular situs and organism being treated. Dosages for a given host can be determined using conventional considerations, e.g., by customary comparison of the differential activities of the subject compounds and of a known agent, e.g., by means of an appropriate, conventional pharmacological protocol.
The great water solubility of the substances according to the invention further also make possible the production of aqueous solutions, which, for example, are suitable for infusion or injection, which can advantageously be used for treatment of primary biliary cirrhosis and primary sclerosing cholangitis as well as also for treatment of organ-caused acute disturbances of the bile flow or of intestinal absorption or which are suitable for irrigation of the bile duct or of the gallbladder by percutaneous transhepatic drainage.
Further, the substances according to the invention are also suitable for making into water/oil and/or oil/water emulsions. The lotions, creams or ointments are suitable as dermatological preparations, for example, for treatment of wounds or as cosmetics. Production of these lotions, creams or ointments takes place according to methods as they are well known to one skilled in the art (Dr. J. Stephen Jellinek "Kosmetologie" [Cosmetology]
2nd edition, 1967, Dr. Alfred Huethig Verlag, Heidelberg (West Germany) and European patent specification 0065 929).
The substances according to the invention are further suitable as galenical auxiliary agents for pharmaceutical preparations of active ingredients to improve their transdermal resorption.
Without further elaboration, it is believed that one ~killed in the art can, using the preceding description, utilize the present invention to its fullest extent. The following preferred specific embodiments are, therefore, to be construed as merely illustrative, and not 19 limitative of the remainder of the disclosure in any way whatsoever.
In the foregoing and in the following examples, all temperatures are set forth uncorrected in degrees Celsius and unless otherwise indicated, all parts and percentages are by weight.
Example 1 21.6 g of sodium salt of 3alpha,7beta-dihydroxy-Sbeta-cholanic-24 acid (= 0.052 mol) is dissolved in 250 ml of ethanol with warming, mixed with a solution of 7.0 g of choline chloride in 50 ml of ethanol and reacted for 2 hours. Then the reaction mixture is allowed to cool, the precipitated common salt is filtered out and the filtrate is largely concentrated by evaporation and the still flowable residue is instilled in 0.5 1 of acetone.
The mixture is stirred for two hours more, the product is suctioned off and dried in a vacuum. Thus, 17.9 g of 2-hydroxy-N,N,N-trimethylethanaminium salt of 3alpha,7beta-dihydroxy-Sbeta-cholanic-24 acid with a melting point of 185 to 190C is obtained.
Example 2 6.05 g of choline (=0.05 mol) is dissolved in S0 ml of ethanol, mixed with 19.6 g of 3alpha,7beta-dihydroxy-Sbeta-cholanic-24 acid (= 0.05 mol) and after dissolution is completed, is evaporated to dryness. The residue is taken up in acetone, the separated crystallizate is suctioned off and dried. 21.6 g of 2-hydroxy-N,N,N-trimethyleth~n~rinium salt of 3alpha,7beta-dihydroxy-Sbeta-cholanic-24 acid with a melting point of 186 to 190C is obtained.
Example 3 6.05 g of choline (0.05 mol) is dissolved in 50 ml of ethanol, mixed with 19.6 of 3alpha,7alpha-5beta-cholanic-24 acid (= 0.05 mol) and, after dissolution is completed, is instilled in 200 ml of acetone. It is stirred for another hour, the separated crystallizate is suctioned off and dried in a vacuum. Thus 20.0 g of 2-hydroxy-N,N,N-trimethylethanaminium salt of 3alpha,7alpha-dihydroxy-5beta-cholanic-24 acid with a melting point of 70 to 75C is obtained.
Example 4 11.7 g of 3alpha,12alpha-dihydroxy-5beta-cholanic-24 acid (= 0.030 mol) is dissolved in 30 ml of ethanol and mixed with 14.3 ml (= 0.030 mol) of a 2.1 molar solution of choline base in ethanol. Then the reaction mixture is instilled in 250 ml of acetone, the precipitate is suctioned off and dried in a vacuum. 12.8 g of 2-hydroxy-N,N,N-trimethylethanaminium salt of 3alpha,12alpha-dihydroxy-5beta-cholanic-24 acid with a melting point of 253 to 255C is obtained.
ExamPle 5 57 g of 3alpha,12beta-dihydroxy-5beta-cholanic-24 acid (= 0.145 mol) is dissolved in 100 ml of ethanol and mixed with a solution of 17.5 g of choline base (145 mmol) in ethanol. Then the ethanol is distilled off, the residue is mixed with 200 ml of acetone, the precipitate is suctioned off and dried in a vacuum.
60 g of 2-hydroxy-N,N,N-trimethylethanaminium salt of 3alpha,12beta-dihydroxy-5beta-cholanic-24 acid with a melting point of 170 to 174.5C is obtained.
Example 6 4.6 g of N-(3alpha,7alpha-dihydroxy-24-oxo-5beta-cholan-24-yl) glycine (= 0.00832 mol) is dissolved in 10 9 _ 1 3 3 8 9 0 7 ml of ethanol and mixed with a solution of 1.0 g of choline base (= 0.00832 mol) in 10 ml of ethanol. Then the mixture is instilled in 200 ml of acetone, stirred for some additional time, the crystals are suctioned off s and dried in a vacuum.
3.6 g of 2-hydroxy-N,N,N-trimethylethanaminium salt of N-(3alpha,7alpha-dihydroxy-24-oxo-5beta-cholan-24-yl) glycine with a melting point of 80 to 83C is obtained.
ExamPle 7 8.04 g of 2-[(3alpha,7beta-dihydroxy-24-oxo-5beta-24-yl)-amino]-ethane sulfonic acid (= 0.0133 mol) is dissolved in 30 ml of ethanol and mixed with a solution of 1.61 g of choline base (= 0.0133 mol) in 16 ml of ethanol. Then the mixture is instilled in 200 ml of acetone, stirred for some additional time, the crystals are suctioned off and dried in a vacuum.
Thus, 6.9 g of 2-hydroxy-N,N,N-trimethylethanaminium salt of 2-t(3alpha,7beta-dihydroxy-24-oxo-5beta-cholan-24-yl)-amino]-ethane sulfonic acid with a melting point of 80 to 85C is obtained.
- lo 1 338 90 7 Example 8 30 g of 3alpha-hydroxy-7-oxo-5beta-cholanic-24 acid (0.1 mol) is suspended in 200 ml of ethanol and mixed with a solution of 12.1 g of choline base (0.1 mol) in 100 ml of ethanol. Then the solvent is distilled off in a vacuum, the residue is mixed with 500 ml of acetone, the precipitate is filtered off and dried in a vacuum.
Thus 37.7 g of 2-hydroxy-N,N,N-trimethylethanaminium salt of 3alpha-hydroxy-7-oxo-5beta-cholanic-24 acid with an indefinite melting point is obtained.
t ~]20 = 11.2 (ethanol).
The preceding examples can be repeated with similar success by substituting the generically or specifically described reactants and/or operating conditions of this invention for those used in the preceding examples.
From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions.
Claims (7)
1. 2-hydroxy-N,N,N-trimethylethanaminium salts of 3.alpha.-7-dihydroxy-5.beta.-cholanic-24 acids of formula (I) (I) wherein the OH group of position 7 can be in .alpha. or .beta.
position.
position.
2. 2-hydroxy-N,N,N-trimethylethanaminium salts of 2-[(3.alpha.-7-dihydroxy-24 oxo-5.beta.-cholane-24-yl)amino]-ethane sulfonic acids of formula (II) (II) wherein the OH group of position 7 can be in .alpha. or .beta.
position.
position.
3. 2-hydroxy-N,N,N-trimethylethanaminium salts of N-(3.alpha.-7-dihydroxy-24-oxo-5.beta.-cholane-24-yl)glycine of formula (III) (III) wherein the OH group of position 7 can be in .alpha. or .beta.
position.
position.
4. A pharmaceutical composition, comprising: a pharmaceutically effective amount of a salt according to any one of claims 1 to 3; and a pharmaceutically acceptable carrier.
5. A cosmetic composition, comprising: a cosmetically effective amount of salt according to any one of claims 1 to 3; and a cosmetically acceptable carrier.
6. Use of a salt according to any one of claims 1 to 3, for dissolving gallstones, treating primary biliary cirrhosis, treating primary sclerosing cholangitis, or treating bacterial or viral infections.
7. Use of an aqueous solution of a salt according to any one of claims 1 to 3, for irrigating the bile duct or the gallbladder.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP3830932.7 | 1988-09-12 | ||
| DE3830932A DE3830932A1 (en) | 1988-09-12 | 1988-09-12 | 2-HYDROXY-N, N, N-TRIMETHYL ETHANAMINIUM SALTS OF 5SS-CHOLAN-24-ACID DERIVATIVES |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1338907C true CA1338907C (en) | 1997-02-11 |
Family
ID=6362765
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000610954A Expired - Fee Related CA1338907C (en) | 1988-09-12 | 1989-09-11 | 2-hydroxy-n,n,n-trimethylethanaminium salts of 5 beta-cholanic-24 acid derivatives |
Country Status (7)
| Country | Link |
|---|---|
| EP (2) | EP0387325B1 (en) |
| AT (1) | ATE118218T1 (en) |
| AU (1) | AU4131089A (en) |
| CA (1) | CA1338907C (en) |
| DE (2) | DE3830932A1 (en) |
| NZ (1) | NZ230605A (en) |
| WO (1) | WO1990002748A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9212511D0 (en) * | 1992-06-12 | 1992-07-22 | Cortecs Ltd | Pharmaceutical compositions |
| BR112012020110B1 (en) * | 2010-02-10 | 2021-06-08 | Kissei Pharmaceutical Co., Ltd. | fused heterocyclic derivative compound, pharmaceutical composition comprising the same and therapeutic use of said compound |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE593258C (en) * | 1931-09-12 | 1934-02-23 | Egon Gluecksmann | Process for the preparation of salts of bile acids |
| US2589840A (en) * | 1948-08-14 | 1952-03-18 | Fellows Medical Mfg Co Inc | Method of preparing choline salts of bile acids |
| FR2074736A1 (en) * | 1970-01-22 | 1971-10-08 | Prugnaud Robert | Choline dehydrocholate - for treating hepatic and biliary disorders |
| ATA207181A (en) | 1981-05-08 | 1983-09-15 | Schering Wien | COSMETIC AGENT AND METHOD FOR THE PRODUCTION THEREOF |
-
1988
- 1988-09-12 DE DE3830932A patent/DE3830932A1/en not_active Withdrawn
-
1989
- 1989-09-01 DE DE58908984T patent/DE58908984D1/en not_active Expired - Fee Related
- 1989-09-01 EP EP89909564A patent/EP0387325B1/en not_active Expired - Lifetime
- 1989-09-01 EP EP89116158A patent/EP0359058A1/en active Pending
- 1989-09-01 WO PCT/EP1989/001023 patent/WO1990002748A1/en active IP Right Grant
- 1989-09-01 AT AT89909564T patent/ATE118218T1/en not_active IP Right Cessation
- 1989-09-11 CA CA000610954A patent/CA1338907C/en not_active Expired - Fee Related
- 1989-09-11 NZ NZ230605A patent/NZ230605A/en unknown
- 1989-09-12 AU AU41310/89A patent/AU4131089A/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP0387325A1 (en) | 1990-09-19 |
| DE58908984D1 (en) | 1995-03-23 |
| ATE118218T1 (en) | 1995-02-15 |
| AU4131089A (en) | 1990-03-15 |
| DE3830932A1 (en) | 1990-03-15 |
| WO1990002748A1 (en) | 1990-03-22 |
| EP0387325B1 (en) | 1995-02-08 |
| EP0359058A1 (en) | 1990-03-21 |
| NZ230605A (en) | 1992-06-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20080214516A1 (en) | Methods and compositions for inhibiting tumor growth | |
| HU211971A9 (en) | Alkali metal 8,9-dehydroestrone sulfate esters | |
| JPH0137398B2 (en) | ||
| IE860931L (en) | Phenylnaphthalene derivatives | |
| KR970002905B1 (en) | S-(lower fatty acid)-substituted glutathione derivative | |
| US5489576A (en) | Therapeutic agent for hemorrhoidal diseases | |
| JP2921124B2 (en) | Oxidized glutathione alkyl ester | |
| TWI564291B (en) | Agent for regulating the formation of nitrogen monoxide | |
| JP2815179B2 (en) | Anti-inflammatory and / or anti-allergic agent | |
| US4448788A (en) | 11-Deoxoglycyrrhetinic acid hydrogen maleate, process for its production, and its use as a medicine | |
| CA1338907C (en) | 2-hydroxy-n,n,n-trimethylethanaminium salts of 5 beta-cholanic-24 acid derivatives | |
| EP0583566A2 (en) | Process for the preparation of glycine-conjugated bile acids and relative pharmaceutical compositions useful for treating hepatic insufficiency | |
| JP2919870B2 (en) | Liver damage inhibitor | |
| JPS6041658A (en) | Manufacture of novel amino acid derivative | |
| CA2087145C (en) | Composition for accelerating wound healing | |
| WO1990013557A1 (en) | New s-adenosylmethionine derivative | |
| JPH05112463A (en) | Therapeutic agent for cataract | |
| LU81745A1 (en) | N- (1-METHYL-2-PYRROLIDINYL METHYL) -2,3-DIMETHOXY 5-METHYL-SULFAMOYL BENZAMIDE AND DERIVATIVES THEREOF, THEIR PREPARATION METHODS AND THEIR APPLICATION IN THE TREATMENT OF LOWER URINARY DISORDERS | |
| EA008003B1 (en) | Cetylpyridinium salt of an anti-inflammatory agent and pharmaceutical compositions containing it | |
| JPH0667846B2 (en) | Choleretic agent | |
| KR970008483B1 (en) | New n-4-salisylamide -2-amino-6-piperidimopyridine-3-oxide, process for preparing the same and a hair tonic composition containing the same | |
| CA1243682A (en) | Pharmaceutical addition compound between econazole and acexamic acid | |
| JPH04500514A (en) | 2-Hydroxy-N,N,N-trimethyl-ethanaminium salt of 5β-cholan-24-acid derivative | |
| JPS60132956A (en) | S-alkylthio-l-cysteine sulfoxide compound and its preparation, drug for alleviating hyperlipemia and liver enhancing gent containing it | |
| JPS63258421A (en) | Anti-inflammatory drug containing sugar lactam |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKLA | Lapsed |