CN102283831B - Western medicine compound for curing coronary diseases and application - Google Patents
Western medicine compound for curing coronary diseases and application Download PDFInfo
- Publication number
- CN102283831B CN102283831B CN201110258892.1A CN201110258892A CN102283831B CN 102283831 B CN102283831 B CN 102283831B CN 201110258892 A CN201110258892 A CN 201110258892A CN 102283831 B CN102283831 B CN 102283831B
- Authority
- CN
- China
- Prior art keywords
- aliskiren
- heart disease
- coronary heart
- western medicine
- medicine compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Abstract
The invention relates to a western medicine compound for curing coronary diseases and medical application thereof. The active ingredients of the western medicine compound comprise the following two medicines: (1) aliskiren or pharmaceutically acceptable salts thereof; and (2) statins, wherein the statins include simvastatin or rosuvastatin calcium. The compound medicine disclosed by the invention has obvious curable effects on myocardial ischemia type coronary diseases, myocardial infarction type diseases and angina type coronary diseases.
Description
Technical field
The present invention relates to a kind of medical composition and its use, particularly a kind of Western medicine compound and medical usage for the treatment of coronary heart disease, belongs to technical field of western medicines.
Background technology
Coronary heart disease is the main killer of human health, and along with the acceleration of globalization process, cardiovascular and cerebrovascular disease begins to extend in developing country, becomes the cause of death of No. 1 in the world.World Health Organization (WHO) is classified as follows coronary heart disease: (1) silent myocardial ischemia type: be again silent myocardial ischemia or invisible myocardial ischemia, refer to truly have the objective evidence (electrocardio-activity, left chamber function, Myocardial Perfusion and myocardial metabolism etc. are abnormal) of myocardial ischemia, but lack chest pain or the subjective symptom relevant to myocardial ischemia.(2) angina pectoris: refer to by coronary insufficiency, cardiac muscle sharply, temporary transient ischemia and anoxia is caused take one group of clinical syndrome that ictal chest pain or chest discomfort be main manifestations.(3) myocardial infarction (extremely) type: refer to that atherosclerotic plaque or thrombosis on this basis appear in coronary artery, cause blood flow coronarius sharply reduce or interrupt, make corresponding cardiac muscle occur seriously and enduringly acute ischemia, finally cause myocardium ischemic necrosis, belong to the serious type of coronary heart disease.(4) ischemic cardiomyopathy type: refer to because long-term myocardial ischemia causes myocardium limitation or diffuse fibrosis, thereby it is impaired to produce heart contraction and (or) diastolic function, cause the clinical syndrome of the series of clinical manifestations such as cardiac dilatation or stiff, congestive heart failure, arrhythmia.(5) sudden death type: think at present, this patient's sudden cardiac arrest be on the basis of coronary atherosclerosis, there is coronary vasospasm or microcirculation thromboembolism and cause Acute myocardial ischemia, cause local electric physiologic derangement, cause due to temporary transient severe arrhythmia (particularly ventricular fibrillation).
Statins (statins) is hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor, this type of medicine is by synthetic rate-limiting enzyme (HMG-CoA) reductase of competitive inhibition endogenous cholesterol, hydroxyl first valeric acid metabolic pathway in blocking-up cell, make the synthetic minimizing of cell inner cholesterol, thereby feedback irritation cell film surface (being mainly hepatocyte) low density lipoprotein, LDL (low density lipoprotein, LDL) acceptor quantity and activity increase, make serum cholesterol to remove to be increased, level reduces.Statins also can suppress the synthetic Apolipoprotein B-100 of liver, thereby reduces the synthetic and secretion of being rich in triglyceride AV, lipoprotein.Statins is divided into native compound (as lovastatin, simvastatin, pravastatin, mevastatin) and complete artificial-synthetic compound's (as fluvastatin, atorvastatin, cerivastatin, Rosuvastatin, Pitavastatin) is the most classical and effective fat-reducing medicament, is widely used in the treatment of hyperlipemia.
Aliskiren (Aliskiren) is non-peptide class feritin blocade of new generation, can reduce renin activity in the first link blocking-up RAS system, reduce the generation of AngII and aldosterone, do not affect the metabolism of Kallidin I and prostaglandin, play the effect of blood pressure lowering and Cardiovarscular.From current research aliskiren, it is potent, high selectivity, orally active, long-acting antihypertensive drug of new generation.This medicine acts on renin dependent, so escalated dose administration only understands time expand and can not cause blood pressure rapid drawdown, and similar to ARB (losartan, telmisartan), the incidence rate of untoward reaction is compared without significant difference with placebo group.Aliskiren can be blocked reactive rising of feritin that thiazide diuretic, angiotensin converting enzyme inhibitor and angiotensin receptor antagonist cause, when small sample test is combined with hydrochlorothiazide, ramipril and irbesartan, plasma renin activity does not raise.
Also do not have at present the use in conjunction of bibliographical information aliskiren and statins to report there is no the Western medicine compound in bibliographical information aliskiren/his spit of fland yet.
Summary of the invention
The object of the present invention is to provide a kind of Western medicine compound and medical usage thereof for the treatment of coronary heart disease, this compound medicine all has significant curative effect to myocardial ischemia type, myocardial infarction type and angina pectoris coronary heart disease.
The object of the present invention is achieved like this:
Treat a Western medicine compound for coronary heart disease, active component is by following two kinds of ingredients:
(1) aliskiren or its officinal salt;
(2) statins;
Described statins is simvastatin or rosuvastain calcium.
The Western medicine compound of described treatment coronary heart disease, the weight ratio of aliskiren and simvastatin is 10～80: 1.
Preferably, the weight ratio of aliskiren and simvastatin is 25～50: 1.
The Western medicine compound of described treatment coronary heart disease, the weight ratio of aliskiren and rosuvastain calcium is 5～60: 1.
Preferably, the weight ratio of aliskiren and rosuvastain calcium is 10～30: 1.
Preferably, the officinal salt of aliskiren is fumarate, nitrate, sulfate, Orotate.
By animal experiment, study, inventor is surprised to find that described aliskiren/his spit of fland compound recipe has shown unforeseeable technique effect in prevention or treatment coronary heart disease rat.Therefore, second object of the present invention is to provide the described Western medicine compound purposes in the medicine of preparation prevention or treatment coronary heart disease.
Described coronary heart disease is myocardial ischemia type coronary heart disease.
Described coronary heart disease is angina pectoris coronary heart disease.
Described coronary heart disease is myocardial infarction type coronary heart disease.
Pharmaceutical composition of the present invention is when treatment coronary heart disease, and the people of each compound recipe is respectively with oral every daily dose:
Simvastatin/aliskiren compound recipe: simvastatin 4-10mg, aliskiren 75-300mg.
Rosuvastain calcium/aliskiren compound recipe: Rosuvastatin 5-20mg, aliskiren 75-300mg.
Compared with prior art, the Western medicine compound tool the present invention relates to has the following advantages and is significant progressive: known by the result of the test that can be effectively treated after myocardial infarction model rat, the administration of chronic myocardial ischemia rat model, the present invention containing simvastatin/aliskiren or the Western medicine compound of rosuvastain calcium/aliskiren can Synergistic treatment myocardial ischemia type, myocardial infarction type and angina pectoris coronary heart disease, give and increased clinically a kind of new medicine.
Specific embodiment
Form by animal experiment example is described in further detail foregoing of the present invention again below, but this should be interpreted as to the scope of the above-mentioned theme of the present invention only limits to following example, all technology realizing based on foregoing of the present invention all belong to scope of the present invention.
The preparation of embodiment 1 rosuvastain calcium/aliskiren compound tablet
Prescription content:
Preparation technology: take aliskiren, rosuvastain calcium, starch, lactose, low-substituted hydroxypropyl cellulose mix homogeneously.Separately get appropriate 60% ethanol and add in mixed-powder, mix homogeneously, soft material processed, makes wet granular by 18 mesh sieves, and 60 ℃ of left and right are dry, with 20 mesh sieve granulate, add magnesium stearate, mix, and tabletting, obtains.
The preparation of embodiment 2 simvastatins/aliskiren compound tablet
Prescription content:
Preparation technology: take aliskiren, simvastatin, pregelatinized Starch, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose mix homogeneously.Separately get appropriate 60% ethanol and add in mixed-powder, mix homogeneously, soft material processed, makes wet granular by 18 mesh sieves, and 60 ℃ of left and right are dry, with 20 mesh sieve granulate, add magnesium stearate, mix, and tabletting, obtains.
The impact of embodiment 3 simvastatins/aliskiren compound recipe on myocardial infarction model rat
Select body weight 230-260g male SD rat, reserve 10 rats as outside normal group, residue rats by intraperitoneal injection 30mg/kg pentobarbital anesthetized rat.Back of the body position is fixing, with more than half suction ball (size is just in time enclosed within on rat head), and with ALC-V8 type animal respirator, tidal volume 10ml/kg, 45～50 times/min of respiratory frequency, respiratory quotient is 1: 1.Chest unhairing, sterilization, longitudinally cuts skin 20mm along left mid-clavicular line, at the 4th, 5 intercostal blunt separation flesh layers, with curved hemostat, strut Intercostal muscle and pleura enters thoracic cavity, cut off pericardium, with middle finger, gently press breast corridor, right side, thumb is pressed xiphoid-process bottom, extrude heart, take great cardiac vein as sign between left auricle and pulmonary conus, under left auricle root, 2～3mm passes left anterior descending coronary artery with 6-0 without wound suture, the about 0.5mm of depth of needle, ligation ramus descendens anterior arteriae coronariae sinistrae.Heart is sent back in thoracic cavity, push gently thoracic cavity, get rid of thoracic cavity air, layer-by-layer suture thoracic incision, closes breast.Three days prevention infection of postoperative intramuscular injection penicillin.After modeling success, by table 1 random packet gastric infusion 2 weeks, administration finished, rat anesthesia, and abdomen cardinal vein is got hematometry CK, AST and LDH, and testing result is in Table 2.
The grouping of table 1 laboratory animal and administration
The impact of table 2 simvastatin/aliskiren compound recipe on myocardial infarction model rat
Note: with model group comparison,
★p < 0.05,
★ ★p < 0.01;
With the comparison of simvastatin group,
▲p < 0.05,
▲ ▲p < 0.01;
With the comparison of aliskiren group,
■p < 0.05,
■ ■p < 0.01;
Compare with A-A Zu,
◆p < 0.05,
◆ ◆p < 0.01.
Creatine kinase (CK), aspartate amino transferase (AST) and lactic acid dehydrogenase (LDH) are the protease being present in myocardial cell, when cell injury or necrosis, therefore CK, AST, LDH just can be discharged into blood in cell, measure the index that serum CK, AST, LDH can be used as reflecting myocardium degree of necrosis.According to the result of this test card 2, show, the CK of model group rat, AST, the horizontal compared with normal group of LDH significantly increases, the CK of rat after administration, AST, LDH level significantly reduces, especially simvastatin/aliskiren compound recipe group is compared with model group, there is utmost point significant difference (P < 0.01), with single medicine group (simvastatin group, aliskiren group) compare also there is significance (P < 0.05) or utmost point significant difference (P < 0.01), after this explanation aliskiren and simvastatin prescription, myocardial infarction model rat is had to good synergistic therapeutic action.It should be noted that, the use in conjunction of aliskiren and atorvastatin does not but reach the synergistic therapeutic action to myocardial infarction model rat.
The impact of embodiment 4 Rosuvastatins/aliskiren compound recipe on myocardial infarction model rat
Select body weight 230-260g male SD rat, reserve 10 rats as outside normal group, residue rats by intraperitoneal injection 30mg/kg pentobarbital anesthetized rat.Back of the body position is fixing, with more than half suction ball (size is just in time enclosed within on rat head), and with ALC-V8 type animal respirator, tidal volume 10ml/kg, 45～50 times/min of respiratory frequency, respiratory quotient is 1: 1.Chest unhairing, sterilization, longitudinally cuts skin 20mm along left mid-clavicular line, at the 4th, 5 intercostal blunt separation flesh layers, with curved hemostat, strut Intercostal muscle and pleura enters thoracic cavity, cut off pericardium, with middle finger, gently press breast corridor, right side, thumb is pressed xiphoid-process bottom, extrude heart, take great cardiac vein as sign between left auricle and pulmonary conus, under left auricle root, 2～3mm passes left anterior descending coronary artery with 6-0 without wound suture, the about 0.5mm of depth of needle, ligation ramus descendens anterior arteriae coronariae sinistrae.Heart is sent back in thoracic cavity, push gently thoracic cavity, get rid of thoracic cavity air, layer-by-layer suture thoracic incision, closes breast.Three days prevention infection of postoperative intramuscular injection penicillin.After modeling success, by table 3 gastric infusion 2 weeks, administration finished, rat anesthesia, and abdomen cardinal vein is got hematometry CK, AST and LDH, and testing result is in Table 4.
The grouping of table 3 laboratory animal and administration
The impact of table 4 Rosuvastatin/aliskiren compound recipe on myocardial infarction model rat
Note: with model group comparison,
★p < 0.05,
★ ★p < 0.01;
With the comparison of Rosuvastatin group,
▲p < 0.05,
▲ ▲p < 0.01;
With the comparison of aliskiren group,
■p < 0.05,
■ ■p < 0.01;
Creatine kinase (CK), aspartate amino transferase (AST) and lactic acid dehydrogenase (LDH) are the protease being present in myocardial cell, when cell injury or necrosis, therefore CK, AST, LDH just can be discharged into blood in cell, measure the index that serum CK, AST, LDH can be used as reflecting myocardium degree of necrosis.According to the result of this test card 4, show, the CK of model group rat, AST, the horizontal compared with normal group of LDH significantly increases, the CK of rat after administration, AST, LDH level significantly reduces, especially aliskiren Rosuvastatin drug combination group is compared with model group, there is utmost point significant difference (P < 0.01), with single medicine group (simvastatin group, aliskiren group) compare also there is significance (P < 0.05) or utmost point significant difference (P < 0.01), after this explanation aliskiren and Rosuvastatin prescription, myocardial infarction model rat is had to good synergistic therapeutic action.
Embodiment 5 aliskirens/he feeds on high fat by spit of fland compound recipe and isoproterenol causes the impact of chronic myocardial ischemia model
1, animal grouping
SD rat is divided into 6 groups at random by body weight, and 10 every group, male and female half and half.After modeling success, each organizes rat according to as table 5 administration.
The grouping of table 5 laboratory animal and administration
2, modeling and administration
After animal adapts to 5 days, normal group detoxification rat complete feed, freely drinks purified water.The high lipoprotein emulsion of other animal every morning gavages 1 month, 10ml/kg, the freezing stimulation of afternoon-20 degree refrigerator-freezer every other day, every group of 15min.Rat freely drinks purified water, since 31d, and continuous 3d subcutaneous injection isoproterenol 20mg/kg (morning).During modeling, press the scheme administration of table 3.After administration finishes, rat anesthesia, abdomen cardinal vein is got hematometry AST, CK, LDH.
3, experimental result and conclusion
Table 6 aliskiren/he feeds on high fat by spit of fland compound recipe and IS0 causes the impact of chronic myocardial ischemia model
Note: with model group comparison,
★p < 0.05,
★ ★p < 0.01;
According to the result of this test card 6, show, the CK of model group rat, AST, the horizontal compared with normal group of LDH significantly increase, after administration, the CK of rat, AST, LDH level significantly reduce, compound recipe administration group is compared with model group, has significant difference (P < 0.05) or utmost point significant difference (P < 0.01).After this explanation aliskiren Rosuvastatin or aliskiren simvastatin prescription, myocardial infarction model rat is had to very significant therapeutical effect.
Claims (2)
1. a Western medicine compound for the treatment of myocardial infarction type coronary heart disease and myocardial ischemia type coronary heart disease, is characterized in that: active component is by following two kinds of ingredients:
(1) aliskiren or its officinal salt;
(2) statins;
Described statins is simvastatin or rosuvastain calcium;
When described statins is simvastatin, the weight ratio of aliskiren and simvastatin is 60:1;
When described statins is rosuvastain calcium, the weight ratio of aliskiren and rosuvastain calcium is 10:1 or 60:1.
2. according to the Western medicine compound of the treatment myocardial infarction type coronary heart disease of claim 1 and myocardial ischemia type coronary heart disease, it is characterized in that: the officinal salt of aliskiren is fumarate, nitrate, sulfate, Orotate.
3. the purposes of the Western medicine compound described in claim 1 or 2 in the medicine of preparation prevention or treatment myocardial infarction type coronary heart disease and myocardial ischemia type coronary heart disease.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110258892.1A CN102283831B (en) | 2011-09-03 | 2011-09-03 | Western medicine compound for curing coronary diseases and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110258892.1A CN102283831B (en) | 2011-09-03 | 2011-09-03 | Western medicine compound for curing coronary diseases and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102283831A CN102283831A (en) | 2011-12-21 |
| CN102283831B true CN102283831B (en) | 2014-08-06 |
Family
ID=45330770
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201110258892.1A Expired - Fee Related CN102283831B (en) | 2011-09-03 | 2011-09-03 | Western medicine compound for curing coronary diseases and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102283831B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105726576A (en) * | 2016-02-04 | 2016-07-06 | 刘玉财 | Tablet used for treating angina in slow-release stage and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102014881A (en) * | 2008-02-22 | 2011-04-13 | 韩兀生物制药株式会社 | Pharmaceutical preparation |
-
2011
- 2011-09-03 CN CN201110258892.1A patent/CN102283831B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102014881A (en) * | 2008-02-22 | 2011-04-13 | 韩兀生物制药株式会社 | Pharmaceutical preparation |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102283831A (en) | 2011-12-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9168308B2 (en) | Compositions and methods for nutritional supplementation | |
| JP2003206238A (en) | Medicinal composition | |
| MX2014000971A (en) | Left ventricular diastolic function improving agent. | |
| KR20210139293A (en) | Pulmonary Arterial Hypertension and Associated Pulmonary Arterial Hypertension Treatment and Daily Administration | |
| AU2019382168A1 (en) | A method for treating pulmonary arterial hypertension and associated pulmonary arterial hypertension | |
| EP3536331B1 (en) | Medical formulation for treating hypercholesterolemia | |
| CN102283831B (en) | Western medicine compound for curing coronary diseases and application | |
| CN101559228B (en) | Pharmaceutical composition for treating chronic stable angina pectoris with hyperlipemia | |
| CN1183935C (en) | Notoginseng and fermented red rice composition for preventing and treating cardiac and cerebral vascular diseases | |
| CN1299676C (en) | Anti-anoxia medicinal composition | |
| WO2006011495A1 (en) | Remedy for hypercholesterolemia and/or hypertriglyceridemia | |
| CN110013474A (en) | The new application of fenofibrate and drug for new application | |
| WO2011027021A1 (en) | A method for the treatment of hypertension | |
| CN102416015B (en) | Composition containing statins and application thereof | |
| CN101884634A (en) | Composition for treating cardiovascular diseases | |
| CN1943573A (en) | Use of vitamin C and arginine composition in anti-anoxic medicine and health product | |
| CN103316004B (en) | Pharmaceutical composition used for preventing and controlling metabolic syndrome and application thereof | |
| CN101073565A (en) | Use of arginine and taurine composition in anti-hypoxia medicine and health food | |
| CN101897967A (en) | Seabuckthorn flavone compound preparation for treating dyslipidemia | |
| CN101879168B (en) | Antihypertensive drug compound preparation | |
| CN113134086A (en) | Pharmaceutical composition for reducing blood fat | |
| CN101897735A (en) | Ginkgo flavone complex preparation for treating dyslipidemia | |
| CN106727505A (en) | A kind of Western medicine combination for treating coronary heart disease and preparation method thereof | |
| CN106551932A (en) | A kind of antihypertensive drugs compound preparation of better tolerance | |
| CN101897968A (en) | Compound preparation for treating dyslipidemia |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| ASS | Succession or assignment of patent right |
Owner name: THE FIRST AFFILIATED HOSPITAL OF XINXIANG MEDICAL Free format text: FORMER OWNER: NANJING ZHENGKUAN PHARMACEUTICAL SCIENCE AND TECHNOLOGY CO., LTD. Effective date: 20140711 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| C53 | Correction of patent for invention or patent application | ||
| CB03 | Change of inventor or designer information |
Inventor after: Yan Haiqing Inventor after: Zhang Ping Inventor after: Yan Zhixin Inventor after: Chang Li Inventor after: Gui Yongkun Inventor before: The inventor has waived the right to be mentioned |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: REQUEST NOT TO RELEASE THE NAME TO: YAN HAIQING ZHANG PING YAN ZHIXIN CHANG LI GUI YONGKUN Free format text: CORRECT: ADDRESS; FROM: 211200 NANJING, JIANGSU PROVINCE TO: 453100 XINXIANG, HENAN PROVINCE |
|
| TA01 | Transfer of patent application right |
Effective date of registration: 20140711 Address after: 453100 No. 88 health Road, Weihui, Henan, Xinxiang Applicant after: The First Affiliated Hospital of Xinxiang Medical University Address before: Qingfeng Village Yong Yang town of Lishui County of Nanjing City, Jiangsu province 211200 Green Village building 301 room 22 Applicant before: Nanjing Zhengkuan Pharmaceutical Science and Technology Co., Ltd. |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20140806 Termination date: 20150903 |
|
| EXPY | Termination of patent right or utility model |