CN102018795A - Traditional Chinese medicine composition for improving endometrial receptivity - Google Patents
Traditional Chinese medicine composition for improving endometrial receptivity Download PDFInfo
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- CN102018795A CN102018795A CN 201010603410 CN201010603410A CN102018795A CN 102018795 A CN102018795 A CN 102018795A CN 201010603410 CN201010603410 CN 201010603410 CN 201010603410 A CN201010603410 A CN 201010603410A CN 102018795 A CN102018795 A CN 102018795A
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Abstract
The invention belongs to the technical field of traditional Chinese medicines, relating to a traditional Chinese medicine composition for improving endometrial receptivity. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 15-20 of epimedium, 10-15 of morindae officinalis, 20-25 of south dodder seed and 15-20 of eucommia. The preparation method of the traditional Chinese medicine composition is as follows: soaking bulk drugs weighed proportionally with clear water; and boiling the cleared bulk drugs for 40-60 minutes to prepare decoction. The traditional Chinese medicine composition can improve the endometrial receptivity, can be used as an adjuvant drug for external fertilization-embryo transplantation, has the advantages of rich drug sources, simple composition, cheap price, precise curative effect and no toxic and side effects, and can treat both principal and secondary aspect of disease.
Description
Technical field
The present invention relates to a kind of Chinese medicine composition that improves the endometrium endometrial receptivity and preparation method thereof, belong to technical field of Chinese medicines.
Background technology
How to improve the pregnancy rate of vitro fertilization-embryo implanting (IVF-ET), be still the clinical problem demanding prompt solution of reproductive medicine.The normal implantation of blastocyst is a pregnant clinically successful key factor.At the natural conception state, approximately have only 30% the blastocyst can successful implantation, and in vitro fertilization-embryo implanting (IVF-ET), the implantation success rate be just lower, only is about 10%-15%, shows that implantation process has great influence to successful pregnancy.And the parent endometrium is that the endometrium endometrial receptivity is closely related with implantation process to embryo's ability to accept, has only when the intrauterine film has endometrial receptivity " implantation window ", and blastocyst just can be attracted on the endometrium.
Chinese medicine is used for gravidity assisting early historical records, also has the people Chinese medicine to be used to improve the research of patient's endometrium endometrial receptivity of induced ovulation now.Zhou Bin etc. are applied to the infertile patient of induced ovulation with female precious granule, and the result shows, with matched group relatively, female precious granule can significantly increase the endometrium thickness of HCG injection day and improve the inner membrance typing, thereby increase the endometrium blood supply, significantly improve the endometrium endometrial receptivity, improve pregnancy rate.The tonify Qi of the kidney influence of the blastocyst implantation obstacle endometrium of mouse endometrial receptivity that blood circulation promoting recipe causes mifepristone of research Chinese medicines such as Huang Dongmei, find that Chinese medicine can significantly improve the prominent sequential expression of pinocytosis, improve estrogen and progestogen and expression of receptor thereof, promote the activation of proteic expression of endometrial gland bax and Caspase-3 and then regulate the balance of implanting window phase gland cell propagation and apoptosis, promote implantation position local vascular to form improving its blood circumstance, in time express in an orderly manner or disappear and promote endometrial decidua reaction to improve blastocyst implantation thereby regulate PCNA and P21.Also have in addition such as Chinese medicines such as Colla Corii Asini, the kidney invigorating gravidity assisting soup and invigorating kidney, promoting blood circulation sides and confirm that after deliberation it has all played the effect that increases the endometrium endometrial receptivity.
But original Chinese medicine is formed complicated, for example gravidity assisting soup is by Fructus Lycii 10~15 grams, Fructus Rubi, Fructus Leonuri, Semen Cuscutae, Radix Paeoniae Rubra, Herba Lycopi, Rhizoma Cyperi, each 9~10 gram of Radix Salviae Miltiorrhizae, Fluoritum 15~30 grams are formed, if insufficiency of kidney-YANG adds Herba Epimedii, Rhizoma Curculiginis, deficiency of the kidney yin and adds Shandong bean, the Radix Paeoniae Alba, Fructus Ligustri Lucidi, Herba Ecliptae, hyperactivity of fire caused by deficiency of YIN adds the Rhizoma Anemarrhenae, Cortex Phellodendri, and phlegm-damp adds Poria, the Rhizoma Pinelliae, cold-damp adds Radix Aconiti Lateralis Preparata, Rhizoma Atractylodis, and qi stagnation blood stasis adds Caulis Spatholobi, Radix Angelicae Sinensis, Semen Persicae.Gravidity assisting is educated squama side by at sweet smell, Herba Epimedii, Rhizoma Polygonati (processed), each 12 gram of unfamiliar to the ear ground, Radix Cyathulae, stone bucket leaf, processs each 9 gram of first sheet, and Flos Caryophylli, each 2.5 gram ancestral of school, osmanthus form.Offspring's soup is by Herba Pyrolae 60 grams, and silk, Fructus Atriplicis Sibiricae, Semen Arecae be 15 grams respectively, Flos Magnoliae, Rhizoma Alpiniae Officinarum, Rhizoma Cyperi, each 10 gram of Radix Angelicae Sinensis, Herba Asari 6 gram compositions.The composition of these Chinese medicinal formulaes is not only complicated, and curative effect and imprecise, so a kind of prescription of forming simple determined curative effect of urgent clinical needs.
Summary of the invention
At original Chinese medicine gravidity assisting side form complicated, uncertain therapeutic efficacy is cut, inconvenient problem with use, technical problem to be solved by this invention is to propose a kind of Chinese medicine composition that improves the endometrium endometrial receptivity simple, determined curative effect of forming.
In order to solve the problems of the technologies described above, the Chinese medicine composition that improves the endometrium endometrial receptivity provided by the invention is prepared from by following raw medicaments in portion by weight: Herba Epimedii 15-20; Radix Morindae Officinalis 10-15; Semen Cuscutae 20-25; Cortex Eucommiae 15-20.
Optimum proportion scheme: Herba Epimedii 15, Radix Morindae Officinalis 12, Semen Cuscutae 20, the Cortex Eucommiae 15.
The present invention also provides the preparation method of above-mentioned Chinese medicine composition, i.e. weighting raw materials in proportion, and clear water decocts and made decoction in 40-60 minute after soaking.
Usage and consumption: for the patient who carries out vitro fertilization-embryo implanting, be expert at bright embryo or transplant when freezing embryonic implantation before begin the above-mentioned decoction of decoction being taken warmly 3-5 day, twice, 10 day on the one is a course of treatment.
Modern pharmacological research shows: Herba Epimedii has gonadal hormone sample activity, and the effect of kidney invigorating and YANG supporting is arranged; Radix Morindae Officinalis can increase ovary, uterus weight and hypophysis weight, obviously improves HCG/LH receptor-specific adhesion in the ovary, increases the receptor number, can warm up the uterus by kidney-replenishing; Semen Cuscutae can promote the hypothalamic pituitary gonadal axis function, improves the reactivity of hypophysis to gonadotropin releasing hormone, promotes follicular development, also can improve the level of hypophysis interstitialcellstimulating hormone (ICSH) and hypothalamus-endorphins simultaneously; The Cortex Eucommiae has certain influence to the normal contraction of uterine smooth muscle, and strong contraction of uterine smooth muscle due to the lobus posterior hypophyseos had significant antagonism, it has pregnancy hormone like-effect, the mice miscarriage that pituitrin is caused has obvious antagonism, the miscarriage number of animals is obviously reduced, and farrowing quantity increases relatively.The present invention selects Herba Epimedii, Radix Morindae Officinalis, Semen Cuscutae, the Cortex Eucommiae four flavor Chinese medicines for use according to traditional theory of Chinese medical science and in conjunction with above-mentioned pharmacology's knowledge, forms determined curative effect and forms the Chinese medicine composition that simply improves the endometrium endometrial receptivity.
The present invention is according to traditional theory of Chinese medical science, from whole determination of treatment based on pathogenesis obtained through differentiation of symptoms and signs, select the product of warming and recuperating the kidney-YANG for use, make the essence and blood abundance, dash to appoint have foster, promote the body equilibrium between yin and yang, regulate gonad function, improve the endometrium blood circulation, increase the local blood perfusion flow, promote endometrial growth, improve the endometrium endometrial receptivity, thereby improve pregnancy rate.Chinese medicine composition of the present invention improves the endometrium endometrial receptivity, and as the adjuvant drug of vitro fertilization-embryo implanting, the medicine source is abundant, it is simple to form, low price, treating both the principal and secondary aspects of a disease, determined curative effect, have no side effect.
Description of drawings
Fig. 1: in the zoopery, each organizes endometrium of mouse LIF albumen average optical density value situation: a, compares P<0.01 with the A group; B, the C group is compared P<0.01 with the B group; C, the E group is compared P<0.01 with the D group.
In Fig. 2 zoopery, Real Time-PCR detects and respectively organizes the in utero expression of film LIFmRNA of pregnant mouse implantation window, compares a.P<0.01 with the A normal group; Compare b.P<0.05 with B induced ovulation group; Compare c.P<0.05 with D implantation barrier group.
The specific embodiment
Below in conjunction with embodiment the present invention is further described.
The preparation embodiment of herb mixture.
Embodiment 1
Take by weighing Herba Epimedii 15g, Radix Morindae Officinalis 10g, Semen Cuscutae 20g, Cortex Eucommiae 18g, clear water decocts and made decoction in 40 minutes after soaking.
Embodiment 2
Take by weighing Herba Epimedii 20g, Radix Morindae Officinalis 13g, Semen Cuscutae 22g, Cortex Eucommiae 20g, clear water decocts and made decoction in 40 minutes after soaking.
Embodiment 3
Take by weighing Herba Epimedii 15g, Radix Morindae Officinalis 15g, Semen Cuscutae 25g, Cortex Eucommiae 15g, clear water decocts and made decoction in 50 minutes after soaking.
Embodiment 4
Take by weighing Herba Epimedii 15g, Radix Morindae Officinalis 12g, Semen Cuscutae 20g, Cortex Eucommiae 15g, clear water decocts and made decoction in 60 minutes after soaking.
For the patient who carries out vitro fertilization-embryo implanting, be expert at bright embryo or transplant when freezing embryonic implantation before begin the above-mentioned decoction of decoction being taken warmly 3-5 day, twice, 10 day on the one is a course of treatment.
Pharmacological effect research:
Carry out relevant pharmacological effect research with Chinese medicine composition of the present invention, utilize pregnant mare serum gonadotrop(h)in (PMSG) (PMSG) and human chorionic gonadotropin (HCG) to cause super ovulation model, cause the implantation barrier model with mifepristone, setting up several different methods comprehensive observings such as using histopathology, electron microscopy, immunohistochemistry and Real Time-PCR on this model based.
1. the preparation of Chinese medicine composition
Take by weighing Herba Epimedii 15g, Morinda officinalis How root 12g, Semen Cuscutae 20g, Cortex Eucommiae 15g, clear water decocts and made decoction in 60 minutes after soaking.Every milliliter contains Chinese medicine 0.6g, is sub-packed in the sterile vials, and-20 ℃ of refrigerators are preserved.
2. the relevant treatment of laboratory animal
Pregnant mouse is divided into 6 groups, and the A group is the normal control group, gives the normal saline of oral equivalent; 1 group of B group model (induced ovulation model group) gives induced ovulation and handles (PMSG+HCG lumbar injection); The C group is studied 1 group (induced ovulation+Chinese drug-treated group), gives induced ovulation processing back and gavages Chinese medicine 0.4ml every day from gestation beginning in the 1st day, up to pregnant the 4th day; 2 groups of D group models (implantation barrier model group) give the mifepristone subcutaneous injection, cause implantation barrier; 2 groups (implantation barrier+Chinese drug-treated group) of E group research gavages Chinese medicine 0.4ml every day from gestation beginning in the 1st day, up to gestation the 4th day, 9 of the 4th day mornings gives the mifepristone subcutaneous injection and handles; 3 groups (only Chinese drug-treated group) of F group research gavages Chinese medicine 0.4ml from gestation beginning in the 1st day, up to pregnant the 4th day every day.
3. the observation of average implantation blastocyst number and pregnancy rate
Every group of female mice gestation was killed on the 8th day, observed every group of gestation number of elements and write down its implantation blastocyst number, calculated its average implantation blastocyst number and pregnancy rate.Found that: find out from B group induced ovulation model group and D group implantation barrier model group result, induced ovulation model and implantation barrier model are more successful, its implantation blastocyst number and pregnancy rate all reduce than A group normal control group, and C group and E group model add the result of Chinese drug-treated group and find out, Chinese medicine composition of the present invention has the improvement effect to the endometrium endometrial receptivity, and it has effectively improved implantation blastocyst number and pregnancy rate.See Table 1.
Table 1 is respectively organized the comparison of mouse pregnancy rate and average implantation blastocyst number
Pregnancy rate: a compares P<0.001 with the A group; B, the C group is compared P<0.01 with the B group; C, the E group is compared P<0.01 with the D group.Average implantation blastocyst number: * compares P<0.001 with the A group; * E group is compared P<0.05 with the D group
4. the mechanism research of endometrium endometrial receptivity improvement
4.1 morphology aspect research
Pinocytosis is prominent to be implantation the window phase big and level and smooth kytoplasm projection that finding endometrial epithelial cell top occurs under scanning electron microscope, for the of short duration fusion of fine hair columnar epithelium cell microvillus forms.Its time that occurs, grows fully and degenerate fits like a glove with the plantation window.This experiment is respectively organized the prominent expression of pinocytosis with the electron microscopic observation implantation window phase, discovers and used after the Chinese medicine that sequential expression and fetal development that pinocytosis is dashed forward are synchronous, help the foundation of endometrium endometrial receptivity, thereby improve blastocyst implantation.
4.2 genital regulating factor aspect research
By SABC and the expressed in situ of Real Time-PCR technology for detection LIF and the expression of mRNA thereof, the LIF of display model group expresses and significantly reduces (P<0.001) than matched group as a result.And after having used Chinese medicine, the implantation window phase LIF of induced ovulation+Chinese drug-treated group and implantation barrier+Chinese drug-treated group mice expresses and compares remarkable increase with corresponding model group, near the normal group level.Only prominent the comparing with matched group with the expression of LIF of Chinese drug-treated group pinocytosis do not have significant difference.Above result shows that Chinese medicine composition of the present invention can obviously improve the expression of induced ovulation and implantation barrier mice LIF, and research finds that also list does not have negative effect with Chinese medicine to the endometrium endometrial receptivity, is safe and reliable.As Fig. 1 and Fig. 2.
In sum, Chinese medicine composition of the present invention can significantly improve the average implantation blastocyst number and the pregnancy rate of implantation barrier model mice, and the average implantation blastocyst number and the pregnancy rate of induced ovulation model mice also had raising, show and help Chinese medicine composition of the present invention that the endometrium endometrial receptivity is had the improvement effect really; Preliminary its mechanism of inquiring into of research, discovery gives the endometrial pinocytosis of its implantation period of mice that Chinese medicine composition gavages, and prominent to be expressed in sequential consistent with the normal control group, it is synchronous that a glandular development and a matter are grown, make inner membrance plantation window open synchronous with fetal development, thereby raising implantation rate, and in the research aspect the regulatory factor, Chinese medicine composition of the present invention can significantly improve the expression of the leukaemia inhibitory factor that implantation is played an important role.
Claims (3)
1. a Chinese medicine composition that improves the endometrium endometrial receptivity is characterized in that it is prepared from by following raw medicaments in portion by weight: Herba Epimedii 15-20; Radix Morindae Officinalis 10-15; Semen Cuscutae 20-25; Cortex Eucommiae 15-20.
2. Chinese medicine composition as claimed in claim 1 is characterized in that it is prepared from by following raw medicaments in portion by weight: Herba Epimedii 15, Radix Morindae Officinalis 12, Semen Cuscutae 20, the Cortex Eucommiae 15.
3. the preparation method of Chinese medicine composition as claimed in claim 1 or 2 is characterized in that, weighting raw materials after the clear water immersion, decocts and made decoction in 40-60 minute in proportion.
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
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CN108715829A (en) * | 2018-05-25 | 2018-10-30 | 大连医科大学 | A method of improving Human in vitro Fertilization embryo development rate |
CN109805963A (en) * | 2019-03-22 | 2019-05-28 | 深圳开立生物医疗科技股份有限公司 | The determination method and system of one Endometrium parting |
CN112263585A (en) * | 2020-11-04 | 2021-01-26 | 复旦大学附属妇产科医院 | Application of protopanoxadiol PPD in preparing medicine for treating infertility and abortion |
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CN101053613A (en) * | 2007-05-16 | 2007-10-17 | 北京艺信堂医药研究所 | Traditional Chinese medicine preparations for treating luteal phase defect sterility |
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CN101053613A (en) * | 2007-05-16 | 2007-10-17 | 北京艺信堂医药研究所 | Traditional Chinese medicine preparations for treating luteal phase defect sterility |
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《现代中西医结合杂志》 20061231 周彬;等 坤宝颗粒改善子宫内膜容受性的研究 2886-2887 1-3 第15卷, 第21期 2 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108715829A (en) * | 2018-05-25 | 2018-10-30 | 大连医科大学 | A method of improving Human in vitro Fertilization embryo development rate |
CN109805963A (en) * | 2019-03-22 | 2019-05-28 | 深圳开立生物医疗科技股份有限公司 | The determination method and system of one Endometrium parting |
CN109805963B (en) * | 2019-03-22 | 2022-07-05 | 深圳开立生物医疗科技股份有限公司 | Method and system for judging endometrium typing |
CN112263585A (en) * | 2020-11-04 | 2021-01-26 | 复旦大学附属妇产科医院 | Application of protopanoxadiol PPD in preparing medicine for treating infertility and abortion |
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