Application of isoginkgetin in treatment of hyperlipidemia and atherosclerosis diseases

Abstract

The invention provides an application of isoginkgetin (alias: isoginkgetin) or pharmaceutically acceptable salt or hydrate thereof in preparation of drugs for preventing or treating hyperlipidemia and atherosclerotic diseases, and belongs to the technical field of medicine and pharmacology. The isoginkgetin disclosed by the invention can be used for remarkably reducing the level of blood fat in liver and serum in a high-cholesterol diet induced ApoE- / -mouse model, so that the formation of atherosclerotic plaques is relieved, and the plaque area is reduced. Furthermore, the isoginkgetin or the pharmaceutically acceptable salt or hydrate thereof can be applied to the preparation of medicines for preventing or treating hyperlipidemia and atherosclerotic diseases, can play roles in reducing blood fat and reducing the formation of atherosclerotic plaques, can also be combined with other medicines for use, and can be used for preparing medicines for preventing or treating hyperlipidemia and atherosclerotic diseases. Therefore, diversified clinical requirements of hyperlipidemia and atherosclerosis can be met.

Description

Technical Field

[0001] The present invention relates to the technical field of medicine, and in particular to the use of isoginkgetin, a traditional Chinese medicine active monomer, in the preparation of medicines for preventing or treating hyperlipidemia and atherosclerotic diseases. Background Art

[0002] Atherosclerotic Cardiovascular Disease (ASCVD) is one of the leading causes of disease and death worldwide. Atherosclerosis (AS), as the common pathological basis of many cardiovascular and cerebrovascular diseases, is the result of genetic, environmental and multifactorial influences. Its core feature is the dysfunction of arterial endothelial cells, which leads to lipid deposition in the arterial intima and beneath it. Subsequently, monocytes begin to aggregate, adhere to and phagocytose lipids to form foam cells and fatty plaques, accompanied by the proliferation of smooth muscle cells in the middle layer of blood vessels and the hyperplasia of connective tissue. The thickness of the intima increases, and eventually degeneration and calcification occur, forming intravascular fibrous plaques, leading to stenosis of the arterial lumen and ultimately causing target organ ischemia.

[0003] At the same time, there is a close relationship between blood lipids and atherosclerosis. Low-density lipoprotein (LDL) in the blood is one of the main pathogenic factors of atherosclerosis. LDL is deposited under the intima of the artery and forms oxidized low-density lipoprotein (Ox-LDL) after oxidation, which triggers inflammatory response and plaque formation. A large number of studies have confirmed that increased LDL levels are closely related to increased incidence of atherosclerosis and related complications. In contrast, high-density lipoprotein (HDL) can carry excess cholesterol from the arterial wall back to the liver for metabolism through reverse cholesterol transport, thereby protecting blood vessel health. Therefore, high blood lipids are closely related to atherosclerosis. Controlling blood lipid levels is essential for the prevention and management of atherosclerosis and its related cardiovascular diseases.

[0004] In the process of treating atherosclerosis, drug therapy is one of the commonly used methods. Lipid-lowering drugs represented by statins are considered to be the first choice for treating atherosclerosis. However, long-term and high-dose use of statins can cause muscle toxicity and increase the risk of new-onset diabetes, and some patients are not sensitive to statin treatment. Therefore, it is necessary to find safer and more effective lipid-lowering drugs and drugs for preventing and treating atherosclerosis. Summary of the invention

[0005] In view of this, in order to at least partially solve one of the above-mentioned technical problems, the present invention provides a use of isoginkgetin or a pharmaceutically acceptable salt or hydrate thereof in the preparation of a medicament for preventing or treating hyperlipidemia and / or atherosclerotic diseases.

[0006] According to an embodiment of the present invention, the salt includes at least one of maleate, nitrate, hydrochloride, phosphate and carbonate.

[0007] According to an embodiment of the present invention, isoginkgetin or a pharmaceutically acceptable salt or hydrate thereof is used to reduce total cholesterol in serum or liver.

[0008] According to an embodiment of the present invention, isoginkgetin or a pharmaceutically acceptable salt or hydrate thereof is used to reduce triglycerides in serum or liver.

[0009] According to an embodiment of the present invention, isoginkgetin or a pharmaceutically acceptable salt or hydrate thereof is used to reduce low-density lipoprotein in serum.

[0010] According to an embodiment of the present invention, isoginkgetin or a pharmaceutically acceptable salt or hydrate thereof is used to reduce the area of ​​atherosclerotic plaques.

[0011] According to an embodiment of the present invention, the dosage form of the drug is selected from at least one of the following: emulsion, oil, powder, aqueous solution, suspension, tablet, granule, capsule, nano preparation.

[0012] According to an embodiment of the present invention, the drug further includes a pharmaceutically acceptable carrier.

[0013] According to an embodiment of the present invention, in the case where the drug is an oral preparation, the carrier includes at least one of a binder, a lubricant, a disintegrant, a solubilizer, a diluent, a stabilizer, a suspending agent, a pigment, and a flavoring agent;

[0014] In the case where the drug is an injectable preparation, the carrier includes at least one of a preservative, a solubilizer, and a stabilizer;

[0015] In the case where the drug is a topical preparation, the carrier includes at least one of a base, a diluent, a lubricant, and a preservative.

[0016] According to an embodiment of the present invention, the administration method of the drug includes at least one of oral administration, intravenous administration, subcutaneous administration, intramuscular administration, intraperitoneal administration, and local administration.

[0017] According to the embodiments of the present invention, isoginkgetin can significantly reduce ApoE induced by high cholesterol diet. - / -The blood lipid levels in the liver and serum of the mouse model can be reduced, thereby reducing the formation of atherosclerotic plaques and reducing the plaque area. Furthermore, the isoginkgetin or its pharmaceutically acceptable salt or hydrate in the present invention can be used in the preparation of drugs for preventing or treating hyperlipidemia and / or atherosclerotic diseases, and can play a role in lowering blood lipids and reducing the formation of atherosclerotic plaques. It can also be used in combination with other drugs to meet the diverse clinical needs of hyperlipidemia and atherosclerosis. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The above and other objects, features and advantages of the present invention will become more apparent through the following description of the embodiments of the present invention with reference to the accompanying drawings, in which:

[0019] Figure 1 ApoE in the embodiment of the present invention - / - Schematic diagram of the experimental process and body weight changes of the mouse atherosclerosis model;

[0020] Figure 2 This is a comparison chart of the changes in total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglycerides after administration of isoginkgetin in the examples of the present invention;

[0021] Figure 3 This is a graph showing the results of Oil Red O staining of whole blood vessels and quantification of plaque area in mice according to an embodiment of the present invention;

[0022] Figure 4 This is a diagram of Oil Red O, H&E staining and quantitative results of the aortic sinus of mice in an example of the present invention. DETAILED DESCRIPTION

[0023] Below, embodiments of the present invention will be described with reference to the accompanying drawings. However, it should be understood that these descriptions are exemplary only and are not intended to limit the scope of the present invention. In the following detailed description, for ease of explanation, many specific details are set forth to provide a comprehensive understanding of embodiments of the present invention. However, it is apparent that one or more embodiments may also be implemented without these specific details. In addition, in the following description, descriptions of known structures and technologies are omitted to avoid unnecessary confusion of concepts of the present invention.

[0024] The terms used herein are only for describing specific embodiments and are not intended to limit the present invention. The term "comprising" used herein indicates the existence of features, steps, operations, but does not exclude the existence or addition of one or more other features.

[0025] In the case of using expressions such as "at least one of A, B, and C, etc.", it should generally be interpreted in accordance with the meaning of the expression generally understood by those skilled in the art (for example, "a system having at least one of A, B, and C" should include but is not limited to a system having A alone, B alone, C alone, A and B, A and C, B and C, and / or A, B, C, etc.). In the case of using expressions such as "at least one of A, B, or C, etc.", it should generally be interpreted in accordance with the meaning of the expression generally understood by those skilled in the art (for example, "a system having at least one of A, B, or C" should include but is not limited to a system having A alone, B alone, C alone, A and B, A and C, B and C, and / or A, B, C, etc.).

[0026] In the present invention, the term "pharmaceutically acceptable" refers to compounds, substances, compositions and / or dosage forms that are suitable for use in contact with human and animal tissues within the scope of reasonable medical judgment without excessive toxicity, irritation, allergic response, or other problems or complications, and commensurate with a reasonable benefit / risk ratio.

[0027] In the present invention, the term "hydrate" refers to a complex formed by combining a compound of formula (I) or a pharmaceutically acceptable salt thereof and water. Further, the compound of formula (I) or a pharmaceutically acceptable salt thereof can be isolated in the form of a hydrate, and any hydrate is included in the protection scope of the present invention.

[0028] In the present invention, the term "pharmaceutically acceptable salt" refers to a relatively non-toxic organic acid or inorganic acid addition salt of the compound of formula (I), wherein inorganic acids include hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, phosphoric acid, nitric acid, etc., and organic acids include formic acid, acetic acid, acetoacetic acid, pyruvic acid, butyric acid, caproic acid, heptanoic acid, undecanoic acid, lauric acid, benzoic acid, cinnamic acid, picric acid, trifluoromethanesulfonic acid, dodecylsulfuric acid, benzenesulfonic acid, p-toluenesulfonic acid, itaconic acid, naphthalene disulfonic acid, malic acid, adipic acid, alginic acid, maleic acid, D-gluconic acid, aspartic acid, etc.

[0029] The term "treatment" means that after a subject has a disease, the subject is exposed to (e.g., administered) a drug, composition, etc. according to the present invention, thereby alleviating the symptoms of the disease compared to when the subject has not been exposed to the drug, composition, etc., and does not necessarily mean that the symptoms of the disease are completely suppressed. Suffering from a disease means that the body has symptoms of the disease.

[0030] The term "prevention" means that before a subject develops a disease, the symptoms after developing the disease are alleviated compared to when the subject does not develop the disease by contacting (eg administering) the drug, composition, etc. according to the present invention, but does not necessarily mean that the disease must be completely suppressed.

[0031] In the process of realizing the concept of the present invention, it is found that in the process of treating atherosclerosis, drug therapy is one of the commonly used methods, and lipid-lowering drugs represented by statins are considered to be the first choice for treating atherosclerosis. Statins can block the cholesterol synthesis pathway by inhibiting hydroxymevalonate coenzyme A reductase (HMG-CoA reductase), which is the key rate-limiting enzyme in the cholesterol biosynthesis pathway in the liver, thereby reducing the total cholesterol and LDL levels in the blood. In addition, statins can increase the number of LDL receptors on the surface of hepatocytes, promote the clearance of LDL-C in the blood, and further reduce the LDL-C level in the blood. Although statins are the most widely used drugs for treating hypercholesterolemia, one-fifth of patients are still not sensitive to statin treatment, and long-term high-dose use of statins can cause muscle toxicity and increase the risk of new-onset diabetes. Therefore, finding new lipid-lowering drugs is a research hotspot and difficulty in the cardiovascular field.

[0032] Ginkgo biloba L., the main components of ginkgo extract include ginkgo flavonoids, ginkgolides, biflavonoids, organic acids and other terpenoids. Among them, isoginkgetin (ISOGK), a biflavonoid extracted from ginkgo leaves, has a structural formula as shown in the following formula (1). It has been studied in the fields of anti-inflammatory, antioxidant and anti-tumor. However, it has not been used in the fields of lipid-lowering and treatment of arteriosclerosis.

[0033] Formula (1).

[0034] Based on this, according to an embodiment of one aspect of the present invention, there is provided a use of isoginkgetin or a pharmaceutically acceptable salt or hydrate thereof in the preparation of a medicament for preventing or treating hyperlipidemia and / or atherosclerotic diseases.

[0035] According to the embodiments of the present invention, isoginkgetin can significantly reduce ApoE induced by high cholesterol diet. - / - The blood lipid levels in the liver and serum of the mouse model can be reduced, thereby reducing the formation of atherosclerotic plaques and reducing the plaque area. Furthermore, the isoginkgetin or its pharmaceutically acceptable salt or hydrate in the present invention can be used in the preparation of drugs for preventing or treating hyperlipidemia and / or atherosclerotic diseases, and can play a role in lowering blood lipids and reducing the formation of atherosclerotic plaques. It can also be used in combination with other drugs to meet the diverse clinical needs of hyperlipidemia and atherosclerosis.

[0036] According to an embodiment of the present invention, the salt includes at least one of maleate, nitrate, hydrochloride, phosphate and carbonate.

[0037] According to the embodiments of the present invention, drug salt formation is an important means to increase drug solubility and improve bioavailability, which can increase the water solubility of the drug and at the same time increase the stability of the drug, including thermal stability, light stability and stability to humidity, thereby improving the bioavailability of the drug.

[0038] According to an embodiment of the present invention, isoginkgetin or a pharmaceutically acceptable salt or hydrate thereof is used to reduce total cholesterol in serum or liver.

[0039] According to an embodiment of the present invention, isoginkgetin or a pharmaceutically acceptable salt or hydrate thereof is used to reduce triglycerides in serum or liver.

[0040] According to an embodiment of the present invention, isoginkgetin or a pharmaceutically acceptable salt or hydrate thereof is used to reduce low-density lipoprotein in serum.

[0041] According to an embodiment of the present invention, isoginkgetin or a pharmaceutically acceptable salt or hydrate thereof is used to reduce the area of ​​atherosclerotic plaques.

[0042] According to an embodiment of the present invention, cholesterol is the main component of atherosclerotic plaques. Lowering cholesterol levels, especially low-density lipoprotein cholesterol (LDL-C), has been shown to significantly reduce the risk of atherosclerotic cardiovascular diseases such as coronary heart disease. When LDL, especially oxidized LDL (Ox-LDL), is excessive, the cholesterol it carries may accumulate on the arterial wall, and long-term accumulation can easily cause arteriosclerosis.

[0043] According to an embodiment of the present invention, hyperlipidemia refers to the increase of blood lipid components such as cholesterol, triglycerides and lipids in plasma. High triglyceride levels can promote the formation of atherosclerosis. Triglycerides are metabolized into free fatty acids, which enter the blood circulation through lipoproteins synthesized by the liver and are transported to various organs and tissues. Excessive free fatty acids can cause an increase in the number of lipoproteins in the blood, and lipids are deposited on the inner wall of blood vessels, thereby leading to the formation of atherosclerosis. High triglycerides can also cause inflammatory reactions, causing vascular endothelial cells and leukocytes to gather in the arterial wall, increase the thickness of the inner wall of blood vessels, form plaques, and ultimately lead to the formation of atherosclerosis. Hyperlipidemia, especially the increase of serum cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C), is the main risk factor for the onset of atherosclerosis. Reducing triglycerides and cholesterol in serum can reduce the level of inflammatory factors in plasma, inhibit liver fatty degeneration and reduce the formation of aortic atherosclerosis plaques, and delay the progression of atherosclerosis.

[0044] According to an embodiment of the present invention, the dosage form of the drug is selected from at least one of the following: emulsion, oil, powder, aqueous solution, suspension, tablet, granule, capsule, nano preparation.

[0045] According to the embodiments of the present invention, the dosage forms of various drugs meet different treatment needs, improve patient compliance, optimize drug efficacy and safety, can meet different clinical needs and patient preferences, and adapt to different administration routes.

[0046] According to an embodiment of the present invention, the drug further includes a pharmaceutically acceptable carrier.

[0047] According to an embodiment of the present invention, the drug carrier can improve the oral absorption of poorly soluble drugs. By encapsulating the drug in the carrier, the solubility and bioavailability of the drug can be increased. At the same time, the drug carrier can escape the rapid capture of the reticuloendothelial system in the body, prolong the exposure time of the drug in the systemic circulation, and enhance the efficacy of the drug.

[0048] According to an embodiment of the present invention, in the case where the drug is an oral preparation, the carrier includes at least one of a binder, a lubricant, a disintegrant, a solubilizer, a diluent, a stabilizer, a suspending agent, a pigment, and a flavoring agent;

[0049] In the case where the drug is an injectable preparation, the carrier includes at least one of a preservative, a solubilizer, and a stabilizer;

[0050] In the case where the drug is a topical preparation, the carrier includes at least one of a base, a diluent, a lubricant, and a preservative.

[0051] According to embodiments of the present invention, in oral preparations, adhesives, lubricants, disintegrants, cosolvents, diluents, stabilizers, suspending agents, no pigment, flavoring agents play a key role, they not only improve the physicochemical properties of the drug, improve the efficacy and safety of the drug, but also increase the acceptability of the preparation, meet different clinical needs and patient preferences. In injections, preservatives, solubilizers, stabilizers can ensure the safety, effectiveness and stability of the drug, while improving the medication compliance of patients. In topical preparations, matrix, diluents, lubricants, preservatives contribute to the stable release and effective delivery of the drug, and also improve the safety of the preparation. By rationally selecting and using these adjuvants, the dosage form of the drug can be optimized to improve the therapeutic effect.

[0052] According to an embodiment of the present invention, the administration method of the drug includes at least one of oral administration, intravenous administration, subcutaneous administration, intramuscular administration, intraperitoneal administration, and local administration.

[0053] According to the embodiments of the present invention, isoginkgetin has no obvious toxicity at a dose of 20 mg / kg in mice. According to the calculation of body surface area, the effective and safe dosage for human use is estimated to be 2.2 mg / kg. The effective dose of the drug can be adjusted according to the pharmacokinetic parameters of isoginkgetin, the patient's health status, body weight and route of administration, and is determined by comprehensive consideration by those skilled in the art.

[0054] The technical solution of the present invention is further described below by specific examples in combination with the accompanying drawings. It should be noted that the following specific examples are only used as examples, and the protection scope of the present invention is not limited thereto. The drugs or reagents used in the following examples are all commercially available or homemade by known preparation methods. The methods used in the following examples, such as Image J, are all well-known methods in the art and can be carried out by description in textbooks or relevant literature, and will not be repeated here.

[0055] All data were processed and analyzed using statistical analysis software, and the mean comparison of all samples was analyzed using independent sample t-test. p<0.05 indicated statistically significant differences.

[0056] Example 1 Isoginkgetin reduces serum total cholesterol, low-density lipoprotein cholesterol, triglycerides, and total cholesterol and triglyceride levels in the liver

[0057] Preparation of experimental mice: SPF grade ApoE - / - Mice, 7 weeks old, were kept on sterile bedding changed weekly with free access to food and water.

[0058] Animal administration and treatment: ApoE - / - After one week of adaptation in the animal room, the mice were fed with high cholesterol (1.25% cholesterol) feed for 7 weeks, and then randomly divided into two groups (0.1% DMSO solvent control group and 20 mg / kg / day administration), and the administration method was intraperitoneal injection for 8 consecutive weeks. After the 15th week, the mice were weighed and samples were collected for subsequent molecular and pathological experiments. The results are as follows Figure 1 shown.

[0059] Figure 1 ApoE in the embodiment of the present invention - / - Schematic diagram of the experimental process and body weight changes of the mouse atherosclerosis model.

[0060] according to Figure 1 It can be seen that after continuous administration of 20 mg / kg / day for 8 weeks, the body weight of the mice in the ISOGK group did not change significantly compared with the vehicle control group. Further, based on the calculation of body surface area, the effective and safe dosage for human use is expected to be 2.2 mg / kg / day. The effective dose of the drug can be adjusted according to the pharmacokinetic parameters of isoginkgetin, the patient's health status, body weight, and route of administration, and is determined by a person of ordinary skill in the art.

[0061] Total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride detection: At the end of the sampling, mice in each group were anesthetized with 5% sodium pentobarbital intraperitoneally, and the mice were left unconscious. Wrap the mice with a towel to expose their heads, and fix the heads of the mice with hands. Using a capillary, gently pull open the eyelids of the mice to expose the eyeballs. Insert the capillary into the venous sinus at the inner corner of the eyeball. Gently turn the capillary to help the blood flow into a 1.5 ml centrifuge tube to collect the required amount of blood. Let stand at room temperature for about 2 hours, centrifuge at 3000 rpm for 10-15 minutes to separate the serum. After centrifugation, carefully remove the test tube, and the serum will be on the upper layer of the test tube (transparent liquid). Use a micropipette to transfer the serum to a new centrifuge tube and store it in a -80°C refrigerator.

[0062] At the same time, the anesthetized mice were euthanized, and part of the liver was removed, quickly frozen in liquid nitrogen, and stored in a -80°C refrigerator.

[0063] Purchase the corresponding lipid profile test kit. Prepare the working solution and standard according to the kit instructions, add the reagents and samples to the 96-well ELISA plate, add the same volume of reagents to each sample well, and react for the time required by the kit instructions. After the reaction is completed, use a spectrophotometer to read the absorbance at a wavelength of 500 nm, and calculate the concentration of the corresponding lipid profile in the sample according to the standard curve. The results are as follows: Figure 2 shown.

[0064] Figure 2 This is a comparison chart of the changes in total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglycerides after administration of isoginkgetin in the examples of the present invention.

[0065] according to Figure 2 It can be seen that after administration, in the serum (Serum) of mice, triglycerides (TG), total cholesterol (TC), and low-density lipoprotein (LDL) were significantly reduced compared with the solvent control group, and high-density lipoprotein (HDL) had no significant change. In the liver (Hepatic), total cholesterol (TC) and triglycerides (TG) in the medication group were significantly reduced. It can be seen that compared with the solvent control group, the blood lipids in the serum and liver of the mice in the medication group were significantly reduced.

[0066] Example 2 Effect of Isoginkgetin on ApoE - / - Effects of whole-vessel plaque area on mice

[0067] At the end of sampling, the aorta (including the aortic arch and thoracic aorta) was removed from each group of mice. After the fresh aortic specimens were removed, the peripheral excess fat and tissue were stripped under a stereomicroscope, and the specimens were fixed in paraformaldehyde overnight. The next day, they were washed with PBS, cut open longitudinally, and placed in PBS for later use.

[0068] Before Oil Red O staining, the aorta was placed in 60% isopropanol for 10 seconds, then placed in 0.3% Oil Red O solution for staining for 5 minutes, rinsed in 60% isopropanol again until the vessel wall turned white, then washed with PBS, and photographed and recorded.

[0069] Image J software was used to analyze the plaque deposition in the aorta, and the plaque area ratio was calculated as the ratio of the plaque deposition area to the total aortic area. Figure 3 shown.

[0070] Figure 3 This is a graph showing the results of whole-vessel Oil Red O staining and plaque area quantification in mice according to an embodiment of the present invention.

[0071] according to Figure 3 It can be seen that compared with the vehicle control group, the total vascular plaque area of ​​mice in the drug-treated group was significantly reduced.

[0072] Example 3 Effect of Isoginkgetin on ApoE - / - Effects of aortic sinus lesions in mice

[0073] At the end of sampling, the hearts of mice in each group were removed and placed in paraformaldehyde overnight. The hearts were washed with PBS on the second day and placed in 30% sucrose for dehydration. On the third day, the hearts were embedded in freezing embedding medium and sliced ​​continuously in a freezing microtome to obtain slices of the aortic sinus. The slices were stored at -80℃ and taken out to room temperature for 20 minutes before use.

[0074] First, soak the slides in PBS for 5 minutes, stand the sections upright and blot with filter paper, then draw circles with a tissue pen. Next, wash with 60% isopropanol for 10 seconds. Then, immerse the sections in 0.3% Oil Red O for 5 minutes, then wash with 60% isopropanol for 10 seconds, and pour off the floating liquid. Next, wash slowly with PBS once, pour off the floating liquid and blot with paper. Finally, use 75°C preheated glycerol gelatin to seal the slide, drop a drop on the slide, cover with a coverslip, and take a photo under a microscope after completion.

[0075] Image J software was used to analyze the plaque deposition in the aortic sinus, and the plaque area ratio was calculated as the ratio of the aortic sinus atheromatous plaque area to the total lumen area. Figure 4 shown.

[0076] Figure 4 This is a diagram of Oil Red O, H&E staining and quantitative results of the aortic sinus of mice in an example of the present invention.

[0077] according to Figure 4 It can be seen that the plaque area of ​​the aortic sinus in the drug-treated group was significantly reduced compared with the vehicle control group. H&E staining of the aortic sinus showed that treatment with isoginkgetin significantly reduced the plaque and necrotic core area of ​​the aortic sinus compared with the vehicle control group.

[0078] The specific embodiments described above further illustrate the objectives, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above description is only a specific embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. Use of isoginkgetin or a pharmaceutically acceptable salt or hydrate thereof in the preparation of a medicament for preventing or treating hyperlipidemia and / or atherosclerotic diseases.

2. The use according to claim 1, wherein the salt comprises at least one of maleate, nitrate, hydrochloride, phosphate and carbonate.

3. The use according to claim 1 or 2, wherein the isoginkgetin or a pharmaceutically acceptable salt or hydrate thereof is used to reduce total cholesterol in serum or liver.

4. The use according to claim 1 or 2, wherein the isoginkgetin or a pharmaceutically acceptable salt or hydrate thereof is used to reduce triglycerides in serum or liver.

5. The use according to claim 1 or 2, wherein the isoginkgetin or a pharmaceutically acceptable salt or hydrate thereof is used to reduce low-density lipoprotein in serum.

6. The use according to claim 1 or 2, wherein the isoginkgetin or a pharmaceutically acceptable salt or hydrate thereof is used to reduce the area of ​​atherosclerotic plaques.

7. The use according to claim 1, wherein the drug is in a dosage form selected from at least one of the following: emulsion, oil, powder, aqueous solution, suspension, tablet, granule, capsule, nano preparation.

8. The use according to claim 1 or 7, wherein the medicine further comprises a pharmaceutically acceptable carrier.

9. The use according to claim 8, wherein: In the case where the drug is an oral preparation, the carrier includes at least one of a binder, a lubricant, a disintegrant, a solubilizer, a diluent, a stabilizer, a suspending agent, a pigment, and a flavoring agent; In the case where the drug is an injection preparation, the carrier includes at least one of a preservative, a solubilizer, and a stabilizer; In the case where the drug is a topical preparation, the carrier includes at least one of a base, a diluent, a lubricant, and a preservative.

10. The use according to claim 1, wherein: The administration method of the drug includes at least one of oral administration, intravenous administration, subcutaneous administration, intramuscular administration, intraperitoneal administration, and local administration.

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