Application of ginkgo terpene lactones in preparation of medicines for preventing or treating obesity and obesity complications and preparation of anti-aging medicines or health-care products

Abstract

The invention relates to the technical field of medicines, in particular to application of ginkgo terpene lactone to preparation of medicines for preventing or treating obesity and obesity complications and preparation of anti-aging medicines or health-care products. In a high-fat feed induced obesity model, the ginkgo terpene lactone disclosed by the invention can effectively control the weight gain of a mouse and reduce the weight of epididymis fat of the mouse, and can be used for preparing medicines for preventing and treating diet induced obesity and the like. The ginkgo terpene lactones can improve the holding power of mice and increase the muscle proportion of the mice, which shows that the ginkgo terpene lactones have a good anti-aging effect and can be used for preparing anti-aging drugs or health-care products.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technology, and particularly to the use of ginkgolide in the preparation of drugs for preventing or treating obesity and obesity complications, and in the preparation of anti-aging drugs or health products. Background Art

[0002] Obesity is a chronic disease. According to the World Health Organization's estimate, it is one of the most easily overlooked diseases that humans are currently facing, but its incidence is rising rapidly.

[0003] When the calories ingested by the human body are more than the calories consumed, the excess calories are stored in the body in the form of fat. When the amount exceeds the normal physiological requirement and reaches a certain value, it evolves into obesity. In normal adult men, the weight of adipose tissue accounts for about 15% - 18% of the body weight, and in women, it accounts for about 20% - 25%. With age, the proportion of body fat increases accordingly. When the body fat increases and the weight exceeds the standard weight by 20% or the body mass index [BMI = weight (Kg) / (height) 2 (m 2 )] is greater than 24, it is called obesity. If there is no obvious cause, it is called simple obesity; if there is a clear cause, it is called secondary obesity.

[0004] Obesity brings many harms to humans. It not only affects the quality of life but also poses a huge threat to health, and can cause many complications such as various cardiovascular diseases. Therefore, it is very necessary to develop some new drugs for preventing or treating obesity. Summary of the Invention

[0005] The purpose of the present invention is to provide the use of ginkgolide in the preparation of drugs for preventing or treating obesity and obesity complications, and in the preparation of anti-aging drugs or health products.

[0006] The technical problem of the present invention is solved by the following technical solutions:

[0007] In the first aspect of the present invention, there is provided the use of ginkgolide in the preparation of drugs for preventing or treating obesity and obesity complications, wherein the ginkgolide includes at least one of ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, and ginkgolide K.

[0008] In some embodiments of the present invention, the weight ratio of ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, and ginkgolide K is selected from one of the following:

[0009] Ginkgolide A: Ginkgolide B = (10 - 45):(5 - 40);

[0010] Ginkgolide A: Ginkgolide C = (10 - 45):(3 - 35);

[0011] Ginkgolide B: Ginkgolide C = (5 - 40):(3 - 35);

[0012] Ginkgolide A: Ginkgolide B: Ginkgolide C = (10 - 45):(5 - 40):(3 - 35);

[0013] Ginkgolide A: Ginkgolide B: Ginkgolide C: Ginkgolide J = (10 - 45):(5 - 40):(3 - 35):(1 - 10);

[0014] Ginkgolide A: Ginkgolide K = (3 - 40):(0.01 - 5);

[0015] Ginkgolide B: Ginkgolide K = (5 - 75):(0.01 - 5);

[0016] Ginkgolide A: Ginkgolide B: Ginkgolide K = (3 - 40):(5 - 75):(0.01 - 5).

[0017] In some embodiments of the present invention, the ginkgolides further include bilobalide.

[0018] In some embodiments of the present invention, the mass ratio of ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, ginkgolide K, and bilobalide is selected from one of the following:

[0019] Ginkgolide A: Ginkgolide B: Bilobalide = (10 - 45):(5 - 40):(10 - 70);

[0020] Ginkgolide A: Ginkgolide C: Bilobalide = (10 - 45):(3 - 35):(10 - 70);

[0021] Ginkgolide B: Ginkgolide C: Bilobalide = (5 - 40):(3 - 35):(10 - 70);

[0022] Ginkgolide A: Ginkgolide B: Ginkgolide C: Bilobalide = (10 - 45):(5 - 40):(3 - 35):(10 - 70);

[0023] Ginkgolide A: Ginkgolide B: Ginkgolide C: Ginkgolide J: Bilobalide = (10 - 45):(5 - 40):(3 - 35):(1 - 10):(10 - 70);

[0024] Ginkgolide A: Ginkgolide K: Bilobalide = (3 - 40):(0.01 - 5):(10 - 70);

[0025] Ginkgolide B: Ginkgolide K: Bilobalide = (5 - 75):(0.01 - 5):(10 - 70);

[0026] Ginkgolide A: Ginkgolide B: Ginkgolide K: Bilobalide = (3 - 40):(5 - 75):(0.01 - 5):(10 - 70).

[0027] In some embodiments of the present invention, the mass parts of ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, and bilobalide are selected from: 40 - 43 parts of bilobalide, 25 - 27 parts of ginkgolide A, 15 - 17 parts of ginkgolide B, 14 - 16 parts of ginkgolide C, and 3.5 - 5 parts of ginkgolide J.

[0028] In some embodiments of the present invention, the dosage of the ginkgolide is 0.1 - 400 mg / kg / day.

[0029] In some embodiments of the present invention, the dosage of the ginkgolide is 1 - 200 mg / kg / day.

[0030] In some embodiments of the present invention, the use of the ginkgolide in the preparation of a drug for preventing or treating diet-induced obesity.

[0031] In some embodiments of the present invention, the use of the ginkgolide in the preparation of a drug for preventing or treating diet-induced obesity complications and obesity complications caused by hypertriglyceridemia.

[0032] In some embodiments of the present invention, the use of the ginkgolide in the preparation of a drug for preventing or treating obesity caused by hypertriglyceridemia.

[0033] In some embodiments of the present invention, the diet-induced obesity complications are metabolic disorders, muscle function decline, or insulin resistance.

[0034] In some embodiments of the present invention, the metabolic disorder is diabetes.

[0035] The use of ginkgolide in the preparation of an anti-aging drug or health product, and the ginkgolide includes at least one of ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, and ginkgolide K.

[0036] In some embodiments of the present invention, the weight ratio of ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, and ginkgolide K is selected from one of the following:

[0037] Ginkgolide A: Ginkgolide B = (10 - 45):(5 - 40);

[0038] Ginkgolide A: Ginkgolide C = (10 - 45):(3 - 35);

[0039] Ginkgolide B: Ginkgolide C = (5 - 40):(3 - 35);

[0040] Ginkgolide A: Ginkgolide B: Ginkgolide C = (10 - 45):(5 - 40):(3 - 35);

[0041] Ginkgolide A: Ginkgolide B: Ginkgolide C: Ginkgolide J = (10 - 45):(5 - 40):(3 - 35):(1 - 10);

[0042] Ginkgolide A: Ginkgolide K = (3 - 40):(0.01 - 5);

[0043] Ginkgolide B: Ginkgolide K = (5 - 75):(0.01 - 5);

[0044] Ginkgolide A: Ginkgolide B: Ginkgolide K = (3 - 40):(5 - 75):(0.01 - 5).

[0045] In some embodiments of the present invention, the ginkgolides further include bilobalide.

[0046] In some embodiments of the present invention, the mass ratio of ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, ginkgolide K, and bilobalide is selected from one of the following:

[0047] Ginkgolide A: Ginkgolide B: Bilobalide = (10 - 45):(5 - 40):(10 - 70);

[0048] Ginkgolide A: Ginkgolide C: Bilobalide = (10 - 45):(3 - 35):(10 - 70);

[0049] Ginkgolide B: Ginkgolide C: Bilobalide = (5 - 40):(3 - 35):(10 - 70);

[0050] Ginkgolide A: Ginkgolide B: Ginkgolide C: Bilobalide = (10 - 45):(5 - 40):(3 - 35):(10 - 70);

[0051] Ginkgolide A: Ginkgolide B: Ginkgolide C: Ginkgolide J: Bilobalide = (10 - 45):(5 - 40):(3 - 35):(1 - 10):(10 - 70);

[0052] Ginkgolide A: Ginkgolide K: Bilobalide = (3 - 40):(0.01 - 5):(10 - 70);

[0053] Ginkgolide B: Ginkgolide K: Bilobalide = (5 - 75):(0.01 - 5):(10 - 70);

[0054] Ginkgolide A: Ginkgolide B: Ginkgolide K: Bilobalide = (3 - 40):(5 - 75):(0.01 - 5):(10 - 70).

[0055] In some embodiments of the present invention, the mass parts of ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, and bilobalide are selected from: 40 - 43 parts of bilobalide, 25 - 27 parts of ginkgolide A, 15 - 17 parts of ginkgolide B, 14 - 16 parts of ginkgolide C, and 3.5 - 5 parts of ginkgolide J.

[0056] In some embodiments of the present invention, the dosage of the ginkgolide is 0.1 - 400 mg / kg / day.

[0057] In some embodiments of the present invention, the dosage of the ginkgolide is 1 - 200 mg / kg / day.

[0058] In some embodiments of the present invention, the anti - aging drug or health product is an anti - aging drug or health product for increasing muscle proportion.

[0059] In some embodiments of the present invention, the anti - aging drug or health product is an anti - aging drug or health product for increasing muscle grip strength.

[0060] The present invention includes the following beneficial effects:

[0061] The ginkgolide of the present invention can effectively control the weight gain of mice and reduce the weight of epididymal fat in a high - fat diet - induced obesity model, and can be used for preparing drugs for preventing and treating diet - induced obesity, etc.

[0062] The ginkgolide of the present invention can improve the grip strength of mice and increase the muscle proportion of mice, indicating that the ginkgolide has a good anti - aging effect and can be used for preparing anti - aging drugs or health products. Description of the Drawings

[0063] Figure 1 It is the weight change curve of the diet - induced obesity model in Example 1 after 8 - week drug administration.

[0064] Figure 2 It is the change curve of the weight change rate in Example 1.

[0065] Figure 3 It is the Lee's index of the diet - induced obesity model in Example 1 after 8 - week drug administration.

[0066] Figure 4Fasting blood glucose results of the diet-induced obesity model in Example 1.

[0067] Figure 5 Hemoglobin A1c results of the diet-induced obesity model at the experimental endpoint in Example 1.

[0068] Figure 6 OGTT test results of the diet-induced obesity model in Example 1.

[0069] Figure 7 Results of the forelimb grip strength test of the diet-induced obesity model in Example 1.

[0070] Figure 8 Results of the wet weight of adipose tissue of the diet-induced obesity model in Example 1.

[0071] Figure 9 Results of the cell area of adipose tissue of the diet-induced obesity model in Example 1.

[0072] Figure 10 Serum insulin results of the diet-induced obesity model in Example 1.

[0073] Figure 11 Body weight change curve of the diet-induced obesity model administered drugs for 8 weeks in Example 2.

[0075] Figure 12 Change curve of the weight change rate in Example 2.

[0076] Figure 13 Lee's index after administering drugs for 8 weeks in the diet-induced obesity model in Example 2.

[0077] Figure 14 Fasting blood glucose results of the diet-induced obesity model in Example 2.

[0078] Figure 15 Hemoglobin A1c results of the diet-induced obesity model at the experimental endpoint in Example 2.

[0079] Figure 16 OGTT test results of the diet-induced obesity model in Example 2.

[0080] Figure 17 Rotarod test results of the diet-induced obesity model in Example 2.

[0081] Figure 18 Results of the wet weight of adipose tissue of the diet-induced obesity model in Example 2.

[0082] Figure 19 Results of the gastrocnemius muscle / body weight of the diet-induced obesity model in Example 2.

[0083] Figure 20 Plasma insulin results of the diet-induced obesity model in Example 2.

[0084] Figure 21 Weight change curve of the diet-induced hypertriglyceridemia model in Example 3 after 6 weeks of drug administration.

[0085] Figure 22 Weight change rate curve of Example 3.

[0086] Unless otherwise stated, the terms used in the specification and claims have the following meanings.

[0087] As used in the present invention, the term "prevention" refers to preventing the occurrence of a disease and / or preventing the recurrence of a disease.

[0088] The ginkgolides of the present invention can be prepared by separation and purification using existing techniques, or can be composed of corresponding monomeric ginkgolide compounds.

[0089] When the ginkgolides of the present invention contain two or more monomeric ginkgolide compounds, they can be composed by combining the corresponding monomeric compounds.

[0090] The composition containing ginkgolide A, ginkgolide B, ginkgolide C and bilobalide of the present invention can directly purchase commercially available ginkgolide injection, or can be prepared by the methods of ZL200610103626.0 or ZL200610103625.6, and can also be composed by combining monomeric compounds.

[0091] The monomeric ginkgolide compounds of the present invention can all be obtained by purchasing commercially available products, or can be prepared by separation and purification using existing methods.

[0092] The monomeric ginkgolides of the present invention, specifically, can be monomeric ginkgolide compounds such as ginkgolide A, B, C, M, J, K, L, N, P, Q or bilobalide. Detailed implementation manners

[0093] The specification of the present invention has described the specific implementation manners in detail. Those skilled in the art should recognize that the following implementation manners are exemplary and should not be construed as limiting the present invention. For those skilled in the art, without departing from the principle of the present invention, by making several improvements and modifications to the present invention, the technical solutions obtained by these improvements and modifications also fall within the protection scope of the claims of the present invention. The beneficial effects of the present invention are specifically described below through examples.

[0094] Composition A comprises the following components in parts by weight: 41.5 parts of bilobalide, 26 parts of ginkgolide A, 16 parts of ginkgolide B, 15 parts of ginkgolide C, and 4.3 parts of ginkgolide J.

[0095] Composition B comprises the following components in parts by weight: 41 parts of bilobalide, 26 parts of ginkgolide A, 16 parts of ginkgolide B, 15 parts of ginkgolide C, and 4 parts of ginkgolide J.

[0096] Composition C comprises the following components in parts by weight: 40 parts of bilobalide, 25 parts of ginkgolide A, 15 parts of ginkgolide B, 14 parts of ginkgolide C, and 3.5 parts of ginkgolide J.

[0097] Composition D comprises the following components in parts by weight: 42 parts of bilobalide, 26.5 parts of ginkgolide A, 16.5 parts of ginkgolide B, 15.5 parts of ginkgolide C, and 4.5 parts of ginkgolide J.

[0098] Composition E comprises the following components in parts by weight: 43 parts of bilobalide, 27 parts of ginkgolide A, 17 parts of ginkgolide B, 16 parts of ginkgolide C, and 5 parts of ginkgolide J.

[0099] Among them, bilobalide, ginkgolide A, ginkgolide B, ginkgolide C, and ginkgolide J are all from Chengdu Baiyu Pharmaceutical Co., Ltd.

[0100] Example 1

[0101] Preventive efficacy experiment in a diet-induced obesity model of C57 mice

[0102] 1. Experimental steps

[0103] 1.1 Test animals and reagents

[0104] SPF-grade 5-week-old male C57BL / 6J mice were purchased from Chengdu Yakang Biotechnology Co., Ltd.

[0105] Composition A comprises the following components in parts by weight: 41.5 parts of bilobalide, 26 parts of ginkgolide A, 16 parts of ginkgolide B, 15 parts of ginkgolide C, and 4.3 parts of ginkgolide J.

[0106] Among them, bilobalide, ginkgolide A, ginkgolide B, ginkgolide C, and ginkgolide J are all from Chengdu Baiyu Pharmaceutical Co., Ltd.

[0107] Feed: High-fat feed 60% kcal, product number: XTHF60; maintenance feed, product number: 1010088, and the feeds were all purchased from Jiangsu Xietong Pharmaceutical Biotechnology Co., Ltd.

[0108] 1.2 Establishment of diet-induced obesity model:

[0109] Animals in the blank control group were fed maintenance feed. Eight animals were selected from the blank control group according to their body weight levels and continuously fed maintenance feed until the end of the experiment.

[0110] Animals in the model group and each drug administration group were fed high-fat feed. After the maintenance feed and high-fat feed were transitioned according to 3:7, 5:5, and 7:3, the animals were fed high-fat feed to establish a diet-induced obesity model. One week after diet induction, the body weight levels of the animals were measured. Compared with the animals fed maintenance feed, the body weight of the animals increased significantly and there was a statistical difference. Then, the animals were grouped. First, the animals fed high-fat feed were sorted according to their body weight values, and 1 / 4 of the diet-induced obesity-resistant animals with lower body weight were excluded. Then, they were randomly divided into 4 groups according to the S-shaped grouping method according to body weight, with 9 animals in each group. After grouping and drug administration, they continued to be fed high-fat feed until the end of the experiment.

[0111] 1.3 Drug administration method:

[0112] After the animals were randomly grouped, drug administration began. The groups included: G1 blank control group (maintenance feed, Vehicle), G2 model control group (high-fat feed, Vehicle), G4 high-dose group of composition A (high-fat feed, 200 mg / kg), and G5 low-dose group of composition A (high-fat feed, 50 mg / kg). The drug administration volume was 5 mL / kg. The control group and the model group were gavaged with an equal volume of solvent. Vehicle: DMSO: 0.5% MC = 5:95 (v / v). The drug was administered by gavage once a day, QD, for 8 weeks.

[0113] 2. Detection indicators

[0114] 2.1 Animal body weight

[0115] Once a week, the animals were weighed at a fixed time period to monitor the change in body weight and calculate the body weight change rate.

[0116] 2.2 Fasting blood glucose

[0117] Once a month, the animals were fasted overnight, and blood was collected from the tip of the tail on the second day. To reduce the influence of animal stress, etc., the first drop of blood was discarded, and the subsequent blood was collected with a blood glucose test strip to read the blood glucose meter reading to monitor fasting blood glucose.

[0118] 2.3 OGTT

[0119] Before the end of the experiment, the animals were fasted overnight, and drugs were administered on the second day. After 30 minutes, a glucose solution was given at 2 g / kg for model establishment, and blood was collected from the tip of the tail at 0 min, 15 min, 30 min, 60 min, and 120 min after model establishment. The change in blood glucose was recorded, and the area under the blood glucose curve AUC was calculated.

[0120] AUC: (t 15min + t 0min ) x 0.25 / 2 + (t 30mi n + t 15min ) x 0.25 / 2 + (t 30min + t 60min ) x 0.5 / 2 + (t 120min + t 60min ) x 1 / 2。

[0121] 2.4 Forelimb Grip Strength

[0122] Before the end of the experiment, grip strength tests were conducted. The animals were allowed to adapt to the testing instrument and restraint method in advance. Before the test, the animals were weighed. The animals were held by the tail and allowed to grasp a digital dynamometer. At the same time, the animals were gently pulled parallel to the test rod by the tail. When the maximum force was applied to the experimental mice, the reading on the grip strength meter was recorded. The measurements were repeated multiple times to ensure the results, and the force / body weight (g / g) was calculated.

[0123] 2.5 Lee's Index

[0124] At the end of the experiment, the animals were weighed and their body lengths were measured. The body length was defined as the length from the tip of the mouse's nose to the base of the tail. The mouse was fixed when measuring the body length to avoid arching its back, and Lee's Index was calculated.

[0125] Lee's Index = body weight / 3 * 1000 / body length.

[0126] 2.6 Tissue Weighing

[0127] At the end of the experiment, after the animals were euthanized, bilateral epididymal fat, perirenal fat, and gastrocnemius muscle tissues were dissected and weighed separately. The weight of the adipose tissue was recorded, and the gastrocnemius muscle / body weight (mg / g) ratio was calculated.

[0128] 2.7 Glycated Hemoglobin

[0129] At the end of the experiment, the animals were fasted overnight. The next day, blood was collected by eye removal. The upper serum was collected after centrifugation, and glycated hemoglobin was detected using a kit.

[0130] 2.8 Insulin

[0131] At the end of the experiment, the animals were fasted overnight. The next day, blood was collected by eye removal. The upper serum was collected after centrifugation, and serum insulin was detected using a kit.

[0132] 2.9 Data Statistics

[0133] Data were statistically analyzed by one-way ANOVA and post hoc tests were performed using Dunnett’s. The significance levels are as follows: #P≤0.05, ##P≤0.01, P≤0.001, model group vs. control group; *P≤0.05, **P≤0.01, ***P≤0.001, treatment group vs. model group.

[0134] 3. Experimental results

[0135] 3.1 Effects of Composition A on the body weight of diet-induced obese model mice

[0136] Figure 1 It is the body weight change curve of the diet-induced obese model in Example 1 after 8 weeks of drug administration. Figure 2 It is the change rate curve of body weight in Example 1. Figure 3 It is the Lee's index of the diet-induced obese model in Example 1 after 8 weeks of drug administration.

[0137] The results showed that: before drug administration (D0), there was no significant difference in body weight between the model group and each drug administration group. Compared with the G1 blank control group, the body weights of the model group and each drug administration group were significantly increased, showing statistical differences. At the experimental endpoint, compared with the G1 control group, the body weight of the G2 model group was significantly increased. Compared with the body weight of the G2 model group, the body weights of each drug administration group decreased. Among them, both the high and low dose groups of Composition A showed statistical differences and were dose-dependent. At the end of the experiment, compared with the initial body weight, the body weights of all groups showed an increasing trend. Compared with the G1 blank control group, the Lee's index of the G2 model group was significantly increased. Compared with the model group, the Lee's index of each drug administration group decreased. Among them, the high dose group of Composition A showed statistical differences. Composition A had a better effect on body weight loss, with a smaller body weight change rate and a lower Lee's index.

[0138] After diet induction in the mice of Example 1, the initial body weight was below 25 g. At this time, the body weight was relatively small and an obese model had not been fully formed. In the subsequent experiment, the body weight of the mice in Example 1 gradually increased, forming a stable obese model. The model in Example 1 was a preventive drug administration model, indicating that Composition A can prevent obesity.

[0139] The results showed that Composition A had a controlling effect on the body weight of high-fat diet-induced obese mice.

[0140] 3.2 Effects of Composition A on the blood glucose of diet-induced obese model mice

[0141] Figure 4 It is the fasting blood glucose result of the diet-induced obese model in Example 1. Figure 5 It is the glycated hemoglobin result of the diet-induced obese model at the experimental endpoint in Example 1.

[0142] The results showed that compared with the G1 blank control group, the fasting blood glucose and glycated hemoglobin in the G2 model control group were significantly increased, showing statistical differences; compared with the G2 model control group, the fasting blood glucose decreased in each administration group, and the concentration of glycated hemoglobin in the blood decreased. The high-dose group of Composition A in G4 had statistical differences and showed a dose-dependent relationship, indicating that Composition A has a control effect on blood glucose in obese mice.

[0143] 3.3 Effect of Composition A on Oral Glucose Tolerance in Diet-Induced Obese Model Mice

[0144] Figure 6 It is the OGTT experimental result of the diet-induced obese model in Example 1.

[0145] The results showed that compared with the G1 blank control group, after glucose modeling in the G2 model control group, the blood glucose increased rapidly and decreased slowly, and the area under the blood glucose curve (AUC) had statistical differences, indicating that the glucose tolerance of the model group was impaired; compared with the G2 model control group, the high and low dose groups of Composition A improved the ability of the mice's body to regulate blood glucose concentration, and the AUC decreased, showing statistical differences and a dose-dependent relationship.

[0146] 3.4 Effect of Composition A on Forelimb Grip Strength in Diet-Induced Obese Model Mice

[0147] Figure 7 It is the test result of forelimb grip strength of the diet-induced obese model in Example 1.

[0148] The results showed that compared with the G1 blank control group, both the grip strength and the grip strength / body weight ratio in the G2 model control group decreased, and there were statistical differences, indicating that the muscle strength of the model group was impaired; compared with the G2 model control group, the forelimb grip strength / body weight ratio of the mice in each administration group increased, and the high-dose group of Composition A in G4 had statistical differences, indicating that Composition A improved the muscle strength impairment caused by obesity.

[0149] 3.5 Effect of Composition A on Adipose Tissue in Diet-Induced Obese Model

[0150] Figure 8 It is the wet weight result of adipose tissue of the diet-induced obese model in Example 1. Figure 9 It is the cell area result of adipose tissue of the diet-induced obese model in Example 1.

[0151] The results showed that compared with the G1 blank control group, the wet weight of adipose tissue in the G2 model control group increased significantly, and the adipose cell area increased significantly; compared with the G2 model control group, the wet weight of adipose tissue decreased in each administration group, and the adipose cell area decreased. Composition A showed a dose-dependent relationship and had statistical differences. The data showed that Composition A has a control effect on the weight and cell area of adipose tissue in animals with diet-induced obesity.

[0152] 3.6 Effect of Composition A on Serum Insulin in Diet-Induced Obesity Model

[0153] Figure 10 It is the result of serum insulin in the diet-induced obesity model of Example 1.

[0154] The results showed that: compared with the G1 blank control group, the serum insulin in the G2 model control group increased significantly; compared with the G2 model control group, the serum insulin levels in each administration group decreased, and there was a statistical difference in the high-dose group of Composition A in G4. The data indicated that Composition A could improve the insulin resistance in animals with diet-induced obesity model.

[0155] To sum up, it shows that: in the obesity model induced by high-fat diet, Composition A of the present invention can effectively control the weight gain of mice, control the blood glucose of mice, improve the grasping force of mice, reduce the fat weight and cell area of mice, and reduce the serum insulin level. It can be used to prepare drugs for preventing and treating complications such as diet-induced obesity, metabolic disorders, insulin resistance, type 2 diabetes, and muscle function decline. In addition, in the obesity model induced by high-fat diet, Composition A increases the grasping force of mice and improves the proportion of muscle tissue, and can be used to prevent and treat muscle function decline, etc., so as to achieve the effect of anti-aging.

[0156] Example 2

[0157] Therapeutic Efficacy Experiment in C57 Mouse Diet-Induced Obesity Model

[0158] 1. Experimental Procedures

[0159] 1.1 Experimental Animals and Reagents

[0160] SPF-grade 5-week-old male C57BL / 6J mice were purchased from Chengdu Yakang Biotechnology Co., Ltd.

[0161] Composition B includes the following components in parts by weight: 42.5 parts of bilobalide, 27 parts of ginkgolide A, 17 parts of ginkgolide B, 16 parts of ginkgolide C, and 5 parts of ginkgolide J.

[0162] Among them, bilobalide, ginkgolide A, ginkgolide B, ginkgolide C, and ginkgolide J are all from Chengdu Baiyu Pharmaceutical Co., Ltd.

[0163] Feed: High-fat feed 60% kcal, product number: XTHF60; maintenance feed, product number: 1010088, and the feeds were all purchased from Jiangsu Xietong Pharmaceutical Biotechnology Co., Ltd.

[0164] 1.2 Establishment of Diet-Induced Obesity Model:

[0165] Animals in the blank control group were fed maintenance feed. Eight animals were selected for the blank control group according to their body weight levels and continuously fed maintenance feed until the end of the experiment.

[0166] Animals in the model group and each drug administration group were fed a high-fat diet. After the maintenance feed and the high-fat diet were transitioned according to 3:7, 5:5, and 7:3, the animals were fed a high-fat diet to establish a diet-induced obesity model. After diet induction, the body weight levels of the animals were measured. Compared with the animals fed maintenance feed, the body weight of the animals increased significantly and showed statistical differences. Then, the animals were grouped. First, the animals fed a high-fat diet were sorted according to their body weight values, and 1 / 4 of the diet-induced obesity-resistant animals with lower body weight were excluded. Then, according to their body weight, they were randomly divided into 3 groups of 8 animals each using the S-shaped grouping method. After grouping and drug administration, they continued to be fed a high-fat diet until the end of the experiment.

[0167] 1.3 Administration method:

[0168] After the animals were randomly grouped, drug administration began. The groups included: G1 blank control group (maintenance feed, Vehicle), G2 model control group (high-fat diet, Vehicle), G3 composition B group (high-fat diet, 150 mg / kg), and G4 positive control orlistat group (high-fat diet, 20 mg / kg). The administration volume was 5 mL / kg. The control group and the model group were gavaged with an equal volume of solvent. Vehicle: DMSO: 0.5% MC = 5:95 (v / v). The drug was administered by gavage once a day, QD, for 8 weeks.

[0169] 2. Detection indicators

[0170] 2.1 Animal body weight

[0171] Once a week, the animals were weighed at a fixed time period to monitor the change in their body weight and calculate the body weight change rate.

[0172] 2.2 Fasting blood glucose

[0173] Once a month, the animals were fasted overnight, and blood was collected from the tip of the tail on the second day. To reduce the impact of animal stress, etc., the first drop of blood was discarded, and the subsequent blood was collected with a blood glucose test strip to read the blood glucose meter reading to monitor fasting blood glucose.

[0174] 2.3 OGTT

[0175] Before the end of the experiment, the animals were fasted overnight, and drugs were administered on the second day. 30 minutes later, a glucose solution was given at 2 g / kg to establish a model, and blood was collected from the tip of the tail at 0 min, 15 min, 30 min, 60 min, and 120 min after model establishment. The change in blood glucose was recorded, and the area under the blood glucose curve AUC was calculated.

[0176] AUC: (t 15min +t 0min )x0.25 / 2+(t30mi n + t 15min )x0.25 / 2 + (t 30min + t 60min )x0.5 / 2 + (t 120min + t 60min )x1 / 2。

[0177] 2.4 Forelimb Grip Strength

[0178] Before the end of the experiment, a grip strength test was conducted. The animals were allowed to adapt to the test instrument and restraint method in advance. Before the test, the animal's body weight was measured. The animal's tail was grasped, and it was allowed to grasp the digital dynamometer. At the same time, it was gently pulled parallel to the test rod by the tail. When the maximum force was applied to the experimental mice, the reading on the grip strength meter was recorded. The measurement was repeated multiple times to ensure the results, and the force / body weight (g / g) was calculated.

[0179] 2.5 Treadmill Test

[0180] Before the formal experiment, the mice were subjected to running training. The training conditions were as follows: D1 training: free movement on a stationary runway for 10 min; 5 m / min for 5 min; 8 m / min for 5 min; D2 training: 5 m / min for 4 min; 8 m / min for 3 min; 12 m / min for 3 min; D3 training: 5 m / min for 4 min; 10 m / min for 3 min; 15 m / min for 3 min. During the training, the number of electric shocks did not exceed 5 times, and the time did not exceed 1 s. When the animal left the runway, it was forced to return to the runway by humans to continue training. After the training, the formal experimental conditions were: 10 m / min, acceleration duration of 3 min, maintenance for 5 min, and then directly 18 m / min, acceleration duration of 15 min, maintenance for 900 s, electric shock for 10 s, 50 times, 0.4 mA. During this period, each mouse was placed separately in a runway. After changing the mouse, the runway was cleaned with water and alcohol to avoid odor interference with the mouse's behavior. Each animal had at least a 1-h rest interval between formal experiments. During the experiment, conversations and movements were minimized to avoid noise interference.

[0181] 2.6 Rotarod Test

[0182] Before the formal experiment, the mice were subjected to rotarod training under the following conditions: Training D1: 5 r / min for 1 min, 10 r / min for 1 min, 5 - 20 r / min for 3 min, with an experimental duration of 5 min; Training D2: 5 r / min for 1 min, 10 r / min for 1 min, 5 - 30 r / min for 3 min, with an experimental duration of 5 min. During the training, when the animal fell off the rotarod, it was manually placed back on the rotarod to continue the training until the training duration was reached. After the training, the formal experimental conditions were: 5 - 40 r / min, with an acceleration time of 5 min and a total experimental duration of 10 min. During this period, each mouse was placed individually in a rotarod compartment. After changing the mice, the rotarod needed to be cleaned with water and alcohol to avoid odor interference with the mouse behavior. There should be at least a 1-hour rest interval between each formal experiment for the animals. During the experiment, attention should be paid to reducing conversation and movement to avoid noise interference.

[0183] 2.6 Lee's index

[0184] At the end of the experiment, the animals were weighed and their body lengths were measured. The body length was defined as the length from the tip of the mouse's nose to the base of the tail. When measuring the body length, the mouse was fixed to avoid arching its back, and the Lee's index was calculated.

[0185] Lee's index = body weight / 3 * 1000 / body length.

[0186] 2.7 Tissue weighing

[0187] At the end of the experiment, after the animals were euthanized, the bilateral epididymal fat, perirenal fat, and gastrocnemius muscle tissues were dissected and weighed separately. The weight of the adipose tissue was recorded, and the gastrocnemius muscle / body weight (mg / g) ratio was calculated.

[0188] 2.8 Glycated hemoglobin

[0189] At the end of the experiment, the animals were fasted overnight. On the second day, blood was collected by eye enucleation. After centrifugation, the lower layer of red blood cells was collected, and purified water was added to prepare a hemolysate sample. A kit was used to detect glycated hemoglobin.

[0190] 2.9 Insulin

[0191] At the end of the experiment, the animals were fasted overnight. On the second day, blood was collected by eye enucleation. After centrifugation, the upper layer of plasma was collected, and a kit was used to detect plasma insulin.

[0192] 2.10 Data statistics

[0193] The data were statistically analyzed by one-way analysis of variance and post hoc test using Dunnett's. The significance markers were as follows: #P ≤ 0.05, ##P ≤ 0.01, P ≤ 0.001, model group vs. control group; *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, treatment group vs. model group.

[0194] 3. Experimental Results

[0195] 3.1 Effect of Composition B on the Body Weight of Mice in a Diet-Induced Obesity Model

[0196] Figure 11 It is the body weight change curve of the diet-induced obesity model in Example 2 after 8 weeks of drug administration. Figure 12 It is the change curve of the body weight change rate in Example 2. Figure 13 It is the Lee's index of the diet-induced obesity model in Example 2 after 8 weeks of drug administration.

[0197] The results show that: before drug administration (D0), there was no significant difference in body weight between the model group and each drug administration group. Compared with the G1 blank control group, the body weight of the model group and each drug administration group was significantly increased, with statistical differences. At the experimental end point, compared with the G1 control group, the body weight of the G2 model group was significantly increased; compared with the body weight of the G2 model group, the body weight of each drug administration group decreased, and there was a statistical difference in the G3 Composition B group. At the end of the experiment, compared with the initial body weight, the body weight of each group showed an increasing trend; compared with the G1 blank control group, the Lee's index of the G2 model group was significantly increased; compared with the model group, the Lee's index of each drug administration group decreased, and there was a statistical difference in the Composition B group. Compared with the G4 positive control orlistat group, the body weight of the G3 Composition B group was significantly lower than that of the positive control group, that is, the weight-reducing effect of Composition B was better than that of the positive control orlistat.

[0198] After the diet induction of the mice in Example 2, the initial body weight was above 25 g, and the body weight was relatively large at this time, forming a stable obesity model. The model in Example 2 was a treatment drug administration model, indicating that Composition A can treat obesity.

[0199] The results show that Composition B has a controlling effect on the body weight of mice induced by a high-fat diet.

[0200] 3.2 Effect of Composition B on the Blood Glucose of Mice in a Diet-Induced Obesity Model

[0201] Figure 14 It is the fasting blood glucose result of the diet-induced obesity model in Example 2. Figure 15 It is the glycated hemoglobin result of the diet-induced obesity model at the experimental end point in Example 2.

[0202] The results show that: compared with the G1 blank control group, the fasting blood glucose and glycated hemoglobin of the G2 model control group were significantly increased, with statistical differences; compared with the G2 model control group, the fasting blood glucose of the G3 Composition B group and the G4 orlistat group decreased, and the concentration of glycated hemoglobin in the blood decreased, with statistical differences, indicating that Composition B has a controlling effect on the blood glucose of obese mice.

[0203] 3.3 Effect of Composition B on Oral Glucose Tolerance in Diet-Induced Obesity Model Mice

[0204] Figure 16 It is the OGTT experimental result of the diet-induced obesity model in Example 2.

[0205] The results showed that: compared with the G1 blank control group, after glucose modeling in the G2 model control group, the blood glucose increased rapidly and decreased slowly, and there was a statistically significant difference in the area under the blood glucose curve (AUC), indicating that the glucose tolerance of the model group was impaired; compared with the G2 model control group, the G3 Composition B group improved the ability of the mouse body to regulate blood glucose concentration, and the AUC decreased, with a statistically significant difference. Under this dosing condition, the G4 orlistat group had no obvious improvement in glucose tolerance.

[0206] 3.4 Effect of Composition B on Forelimb Grip Strength in Diet-Induced Obesity Model Mice

[0207] Figure 17 It is the test result of forelimb grip strength of the diet-induced obesity model in Example 2.

[0208] The results showed that: compared with the G1 blank control group, both the grip strength and the grip strength / body weight ratio in the G2 model control group decreased, and there was a statistically significant difference, indicating that the muscle strength of the model group was impaired; compared with the G2 model control group, the forelimb grip strength and the grip strength / body weight ratio of the mice in each dosing group increased, and there was a statistically significant difference, indicating that Composition B improved the muscle strength impairment caused by obesity and increased the muscle grip strength.

[0209] 3.5 Effect of Composition B on Running Distance in Diet-Induced Obesity Model Mice

[0210] The results showed that: compared with the G1 blank control group, the running distance in the G2 model control group decreased; compared with the G2 model control group, the running distance in the G4 orlistat group and the G3 Composition B group showed an upward trend.

[0211] 3.6 Effect of Composition B on Duration on the Rod in Diet-Induced Obesity Model Mice

[0212] The results showed that: compared with the G1 blank control group, the duration on the rod in the G2 model control group decreased, indicating that the endurance or motor coordination performance of the model group was impaired; compared with the G2 model control group, the duration on the rod in the G4 orlistat group and the G3 Composition B group showed an upward trend.

[0213] 3.7 Effect of Composition B on Wet Weight of Tissues in Diet-Induced Obesity Model

[0214] Figure 18 It is the wet weight result of adipose tissue of the diet-induced obesity model in Example 2, Figure 19 It is the gastrocnemius muscle / body weight result of the diet-induced obesity model in Example 2.

[0215] The results showed that: compared with the G1 blank control group, the wet weight of adipose tissue in the G2 model control group was significantly increased, and the gastrocnemius muscle / body weight was significantly decreased; compared with the G2 model control group, the wet weight of adipose tissue in the G3 composition B group and the G4 orlistat group decreased, and the gastrocnemius muscle / body weight increased, and there was a statistical difference in the composition B group. The data indicated that composition B had a controlling effect on the adipose tissue weight of animals in the diet-induced obesity model, and could improve the proportion of muscle tissue and increase the muscle proportion.

[0216] 3.8 Effect of composition B on plasma insulin in the diet-induced obesity model

[0217] Figure 20 It was the result of plasma insulin in the diet-induced obesity model of Example 2.

[0218] The results showed that: compared with the G1 blank control group, the plasma insulin in the G2 model control group was significantly increased; compared with the G2 model control group, the plasma insulin levels in the G3 composition B group and the G4 orlistat group decreased. The data indicated that composition B could improve the insulin resistance phenomenon of animals in the diet-induced obesity model to a certain extent.

[0219] In summary, it was shown that: in the obesity model induced by high-fat diet, composition B of the present invention could effectively control the body weight gain of mice, control the blood glucose of mice, improve the grasping force of mice, reduce the adipose weight of mice, increase the muscle proportion of mice, and reduce the plasma insulin level, and could be used for preparing drugs for preventing and treating obesity or obesity complications such as diet-induced obesity, insulin resistance, type 2 diabetes, and muscle function decline. In addition, in the obesity model induced by high-fat diet, composition B increased the grasping force and running distance of mice, improved the proportion of muscle tissue, reduced the adipose weight and muscle proportion of mice, and could be used for preventing and treating muscle function decline, etc., so as to achieve the anti-aging effect.

[0220] Example 3

[0221] Pharmacodynamic experiment in the hypertriglyceridemia model of golden hamsters

[0222] 1. Experimental procedures

[0223] 1.1 Experimental animals and reagents

[0224] SPF-grade 7-week-old male golden hamsters (strain name: LVG Hamster, code: 501) were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd.

[0225] Composition C included the following components in parts by weight: 40 parts of bilobalide, 25 parts of ginkgolide A, 15 parts of ginkgolide B, 14 parts of ginkgolide C, and 3.5 parts of ginkgolide J.

[0226] Among them, bilobalide, ginkgolide A, ginkgolide B, ginkgolide C, and ginkgolide J are all from Chengdu Baiyu Pharmaceutical Co., Ltd.

[0227] Feed: High-fructose feed 60% kcal%, product number: XT-704; maintenance feed, product number: 1010088. All feeds are purchased from Jiangsu Xietong Pharmaceutical Biotechnology Co., Ltd.

[0228] 1.2 Establishment of diet-induced hypertriglyceridemia model:

[0229] Animals in the blank control group were fed maintenance feed. Eight animals were selected from the blank control group according to the serum triglyceride level and continuously fed maintenance feed until the end of the experiment.

[0230] Animals in the model group and each administration group were fed high-fructose feed. After the maintenance feed and high-fructose feed were transitioned according to 3:7, 5:5, and 7:3, the animals were fed high-fructose feed to establish a hypertriglyceridemia model. After one to two weeks of diet induction, the serum triglyceride level was detected. Compared with the animals fed maintenance feed, the serum triglyceride level was significantly increased and there was a statistical difference. Then, the animals were grouped, and the animals with serum triglyceride ≥ 2.3 mmol / L were selected. According to the serum triglyceride level, they were randomly divided into 3 groups with 8 animals in each group. After grouping and administration, they continued to be fed high-fructose feed until the end of the experiment.

[0231] 1.3 Administration method:

[0232] After the animals were randomly grouped, administration began. The groups included: G1 blank control group (maintenance feed, Vehicle), G2 model control group (high-fructose feed, Vehicle), G3 high-dose group of composition C (high-fructose feed, 150 mg / kg), and G4 low-dose group of composition C (high-fructose feed, 50 mg / kg). The administration volume was 5 mL / kg. The control group and the model group were gavaged with an equal volume of solvent. Vehicle: DMSO: 0.5% MC = 5:95 (v / v). Administration was carried out once a day, QD, for 6 weeks.

[0233] 2. Detection indicators

[0234] 2.1 Animal body weight

[0235] Twice a week, monitor the change in animal body weight and calculate the body weight change rate.

[0236] 3. Experimental results

[0237] 3.1 Effect of composition C on the body weight of golden hamsters with diet-induced hypertriglyceridemia model

[0238] Figure 21Weight change curve after 6 weeks of administration for the diet-induced hypertriglyceridemia model in Example 3 Figure 22 Weight change rate curve in Example 3

[0239] The results showed that: before administration (D0), there were no significant differences in body weight among groups. By the last observation before the end of administration (D47), compared with the G2 model control group, the body weights of the high and low dose groups of Composition C in G3 and G4 decreased after administration. Among them, the body weight of the high dose group of Composition C in G3 decreased by 12.7%, showing a statistically significant difference, and the body weight decrease was dose-dependent on Composition C. At the end of the experiment, compared with the initial body weight, the body weights of all groups showed an increasing trend. Composition C had a controlling effect on the body weight of golden hamsters induced by a high fructose diet.

[0240] In summary, it is shown that: in the high fructose-induced hypertriglyceridemia model, Composition C of the present invention can effectively control body weight gain and can be used for preparing drugs for preventing or treating obesity caused by hypertriglyceridemia, etc.

[0241] The description of specific implementation modes in the specification of the present invention has been detailed. Those skilled in the art should recognize that the above implementation modes are exemplary and should not be construed as limitations on the present invention. For those skilled in the art, without departing from the principle of the present invention, by making several improvements and modifications to the present invention, the technical solutions obtained by these improvements and modifications also fall within the protection scope of the claims of the present invention.

Claims

1. Use of ginkgolide in the preparation of a medicament for preventing or treating obesity and obesity complications, wherein the ginkgolide comprises at least one of ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, and ginkgolide K.

2. The use according to claim 1, wherein: The weight ratio of ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, and ginkgolide K is selected from one of the following: Ginkgolide A: Ginkgolide B = (10 - 45):(5 - 40); Ginkgolide A: Ginkgolide C = (10 - 45):(3 - 35); Ginkgolide B: Ginkgolide C = (5 - 40):(3 - 35); Ginkgolide A: Ginkgolide B: Ginkgolide C = (10 - 45):(5 - 40):(3 - 35); Ginkgolide A: Ginkgolide B: Ginkgolide C: Ginkgolide J = (10 - 45):(5 - 40):(3 - 35):(1 - 10); Ginkgolide A: Ginkgolide K = (3 - 40):(0.01 - 5); Ginkgolide B: Ginkgolide K = (5 - 75):(0.01 - 5); Ginkgolide A: Ginkgolide B: Ginkgolide K = (3 - 40):(5 - 75):(0.01 - 5).

3. The use according to claim 1, wherein: The mass ratio of ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, ginkgolide K, and bilobalide is selected from one of the following: Ginkgolide A: Ginkgolide B: Bilobalide = (10 - 45):(5 - 40):(10 - 70); Ginkgolide A: Ginkgolide C: Bilobalide = (10 - 45):(3 - 35):(10 - 70); Ginkgolide B: Ginkgolide C: Bilobalide = (5 - 40):(3 - 35):(10 - 70); Ginkgolide A: Ginkgolide B: Ginkgolide C: Bilobalide = (10 - 45):(5 - 40):(3 - 35):(10 - 70); Ginkgolide A: Ginkgolide B: Ginkgolide C: Ginkgolide J: Bilobalide = (10 - 45):(5 - 40):(3 - 35):(1 - 10):(10 - 70); Ginkgolide A: Ginkgolide K: Bilobalide = (3 - 40):(0.01 - 5):(10 - 70); Ginkgolide B: Ginkgolide K: Bilobalide = (5 - 75):(0.01 - 5):(10 - 70); Ginkgolide A: Ginkgolide B: Ginkgolide K: Bilobalide = (3 - 40):(5 - 75):(0.01 - 5):(10 - 70).

4. The use according to claim 1, characterized in that: The mass parts of ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, and bilobalide are selected as follows: 40 - 43 parts of bilobalide, 25 - 27 parts of ginkgolide A, 15 - 17 parts of ginkgolide B, 14 - 16 parts of ginkgolide C, and 3.5 - 5 parts of ginkgolide J.

5. The use according to any one of claims 1 to 4, characterized in that: The dosage of the ginkgolide is 0.1 - 400 mg / kg / day; preferably, the dosage of the ginkgolide is 1 - 200 mg / kg / day.

6. The use according to any one of claims 1 to 6, characterized in that: Use of the ginkgolide in the preparation of a medicament for preventing or treating diet-induced obesity.

7. Use according to any one of claims 1 to 6, characterized in that: Use of the ginkgolide in the preparation of a medicament for preventing or treating obesity caused by hypertriglyceridemia.

8. The use according to any one of claims 1 to 6, characterized in that: Use of the ginkgolide in the preparation of a medicament for preventing or treating complications of diet-induced obesity and obesity complications caused by hypertriglyceridemia.

9. The use according to claim 8, wherein: The obesity complications are metabolic disorders, decreased muscle function or insulin resistance.

10. Use of the ginkgolide in the preparation of an anti-aging medicament or health product, wherein the ginkgolide comprises at least one of ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, and ginkgolide K.

11. According to the use described in claim 10, it is characterized in that: The weight ratios of the ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, and ginkgolide K are selected from one of the following: Ginkgolide A:Ginkgolide B = (10 - 45):(5 - 40); Ginkgolide A:Ginkgolide C = (10 - 45):(3 - 35); Ginkgolide B:Ginkgolide C = (5 - 40):(3 - 35); Ginkgolide A:Ginkgolide B:Ginkgolide C = (10 - 45):(5 - 40):(3 - 35); Ginkgolide A:Ginkgolide B:Ginkgolide C:Ginkgolide J = (10 - 45):(5 - 40):(3 - 35):(1 - 10); Ginkgolide A:Ginkgolide K = (3 - 40):(0.01 - 5); Ginkgolide B:Ginkgolide K = (5 - 75):(0.01 - 5); Ginkgolide A:Ginkgolide B:Ginkgolide K = (3 - 40):(5 - 75):(0.01 - 5).

12. The use according to claim 11, wherein: The mass ratios of the ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, ginkgolide K, and bilobalide are selected from one of the following: Ginkgolide A:Ginkgolide B:Bilobalide = (10 - 45):(5 - 40):(10 - 70); Ginkgolide A:Ginkgolide C:Bilobalide = (10 - 45):(3 - 35):(10 - 70); Ginkgolide B:Ginkgolide C:Bilobalide = (5 - 40):(3 - 35):(10 - 70); Ginkgolide A:Ginkgolide B:Ginkgolide C:Bilobalide = (10 - 45):(5 - 40):(3 - 35):(10 - 70); Ginkgolide A:Ginkgolide B:Ginkgolide C:Ginkgolide J:Bilobalide = (10 - 45):(5 - 40):(3 - 35):(1 - 10):(10 - 70); Ginkgolide A:Ginkgolide K:Bilobalide = (3 - 40):(0.01 - 5):(10 - 70); Ginkgolide B:Ginkgolide K:Bilobalide = (5 - 75):(0.01 - 5):(10 - 70); Ginkgolide A:Ginkgolide B:Ginkgolide K:Bilobalide = (3 - 40):(5 - 75):(0.01 - 5):(10 - 70).

13. The use according to claim 12, wherein: The mass parts of ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, and bilobalide are selected from: 40 to 43 parts of bilobalide, 25 to 27 parts of ginkgolide A, 15 to 17 parts of ginkgolide B, 14 to 16 parts of ginkgolide C, and 3.5 to 5 parts of ginkgolide J.

14. Use according to any one of claims 10 to 13, characterized in that: The dosage of the ginkgo diterpenoid lactones is 0.1 - 400 mg / kg / day; preferably, the dosage of the ginkgo diterpenoid lactones is 1 - 200 mg / kg / day.

15. The use according to any one of claims 10 to 13, characterized in that: The anti-aging drug or health product is an anti-aging drug or health product that increases muscle proportion.

16. The use according to any one of claims 10 to 13, characterized in that: The anti-aging drug or health product is an anti-aging drug or health product that increases muscle grip strength.

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