Traditional Chinese medicine composition for assisting pregnancy and preventing miscarriage and application thereof

Abstract

The invention relates to a traditional Chinese medicine composition for assisting pregnancy and preventing miscarriage and application thereof. The traditional Chinese medicine composition is prepared from, by weight, 5-30 parts of semen cuscutae, 1-20 parts of herba taxilli, 1-20 parts of radix dipsaci, 1-20 parts of colla corii asini, 1-20 parts of radix codonopsis, 1-20 parts of rhizoma atractylodis macrocephalae, 1-20 parts of poria cocos and 1-15 parts of radix glycyrrhizae preparata. The traditional Chinese medicine composition provided by the invention can be used for treating PCOS threatened abortion, and has the comprehensive effects of radically treating, integrally recovering and treating both symptoms and root causes.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to a traditional Chinese medicine composition for assisting pregnancy and stabilizing tocopherols and an application thereof. Background Art

[0002] Polycystic ovary syndrome (PCOS) is a major cause of fertility problems, even affecting offspring health. It remains a challenging and hot topic in international gynecological reproductive research. With the continuous advancement of traditional Chinese and Western medicine treatment strategies and assisted reproductive technologies, the pregnancy rate for PCOS has gradually increased to 71.70%. However, the early pregnancy loss rate in women with PCOS is as high as 40%, three times higher than that of normal women. This presents a "double blow" to patients, both physically and psychologically, and severely impacts their desire to have children. Preventing and controlling early pregnancy loss in PCOS is crucial to curbing further declines in fertility and is of great significance.

[0003] In Traditional Chinese Medicine (TCM), this condition encompasses more than just one illness; it encompasses a wide range of conditions, including "abdominal pain during pregnancy," "fetal leakage," and "fetal movement disorder." Ancient traditional medicine already provided detailed discussions of pregnancy disorders. The "Jinkui Yaolue Fanglun" states, "If abdominal pain during pregnancy is caused by obstruction of the uterine vessels, Jiao Ai Tang is the main treatment." Chen Su'an's "Fu Ke Bu Jie" states, "Irregular menstrual bleeding during pregnancy is called fetal leakage." The "Mai Jing" notes, "A woman experiencing abdominal pain during pregnancy is restless." Regarding its pathogenesis, abdominal pain during pregnancy is often caused by blockage or malnutrition of the uterine vessels, embodying the TCM principle that pain is caused by obstruction of excess, and pain is caused by deficiency of nourishment. It is often caused by blood deficiency, deficiency-cold, or qi stagnation. The condition is mild and superficial, with damage to the uterine vessels rather than the fetus. Fetal leakage and fetal movement disorder arise from weak Chong and Ren meridians, which are unable to absorb blood and nourish the fetus. These conditions are often caused by kidney deficiency, qi and blood deficiency, blood heat, trauma, or damage to the fetus caused by lumps or masses.

[0004] Treatment options for early threatened abortion in PCOS include general treatment, medication, and surgical therapy. However, the pathogenesis of this disease is complex, and Western medicine alone is unlikely to achieve ideal results. For pre-pregnancy management of PCOS patients, it is generally recommended to control weight within an ideal range (BMI 18.5-23.9 kg / m2) through lifestyle intervention. 2), which can effectively reduce the incidence of early threatened miscarriage. Luteal insufficiency is common in this group after pregnancy, and luteal support therapy is often used clinically, including intramuscular injection of progesterone, human chorionic gonadotropin (hCG), and oral dydrogesterone or vaginal progesterone preparations. It is worth noting that compared with healthy pregnant people, pregnant women with PCOS are more likely to develop insulin resistance (IR) and compensatory hyperinsulinemia. In response to this pathological feature, metformin is clinically recommended for blood sugar regulation. This drug can regulate the metabolic microenvironment by improving insulin sensitivity, thereby maintaining endocrine homeostasis during pregnancy. Its use can reduce the risk of miscarriage by approximately 30%. However, Western medicine still has limitations. First, luteal support therapy treats the symptoms, not the root cause. While progesterone supplementation can temporarily maintain pregnancy, it does not address the underlying cause of luteal insufficiency, and hormone levels may rebound after discontinuation. Second, individual responses vary (approximately 20%-30% of patients experience progesterone resistance), making it difficult to achieve the desired serum concentration with conventional doses. Third, the route of administration is limited. Intramuscular progesterone injection can easily lead to local induration, while vaginal administration may cause irritation and bleeding, affecting patient compliance. Large-scale randomized controlled trials (RCTs) are lacking to confirm the safety of metformin continued use during pregnancy. Summary of the Invention

[0005] Based on the above-mentioned defects of the prior art, the present invention provides a new Chinese medicine composition for treating PCOS threatened abortion.

[0006] Solutions for solving problems

[0007] The invention provides a traditional Chinese medicine composition for aiding pregnancy and stabilizing tocopheryl acetate. The traditional Chinese medicine composition is composed of the following components in parts by weight: 5-30 parts of dodder seeds, 1-20 parts of mistletoe, 1-20 parts of dipsaccharin, 1-20 parts of donkey-hide gelatin, 1-20 parts of codonopsis pilosula, 1-20 parts of atractylodes macrocephala, 1-20 parts of poria cocos, and 1-15 parts of roasted liquorice.

[0008] Preferably, the traditional Chinese medicine composition is composed of the following components in parts by weight: 10-25 parts of Cuscuta seeds, 5-15 parts of Morus alba, 5-15 parts of Dipsacus asper, 5-15 parts of donkey-hide gelatin, 5-15 parts of Codonopsis pilosula, 5-15 parts of Atractylodes macrocephala, 5-15 parts of Poria cocos, and 1-10 parts of roasted Licorice root.

[0009] Preferably, the traditional Chinese medicine composition is composed of the following components in parts by weight: 10-20 parts of Cuscuta seeds, 6-12 parts of Morus alba, 6-12 parts of Dipsacus asper, 6-12 parts of donkey-hide gelatin, 6-12 parts of Codonopsis pilosula, 6-12 parts of Atractylodes macrocephala, 8-12 parts of Poria cocos, and 3-8 parts of roasted Licorice root.

[0010] Preferably, the traditional Chinese medicine composition is composed of the following components in parts by weight: 15 parts of Cuscuta seeds, 10 parts of Morus alba, 10 parts of Dipsacus asper, 10 parts of donkey-hide gelatin, 10 parts of Codonopsis pilosula, 10 parts of Atractylodes macrocephala, 10 parts of Poria cocos, and 6 parts of prepared Licorice root.

[0011] The present invention provides a traditional Chinese medicine preparation, which comprises any one of the traditional Chinese medicine compositions described above.

[0012] The present invention provides a drug combination, the active ingredients of which include any one of the above-mentioned traditional Chinese medicine compositions.

[0013] Preferably, the drug combination further comprises a progestogen drug;

[0014] Preferably, the progestogen drug includes dydrogesterone tablets.

[0015] The present invention provides use of any one of the above-mentioned traditional Chinese medicine compositions, the above-mentioned traditional Chinese medicine preparations or the above-mentioned drug combinations in the preparation of drugs for preventing and treating early threatened abortion or habitual abortion.

[0016] Preferably, the early threatened abortion or habitual abortion is caused by polycystic ovary syndrome.

[0017] Preferably, the drug for preventing and treating early threatened abortion is a drug that improves the expression level of the sweet taste receptors T1R2 and / or T1R3 in decidual tissue.

[0018] Effects of the Invention

[0019] The present invention is based on the concept of "preventive treatment" and combines the latest progress in PCOS threatened abortion, giving full play to the characteristics of traditional Chinese medicine differentiation and treatment and holistic concept, to form a new traditional Chinese medicine composition for treating PCOS threatened abortion. The composition is applied to PCOS threatened abortion, especially early PCOS threatened abortion, and can effectively increase serum progesterone, estradiol and β-HCG levels, reduce fasting plasma glucose (FPG), fasting insulin (FINS) levels and insulin resistance index (HOMA-IR), provide a basis for continuing normal pregnancy, effectively increase live birth rate, improve clinical symptoms and quality of life, prevent and delay the occurrence and development of pregnancy complications, improve long-term medication compliance, and provide more optional treatment options for patients with early PCOS threatened abortion. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 The expression levels of cellular sweet taste receptors T1R2, T1R3 and mTORC1 in different tissue groups in Example 2;

[0021] Figure 2The activity levels of HK2, PKM2, and LDHA in different tissue groups in Example 2;

[0022] Figure 3 This is an SDS-PAGE gel image of tissues from different groups in Example 2;

[0023] Figure 4 This is a schematic diagram of the changes in fasting blood glucose (FPG) indicators before and after treatment in the combined group and the western medicine group in the clinical trial;

[0024] Figure 5 This is a schematic diagram of the changes in fasting insulin levels (FINS) before and after treatment in the combined group and the western medicine group in the clinical trial;

[0025] Figure 6 Schematic diagram of the changes in the insulin resistance index (HOMA-IR) before and after treatment in the combined group and western medicine group in the clinical trial. DETAILED DESCRIPTION

[0026] To make the technical solutions and beneficial effects of the present invention more clearly understood, the following detailed description is given by way of specific embodiments. The accompanying drawings are not necessarily drawn to scale, and local features may be enlarged or reduced to more clearly illustrate the details of the local features. Unless otherwise defined, the technical and scientific terms used herein have the same meanings as those in the technical field to which this application belongs.

[0027] Traditional Chinese Medicine (TCM) has unique advantages and features for treating early threatened abortion in PCOS. Fetal leakage and restless fetal movements caused by "kidney deficiency, Chong and Ren meridian damage, and a weak fetal foundation" are similar to those of early threatened abortion. Therefore, kidney tonification is the primary focus of maintaining pregnancy. However, with the continuous changes in dietary structure and food culture, "spleen deficiency, phlegm and dampness blocking the uterus, and malnutrition of the fetal foundation" has gradually become an inseparable synergistic pathogenesis of early threatened abortion in PCOS. Synergistic pathogenicity of spleen and kidney deficiency is the core pathogenesis of early threatened abortion in PCOS, and kidney tonification and spleen invigoration are its fundamental treatment, consistent with previous data mining conclusions and in line with PCOS threatened abortion guidelines. Modern medicine also believes that the primary pathogenesis of early threatened abortion in PCOS is spleen and kidney deficiency, and clinical treatment often focuses on kidney tonification and spleen invigoration. Based on this, the inventors, after extensive experimental research, have discovered and proposed a novel traditional Chinese medicine composition for treating early threatened abortion in PCOS, which includes Cuscuta chinensis, Morus alba, Dipsacus asper, donkey-hide gelatin, Codonopsis pilosula, Atractylodes macrocephala, Poria cocos, and prepared liquorice.

[0028] Cuscuta: Sweet in flavor and warm in nature, it enters the liver, spleen, and kidney meridians. It has the effects of nourishing the liver and kidneys, consolidating essence and reducing urination, improving eyesight, and stabilizing pregnancy. It primarily contains flavonoids, lignans, and polysaccharides. Modern research indicates that Cuscuta has pharmacological effects such as protecting the reproductive system, mimicking estrogens, promoting immunomodulation, and having anti-tumor effects.

[0029] Mistletoe: bitter and sweet in taste, neutral in nature, enters the liver and kidney meridians, and was first recorded in "Shennong's Herbal Classic". It has the effects of dispelling rheumatism, relieving pain, nourishing the liver and kidneys, strengthening muscles and bones, and calming the fetus. It mainly includes chemical components such as flavonoids, sterols, terpenes, phenolic acids, phenylpropanoids, lignans, and volatile oils. It has anti-tumor, antihypertensive, antihyperglycemic, antilipidemic, anti-inflammatory, analgesic, antibacterial, antiviral, anti-osteoporosis, diuretic, cardiotonic, nerve protective, and memory enhancing pharmacological effects.

[0030] Dipsacus root: Slightly warm in nature, with a bitter and pungent flavor. It enters the liver and kidney meridians and is primarily used to treat tendon injuries and fractures, injuries from falls, rheumatic pain, liver and kidney deficiency, soreness of the waist and knees, metrorrhagia, and miscarriage. Modern pharmacological research indicates that Dipsacus root has the potential to regulate glucose metabolism, stop bleeding, relieve pain, and combat vitamin E deficiency.

[0031] Donkey-hide gelatin: Sweet in flavor and neutral in nature, it enters the lung, liver, and kidney meridians, nourishing yin, replenishing blood, stopping bleeding, and calming the fetus. The 2020 edition of the Pharmacopoeia of the People's Republic of China states that donkey-hide gelatin is used for conditions such as blood deficiency and sallow complexion, dizziness and palpitations, muscle atrophy and weakness, restlessness and insomnia, internal wind-induced dysphoria, dry cough, hemoptysis caused by exertional cough, hematemesis and hematuria, hematochezia and metrorrhagia, and miscarriage during pregnancy.

[0032] Codonopsis: Sweet in flavor, neutral in nature, it enters the lung and spleen meridians. According to the "Compendium of Materia Medica," it can tonify the middle qi, harmonize the spleen and stomach, promote fluid production, and relieve thirst. Modern pharmacological research indicates that Codonopsis has multiple effects, including promoting hematopoiesis, lowering blood pressure, regulating blood sugar, combating hypoxia, enhancing immunity, and combating ulcers.

[0033] Atractylodes macrocephala: Bitter and sweet in flavor, warm in nature, it enters the spleen and stomach meridians, and has the benefits of strengthening the spleen and replenishing qi, drying dampness and promoting diuresis, stopping sweating, and stabilizing pregnancy. The Compendium of Materia Medica states, "Atractylodes macrocephala can replenish spleen deficiency and support stomach deficiency." Modern pharmacological research suggests that Atractylodes macrocephala can enhance immunity, promote protein synthesis and hematopoiesis, lower blood sugar, act as a diuretic, act as an anticoagulant, and have anti-tumor effects.

[0034] Poria: sweet and light in taste, enters the heart, lung, spleen and kidney meridians. Modern pharmacological research mainly includes: anti-tumor, immune regulation, effects on diabetes and related complications, regulation of lipid metabolism, kidney protection, cardioprotection, liver protection and other effects.

[0035] Roasted licorice root (Licorice Root): Sweet and neutral in nature, it enters the Heart, Lung, Spleen, and Stomach meridians. It tonifies the spleen and replenishes Qi, clears heat and detoxifies, eliminates phlegm and relieves cough, relieves pain, and harmonizes various medicinal herbs. The "Compendium of Materia Medica" records licorice as a tonic and detoxifying herb. Modern pharmacological research indicates that roasted licorice root exhibits anti-tumor, antidepressant, anti-inflammatory, antiarrhythmic, hepatoprotective, antioxidant, and immunomodulatory effects.

[0036] Therefore, in the composition provided by the present invention, Cuscuta chinensis nourishes the kidney and nourishes essence, replenishes yin and consolidates yang, Morus alba and Dipsacus root strengthen the kidney and strengthen the waist and tie the fetus and relieve pain, donkey-hide gelatin nourishes yin and blood to stop bleeding, Codonopsis pilosula and Atractylodes macrocephala strengthen the spleen and replenish qi and help carry the fetus, Poria strengthens the spleen, and Radix Glycyrrhizae Preparata replenishes qi and harmonizes the middle and harmonizes the various medicines. The above medicines are combined to play the effects of tonifying the kidney and strengthening the spleen, replenishing qi and stabilizing the fetus, which is highly consistent with the consensus treatment method of tonifying the kidney and strengthening the spleen. Improving metabolic disorders is one of its main effect characteristics. The composition provided by the present invention can tonify the kidney and strengthen the spleen, replenish qi, nourish blood and stabilize the fetus, and reduce the miscarriage rate and pregnancy complications of PCOS pregnancy.

[0037] The invention provides a traditional Chinese medicine composition for aiding pregnancy and stabilizing tocopheryl acetate. The traditional Chinese medicine composition is composed of the following components in parts by weight: 5-30 parts of dodder seeds, 1-20 parts of mistletoe, 1-20 parts of dipsaccharin, 1-20 parts of donkey-hide gelatin, 1-20 parts of codonopsis pilosula, 1-20 parts of atractylodes macrocephala, 1-20 parts of poria cocos, and 1-15 parts of roasted liquorice.

[0038] In a certain embodiment, the traditional Chinese medicine composition is composed of the following components in parts by weight: 10-25 parts of Cuscuta seeds, 5-15 parts of Morus alba, 5-15 parts of Dipsacus asper, 5-15 parts of donkey-hide gelatin, 5-15 parts of Codonopsis pilosula, 5-15 parts of Atractylodes macrocephala, 5-15 parts of Poria cocos, and 1-10 parts of roasted Licorice root.

[0039] In a certain embodiment, the traditional Chinese medicine composition is composed of the following components in parts by weight: 10-20 parts of Cuscuta seeds, 6-12 parts of Morus alba, 6-12 parts of Dipsacus asper, 6-12 parts of donkey-hide gelatin, 6-12 parts of Codonopsis pilosula, 6-12 parts of Atractylodes macrocephala, 8-12 parts of Poria cocos, and 3-8 parts of roasted Licorice root.

[0040] In a certain embodiment, the traditional Chinese medicine composition is composed of the following components in parts by weight: 12-16 parts of Cuscuta seeds, 9-12 parts of Morus alba, 9-12 parts of Dipsacus asper, 9-12 parts of donkey-hide gelatin, 9-12 parts of Codonopsis pilosula, 9-12 parts of Atractylodes macrocephala, 9-12 parts of Poria cocos, and 5-7 parts of roasted Licorice root.

[0041] In one embodiment, the traditional Chinese medicine composition is composed of the following components in parts by weight: 15 parts of Cuscuta seeds, 10 parts of Morus alba, 10 parts of Dipsacus asper, 10 parts of donkey-hide gelatin, 10 parts of Codonopsis pilosula, 10 parts of Atractylodes macrocephala, 10 parts of Poria cocos, and 6 parts of prepared Licorice root.

[0042] The present invention provides a traditional Chinese medicine preparation, which comprises any one of the traditional Chinese medicine compositions described above.

[0043] In one embodiment, the traditional Chinese medicine preparation further comprises a pharmaceutically acceptable carrier.

[0044] The present invention provides a drug combination, the active ingredients of which include any one of the above-mentioned traditional Chinese medicine compositions.

[0045] In one embodiment, the drug combination further comprises a progestogen drug.

[0046] In one embodiment, the progestogen drug includes dydrogesterone tablets.

[0047] The present invention provides use of any one of the above-mentioned traditional Chinese medicine compositions, the above-mentioned traditional Chinese medicine preparations or the above-mentioned drug combinations in the preparation of drugs for preventing and treating early threatened abortion or habitual abortion.

[0048] In one embodiment, the early threatened abortion or habitual abortion is caused by polycystic ovary syndrome.

[0049] In one embodiment, the drug for preventing and treating early threatened abortion is a drug that improves the expression level of the sweet taste receptors T1R2 and / or T1R3 in decidual tissue.

[0050] In a certain embodiment, the drug for preventing and treating early threatened abortion improves glucose uptake, HK2, PKM2, LDHA activity and lactate level in decidual tissue.

[0051] In one embodiment, the preparation of the traditional Chinese medicine composition in the medicine is an oral preparation.

[0052] In one embodiment, the oral preparation is selected from one or more of decoctions, powders, capsules, tablets, honey pills, water-honey pills, water pills, concentrated pills, paste pills, wax pills, granules, oral liquids or dropping pills, more preferably decoctions, powders, capsules or tablets.

[0053] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are intended to illustrate the present invention and are not intended to limit the scope of the invention. The experimental methods in the following examples, for which no specific conditions are specified, are generally based on conventional conditions or the conditions recommended by the manufacturer. Unless otherwise stated, percentages and parts are by weight.

[0054] Example 1

[0055] The dosage of the pregnancy-assisting and fetal-stabilizing drink is: Cuscuta 15g, Morus alba 10g, Dipsacus asper 10g, donkey-hide gelatin 10g, Codonopsis pilosula 10g, Atractylodes macrocephala 10g, Poria 10g, and roasted Licorice root 6g.

[0056] The dosage of the kidney-tonifying and spleen-strengthening prescription is: Cuscuta 10g, Morus alba 8g, Dipsacus asper 8g, donkey-hide gelatin 8g, Codonopsis pilosula 8g, Atractylodes macrocephala 8g, Poria 6g, and roasted Licorice root 6g.

[0057] Preparation and administration of the assisted pregnancy and fetal health drink and the kidney-tonifying and spleen-strengthening formula: Combine all the ingredients in the formula according to the above proportions and soak in a casserole for 30 minutes. Add water to cover the ingredients and boil over medium heat until the liquid is reduced to approximately 200 mL. Pour the boiling liquid out and add water again to cover the ingredients. Pour the boiling liquid out and mix with the first solution. The kidney-tonifying and spleen-strengthening formula is prepared the same way as above.

[0058] Example 2

[0059] (1) Cell source: human endometrial stromal cells.

[0060] (2) Experimental groups: ① Endometrial stromal cells (non-decidualization group); ② Endometrial stromal cells decidualization induced group; ③ Endometrial stromal cells decidualization induced group + sweet taste receptor inhibition group (2-(4-methoxyphenoxy) propionate sodium) lactisole (20 mM); ④ Endometrial stromal cells decidualization induced group + 3DG intervention group (administering high concentration of 3DG (300 ng / ml) to cause abnormal glucose transport function, leading to abnormal glucose metabolism); ⑤ Endometrial stromal cells decidualization induced group + sweet taste receptor inhibition group (2-(4-methoxyphenoxy) propionate sodium) lactisole (20 mM); ④ Endometrial stromal cells decidualization induced group + 3DG intervention group (administering high concentration of 3DG (300 ng / ml) to cause abnormal glucose transport function, leading to abnormal glucose metabolism); Induction group + 3DG (300ng / ml) + pregnancy-assisting and fetal-protecting drink group (15g of Cuscuta chinensis, 10g of mistletoe, 10g of Dipsacus asper, 10g of donkey-hide gelatin, 10g of Codonopsis pilosula, 10g of Atractylodes macrocephala, 10g of Poria cocos, 6g of roasted licorice, 8.505g / kg of extract); ⑥ Endometrial stromal cell decidualization induction group + 3DG + kidney-tonifying and spleen-strengthening prescription group (10g of Cuscuta chinensis, 8g of mistletoe, 8g of Dipsacus asper, 8g of donkey-hide gelatin, 8g of Codonopsis pilosula, 8g of Atractylodes macrocephala, 6g of Poria cocos, 6g of roasted licorice, 6.51g / kg of extract).

[0061] (3) Experimental administration: Group ① was the negative control group and was not treated with medication. Groups ② to ⑥ were treated with decidualization inducers and were administered according to the above groupings. Decidualization was induced for 6 days using a reagent containing 1 μM MPA and 0.5 mM 8-Bromo-cAMP. On the fourth day, the corresponding drug intervention was given according to the above groupings. After 48 hours, cells and supernatants were collected for later testing. In Groups ⑤ and ⑥, the Auxiliary Pregnancy and Antai Drink and the Spleen-Strengthening Kidney-Invigorating Spleen Recipe prepared in Example 1 were administered by gavage.

[0062] (4) Detection content: Elisa and SDS-PAGE were used to detect changes in the content of decidualization markers IGFBP1 and PRL, glucose uptake capacity, lactate content, glycolysis (hexokinase (HK) 2, M2 pyruvate kinase (PKM2), lactate dehydrogenase (LDH) A) and sweet taste receptors (T1R2 and T1R3), and mTOR protein expression.

[0063] The results of cell experiments are as follows Figure 1 、 2 and Figure 3 As shown, the results showed that compared with endometrial stromal cells that were not induced to decidualize, the sweet taste receptors (T1R2 / 3) of decidual stromal cells were highly expressed; after the application of T1R2 / 3 inhibitors, the expression of T1R2 / 3 in decidual stromal cells was downregulated; the expression of active proteins of the three rate-limiting enzymes of aerobic glycolysis (HK2, PKM2, LDHA) decreased, and the levels of decidualization markers (PRL, IGFBP-1) decreased. 3-Deoxyglucosone (3DG) can cause the downregulation of T1R2 / 3 expression in decidual stromal cells, decreased HK2, PKM2, and LDHA activities, and decreased PRL and IGFBP-1 levels. The present invention can upregulate the T1R2 / 3 levels of decidual stromal cells damaged by 3DG, increase glucose uptake, HK2, PKM2, LDHA activities and lactate levels, promote aerobic glycolysis, and improve impaired decidualization.

[0064] Figure 3 This is an SDS-PAGE gel image. The T1R2 / 3 pathway mediates aerobic glycolysis in decidual stromal cells and maintains the decidualization process. High 3DG characteristics can damage the T1R2 / 3 function of the endometrium. Zhuyun Antai Wan promotes the aerobic glycolysis level of decidual stromal cells by regulating the T1R2 / 3 pathway, thereby improving the damage to decidualization caused by 3DG.

[0065] Example 3

[0066] clinical trials

[0067] 62 patients with clinical symptoms of PCOS threatened abortion were selected and divided into two groups according to the random number table method, 31 cases in the combined group and 31 cases in the western medicine group. The combined group took the pregnancy-enhancing drink and dydrogesterone tablets, and the western medicine group only took dydrogesterone tablets. The pregnancy-enhancing drink prepared according to Example 1 was orally taken 2 times / d.

[0068] Treatment options

[0069] A total of 62 patients with PCOS and threatened abortion (deficiency of both spleen and kidney) who visited the gynecology outpatient clinic and hospitalization of our hospital from November 2021 to March 2023 were selected as research subjects and divided into a Western medicine group (oral dydrogesterone to maintain pregnancy, control group) and a combined medication group (application of assisted pregnancy and fetal protection drink + dydrogesterone to maintain pregnancy, experimental group), with 31 cases in each group. Treatment was started after confirmation of intrauterine pregnancy, and the treatment time was 8 weeks. Follow-up was performed until full-term delivery. Venous blood was collected from the two groups of patients at enrollment and 8 weeks after enrollment, and the changes in serum progesterone, estrogen and β-HCG levels of the two groups of patients before and after medication were monitored. The changes in fasting plasma glucose (FPG) and fasting insulin (FINS) levels of the two groups of patients before and after medication were monitored, the insulin resistance index (HOMA-IR) was calculated, and the live birth rates of the two groups were counted.

[0070] Efficacy indicators

[0071] Blood glucose levels were measured using an automatic biochemical analyzer, and insulin levels and changes in serum progesterone, estrogen, and β-HCG levels before and after medication were detected using ELISA.

[0072] Experimental procedures

[0073] (1) Sample pretreatment: Thaw the serum to be tested at room temperature;

[0074] (2) Place the test kit at room temperature for 40 minutes and shake well before use;

[0075] (3) Standard dilution: Set up 10 standard wells on the ELISA plate. After dilution, the sample volume in each well is 50 μl. The concentrations of IL-2 after dilution are 900 pg / mL, 600 pg / mL, 150 pg / mL, and 75 pg / mL. The concentrations of IL-6 after dilution are 6 ng / L, 4 ng / L, 2 ng / L, 1 ng / L, and 0.5 ng / L.

[0076] (4) Sample addition: First add 40 μl of sample diluent to the sample wells on the enzyme-labeled plate, and then add 10 μl of the sample to be tested (the final sample dilution is 5 times). (5) Incubation: After sealing with a sealing film, incubate at 37°C for 30 minutes;

[0077] (6) Liquid preparation: dilute the 30-fold concentrated washing solution with 30-fold distilled water for later use;

[0078] Washing: Carefully peel off the sealing film, discard the liquid, spin dry, fill each microwell with washing solution, let it stand for 30 seconds and then discard, repeat this 5 times, and drain;

[0079] (7) Enzyme addition: Add 50 μl of enzyme-labeled reagent to each well and remove the blank wells;

[0080] (8) Incubation: Same operation as (5);

[0081] (9) Washing: the same operation as (7);

[0082] (10) Color development: Add 50 μl of color developer A to each microwell, then add 50 μl of color developer B, gently shake to mix, and develop the color at 37°C in the dark for 15 min;

[0083] (11) Termination: Add 50 μl of stop solution to each microwell to terminate the reaction (the blue color immediately turns yellow);

[0084] (12) Determination: Use blank air conditioning as zero and measure the absorbance (OD value) of each well in sequence at a wavelength of 450 nm.

[0085] 3.4 Result judgment

[0086] Use the concentration of the standard substance and the OD value to calculate the linear regression equation of the standard curve. Substitute the OD value of the sample into the equation to calculate the sample concentration, and then multiply it by the dilution factor to get the actual concentration of the sample.

[0087] 3.5 Data Processing

[0088] All data were statistically analyzed using SPSS 19.0 statistical software, and the experimental data were expressed as mean ± standard deviation. The paired sample t-test was used to analyze the data within the group, and P < 0.01 showed statistical significance; the independent t-test was used to analyze the data between the groups, and P < 0.01 showed statistical significance.

[0089] Study Results

[0090] The clinical live birth rates of the two groups of PCOS patients with threatened abortion are shown in Table 1. Among them, the comparison of the total effective rates between the two groups was *P<0.05.

[0091] Table 1

[0092]

[0093] The results of serum progesterone levels in the two groups of PCOS patients with threatened abortion are shown in Table 2. The unit is nmol / L, * P<0.05, compared with the same group before treatment; # P<0.05, compared with the Western medicine group after treatment.

[0094] Table 2

[0095]

[0096] The results of serum estradiol levels in two groups of PCOS patients with threatened abortion are shown in the table. The unit is pmol / L, * P<0.05, compared with the same group before treatment; # P<0.05, compared with the Western medicine group after treatment.

[0097] Table 3

[0098]

[0099] The results of serum β-HCG levels in the two groups of PCOS patients with threatened abortion are shown in Table 4. The unit is mIU / mL, * P<0.05, compared with the same group before treatment; # P<0.05, compared with the Western medicine group after treatment.

[0100] Table 4

[0101]

[0102]

[0103] Changes of glucose metabolism related indicators before and after treatment in the two groups of PCOS patients with threatened abortion Figures 4-6 . Clinical trials have shown that the total effective rate of the present invention in treating patients with threatened abortion due to PCOS is significantly better than that of the Western medicine group alone (Table 1). After treatment, the combination of the Assisted Pregnancy and Anti-abortion Drink + Dydrogesterone Tablets (combined group) significantly improved serum progesterone, estrogen and β-HCG levels compared to the Dydrogesterone Tablets alone (Western medicine group) (Tables 2-4). It also has significant effects in improving fasting blood glucose (FPG), fasting insulin level (FINS) and insulin resistance index (HOMA-IR). The Chinese medicine composition provided by the present invention has multi-target efficacy, is used to treat threatened abortion due to PCOS, and has the efficacy of treating both the symptoms and the root cause.

[0104] The above results show that the pregnancy-assisting and fetal-maintaining drink can significantly increase the levels of P, E2, and HCG in the peripheral blood of PCOS patients with threatened abortion, reduce FPG, FINS, and HOMA-IR, and provide a basis for continuing normal pregnancy. The pregnancy-assisting and fetal-maintaining drink can effectively improve the live birth rate.

[0105] It should be understood that the above embodiments are exemplary and are not intended to encompass all possible implementations of the claims. Various modifications and variations may be made to the above embodiments without departing from the scope of this disclosure. Similarly, the various technical features of the above embodiments may be arbitrarily combined to form additional embodiments of the present invention that may not be explicitly described. Therefore, the above embodiments merely illustrate several implementations of the present invention and do not limit the scope of protection of the patent of this invention.

Claims

1. A Chinese medicine composition for aiding pregnancy and maintaining tocolysis, characterized in that: The traditional Chinese medicine composition consists of the following components in parts by weight: 5-30 parts of Cuscuta seeds, 1-20 parts of Morus alba, 1-20 parts of Dipsacus asper, 1-20 parts of donkey-hide gelatin, 1-20 parts of Codonopsis pilosula, 1-20 parts of Atractylodes macrocephala, 1-20 parts of Poria cocos, and 1-15 parts of roasted Licorice root.

2. The Chinese medicine composition according to claim 1, characterized in that The traditional Chinese medicine composition consists of the following components in parts by weight: 10-25 parts of Cuscuta seeds, 5-15 parts of Morus alba, 5-15 parts of Dipsacus asper, 5-15 parts of donkey-hide gelatin, 5-15 parts of Codonopsis pilosula, 5-15 parts of Atractylodes macrocephala, 5-15 parts of Poria cocos, and 1-10 parts of roasted Licorice root.

3. The Chinese medicine composition according to claim 1, characterized in that The traditional Chinese medicine composition consists of the following components in parts by weight: 10-20 parts of Cuscuta seeds, 6-12 parts of Morus alba, 6-12 parts of Dipsacus asper, 6-12 parts of donkey-hide gelatin, 6-12 parts of Codonopsis pilosula, 6-12 parts of Atractylodes macrocephala, 8-12 parts of Poria cocos, and 3-8 parts of roasted Licorice root.

4. The Chinese medicine composition according to claim 1, characterized in that The traditional Chinese medicine composition consists of the following components in parts by weight: 15 parts of Cuscuta seeds, 10 parts of Morus alba, 10 parts of Dipsacus asper, 10 parts of donkey-hide gelatin, 10 parts of Codonopsis pilosula, 10 parts of Atractylodes macrocephala, 10 parts of Poria cocos, and 6 parts of roasted Licorice root.

5. A Chinese medicine preparation, characterized in that The traditional Chinese medicine preparation comprises the traditional Chinese medicine composition according to any one of claims 1 to 4.

6. A pharmaceutical combination, characterized in that The effective ingredients include the traditional Chinese medicine composition according to any one of claims 1 to 4.

7. The pharmaceutical combination according to claim 6, characterized in that The drug combination also includes a progestogen drug; Preferably, the progestogen drug includes dydrogesterone tablets.

8. Use of the Chinese medicine composition according to any one of claims 1 to 4, the Chinese medicine preparation according to claim 5, or the drug combination according to claim 6 or 7 in the preparation of a medicament for preventing and treating early threatened abortion or habitual abortion.

9. The use according to claim 8, characterized in that The early threatened abortion or habitual abortion is caused by polycystic ovary syndrome.

10. The use according to claim 8, characterized in that The drug for preventing and treating early threatened abortion is a drug for improving the expression level of the sweet taste receptors T1R2 and / or T1R3 in decidual tissue.

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