CN1332973C - Extraction process of conjugated female hormone - Google Patents
Extraction process of conjugated female hormone Download PDFInfo
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- CN1332973C CN1332973C CNB031138586A CN03113858A CN1332973C CN 1332973 C CN1332973 C CN 1332973C CN B031138586 A CNB031138586 A CN B031138586A CN 03113858 A CN03113858 A CN 03113858A CN 1332973 C CN1332973 C CN 1332973C
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Abstract
The present invention relates to a method for extracting female hormone from the urine of a pregnant mare by using polar adsorption resin containing sulfoxide radicals. Extraction elution is adopted to elute the resin. The combination of the extraction elution with the polar adsorption resin containing sulfoxide radicals can improve the selective adsorption and desorption of the female hormone and raise the recovery rate of the female hormone. The method of the present invention has the advantages of simple technology and low cost, and is favorable for industrialized production.
Description
The present invention relates to a kind of from pregnant horse urine liquid (Pregnant Mare ' s Urine, PMU) the middle method of extracting combined female hormone (Conjugated Estrogen).
The combined female hormone that extracts from pregnant horse urine liquid is mainly used in Hormone Replacement Therapy (Estrogen Replacement Therapy, ERT), be used for the treatment of climacteric syndrome, cardiovascular system diseases and the osteoporosis that can effectively prevent and treat.
Oestrogenic hormon is the class importance glandular hormone in the animal body, belongs to the steroid hormone of steroid.The breeding physiology of jenny is subjected to the dominant force of nervus centralis and pituitary gland portion, is also directly accepting main hormonal effects by ovarian secretion.The dam Gestation period and just before giving birth before and after, the significant variation takes place in internal secretion, estrogenic physiological action is suppressed, but its generation still carrying out, so the estrogen content in the Gestation period dam movement significantly increase, particularly remarkable in this phenomenon of mare.
In the sixties in 20th century, adopt the estrogenic Hormone Replacement Therapy of pregnant horse urine to begin to rise in the U.S. and Canada, the consequent is Hormone Replacement Therapy and climacteric women carcinoma of endometrium, the pass that mammary cancer takes place ties up to medical circle and also has dispute, and view differs.But along with the aging problem becomes increasingly conspicuous in many countries, the threat that the fracture that the cardiovascular system diseases of the low initiation of body inner estrogen level and osteoporosis cause causes elderly woman life again day by day seriously, the nineties in 20th century coronary heart disease become postmenopausal women's first cause of the death in developed country.Still do not have other treatment except that Hormone Replacement Therapy, oestrogenic hormon lacks the effective ways of the climacteric syndrome of initiation.
The main method of extraction that adopts is separated extraction combined oestrogenic hormon from pregnant horse urine in the research in early days, United States Patent (USP) 2519516 is arranged, 2696265,2834712, English Patent 2017906, Australian Patent 6426999, the method of its extraction adopts organic low-carbon alcohol, ester, halohydrocarbon etc., the method of abstraction purification removal of impurities through three to eight steps is carried out, and main problem is that the extracting and emulsifying problem is serious, causes problems such as the low and oestrogenic hormon rate of recovery of separation efficiency is low.In the research in later stage, adopt absorption to resolve technology, comprise United States Patent (USP) 2551205,5723454, Russ P 2179028, Slovakia's patent 24499 mainly adopts gac, silica gel, ion exchange resin etc.; And Chinese patent 1308083,1228027,1234740, adopt polar resin, silica gel and the semi-polarity resin of cyano-containing respectively.There are the regeneration difficulty in early stage sorbent material such as activated carbon, silica gel etc., the problem that adsorption efficiency is low, and the later stage sorbent material comprises ion exchange resin, and the Polar Adsorbent Resin of cyano-containing is regenerated easily but saturated capacity is low, and adsorption selectivity is poor.
The present invention mainly describes the estrogenic method of Polar Adsorbent Resin extraction pregnant horse urine that a kind of utilization contains sulfoxide group, and a kind of eluex process that is applied to the resin parsing of initiative proposition.
Make the polymeric adsorbent of load with the Polar Adsorbent Resin that contains sulfoxide group, mainly be to have utilized the sulfoxide group Polar Adsorbent Resin of macroporous netlike to carry out isolating to the selective adsorption effect of effective constituent, elder generation is with pregnant horse urine and resin is dynamic or Static Contact, the combined mixed estrin just is attracted on the post, use the organic solvent wash-out again, resolve afterwards, through concentrating, be drying to obtain the pregnant Sterones mixture of combined.
The brand-new type of elution of a kind of resin absorption material of Kai Chuanxing proposition is drenched the collection process in the present invention.This is a kind of separating substances process of physics, and principle is in the drip washing equilibrium process, has the secondary distribution balance of extraction process simultaneously.Conventional resin elution liquid is generally used low-carbon alcohol, ketone, and ether, ester isopolarity material washs.The drip washing flow process that the present invention proposes just is to exist twice partition equilibrium, estrogenic once balance in leacheate and the resin, and the secondary balancing of wash-out host and extraction agent in the washings, this chemical separation process has been successfully applied to nuclear industry at present, obtains the unusual effect that improves partition ratio.
In the process of the wash-out effective ingredient of resin, there is the partition equilibrium process that is incorporated on the resin and is dissolved in elutriant in effective ingredient.In static resolving, use a certain amount of elutriant to soak saturated resin, stir and make resin and elutriant thorough mixing, make after a period of stabilisation, change elutriant.In the static mixing elution process, along with the increase of time, do not have more effective ingredient and eluted, must change fresh Xian and take off agent, can prove thus to have effective constituent in the partition equilibrium on the resin and between the elutriant.Owing to have this partition equilibrium, so elutriant can elute effective ingredient in batches.We call the drip washing balance to this partition equilibrium.
Drenching the collection process is exactly to increase one or several organic solvents in elutriant, makes to remove in the elution process to have the drip washing balance external, increases the secondary distribution balance, i.e. extraction equilibrium.Organic solvent adopts the insoluble or sl. sol. organic solvent of water, and this organic solvent can be polar solvent or non-polar solvent.General resin elution liquid is the aqueous solution that contains water-miscible organic solvent, and minority can adopt pure organic solvent.Organic component in these elutriants can make to the extraction agent of realizing that eluex process adds, is dissolved in the stable homogeneous phase of formation in the elutriant; Perhaps the part extraction agent can not be dissolved in eluent fully, and the suitable tensio-active agent of suitable interpolation can form stable homogeneous phase.
The key of drenching the collection process is that water does not dissolve or sl. sol. organic solvent at the organic solvent that is used to extract purpose.
The treatment process of drenching the collection elutriant has two kinds, and a kind of is to handle according to normal elutriant, and another kind is to increase tensio-active agent to make the elutriant layering in elutriant, forms biphasic system, will contain a phase of high-purity effective ingredient, further processes.
The major advantage of drenching the collection process is to have twice or twice above partition equilibrium, can effective constituent be got off from resin drip washing with less elutriant, improve the concentration of effective ingredient in the elutriant, improve the separation factor between the isolate simultaneously, obtain the higher effective ingredient of purity.
Drench the polar resin of finding to contain sulfoxide group in the collection process in research, help the estrogenic absorption of combined and drench collection resolving.
The step of extracting combined female hormone from pregnant horse urine liquid that the present invention describes comprises following content:
1, with pregnant horse urine by containing the polar resin of sulfoxide group, online detection.
2, wash resin with water.
3, the elutriant with preparation drenches collection resolving.
4, the elutriant that will drench collection carries out aftertreatment, and concentrate drying obtains combined estrogen mixture solid.
The pregnant horse urine of mentioning in step 1 is not for containing or contain the pregnant horse urine of a small amount of suspended substance.Contain suspended substance and be unfavorable for resin absorption, should advanced processing to remove most suspended substances, method can be conventional process such as ultrafiltration, centrifuging, press filtration.
The resin of mentioning in step 1 is the polar resin that contains sulfoxide group.
That mentions in step 2 washes resin with water, can adopt the neutral water washing, or the alkaline water washing, or earlier with the neutral water washing, uses the alkaline water washing resin again.
Elutriant composition in step 3 is: water; A kind of can with the low-carbon alcohol of water mutual solubility, ketone, ester isopolarity organic solvent, including but not limited to ethanol, methyl alcohol, acetone; And the insoluble or sl. sol. low-carbon alcohol of one or several water, ketone, organic solvents such as haloalkane, including but not limited to ethyl acetate, hexanol, ring is alcohol, propyl carbinol, chloroform.
Elutriant in step 3 can be pH value neutrality.
Elutriant in step 3 can be regulated
DH is an alkalescence, increases elute effect, and the PH scope is 8～13, need in the last handling process in step 5 to require to regulate earlier pH value simultaneously for neutral;
In step 3, drenching the collection temperature is normal temperature wash-out or heating wash-out, heats favourable to resolving.Temperature range is below 65 ℃.
Last handling process in step 4 can be for directly concentrated, dry; Also can add tensio-active agent and make water-insoluble organic solvent and aqueous phase separation.The reconcentration drying.If elutriant is an alkalescence in the step 3, it is neutral needing to regulate earlier pH value.
The renovation process of polymeric adsorbent can adopt conventional polymeric adsorbent treatment process, with 75% left and right sides ethanol elution regeneration, can adopt 1NHCL and 1NNaOH to handle in case of necessity.
In the following embodiments, merge second and third column volume elutriant, spraying drying obtains containing the light yellow solid powder of combined mixed estrin, and wherein the combined estrogen content can reach more than 15%.Be better than adopting the effect of ordinary resin wash-out, and the oestrogenic hormon wash-out is more concentrated, can form hangover.
The oestrogenic hormon of mentioning in the following example of the present invention all refers to combined oestrogenic hormon, and the estrogenic analytical procedure of combined is that HPLC detects, and column volume refers to be equivalent to the resin column volume in the following example.
Embodiment one:
Contain the estrogenic horse urine of 40mg/l with 2.5 liters and pass through 30 milliliters of Polar Adsorbent Resin (commercially available, Chemical Plant of Nankai Univ.) that contain sulfoxide group, dynamic adsorption.Wash resin with water to colourless, shared water 90ml.Be 10 water washing resin then with pH value, to colourless, shared water 90ml.Eluent is a water: ethanol: the ethyl acetate ratio is 45: 35: 20.The normal temperature wash-out, elutriant is collected four column volumes.
Embodiment two:
Contain the estrogenic horse urine of 35mg/l with 3 liters and pass through 30 milliliters of Polar Adsorbent Resin that contain sulfoxide group, dynamic adsorption.Washing resin with water to colourless, is 11 water washing resin with pH value, to colourless then.Eluent is a water: ethanol: the hexalin ratio is 50: 30: 20, pH value 11.55 ℃ of wash-outs are collected four column volumes.
| Embodiment number | One | Two | Three |
| Horse urine initial concentration | 40mg/l | 35mg/l | 35mg/l |
| Elutriant | Water/ethanol/ethyl acetate 45: 35: 20 | Water/ethanol/50: 30: 20 PH 11 of hexalin | Water/ethanol/50: 25: 25 PH 10 of propyl carbinol |
| Eluting temperature | Normal temperature | 55℃ | Normal temperature |
| The first column volume concentration | 0 | 0 | 0 |
| The second column volume concentration | 1246mg/l | 1356mg/l | 954mg/l |
| The 3rd column volume concentration | 939mg/l | 856mg/l | 1183mg/l |
| The 4th column volume concentration | 32mg/l | 29mg/l | 83mg/l |
Embodiment three:
Contain the estrogenic horse urine of 35mg/l with 3 liters and pass through 30 milliliters of Polar Adsorbent Resin that contain sulfoxide group, dynamic adsorption.Washing resin with water to colourless, is 10 water washing resin with pH value, to colourless then.Eluent is a water: ethanol: the propyl carbinol ratio is 50: 25: 25, and elutriant is transferred pH value 10.The normal temperature wash-out is collected four column volumes.
Claims (4)
1, a kind of method of extracting combined female hormone from pregnant horse urine liquid is characterized in:
A) with pregnant horse urine by containing the Polar Adsorbent Resin of sulfoxide group.
B) wash resin with water.
C) elutriant with preparation drenches collection resolving.
D) elutriant that will drench after coming together carries out aftertreatment, and concentrate drying obtains combined estrogen mixture solid.
2, according to the requirement of right 1, it is characterized in that, at method steps A) in applied resin be the Polar Adsorbent Resin that contains sulfoxide group.
3, according to the requirement of right 1, it is characterized in that, at method steps C) in the elutriant composition used be: water, a kind of can with the organic solvent of water mutual solubility, one or several are water insoluble or be slightly soluble in the organic solvent of water.
4, according to the requirement of right 1, it is characterized in that, at method steps C) in applied elutriant can be pH value neutrality; Perhaps PH is an alkalescence, and alkaline range is 8～13.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031138586A CN1332973C (en) | 2003-03-06 | 2003-03-06 | Extraction process of conjugated female hormone |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031138586A CN1332973C (en) | 2003-03-06 | 2003-03-06 | Extraction process of conjugated female hormone |
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| Publication Number | Publication Date |
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| CN1526721A CN1526721A (en) | 2004-09-08 |
| CN1332973C true CN1332973C (en) | 2007-08-22 |
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| CNB031138586A Expired - Fee Related CN1332973C (en) | 2003-03-06 | 2003-03-06 | Extraction process of conjugated female hormone |
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Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1325062C (en) | 2005-12-06 | 2007-07-11 | 新疆特丰药业股份有限公司 | Method for obtaining binded estrogen mixture from pregnant horse urine, and its uses of big pore adsorption resin in the method |
| CN101949907A (en) * | 2010-06-30 | 2011-01-19 | 北京六角体科技发展有限公司 | Steroid pretreatment and detection method |
| CN114588179A (en) * | 2020-12-03 | 2022-06-07 | 中国科学院大连化学物理研究所 | Method for separating and purifying conjugated estrogens from pregnant mare urine by using preparative chromatography |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998008526A1 (en) * | 1996-08-30 | 1998-03-05 | Solvay Deutschland Gmbh | Method to obtain oestrogens from mare's urine |
| WO1998008525A1 (en) * | 1996-08-30 | 1998-03-05 | Solvay Deutschland Gmbh | Process to obtain oestrogens from mare's urine |
| CN1278432A (en) * | 1999-06-22 | 2001-01-03 | 中国科学院新疆化学研究所 | Method of extracting female hormone from pregnant woman's urine |
| CN1308083A (en) * | 2001-02-19 | 2001-08-15 | 中国科学院新疆化学研究所 | Extraction method of combined mixed estrin of pregnant mare |
| CN1381240A (en) * | 2001-04-18 | 2002-11-27 | 台湾神隆股份有限公司 | Process for preparing conjugated oestrogens from urine of pregnant mare |
-
2003
- 2003-03-06 CN CNB031138586A patent/CN1332973C/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998008526A1 (en) * | 1996-08-30 | 1998-03-05 | Solvay Deutschland Gmbh | Method to obtain oestrogens from mare's urine |
| WO1998008525A1 (en) * | 1996-08-30 | 1998-03-05 | Solvay Deutschland Gmbh | Process to obtain oestrogens from mare's urine |
| CN1278432A (en) * | 1999-06-22 | 2001-01-03 | 中国科学院新疆化学研究所 | Method of extracting female hormone from pregnant woman's urine |
| CN1308083A (en) * | 2001-02-19 | 2001-08-15 | 中国科学院新疆化学研究所 | Extraction method of combined mixed estrin of pregnant mare |
| CN1381240A (en) * | 2001-04-18 | 2002-11-27 | 台湾神隆股份有限公司 | Process for preparing conjugated oestrogens from urine of pregnant mare |
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Effective date of registration: 20051230 Address after: Nanshan District Ma Liuzhou Industrial Zone of Shenzhen City, Guangdong Province, building 202 day flight Applicant after: Shenzhen Hadak Industrial Co.,Ltd. Address before: Nanshan District Ma Liuzhou Industrial Zone of Shenzhen City, Guangdong Province, building 202 day flight Applicant before: Zhou Tao Co-applicant before: Wang Yongli Co-applicant before: Jiang Feng |
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