CN1284510A - 利用猪、牛、羊肺沉淀法生产肝素钠 - Google Patents
利用猪、牛、羊肺沉淀法生产肝素钠 Download PDFInfo
- Publication number
- CN1284510A CN1284510A CN 99111447 CN99111447A CN1284510A CN 1284510 A CN1284510 A CN 1284510A CN 99111447 CN99111447 CN 99111447 CN 99111447 A CN99111447 A CN 99111447A CN 1284510 A CN1284510 A CN 1284510A
- Authority
- CN
- China
- Prior art keywords
- heparin
- pig
- heparin sodium
- sodium
- cattle
- 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
- 229920000669 heparin Polymers 0.000 title claims abstract description 26
- 238000000034 method Methods 0.000 title claims abstract description 17
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 title claims abstract description 14
- 229960001008 heparin sodium Drugs 0.000 title claims abstract description 14
- 210000004072 lung Anatomy 0.000 title claims abstract description 11
- 241001494479 Pecora Species 0.000 title claims abstract description 10
- 238000001556 precipitation Methods 0.000 title claims abstract description 6
- 238000004519 manufacturing process Methods 0.000 title description 5
- 241000283690 Bos taurus Species 0.000 title 1
- 241000282898 Sus scrofa Species 0.000 title 1
- 238000000605 extraction Methods 0.000 claims abstract description 6
- 239000011347 resin Substances 0.000 claims abstract description 4
- 229920005989 resin Polymers 0.000 claims abstract description 4
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 12
- 229960002897 heparin Drugs 0.000 claims description 12
- 239000012716 precipitator Substances 0.000 claims description 4
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 abstract description 2
- 239000002244 precipitate Substances 0.000 abstract description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 abstract 3
- 239000003513 alkali Substances 0.000 abstract 1
- ZQLAOWZUUCJIPG-UHFFFAOYSA-N azane;1-bromohexadecane Chemical compound N.CCCCCCCCCCCCCCCCBr ZQLAOWZUUCJIPG-UHFFFAOYSA-N 0.000 abstract 1
- -1 cetyl trimethyl pyridinium bromide Chemical compound 0.000 abstract 1
- 230000001105 regulatory effect Effects 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 2
- 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 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 2
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 2
- 235000011130 ammonium sulphate Nutrition 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 210000000813 small intestine Anatomy 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- BOGUPGVJPYQSQC-UHFFFAOYSA-N 2-hexadecyl-1h-pyrrole Chemical compound CCCCCCCCCCCCCCCCC1=CC=CN1 BOGUPGVJPYQSQC-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000000409 membrane extraction Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229920000447 polyanionic polymer Polymers 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一种利用猪、牛、羊肺替代树脂法,采用十六烷基三甲基溴化吡啶铵沉淀法提取肝素钠工艺。它由苯、铵、碱调解、分解、析出肝素－蛋白络合物沉淀加十六烷基溴化铵后离心分离,使肝素沉淀析出。从而使生产肝素钠的操作工艺难度降低,且提取率提高。
Description
本发明涉及一种采用长链季铵盐沉淀法提取肝素钠的新工艺。
目前，现有肝素钠生产工艺中，多数采用树脂法提取，原料为猪、羊小肠。而采用猪、牛、羊肺为原料生产肝素其中如：河南富程生化研究所采用D-254树脂吸附法。每1000克肺、只能提取肝素4.5万单位，效价70单位/毫克。
上海生化制药厂引进英国专利采用十六烷基吡定铵沉淀肝素，只能用于猪、羊小肠粘膜提取肝素。
台湾畜产研究所宜兰分所与台湾大学合作开发成功的利用猪肺生产工艺，属萃取法，其产量每1000克原料可提取肝素5万单位，效价恒定80单位/毫克，但其工艺操作比较复杂，提取率也未有大幅度提高。
本发明目的是提供一种方法简单，提取率高的生产肝素的工艺操作规程。
本发明是基于下面的原理而实现的：
肝素钠是一种硫酸氨基葡聚糖的钠盐，属粘多糖类物质。肝素在溶液中作为聚阴离子(有独特的临界盐浓度和高电荷密度)或者同各种阳离子(包括胺)结合而从水溶液中沉淀出来。
下面对本发明提出的利用猪、牛、羊肺沉淀肝素钠具体方式做进一步描述：
1、将猪、牛、羊肺体搅碎、磨浆加入等量的水、然后加热至一定温度、继续加入一定比例的甲苯、冷却、定时搅拌、加入硫酸铵水，制成溶液。加氢氧化钠调整PH值，水溶液加热至一定温度，保温一定时间，冷却过滤。
2、滤渣加入硫酸铵及水、混合液中加入氢氧化钠调整PH加热，过滤、冷却、加适度硫酸调整PH值，析出肝素一蛋白络合物沉淀。虹吸清液离心分离。固体用酒精洗涤、除脂肪、调整PH值，加氯化钠溶液，调整PH值，沉淀蛋白质，得黄色透明肝素溶液。
3、将黄色溶液调整PH值后加入蒸馏水、再加入十六烷基三甲基溴化铵溶液，搅拌静置，虹吸清液，沉淀物离心分离。继续加入十六烷基三甲基溴化铵、氯化钠溶液，乙醇、使肝素沉淀析出。脱色、除氧化物。稀释、再脱色、离心后加乙醇，静置后离心分离，丙酮洗涤后干燥、即为肝素钠。
大量实验表明，本发明提取肝素钠每1000克肺可提取肝素钠80000单位，效价恒定在90-95单位/毫克以上。
本发明写明了利用猪、牛、羊肺沉淀法生产肝素钠的工艺操作规程，用此方法生产肝素钠，提取率高且工艺简单，易于实际操作。
Claims (2)
1、一种替代树脂法、利用猪、牛、羊肺采用十六烷基溴化铵沉淀法提取肝素钠的工艺。
2、根据权利要求的工艺，其特征在于长链季铵盐沉淀析出肝素，使肝素外观白，提取率高、效价高。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 99111447 CN1284510A (zh) | 1999-08-17 | 1999-08-17 | 利用猪、牛、羊肺沉淀法生产肝素钠 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 99111447 CN1284510A (zh) | 1999-08-17 | 1999-08-17 | 利用猪、牛、羊肺沉淀法生产肝素钠 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1284510A true CN1284510A (zh) | 2001-02-21 |
Family
ID=5275096
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 99111447 Pending CN1284510A (zh) | 1999-08-17 | 1999-08-17 | 利用猪、牛、羊肺沉淀法生产肝素钠 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1284510A (zh) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101218259B (zh) * | 2005-05-09 | 2011-06-15 | 赫普马林公司 | 制备低分子量肝素的方法 |
| CN103951768A (zh) * | 2014-04-29 | 2014-07-30 | 贵州慧静生物科技有限公司 | 利用猪、牛肺提取肝素钠并联产多肽蛋白粉、氨基酸蛋白粉的方法 |
-
1999
- 1999-08-17 CN CN 99111447 patent/CN1284510A/zh active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101218259B (zh) * | 2005-05-09 | 2011-06-15 | 赫普马林公司 | 制备低分子量肝素的方法 |
| CN103951768A (zh) * | 2014-04-29 | 2014-07-30 | 贵州慧静生物科技有限公司 | 利用猪、牛肺提取肝素钠并联产多肽蛋白粉、氨基酸蛋白粉的方法 |
| CN103951768B (zh) * | 2014-04-29 | 2016-05-11 | 贵州慧静生物科技有限公司 | 利用猪、牛肺提取肝素钠并联产多肽蛋白粉、氨基酸蛋白粉的方法 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103601815B (zh) | 碱解-酶解法结合絮凝沉淀法提取硫酸软骨素钠 | |
| CN103467621B (zh) | 一种高纯度鲟鱼硫酸软骨素的制备方法 | |
| CN103160482B (zh) | 一种共分离制备鸡蛋清溶菌酶与活性蛋白的方法 | |
| CN102295711A (zh) | 从猪肺中提取肝素钠并联产多肽蛋白粉的工艺 | |
| CN103951768B (zh) | 利用猪、牛肺提取肝素钠并联产多肽蛋白粉、氨基酸蛋白粉的方法 | |
| CN113234181B (zh) | 一种硫酸软骨素的制备方法 | |
| CN103848929B (zh) | 一种肝素钠的高效提取工艺 | |
| CN109957045A (zh) | 一种从动物肝脏中提取肝素钠和蛋白肽的联产工艺 | |
| CN1284510A (zh) | 利用猪、牛、羊肺沉淀法生产肝素钠 | |
| CN105777567B (zh) | 一种复合氨基酸螯合钙的制备方法 | |
| CN103804517A (zh) | 提高硫酸软骨素收率的制备方法 | |
| CN1624004A (zh) | 硫酸软骨素的提取方法 | |
| CN1544645A (zh) | 双酶法生产硫酸软骨素 | |
| CN109384861A (zh) | 一种肝素钠废液提取硫酸皮肤素的方法 | |
| CN102961403B (zh) | 一种从动物器官提取的组合物 | |
| US20240247293A1 (en) | Method for increasing the extraction rate of chondroitin sulfate prepared from tilapia skull | |
| CN114539132A (zh) | 一种水热酸控醇提桑叶中dnj方法 | |
| KR100343781B1 (ko) | 가오리류로부터 콘드로이틴황산의 추출 및 정제방법 | |
| CN105622779A (zh) | 澄清硫酸软骨素酶解液的制备方法 | |
| CN101480255A (zh) | 利用猪血清和肽铁制作新型猪血豆腐的方法 | |
| CN86100551A (zh) | 超氧化歧化酶(sod)的提纯方法 | |
| RU2061485C1 (ru) | Способ выделения хондроитинсульфата из животных тканей | |
| KR100618073B1 (ko) | 홍어연골 추출물의 추출방법 | |
| CN112159486B (zh) | 利用猪小肠粘膜低盐制备粗品肝素钠的方法 | |
| RU2139716C1 (ru) | Способ получения агрегатов протеогликанов из хряща сельскохозяйственных животных |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C57 | Notification of unclear or unknown address | ||
| DD01 | Delivery of document by public notice |
Addressee: Sun Runwei Document name: Notice of publication of application for patent for invention |
|
| C57 | Notification of unclear or unknown address | ||
| DD01 | Delivery of document by public notice |
Addressee: Sun Runwei Document name: Notification before expiration of term |
|
| C57 | Notification of unclear or unknown address | ||
| DD01 | Delivery of document by public notice |
Addressee: Sun Runwei Document name: Deemed as a notice of withdrawal |
|
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |