CN101461894A - A pharmaceutical composition for treating female climacteric syndrome and delaying aging - Google Patents

Abstract

The invention discloses a pharmaceutical composition for treating female climacteric syndrome and delaying senility, which is prepared from epimedium, glossy privet fruit, fragrant solomonseal rhizome, black soybean, sophora flower, American ginseng, mulberry, raspberry, donkey-hide gelatin and cordyceps sinensis. The raw materials are added with conventional auxiliary materials and prepared into various clinically acceptable dosage forms according to a conventional process, such as: capsule, granule, tablet, oral liquid, injection or lyophilized powder for injection. The invention also provides the application of the pharmaceutical composition preparation in preparing medicines for treating female climacteric syndrome, delaying senility, enhancing immunity and increasing bone density.

Description

A pharmaceutical composition for treating climacteric syndrome and delaying aging

technical field

The invention relates to a traditional Chinese medicine composition, in particular to a pharmaceutical composition for treating climacteric syndrome, delaying aging, enhancing immunity and increasing bone density.

Background technique

After women enter menopause, they are prone to symptoms such as hot flashes, sweating, heart palpitations, unstable blood pressure, dizziness, tinnitus, irritability, insomnia, forgetfulness, constipation, and fatigue, collectively known as menopausal syndrome. In addition, the incidence of diseases such as osteoporosis, elevated blood lipids, arteriosclerosis, diabetes, coronary heart disease and stroke also increased significantly. Because these menopause-related diseases are closely related to the decrease of estrogen secretion caused by ovarian function decline, Western medicine treatment is mainly to supplement estrogen. This "hormone replacement therapy" has been widely used for more than 30 years and can effectively improve some symptoms of menopausal syndrome, but long-term use may increase the incidence of breast cancer and endometrial cancer.

The research on female menopause in traditional Chinese medicine generally discusses the pathogenesis according to the categories of TCM diseases such as "syndrome before and after menopause", "dampness syndrome" and "stagnation syndrome". According to the reports of experts, each school has its own emphasis, and for treatment from the kidney, Liuwei Dihuang Pill, Zhibai Dihuang Pill, Yougui Pill, and Erxian Decoction are mostly used; for liver treatment, Sini Powder, Erzhi Pill, and Chai Decoction are mostly used. Hu Shugan San, Danzhi Xiaoyao San, Yiguan Jian, etc.; for the treatment of the spleen, Wuwei Yigong San, Shipi Yin, Fuzi Lizhong Pills, etc.; for the treatment of the lung, Baihe Gujin Decoction and dried licorice Ginger Decoction and Bufei Decoction combined with addition and subtraction; for treatment from the heart, Baizi Yangxin Pills are often used; for five internal organs diseases, Liuwei Dihuang Pills, Yiguanjian, Yougui Pills, Jiaotai Pills, Guipi Decoction, Xiaoyaosan and so on. These additions and subtractions of medication can significantly improve menopausal symptoms clinically, but they are highly individualized and difficult to conduct standardized scientific research, which may affect the judgment of curative effect.

At present, many medical colleges and universities in China have carried out active excavation and research, and many achievements have been marketed as Chinese patent medicines, such as Gengnianan Sugar-coated Tablets, Gengniankang produced by Guangzhou Baiyunshan Pharmaceutical Factory, and Gengniankang produced by Shanghai Third Traditional Chinese Medicine Factory. Huazhen Heling Tablets, Dizhen Granules from Hunan Medical University. In Yu Zhimin's article, Gengniankang Tablets, Funing Capsules, and Gengnian Nvbao Tablets are suitable for kidney yin deficiency; Gengnianle, Shenqi Sanxian Tablets, and Cistanche Bushen Pills are suitable for kidney yang deficiency. Annian Gengnian Tablets have obvious curative effects on hot flashes and sweating, insomnia, dreaminess, upset and irritability, dizziness and headache, memory loss and blood pressure balance of menopausal syndrome. Jin Xiangshu and others treated 65 cases of menopausal syndrome with Zishen Tiaogan Decoction, and Zhang Xin treated 53 cases of this disease with Bushen Yangxin Decoction.

Contents of the invention

The purpose of the present invention is to provide a pharmaceutical composition, and another purpose of the present invention is to provide the application of the pharmaceutical composition.

The purpose of the invention is to realize through the following technical solutions

The bulk drug of the pharmaceutical composition of the present invention consists of:

Epimedium 15-35 weight parts Ligustrum lucidum 10-20 weight parts Polygonatum 5-15 weight parts

5-15 parts by weight of black soybean, 5-15 parts by weight of Sophora japonica, 5-15 parts by weight of mulberry

5-15 parts by weight of raspberry, 1-5 parts by weight of American ginseng, 2-9 parts by weight of donkey-hide gelatin

1-5 parts by weight of Cordyceps sinensis.

The preferred weight ratio of the above-mentioned raw materials is as follows:

Epimedium 25 parts by weight Ligustrum lucidum 15 parts by weight Polygonatum odoratum 10 parts by weight

10 parts by weight of black soybeans 10 parts by weight of Sophora japonica 2.5 parts by weight of American ginseng

10 parts by weight of mulberries 10 parts by weight of raspberries 5 parts by weight of donkey-hide gelatin

2.5 parts by weight of Cordyceps sinensis.

The preferred weight ratio of the above-mentioned raw materials is as follows:

Epimedium 16 parts by weight Ligustrum lucidum 18 parts by weight Polygonatum 6 parts by weight

13 parts by weight of black soybeans 7 parts by weight of Sophora japonica 14 parts by weight of mulberries

Raspberry 8 parts by weight American ginseng 4 parts by weight Ejiao 3 parts by weight

4.5 parts by weight of Cordyceps sinensis.

The preferred weight ratio of the above-mentioned raw materials is as follows:

Epimedium 32 parts by weight Ligustrum lucidum 12 parts by weight Polygonatum odoratum 14 parts by weight

7 parts by weight of black soybeans 12 parts by weight of Sophora japonica 6 parts by weight of mulberries

Raspberry 13 parts by weight American ginseng 2 parts by weight Ejiao 8 parts by weight

1.5 parts by weight of Cordyceps sinensis.

Take the above-mentioned crude drug of the pharmaceutical composition of the present invention, add conventional auxiliary materials, and prepare various clinically acceptable dosage forms according to conventional techniques, such as: capsules, granules, tablets, oral liquid preparations, aqueous injections or freeze-dried powder injections.

The pharmaceutical composition of the present invention is a kind of traditional Chinese medicine mainly used for nourishing the kidney, and is used for female menopause. It has obvious effects on osteoporosis, improving immune function, anti-aging, and improving cardiovascular function. The preparation of the pharmaceutical composition of the invention has the characteristics of small dosage, high active ingredients, safe taking, strong pertinence and wide range of suitable people.

The pharmaceutical composition of the present invention is based on the concept of Chinese original medicine - traditional Chinese medicine: "tonifying kidney qi and benefiting life", "food and medicine are the same", "kidney governs reproduction", "kidney governs bone", "kidney stores essence and secretes Tiangui" , theory, nourishing yin by invigorating kidney qi, nourishing essence and blood to contain yang, so as to achieve "yin and yang secret, spirit and evenness", thereby improving the physiological environment of menopause, improving female menopausal syndrome, osteoporosis, improving immune function, and anti-aging. Aging, improve cardiovascular function. Both the experiment and the clinic of this study set up a control group, among which the control study with the HRT method has the same effect and no side effects of sex hormones.

Experimental research shows that the pharmaceutical composition of the present invention can improve the thymus body weight ratio and the half hemolysis value of mice, and the result of NK cell activity measurement in mice is positive, and has the function of enhancing immunity and increasing the bone density of rats.

The following experimental examples and examples are used to further illustrate but not limit the present invention.

Experimental example 1 The pharmaceutical composition of the present invention enhances immune function animal experiment

The capsule preparation of the pharmaceutical composition of the present invention is a capsule filled with tan powder contents. Store at room temperature for experimental use.

SPF level healthy ICR mice were selected as experimental animals, among which 60 female mice weighing 19.4-21.9 g were divided into 4 groups, 15 in each group, as the immune group I, and the organ weight ratio determination, delayed type hypersensitivity experiment, Mouse peritoneal macrophage phagocytosis experiment of chicken red blood cells, determination of half hemolysis value (HC ₅₀ ) and determination of the number of antibody-producing cells; 60 female mice weighing 18.1 to 19.7 g were divided into 4 groups, 15 in each group. In group II, carbon clearance experiments were performed; 60 female mice weighing 18.0-18.9 g were divided into 4 groups, 15 mice in each group, and used as immune group III to conduct ConA-induced mouse lymphocyte transformation experiments and NK cell activity assays.

1.1 Dosage group selection and test substance administration method:

The recommended dosage is 2.1g of the pharmaceutical composition of the present invention per person (calculated by 60kg body weight) per day, which is equivalent to 0.035g/kg BW. In the experiment, 10 times the recommended amount for the human body was set, that is, 0.350g/kg BW per day, and a dose group was set for the upper and lower dose groups: 1.050g/kg BW (30 times) and 0.035g/kg BW (1 time). The samples were prepared with sterilized water, and the 0.000g/kg BW dose group replaced the test substance with sterilized water. The experimental mice were fed with the special feed for outbred mice, and the mice were given the test substance by oral gavage once a day, and the indicators were measured after continuous administration for 30 days. The amount of intragastric administration to mice was 30mL/kg BW.

1.2 Main instruments and reagents:

Animal balance, electronic balance, clean bench, carbon dioxide incubator, centrifuge, 721 spectrophotometer, constant temperature water bath, microplate reader, microscope, etc.

Sterile surgical instruments, vernier calipers (precision 0.01mm), micro syringes, cell counters, 24-well and 96-well flat-bottomed cell culture plates, 96-well U-shaped cell culture plates, 96-well enzyme-labeled microplates, glass plates, gauze, Test tubes, slide racks, timers, hemoglobin pipettes, slides, etc.

Sheep red blood cells (SRBC), normal saline, Hank's solution (pH7.2-7.4), RPMI1640 culture medium, niche serum, penicillin, concanavalin A (ConA), 1% glacial acetic acid, 1mol/L HCI solution , acidic isopropanol (96mL isopropanol plus 4ml of 1mol/L HCl solution), MTT, PBS buffer (pH7.2-7.4), complement (guinea pig serum), SA buffer, agarose, Douglas reagent ( Sodium bicarbonate 1.0g, potassium ferricyanide 0.2g, potassium cyanide 0.05g, add distilled water to 1000mL), YAC-1 cells, sodium lactate, nitro tetrazolium chloride, phenazine dimethyl sulfate, oxidized form Coenzyme I, 0.2moI/L Tris-HCl buffer solution (PH8.2), 2.5% Triton, India ink, 0.1% Na ₂ CO ₃ , chicken red blood cells, methanol, Giemsa staining solution, etc.

1.3 Experimental method:

1.3.1 Determination of organ weight ratio

The mice were killed by dislocation after weighing, the spleen and thymus were removed, the fascia was removed, the blood stains on the surface of the organs were blotted with filter paper, weighed, and the weight ratio of the thymus was calculated.

1.3.2 Determination of half hemolysis value (HC ₅₀ )

Take sheep's blood. After washing with normal saline for 3 times, each mouse was injected intraperitoneally with 0.2 mL of 2% (v/v, prepared with normal saline) packed volume of SRBC for immunization. After 5 days, the eyeballs were removed, and the blood was collected in a centrifuge tube for about 1 hour. The coagulated blood was separated from the tube wall to allow the serum to be fully separated, and the serum was collected by centrifugation at 6000 rpm for 4 minutes. Dilute the serum 400 times with SA buffer, put 1 mL into a test tube, add 10% (v/v, prepared with SA buffer) 0.5 mL of packed SRBC, and 1 mL of complement (dilute 1:8 with SA buffer) . Set up a control tube without serum (replaced with SA buffer). Place it in a constant temperature water bath at 37°C for 15 minutes, and then stop the reaction in an ice bath. Centrifuge at 2000rpm for 10min, take 1mL of supernatant, add 3mL of Douglas reagent. At the same time, take 0.25mL of 10% (v/v, prepared with SA buffer) packed volume SRBC, add Douglas reagent to 4mL in another test tube, mix well, let it stand for 10min, and use the control tube as a blank at 540nm. Measure the optical density of each tube separately. The amount of hemolysin is represented by the half hemolysis value (HC ₅₀ ), and the obtained data are measurement data. If the half hemolysis value of the test substance group is significantly higher than that of the 0.000g/kg BW group, and the difference is significant (P<0.05), It can be judged that the test substance has the effect of increasing the half hemolysis value of mice.

1.3.3 Determination of NK cell activity (lactate dehydrogenase LDH assay)

The target cell YAC-1 was subcultured 24 hours before the experiment, washed 3 times with Hank's solution before application, and the cell concentration was adjusted to 4×10 ⁵ cells/mL with RPMI1640 complete culture medium containing 10% calf serum. The tested mice were sacrificed by cervical dislocation, and the spleen was aseptically removed to make a spleen cell suspension, washed twice with Hank's solution, and centrifuged for 10 min each time (1000r/min). After lysing red blood cells, resuspend with 1 mL of RPMI1640 complete culture medium containing 10% calf serum, count the number of living cells (should be above 95%), adjust the cell concentration to 2×10 ⁷ mL, and make the effect-to-target ratio 50 :1. Take 100 μL each of target cells and effector cells and add them to a U-shaped 96-well culture plate; add 100 μL each of target cells and culture medium to the target cell natural release well, add 100 μL each of target cells and 2.5% Triton to the target cell maximum release well; Set up three parallel wells, culture in 37°C, 5% _CO2 incubator for 4h, centrifuge the 96-well plate at 1500rpm for 5min, absorb 100μL of the supernatant from each well and put it into the 96-well ELISA plate, add 100μL of LDH matrix solution, and react After 10 min, 30 μL of 1 mol/L HCl solution was added to each well to terminate the reaction, and the OD value was measured at 490 nm in a microplate reader, and the NK cell activity was calculated according to the following formula:

NK%=(reaction well OD-natural release well OD)/(maximum release well OD-natural release well OD)×100LDH matrix solution preparation: sodium lactate 5×10 ^-2 mol/L

Nitrotetrazolium chloride 6.6×10 ^-4 mol/L

Phenazine dimethyl sulfate 2.8×10 ^-4 mol/L

Oxidized coenzyme I1.3×10 ^-3 mol/L

Dissolve the above reagents in 0.2mol/L Tris-HCl buffer (pH8.2)

The obtained data are quantitative data. If the NK cell activity of the test substance group is significantly higher than that of the 0.000g/kg BW group, and the difference is significant (p<0.05), it can be judged that the test substance has the ability to improve the NK cell activity of mice. .

1.4 Experimental results

1.4.1 The influence of pharmaceutical composition capsule preparation of the present invention on mouse organ body weight

Table 1 The influence (X ± SD) of pharmaceutical composition capsule preparation of the present invention on mouse thymus body weight ratio

*P<0.05

Oral administration of different doses of the pharmaceutical composition capsule preparation of the present invention (made by Example 1) to mice for 30 days, after the original data was tested for homogeneity of variance, it met the requirement of homogeneity of variance, and the single factor analysis of variance method and multiple experiments The method of pairwise comparison of the means between a group and a control group was used for statistical processing. As can be seen from Table 1, there is a significant difference between the 0.035g/kg BW group and the 0.000g/kg BW group (p<0.05). There was no significant difference between other dosage groups and 0.000g/kg BW group (p>0.05). That is, the pharmaceutical composition capsule preparation of the present invention can improve the thymus body weight ratio of mice in the 0.035g/kg BW group.

1.4.2 The influence of pharmaceutical composition capsule preparation of the present invention on mouse humoral immune function

Table 2 The influence of the capsule preparation of the pharmaceutical composition of the present invention on the half hemolysis value (HC ₅₀ ) of mice (X±SD)

*p<0.05 **P<0.01

Oral administration of different doses of the pharmaceutical composition capsule preparation of the present invention to mice for 30d, (made by Example 1), after the original data was carried out the homogeneity of variance test, it met the requirement of homogeneity of variance, and the single factor analysis of variance method and multiple Statistical processing was performed by means of pairwise comparisons between the experimental group and a control group. It can be seen from Table 2 that the difference between the 0.035g/kg BW group and the 0.000g/kg BW group is extremely significant (P<0.01), and between the 0.350g/kg BW group and the 0.000g/kg BW group, The difference was significant (P<0.05), but there was no significant difference between d1.050g/kg BW group and 0.000g/kg BW group (P>0.05). That is, the capsule preparation of the pharmaceutical composition of the present invention can increase the half hemolysis value of the mice in both the 0.035g/kg BW group and the 0.350g/kg BW group.

As can be seen from Table 2, the results of the determination of the mouse humoral immune function of the capsule preparation of the pharmaceutical composition of the present invention are positive.

1.4.3 The influence of pharmaceutical composition capsule preparation of the present invention on mouse NK cell activity

Table 3 The influence (X ± SD) of pharmaceutical composition capsule preparation of the present invention on mouse NK cell activity

P<0.05

That is, the capsule preparation of the pharmaceutical composition of the present invention (made by Example 2) can improve the NK cell activity of mice in the 0.035g/kg BW group and the 0.350g/kg BW group, that is, the mouse NK cell activity assay result is positive .

1.5 Experimental summary

Oral administration of different doses of the capsule preparation of the pharmaceutical composition of the present invention to mice for 30 days can increase the ratio of thymus body weight in mice, and the results of humoral immune function and NK cell activity of mice are all positive. It can be seen that the pharmaceutical composition of the present invention has the function of enhancing immunity.

Experimental example 2 The pharmaceutical composition of the present invention increases bone density animal experiment

The pharmaceutical composition of the present invention has a recommended dosage for human body of 0.035g/kg BW (based on 60kg for adults). The low, medium and high doses of rats are 0.175, 0.350, 1.050g/kg.BW respectively, equivalent to 5, 10, and 30 times the recommended dose for the human body. Daily 10ml/kg.BW gavage dose was administered to the test substance.

2.1 Experimental animals

Select female Wistar rats, weighing about 280 g, and feed them adaptively for 3 days after receiving them.

2.2 Main instruments and reagents

Surgical scissors, hemostatic forceps, needle holder, suture needle, suture thread, scalpel, ophthalmic forceps; gavage needle, syringe, electronic balance (0.1g), ruler, vernier caliper, electronic balance (0.0001g, FISHER), LG100B Ventilation drying oven, SD-1000 bone mineral measuring instrument, AA200 atomic absorption spectrophotometer. Absolute ethanol, iodine tincture, pentobarbital sodium, alendronate sodium tablets, GBW08551-2004 calcium element standard solution (National Center for Standard Materials), lanthanum oxide, perchloric acid, nitric acid.

2.3 Experimental method

2.3.1 Ovariectomy

Rats were intraperitoneally injected with pentobarbital sodium solution at 30 mg/kg.BW, underwent bilateral ovariectomy after anesthesia, and intramuscularly injected 20,000 units of penicillin after the operation for 3 consecutive days. In the sham operation group, only about 0.5 g of fat was removed after the abdominal cavity was opened, and both ovaries were reserved.

2.3.2 Feed preparation

According to the American Institute of Nutrition (AIN) semi-finished feed formula and the national standard of complete nutritional feed for experimental rats (GB14924-94), the feed without estrogenic active ingredients was self-prepared.

2.3.3 Grouping of animals

Female Wistar rats were randomly divided into sham operation group, model control group, positive control group and pharmaceutical composition of the present invention according to body weight, low dose group, middle dose group and high dose group, with 10 rats in each group. On the 3rd day after the operation, the test substance was administered. The sham operation group and the model control group were gavaged with deionized water, and the positive control group was given 1.0 mg/kg.BW of alendronate sodium orally. The medium and high dose groups were orally administered 0.175, 0.350, and 1.050 g/kg.BW of the test substance, and the daily gavage volume of rats in each group was 10 ml/kg.BW. During the experiment, each rat was housed in a single cage, fed with homemade feed, and drank deionized water freely. The experiment period was three months.

2.3.4.1 Femoral dry weight and length determination

The rats were killed 24 hours after the last gavage, the right femur was quickly stripped, muscle and soft tissue were removed, and its length was measured with a vernier caliper. Bake the femur at 105°C for 48 hours, then weigh the dry weight of the femur with an electronic balance of 1/10,000, continue baking for another 2 hours, and weigh the dry weight of the femur again. constant weight.

2.3.4.2 Bone Densitometry

After the femur with soft tissue removed was baked to constant weight, under the same conditions, the bone mineral content (BMC) and bone mineral density at the midpoint and metaphysis of the femur were measured using a SD-1000 bone mineral measuring instrument calibrated with a standard bone model (BW), calculate the bone mineral density (BMD) at each measurement point according to the following formula:

Each point was measured twice.

2.3.4.3 Bone Calcium Determination

Measured according to the national standard GB/T5009.92-2003 of the People's Republic of China. Put the dried femur into the digestive tube, add 10ml of mixed acid (nitric acid 4: perchloric acid 1), overnight, and put it into a self-controlled electric digester for digestion the next day; The deionized water was quantitatively transferred and the volume was adjusted to 10.0ml; 2% lanthanum oxide solution was added to dilute. Dilute GBWO8551-2004. Calcium element standard solution with 2% lanthanum oxide solution to 0.0, 1.0, 2.0, 3.0, 4.0, and 5.0 μg/ml standard series. Measure the calcium concentration in each standard tube and sample tube with an AA200 atomic absorption spectrophotometer at 422.7 nm, and calculate the bone calcium content according to the following formula:

In the formula: C, CO_—respectively the calcium concentration (mg/L) in the measured sample and blank solution; v—sample constant volume (ml); B—dilution multiple; m—bone sample dry weight (g) .

2.4 Experimental results

2.4.1 Effect of pharmaceutical composition of the present invention on rat femoral dry weight and bone length

Table 4 Effect of pharmaceutical composition of the present invention on rat femur dry weight and bone length

Compared with the sham operation group **P<0.01 Compared with the model control group #P<0.05, ##P<0.01

As can be seen from Table 4, the femoral dry weight of the model control group rats has significantly decreased compared with the sham operation group, and there is a statistical difference (P<0.01); the positive control group has increased the femoral dry weight compared with the model control group, and Significant difference is arranged (P<0.01); Pharmaceutical composition of the present invention (made by embodiment 3) low, middle and high dose group femoral dry weights have significant difference (P<0.05 or P<0.01) compared with model control group ), there was no significant difference in the length of rat femur in each dose group (P>0.05).

2.4.2 Effect of pharmaceutical composition of the present invention on rat bone mineral content (BMC) bone mineral density (BMD)

Table 5 The influence of pharmaceutical composition of the present invention on rat femur midpoint and femoral metaphysis bone mineral content (BMC) and bone mineral density (BMD)

Compared with the sham operation group **P<0.01; compared with the model control group #P<0.05; ##P<0.01

As can be seen from Table 5, the femur midpoint and femoral metaphysis bone mineral density (BMD) and bone mineral content (BMC) of the rats in the sham operation group were significantly different from those of the model control group (P<0.01); Midpoint and femoral metaphysis bone mineral density (BMD), bone mineral content (BMC) have significant difference (P<0.01) compared with model control group; Pharmaceutical composition of the present invention (made by embodiment 4) middle and high dosage The bone mineral density (BMD) and bone mineral content (BMC) of the femoral midpoint and femoral metaphysis of rats in the control group were significantly different from those in the model control group (P<0.05 or P<0.01).

2.4.3 Effect of the pharmaceutical composition of the present invention on rat bone calcium content

Table 6 The influence of pharmaceutical composition of the present invention on rat bone calcium content

Compared with the sham operation group **P<0.01 Compared with the model control group #P<0.05, ##P<0.01

As can be seen from Table 6, there is a significant difference (P<0.01) in the bone calcium content of the sham operation group rats compared with the model control group, and the positive control group and the pharmaceutical composition of the present invention (made by embodiment 1) middle and high dose groups are significantly different. Compared with the model control group, the bone calcium content of rats was significantly different (P<0.05 or P<0.01).

2.5 Experimental summary

The experimental results of the pharmaceutical composition of the present invention given different dosages orally show that the femur dry weight of the model control group is significantly reduced compared with the sham operation group, and there is a statistical difference (P<0.01) between the positive control group and the model control group. Group comparison femoral dry weight has increase, and significant difference is arranged (P<0.01); Femoral dry weight of pharmaceutical composition low, middle and high dose group of the present invention has significant difference (P<0.05 or P<0.05) compared with model control group. 0.01), there was no significant difference in the femur length of rats in each group (P>0.05). The bone mineral density (BMD) and bone mineral content (BMC) of the midpoint of the femur and the metaphysis of the femur in the sham operation group were significantly different from those in the model control group (P<0.01); the midpoint of the femur and the femoral shaft of the rats in the positive control group Epiphyseal bone mineral density (BMD), bone mineral content (BMC) have significant difference (P<0.01) compared with model control group; In the pharmaceutical composition of the present invention, rat femur midpoint and femoral metaphyseal bone density (BMD), bone mineral content (BMC) were significantly different from the model control group (P<0.05 or P<0.01); the bone calcium content of the rats in the sham operation group was significantly different from the model control group (P<0.01), Compared with the model control group, there are significant differences (P<0.05 or P<0.01) in the bone calcium content of the rats in the positive control group and the middle and high dose groups of the pharmaceutical composition of the present invention. Therefore, the pharmaceutical composition of the present invention has the effect of increasing the bone density function of rats.

Experimental Example 3 Clinical verification of capsules of the present invention

1. Diagnostic criteria:

1. Diagnostic criteria for postmenopausal symptoms:

Symptoms include weakness of the waist and knees, dizziness and headache, forgetfulness and palpitations, insomnia and waking up easily, menstrual disorders, hair loss, gray hair increase, loose teeth, tinnitus and dizziness, loss of libido, dry genitals, general bone pain or combined with edema, and restlessness Anger, itchy skin, sore neck and back, joint discomfort, throat discomfort, dry stool, nocturnal urination, hot sweating, these symptoms appear for a long time or temporarily as a syndrome, women aged 40-60.

2. Western medicine diagnostic criteria: the diagnostic criteria for perimenopausal syndrome issued by the Ministry of Health, and other diseases can be excluded. Women aged 40-60 can be diagnosed as menopausal syndrome.

3. Inclusion criteria: Only women aged 40-60 who meet the above diagnostic criteria of traditional Chinese and Western medicine can be included.

4. Exclusion criteria: Those who meet the inclusion criteria but have one of the following conditions should be excluded from this trial.

①Those with mental illness or nervous system disease; ②Those with hyperthyroidism; ③Those with organic cardiovascular disease; ④Have taken sex hormone drugs including contraceptives in the past six months.

5. Exclusion criteria: Those who meet the inclusion criteria and fail to receive treatment or examination as required after participating in the trial.

2. Test method:

1. Test drug: capsules of the present invention: pharmaceutical composition capsule preparations of the present invention, which are capsules with tan powder contents inside. Placebo capsules: composed of medicinal starch and capsules without pharmacological effects, used as a blank control.

2. Routine administration in groups

3. Judgment criteria for curative effect: ①cured: the symptoms disappeared completely; ②markedly effective: the symptoms basically disappeared; ③effective: the symptoms were significantly relieved or improved; ④ineffective: the symptoms were not significantly relieved or worse; 3. Test results

Compared with the placebo group, the treatment of the Chinese medicine group of the present invention can obviously improve 17 clinical symptoms. In the total effective rate of treatment, the total effective rate of the capsule group of the present invention for the treatment of 17 symptoms is above 84% (all have statistical significance). Among them, the effective rates for symptoms such as irritability, depression, suspiciousness, headache, tinnitus, gastrocnemius spasm, fatigue, bone and joint pain, and frequent urination were all 100%; Difference test result shows between two groups, the Kupperman scoring total value of capsule group of the present invention significantly reduces after treatment, and the magnitude of reduction is significantly larger than placebo group; The results show that after the treatment of the capsule group of the present invention, the various TCM syndrome differentiation scores of viscera all have a significant decline; compared with the placebo group, the capsule group of the present invention has the most significant effect on improving the scores of various syndromes of kidney deficiency, and the decline range is respectively Yin deficiency, kidney qi deficiency, kidney yin and yang deficiency. The curative effect of the capsule of the present invention on improving the scores of symptoms of kidney qi deficiency is significantly higher than that of the control group (P<0.05).

The following embodiments can all achieve the effects described in the above experimental examples.

Detailed ways

Embodiment 1: the preparation of capsule

Epimedium 25kg Ligustrum lucidum 15kg Polygonatum 10kg Black soybean 10kg

Sophora japonica 10kg American ginseng 2.5kg Mulberry 10kg Raspberry 10kg

Donkey-hide gelatin 5kg Cordyceps sinensis 2.5kg.

The above-mentioned raw materials are taken, added with conventional auxiliary materials, boiled in water, alcoholized, dried and pulverized according to the conventional process to make powder into capsules.

Embodiment 2: the preparation of capsule

Epimedium 16kg Ligustrum lucidum 18kg Polygonatum 6kg Black soybean 13kg

Sophora japonica 7kg mulberry 14kg raspberry 8kg American ginseng 4kg

Donkey-hide gelatin 3kg Cordyceps sinensis 4.5kg.

The above-mentioned raw materials are taken, added with conventional auxiliary materials, boiled in water, alcoholized, dried and pulverized according to the conventional process to make powder into capsules.

Embodiment 3: the preparation of capsule

Epimedium 32kg Ligustrum lucidum 12kg Polygonatum 14kg Black soybean 7kg

Sophora japonica 12kg mulberry 6kg raspberry 13kg American ginseng 2kg

Donkey-hide gelatin 8kg Cordyceps sinensis 1.5kg.

The above-mentioned raw materials are taken, added with conventional auxiliary materials, boiled in water, alcoholized, dried and pulverized according to the conventional process to make powder into capsules.

Embodiment 4: the preparation of granule

Epimedium 25kg Ligustrum lucidum 15kg Polygonatum odoratum 10kg Black soybean 10kg

Sophora japonica 10kg American ginseng 2.5kg Mulberry 10kg Raspberry 10kg

Donkey-hide gelatin 5kg Cordyceps sinensis 2.5kg.

Take the above-mentioned raw materials, add conventional auxiliary materials, and make granules according to conventional processes.

Embodiment 5: the preparation of tablet

Epimedium 16kg Ligustrum lucidum 18kg Polygonatum 6kg Black soybean 13kg

Sophora japonica 7kg mulberry 14kg raspberry 8kg American ginseng 4kg

Ejiao 3kg Cordyceps 4.5kg.

Get above-mentioned raw material drug, add conventional excipient, make tablet according to conventional process.

Embodiment 6: the preparation of oral liquid

Epimedium 32kg Ligustrum lucidum 12kg Polygonatum 14kg Black soybean 7kg

Sophora japonica 12kg mulberry 6kg raspberry 13kg American ginseng 2kg

Donkey-hide gelatin 8kg Cordyceps sinensis 1.5kg.

The above-mentioned raw materials are taken, added with conventional auxiliary materials, and prepared into an oral liquid according to a conventional process.

Embodiment 7: the preparation of freeze-dried powder injection

Epimedium 16kg Ligustrum lucidum 12kg Polygonatum odoratum 14kg Black soybean 13kg

Sophora japonica 7kg mulberry 6kg raspberry 12kg American ginseng 4kg

Ejiao 3kg Cordyceps sinensis 1.5kg.

Take the above-mentioned raw materials, add conventional auxiliary materials, and prepare freeze-dried powder injection according to conventional processes.

Embodiment 8: the preparation of capsule

Epimedium 32kg Ligustrum lucidum 18kg Polygonatum 6kg Black soybean 7kg

Sophora japonica 12kg mulberry 14kg raspberry 5kg American ginseng 2kg

Donkey-hide gelatin 8kg Cordyceps sinensis 4kg.

The above-mentioned raw materials are taken, added with conventional auxiliary materials, boiled in water, alcoholized, dried and pulverized according to the conventional process to make powder into capsules.

Claims (8)

1. A pharmaceutical composition for treating climacteric syndrome and delaying aging, characterized in that the raw material of the pharmaceutical composition consists of: Epimedium 15-35 parts by weight Ligustrum lucidum 10-20 parts by weight Polygonatum 5-15 parts by weight 5-15 parts by weight of black soybean, 5-15 parts by weight of Sophora japonica, 5-15 parts by weight of mulberry 5-15 parts by weight of raspberry, 1-5 parts by weight of American ginseng, 2-9 parts by weight of donkey-hide gelatin 1-5 parts by weight of Cordyceps sinensis. 2. The pharmaceutical composition according to claim 1, characterized in that the raw material of the pharmaceutical composition consists of: Epimedium 25 parts by weight Ligustrum lucidum 15 parts by weight Polygonatum 10 parts by weight 10 parts by weight of black soybeans 10 parts by weight of Sophora japonica flower 2.5 parts by weight of American ginseng 10 parts by weight of mulberries 10 parts by weight of raspberries 5 parts by weight of donkey-hide gelatin 2.5 parts by weight of Cordyceps sinensis. 3. The pharmaceutical composition according to claim 1, characterized in that the raw material drug of the pharmaceutical composition consists of: Epimedium 16 parts by weight Ligustrum lucidum 18 parts by weight Polygonatum 6 parts by weight 13 parts by weight of black soybeans 7 parts by weight of Sophora japonica 14 parts by weight of mulberries Raspberry 8 parts by weight American ginseng 4 parts by weight Ejiao 3 parts by weight 4.5 parts by weight of Cordyceps sinensis. 4. The pharmaceutical composition according to claim 1, characterized in that the raw material drug of the pharmaceutical composition consists of: Epimedium 32 parts by weight Ligustrum lucidum 12 parts by weight Polygonatum odoratum 14 parts by weight Black soybean 7 parts by weight Sophora japonica 12 parts by weight mulberry 6 parts by weight 13 parts by weight of raspberry 2 parts by weight of American ginseng 8 parts by weight of donkey-hide gelatin 1.5 parts by weight of Cordyceps sinensis. 5. The pharmaceutical composition according to any one of claims 1-4, characterized in that taking the raw material drug of the above composition, adding conventional excipients, and making capsules, granules, tablets, oral liquid preparations, Water injection or freeze-dried powder injection. 6. The preparation method of the pharmaceutical composition according to any one of claims 1-4, characterized in that the method is: take the raw material drug, add conventional auxiliary materials, and make capsules, granules, tablets, Oral liquid preparation, water injection or freeze-dried powder injection. 7. The use of the pharmaceutical composition according to any one of claims 1-4 in the preparation of medicines for treating climacteric syndrome in women. 8. The use of the pharmaceutical composition according to any one of claims 1-4 in the preparation of medicines for delaying aging, enhancing immunity or increasing bone density.