Application of fructus lycii and cortex phellodendri hypoglycemic capsule in preparation of medicine for treating or preventing climacteric syndrome

Abstract

The invention belongs to the technical field of medicines, and relates to a new application of a wolfberry-phellodendron hypoglycemic capsule medicine, in particular to an application of a wolfberry-phellodendron hypoglycemic capsule in preparation of a medicine for treating or preventing climacteric syndrome. According to the invention, it is found for the first time that the wolfberry-huang hypoglycemic capsule can significantly improve various typical symptoms of the climacteric syndrome and regulate the in-vivo estrogen level; the traditional Chinese medicine composition is free of obvious toxic and side effects after being used for a long time, high in safety and free of drug dependence, and compared with hormone replacement treatment drugs, the risks of inducing tumors, thrombus and the like are avoided, and the patient tolerance is better; the wolfberry-huang hypoglycemic capsule used in the invention is an existing mature preparation, the preparation process is stable, the quality is controllable, a new preparation technology does not need to be developed, industrial conversion is easy to realize, and the clinical popularization value is good.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology and relates to a new use of the Qihuang hypoglycemic capsule, specifically its application in the preparation of drugs for the treatment or prevention of menopausal syndrome. Background Technology

[0002] Menopausal syndrome refers to a series of physiological and psychological symptoms experienced by women during the perimenopausal and postmenopausal periods due to declining ovarian function and estrogen levels. It is an inevitable physiological stage for women transitioning from middle age to old age. Common clinical symptoms include hot flashes and night sweats, dizziness, insomnia, forgetfulness, emotional tension, irritability, anxiety, depression, memory loss, fatigue, and menstrual irregularities. It can also lead to obesity, itchy skin, and some patients may experience metabolic problems such as elevated blood sugar and dyslipidemia, significantly impacting their quality of life. With the increasing aging of the population, the incidence of menopausal syndrome is rising year by year, becoming one of the important diseases affecting the health of middle-aged and elderly women.

[0003] Currently, medications for treating menopausal syndrome are mainly divided into two categories: one is hormone replacement therapy drugs, such as estrogen and progesterone preparations. Although they can quickly relieve symptoms, long-term use may increase the risk of diseases such as breast cancer, endometrial cancer, and thrombosis, posing certain safety risks, and are not suitable for patients with contraindications to hormone therapy; the other is non-hormonal therapy drugs, including anti-anxiety and antidepressant drugs and herbal medicines. Among them, herbal medicines have received widespread attention due to their relatively high safety, but some drugs have problems such as unstable efficacy and slow onset of action.

[0004] The formula for Qihuang hypoglycemic capsules originates from a classic traditional Chinese medicine prescription, composed of multiple Chinese herbs including American ginseng, anemarrhena, gypsum, astragalus, yam, rehmannia, scrophularia, north ginseng, ophiopogon, polygonatum, and polygonatum. It has the effects of nourishing yin and kidneys, replenishing qi and nourishing yin, and promoting body fluid production and quenching thirst. The current drug approval number is Z20174016. Research and clinical applications by Zhao Nengjiang et al. have found that Qihuang hypoglycemic capsules improve the quality of life of patients with type 2 diabetes by alleviating symptoms and syndromes of qi and yin deficiency with heat, such as bitter taste in the mouth, dry throat, shortness of breath, and lethargy. Research by Teng Jiali et al. has found that Qihuang hypoglycemic capsules effectively reduce blood glucose and blood lipid levels in newly diagnosed type 2 diabetes patients, as well as reduce insulin resistance and improve pancreatic function. To date, no research has been found on the effects of Qihuang hypoglycemic capsules on improving menopausal syndrome-related symptoms. Summary of the Invention

[0005] To address the research gaps in the existing technology, this invention provides an application of Lycium barbarum hypoglycemic capsules in the preparation of drugs for the treatment or prevention of menopausal syndrome.

[0006] The formula of the Qihuang hypoglycemic capsules of this invention consists of 20 Chinese medicinal herbs: American ginseng, anemarrhena, gypsum, dried bitter melon, silkworm cocoon, astragalus, yam, rehmannia, scrophularia, north ginseng, ophiopogon, polygonatum, polygonatum, trichosanthes, chicken gizzard lining, coptis, cornus, wolfberry, privet fruit, and epimedium. Among them, silkworm cocoon, astragalus, yam, and American ginseng invigorate qi and clear heat, serving as the principal herbs; rehmannia, ophiopogon, gypsum, polygonatum, anemarrhena, scrophularia, coptis, north ginseng, trichosanthes, and polygonatum nourish yin and generate fluids, serving as the assistant herbs; wolfberry, dried bitter melon, and cornus fruit are added to enhance the effects of invigorating qi and nourishing yin; chicken gizzard lining, privet fruit, and epimedium are added as guiding herbs to strengthen the stomach and kidneys, and to promote circulation while tonifying. When used together, these herbs can nourish yin and kidneys, replenish qi and nourish yin, and effectively improve various symptoms caused by liver and kidney yin deficiency and qi and blood deficiency. They are suitable for menopausal syndrome belonging to the category of qi and yin deficiency and yin deficiency with fire excess.

[0007] To achieve the above objectives, the technical solution of the present invention is as follows: This invention provides the application of Lycium barbarum hypoglycemic capsules in the preparation of drugs for the treatment or prevention of menopausal syndrome.

[0008] Furthermore, the menopausal syndrome mentioned is an artificial menopausal syndrome.

[0009] The aforementioned artificial menopausal syndrome refers to menopausal syndrome caused by bilateral oophorectomy or by radiotherapy and chemotherapy.

[0010] Preferably, the dosage of the wolfberry and huang hypoglycemic capsules is 0.3g / kg / d to 3.0g / kg / d.

[0011] The most preferred dosage of the wolfberry and huang hypoglycemic capsules is 0.6g / kg / d to 1.8g / kg / d.

[0012] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) This invention is the first to discover that Qihuang hypoglycemic capsules can significantly improve various typical symptoms of menopausal syndrome and regulate the level of estrogen in the body; (2) The wolfberry and huang hypoglycemic capsules provided by the present invention are pure Chinese medicine preparations. Long-term use has no obvious toxic side effects, high safety, no drug dependence, and compared with hormone replacement therapy drugs, it avoids the risks of inducing tumors, thrombosis and other diseases, and patients tolerate it better. (3) The wolfberry hypoglycemic capsules used in this invention are existing mature preparations with stable preparation processes and controllable quality. There is no need to develop new preparation technologies, making it easy to achieve industrialization and clinical promotion value. Attached Figure Description

[0013] Figure 1The effects of Qihuang hypoglycemic capsules on the behavior of menopausal rats: (a) open field trajectory diagram, (b) cross-shaped elevated trajectory diagram, (c) sugar water preference results, (d) total movement distance in the central area of ​​the open field, (e) percentage of rats entering the arms, and (f) results of the forced swimming test. Figure 2 The effects of Qihuang hypoglycemic capsules on uterine pathology in menopausal rats; Figure 3 Effects of Qihuang hypoglycemic capsules on serum hormone levels in menopausal model rats; where (a) represents estradiol content, (b) represents follicle-stimulating hormone content, and (c) represents dopamine content. Detailed Implementation

[0014] To enable those skilled in the art to fully understand the present invention, the present invention is further illustrated below through specific embodiments. However, those skilled in the art should understand that the embodiments of the present invention do not limit the present invention in any way.

[0015] Example 1: Effects of Lycium barbarum and Lycium barbarum hypoglycemic capsules on a menopausal model rat induced by bilateral oophorectomy 1. Materials 1.1 Drug: Qihuang hypoglycemic capsules (provided by Shandong Yidaokang Pharmaceutical Co., Ltd., specification: 0.3g / capsule); Positive control drug: Estradiol valerate tablets (specification: 1mg).

[0016] 1.2 Animals: Sixty healthy female SD rats, weighing 220-250g, were used. The experimental animal use license number was SYXL (Lu) 2022-0009. This experiment was approved by the Experimental Animal Ethics Committee of Shandong University of Traditional Chinese Medicine (Approval No.: SDUTCM20250529002).

[0017] 2. Experimental Methods 2.1 Model Establishment: Except for the sham-operated group, all other rats underwent bilateral ovariectomy to establish a menopausal model. Rats were fasted for 12 hours preoperatively, anesthetized with isoflurane, fixed in a dorsal position, and their abdomens were shaved and disinfected. The skin and abdominal muscles were incised along the midline to expose both ovaries. After ovarian removal, the incision was sutured layer by layer. Postoperatively, penicillin was administered intramuscularly for 3 days to prevent infection. In the sham-operated group, the abdominal cavity was opened and immediately sutured; the ovaries were not removed.

[0018] 2.2 Grouping and Administration: After successful model establishment, rats were randomly divided into a sham-operated group (n=10) and a surgical group (n=50) according to body weight. The surgical group was further randomly divided into a model group, low-, medium-, and high-dose groups of Qihuang hypoglycemic capsules, and a positive control group. Administration began after 5 days of acclimatization. The positive control group received estradiol valerate tablets 0.09 mg / kg / d (by gavage). The low-, medium-, and high-dose groups of Qihuang hypoglycemic capsules received 0.88 g / kg / d, 1.76 g / kg / d, and 3.56 g / kg / d (by gavage, based on the amount of raw drug), respectively. The sham-operated group and the model group received an equal volume of physiological saline. All groups were administered the medication once daily for 8 consecutive weeks.

[0019] 2.3 Indicator Testing: (1) Open field test (OFT): The rat was placed in the central grid at the bottom of the open field device, and the total number of grids crossed within 5 minutes was recorded to assess the rat’s activity level and anxiety state.

[0020] (2) Elevated cross maze test (EPMT): The rat was placed on the central platform of the elevated cross maze and allowed to move freely for 5 minutes. The time spent in the closed arm and the open arm were recorded. The lower the proportion of time spent in the open arm, the higher the anxiety level.

[0021] (3) Forced swimming test (FST): Rats were placed in a forced swimming device at a constant temperature (25±0.5℃) for a total test duration of 6 minutes. The first 2 minutes were the adaptation period, and the resting time in the last 4 minutes was recorded. The longer the resting time, the more significant the depressive-like behavior.

[0022] (4) Sucrose preference test (SPT): Before the experiment, rats were acclimatized to sucrose water, and then given 1% sucrose solution and pure water. They were allowed to drink freely for 24 hours. The amount of sucrose water and pure water consumed was recorded, and the sucrose preference rate (sucrose water consumption / total water consumption × 100%) was calculated.

[0023] (5) Serum hormone level detection: Eight weeks after administration, blood was collected from the abdominal main vein of rats after anesthesia, and the serum was separated by centrifugation. The levels of estradiol, follicle-stimulating hormone (FSH), and dopamine (DA) in the serum were detected by enzyme-linked immunosorbent assay (ELISA).

[0024] (6) Observation of uterine morphology: After the experiment, the rats were sacrificed, the uterine tissue was dissected, fixed with formaldehyde, embedded in paraffin, sectioned, dewaxed with clearing agent, dehydrated with gradient concentration of ethanol, stained with hematoxylin and eosin, dehydrated and cleared, mounted with neutral resin, and observed under a microscope for morphological and structural changes of the endometrium, uterine glands and myometrium.

[0025] 2.4 Statistical analysis: SPSS 26.0 software was used for data processing. Experimental data are expressed as mean ± standard deviation. One-way ANOVA was used for comparison between groups. P < 0.05 was considered statistically significant.

[0026] 3. Experimental Results As shown in Figure 1(c), compared with the sham-operated group, the total water intake of rats in the model group did not change significantly, but the intake of saccharide water decreased significantly, the intake of pure water increased significantly, and the saccharide water preference rate decreased extremely significantly, suggesting that menopausal rats exhibit significant anhedonia-like depressive behavior. The saccharide water preference rate increased in all dose groups of the Lycium barbarum and Lycium barbarum hypoglycemic capsules, and the difference between the high-dose group and the model group was statistically significant.

[0027] As shown in Figures 1(a) and (d), the open field test results indicated that the model group rats crossed a significantly fewer grids within 6 minutes than the sham-operated group, suggesting reduced activity and significant anxiety. The total number of grids crossed by rats in all dose groups of the Lycium barbarum hypoglycemic capsules increased, with a statistically significant difference between the high-dose group and the model group.

[0028] As shown in Figures 1(b) and (e), the elevated cruciate maze test revealed that the proportion of time spent in the open arm was significantly lower in the model group than in the sham-operated group, indicating significant anxiety. The proportion of time spent in the open arm was increased in all dose groups of the Lycium barbarum hypoglycemic capsules, with a statistically significant difference between the high-dose group and the model group.

[0029] Figure 1 As shown in (f), the forced swimming test results showed that the resting time of rats in the model group was significantly longer than that in the sham-operated group after 4 minutes, indicating significant depressive-like behavior. The resting time of rats in all dose groups of the Lycium barbarum hypoglycemic capsule was shortened, and the difference between the high-dose group and the model group was statistically significant.

[0030] like Figure 2 HE staining results showed that the sham-operated group rats had the largest uterine volume, with a harmonious ratio of endometrial to myometrial thickness and a full structure; the endometrial thickness was moderate, the epithelium was tall columnar epithelium, and the cells were neatly arranged; the lamina propria had abundant uterine glands with dilated lumens; the myometrium was thick, and the smooth muscle cells were plump. In the model group rats, the uterine volume was significantly reduced, exhibiting an overall atrophic state, with a significantly decreased proportion of endometrial thickness; the endometrium was significantly thinner, the epithelial cells degenerated into flattened shapes, and the cells were disordered; the number of uterine glands sharply decreased, and the lumens collapsed and became blocked; the myometrium was thinner, and the smooth muscle cells atrophied, presenting typical menopausal uterine changes. The low- and medium-dose groups of the Qihuang hypoglycemic capsules showed some improvement in uterine morphology, while the high-dose group showed good recovery of endometrial thickness, with tall columnar epithelium, abundant and intact uterine glands, sufficient myometrial thickness, and plump smooth muscle cells.

[0031] Depend on Figure 3As shown in (a), (b), and (c), compared with the sham-operated group, the model group rats had decreased serum E2 levels, significantly increased FSH levels, and significantly downregulated DA levels, indicating that menopausal rats had significant endocrine disorders and imbalances in central monoamine neurotransmitters. After treatment with Qihuang hypoglycemic capsules, the E2 levels of rats in each dose group increased, the FSH levels decreased, and the DA and 5-HT levels were upregulated. The high-dose group showed the most significant regulatory effect, with a statistically significant difference compared with the model group; the positive control group also showed a similar regulatory effect.

Claims

1. The application of a Lycium barbarum hypoglycemic capsule in the preparation of a drug for the treatment or prevention of menopausal syndrome.

2. The application according to claim 1, characterized in that, The menopausal syndrome mentioned is an artificial menopausal syndrome.

3. The application according to claim 2, characterized in that, The artificial menopausal syndrome refers to menopausal syndrome caused by bilateral oophorectomy or by radiotherapy and chemotherapy.

4. The application according to any one of claims 1-3, characterized in that, The dosage of the Qihuang hypoglycemic capsules is 0.3g / kg / d-3.0g / kg / d.

5. The application according to claim 4, characterized in that, The dosage of the Qihuang hypoglycemic capsules is 0.6g / kg / d-1.8g / kg / d.

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