Taxillus sutchuenensis-semen cuscutae composition and application thereof in preventing and treating recurrent abortion

Abstract

The invention discloses a loranthus parasiticus-semen cuscutae composition and application thereof in preventing and treating recurrent abortion, and relates to the technical field of reproductive hormone regulators. The traditional Chinese medicine composition is prepared from loranthus parasiticus, semen cuscutae and physiologically / pharmaceutically acceptable carriers. The loranthus parasiticus-semen cuscutae composition provided by the invention has positive influence on pregnancy egg implantation, and can improve the implantation rate and improve the influence of luteal insufficiency, thereby playing a role in preventing miscarriage.

Description

Technical Field

[0001] The invention relates to the technical field of reproductive hormone regulators, in particular to a lonicera japonica-cuscuta seed composition and application thereof in preventing and treating recurrent spontaneous abortion. Background Art

[0002] Female reproductive hormones mainly include follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, progesterone, testosterone, etc. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are involved in regulating ovarian function and menstrual cycle. FSH promotes follicle development and LH promotes ovulation of eggs. Estradiol (E2) plays a vital role in the female reproductive system, including promoting follicle development, endometrial hyperplasia and breast development. Progesterone (P) plays an important role in pregnancy, maintaining the endometrium and supporting embryo implantation and development. Although testosterone (T) is mainly related to male hormones, there is also a small amount of testosterone in women, which also affects women's reproductive health. Prolactin (PRL) is mainly related to breast development and lactation, and also affects women's menstrual cycle. The balance and stability of the six indicators are crucial to female fertility. If these hormone levels are abnormal, it may cause ovulation disorders, irregular menstrual cycles, or affect the preparation and stability of the endometrium, thereby reducing the success rate of pregnancy or affecting the quality of the embryo, leading to miscarriage.

[0003] Recurrent spontaneous abortion (RSA) refers to two or more consecutive spontaneous abortions before 24 weeks of pregnancy with the same sexual partner. The etiology is complex. At present, the etiology of about 50% of RSA is unclear. However, the identifiable causes mainly include chromosomal abnormalities, maternal reproductive tract abnormalities, maternal endocrine abnormalities, immune dysfunction, reproductive tract infection, cervical insufficiency, thrombotic tendency and genetic factors. Among them, maternal endocrine abnormalities mainly include: 1. Luteal insufficiency: accounting for about 23%-60%. Luteal progesterone lower than 15ng / ml causes poor decidual reaction during pregnancy, and luteal insufficiency affects the implantation of fertilized eggs. 2. Polycystic ovary syndrome: The incidence of polycystic ovary syndrome in patients with recurrent spontaneous abortion is 58%. High concentrations of luteinizing hormone, high androgen and hyperinsulinemia reduce egg quality and endometrial receptivity. 3. Hyperprolactinemia: There are prolactin receptors in luteal cells. High prolactin inhibits luteinization of granulosa cells and steroid hormones, leading to luteal insufficiency and decreased egg quality.

[0004] RSA lacks typical clinical symptoms, and its treatment is mainly aimed at preventing its cause. Commonly used drugs in clinical practice include progesterone, metformin, dydrogesterone, immunomodulators and anticoagulants, but the uncertainty of its benefits and risks remains a major challenge in clinical practice. There is no uniformly effective and safe perfect pregnancy-preserving drug on the market.

[0005] Under the guidance of traditional Chinese medicine theory, mistletoe and dodder seed are components of a commonly used Chinese herbal compound for the clinical treatment of recurrent spontaneous abortion. Mistletoe can dispel rheumatism and stabilize the fetus, while dodder seed can nourish the kidney and improve essence, nourish the liver and improve eyesight, and consolidate the Chong meridians and stabilize the fetus. However, the ingredients and mechanism of action of the compound are very complex, which has hindered its application and development in clinical practice.

[0006] Therefore, based on the existing drugs for preventing and treating recurrent spontaneous abortion, we propose a loquat-cuscuta composition and its application in preventing and treating recurrent spontaneous abortion, so as to solve the above-mentioned problems. Summary of the invention

[0007] The purpose of the present invention is to provide a loquat-cuscuta composition and its application in preventing and treating recurrent spontaneous abortion, so as to solve the problems in the current market raised by the above background technology.

[0008] To achieve the above object, the present invention provides the following technical solution: a loquat-cuscuta composition, wherein the composition is prepared from loquat, cuscuta and a physiologically / pharmaceutically acceptable carrier.

[0009] Preferably, the mass ratio of the loranthus parasiticus to the dodder seed is 2:1.

[0010] Preferably, the composition is formulated for oral administration in solid or liquid form, solid dosage forms for oral administration include capsules, tablets, pills, powders and granules, and liquid dosage forms for oral administration include physiologically / pharmaceutically acceptable emulsions, solutions, suspensions and syrups.

[0011] Preferably, the carrier comprises one or more of a filler, a binder, a disintegrant, a solution retardant, an absorption accelerator, an inert diluent and a solubilizer.

[0012] Preferably, the filler includes one or more of starch, lactose, sucrose, glucose and mannitol, the binder includes one or more of sodium alginate, gelatin and gum arabic, the disintegrant includes one or more of agar, calcium carbonate and potato starch, the absorption accelerator is a quaternary ammonium compound, and the solubilizer includes one or more of isopropyl alcohol, propylene glycol, cottonseed oil, olive oil, castor oil and glycerol.

[0013] Preferably, the specific preparation process of the composition comprises the following steps:

[0014] S1: Weigh 20g of Morus alba and 10g of Cuscuta australis, add clean water to cover the medicinal materials by 1-2cm, soak for 30-60min, and boil for 20min to obtain the first extract;

[0015] S2: taking the first extract and adding water to boil it again to obtain the second extract;

[0016] S3: The two extracts of S1 and S2 are combined, concentrated by heating, and prepared into a solid or liquid form for oral administration by means of a physiologically / pharmaceutically acceptable carrier.

[0017] The present invention also provides the use of the above-mentioned Morus alba-cuscuta composition in preventing and treating recurrent spontaneous abortion.

[0018] Compared with the prior art, the present invention has the following beneficial effects:

[0019] The loquat-cuscuta composition of the present invention has a positive effect on the implantation of pregnant eggs in mice, can improve the implantation rate, and improve the influence of corpus luteum insufficiency, thereby playing a role in protecting the embryo.

[0020] The above summary is for illustrative purposes only and is not intended to be limiting in any way. In addition to the illustrative aspects, embodiments and features described above, further aspects, embodiments and features of the present invention will be readily apparent by reference to the accompanying drawings and the following detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 The figure is a schematic diagram of the preparation process of the loranthus parasiticus-cuscuta composition of the present invention;

[0022] Figure 2 This is a schematic diagram of the comparison of progesterone levels in pregnant mice in the treatment groups. * indicates P < 0.05, and the difference is statistically significant; ns: no significant (P> 0.05). DETAILED DESCRIPTION

[0023] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0024] See also Figure 1 , a mistletoe-cuscuta composition is prepared from mistletoe, cuscuta and a physiologically / pharmaceutically acceptable carrier.

[0025] The mass ratio of mistletoe and dodder seed is 2:1.

[0026] The mistletoe and dodder composition is formulated for oral administration in solid or liquid form. Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. Liquid dosage forms for oral administration include physiologically / pharmaceutically acceptable emulsions, solutions, suspensions and syrups.

[0027] The carrier includes one or more of a filler, a binder, a disintegrant, an absorption accelerator and a solubilizer.

[0028] The filler includes one or more of starch, lactose, sucrose, glucose and mannitol, the binder includes one or more of sodium alginate, gelatin and gum arabic, the disintegrant includes one or more of agar, calcium carbonate and potato starch, the absorption accelerator is a quaternary ammonium compound, and the solubilizer includes one or more of isopropyl alcohol, propylene glycol, cottonseed oil, olive oil, castor oil and glycerin.

[0029] The specific preparation process of a loranthus parasiticus-cuscuta seed composition comprises the following steps:

[0030] S1: Weigh 20g of Morus alba and 10g of Cuscuta australis, add clean water to cover the medicinal materials by 1-2cm, soak for 30-60min, and boil for 20min to obtain the first extract;

[0031] S2: taking the first extract and adding water to boil it again to obtain the second extract;

[0032] S3: Combine the two leaching solutions of S1 and S2, heat and concentrate, and prepare into a solid or liquid form for oral administration through a physiologically / pharmaceutically acceptable carrier. Carrier embedding is a conventional method in the prior art and will not be described in detail here.

[0033] The invention also provides application of the loquat-cuscuta composition in preventing and treating recurrent spontaneous abortion.

[0034] Embodiment 1

[0035] Preparation of the mistletoe-cuscuta composition solution: weigh 20g of mistletoe and 10g of dodder, add clean water to cover the medicinal materials by 1-2cm, soak for 30-60min, decoct for 20min, add water and decoct again, combine the two extracts, heat and concentrate to 163mL, the final concentration is 0.184g (raw drug amount) / mL, and the relative density is 1.21.

[0036] Embodiment 2

[0037] Effect of the parasitic loranthus-cuscuta composition of the present invention on implantation of pregnant eggs in mice

[0038] A model of spontaneous abortion mice (♀CBA / J×♂DBA / 2 mice mating) and normal pregnancy control mice (♀CBA / J×♂BALB / c mice mating) was established. Among them, nulliparous CBA / J female mice (6-8 weeks old, SPF grade) were purchased from Beijing Huafukang Biotechnology Co., Ltd., and BALB / c and DBA / 2 male mice (6-8 weeks old, SPF grade) were purchased from Sibeifu (Beijing) Biotechnology Co., Ltd. All mice were adaptively raised for one week, and male and female mice were mated in a 2:1 cage. The first day of pregnancy was recorded when a vaginal plug was found. CBA / J female mice were randomly divided into normal control group, model group, treatment group (high-dose group, medium-dose group, low-dose group, dydrogesterone group), with 5 mice in each group.

[0039] According to the drug conversion coefficient between humans and mice (0.0026), the daily dosage of mice was calculated, and the high, medium and low doses were 7.72g, 3.86g and 1.93g (raw drug amount) / (kg·d), respectively. The dydrogesterone group was given dydrogesterone tablets by gavage every day, with a dose of 3.0mg / (kg·d). The normal pregnancy group and the model group were not given drugs. The mice in the treatment group were given oral administration once a day from the 1st to the 7th day of pregnancy. The pregnant mice were killed and dissected on the 14th day of pregnancy. The total number of embryos and the number of absorbed embryos were counted, and the embryo absorption rate was calculated: (absorbed embryos / total number of embryos)×100%. During the feeding process, one mouse in the high-dose group died unexpectedly.

[0040] SPSS 21.0 software was used for statistical analysis. The data were first tested for homogeneity of variance and normality. For data with homogeneous variance and normal distribution, independent sample t-test was used for inter-group comparison. Otherwise, the non-parametric Mann–Whitney U test was used. The data were expressed as mean ± standard error, and P < 0.05 (two-tailed) was considered to be statistically significant.

[0041] The embryo absorption of CBA / J female mice at 14 days of pregnancy is as follows:

[0042]

[0043]

[0044] Note: The results are expressed as mean ± standard error, and P < 0.05 (two-tailed) is considered statistically significant. ** P<0.01; compared with the model group, # P<0.05; there was no significant difference between the high-dose group, medium-dose group, low-dose group and the dydrogesterone group (P>0.05).

[0045] As can be seen from the above, compared with the normal pregnancy group, the embryo absorption rate of the model group was significantly higher than that of the normal pregnancy control group (P < 0.01), indicating that the spontaneous abortion model was successfully constructed; compared with the model group, the average embryo absorption rate of the treatment groups (high-dose group, medium-dose group, low-dose group, dydrogesterone group) was significantly reduced (P < 0.05), indicating that the pharmaceutical composition of the present invention has a positive effect on the implantation of pregnant eggs in mice, can increase the number of implanted embryos, and reduce the abortion rate; compared with the dydrogesterone group, the high-dose group, the medium-dose group, and the low-dose group had no statistically significant difference (P>0.05), but the effect was relatively better than that of dydrogesterone, indicating that the present invention can also make some improvements and supplements.

[0046] Embodiment 3

[0047] Effect of the parasitic loranthus-cuscuta composition of the present invention on reproductive hormone (progesterone) in mice

[0048] When the CBA / J female mice were 14 days pregnant, their eyeballs were removed and their serum was collected. The hormone levels were detected by magnetic microparticle chemiluminescence method. SPSS and GraphPad Prism 8.0 software were used for statistical analysis and graphing. The results showed that the serum progesterone levels of pregnant mice in the medium-dose group and the low-dose group were significantly higher than those in the dydrogesterone group, while there was no significant difference in the serum progesterone level of pregnant mice in the high-dose group compared with the dydrogesterone group ( Figure 2 ), suggesting that the combination of Morus alba and Cuscuta australis may play a role in preserving pregnancy by regulating the level of reproductive hormone (progesterone), but the dosage should not be too high and further research is still needed.

[0049] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, unless they are contradictory.

[0050] Although the embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are exemplary and are not to be construed as limitations of the present invention. A person skilled in the art may change, modify, replace and vary the above embodiments within the scope of the present invention.

Claims

1. A parasitic loranthus-cuscuta composition, characterized in that: The composition is prepared from loranthus parasiticus, dodder seeds and a physiologically / pharmaceutically acceptable carrier.

2. The loranthus parasiticus-cuscuta composition according to claim 1, characterized in that: The mass ratio of the loranthus parasiticus and dodder seed is 2:

1.

3. The loranthus parasiticus-cuscuta composition according to claim 1, characterized in that: The composition is formulated for oral administration in solid or liquid form, solid dosage forms for oral administration include capsules, tablets, pills, powders and granules, and liquid dosage forms for oral administration include physiologically / pharmaceutically acceptable emulsions, solutions, suspensions and syrups.

4. The loranthus parasiticus-cuscuta composition according to claim 1, characterized in that: The carrier includes one or more of a filler, a binder, a disintegrant, an absorption accelerator and a solubilizer.

5. The loquat-cuscuta composition according to claim 4, characterized in that: The filler includes one or more of starch, lactose, sucrose, glucose and mannitol, the binder includes one or more of sodium alginate, gelatin and gum arabic, the disintegrant includes one or more of agar, calcium carbonate and potato starch, the absorption accelerator is a quaternary ammonium compound, and the solubilizer includes one or more of isopropyl alcohol, propylene glycol, cottonseed oil, olive oil, castor oil and glycerol.

6. The loranthus parasiticus-cuscuta composition according to claim 5, characterized in that: The specific preparation process of the composition comprises the following steps: S1: Weigh 20g of Morus alba and 10g of Cuscuta australis, add clean water to cover the medicinal materials by 1-2cm, soak for 30-60min, and boil for 20min to obtain the first extract; S2: taking the first extract and adding water to boil it again to obtain the second extract; S3: The two extracts of S1 and S2 are combined, concentrated by heating, and prepared into a solid or liquid form for oral administration by means of a physiologically / pharmaceutically acceptable carrier.

7. Use of the Morus alba-cuscuta composition according to any one of claims 1 to 6 in preventing and treating recurrent spontaneous abortion.

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