CN103739700B - 一种苯甲酸钠提取绒促性素的方法 - Google Patents
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- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 title claims abstract description 15
- 235000010234 sodium benzoate Nutrition 0.000 title claims abstract description 15
- 239000004299 sodium benzoate Substances 0.000 title claims abstract description 15
- 229960004407 chorionic gonadotrophin Drugs 0.000 title claims abstract description 14
- 238000000034 method Methods 0.000 title claims abstract description 12
- 239000000284 extract Substances 0.000 title claims abstract description 5
- 210000002700 urine Anatomy 0.000 claims abstract description 26
- 238000010521 absorption reaction Methods 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000002244 precipitate Substances 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 239000002156 adsorbate Substances 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 5
- 238000001179 sorption measurement Methods 0.000 claims description 5
- 239000002699 waste material Substances 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 3
- 239000011265 semifinished product Substances 0.000 claims description 3
- 238000001291 vacuum drying Methods 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 230000001186 cumulative effect Effects 0.000 claims description 2
- 239000004744 fabric Substances 0.000 claims description 2
- 238000007689 inspection Methods 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 239000004033 plastic Substances 0.000 claims description 2
- 229920003023 plastic Polymers 0.000 claims description 2
- 238000012360 testing method Methods 0.000 claims description 2
- 238000000605 extraction Methods 0.000 abstract description 4
- 238000003795 desorption Methods 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- 239000005995 Aluminium silicate Substances 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 3
- 239000003463 adsorbent Substances 0.000 description 3
- 235000012211 aluminium silicate Nutrition 0.000 description 3
- 235000010233 benzoic acid Nutrition 0.000 description 3
- 239000002253 acid Substances 0.000 description 2
- PZZYQPZGQPZBDN-UHFFFAOYSA-N aluminium silicate Chemical compound O=[Al]O[Si](=O)O[Al]=O PZZYQPZGQPZBDN-UHFFFAOYSA-N 0.000 description 2
- 229910000323 aluminium silicate Inorganic materials 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 230000000938 luteal effect Effects 0.000 description 1
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- 230000001817 pituitary effect Effects 0.000 description 1
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- 239000000843 powder Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
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- 230000002381 testicular Effects 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 210000002993 trophoblast Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/59—Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g.hCG [human chorionic gonadotropin]; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
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Abstract
本发明公开了一种用苯甲酸钠提取绒促性素的方法,具体方法是向孕妇尿中加入苯甲酸钠,再降温与调pH值,达到从尿液中高效提取绒促性素的目的。本方法通过改良的苯甲酸钠法提取绒促性素,不仅可以更高效的从尿液中提取绒促性素,还大大降低了脱附的难度,保证了成本得到有效的控制,实现大规模工业生产。
Description
技术领域
本发明涉及生物技术领域,利用苯甲酸钠提取尿液中的绒促性素,再利用低温与强酸的环境,使提取更加完全,达到提高提取率的效果。
背景技术
绒促性素为促性腺激素药。是从受精卵着床第1天,由胎盘滋养层合体细胞分泌的,60-70天时达到高峰。此后逐渐下降,分娩后4天左右消失。对女性能促进和维持黄体功能,可促进卵泡生成和成熟。对男性能使垂体功能不足者的睾丸产生雄激素,促使睾丸下降和男性第二性征的发育。
1928年Zondek和Ascbheim首先用乙醇沉淀法,从孕妇尿中取得了活性物质,其他研究者则进行应用吸附剂从尿中直接吸附绒促性素的研究,这包括苯甲酸吸附法,人造沸石层析吸附法,高岭土吸附法,用离子交换树脂吸附法等,用这些方法所取得的绒促性素再用各种纯化方法进行纯化。
传统的苯甲酸钠吸附法粗品效价和回收率很低,其他吸附剂在吸附绒促性素时,虽然吸附效果好,吸附量大,但在脱附时难度较大,工序也非常复杂繁琐,大大增加了工作量和成本。近几年也有使用硅酸铝作为HCG的吸附剂,效价和回收率均有不同程度的提高,但由于硅酸铝生产没有形成规模,或需从国外进口,因此,同样大大增加了生产成本,不易推广。本发明针对以上问题,通过改变苯甲酸钠吸附时的温度、pH值和添加酸的比例,不仅大幅度的提高了产品吸附率及效价,而且很好的控制了生产成本。
本发明提出的苯甲酸钠吸附绒促性素的具体方法,包括以下步骤:
1)检查尿液是否澄清,用pH1-14试纸检查尿的pH值是否在5.0-7.0之间;若不符合要求,将尿液弃去。
2)将尿液称重后用14目纱网过滤,然后用泵输送到反应罐中。
3)量取尿液的总体积,按体积1%-5%的比例加苯甲酸钠,搅拌15分钟,使苯甲酸钠全部溶解。
4)不断搅拌,待尿液温度为5-12℃条件下,缓慢加入工业盐酸,调节到3.8~5.2,并用pH3.8~5.4精密试纸测定,pH调好后继续搅拌1.5h,使吸附完全。
5)将吸附液放入白细布袋内,废尿液弃去,取白色沉淀物。然后再放在甩干机中甩干吸附物。
6)将甩干的白色吸附物放在塑料白桶中,以尿液重量的0-1.2:2.3-4.0比例加95%乙醇充分搅拌,有絮状沉淀后静置8-10小时。
7)弃去上层废液,底部絮状沉淀物用布氏漏斗过滤,将抽滤干之沉淀物取出,置真空干燥器中真空干燥后即得粗制品。
具体实施例
实施例1
1)取合格孕妇尿液1T入反应罐中加20kg苯甲酸钠,搅拌使苯甲酸纳全部溶解,以缓慢的速度加入工业盐酸,调节尿液pH到4.5,不断搅拌1小时,使吸附完全;
2)过滤,弃去废尿液,得吸附物60kg;
3)取吸附物加乙醇240kg,充分搅拌,直到白色苯甲酸全部溶解,有絮状沉淀产生为止,静置过夜;
4)虹吸上清液,向底部絮状沉淀物加入1倍量95%乙醇稍加搅拌后,放置4小时以上,待沉淀完全;
5)弃去上层液,过滤底部絮状沉淀,将过滤物取出,置用工业无水五氧化二磷作吸水剂的真空干燥器中真空干燥,得干燥物;
6)将干燥物研磨成粉末即得粗制品,称重700g。即每吨尿液中可得700g绒促性素粗品。
以上所述,仅是本发明的较佳实施例而已,并非是对本发明作其它形式的限制,任何熟悉本专业的技术人员可能利用上述揭示的技术内容加以变更或改型为等同变化的等效实施例。但是凡是未脱离本发明技术方案内容,依据本发明的技术实质对以上实施例所作的任何简单修改、等同变化与改型,仍属于本发明技术方案的保护范围。
Claims (1)
1.一种苯甲酸钠提取绒促性素的方法,包括以下步骤:
1)检查尿液是否澄清,用pH1-14试纸检查尿的pH值是否在5.0-7.0之间;若不符合要求,将尿液弃去;
2)将尿液称重后用14目纱网过滤,然后用泵输送到反应罐中;
3)量取尿液的总体积,按体积1%-5%的比例加苯甲酸钠,搅拌15分钟,使苯甲酸钠全部溶解;
4)不断搅拌,待尿液温度为5-12℃条件下,缓慢加入工业盐酸,调节到3.8~5.2,并用pH3.8~5.4精密试纸测定,PH调好后继续搅拌1.5h,使吸附完全;
5)将吸附液放入白细布袋内,废尿液弃去,取白色沉淀物,然后再放在甩干机中甩干吸附物;
6)将甩干的白色吸附物放在塑料白桶中,以尿液重量的0-1.2∶2.3-4.0比例加95%乙醇充分搅拌,有絮状沉淀后静置8-10小时;
7)弃去上层废液,底部絮状沉淀物用布氏漏斗过滤,将抽滤干之沉淀物取出,置真空干燥器中真空干燥后即得粗制品。
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CN1302818A (zh) * | 2000-12-12 | 2001-07-11 | 上海惠海生化制品厂 | 一种人绒毛膜促性腺激素及其制备方法 |
CN103084149A (zh) * | 2013-02-25 | 2013-05-08 | 常军强 | 一种高效低温绒促性素吸附剂及其制备方法 |
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CN1302818A (zh) * | 2000-12-12 | 2001-07-11 | 上海惠海生化制品厂 | 一种人绒毛膜促性腺激素及其制备方法 |
CN103084149A (zh) * | 2013-02-25 | 2013-05-08 | 常军强 | 一种高效低温绒促性素吸附剂及其制备方法 |
Non-Patent Citations (2)
Title |
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HCG粗品生产中对时间、温度和PH值三要素的掌握;吴盛铨;《今日科技》;19950815(第8期);第8页右栏第二节 * |
人绒毛膜促性腺激素(HCG)粗品新工艺研究;张培培;《中国生化药物杂志》;19950215;第16卷(第1期);第26页材料和方法部分 * |
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