Use of Yuzhizhixue granules in preparing medicine for preventing or treating polycystic ovary syndrome

Abstract

The invention discloses the use of Yuzhi hemostatic granules in preparing a drug for treating polycystic ovary syndrome, wherein the Yuzhi hemostatic granules are refined from 17 traditional Chinese medicines, including Sanguisorba officinalis charcoal, Eclipta prostrata, fried Gardenia jasminoides, Cynomorium mianma, Agrimoniae herba, fried Sophora japonica flower, Polygonum bistorta, Cirsium citrinum, Platycladus orientalis leaf, palm charcoal, Peony bark, Rubia cordifolia, Pollen Typhae charcoal, Radix Rehmanniae, Radix Paeoniae Alba, Radix Scutellariae, and Radix Angelicae Sinensis. Experimental results show that Yuzhi hemostatic granules reduce TG levels in polycystic ovary syndrome, increase HDL‑C / LDL‑C ratio, reduce serum testosterone levels, increase estradiol levels, improve imbalance in sex hormone secretion, thereby promoting follicle maturation, and have broad prospects for clinical application.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology and relates to the medical use of Yuzhi hemostatic granules, and in particular, to the use of Yuzhi hemostatic granules in preparing a drug for preventing and / or treating polycystic ovary syndrome. Background Art

[0002] Polycystic ovary syndrome (PCOS) is a common endocrine disorder of sugar and lipid metabolism in women of childbearing age. Clinically, it is characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian changes. Patients may also have symptoms such as abnormal menstruation, obesity, and acne. Studies have shown that PCOS also increases the risk of related complications, causing diseases such as type II diabetes, insulin resistance, and dyslipidemia, causing serious damage to the patient's physical and mental health.

[0003] At present, the treatment of PCOS mainly includes oral contraceptives, anti-androgen drugs, ovarian wedge resection and other therapies. Although these methods have achieved certain efficacy, they have limitations such as low pregnancy rate, ovarian hyperstimulation, and postoperative adhesions. Traditional Chinese medicine has the characteristics of multi-component and multi-target treatment. It has inherent advantages in the treatment of chronic diseases. It can improve the gastrointestinal tract by regulating the structure and metabolism of intestinal microorganisms in the body, thereby maintaining overall metabolic balance.

[0004] Yuzhi hemostatic granules are made of 17 Chinese medicines such as Sanguisorba officinalis charcoal, Eclipta prostrata, fried Gardenia jasminoides, Rhizoma Cynomorii, Herba Agrimoniae, fried Sophora japonicae, Rhizoma Bistortae, Cirsium japonicum, Folium Platycladi (fried), palm charcoal, Cortex Moutan, Rubia cordifolia, Pollen Typhae charcoal, Radix Rehmanniae, Radix Paeoniae Alba, Radix Scutellariae, Radix Angelicae Sinensis, etc., and have the effects of consolidating menstruation and stopping bleeding, nourishing yin and clearing away heat. It is used for menorrhagia and prolonged menstruation caused by Chong Ren instability, yin deficiency and blood heat, and symptoms include excessive menstruation or prolonged menstruation, dark red menstrual color, thick quality, or small blood clots, soreness of waist and knees, less or no fur, and a thin and rapid pulse, which is seen in the above-mentioned syndromes. Chinese patent CN115721688A discloses the use of Yuzhi hemostatic granules in the preparation of medicines for improving kidney yin deficiency type gynecological diseases.

[0005] After searching, there is no report in the prior art on the use of Yuzhi hemostatic granules in the preparation of drugs for preventing or treating polycystic ovary syndrome. Summary of the invention

[0006] The invention provides use of a traditional Chinese medicine composition in preparing a medicine for preventing and / or treating polycystic ovary syndrome. The traditional Chinese medicine composition is Yuzhi hemostatic granules.

[0007] Furthermore, the Yuzhi hemostatic granules are mainly refined from 17 traditional Chinese medicinal materials, including Sanguisorba officinalis charcoal, Eclipta prostrata, fried Gardenia jasminoides, Cynomorium wilfordii, Agrimoniae scabra, fried Sophora japonica flower, Polygonum multiflorum, Cirsium japonicum, Platycladus orientalis leaf (fried), palm charcoal, Paeonia suffruticosa, Rubia cordifolia, Pollen pollen charcoal, Rehmannia root, White Peony Root, Scutellaria baicalensis, and Angelica sinensis.

[0008] Furthermore, the drug reduces Lee's index of patients with polycystic ovary syndrome.

[0009] Furthermore, the drug reduces insulin concentration in patients with polycystic ovary syndrome.

[0010] Furthermore, the drug reduces TG levels in patients with polycystic ovary syndrome and increases the HDL-C / LDL-C ratio.

[0011] Furthermore, the drug reduces serum testosterone levels and increases estradiol levels in patients with polycystic ovary syndrome.

[0012] Yuzhizhixue granules are a traditional Chinese medicine commonly used in gynecology to treat menstrual disorders caused by blood heat syndrome, which can clear away heat and cool blood, regulate menstruation and relieve pain. Its drug composition includes sanguisorba officinalis, eclipta prostrata, gardenia, agrimony, Sophora japonica, bistort, madder, pollen, raw rehmannia root, white peony root, scutellaria baicalensis, angelica, peony bark, cyperus rotundus, cirsium sibiricum, and orientalis leaf. Sanguisorba officinalis and gardenia are the main drugs in this prescription, sanguisorba officinalis, gardenia, and scutellaria baicalensis can clear away heat and cool blood, while peony bark, madder, pollen, and angelica can promote blood circulation and remove blood stasis, raw rehmannia root and white peony root can restrain yin and promote body fluid, while eclipta prostrata and agrimony can replenish deficiency and benefit yin.

[0013] Compared with the prior art, the technical solution of the present invention has the following beneficial effects:

[0014] The efficacy examples of the present invention show that the Yuzhi hemostatic granules significantly reduce Lee's index in polycystic ovary syndrome, reduce insulin concentration, reduce TG level, increase HDL-C / LDL-C ratio, reduce serum testosterone level, increase estradiol level, and improve ovarian tissue pathological changes. The Yuzhi hemostatic granules of the present invention have a significant therapeutic effect on polycystic ovary syndrome. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 Vaginal smear of rats in the normal group (×10).

[0016] Figure 2 Vaginal smears of rats in the model group (×10), E, ​​F, G, and H are all in diestrus.

[0017] Figure 3 Effects of YZ on Lee's index and food intake in PCOS rats ( , n=10),

[0018] Note: (1) Compared with the normal group, ＊ P<0.05, ＊＊ P<0.01, ＊＊＊ P < 0.001, ＊＊＊＊ P<0.0001; compared with the model group, # P<0.05,## P<0.01, ### P<0.001( Figures 4 to 6 );

[0019] (2) Figure 3 In B, the horizontal axes 1 and 2 are before administration; and 3, 4, 5, 6, 7, and 8 are after administration.

[0020] Figure 4 Effects of YZ on oral glucose tolerance, insulin concentration and area under the curve in PCOS rats ( , n=6).

[0021] Figure 5 Effects of YZ on blood lipid levels in PCOS rats ( , n=10).

[0022] Figure 6 Effects of YZ on LH, FSH, E2, and T levels in PCOS rats ( , n=8).

[0023] Figure 7 The effect of YZ on ovarian tissue pathology in PCOS rats (HE staining, ×6, n=6).

[0024] A: normal group; B: model group; C: YZ 0.5 g·kg -1 ·d -1 Group; D: YZ 1.5 g kg -1 ·d -1 Group; E: YZ4.5g·kg -1 ·d -1 Group; F: positive drug group. DETAILED DESCRIPTION

[0025] In order to verify the effect of the Chinese medicine composition of the present invention in preventing and / or treating polycystic ovary syndrome, the inventors have carried out corresponding animal experiments. According to the above content of the present invention, according to the common technical knowledge and conventional means in the field, without departing from the above basic technical ideas of the present invention, other various forms of modification, replacement or change can also be made.

[0026] The above contents of the present invention are further described in detail below through specific implementation methods in the form of embodiments. However, this should not be understood as the scope of the above subject matter of the present invention being limited to the following examples. All technologies realized based on the above contents of the present invention belong to the scope of the present invention.

[0027] Efficacy Example 1 Study on the effect of Yuzhizhixue granules on rats with polycystic ovary syndrome

[0028] 1 Materials and methods

[0029] 1.1 Experimental animals

[0030] Sixty female SD rats, weighing 60-70 g, were purchased from Beijing Huafukang Biotechnology Co., Ltd., with production license number: SCXK (Beijing) 2019-0008, use license number: SYXK (Lu) 20180008, and experimental animal operations were approved by the Animal Care and Use Committee of Lunan Pharmaceutical Group Co., Ltd., approval number: AN-IACUC-2023-047. The animals were adaptively fed with ordinary feed for 7 days after entering the room.

[0031] 1.2 Experimental drugs

[0032] Yuzhi hemostatic granules, batch number 220501, were provided by Shandong Xinshidai Pharmaceutical Co., Ltd.; letrozole, 2.5 mg / tablet, batch number 210114KL, was purchased from Jiangsu Hengrui Medicine Co., Ltd.; metformin hydrochloride enteric-coated tablets, batch number 20210939, were purchased from Guizhou Tianan Pharmaceutical Co., Ltd.

[0033] 1.3 Main reagents and instruments

[0034] Main reagents: 0.9% sodium chloride injection, batch number 2301112, purchased from Jiangsu Changjiang Pharmaceutical Co., Ltd.; sodium carboxymethyl cellulose, batch number 211210, purchased from Anhui Shanhe Pharmaceutical Excipients Co., Ltd.; insulin ELISA kit, batch number 33553, purchased from Mercodia;

[0035] Main instruments: blood glucose meter and blood glucose test strips (Lifescan Medical Devices Co., Ltd.); DM2500 biological microscope (Leica); Multiskan GO microplate reader (Thermo); BS-800 fully automatic biochemical analyzer (Shenzhen Mindray Bio-Medical Co., Ltd.).

[0036] The maintenance feed and high-fat feed for mice and rats were purchased from Ke'ao Xieli Feed Co., Ltd.

[0037] Functional ratio of high-fat feed: 68.5% maintenance feed for mice and rats + 20% lard + 10% sucrose + 1.25% cholesterol + 0.25% bile salt (Ke'ao Xieli Feed Co., Ltd.).

[0038] 1.4 Methods

[0039] 1.4.1 Animal modeling

[0040] The animals were fed a high-fat diet for seven days and gavaged with 1 mg kg -1 ·d -1Letrozole solution (dissolved in 1% CMC-Na solution) was used for 30 consecutive days to establish PCOS model rats. From the 31st day of modeling, vaginal smear observation was performed at 9:00 am every day for two consecutive estrous cycles. The modeling was considered successful if the rats had estrous cycle disorder.

[0041] 1.4.2 Grouped Dosing

[0042] Rats were randomly divided into a normal group, a model group, a low-, medium-, and high-dose group of Yuzhizhixue Granule (YZ), and a positive drug metformin group according to their body weight, with 10 rats in each group. Based on the conversion of the surface area of ​​rats and humans, the clinical equivalent dose of Yuzhizhixue Granule (YZ) is 1 g kg -1 , take 1.5 times the clinical equivalent dose as the medium dose (i.e. 1.5 g kg -1 ·d -1 ), 3 times of the medium dose, 1 / 3 times of the high dose, and low dose group (4.5 g·kg -1 ·d -1 , 0.5g·kg -1 ·d -1 ), the clinical equivalent dose of positive drug metformin is 0.2 g·kg -1 ·d -1 The drug group and the positive drug group were prepared with distilled water and intragastrically administered with corresponding concentrations of YZ and metformin, with a volume of 10 mL kg -1 The normal group was gavaged with an equal volume of distilled water, and the other groups were gavaged with 1 mg·kg -1 -d -1 Letrozole solution, for 50 consecutive days.

[0043] 1.4.3 Rat estrous cycle detection

[0044] The morphology of vaginal exfoliated cells was stained and observed by Wright staining.

[0045] 1.4.4 Lee's Index and Food Intake

[0046] Lee's index was calculated using the formula [body weight (g) × 10 3 / Body length (cm)] 1 / 3 The food intake of each group of rats was measured before and after administration.

[0047] 1.4.5 Oral glucose tolerance and insulin concentration

[0048] According to 2g kg -1 The rats were intragastrically gavaged with 50% glucose solution at a given dose, and blood was collected from the jugular vein before and 30min, 60min, 90min, and 120min after gavage to test blood sugar and determine insulin concentration.

[0049] 1.4.6 Serum lipid level detection

[0050] Detect high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), and triglycerides (TG).

[0051] 1.4.7 Radioimmunoassay for testing sex hormone levels

[0052] The levels of serum luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2) and testosterone (T) in rats were detected by radioimmunoassay.

[0053] 1.4.8 Ovarian histopathology

[0054] The left ovary of the rats was removed and HE staining was performed, and the pathological morphological changes of the ovarian tissue in each group were observed under a microscope.

[0055] 1.5 Statistical analysis

[0056] GraphPad Prism 9.5.0 software was used for statistical analysis, and the measured data were expressed as mean ± standard deviation. The data among the groups were compared by one-way analysis of variance. P < 0.05 indicated statistically significant differences.

[0057] 2 Results

[0058] 2.1 Changes in the estrous cycle of rats

[0059] In the normal group, vaginal cells showed periodic changes, with a cycle of 4-5 days. Figure 1 ; A large number of neutrophils were observed in the vaginal cell smears of the rats in the model group, and they were in estrus for a long time. Figure 2 . This indicates that the estrous cycle is disordered and the model is successful.

[0060] Effects of 2.2YZ on Lee's index and food intake in PCOS rats

[0061] Compared with the normal group, the Lee's index of the model group was significantly increased (P < 0.0001); compared with the model group, the Lee's index of the YZ medium and high dose groups and the positive drug group was significantly decreased (P < 0.05, P < 0.001, P < 0.05). There was no significant change in the food intake of each group before and after drug administration. Figure 3 .

[0062] Effects of 2.3YZ on OGTT and insulin release in PCOS rats

[0063] Compared with the normal group, the peak time of blood glucose value in the model group was delayed and maintained at a high level until 2 hours. The blood glucose concentration-time AUC increased significantly (P < 0.05), the fasting insulin level increased, and the insulin concentration AUC increased (P < 0.05). Compared with the model group, the blood glucose concentration-time AUC of the YZ low, medium, high dose and positive control group decreased, among which the high dose and positive control group decreased significantly (P < 0.01), and the insulin concentration AUC decreased, among which the high dose group decreased significantly (P < 0.05). Figure 4 .

[0064] Effects of 2.4YZ on serum HDL-C, LDL-C and TG in PCOS rats

[0065] Compared with the normal group, the TG and LDL-C levels of the rats in the model group were significantly increased (P < 0.0001), and the HDL-C and HDL-C / LDL-C values ​​were significantly decreased (P < 0.0001); compared with the model group, the TG levels of the YZ medium and high dose groups were significantly decreased (P < 0.001, P < 0.05); the HDL-C of the YZ medium and high dose groups was significantly increased (P < 0.05, P < 0.001), and the HDL-C / LDL-C of the high dose group was significantly increased (P < 0.01). Figure 5 .

[0066] Effects of 2.5YZ on serum hormone levels in PCOS rats

[0067] Compared with the normal group, the T level in the serum of the rats in the model group was significantly increased (P < 0.0001), and the E2 level was significantly decreased (P < 0.01); compared with the model group, the T levels in the YZ low, medium and high dose groups were all decreased, and the YZ high dose group was significantly decreased (P < 0.05); the E2 levels in the YZ low, medium and high dose groups and the positive drug group were all increased, and the YZ medium and high dose groups were significantly increased (P < 0.0001, P < 0.05). There was no statistically significant difference in LH, FSH, and LH / FSH among the groups. Figure 6 .

[0068] Effects of 2.6YZ on the morphology of ovarian tissue in PCOS rats

[0069] The granulosa cell layers of the ovarian tissue in the normal group were arranged neatly and had more layers. The ovarian tissue of the rats in the model group had more cystic cavitary follicles and the granulosa cell layers were significantly reduced. Compared with the model group, the cystic expansion of the ovarian tissue in the YZ dose groups and the positive drug group was significantly reduced, and the granulosa cell layers were arranged tightly. Figure 7 .

[0070] The yuzhi hemostatic granules of the present invention significantly reduce Lee's index in polycystic ovary syndrome, reduce insulin concentration, reduce TG level, increase HDL-C / LDL-C ratio, reduce serum testosterone level, increase estradiol level, and improve pathological changes in ovarian tissue.

[0071] The above embodiments are not any form of limitation to the present invention. For those skilled in the art, any modification, replacement, etc. made within the scope of the technical solution of the present invention based on the technical essence of the present invention still falls within the protection scope of the technical solution of the present invention.

Claims

1. Use of Yuzhizhixue granules in preparing a drug for preventing and / or treating polycystic ovary syndrome, characterized in that: The drug reduces the Lee's index of patients with polycystic ovary syndrome; the drug reduces the insulin concentration of patients with polycystic ovary syndrome; the drug reduces the TG level of patients with polycystic ovary syndrome and increases the HDL-C / LDL-C content; the drug reduces the serum testosterone level of patients with polycystic ovary syndrome and increases the estradiol level.

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