Production of bile acids

Claim 1

THE METHOD OF PRODUCING SUBSTANTIALLY PURE BILE ACIDS FROM NATURAL ANIMAL BILE, WHICH COMPRISES A. SUBSTANTIALLY DEGYDRAWTING THE NATURAL ANIMAL BILE, B. ESTERFIYING THE SAID DEHYDRATED ANIMAL BILE TREATMENT WITH A SUITABLE ESTERIFICATION AGENT C. SUBJECTING THE THUS ESTERFIED ANIMAL BILE TO A MULTIPHASIC ORGANIC SOLVENT SYSTEM IN ONE PHASE OF WHICH THE BILE ACID FRACTION OF SAID ANIMAL BILE IS SOLUBLE AND THE PIGMENTS AND THE OTHER IMPUTITIES THEREOF ARE NOT SOLUBLE, AND IN THE REMAINING PHASE OF WHICH, THE SAID PIGMENTS AND OTHER IMPURITIES ARE SOLUBLE AND THE BILE ACID FRACTION IS NOT SOLUBLE, D. SEPARATING AND RECOVERING THE BILE ACID FRACTION OF THE ANIMAL BILE, E. TREATING THE SAID BILE ACID FRACTION WITH A SUITABLE GROUP LLA METAL SALT TO OBTAIN THE CORRESPONDING GROUP LLA METAL BILE ACID SALTS, F. TREATING SAID BILE ACID WITH AN ORGANIC SOLVENT IN WHICH SAIDBILE POSSESS DIFFERENTIAL SOLUBILITY PROPERITIES, TO CAUSE THE SEPARATION OF THE DESIRED BILE ACID SALT, G. RECOVERING SAID SEPARATED BILE ACID SALT AND SUBJECTING SAID SALT TO DISSOCATION BY TREATMENT WITH A MINERAL ACID, AND H. RECOVERING THE DESIRED FREE BILE ACID.

Claim 2

THE METHOD OF PRODUCING SUBSTANTIALLY PURE BILE ACIDS FROM NATURAL ANIMAL BILE, WHICH COMPRISES A. SUBSTANTIALLY DEGYDRAWTING THE NATURAL ANIMAL BILE, B. ESTERFIYING THE SAID DEHYDRATED ANIMAL BILE TREATMENT WITH A SUITABLE ESTERIFICATION AGENT C. SUBJECTING THE THUS ESTERFIED ANIMAL BILE TO A MULTIPHASIC ORGANIC SOLVENT SYSTEM IN ONE PHASE OF WHICH THE BILE ACID FRACTION OF SAID ANIMAL BILE IS SOLUBLE AND THE PIGMENTS AND THE OTHER IMPUTITIES THEREOF ARE NOT SOLUBLE, AND IN THE REMAINING PHASE OF WHICH, THE SAID PIGMENTS AND OTHER IMPURITIES ARE SOLUBLE AND THE BILE ACID FRACTION IS NOT SOLUBLE, D. SEPARATING AND RECOVERING THE BILE ACID FRACTION OF THE ANIMAL BILE, E. TREATING THE SAID BILE ACID FRACTION WITH A SUITABLE GROUP LLA METAL SALT TO OBTAIN THE CORRESPONDING GROUP LLA METAL BILE ACID SALTS, F. TREATING SAID BILE ACID WITH AN ORGANIC SOLVENT IN WHICH SAIDBILE POSSESS DIFFERENTIAL SOLUBILITY PROPERITIES, TO CAUSE THE SEPARATION OF THE DESIRED BILE ACID SALT, G. RECOVERING SAID SEPARATED BILE ACID SALT AND SUBJECTING SAID SALT TO DISSOCATION BY TREATMENT WITH A MINERAL ACID, AND H. RECOVERING THE DESIRED FREE BILE ACID.

Claim 3

The method of proDucing substantially pure 3 Alpha ,7 Alpha -dihydroxy5 Beta -cholanic acid from natural animal bile, which comprises: a. Substantially dehydrating natural animal bile derived from chickens, turkeys, geese, pheasant, pidgeon or duck; b. Esterifying said dehydrated bile by treatment with a suitable organic esterification agent; c. Subjecting the thus esterified bile to a multiphasic organic solvent system containing at least two phases, in one phase of which the bile acid fraction of said natural animal bile is soluble and the pigments and other impurities thereof are not soluble, and in the remaining phases of which the said bile acids are not soluble and the pigments and other impurities are soluble; d. Separating and recovering the bile acid fraction of said animal bile; e. Treating the thus recovered bile acids with a Group IIa metal salt, said Group IIa metal selected from the group consisting of calcium, barium and strontium, to yield the corresponding Group IIa metal bile acid salts; f. Treating said Group IIa metal acid salts with an organic solvent in which the Group IIa metal salt of 3 Alpha ,7 Alpha -dihydroxy-5 Beta -cholanic acid is not soluble, and in which the remaining group IIa metal bile acid salts are soluble; g. Recovering the Group IIa metal salt of 3 Alpha ,7 Alpha -dihydroxy-5 Beta -cholanic acid and subjecting it to dissociation by treatment with a mineral acid; and h. Recovering the resultant free 3 Alpha ,7 Alpha -dihydroxy-5 Beta -cholanic acid.

Claim 4

The method of proDucing substantially pure 3 Alpha ,7 Alpha -dihydroxy5 Beta -cholanic acid from natural animal bile, which comprises: a. Substantially dehydrating natural animal bile derived from chickens, turkeys, geese, pheasant, pidgeon or duck; b. Esterifying said dehydrated bile by treatment with a suitable organic esterification agent; c. Subjecting the thus esterified bile to a multiphasic organic solvent system containing at least two phases, in one phase of which the bile acid fraction of said natural animal bile is soluble and the pigments and other impurities thereof are not soluble, and in the remaining phases of which the said bile acids are not soluble and the pigments and other impurities are soluble; d. Separating and recovering the bile acid fraction of said animal bile; e. Treating the thus recovered bile acids with a Group IIa metal salt, said Group IIa metal selected from the group consisting of calcium, barium and strontium, to yield the corresponding Group IIa metal bile acid salts; f. Treating said Group IIa metal acid salts with an organic solvent in which the Group IIa metal salt of 3 Alpha ,7 Alpha -dihydroxy-5 Beta -cholanic acid is not soluble, and in which the remaining group IIa metal bile acid salts are soluble; g. Recovering the Group IIa metal salt of 3 Alpha ,7 Alpha -dihydroxy-5 Beta -cholanic acid and subjecting it to dissociation by treatment with a mineral acid; and h. Recovering the resultant free 3 Alpha ,7 Alpha -dihydroxy-5 Beta -cholanic acid.

Claim 9

The method of producing substantially pure bile acids from natural animal bile, which comprises: a. Substantially dehydrating the natural animal bile; b. Esterifying the said dehydrated animal bile; c. Treating the thus esterified animal bile with a multiphasic organic solvent system, in one phase of which the bile acid fraction of said animal bile is soluble and the pigments and other impurities of said animal bile are not soluble, and in the remaining phases of said solvent system, the said pigments and impurities are soluble and the said bile acid fraction is not soluble; d. Removing the pigment and other impurity fraction of the animal bile; e. Treating the remaining bile acid fraction with a suitable salt to obtain the corresponding bile acid salts, which possess differential solubilities in an organic solvent; f. Treating said bile acid salts with an organic solvent, in which said bile acid salts possess differential solubility properties to cause separation of the desired bile acid salt; g. Recovering the said separated bile acid salt; h. Dissociating said separated bile acid salt to yield the desired free bile acid.

Claim 10

The method of producing substantially pure bile acids from natural animal bile, which comprises: a. Substantially dehydrating the natural animal bile; b. Esterifying the said dehydrated animal bile; c. Treating the thus esterified animal bile with a multiphasic organic solvent system, in one phase of which the bile acid fraction of said animal bile is soluble and the pigments and other impurities of said animal bile are not soluble, and in the remaining phases of said solvent system, the said pigments and impurities are soluble and the said bile acid fraction is not soluble; d. Removing the pigment and other impurity fraction of the animal bile; e. Treating the remaining bile acid fraction with a suitable salt to obtain the corresponding bile acid salts, which possess differential solubilities in an organic solvent; f. Treating said bile acid salts with an organic solvent, in which said bile acid salts possess differential solubility properties to cause separation of the desired bile acid salt; g. Recovering the said separated bile acid salt; h. Dissociating said separated bile acid salt to yield the desired free bile acid.

Claim 13

The method of producing substantially pure 3 Alpha ,7 Alpha -dihydroxy-5 Beta -cholanic acid from natural animal bile, which comprises a. Substantially dehydrating natural animal bile derived from birds; b. Esterifying said dehydrated bile by treatment with a suitable organic esterification agent; c. Subjecting the thus esterified bile to a multiphasic organic solvent system selected from the group consisting of halogenated hydrocarbon: alcohol; aromatic organic solvent: alcohol; aromatic organic solvent: alkane, ether: alcohol; and halogenated hydrocarbon: ketone; to separate the pigment and other impurity fraction of said bile from the bile acid fraction thereof; d. Treating the said bile acid fraction to obtain the corresponding free bile acids; e. Treating said free bile acids with a Group IIa metal salt to obtain the corresponding Group IIa metal bile acid salts; f. Treating said Group IIa metal bile acid salts with an organic solvent selected from the group consisting of alcohols, ethyl acetate, hexane and acetic acid to cause separation of the desired Group IIa metal salt of 3 Alpha ,7 Alpha -dihydroxy-5 Beta -cholanic acid and treating same to yield the desired, substantially pure 3 Alpha ,7 Alpha -dihydroxy-5 Beta -cholanic acid.

Claim 14

The method of producing substantially pure 3 Alpha ,7 Alpha -dihydroxy-5 Beta -cholanic acid from natural animal bile, which comprises a. Substantially dehydrating natural animal bile derived from birds; b. Esterifying said dehydrated bile by treatment with a suitable organic esterification agent; c. Subjecting the thus esterified bile to a multiphasic organic solvent system selected from the group consisting of halogenated hydrocarbon: alcohol; aromatic organic solvent: alcohol; aromatic organic solvent: alkane, ether: alcohol; and halogenated hydrocarbon: ketone; to separate the pigment and other impurity fraction of said bile from the bile acid fraction thereof; d. Treating the said bile acid fraction to obtain the corresponding free bile acids; e. Treating said free bile acids with a Group IIa metal salt to obtain the corresponding Group IIa metal bile acid salts; f. Treating said Group IIa metal bile acid salts with an organic solvent selected from the group consisting of alcohols, ethyl acetate, hexane and acetic acid to cause separation of the desired Group IIa metal salt of 3 Alpha ,7 Alpha -dihydroxy-5 Beta -cholanic acid and treating same to yield the desired, substantially pure 3 Alpha ,7 Alpha -dihydroxy-5 Beta -cholanic acid.

Claim 22

The method of producing substantially pure bile acids from natural bile, which comprises: a. Substantially dehydrating said natural animal bile; b. Esterifying said substantially dehydrated natural animal bile by treatment with a suitable organic esterification agent; c. Subjecting said esterified natural animal bile to a multiphasic organic solvent system in one phase of which the bile acid fraction of said animal bile is soluble and the pigments and other impurities thereof are not soluble, and in the remaining phases of which the said pigments and other impurities are soluble and the bile acid fraction is not soluble; d. Separating and recovering the substantially pigment and impurity-free bile acid fraction of the natural animal bile; and e. Treating said bile acid fraction to isolate and recover the desired, substantially pure, individual bile acid components of said bile acid fraction.

Claim 23

The method of producing substantially pure bile acids from natural bile, which comprises: a. Substantially dehydrating said natural animal bile; b. Esterifying said substantially dehydrated natural animal bile by treatment with a suitable organic esterification agent; c. Subjecting said esterified natural animal bile to a multiphasic organic solvent system in one phase of which the bile acid fraction of said animal bile is soluble and the pigments and other impurities thereof are not soluble, and in the remaining phases of which the said pigments and other impurities are soluble and the bile acid fraction is not soluble; d. Separating and recovering the substantially pigment and impurity-free bile acid fraction of the natural animal bile; and e. Treating said bile acid fraction to isolate and recover the desired, substantially pure, individual bile acid components of said bile acid fraction.