Application of the active ingredients of Manlong Liquid in the preparation of drugs for preventing myocardial ischemia

Abstract

The present invention discloses the use of an effective component of Manlong liquid in the preparation of a drug for preventing myocardial ischemia, wherein the effective components of Manlong liquid are syringin and verbascoside; the mass ratio of syringin to verbascoside is 1:(0.5-2), preferably the mass ratio of syringin to verbascoside is 1:1. The composition of the present invention can be further prepared into one of granules, tablets and capsules, and has great application prospects.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical preparations, and more specifically, relates to the application of effective ingredients of Manlong Liquid in the preparation of medicines for preventing myocardial ischemia. Background Art

[0002] Manlong Liquid is a drug exclusively produced by Yunnan Yunlong Pharmaceutical Co., Ltd. It is composed of male silkworm moth, Acanthopanax senticosus, Epimedium, Cuscuta australis (made with wine), Rehmannia glutinosa (made with salt), and Psoralea corylifolia (made with salt). It has the effects of nourishing the kidney and strengthening yang, replenishing essence and nourishing marrow. It is used for kidney deficiency and essence deficiency, impotence and premature ejaculation, nocturnal emission and spermatorrhea, soreness of waist and knees, and frequent urination.

[0003] Male silkworm moth is the whole male silkworm moth of the Bombyx mori family. In summer, take male silkworm moths, scald them to death with boiling water, and dry them in the sun. It nourishes the liver and kidneys, strengthens yang and astringes semen. It treats impotence, spermatorrhea, leucorrhea, hematuria, trauma, ulcers and burns. Male silkworm moths contain a variety of amino acids, vitamins and trace elements, especially male silkworm moths contain a large number of male hormones, juvenile hormones, brain hormones and molting hormones and other biologically active substances. It is a "medicine and food of the same origin" product that combines blood sugar reduction, elimination of complications, health preservation, health care, and yang strengthening. The main components of Acanthopanax senticosus are glycosides, polysaccharides, etc. Among them, glycosides are its characteristic components and effective ingredients. 1. Glycosides syringin, Acanthopanax senticosus glycoside A, B, B1, C, D, E, F, G, etc. 2. Polysaccharides The content of alkaline polysaccharides is generally 2% to 6%, and the content of water-soluble polysaccharides is 2.3% to 5.7%. 3. Other ingredients: isoflurane, chlorogenic acid, sesame, stearic acid, β-sitosterol, etc. Epimedium contains icariin, volatile oil, wax alcohol, phytosterol, tannin, vitamin E and other ingredients. It can stimulate sexual function and promote semen secretion in animals. It also has antihypertensive (causing peripheral vasodilation), hypoglycemic, diuretic, antitussive and expectorant effects, as well as vitamin E-like effects. Pharmacological experimental studies have shown that epimedium can increase cardiovascular and cerebrovascular blood flow, promote hematopoietic function, immune function and bone metabolism, and has anti-aging and anti-tumor effects. Cuscuta contains alkaloids, anthraquinones, coumarins, flavonoids, glycosides, sterols, tannic acid, sugars, etc. Flavonoids include: quercetin, astragaloside, hyperoside; sterols include: cholesterol, campesterol, β-sitosterol, stigmasterol, β-amyrin alcohol. The main components of Rehmannia glutinosa are various iridoids, monoterpenes and their glycosides, various sugar components, more than 20 kinds of amino acids (of which arginine and alanine are high in content), various organic acids, and more than 20 elements such as iron, zinc, manganese, chromium, including verbascoside, etc. Psoralea corylifolia contains coumarin components such as psoralen, isopsoralen, cyperus rotundus, psoralen, isopsoralen, psoralen furanocoumarin, etc.; it also contains flavonoids, benzofurans, fatty acids, etc.; secondly, it also contains psoralen polysaccharides, amino acids, etc. In clinical practice, Manlong Liquid has been found to have various therapeutic effects, but the mechanism is unclear. Summary of the invention

[0004] The technical problem to be solved by the present invention is to provide the application of the effective ingredients of Manlong Liquid in the preparation of medicines for preventing myocardial ischemia in view of the defects and shortcomings of the technology. The effective ingredients of Manlong Liquid are syringoside and verbascoside.

[0005] When the company's scientific and technological personnel were studying the effective ingredients of Manlong Liquid, after a large number of experimental studies, they unexpectedly discovered that syringoside and verbascoside have a synergistic effect in preventing myocardial ischemia.

[0006] The first object of the present invention is to provide the use of the effective ingredients of Manlong Liquid in the preparation of medicines for preventing myocardial ischemia.

[0007] The second object of the present invention is to provide a pharmaceutical composition of syringoside and verbascoside.

[0008] The third object of the present invention is to provide a preparation comprising the syringin and verbascoside composition.

[0009] The above-mentioned object of the present invention is achieved through the following technical solutions:

[0010] The invention discloses an application of the effective ingredients of Manlong liquid in the preparation of medicines for preventing myocardial ischemia. The effective ingredients of Manlong liquid are syringin and verbascoside; the mass ratio of syringin to verbascoside is 1:(0.5-2).

[0011] The effective ingredients of Manlong Liquid are used in the preparation of medicines for preventing myocardial ischemia, wherein the mass ratio of syringin to verbascoside is 1:1.

[0012] The effective ingredients of Manlong Liquid are used in the preparation of medicines for preventing myocardial ischemia. The effective ingredients of Manlong Liquid are added with auxiliary materials to be prepared into one of granules, tablets and capsules.

[0013] The effective ingredients of Manlong Liquid are used in the preparation of medicines for preventing myocardial ischemia, and the auxiliary materials are one or more of starch, pregelatinized starch, mannitol, chitin, microcrystalline cellulose, sucrose, sodium carboxymethyl cellulose, cross-linked polyvinyl pyrrolidone, low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, magnesium stearate, sodium lauryl sulfate, talc, and silicon dioxide.

[0014] A medicine for preventing myocardial ischemia, containing the effective ingredient of Manlong Liquid.

[0015] The preparation method of the drug for preventing myocardial ischemia is as follows: effective ingredients of Manlong Liquid are mixed, auxiliary materials are added, and the mixture is prepared into one of granules, tablets and capsules.

[0016] The drug for preventing myocardial ischemia, in the preparation method, comprises one or more auxiliary materials selected from the group consisting of starch, pregelatinized starch, mannitol, chitin, microcrystalline cellulose, sucrose, sodium carboxymethyl cellulose, cross-linked polyvinyl pyrrolidone, low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, magnesium stearate, sodium lauryl sulfate, talcum powder, and silicon dioxide.

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

[0018] The present invention provides an application of an effective component of Manlong Liquid in the preparation of a drug for preventing myocardial ischemia, wherein the effective components of Manlong Liquid are syringin and verbascoside; the mass ratio of syringin to verbascoside is 1:(0.5-2), and preferably the mass ratio of syringin to verbascoside is 1:1. The applicant unexpectedly discovered that syringin and verbascoside have a synergistic effect in preventing myocardial ischemia. The composition of the present invention can be further prepared into one of granules, tablets, and capsules, and has great application prospects. DETAILED DESCRIPTION

[0019] The present invention is further described below with reference to specific examples, but the examples do not limit the present invention in any form. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the art.

[0020] Unless otherwise specified, the reagents and materials used in the following examples are commercially available.

[0021] Example 1: Take 10 g of syringin and 10 g of verbascoside, add starch and prepare granules.

[0022] Example 2: Take 10 g of syringoside and 5 g of verbascoside, add dextrin and prepare into tablets.

[0023] Example 3: Take 10 g of syringoside and 20 g of verbascoside, add microcrystalline cellulose and prepare capsules.

[0024] Comparative Example 1: 10 g of syringin was taken and starch was added to prepare granules.

[0025] Comparative Example 2: 10 g of verbascoside was added with starch to prepare granules.

[0026] Example 6: Testing the effect of the present invention in a rat myocardial infarction model

[0027] A total of 70 Wistar rats, half male and half female, weighing 240-260g, were randomly divided into 7 groups, each with 10 rats, namely, sham operation group, infarction model group, Example 1-3 group of the present invention, and Comparative Example 1-2 group. Among them, the sham operation group and the infarction model group were gavaged with 0.5% sodium carboxymethyl cellulose 5ml / kg·d×3d, and the Example 1-3 group of the present invention and the Comparative Example 1-2 group were gavaged with the products prepared by the Example 1-3 group of the present invention and the Comparative Example 1-2 group, respectively, at a dose of 25mg / kg·d×3d. 30min after the last administration, the rats were anesthetized with ether, the left anterior descending branch of the coronary artery was found by thoracotomy, and it was immediately ligated with No. 0 thread at 2-3mm below the left atrial appendage, the heart was returned to the chest cavity, the gas in the chest cavity was quickly squeezed out, and the purse string suture was tightened to ligate to close the chest cavity, and the entire thoracotomy time did not exceed 30 seconds. The sham operation group was not ligated but only the surgical thread was placed. 24 hours after coronary artery ligation, the rats were anesthetized with 30 mg / kg sodium pentobarbital in the abdominal vein, and blood was collected by cannulation of the abdominal aorta. The serum CK, AST and LDH activities were measured using a COBAS-FARA automatic biochemical analyzer. After blood collection, the rat heart was dissected, the blood in the cardiac cavity was washed with physiological saline, the atrial tissue and fat were removed, and the weight was weighed. The left ventricular myocardium was cut into 4 to 5 slices, and then immersed in N-BT phosphate buffer, placed in a 37°C constant temperature water bath, and taken out after complete staining. Normal tissue was stained, and ischemic tissue was not stained. The ischemic myocardium was cut off and weighed, and the myocardial infarction area (MIS) was calculated as the percentage of ischemic myocardium to left ventricular wet weight. The experimental data were processed using SPSS10.0 statistical software, expressed as mean ± standard deviation (x ± s), and variance analysis was used for comparison between multiple groups, and t-test was used for comparison between two groups. The results are shown in Table 1 below:

[0028] Table 1: Test of the inhibitory effects of the present invention on MIS, AST, CK and LDH in rats with myocardial infarction

[0029] Group MIS (%) AST(u / L) CK(u / L) LDH(u / L) Sham operation group 3.34±1.23 875.68±78.3 598.42±69.3 1653.45±324.4 Model Group <![CDATA[42.95±6.72 ## ]]> <![CDATA[1674.54±145.8 # ]]> <![CDATA[1241.38±94.5 # ]]> <![CDATA[2416.74±662.7 # ]]> Example 1 <![CDATA[15.67±4.88 ** ]]> <![CDATA[825.56±92.2 * ]]> <![CDATA[795.62±65.7 * ]]> <![CDATA[1678.62±544.2 * ]]> Example 2 <![CDATA[26.57±3.47 * ]]> <![CDATA[845.09±77.5 * ]]> <![CDATA[804.36±89.4 * ]]> <![CDATA[1883.24±386.6 * ]]> Example 3 34.09±5.69 860.62±73.2 <![CDATA[853.44±67.9 * ]]> 1855.42±304.6 Comparative Example 1 39.41±5.52 1535.73±98.4 1138.74±67.5 2158.40±341.2 Comparative Example 2 32.74±6.47 1373.66±72.6 998.45±66.5 1955.48±524.0

[0030] Note: Compared with the sham operation group, # P<0.05, ## P<0.01 # Compared with the infarction model group, * P<0.05, **P<0.01 The above experimental results showed that compared with the sham operation group, the myocardial infarction area, as well as the serum CK, AST and LDH activities in the infarction model group were significantly increased (P<0.05~P<0.01), indicating that the acute myocardial infarction model of Wistar rats was successfully established. Compared with the infarction model group, groups 1-3 of the present invention can significantly reduce the myocardial infarction area of ​​rats with myocardial infarction (P<0.05-P<0.01), and can significantly reduce the activities of serum CK, AST and LDH (P<0.05-P<0.01), indicating that the composition of the present invention has a significant preventive and therapeutic effect on myocardial infarction, and the mass ratio of syringin to verbascoside of 1:1 is better than the mass ratio of syringin to verbascoside of 1:0.5 and the mass ratio of syringin to verbascoside of 1:2; and is better than the comparative example 1 and comparative example 2 groups using syringin or verbascoside alone, indicating that syringin and verbascoside can be used for the prevention and treatment of myocardial ischemia and have a synergistic effect.

[0031] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. The use of the effective ingredients of Manlong Liquid in the preparation of medicines for preventing myocardial ischemia, characterized in that: The effective ingredients of the Manlong liquid are syringin and verbascoside; the mass ratio of syringin to verbascoside is 1:(0.5-1).

2. The use of the effective ingredients of Manlong Liquid according to claim 1 in the preparation of a drug for preventing myocardial ischemia, characterized in that: The mass ratio of syringin to verbascoside is 1:

1.

3. The use of the effective ingredients of Manlong Liquid according to claim 1 in the preparation of a drug for preventing myocardial ischemia, characterized in that: The effective ingredients of the Manlong liquid are added with auxiliary materials to be prepared into one of granules, tablets and capsules.

4. The use of the effective ingredients of Manlong Liquid in the preparation of a drug for preventing myocardial ischemia according to claim 3, characterized in that: The auxiliary material is one or more of starch, pregelatinized starch, mannitol, chitin, microcrystalline cellulose, sucrose, sodium carboxymethyl cellulose, cross-linked polyvinyl pyrrolidone, low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, magnesium stearate, sodium lauryl sulfate, talc, and silicon dioxide.

5. A drug for preventing and treating myocardial ischemia, characterized in that: Contains the effective ingredients of Manlong Liquid as described in claim 1 or 2.

6. The drug for preventing and treating myocardial ischemia according to claim 5, characterized in that: The preparation method is: take the effective ingredients of the Manlong liquid, mix them, add auxiliary materials, and prepare them into one of granules, tablets and capsules.

7. The drug for preventing and treating myocardial ischemia according to claim 6, characterized in that: The auxiliary materials in the preparation method are one or more of starch, pregelatinized starch, mannitol, chitin, microcrystalline cellulose, sucrose, sodium carboxymethyl cellulose, cross-linked polyvinyl pyrrolidone, low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, magnesium stearate, sodium lauryl sulfate, talc, and silicon dioxide.