CN102838647A - Hyodeoxycholic acid - Google Patents

Abstract

The present invention discloses a hyodeoxycholic acid, which has the following structural formula. According to the present invention, two steps of a crude hyodeoxycholic magnesium extraction part (acidification, saponification, decoloration and precipitation) and a hyodeoxycholic acid purification part (acidification and crystallization) are adopted to obtain the refined hyodeoxycholic acid finished product, wherein a melting point of the hyodeoxycholic acid finished product can be 199-200 DEG C, a melting range is less than 2 DEG C, and content is more than 99%. According to the present invention, a production cycle is greatly shortened, a use amount of the organic solvent is less, and bile acid loss is not substantially generated in the whole process.

Description

Hyodeoxycholic Acid

Technical field

The invention belongs to Hyodeoxycholic Acid and preparation technology thereof.

Background technology

Hyodeoxycholic Acid, chemical name: 3 α, 6 alpha-dihydroxy-s-5 β-ursodeoxycholic acid, former name: hyodeoxycholic acid, structural formula is following:

Hyodeoxycholic Acid is a kind of ursodeoxycholic acid that from Fel Sus domestica, extracts, and can suppress the formation and the dissolved fat of cholic acid, reduces blood cholesterol and triglyceride level, is applicable to II a or IIb type hyperlipidemia, atherosclerosis.Bordetella pertussis, diphtheria corynebacterium, streptococcus aureus etc. there is certain bacteriostatic action.Can be used as antiphlogistic drug, treatment chronic bronchitis, child virus upper respiratory tract infection etc.These article can stimulate choleresis, make bile thinning and do not increase amount of solid, are applicable to biliary tract inflammation, cholecystitis, cholelithiasis and other nonobstructive cholestasis; Also can quicken cholecystic radiopoaque medium discharges liver and helps development.Still can promote enteron aisle steatolysis and liposoluble vitamin to absorb, can be used for the maldigestion that hepatobiliary disease causes.It also is the important component of preparation artificial Calculus Bovis.

The traditional technology of present domestic preparation Hyodeoxycholic Acid adopts acidifying after the saponification, dries again, receive the Hyodeoxycholic Acid bullion, again through ETHYLE ACETATE crystallization twice, crystal is after squeezing, fusing point just can reach more than 190 ℃.Production process is complicated, and the cycle is long, and the ETHYLE ACETATE consumption is big.

Summary of the invention

The object of the present invention is to provide that a kind of product purity is higher, production technique is simple, with short production cycle, Hyodeoxycholic Acid and preparation technology thereof that consumption of organic solvent is little.

The present invention is the Hyodeoxycholic Acid of formula,

The preparation technology of Hyodeoxycholic Acid of the present invention comprises the steps:

1) thick Hyodeoxycholic Acid magnesium extracts:

Get the Fel Sus domestica behind Fel Sus domestica filtrating or the heating and extracting UCB, add Hydrogen chloride and regulate PH to 3.0, promptly produce the thick bile acide deposition of tawny colloidal, leave standstill, the supernatant that inclines, thick bile acide, take out, water washes surperficial acid solution;

With the thick bile acide of sodium hydroxide saponification hydrolysis: the part by weight that feeds intake is thick bile acide: water: sodium hydroxide=1: 8: 1.5; Add water earlier by above-mentioned feed ratio when feeding intake, slowly add the sodium hydroxide stirring again and make dissolving, drop into thick bile acide again; Heated and boiled backflow saponification 24 hours; Be cooled to room temperature, upper strata buck layer is abandoned, and stays lower floor's gelatinous precipitate; Adding weight then is 10 times of water gagings of lower floor's gelatinous precipitate, and stirring and dissolving slowly adds ydrogen peroxide 50 again, makes Solution H ₂O ₂Weight percent concentration is 1～2%, decolours, filters filtrating excessively, and filtrating is heated to 50～60 ℃; Using concentration is that 10% dilute sulphuric acid is transferred PH8～9, and filtrating under agitation slowly adds 5.5% the sal epsom that its weight is Fel Sus domestica weight, filters; The collecting precipitation thing; Be Hyodeoxycholic Acid magnesium,, get thick Hyodeoxycholic Acid magnesium with water washing precipitate twice;

2) Hyodeoxycholic Acid is refining:

Get the thick Hyodeoxycholic Acid magnesium of step 1), be suspended in ETHYLE ACETATE and the water mixed solution by the following weight ratio that feeds intake and form suspension, the weight ratio that feeds intake is thick Hyodeoxycholic Acid magnesium: ETHYLE ACETATE: water=1: 4: 4; 50～60 ℃ of suspension heating, using weight percent concentration is that 10% dilute sulphuric acid is acidified to water layer PH=2, standing demix; Discard water layer, obtain ethyl acetate layer, filtered while hot; Crystallisation by cooling, crystal is collected in centrifuging; Crystal washs with amount of ethyl acetate, and drying through pulverizing, total mixed, packing, promptly gets purified Hyodeoxycholic Acid finished product, and the fusing point of Hyodeoxycholic Acid finished product can reach 199～200 ℃, and molten distance is less than 2 ℃, and content reaches more than 99%.

Advantage of the present invention: adopt new technology (1), directly adds the magnesium salts deposition after the saponification, forms Hyodeoxycholic Acid magnesium, and after the ETHYLE ACETATE crystallization, fusing point just can reach more than 195 ℃.Production cycle shortens greatly, and consumption of organic solvent is few.(2) product purity is higher: novel process receive the purity of the more former technology of Hyodeoxycholic Acid high; Its fusing point can reach 199～200 ℃; Molten distance is less than 2 ℃, and content reaches more than 99%, and the Hyodeoxycholic Acid fusing point that former explained hereafter goes out is generally 191～193; Impurity Chenodiol amount is bigger, and Fig. 1 carries out thin-layer chromatography relatively for the product of novel process and traditional technology production:

(3) the thick relatively bile acide yield of novel process is about 10%, and the traditional technology yield is about 15%, though yield has descended 5%; But saponification adds the Hyodeoxycholic Acid mother liquor of magnesium salts post precipitation; Through the recoverable again bile acide of acidifying, the master contains Chenodiol, can be applied on the feed; Also can further extract Chenodiol as the Chenodiol bullion.So basic free of losses of whole technological process bile acide.

Description of drawings

Fig. 1 carries out the thin-layer chromatography comparison diagram for the product of novel process of the present invention and traditional technology production.

Embodiment

Content of the present invention combines following examples to do explanation further, but content of the present invention is not limited only to content related among the embodiment.

The preparation technology of Hyodeoxycholic Acid of the present invention comprises the steps:

1) thick Hyodeoxycholic Acid magnesium extracts part (acidifying, saponification, decolouring, deposition):

Get Fel Sus domestica (manufacturer: Xiamen hundred million fragrant meats the are united processing ltd) 1000kg behind Fel Sus domestica filtrating or the heating and extracting UCB; Add Hydrogen chloride and regulate PH to 3.0, promptly produce the thick bile acide deposition of tawny colloidal, leave standstill; The supernatant that inclines, thick bile acide.Take out, water washes surperficial acid solution.

With the thick bile acide of sodium hydroxide saponification hydrolysis: the part by weight that feeds intake is thick bile acide: water: sodium hydroxide=1: 8: 1.5 feeds intake Xian Jiashui by the part by weight that feeds intake; Slowly add the sodium hydroxide stirring again and make dissolving, drop into thick bile acide again, heated and boiled refluxes; Saponification 24 hours; Be cooled to room temperature, upper strata buck layer is abandoned, and stays lower floor's gelatinous precipitate.Adding weight then is 10 times of water gagings of lower floor's gelatinous precipitate, and stirring and dissolving slowly adds ydrogen peroxide 50 again, makes Solution H ₂O ₂Concentration is 1.5% (weight percent), decolours 12 hours, crosses and filters filtrating; Filtrating is heated to 55 ℃, transfers PH8.5 with dilute sulphuric acid (weight percent concentration is 10%), and filtrating under agitation slowly adds the sal epsom that its weight is 5.5% (weight percent concentration) of Fel Sus domestica weight; Filter, the collecting precipitation thing is Hyodeoxycholic Acid magnesium; With water washing precipitate twice, get thick Hyodeoxycholic Acid magnesium.

2) Hyodeoxycholic Acid FF (acidifying, crystallization):

Get thick Hyodeoxycholic Acid magnesium, be suspended in ETHYLE ACETATE and water by mixed solution in, the part by weight that feeds intake is thick Hyodeoxycholic Acid magnesium: ETHYLE ACETATE: water=1: 4: 4; 55 ℃ of suspension heating are acidified to water layer PH=2, standing demix with dilute sulphuric acid (weight percent concentration is 10%); Discard water layer, obtain ethyl acetate layer, filtered while hot; Crystallisation by cooling, crystal is collected in centrifuging.Crystal washs with amount of ethyl acetate, and drying through pulverizing, total mixed, packing, promptly gets purified Hyodeoxycholic Acid finished product, and its fusing point can reach 199～200 ℃, and molten distance is less than 2 ℃, and content reaches more than 99%.

Claims (2)

1. the Hyodeoxycholic Acid of a formula,

2. the preparation technology of a Hyodeoxycholic Acid comprises the steps:

1) thick Hyodeoxycholic Acid magnesium extracts:

Get the Fel Sus domestica behind Fel Sus domestica filtrating or the heating and extracting UCB, add Hydrogen chloride and regulate PH to 3.0, promptly produce the thick bile acide deposition of tawny colloidal, leave standstill, the supernatant that inclines, thick bile acide, take out, water washes surperficial acid solution;

With the thick bile acide of sodium hydroxide saponification hydrolysis: the part by weight that feeds intake is thick bile acide: water: sodium hydroxide=1: 8: 1.5; Add water earlier by above-mentioned feed ratio when feeding intake, slowly add the sodium hydroxide stirring again and make dissolving, drop into thick bile acide again; Heated and boiled backflow saponification 24 hours; Be cooled to room temperature, upper strata buck layer is abandoned, and stays lower floor's gelatinous precipitate; Adding weight then is 10 times of water gagings of lower floor's gelatinous precipitate, and stirring and dissolving slowly adds ydrogen peroxide 50 again, makes Solution H ₂O ₂Weight percent concentration is 1～2%, decolours, filters filtrating excessively, and filtrating is heated to 50～60 ℃; Using concentration is that 10% dilute sulphuric acid is transferred PH8～9, and filtrating under agitation slowly adds 5.5% the sal epsom that its weight is Fel Sus domestica weight, filters; The collecting precipitation thing; Be Hyodeoxycholic Acid magnesium,, get thick Hyodeoxycholic Acid magnesium with water washing precipitate twice;

2) Hyodeoxycholic Acid is refining:

Get the thick Hyodeoxycholic Acid magnesium of step 1), be suspended in ETHYLE ACETATE and the water mixed solution by the following weight ratio that feeds intake and form suspension, the weight ratio that feeds intake is thick Hyodeoxycholic Acid magnesium: ETHYLE ACETATE: water=1: 4: 4; 50～60 ℃ of suspension heating, using weight percent concentration is that 10% dilute sulphuric acid is acidified to water layer PH=2, standing demix; Discard water layer, obtain ethyl acetate layer, filtered while hot; Crystallisation by cooling, crystal is collected in centrifuging; Crystal washs with amount of ethyl acetate, and drying through pulverizing, total mixed, packing, promptly gets purified Hyodeoxycholic Acid finished product, and the fusing point of Hyodeoxycholic Acid finished product can reach 199～200 ℃, and molten distance is less than 2 ℃, and content reaches more than 99%.

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