Glycitein and flax lignan composition and its application as GPR30 agonist in myocardial infarction and medicine

Abstract

The present invention discloses a glycitein-flax lignan composition and its use as a GPR30 agonist for treating myocardial infarction, and a medicament thereof, belonging to the technical field of traditional Chinese medicine compositions. The mass ratio of glycitein to flax lignan in the composition is 7:3-9:1. Based on experimental data, the composition can be used as a GPR30 agonist in the treatment of myocardial infarction.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine compositions, and particularly relates to a glycitein and flax lignan composition and its application as a GPR30 agonist in myocardial infarction and a medicine. Background Art

[0002] Glycitin is an organic compound with the molecular formula C 22 H 22 O 10 Flax lignans, a white powder, possess antibacterial, antiviral, and estrogen-like effects. It is a natural isoflavone isolated from legumes that promotes the proliferation of bone marrow stromal cells and osteoblasts and inhibits bone turnover. Flax lignans, also known as secoisolariciphenol diglucoside, are phytoestrogens very similar to human estrogen. They are primarily found in flaxseeds, and their content depends on the flax variety, climate, and ecological conditions. Flax lignans have a preventive effect on estrogen-dependent diseases such as breast cancer, prostate cancer, premenstrual syndrome, and osteoporosis.

[0003] After acute myocardial infarction, oxygen free radicals and inflammatory reactions generated by ischemia damage myocardial tissue, causing the heart to malfunction and, in severe cases, death. Studies have found that stimulating the novel estrogen receptor GPR30 during myocardial infarction can reduce myocardial inflammation, reduce infarct size, alleviate myocardial contractile dysfunction, and promote myocardial functional recovery after myocardial infarction.

[0004] However, no one has yet used glycitein and flax lignans in studies related to myocardial infarction. Summary of the Invention

[0005] The object of the present invention is to provide a glycitein and flax lignan composition and its use as a GPR30 agonist in myocardial infarction and a medicine, so as to broaden the pharmaceutical preparations for preventing and / or treating myocardial infarction.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] The glycitin described in the present invention is an active ingredient in soybeans and is commercially available or can be prepared using existing techniques. Flax lignan is a component in flaxseed and is commercially available or can be prepared using existing techniques. Both are state-of-the-art. The glycitin and flax lignan used in the present invention are pharmaceutically acceptable products, preferably with a purity greater than 50%, and most preferably with a purity greater than 98%.

[0008] The medicine of the present invention is a medicine composition prepared by using glycitein and flax lignan composition as medicine active ingredients.

[0009] The pharmaceutical composition of the present invention may contain a pharmaceutically acceptable carrier as needed. Glycitein and flax lignan are pharmaceutically active ingredients, and their weight percentage in the preparation may be 0.1-99.9%, with the remainder being a pharmaceutically acceptable carrier. The pharmaceutical composition of the present invention is present in a unit dosage form, where the unit dosage form refers to a unit of the preparation, such as each tablet, each capsule, each bottle of oral solution, each bag of granules, and each vial of injection.

[0010] The above-mentioned combination is a combination of glycitein and flax lignan, with a weight ratio of 7:3-9:1, preferably 8:2.

[0011] The pharmaceutical composition of the present invention can be in any pharmaceutically acceptable dosage form, including tablets, sugar-coated tablets, film-coated tablets, enteric-coated tablets, capsules, hard capsules, soft capsules, oral liquids, lozenges, granules, granules, pills, powders, pastes, pills, suspensions, powders, solutions, injections, suppositories, ointments and plasters.

[0012] The pharmaceutical composition of the present invention, and its oral administration preparation may contain commonly used excipients, such as fillers, binders, diluents, flavoring agents, and the tablets may be coated if necessary.

[0013] Suitable fillers include mannitol, cellulose, and similar fillers; suitable disintegrants include starch, polyvinylpyrrolidone, and starch derivatives; and suitable pharmaceutically acceptable wetting agents include sodium lauryl sulfate. Solid oral compositions can also be prepared by conventional methods such as mixing, filling, or tableting. Repeated mixing can distribute the active ingredient throughout compositions using large amounts of fillers.

[0014] Oral liquid preparations can be in the form of aqueous or oily suspensions, solutions, emulsions, or syrups. Such liquid preparations may contain conventional additives, such as suspending agents, for example, sorbitol, syrup, methylcellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminum stearate gel or hydrogenated food fats, emulsifiers, such as lecithin, sorbitan monooleate or gum arabic; non-aqueous vehicles, such as almond oil, ethanol; preservatives, such as methylparaben or propylparaben or sorbic acid, and may contain conventional flavorings or coloring agents.

[0015] For injections, a liquid unit dosage form is prepared containing the active substance of the invention and a sterile carrier. Depending on the carrier and concentration, the mixture can be suspended or dissolved. Solutions are typically prepared by dissolving the active substance in a carrier, filter sterilizing it before filling it into a suitable vial, and then sealing it.

[0016] The pharmaceutical composition of the present invention can be selectively added with a suitable pharmaceutically acceptable carrier when it is prepared into a medicament. The pharmaceutically acceptable carrier is selected from the group consisting of mannitol, sorbitol, sodium metabisulfite, sodium bisulfite, sodium thiosulfate, cysteine ​​hydrochloride, thioglycolic acid, methionine, vitamin C, disodium EDTA, sodium calcium EDTA, carbonates, acetates, phosphates of monovalent alkali metals or their aqueous solutions, saline solutions, acetic acid, sulfuric acid, phosphoric acid, amino acids, sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, and the like.

[0017] Compared with the prior art, the present invention has the following beneficial effects:

[0018] The present invention relates to a glycitein and flax lignan composition. The mass ratio of glycitein to flax lignan in the traditional Chinese medicine composition is 7:3-9:1. Experimental verification shows that the combined use of glycitein and flax lignan has a significant synergistic effect in reducing myocardial infarction area. Therefore, the traditional Chinese medicine composition can be used as a GPR30 agonist in the treatment of myocardial infarction.

[0019] Preferably, the optimal mass ratio of glycitein to flax lignan in the traditional Chinese medicine composition of the present invention is 8:2. When the mass ratio of the two is 8:2, the myocardial infarction area is minimized. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 The combination of glycitein and flax lignans as a GPR30 agonist reduces the peripheral blood CK content in rats with myocardial infarction;

[0021] Figure 2 The combination of glycitein and flax lignans as a GPR30 agonist reduces the LDH content in the peripheral blood of rats with myocardial infarction;

[0022] Figure 3 The combination of glycitein and flax lignan acts as a GPR30 agonist to reduce the MDA content in myocardial tissue;

[0023] Figure 4 The combination of glycitein and flax lignans acts as a GPR30 agonist to increase the SOD content in myocardial tissue of rats with myocardial infarction;

[0024] Figure 5 The combination of glycitin and flax lignan acts as a GPR30 agonist to activate the AKT survival signaling pathway. DETAILED DESCRIPTION

[0025] In order to enable those skilled in the art to better understand the solutions of the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts should fall within the scope of protection of the present invention.

[0026] It should be noted that the terms "first", "second", etc. in the description and claims of the present invention and the above-mentioned drawings are used to distinguish similar objects and are not necessarily used to describe a specific order or sequence. It should be understood that the numbers used in this way can be interchanged where appropriate, so that the embodiments of the present invention described herein can be implemented in an order other than those illustrated or described herein. In addition, the terms "including" and "having" and any variations thereof are intended to cover non-exclusive inclusions. For example, a process, method, system, product or device that includes a series of steps or units is not necessarily limited to those steps or units clearly listed, but may include other steps or units that are not clearly listed or inherent to these processes, methods, products or devices.

[0027] The present invention is described in further detail below with reference to the accompanying drawings:

[0028] 1. Materials and Methods

[0029] 20g Experimental animals: 200 SD rats, weighing 200±, female.

[0030] Experimental drugs: Glycitin (Gly) and flax lignans (FL) mixed preparation.

[0031] Drug grouping:

[0032] 1) Glycitin;

[0033] 2) the group with a mass ratio of glycitein to flax lignan of 2:8;

[0034] 3) group with a mass ratio of glycitein to flax lignan of 5:5;

[0035] 4) the group with a mass ratio of glycitein to flax lignan of 8:2;

[0036] Mixing weight ratio 8:2.

[0037] 2. Construction of animal models

[0038] Animals were anesthetized with 3% pentobarbital and intubated before surgery. A chest skin incision was made, and the muscle layer was removed at the level of the third rib. After rib incision, the left anterior descending coronary artery was ligated with 8-0 polypropylene suture 2 mm horizontally from the right inferior border of the left atrial appendage for 45 minutes. The ligature was then reopened to allow reperfusion for 5 minutes to induce myocardial infarction.

[0039] Relevant indicators (GPR30 expression, myocardial enzyme CK-MB activity, MDA content and myocardial infarction area) were detected 24 hours after successful modeling.

[0040] 3. Determination of myocardial infarction area

[0041] The myocardial infarction area was determined by quantitative histological nitro blue tetrazolium (NBT) staining. The stained samples were photographed and the infarction area of ​​each sample was measured using an image analysis system (Image Pro Plus 4.0).

[0042] The results are shown in Table 1 below:

[0043] Table 1. Glycitein and flax lignan combination as GPR30 agonist reduces myocardial infarction size

[0044]

[0045] *p<0.05VS ischemia+glycitein group, G15 is a GPR30 blocker

[0046] As can be seen from Table 1, the combination of glycitein and flax lignans of the present invention has a significant synergistic effect on reducing the area of ​​myocardial infarction, especially when the mass ratio of the two is 8:2, the myocardial infarction area is minimized.

[0047] 4. Specific experimental tests

[0048] 1) Myocardial enzyme CK activity detection

[0049] The CK-MB content in peripheral blood was detected using an immunochromatographic kit purchased from Nanjing Jiancheng Bioengineering Institute. Figure 1 shown.

[0050] 2) Myocardial enzyme LDH activity detection: The peripheral blood LDH content was detected using an immunochromatographic kit purchased from Nanjing Jiancheng Bioengineering Institute. The results were as follows: Figure 2 shown.

[0051] 3) MDA content detection: The MDA content in myocardial tissue was detected using an immunochromatographic kit purchased from Nanjing Jiancheng Bioengineering Institute. The results are as follows: Figure 3 shown.

[0052] 4) SOD content detection: The SOD content in myocardial tissue was detected using an immunochromatographic kit purchased from Nanjing Jiancheng Bioengineering Institute. The results are as follows: Figure 4 shown.

[0053] pass Figure 1-5 As can be seen, compared with the rat myocardial infarction model group, the 8:2 ratio of glycitein to flax lignans significantly reduced myocardial infarction area, blood CK and LDH levels, and myocardial tissue MDA and SOD levels. Furthermore, all of the changes induced by these drugs were blocked by G15 (a GPR30 blocker), indicating that this ratio was the most effective in inhibiting myocardial infarction (p < 0.05).

[0054] The above content is only for explaining the technical idea of ​​the present invention and cannot be used to limit the protection scope of the present invention. Any changes made on the basis of the technical solution in accordance with the technical idea proposed by the present invention shall fall within the protection scope of the claims of the present invention.

Claims

1. A Chinese medicine composition for treating and / or preventing myocardial infarction, characterized in that: It is composed of glycitein and flax lignan, wherein the mass ratio of glycitein to flax lignan is 7:3-9:

1.

2. The Chinese medicine composition for treating and / or preventing myocardial infarction according to claim 1, wherein The mass ratio of glycitein to flax lignan in the traditional Chinese medicine composition is 8:

2.

3. The Chinese medicine composition for treating and / or preventing myocardial infarction according to claim 1, wherein The purity of the glycitein and flax lignan is greater than or equal to 50%.

4. The Chinese medicine composition for treating and / or preventing myocardial infarction according to claim 3, wherein The purity of the glycitein and flax lignan is greater than 98%.

5. Use of the traditional Chinese medicine composition according to any one of claims 1 to 4 as a GPR30 agonist in the preparation of a medicament for treating and / or preventing myocardial infarction.

6. The use according to claim 5, characterized in that The drug is a drug that inhibits local myocardial necrosis caused by partial myocardial ischemia and hypoxia due to acute occlusion of coronary arteries.

7. A drug for treating and / or preventing myocardial infarction, characterized in that: The composition of glycitein and flax lignan is used as a medicinal active ingredient and a pharmaceutically acceptable carrier is added to prepare the composition; Wherein, in the composition of glycitein and flax lignan, the mass ratio of glycitein to flax lignan is 7:3-9:1; The mass ratio of the medicinal active ingredient to the carrier is (0.1:99.9)~(99.9:0.1).

8. The drug according to claim 7, wherein The pharmaceutically acceptable carrier is selected from the group consisting of sodium metabisulfite, sodium bisulfite, sodium thiosulfate, cysteine ​​hydrochloride, thioglycolic acid, methionine, glycine, vitamin C, disodium EDTA, calcium sodium EDTA, acetic acid, sulfuric acid, phosphoric acid, sodium chloride, potassium chloride, sodium lactate, mannitol, sorbitol, xylitol, maltose, glucose, fructose, dextran, starch, sucrose, lactose or mannitol.

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