CN113893242B - Use of ASH in myocardial protection - Google Patents
Use of ASH in myocardial protection Download PDFInfo
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- CN113893242B CN113893242B CN202111184453.0A CN202111184453A CN113893242B CN 113893242 B CN113893242 B CN 113893242B CN 202111184453 A CN202111184453 A CN 202111184453A CN 113893242 B CN113893242 B CN 113893242B
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/222—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Cardiology (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention discloses application of ASH in myocardial protection, which belongs to the technical field of medicines, wherein the chemical structure of the ASH is shown in figure 1, and pharmacological experiments are carried out on mice around myocardial infarction, so that the compound has the advantages of obvious myocardial protection effect, good safety, simple and convenient administration, low-cost and easily available raw materials and convenience in transportation and storage, and has wide application prospect as a myocardial protection drug.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to application of a compound in myocardial protection.
Background
Cardiovascular disease is a major cause of death in the global population, with mortality being the leading disease, and still rising year by year, severely compromising human health. When myocardial infarction occurs, myocardial ischemia and hypoxia cause infiltration of inflammatory cells such as macrophages and monocytes, induce local inflammatory reaction, and then cause death of myocardial cells, resulting in cardiac dysfunction, myocardial remodeling and heart failure. Heart Failure (HF) is abbreviated as Heart failure, and is a requisite stage of various cardiovascular diseases such as coronary Heart disease, hypertension, myocarditis, etc., and is a worldwide medical and health problem. Heart failure is an obstructive disease of cardiac insufficiency, generally manifested by a decrease or dysfunction of myocardial contractility, resulting in a decrease in cardiac output and a decrease in blood supply to the oxygen supply and metabolism of body tissues, leading to failure of cardiac function. The prevalence rate of cardiovascular diseases in China is in a continuously rising stage, and the mortality rate is far higher than that of countries such as Europe and America, and the prevalence rate of patients with cardiovascular diseases in China is about 2.9 hundred million, wherein the prevalence rate of patients with heart failure is 450 ten thousand.
Clinically, drugs against heart failure are mainly classified into renin-angiotensin system inhibitors, anti-aldosterone drugs, diuretics, beta-blockers, cardiac glycosides, etc., but they all have serious adverse reactions such as dyspnea, heart rate slowing, blood pressure lowering, electrolyte disorders, etc. Therefore, the search for safe and effective anti-heart failure drugs has important significance for the treatment of clinical cardiovascular and cerebrovascular diseases.
Chinese patent 2019109751780 discloses a compound of the structure,
the specification discloses that the composition has an anticoagulant effect, but does not disclose that the composition has an anti-heart failure effect or a myocardial protection effect, and the inventor establishes a myocardial ischemia model by ligating left anterior descending branches of coronary arteries of mice in the process of pharmacodynamics study, and unexpectedly discovers that the composition has a protection effect on experimental ischemic cardiomyopathy mice and can be used for treating ischemic cardiomyopathy.
Disclosure of Invention
In view of the shortcomings in the prior art, the present invention provides a novel myocardial protecting compound and its use. The invention aims to solve the technical problem of providing the myocardial protecting compound which has the advantages of obvious myocardial protecting effect, good safety, simple and convenient medication, low price and convenient transportation and preservation.
The invention provides a compound which has the following structural formula:
herein denominated: ASH (automatic service)
The molecular formula of the compound is as follows: C13H16O5, molecular weight 252.27. This compound has been disclosed in the specification of chinese patent.
The invention unexpectedly discovers that the compound ASH has a myocardial protection effect, and therefore, the invention provides application of the ASH in preparing myocardial protection medicines.
The application of the invention is characterized by comprising the protection of myocardial injury caused by any one of the reasons, such as: myocarditis, myocardial ischemia, arrhythmia, heart failure, myocardial infarction, cardiac insufficiency, and the like.
The use according to the invention, characterized in that the use is ASH can be used for the prevention and treatment of heart failure.
The use according to the invention is characterized in that the use is ASH can be used for the prevention and treatment of heart failure caused by myocardial infarction.
The application of the invention is characterized in that ASH can improve heart function, reduce the weight-to-heart ratio and the fibrosis area increase caused by myocardial infarction.
The application of the invention is characterized in that the medicine is prepared into any medicine dosage form for taking ASH as a medicine active ingredient.
The use according to the invention, wherein the pharmaceutical dosage form is selected from the group consisting of: oral preparation, injection, patch, and suppository.
The use according to the invention, wherein the pharmaceutical dosage form is selected from the group consisting of: oral preparation and injection.
The use according to the invention, wherein the pharmaceutical dosage form is selected from the group consisting of: an injection.
The use according to the invention, wherein the use comprises ASH or a pharmaceutically acceptable salt thereof. Preferably, the drug should facilitate absorption by the organism and increase the availability of the drug.
Compared with the prior art, the invention has the beneficial technical effects that:
(1) The myocardial protection effect is remarkable: can obviously improve cardiac function and fibrosis area, and can be used as a safe and effective medicament for treating ischemic heart disease.
(2) The safety is good: the novel myocardial protecting compound has large tolerance and no obvious toxic side effect.
(3) The medicine is simple and convenient, and is easy to be absorbed by human or animals.
(4) Compared with other imported myocardial protection medicines, the medicine provided by the invention has the advantages of low price, high cost performance and easiness in acceptance by patients.
(5) Is convenient for transportation and storage, is sealed and is placed at a dry place.
Drawings
FIG. 1.ASH block diagram.
FIG. 2. Influence of ASH on cardiac function in myocardial infarction mice.
FIG. 3. Influence of ASH on the weight-to-heart ratio of myocardial infarction mice.
FIG. 4. Influence of ASH on fibrosis area of mice with myocardial infarction.
Data are expressed as mean ± standard error, ×p<0.001vs. sham surgery group, # P<0.05vs. myocardial infarction group, ## P<0.01vs. myocardial infarction group, ### P<0.001vs. myocardial infarction group. Sham, n=7; myocardial infarction group, n=8; fosinopril sodium tablet group (40 mg/kg), n=5; ASH (10 mg/kg), n=10; ASH (20 mg/kg), n=5, ASH (40 mg/kg), n=5.
Detailed Description
The invention will be further described with reference to specific embodiments, and advantages and features of the invention will become apparent from the description. The embodiments are merely exemplary and do not limit the scope of the invention in any way. It will be understood by those skilled in the art that various changes and substitutions of details and forms of the technical solution of the present invention may be made without departing from the spirit and scope of the present invention, but these changes and substitutions fall within the scope of the present invention.
And (3) testing: ASH myocardial preservation pharmacodynamics study
The purpose is as follows: the protective effect of ASH on myocardial infarction of mice was investigated.
The method comprises the following steps: c57BL/6 male mice with SPF grade of 18-22 g are selected, and myocardial infarction models are constructed by ligating left anterior descending branches of coronary arteries and randomly divided into 6 groups, namely a sham operation group (8), a myocardial infarction model group (11), an ASH low dose group (11), an ASH medium dose group (11), an ASH high dose group (11) and a fosinopril sodium group (10). After 3 days of establishment of myocardial infarction model, the stomach is irrigated, the solvent with corresponding dosage is given to the sham operation group and the model group, and ASH 10 mg/kg. D is respectively given to animals with low, medium and high ASH dosages -1 、20mg/kg.d -1 、40mg/kg.d -1 Fosinopril sodium group dose is 40mg/kg. D -1 . After 28 days of gastric lavage, heart function of each group of mice is detected by using cardiac ultrasound, heart weight and body weight are weighed, the heart-weight-to-body weight ratio is calculated, and the myocardial fibrosis degree is detected by using coriaria staining.
1. Purpose of experiment
A myocardial infarction mouse model can be established by ligating the left anterior descending branch of the coronary artery of the mouse, then a test drug is given to the mouse, and the effects of the test drug on the heart function, the weight-to-heart ratio and the fibrosis of the myocardial infarction mouse are judged.
2. Experimental medicine
2.1 test drug
| Name of the name | Shape and physicochemical Properties | Preservation conditions | Source |
| ASH | Orange yellow oily liquid | 4 ℃ and light-shielding |
2.2 Positive control
2.3 negative control and vehicle
Olive oil
3. Experimental animals and experimental environments
3.1 laboratory animals
C57BL/6 mice, SPF grade, male, total 62 animals, weight range: 18-22 g, the initial weight of the animal is not more than or less than 20% of the average weight.
Animal origin: liaoning province laboratory animal resource center.
Production unit license number: SYXK (black) 2019-001.
Receiving date: 2021-3-10
3.2 Experimental Environment
Mice are raised in laboratory animals at a transformation center of Harbin medical university, the raising environment is a barrier system, the room temperature is 20-26 ℃, the humidity is 40-70%, the ventilation is 10-15 times/h of fresh air, and the illumination is 12h.
3.3 feed and drinking Water
The feed is maintained to be the national standard clean feed, vacuum packed and stored at normal temperature.
And (3) feed sources: beijing Fukang biotechnology Co., ltd
Animal feed production license number: beijing feeding certificate (2014) 06054
Drinking water: the purified water after autoclaving is supplied by a drinking bottle, animals drink water freely, and water is changed once a day.
4. Main reagent for detection
5. Main instrument for experiment
| Name of the name | Company (Corp) | Goods number |
| Small animal ultrasonic instrument | VisualSonics | |
| Balance with a balance body | Shimadzu Japan | AUW120D |
| Centrifugal machine | HUNAN XIANGYI LABORATORY INSTRUMENTS DEVELOPMENT Co.,Ltd. | L500 |
| Electronic balance | Sidoris group Germany | BS 124S |
| High-speed refrigerated centrifuge | Japanese Hitachi | CF-16RXII |
| Paraffin slicer | Thermo Co Ltd |
6. Dose selection
ASH group:
ASH low dose group 10 mg/kg.d -1
Dose group 20 mg/kg.d in ASH -1
ASH high dose group 40mg/kg.d -1
Fosinopril sodium tablet group:40mg/kg·d -1
7. methods and frequency of administration
Administration by gastric lavage 1 time/day
8. Experimental procedure
8.1 animal receiving and quarantining
C57BL/6 mice, males, were introduced prior to the formal experiments. All animals were quarantined and observed for a week during the adaptation period, and each was checked for body weight during the introduction and quarantine period. And (5) according to the conditions of weight increase, general signs, activities and the like of the animals in the adaptation period, the qualified animals enter a formal experiment.
8.2 myocardial infarction model establishment
The mouse myocardial ischemia model was established by ligating the left anterior descending branch of the mouse coronary artery. Healthy male C57BL/6 mice (20.+ -.2 g) were anesthetized with amifostine (0.2 g/kg) by intraperitoneal injection, and the anesthetized mice were fixed in a supine position on a mouse console, connected to a ventilator. The left chest skin is cut obliquely from left top to right bottom, about 1.5-2.0 cm is cut, pectoral large muscle and anterior saw muscle are separated, intercostal muscle is separated between the 4 th and 5 th intercostals, heart is gently pushed out, a 7/0 ligature is penetrated at the position 1-2 mm from the anterior descending branch of the left coronary artery to the lower edge of the left auricle, left anterior descending branch ligation of the coronary artery is carried out, the color of the apex of the heart is whitened after ligation, and obvious S-T section is lifted in an electrocardiogram.
8.3 dosing and modeling period:
c57BL/6 mice of SPF grade after adaptive feeding were randomly weighed, randomly divided into 6 groups, i.e., sham surgery group, myocardial infarction model group, ASH low dose group, ASH medium dose group, ASH high dose group, fosinopril sodium group, and after molding, ASH, fosinopril sodium tablet, and blank solvent were administered by gavage, and the stomach was continuously irrigated for 28 days, and the heart function, the material-drawing statistical weight-to-heart ratio, and the fibrosis area of each group of mice were detected at 28 days.
9. Inspection index and frequency and method of measurement
9.1 general observations
General clinical observations were made once daily during the course of the experiment. The appearance, spirit and activity of mice after administration were observed. If the animals die or die, the death cause is known by timely sectioning, and the death number is recorded.
The general status of each group of mice is normal.
9.2 body weight detection
Each mouse was weighed with an electronic balance once a week.
9.3 detection of cardiac function in mice
Detection of cardiac hemodynamic parameters in mice2100 high-resolution animal ultrasonic imaging system and MicroScan MS 250-0206 probe, and experimental mice are anesthetized and fixed in a supine position. The chest region is dehaired, and ultrasound gel is smeared. The probe is placed in front of the left chest of a mouse, the long axis section of the left ventricle is displayed by 2D ultrasonic, the movement condition of the left ventricle is recorded by taking M mode ultrasonic under the guidance of two-dimensional (2D), the Ejection Fraction (EF) and the short axis shortening rate (FS) are measured, and the left ventricle functions of animals in each group are evaluated by the index.
9.4 determination of the weight to weight ratio of mice
Groups of mice were taken, the abdominal cavity was opened, and the heart was taken out and washed with physiological saline. Excess tissue was cut off, and the filter paper was blotted to dry the residual physiological saline, and weighed.
9.5 determination of cardiac fibrosis area in mice
(1) Preparation of paraffin section samples
Mice were anesthetized as described above, and their whole hearts were taken after ischemia reperfusion model establishment and placed in 4% paraformaldehyde solution. After the tissue mass was fixed for 24 hours, the tissue with the lesion site was cut transversely along the longitudinal axis of the heart and placed in a tissue embedding cassette and placed in an automatic dehydrator for dehydration. After 20 hours, the tissue pieces were removed. Paraffin wax was melted and the tissue block was embedded using an automatic embedding machine. When preparing a sample, the tissue wax block is vertically fixed on a machine, a blade is fixed, paraffin sections are prepared, 4 mu m/piece is put into warm water to remove wrinkles, the samples are flatly attached to a glass slide, and an oven at 55 ℃ is used for overnight.
(2) Masson staining
The tissue sections were dewaxed in a basket, immersed in xylene solution, covered with tissue, soaked twice for 5 minutes each, and then sequentially soaked in absolute ethanol, 95% ethanol, 80% ethanol, 70% ethanol for 2 minutes each. After dewaxing was completed, the samples were immersed in distilled water for 2 minutes. The hematoxylin is washed by tap water for 10 minutes after being dyed in the hematoxylin solution for 10 minutes, the hematoxylin is washed by tap water for 1 minute after being dyed in the Brix red solution, the phosphomolybdic acid and phosphotungstic acid mixed solution is differentiated for 15 minutes, the phosphomolybdic acid and phosphotungstic acid mixed solution is washed by tap water for 1 minute after being dyed in the aniline blue solution for 10 minutes, and the acetic acid mixed solution is washed by tap water for 30 seconds after being differentiated for 4 minutes. Finally, dewatering, sequentially adding the glass cover slip into 95% ethanol, 100% ethanol, xylene I and xylene II, soaking for 5 minutes respectively, sealing the glass cover slip with neutral resin sealing tablets, and observing by using an optical microscope after the glass cover slip is dried.
10. Conclusion(s)
As a result, as shown in fig. 2, after 28 days of left anterior descending coronary artery ligation, the Ejection Fraction (EF) and short axis shortening (FS) rate (P <0.001vs. sham) were significantly reduced in the myocardial infarction group compared to the sham group, while ASH group was reversible in the above phenomenon (#p <0.05vs. myocardial infarction group). As shown in fig. 3, ASH can reduce the increase in the heart weight to weight ratio (#p <0.05vs. myocardial infarction group, #p <0.01vs. myocardial infarction group, # #p <0.001vs. myocardial infarction group) in mice caused by myocardial infarction compared to sham operated group. As shown in fig. 4, the myocardial infarction model group showed a significant increase in myocardial fibrosis area compared to the sham surgery group (< 0.001vs. sham surgery group), whereas ASH could reduce the increase in mouse fibrosis area caused by myocardial infarction (# # P <0.001vs. myocardial infarction group).
Claims (4)
- Application of ASH or pharmaceutically acceptable salt thereof in preparing a medicament for preventing and treating heart failure caused by myocardial infarction, wherein the ASH has the following structure:
- 2. the use according to claim 1, wherein the pharmaceutical dosage form is selected from the group consisting of: oral preparation, injection, patch, and suppository.
- 3. The use according to claim 2, wherein the pharmaceutical dosage form is selected from the group consisting of: oral preparation and injection.
- 4. The use according to claim 3, wherein the pharmaceutical dosage form is selected from the group consisting of: an injection.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007054451A1 (en) * | 2005-11-11 | 2007-05-18 | Nicox S.A. | Use of combinations of nitric oxide-releasing aspirin and aspirin for the treatment of cardiovascular diseases |
| CN101811974A (en) * | 2010-04-15 | 2010-08-25 | 合肥医工医药有限公司 | 4-(3-(dimethoxy) propoxy)-3, 5-dimethoxy benzoic acid, and preparation method and medical purpose thereof |
| JP2010189418A (en) * | 2010-04-16 | 2010-09-02 | Inst Of Materia Medica Chinese Acadmy Of Medical Sciences | NEW 2-(alpha-HYDROXYPENTYL)BENZOATE, METHOD FOR PRODUCING THE SAME AND USE THEREOF |
| CN103599547A (en) * | 2012-12-06 | 2014-02-26 | 河北医科大学 | Nitric oxide donor type non-steroidal anti-inflammatory drug beta-cyclodextrin or beta-cyclodextrin derivative inclusion compound as well as preparation method and application thereof |
| CN110668947A (en) * | 2019-10-14 | 2020-01-10 | 新乡海盈生物科技有限责任公司 | O-hydroxybenzoic acid polyglycol ester compound and synthesis preparation method and medical application thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| IT1243367B (en) * | 1990-07-26 | 1994-06-10 | Italfarmaco Spa | BENZOIC ACID DERIVATIVES SUBSTITUTED FOR CARDIOVASCULAR ACTIVITY |
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007054451A1 (en) * | 2005-11-11 | 2007-05-18 | Nicox S.A. | Use of combinations of nitric oxide-releasing aspirin and aspirin for the treatment of cardiovascular diseases |
| CN101811974A (en) * | 2010-04-15 | 2010-08-25 | 合肥医工医药有限公司 | 4-(3-(dimethoxy) propoxy)-3, 5-dimethoxy benzoic acid, and preparation method and medical purpose thereof |
| JP2010189418A (en) * | 2010-04-16 | 2010-09-02 | Inst Of Materia Medica Chinese Acadmy Of Medical Sciences | NEW 2-(alpha-HYDROXYPENTYL)BENZOATE, METHOD FOR PRODUCING THE SAME AND USE THEREOF |
| CN103599547A (en) * | 2012-12-06 | 2014-02-26 | 河北医科大学 | Nitric oxide donor type non-steroidal anti-inflammatory drug beta-cyclodextrin or beta-cyclodextrin derivative inclusion compound as well as preparation method and application thereof |
| CN110668947A (en) * | 2019-10-14 | 2020-01-10 | 新乡海盈生物科技有限责任公司 | O-hydroxybenzoic acid polyglycol ester compound and synthesis preparation method and medical application thereof |
Non-Patent Citations (1)
| Title |
|---|
| Liu C，等."3,5-Dimethoxy-4-(3-(2-carbonyl-ethyldisulfanyl)-propionyl)-benzoic acid 4-guanidino-butyl ester: A novel twin drug that prevents primary cardiac myocytes from hypoxia-induced apoptosis".《 European Journal of Pharmacology》.2013,第700卷(第1-3期),118-126. * |
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