CN103980176B - The joint process of a kind of Fel Sus domestica mesobilirubin and bile acide - Google Patents
The joint process of a kind of Fel Sus domestica mesobilirubin and bile acide Download PDFInfo
- Publication number
- CN103980176B CN103980176B CN201410241948.6A CN201410241948A CN103980176B CN 103980176 B CN103980176 B CN 103980176B CN 201410241948 A CN201410241948 A CN 201410241948A CN 103980176 B CN103980176 B CN 103980176B
- Authority
- CN
- China
- Prior art keywords
- sus domestica
- fel sus
- chloroform
- bile acide
- raffinate
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/44—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses the joint process of a kind of Fel Sus domestica mesobilirubin and bile acide, it is characterized in that, comprise the steps: step one, saponification process is carried out to pending Fel Sus domestica; Step 2, utilize chloroform to extract the Fel Sus domestica that step one obtains, from chloroform extraction liquid, extract bilirubin, from pending raffinate, prepare bile acide; Wherein, the detailed process extracting bile acide from pending raffinate is: (1) carries out continuous print distillation process to remove chloroform from extraction liquid to raffinate, distillation process certain time through three phases and under each stage successively, the temperature of first stage is 55 ~ 60 DEG C, the temperature of subordinate phase is 70 ~ 75 DEG C, and the temperature of phase III is 85 ~ 90 DEG C; (2) raffinate through distillation process is utilized to prepare bile acide.The bilirubin prepared according to the method for the present invention and purity of bile acide is high, yield is high, and cost is low, the present invention can be used for industrialization scale operation.
Description
Technical field
The present invention relates to the joint process of a kind of Fel Sus domestica mesobilirubin and bile acide.
Background technology
Bilirubin and bile acide extract in the bile by animal, is widely used in the middle of various preparation, is the main synthesis material of artificial Calculus Bovis.In bile, major part is water, and its water solubles is bile acide and bilirubin mainly.Bilirubin (bilirubin, BR) have clinically antipyretic, calm, relieving convulsion, press down mattress, step-down, promotion red blood corpuscle regenerate effect, are the staple products that biochemical pharmacy and fine chemistry industry are produced.At present, the most general, that industrial applications is the widest bilirubin production method remains calcium salt method, resin method and rapid method, and wherein, rapid method occupies half of the country because having the advantages such as operating procedure is simple, with short production cycle always in suitability for industrialized production bilirubin.
After produce bilirubin from animal bile, many enterprises all using surplus materials as waste, and extract the residual solution after bilirubin and also leave a certain amount of broad-spectrum bile acide.Swine bile acids is the important component of Fel Sus domestica, play an important role in metabolism of fat, account for 50% ~ 70% of Fel Sus domestica total amount, mainly contain Hyodeoxycholic Acid, Chenodiol, Iocholic acid etc., wherein Hyodeoxycholic Acid accounts for 40%, Chenodiol accounts for 25%.If the residual solution purifying bile acide after extracting bilirubin can be utilized, and utilize it to be separated Hyodeoxycholic Acid and Chenodiol etc., both can improve the utilization ratio of bile, reduce the wasting of resources, can economic benefit be increased again.Current China produces bilirubin and bile acide is all main extracts from Fel Sus domestica, taked technique be generally single line and produce, can only single product be obtained, or for producing bilirubin or be bile acide, waste bile to a great extent, do not reach the efficiency utilization of resource.Surplus for production material is gone to process then again cost is too high.The industrial co-production technology that generally do not adopt also is that process optimization is inadequate, so cause input too high, therefore often adopts single production because technology is not mature enough.Also have the report of application coproduction, but just carry out roughing mutually to upper strata, the cholic acid purity of production is too low.
Summary of the invention
The invention provides the joint process of a kind of Fel Sus domestica mesobilirubin and bile acide, the present invention produces bilirubin rapid method and improves, and the basis keeping high-speed production improves bilirubin productive rate; The bile acide extracting method provided in the present invention, when making full use of resource, achieves the bile acide product of higher degree.
Technical scheme provided by the invention is:
A joint process for Fel Sus domestica mesobilirubin and bile acide, is characterized in that, comprises the steps:
Step one, saponification process is carried out to pending Fel Sus domestica;
Step 2, utilize chloroform to extract the Fel Sus domestica that step one obtains, from chloroform extraction liquid, extract bilirubin, from pending raffinate, prepare bile acide;
Wherein, the detailed process extracting bile acide from pending raffinate is: (1) carries out continuous print distillation process to remove chloroform from extraction liquid to raffinate, distillation process certain time through three phases and under each stage successively, the temperature of first stage is 55 ~ 60 DEG C, the temperature of subordinate phase is 70 ~ 75 DEG C, and the temperature of phase III is 85 ~ 90 DEG C; So only adopt and heat not only escapable cost stage by stage, and heat up evenly, avoid local heating too fast, reduce internal stress, be conducive to ensureing the quality product of bile acide and the removal of chloroform, such distillation process can ensure chloroform all to steam, and does not have peculiar smell to remain.(2) raffinate through distillation process is utilized to prepare bile acide.
Preferably, in described Fel Sus domestica mesobilirubin and the joint process of bile acide, in described step 2, distillation process is at each phase lasts 10min.
Preferably, in described Fel Sus domestica mesobilirubin and the joint process of bile acide, in described step 2, the detailed process utilizing the raffinate through distillation process to prepare bile acide is: in the raffinate through distillation process, add the NaOH solution that mass concentration is 12%, saponification under boiling state, concentrate afterwards and obtain bile acide saponification resultant, by soluble in water for bile acide saponification resultant, after using activated carbon decolorizing, filter the filtrate obtained containing bile acide saponification resultant, hydrochloric acid is added to filtrate, obtain bile acide precipitation, wherein, the consumption of NaOH solution is 0.1 times of the weight of pending raffinate.
Preferably, in described Fel Sus domestica mesobilirubin and the joint process of bile acide, in described step 2, when utilizing chloroform to extract the Fel Sus domestica that step one obtains, first carry out first time extraction, obtain upper strata phase, mesophase spherule and lower floor's chloroform phase, afterwards second time extraction is carried out to mesophase spherule, obtain upper strata phase and lower floor's chloroform phase again, lower floor's chloroform of twice extraction is merged as chloroform extraction liquid mutually, the upper strata of twice extraction is merged mutually as pending raffinate, wherein, during first time extraction, the volume of chloroform is 0.5 times of the volume of the Fel Sus domestica that step one obtains, during second time extraction, the volume of chloroform is 0.25 times of the volume of the Fel Sus domestica that step one obtains.The bilirubin that may contain in mesophase spherule after first time extraction and bile acide can be carried out second time extraction like this, improve productive rate.
Preferably, in described Fel Sus domestica mesobilirubin and the joint process of bile acide, in described step one, during saponification process, the pH value of Fel Sus domestica is 9.0 ~ 9.5, and pH value is herein lower slightly compared with the pH of the traditional rapid method of bilirubin, if basicity is excessive, excessive alkali can form bile salt colloid with bile acide, miscible with bilirubin, affects extraction effect; If basicity is too small, then bilirubin can be made to be hydrolyzed not exclusively, and pH value herein controls accurately, and bilirubin can be made to be hydrolyzed completely and don't to form bile salt colloid.
Preferably, in described Fel Sus domestica mesobilirubin and the joint process of bile acide, in described step one, before saponification process, also in pending Fel Sus domestica, add antioxidant, the consumption of antioxidant is 0.22 ~ 0.25% of pending Fel Sus domestica weight, after saponification process, lowered the temperature by Fel Sus domestica through saponification process, and add antioxidant again, the consumption of antioxidant is 0.07% of pending Fel Sus domestica weight.Because bilirubin is readily oxidizable substance, under the effect of high temperature, high light, oxygenant, be especially very easily oxidized in alkaline environment, therefore, need in operation to add a certain amount of antioxidant, to prevent bilirubin oxidized.
Preferably, in described Fel Sus domestica mesobilirubin and the joint process of bile acide, described antioxidant is the one in sodium bisulfite, xitix and metagallic acid.
Preferably, in described Fel Sus domestica mesobilirubin and the joint process of bile acide, in described step one, the method preparing pending Fel Sus domestica is: Fel Sus domestica is frighten seriously, removing courage skin, bile is crossed 120 eye mesh screens and is removed impurity and grease, obtains pending Fel Sus domestica.
Preferably, in described Fel Sus domestica mesobilirubin and the joint process of bile acide, in described step 2, from chloroform extraction liquid, extract bilirubinic detailed process is: normal heating chloroform extraction liquid, keep micro-boiling, steam chloroform to only remaining a small amount of chloroform and have a large amount of bilirubin to separate out time, now the volume of general leftover materials is less than 18% of chloroform extraction liquid, stops heating; Be cooled to after below 60 DEG C, add the ethanolic soln that volumetric concentration is 95%, the consumption of ethanolic soln is the 0.4%-0.8% of the volume of chloroform extraction liquid; Continue heating, treat only remaining a small amount of solution, and after substantially steaming without chloroform, be cooled to less than 60 DEG C; Again adding about 10-20L volumetric concentration is the ethanolic soln of 95%, and when a large amount of bilirubin is separated out, suction filtration, obtains bilirubin.
Beneficial effect of the present invention is:
1. method of the present invention is produced on bilirubinic basis main, makes full use of resource, under low cost condition, realizes coproduction, and obtain the bile acide product of higher degree;
2. the present invention mainly achieves coproduction, these two kinds of production technique is not only carried out simultaneously, and highly utilizes raw material; And bilirubin and bile acide product are all refined, purity is higher, is more conducive to next step product application;
3. working method of the present invention is simple, quick, the high and low poison of yield, low cost, consumption of organic solvent are few, can be used for industrialization scale operation, and the loss of whole technological process Fel Sus domestica is little.
Accompanying drawing explanation
Fig. 1 is the schema of the joint process of Fel Sus domestica mesobilirubin of the present invention and bile acide.
Embodiment
Below in conjunction with accompanying drawing, the present invention is described in further detail, can implement according to this with reference to specification sheets word to make those skilled in the art.
In following examples, yield of the present invention is defined as: bilirubin yield=bilirubin quality product/Amount of Bile × 100%, bile acide yield=bile acide quality product/Amount of Bile × 100%.
Embodiment one:
As shown in Figure 1, according to the joint process of a kind of Fel Sus domestica mesobilirubin of the present invention and bile acide, comprise the following steps:
1. degreasing: get and freeze Fel Sus domestica 1 ton, be placed on thaw shelf, control room temp at 35 ~ 55 DEG C, until thaw to gall bladder without ice, need to stir between frost free period, the duration that thaws is determined according to season and thawing condition to be advisable for 8-24 hour.Fel Sus domestica vacuum transfer after thawing is in gall bladder temporary storage tank, more frighten seriously through filament cutter, after Vibrationsifter is separated courage skin, about 820kg bile, cross after 120 eye mesh screens remove impurity, grease, transfer to saponification tank.
2. saponification: after adding the antioxidant sodium bisulfite of account for bile weight 0.25%, start to be rapidly heated, wait to be warming up to 60 DEG C, use the NaOH of 25% to regulate pH to be 9.0, continue to be heated to 95 DEG C, maintain 15min, cooling speed is chilled to 40 DEG C, again add account for bile weight 0.07% sodium bisulfite, stir evenly final vacuum and be transferred in extractor, every tank is about 280L.
3. extract: each extractor adds the chloroform accounting for bile weight 0.5 times amount, after stirring 15min, regulate pH to 5.5 with HCl, after maintaining lucifuge stirring 30min, mixing speed is 20-40rpm, stratification.Time of repose is at more than 40min.
After layering terminates, accurately separate lower floor's chloroform to transfer tank, bile acide temporary storage tank is put on upper strata mutually, collect mesophase spherule and continue layering to mesophase spherule temporary storage tank, the chloroform accounting for bile weight 0.25 times is again squeezed in mesophase spherule temporary storage tank, after stirring 15min, after maintaining lucifuge stirring 30min, stratification, time of repose is at more than 30min, after layering, obtain upper strata phase and lower floor's chloroform phase again, lower floor's chloroform of twice extraction is merged as chloroform extraction liquid mutually, the upper strata of twice extraction is merged mutually as pending raffinate, the mesophase spherule again obtained is gone to after mixing with other mesophase spherule in mesophase spherule temporary storage tank and continue to extract.
4. the chloroform extraction liquid in transfer tank is beaten to spherical concentration tank successively, normal heating, keep micro-boiling, reclaim chloroform to only remaining a small amount of chloroform and when having a large amount of bilirubin to separate out, now remaining liquid is less than 50L, in tank, temperature is between 65-68 DEG C, stop heating, interbedded water is cooled to less than 60 DEG C to material in tank, continues heating after adding 10-20L95% ethanol, treats only remaining a small amount of solution, now remaining liquid is less than 50L, in tank, temperature is between 65-68 DEG C, after substantially steaming without chloroform, is cooled to less than 60 DEG C to tank body; Again add about 10-20L ethanol carefully to rinse tank skin, a large amount of red granules shape bilirubin is now had to separate out as seen, solution is all put in bilirubin temporary storage tank, timely suction filtration, period, available jacket steam heated suction filtration tank, finally, use be no less than 5L ethanol again shower filter gained bilirubin to filtrate without obviously heterochromatic, namely obtain product bilirubin after constant pressure and dry, weigh 460g, yield is 0.056%
5. bile acide saponification: by raffinate by suction retort in bile acide temporary storage tank, normal heating, intermittent stirring, temperature controls to distill 10min separately at 55 DEG C, 70 DEG C and 85 DEG C of three phases by steam regulation successively, wherein chloroform is made all to steam and reclaim, then add account for raffinate weight 0.1 times amount 12% NaOH remain on this temperature and carry out saponification, be subsequently concentrated into most of moisture and be distilled out of, obtain lower floor's gelatinous precipitate.
6. decolour: add the water that weight is lower floor's gelatinous precipitate 10 times amount, stir 30min to precipitate dissolves, more slowly add 5% gac reflux decolour 3h, then more than 30min is left standstill, cross leaching clear liquid, wherein, the addition of activated charcoal solid is account for raffinate weight 0.2%.
7. precipitate, evaporate to dryness packs: filtrate squeezed in setting tank, logical cold water is cooled to less than 35 DEG C, under the condition constantly stirred, constantly add below 30%HCl solution adjust ph to 2.0, newly generation is precipitated to nothing, abundant stirring 1h, keep mixing speed at 20rpm, then more than 6h is left standstill, substantially all separate out to bile acide, pump supernatant liquor, precipitation washes 1 time with water, reheat precipitation, keep micro-1h that boils, now in tank, temperature is between 60-68 DEG C, boil off most of moisture, obtain product bile acide, after letting cool sclerosis, weigh as 26kg, yield is 3.17%.
Be 0.056% according to the bilirubinic yield of method of the present invention, general rapid method chloroform extraction can only reach 0.0164-0.0168%, and the yield of bile acide improves more than 2 times, and the remarkable pole of yield is improved; Yield according to the bile acide of method of the present invention is 3.17%, and the yield of general bile acide is 2.6%-2.8%, and yield improves 13.21%-21.92%, and yield also significantly improves, and cost is low, and resource is fully used.
Embodiment two:
As shown in Figure 1, according to the joint process of a kind of Fel Sus domestica mesobilirubin of the present invention and bile acide, comprise the following steps:
1. degreasing: get fresh Fel Sus domestica 2 tons, frighten seriously through filament cutter, after Vibrationsifter is separated courage skin, about obtain 1640kg bile, after crossing 120 eye mesh screens removal impurity, grease, transfer to saponification tank.
2. saponification: after adding the antioxidant metagallic acid of account for bile weight 0.25%, start to be rapidly heated, wait to be warming up to 65 DEG C, use the NaOH of 25% to regulate pH to be 9.5, continue to be heated to 95 DEG C, maintain 15min, cooling speed is chilled to 40 DEG C, again add account for bile weight 0.07% metagallic acid Amount of Bile, stir evenly final vacuum and be transferred in extractor, every tank is about 280L.
3. extract: each extractor adds and accounts for bile weight 0.5 times amount chloroform, after stirring 15min, regulate pH to 6.0 with HCl, maintain after lucifuge stirs 30min, mixing speed is 40rpm, stratification.Time of repose is at more than 40min.
After layering terminates, accurately separate lower floor's chloroform to transfer tank, bile acide temporary storage tank is put on upper strata mutually, collect mesophase spherule and continue layering to mesophase spherule temporary storage tank, the chloroform accounting for bile weight 0.25 times is again squeezed in mesophase spherule temporary storage tank, after stirring 15min, after maintaining lucifuge stirring 30min, stratification, time of repose is at more than 30min, after layering, obtain upper strata phase and lower floor's chloroform phase again, lower floor's chloroform of twice extraction is merged as chloroform extraction liquid mutually, the upper strata of twice extraction is merged mutually as pending raffinate, the mesophase spherule again obtained is gone to after mixing with other mesophase spherule in mesophase spherule temporary storage tank and continue to extract.
4. the chloroform extraction liquid in transfer tank is beaten to spherical concentration tank successively, normal heating, keep micro-and boil, reclaim chloroform to only remaining a small amount of chloroform and when having a large amount of bilirubin to separate out, now, liquid is less than 50L, and in tank, temperature is about 65-68 DEG C, stop heating, interbedded water is cooled to less than 60 DEG C to material in tank, continues heating after adding 20L95% ethanol, treats only remaining a small amount of solution, now remaining liquid is less than 50L, in tank, temperature is between 65-68 DEG C, after substantially steaming without chloroform, is cooled to less than 60 DEG C to tank body; Again add 20L ethanol carefully to rinse tank skin, a large amount of red granules shape bilirubin is now had to separate out as seen, solution is all put in bilirubin temporary storage tank, timely suction filtration, period, available jacket steam heated suction filtration tank, finally, use be no less than 5L ethanol again shower filter gained bilirubin to filtrate without obviously heterochromatic, namely obtain product bilirubin after constant pressure and dry, weigh 910g, yield is 0.055%.
5. bile acide saponification: by raffinate by suction retort in bile acide temporary storage tank, normal heating, intermittent stirring, temperature controls to distill 10min separately at 60 DEG C, 75 DEG C and 90 DEG C of three phases by steam regulation successively, wherein chloroform is made all to steam and reclaim, then add account for raffinate weight 0.1 times amount 12% NaOH remain on this temperature and carry out saponification, be subsequently concentrated into most of moisture and be distilled out of, obtain lower floor's gelatinous precipitate.
6. decolour: add the water that weight is lower floor's gelatinous precipitate 10 times amount, stir 30min to precipitate dissolves, more slowly add 5% gac reflux decolour 5h, then leave standstill more than 30min, cross leaching clear liquid.
7. precipitate, evaporate to dryness packs: filtrate squeezed in setting tank, logical cold water is cooled to less than 35 DEG C, under the condition constantly stirred, constantly add below 30%HCl solution adjust ph to 2.0, newly generation is precipitated to nothing, abundant stirring 1h, keep mixing speed at 40rpm, then more than 6h is left standstill, substantially all separate out to bile acide, pump supernatant liquor, precipitation washes 2 times with water, reheat precipitation, keep micro-boil 3h now in tank temperature between 60-68 DEG C, boil off most of moisture, obtain product bile acide, after letting cool sclerosis, weigh as 51kg, yield is 3.11%.
Be 0.055% according to the bilirubinic yield of method of the present invention, general rapid method chloroform extraction can only reach 0.0164-0.0168%, and the yield of bile acide improves more than 2 times, and the remarkable pole of yield is improved; Yield according to the bile acide of method of the present invention is 3.11%, and the yield of general bile acide is 2.6%-2.8%, and yield improves 11.07%-19.62%, and yield also significantly improves, and cost is low, and resource is fully used.
Embodiment three:
As shown in Figure 1, the joint process of a kind of Fel Sus domestica mesobilirubin and bile acide, comprises the following steps:
1. degreasing: get and freeze Fel Sus domestica 0.5 ton, be placed on thaw shelf, control room temp at 35 ~ 55 DEG C, until thaw to gall bladder without ice, stir between frost free period, the duration that thaws is determined according to season and thawing condition to be advisable for 8-24 hour.Fel Sus domestica vacuum transfer after thawing is in gall bladder temporary storage tank, more frighten seriously through filament cutter, after Vibrationsifter is separated courage skin, about 410kg bile, cross after 120 eye mesh screens remove impurity, grease, transfer to saponification tank.
2. saponification: after adding the antioxidants ascorbic acid of account for bile weight 0.25%, start to be rapidly heated, wait to be warming up to 62.5 DEG C, use the NaOH of 25% to regulate pH to be 9.25, continue to be heated to 95 DEG C, maintain 15min, cooling speed is chilled to 40 DEG C, again add account for bile weight 0.07% xitix, stir evenly final vacuum and be transferred in extractor, every tank is about 280L.
3. extract: each extractor adds and accounts for bile weight 0.5 times amount chloroform, after stirring 15min, regulate pH to 5.75 with HCl, maintain after lucifuge stirs 30min, mixing speed is 30rpm, and stratification, time of repose is at more than 40min.
After layering terminates, accurately separate lower floor's chloroform to transfer tank, bile acide temporary storage tank is put on upper strata mutually, collect mesophase spherule and continue layering to mesophase spherule temporary storage tank, the chloroform accounting for bile weight 0.25 times is again squeezed in mesophase spherule temporary storage tank, after stirring 15min, after maintaining lucifuge stirring 30min, stratification, time of repose is at more than 30min, after layering, obtain upper strata phase and lower floor's chloroform phase again, lower floor's chloroform of twice extraction is merged as chloroform extraction liquid mutually, the upper strata of twice extraction is merged mutually as pending raffinate, the mesophase spherule again obtained is gone to after mixing with other mesophase spherule in mesophase spherule temporary storage tank and continue to extract.
4. the chloroform extraction liquid in transfer tank is beaten to spherical concentration tank successively, normal heating, keep micro-and boil, reclaim chloroform to only remaining a small amount of chloroform and when having a large amount of bilirubin to separate out, now, liquid is less than 50L, and in tank, temperature is between 65-68 DEG C, stop heating, interbedded water is cooled to less than 60 DEG C to material in tank, continues heating after adding 15L95% ethanol, treats only remaining a small amount of solution, remaining liquid is less than 50L, in tank, temperature is at 65-68 DEG C, after substantially steaming without chloroform, is cooled to less than 60 DEG C to tank body; Again add 15L ethanol carefully to rinse tank skin, a large amount of red granules shape bilirubin is now had to separate out as seen, solution is all put in bilirubin temporary storage tank, timely suction filtration, period, available jacket steam heated suction filtration tank, finally, use be no less than 5L ethanol again shower filter gained bilirubin to filtrate without obviously heterochromatic, namely obtain product bilirubin after constant pressure and dry, weigh 235g, yield is 0.057%.
5. bile acide saponification: by raffinate by suction retort in bile acide temporary storage tank, normal heating, intermittent stirring, temperature controls to distill 10min separately at 57.5,72.5 DEG C and 87.5 DEG C of three phases by steam regulation successively, wherein chloroform is made all to steam and reclaim, then add account for raffinate weight 0.1 times amount 12% NaOH remain on this temperature and carry out saponification, be subsequently concentrated into most of moisture and be distilled out of, obtain lower floor's gelatinous precipitate.
6. decolour: add the water that weight is lower floor's gelatinous precipitate 10 times amount, stir 30min to precipitate dissolves, more slowly add 5% gac reflux decolour 4h, then leave standstill more than 30min, cross leaching clear liquid.
7. precipitate, evaporate to dryness packs: filtrate squeezed in setting tank, logical cold water is cooled to less than 35 DEG C, under the condition constantly stirred, constantly add below 30%HCl solution adjust ph to 2.0, newly generation is precipitated to nothing, abundant stirring 1h, keep mixing speed at 30rpm, then more than 6h is left standstill, substantially all separate out to bile acide, pump supernatant liquor, precipitation washes 1 ~ 2 time with water, reheat precipitation, keep micro-2h that boils, now in tank temperature between 60-68 DEG C, boil off most of moisture, obtain product bile acide, after letting cool sclerosis, weigh as 13.2kg, yield is 3.22%.
Be 0.057% according to the bilirubinic yield of method of the present invention, general rapid method chloroform extraction can only reach 0.0164-0.0168%, and the yield of bile acide improves more than 2 times, and the remarkable pole of yield is improved; Yield according to the bile acide of method of the present invention is 3.22%, and the yield of general bile acide is 2.6%-2.8%, and yield improves 15%-23.85%, and yield also significantly improves, and cost is low, and resource is fully used.
Although embodiment of the present invention are open as above, but it is not restricted to listed in specification sheets and embodiment utilization, it can be applied to various applicable the field of the invention completely, for those skilled in the art, can easily realize other amendment, therefore do not deviating under the universal that claim and equivalency range limit, the present invention is not limited to specific details and illustrates here and the legend described.
Claims (9)
1. a joint process for Fel Sus domestica mesobilirubin and bile acide, is characterized in that, comprises the steps:
Step one, saponification process is carried out to pending Fel Sus domestica;
Step 2, utilize chloroform to extract the Fel Sus domestica that step one obtains, from chloroform extraction liquid, extract bilirubin, from pending raffinate, prepare bile acide;
Wherein, the detailed process extracting bile acide from pending raffinate is: (1) carries out continuous print distillation process to remove chloroform from extraction liquid to raffinate, distillation process certain time through three phases and under each stage successively, the temperature of first stage is 55 ~ 60 DEG C, the temperature of subordinate phase is 70 ~ 75 DEG C, and the temperature of phase III is 85 ~ 90 DEG C; (2) raffinate through distillation process is utilized to prepare bile acide.
2. the joint process of Fel Sus domestica mesobilirubin as claimed in claim 1 and bile acide, is characterized in that, in described step 2, distillation process is at each phase lasts 10min.
3. the joint process of Fel Sus domestica mesobilirubin as claimed in claim 1 and bile acide, it is characterized in that, in described step 2, the detailed process utilizing the raffinate through distillation process to prepare bile acide is: in the raffinate through distillation process, add the NaOH solution that mass concentration is 12%, saponification under boiling state, be filtered through the raffinate of saponification process afterwards, hydrochloric acid is added to filtrate, obtain bile acide precipitation, wherein, the consumption of NaOH solution is 0.1 times of the weight of pending raffinate.
4. the joint process of Fel Sus domestica mesobilirubin as claimed in claim 1 and bile acide, it is characterized in that, in described step 2, when utilizing chloroform to extract the Fel Sus domestica that step one obtains, first carry out first time extraction, obtain upper strata phase, mesophase spherule and lower floor's chloroform phase, afterwards second time extraction is carried out to mesophase spherule, obtain upper strata phase and lower floor's chloroform phase again, lower floor's chloroform of twice extraction is merged as chloroform extraction liquid mutually, the upper strata of twice extraction is merged mutually as pending raffinate, wherein, during first time extraction, the volume of chloroform is 0.5 times of the volume of the Fel Sus domestica that step one obtains, during second time extraction, the volume of chloroform is 0.25 times of the volume of the Fel Sus domestica that step one obtains.
5. the Fel Sus domestica mesobilirubin according to any one of Claims 1-4 and the joint process of bile acide, is characterized in that, in described step one, during saponification process, the pH value of Fel Sus domestica is 9.0 ~ 9.5.
6. the joint process of Fel Sus domestica mesobilirubin as claimed in claim 5 and bile acide, it is characterized in that, in described step one, before saponification process, also in pending Fel Sus domestica, add antioxidant, the consumption of antioxidant is 0.22 ~ 0.25% of pending Fel Sus domestica weight, after saponification process, lowered the temperature by Fel Sus domestica through saponification process, and add antioxidant again, the consumption of antioxidant is 0.07% of pending Fel Sus domestica weight.
7. the joint process of Fel Sus domestica mesobilirubin as claimed in claim 6 and bile acide, it is characterized in that, described antioxidant is the one in sodium bisulfite, xitix and metagallic acid.
8. the joint process of Fel Sus domestica mesobilirubin as claimed in claim 6 and bile acide, is characterized in that, in described step one, the method preparing pending Fel Sus domestica is: Fel Sus domestica is frighten seriously, removing courage skin, bile is crossed 120 eye mesh screens and is removed impurity and grease, obtains pending Fel Sus domestica.
9. the joint process of Fel Sus domestica mesobilirubin as claimed in claim 6 and bile acide, it is characterized in that, in described step 2, from chloroform extraction liquid, extract bilirubinic detailed process is: normal heating chloroform extraction liquid, keep micro-boiling, steam chloroform to only remaining a small amount of chloroform and have a large amount of bilirubin to separate out time, stop heating; Be cooled to after below 60 DEG C, add the ethanolic soln that volumetric concentration is 95%, the consumption of ethanolic soln is the 0.4%-0.8% of the volume of chloroform extraction liquid; Continue heating, treat only remaining a small amount of solution, and after substantially steaming without chloroform, be cooled to less than 60 DEG C; Again adding about 10-20L volumetric concentration is the ethanolic soln of 95%, and when a large amount of bilirubin is separated out, suction filtration, obtains bilirubin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410241948.6A CN103980176B (en) | 2014-06-03 | 2014-06-03 | The joint process of a kind of Fel Sus domestica mesobilirubin and bile acide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410241948.6A CN103980176B (en) | 2014-06-03 | 2014-06-03 | The joint process of a kind of Fel Sus domestica mesobilirubin and bile acide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103980176A CN103980176A (en) | 2014-08-13 |
| CN103980176B true CN103980176B (en) | 2016-01-27 |
Family
ID=51272375
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410241948.6A Active CN103980176B (en) | 2014-06-03 | 2014-06-03 | The joint process of a kind of Fel Sus domestica mesobilirubin and bile acide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103980176B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107286071B (en) * | 2017-07-24 | 2019-11-29 | 贵州慧静生物科技有限公司 | A method of extracting bilirubin and cholic acid co-production cholesterol, lecithin from bile |
| CN107383142B (en) * | 2017-09-08 | 2019-11-05 | 安徽科宝生物工程有限公司 | The preparation method of cholesterol in ethanol residues after a kind of processing of gall bladder |
| CN110981780B (en) * | 2019-12-08 | 2021-01-12 | 常德云港生物科技有限公司 | Synchronous production equipment for bile acid and bilirubin in pig bile |
| CN110903232A (en) * | 2019-12-19 | 2020-03-24 | 平顶山市慧鑫源生物科技有限公司 | High-yield bilirubin extraction method |
| CN112939840A (en) * | 2021-02-03 | 2021-06-11 | 宋江 | Bilirubin extraction and purification method |
| CN117843546A (en) * | 2024-01-03 | 2024-04-09 | 四川菲德力制药有限公司 | Bilirubin extraction method |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1088575A (en) * | 1992-12-25 | 1994-06-29 | 郭静峰 | Bilirubin quick extraction method |
| CN101148468A (en) * | 2006-09-19 | 2008-03-26 | 天津科技大学 | High efficiency technique for extracting bilirubin and bile acid by using animal bile as raw material |
-
2014
- 2014-06-03 CN CN201410241948.6A patent/CN103980176B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN103980176A (en) | 2014-08-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103980176B (en) | The joint process of a kind of Fel Sus domestica mesobilirubin and bile acide | |
| CN102492546B (en) | Rice bran oil refinement and byproduct production method | |
| WO2018120574A1 (en) | Method for producing dha by microbial fermentation | |
| CN101337880A (en) | Process for extracting alpha-linolenic acid | |
| CN108893185B (en) | Method for preparing microalgae grease by magnetic hydrophobic eutectic solvent assisted flash extraction | |
| CN106749734A (en) | sweet lily polysaccharide extracting method | |
| CN101402670A (en) | Method simultaneously extracting lipid and protein from corn plantule | |
| CN105713716A (en) | Method for extracting sea buckthorn fruit oil in grading mode through combination of aqueous enzymatic method and ultrasonic assistance | |
| CN104711124A (en) | Soybean lecithin processing technology | |
| CN103254990A (en) | Preparation process of cold-pressed low-temperature rapeseed oil | |
| CN104651434A (en) | Preparation method of bone peptide solution | |
| CN103509028B (en) | The preparation method of a kind of chlorophyll cupric acid and copper sodium | |
| CN103613624B (en) | The process for purification of a kind of Avrmectin | |
| CN106675057B (en) | The preparation method of hard shell calcium alginate oil sac | |
| CN102422975A (en) | Method for pre-extracting peanut protein | |
| CN109880871A (en) | A method of small-molecular peptides are extracted by raw material of euphausia superba powder | |
| CN105129894A (en) | High efficiency extraction method of T-acid mother liquor | |
| CN102146047A (en) | Purification process of diacetone acrylamide | |
| CN107746723A (en) | A kind of method that sludge liquefaction prepares bio-fuel | |
| CN103540396B (en) | Method for producing silkworm chrysalis oil and extracting alpha-linolenic acid by adopting biological enzyme method | |
| CN111889043A (en) | Preparation method of lemon essential oil microcapsules | |
| CN104479864A (en) | Method for separation of alpha-linolenic acid from Chinese prickly ash seed oil | |
| CN106188183A (en) | A kind of combined extracting naringin and method of pectin from pomelo peel | |
| CN105505553A (en) | Method for efficiently extracting aliphatic acid by direct saponification of microalgae dried algae powder | |
| CN108676610A (en) | A method of obtaining active material from Squid By-products |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |