CN102911234A - Method for producing chenodeoxycholic acid by using chicken bile as raw material - Google Patents
Method for producing chenodeoxycholic acid by using chicken bile as raw material Download PDFInfo
- Publication number
- CN102911234A CN102911234A CN 201110217890 CN201110217890A CN102911234A CN 102911234 A CN102911234 A CN 102911234A CN 201110217890 CN201110217890 CN 201110217890 CN 201110217890 A CN201110217890 A CN 201110217890A CN 102911234 A CN102911234 A CN 102911234A
- Authority
- CN
- China
- Prior art keywords
- chenodeoxycholic acid
- bile
- raw material
- acid
- extraction
- 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.)
- Pending
Links
- RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 title claims abstract description 31
- RUDATBOHQWOJDD-BSWAIDMHSA-N chenodeoxycholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-BSWAIDMHSA-N 0.000 title claims abstract description 24
- 210000000941 bile Anatomy 0.000 title claims abstract description 23
- 229960001091 chenodeoxycholic acid Drugs 0.000 title claims abstract description 23
- 241000287828 Gallus gallus Species 0.000 title claims abstract description 12
- 239000002994 raw material Substances 0.000 title claims abstract description 8
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 7
- 230000020477 pH reduction Effects 0.000 claims abstract description 8
- 238000001953 recrystallisation Methods 0.000 claims abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 238000007127 saponification reaction Methods 0.000 claims description 8
- 238000000605 extraction Methods 0.000 claims description 7
- 239000000243 solution Substances 0.000 claims description 7
- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 claims description 7
- 229960001661 ursodiol Drugs 0.000 claims description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- 208000001130 gallstones Diseases 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 238000009835 boiling Methods 0.000 claims description 2
- 239000012043 crude product Substances 0.000 claims description 2
- 239000012047 saturated solution Substances 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims 5
- 230000007062 hydrolysis Effects 0.000 claims 3
- 238000006460 hydrolysis reaction Methods 0.000 claims 3
- 239000007788 liquid Substances 0.000 claims 3
- 238000001556 precipitation Methods 0.000 claims 2
- 238000000746 purification Methods 0.000 claims 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims 1
- 239000001110 calcium chloride Substances 0.000 claims 1
- 229910001628 calcium chloride Inorganic materials 0.000 claims 1
- 239000011259 mixed solution Substances 0.000 claims 1
- 239000002244 precipitate Substances 0.000 claims 1
- 239000003960 organic solvent Substances 0.000 abstract description 3
- 235000013613 poultry product Nutrition 0.000 abstract description 3
- 238000000638 solvent extraction Methods 0.000 abstract description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 abstract 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 abstract 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 abstract 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 abstract 1
- 229910019142 PO4 Inorganic materials 0.000 abstract 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 abstract 1
- 239000011575 calcium Substances 0.000 abstract 1
- 229910052791 calcium Inorganic materials 0.000 abstract 1
- 125000003907 chenodeoxycholic acid group Chemical group 0.000 abstract 1
- 235000012000 cholesterol Nutrition 0.000 abstract 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 abstract 1
- 239000010452 phosphate Substances 0.000 abstract 1
- 150000003904 phospholipids Chemical class 0.000 abstract 1
- 239000011591 potassium Substances 0.000 abstract 1
- 229910052700 potassium Inorganic materials 0.000 abstract 1
- 102000004169 proteins and genes Human genes 0.000 abstract 1
- 108090000623 proteins and genes Proteins 0.000 abstract 1
- 239000011734 sodium Substances 0.000 abstract 1
- 229910052708 sodium Inorganic materials 0.000 abstract 1
- 239000002699 waste material Substances 0.000 abstract 1
- 235000013330 chicken meat Nutrition 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 241000272814 Anser sp. Species 0.000 description 2
- 241000272517 Anseriformes Species 0.000 description 2
- 201000001883 cholelithiasis Diseases 0.000 description 2
- 244000144977 poultry Species 0.000 description 2
- 235000013594 poultry meat Nutrition 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 241000272525 Anas platyrhynchos Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 159000000009 barium salts Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Landscapes
- Steroid Compounds (AREA)
Abstract
鸡胆汁是禽产品加工企业的废弃物，其中的主要有机成分是鹅去氧胆酸，此外还含有磷脂、胆固醇、钠、钾、钙、磷酸盐、碳酸盐以及极少量蛋白质等成分。本发明涉及以鸡胆汁为原料生产高纯度鹅去氧胆酸方法。将鸡胆汁加热皂化后，经酸化、有机溶剂萃取得到鹅去氧胆酸，再应用重结晶方法纯化，得到高纯度鹅去氧胆酸产品。Chicken bile is waste from poultry product processing enterprises. The main organic component is chenodeoxycholic acid, and it also contains phospholipids, cholesterol, sodium, potassium, calcium, phosphate, carbonate and a very small amount of protein. The invention relates to a method for producing high-purity chenodeoxycholic acid using chicken bile as a raw material. After chicken bile is heated and saponified, chenodeoxycholic acid is obtained through acidification and organic solvent extraction, and then purified by recrystallization to obtain a high-purity chenodeoxycholic acid product.
Description
技术领域 technical field
本发明涉及以鸡胆汁为原料生产鹅去氧胆酸方法。其特征在于可以将禽产品加工企业的胆汁副产物加以利用，生产药物原料及药物中间体。The invention relates to a method for producing chenodeoxycholic acid from chicken bile. It is characterized in that bile by-products of poultry product processing enterprises can be utilized to produce pharmaceutical raw materials and pharmaceutical intermediates.
背景技术 Background technique
鹅去氧胆酸(chenodeoxycholic acid，简称CDCA)化学名为3α，7α-二羟基-5β-胆烷酸，分子式C24H40O4，分子量392.58。是1848年首次从鹅胆汁中提取得到的。鹅去氧胆酸具有溶解胆结石的能力和其它药学功能，自上世纪七十年代以来，在临床上被用作溶胆结石的药物。近年的研究发现，在溶解胆结石方面，鹅去氧胆酸的同分异构体熊去氧胆酸的临床应用效果更好，且没有副作用。因此，在溶解胆结石药物的临床应用方面，熊去氧胆酸逐渐取代了鹅去氧胆酸。The chemical name of chenodeoxycholic acid (CDCA for short) is 3α,7α-dihydroxy-5β-cholanic acid, the molecular formula is C 24 H 40 O 4 , and the molecular weight is 392.58. It was first extracted from goose bile in 1848. Chenodeoxycholic acid has the ability to dissolve gallstones and other pharmaceutical functions, and has been clinically used as a gallstone-dissolving drug since the 1970s. Studies in recent years have found that ursodeoxycholic acid, an isomer of chenodeoxycholic acid, has a better clinical effect in dissolving gallstones, and has no side effects. Therefore, ursodeoxycholic acid has gradually replaced chenodeoxycholic acid in the clinical application of gallstone-dissolving drugs.
天然熊去氧胆酸来源于熊胆汁，以前是通过杀熊取胆或通过胆汁导流术从熊体内抽提熊胆汁而得到。目前，这种做法已经被国家明令禁止。随着临床应用的需求量不断增加，天然熊去氧胆酸远远不能满足市场需求。通过化学合成方法获得熊去氧胆酸变得越来越重要。近年，以鹅去氧胆酸为原料，合成熊去氧胆酸工艺过程大大简化。Natural ursodeoxycholic acid is derived from bear bile, which was previously obtained by extracting bear bile from bears by killing bears or by bile diversion. At present, this practice has been banned by the state. As the demand for clinical application continues to increase, natural ursodeoxycholic acid is far from meeting the market demand. Obtaining ursodeoxycholic acid by chemical synthesis is becoming more and more important. In recent years, using chenodeoxycholic acid as raw material, the process of synthesizing ursodeoxycholic acid has been greatly simplified.
鹅去氧胆酸是鸡、鸭与鹅等家禽胆汁的主要成份，可以直接从家禽胆汁中提取得到。随着禽产品加工企业的生产规模不断增大，苦胆产量剧增。传统的从鸡、鸭与鹅等的胆汁中提取鹅去氧胆酸的工艺包括胆汁皂化、酸化、除醇不溶物、除脂、生成钡盐、脱钡等步骤，工艺过程复杂，收率低，产业化应用困难。本专利报道一种以鸡胆汁为原料生产鹅去氧胆酸的方法。Chenodeoxycholic acid is the main component of poultry bile such as chicken, duck and goose, and can be directly extracted from poultry bile. Along with the production scale of poultry product processing enterprises is constantly increasing, the output of bitter gall is increasing sharply. The traditional process of extracting chenodeoxycholic acid from the bile of chickens, ducks and geese includes steps such as bile saponification, acidification, removal of alcohol insolubles, fat removal, formation of barium salts, and removal of barium. The process is complicated and the yield is low. , industrial application is difficult. This patent reports a method for producing chenodeoxycholic acid from chicken bile.
发明内容 Contents of the invention
本发明涉及以鸡胆汁为原料生产鹅去氧胆酸的方法。本发明通过在胆汁中加入一定量碱，经皂化、酸化、有机溶剂萃取、重结晶，得到高纯度鹅去氧胆酸产品。The invention relates to a method for producing chenodeoxycholic acid from chicken bile. In the invention, a certain amount of alkali is added into the bile, and a high-purity chenodeoxycholic acid product is obtained through saponification, acidification, organic solvent extraction and recrystallization.
本发明用于胆汁皂化的碱是氢氧化钠或氢氧化钾。皂化温度是保证反应体系呈微沸状态，皂化时间是10～20小时。The alkali used in the saponification of bile in the present invention is sodium hydroxide or potassium hydroxide. The saponification temperature is to ensure that the reaction system is in a slightly boiling state, and the saponification time is 10 to 20 hours.
酸化步骤中应用的酸是硫酸或盐酸，酸化时调节溶液的pH值为4～6。The acid used in the acidification step is sulfuric acid or hydrochloric acid, and the pH value of the solution is adjusted to 4-6 during the acidification.
萃取步骤中应用的有机溶剂是乙醇、丙酮、乙腈和乙酸乙酯等。The organic solvents used in the extraction step are ethanol, acetone, acetonitrile and ethyl acetate, etc.
重结晶步骤中应用的溶剂是乙腈。The solvent used in the recrystallization step was acetonitrile.
具体的实施步骤：Specific implementation steps:
取鸡胆汁500mL，向其中加入NaOH固体50g，搅拌全溶后，加热回流20h。冷却到室温，向其中滴加5％的硫酸，调节体系的pH到4～6，待析出固体量不增加，沉降后过滤，得固体产物。将所得固体溶于200mL乙醇中，向其中加入100mL汽油萃取，分层后，分液。在乙醇相中加入CaCl2饱和溶液100mL，搅匀后加入200mL乙酸乙酯，分液，得乙酸乙酯溶液。旋蒸此溶液，回收乙酸乙酯，得鹅去氧胆酸粗品。干燥后，用乙腈重结晶，得精品鹅去氧胆酸。所得鹅去氧胆酸产品的检测结果为：m.p.：168～170℃；IR(cm-1)：3410(r OH)，2940(rCH)，1720(r C＝O)，1450(δOH)，1378(δCH)，1250(δCOOH)；1HNMR：δH 0.66(3H，s，C13-CH3)，0.90(3H，s，C10-CH3)，0.92(3H，d，C20-CH3)，3.48(1H，br，C3-H)，3.85(H，br，C7-H)。Take 500mL of chicken bile, add 50g of NaOH solid into it, stir to dissolve completely, and heat to reflux for 20h. Cool to room temperature, add 5% sulfuric acid dropwise therein, adjust the pH of the system to 4-6, wait until the amount of precipitated solid does not increase, settle and filter to obtain a solid product. The resulting solid was dissolved in 200mL of ethanol, 100mL of gasoline was added thereto for extraction, and the layers were separated. Add 100 mL of CaCl 2 saturated solution to the ethanol phase, stir well, add 200 mL of ethyl acetate, and separate the layers to obtain an ethyl acetate solution. The solution was rotary evaporated, and the ethyl acetate was recovered to obtain the crude product of chenodeoxycholic acid. After drying, recrystallize with acetonitrile to obtain fine chenodeoxycholic acid. The detection results of the obtained chenodeoxycholic acid product are: mp: 168-170°C; IR (cm -1 ): 3410 (r OH), 2940 (rCH), 1720 (r C=O), 1450 (δOH), 1378(δCH), 1250(δCOOH); 1 HNMR: δH 0.66(3H, s, C13-CH3), 0.90(3H, s, C10-CH3), 0.92(3H, d, C20-CH3), 3.48(1H , br, C3-H), 3.85 (H, br, C7-H).
Claims (9)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110217890 CN102911234A (en) | 2011-08-01 | 2011-08-01 | Method for producing chenodeoxycholic acid by using chicken bile as raw material |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110217890 CN102911234A (en) | 2011-08-01 | 2011-08-01 | Method for producing chenodeoxycholic acid by using chicken bile as raw material |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102911234A true CN102911234A (en) | 2013-02-06 |
Family
ID=47609834
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201110217890 Pending CN102911234A (en) | 2011-08-01 | 2011-08-01 | Method for producing chenodeoxycholic acid by using chicken bile as raw material |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102911234A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106883281A (en) * | 2017-03-08 | 2017-06-23 | 眉山市新功生物科技有限公司 | The method that chenodeoxycholic acid is extracted from duck bile |
| CN107226832A (en) * | 2017-06-15 | 2017-10-03 | 马鞍山汇智生物技术有限公司 | A kind of new method that chenodeoxycholic acid is prepared by raw material of chicken courage |
| CN111285915A (en) * | 2020-03-26 | 2020-06-16 | 山东中京生物科技有限公司 | Novel process for extracting and refining chenodeoxycholic acid from poultry gall bladder |
| CN113912660A (en) * | 2021-10-29 | 2022-01-11 | 四川澄华生物科技有限公司 | Chenodeoxycholic acid phenethylamine salt, preparation method and refining method thereof, and chenodeoxycholic acid preparation method |
| CN115444865A (en) * | 2022-08-04 | 2022-12-09 | 重庆极泽生物科技有限公司 | A kind of transformed bear bile powder substrate and preparation method thereof |
| CN118909016A (en) * | 2024-07-17 | 2024-11-08 | 北京师范大学珠海校区 | Method for extracting biological medicine chenodeoxycholic acid through gel adsorption |
-
2011
- 2011-08-01 CN CN 201110217890 patent/CN102911234A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106883281A (en) * | 2017-03-08 | 2017-06-23 | 眉山市新功生物科技有限公司 | The method that chenodeoxycholic acid is extracted from duck bile |
| CN107226832A (en) * | 2017-06-15 | 2017-10-03 | 马鞍山汇智生物技术有限公司 | A kind of new method that chenodeoxycholic acid is prepared by raw material of chicken courage |
| CN111285915A (en) * | 2020-03-26 | 2020-06-16 | 山东中京生物科技有限公司 | Novel process for extracting and refining chenodeoxycholic acid from poultry gall bladder |
| CN113912660A (en) * | 2021-10-29 | 2022-01-11 | 四川澄华生物科技有限公司 | Chenodeoxycholic acid phenethylamine salt, preparation method and refining method thereof, and chenodeoxycholic acid preparation method |
| CN115444865A (en) * | 2022-08-04 | 2022-12-09 | 重庆极泽生物科技有限公司 | A kind of transformed bear bile powder substrate and preparation method thereof |
| CN115444865B (en) * | 2022-08-04 | 2025-03-07 | 重庆极泽生物科技有限公司 | A kind of bear bile conversion substrate and preparation method thereof |
| CN118909016A (en) * | 2024-07-17 | 2024-11-08 | 北京师范大学珠海校区 | Method for extracting biological medicine chenodeoxycholic acid through gel adsorption |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102911234A (en) | Method for producing chenodeoxycholic acid by using chicken bile as raw material | |
| CN102627573B (en) | Synthesis method for 5-aminolevulinic acid hydrochloride | |
| CN105330609B (en) | A kind of method for preparing LCZ696 | |
| CN106256824B (en) | Preparation method of high-purity delafloxacin meglumine salt | |
| CN103113447A (en) | Method for extracting chenodeoxycholic acid in duck bile by adopting calcium salt process | |
| CN109422793A (en) | A kind of method of combined extracting hyodesoxycholic acid and chenodeoxycholic acid | |
| JP2016514733A (en) | Purification method of .BETA.-hydroxy-.BETA.-methylbutyric acid. | |
| CN102395591B (en) | Method for preparing prasugrel | |
| CN105294761A (en) | Impurities of tenofovir disoproxil fumarate or tenofovir, and preparation method thereof | |
| CN103420845B (en) | One prepares the method for cinacalcet intermediate R-(+)-1-(1-naphthyl) ethamine | |
| KR20080024092A (en) | How to prepare cholanic acid | |
| CN105801585A (en) | Method for synthesizing relevant matter H, E and G in Tadalafil | |
| CN102653523A (en) | Preparation method of pitavastatin calcium by recrystallization | |
| CN109422794A (en) | A method of extracting chenodeoxycholic acid from duck bile | |
| CN110669091A (en) | The purification method of ursodeoxycholic acid | |
| CN103992263B (en) | A kind of purification process of E2020 | |
| CN105884848A (en) | Hyodeoxycholic acid extraction method | |
| CN104447447A (en) | Novel compound and methods for preparing and eliminating same | |
| JP6670744B2 (en) | Polymorphic forms of sodium hyodeoxycholate (NaHDC) and methods for their preparation | |
| CN104311471A (en) | Improved mitiglinide calcium industrialized preparation method | |
| CN100395230C (en) | A method for preparing high-purity gabapentin | |
| CN107602482A (en) | A kind of 2 methyl 4 amino 5 (formyl aminomethyl) pyrimidine hydrolysis process | |
| AU2017343384B2 (en) | Method for isolation and purification of naltrexone | |
| CN102036950B (en) | A new method for preparing 3-(2,2,2-trimethylhydrazine)propionate dihydrate | |
| CN103588775B (en) | Pralatrexate degradation impurity and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20130206 |