CN1824312A - Compound medicine for preventing and treating cardio vascular cerebral vascular disease and its application - Google Patents
Compound medicine for preventing and treating cardio vascular cerebral vascular disease and its application Download PDFInfo
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- CN1824312A CN1824312A CN 200510200832 CN200510200832A CN1824312A CN 1824312 A CN1824312 A CN 1824312A CN 200510200832 CN200510200832 CN 200510200832 CN 200510200832 A CN200510200832 A CN 200510200832A CN 1824312 A CN1824312 A CN 1824312A
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Abstract
A compound medicine for preventing and treating the cardiovascular and cerebrovascular diseases of climacteric woman and adult man, climacteric syndrome, osteoporosis, endometrial carcinoma, senile dementia, diabetes and metabolism syndrome contains sexual hormones, hypolipemic component, antihypertensive component and anticoagulating component. It features that the ratio of its components is adjustable according to actual disease.
Description
Technical field
A kind of prevention and treatment cardiovascular and cerebrovascular disease compound medicines.Belong to the chemicals field.
Background technology
1. cardiovascular and cerebrovascular disease is first killer who threatens human health.Sickness rate is the highest, and mortality rate is the highest, and still is growing trend.Therefore seek new ideal medicament and therapy, control and prophylactic development are current urgent task and social responsibility.2. the women is before menopause, and the cardiovascular and cerebrovascular disease sickness rate is very low, and its M ﹠ M is identical with the male after menopause.Thinking at present may be relevant with estrogen.3. a large amount of zoopery and clinical observations show: gonadal hormone especially estrogen can alleviate the damage of inflammatory factor to blood vessel, and protection damaged blood vessels and vascular endothelial cell suppress vascular smooth muscle cell curing, slows down the atheromatous plaque development; Can pass through nitric oxide approach blood vessel dilating, bring high blood pressure down; Can reduce low-density lipoprotein cholesterol (LDL_C), high density lipoprotein increasing cholesterol (HDL_C); Can reduce the former activator of fiber in the blood; Can increase myocardial contraction, improve the function and the survival rate of heart failure heart, the cardiac muscle of protection ischemia.Gonadal hormone can alleviate the symptom of female climacteric syndrome in addition, reduces osteoporosis, carcinoma of endometrium, senile dementia, the generation of diabetes etc.4. still gonadal hormone also has side effect, as the rising triglyceride, increases blood viscosity and thrombosis, especially under the situation that forms the blood vessel atheromatous plaque.Therefore especially estrogen should be in the early stage application of vascular injury to think gonadal hormone at present.In addition gonadal hormone especially estrogen can increase the generation of breast carcinoma.5. phytoestrogen conjugated estrogen hormone receptor optionally reduces estrogenic side effect, as the generation of breast carcinoma.6. at present a large amount of evidences show along with hypertension hyperlipidemia, the increase of hyperglycemia and metabolic syndrome sickness rate, the M ﹠ M of cardiovascular and cerebrovascular disease is the increase of corresponding proportion, hypertension, hyperlipidemia, hyperglycemia and metabolic syndrome are the bases of cardiovascular and cerebrovascular disease.Therefore to reduce the M ﹠ M of cardiovascular and cerebrovascular disease, must strictly control hypertension, hyperlipidemia, the development of hyperglycemia and metabolic syndrome, but single bring high blood pressure down or blood fat or blood glucose can not reach best result, have only comprehensive controlling blood pressure, blood fat, blood glucose is in perfect condition (blood pressure: 115/70mmHg; LDL_C:＜3.0mmol/l; HDL_C:＞1.0mmol/l; Blood glucose:＜6.0mmol/l) could reduce the generation of cardiovascular and cerebrovascular disease and reduce mortality rate significantly.7. same a large amount of zooperies and extensive clinical trial show fat-reducing medicament, antihypertensive drugs (beta-blocker, angiotensin transaminase inhibitor and angiotensin receptor blocker, calcium antagonist), anticoagulant can alleviate the damage of inflammatory factor to blood vessel, suppress vascular smooth muscle cell curing, bring high blood pressure down, reduce low-density lipoprotein cholesterol (LDL_C), high density lipoprotein increasing cholesterol (HDL_C) slows down, stable and/or reverse blood vessel atheromatous plaque development, anticoagulant and thrombosis reduce the generation of cardiovascular and cerebrovascular vessel incident etc.But fat-reducing medicament, antihypertensive drugs (beta-blocker, angiotensin transaminase inhibitor and angiotensin receptor blocker, calcium antagonist), anticoagulant also has side effect, as lipid-lowering statins infringement liver and smooth muscle, the beta-blocker decreased heart rate suppresses myocardial contraction, and calcium antagonist increases heart rate and sympathetic activation, the use of angiotensin transaminase inhibitor and angiotensin receptor blocker is influenced by renal function, and anticoagulant causes bleeding etc.These side effect are most relevant with dosage.
Summary of the invention
1. the present invention is sex hormones, the blood fat reducing class, and the blood pressure lowering class, anticoagulant class drug regimen becomes compound medicines; make them from varying level, the position, by way of, more comprehensively; to greatest extent, the protective effect of collaborative performance cardiovascular and cerebrovascular vessel reduces dosage simultaneously, reduces side effect to greatest extent and produces.This compound medicines can also suppress and/or alleviate side effects of pharmaceutical drugs mutually in addition, and share as beta-blocker and calcium antagonist can stable heart-rate, and anticoagulant can reduce gonadal hormone to influence of blood coagulation system etc.It is the desirable combination of comparatively optimizing.2. the medicine that does not still have the prevention cardiovascular and cerebrovascular disease of desirable (be effective in cure have no side effect again) at present.Because any single medicine all can't be competent at the task of the complicated cardiovascular and cerebrovascular disease of control.Be not that dosage is excessive, side effect increases, and is exactly that dosage is too small, and curative effect reduces, and is difficult to become ideal medicament.Just as the therapeuticcocktail of anti-retrovirals of treatment AIDS, have only drug combination could bring into play the effect of protection cardiovascular and cerebrovascular vessel to greatest extent, could on the basis that guarantees curative effect, reduce the generation of side effect to greatest extent simultaneously.This compound medicines has been concentrated the medicine of the most effective current protection cardiovascular and cerebrovascular vessel, optimum organization, and lowest dose level, minimal side effect is the medicine of current comparatively ideal control cardiovascular and cerebrovascular disease.3. this compound medicines is is suitably added and subtracted, to be suitable for different crowd on the basis of basic combination.As can be used for healthy population than low dosage, high-risk group's primary prevention, higher dosage can be used for cardiovascular and cerebrovascular disease patient's secondary prevention, prevent the further generation of cardiovascular and cerebrovascular vessel incident, increase estrogen, progestogen content can be used for the women in menopause, adopts phytoestrogen to can be used for adult male, regulates antihypertensive drugs content to adapt to different blood pressure crowds etc.
The specific embodiment
Embodiment 1: this compound medicines is by 17 β estradiol 0.5mg, medroxyprogesterone 0.3mg, and suffering is cut down its spit of fland 2.5mg, metoprolol 2.0mg, amlodipine 0.5mg, aspirin 75mg makes combination preparation, press oral formulations (conventional tablet, dispersible tablet, thin membrane coated tablet, Sublingual tablet, oral cavity disintegration tablet, enteric coatel tablets, slow releasing tablet, fast-release tablet, controlled release tablet, hard capsule, enteric coated capsule, slow releasing capsule etc.) preparation technology's program carries out.Be used for premature menopause phase women.Controlling blood pressure, blood fat, blood glucose is in perfect condition (blood pressure: 115/70mmHg; LDL_C:＜3.0mmol/l; HDL_C:＞1.0mmol/l; Blood glucose:＜6.0mmol/l).The control metabolic syndrome, the monitoring sex hormone level.
Embodiment 2: this compound medicines is by 17 β estradiol 0.5mg, medroxyprogesterone 0.3mg, and suffering is cut down its spit of fland 5mg, metoprolol 2.0mg
2, amlodipine 0.5mg, aspirin 100mg makes combination preparation, presses oral formulations (conventional tablet, dispersible tablet, thin membrane coated tablet, Sublingual tablet, oral cavity disintegration tablet, enteric coatel tablets, slow releasing tablet, fast-release tablet, controlled release tablet, hard capsule, enteric coated capsule, slow releasing capsule etc.) preparation technology's program carries out.Be used for women in menopause in late period.Controlling blood pressure, blood fat, blood glucose is in perfect condition (blood pressure: 115/70mmHg; LDL_C:＜3.0mmol/l; HDL_C:＞1.0mmol/l; Blood glucose:＜6.0mmol/l).The control metabolic syndrome, the monitoring sex hormone level.
Embodiment 3: this compound medicines is by soybean isoflavone 300mg and/or 17 β estrogen 0.05mg, and suffering is cut down its spit of fland 2.5mg, metoprolol 2.0mg, amlodipine 0.5mg, aspirin 40mg makes combination preparation, presses oral formulations (conventional tablet, dispersible tablet, thin membrane coated tablet, Sublingual tablet, oral cavity disintegration tablet, enteric coatel tablets, slow releasing tablet, fast-release tablet, controlled release tablet, hard capsule, enteric coated capsule, slow releasing capsule etc.) preparation technology's program is carried out.Be used for the adult male high-risk group.Controlling blood pressure, blood fat, blood glucose is in perfect condition (blood pressure: 115/70mmHg; LDL_C:＜3.0mmol/l; HDL_C:＞1.0mmol/l; Blood glucose:＜6.0mmol/l).The control metabolic syndrome, the monitoring sex hormone level.
Embodiment 4: this compound medicines is by soybean isoflavone 300mg and/or 17 β estrogen 0.05mg, lipanthyl 50mg, metoprolol 2.0mg, amlodipine 0.5mg, aspirin 40mg makes combination preparation, presses oral formulations (conventional tablet, dispersible tablet, thin membrane coated tablet, Sublingual tablet, oral cavity disintegration tablet, enteric coatel tablets, slow releasing tablet, fast-release tablet, controlled release tablet, hard capsule, enteric coated capsule, slow releasing capsule etc.) preparation technology's program is carried out.Be used for the high triglyceride crowd of adult male.Controlling blood pressure, blood fat, blood glucose is in perfect condition (blood pressure: 115/70mmHg; LDL_C:＜3.0mmol/l; HDL_C:＞1.0mmol/l; Blood glucose:＜6.0mmol/l).The control metabolic syndrome, the monitoring sex hormone level.
Embodiment 5: this compound medicines is by soybean isoflavone 300mg and/or 17 β estrogen 0.05mg, and suffering is cut down its spit of fland 20mg, metoprolol 12.5mg, amlodipine 2.5mg, aspirin 80mg makes combination preparation, presses oral formulations (conventional tablet, dispersible tablet, thin membrane coated tablet, Sublingual tablet, oral cavity disintegration tablet, enteric coatel tablets, slow releasing tablet, fast-release tablet, controlled release tablet, hard capsule, enteric coated capsule, slow releasing capsule etc.) preparation technology's program is carried out.Be used for the secondary prevention of cardiovascular and cerebrovascular disease.Controlling blood pressure, blood fat, blood glucose is in perfect condition (blood pressure: 115/70mmHg; LDL_C:＜3.0mmol/l; HDL_C:＞1.0mmol/l; Blood glucose:＜6.0mmol/l).The control metabolic syndrome, the monitoring sex hormone level.
The invention is not restricted to above-described embodiment.
Claims (10)
1. one kind is prevented and treatment cardiovascular and cerebrovascular disease compound medicines, it is characterized by this compound medicines and comprises sex hormones, blood fat reducing class, blood pressure lowering class, anticoagulant class medicine.And according to different crowd, on the basis of basic combination, press variety classes, dosage, ratio and dosage form, suitably plus-minus preparation.
2. compound medicines according to claim 1 is applied to climacteric women and adult male cardiovascular and cerebrovascular disease one, secondary prevention and treatment, and other diseases such as climacteric syndrome, osteoporosis, carcinoma of endometrium, senile dementia, diabetes, the control of diseases such as metabolism syndrome.
3. according to claim 1,2 described compound mediciness, wherein sex hormones comprises estrogen (estradiol, 17 β estradiol, estradiol benzoate, estradiol valerate, estradiol cypionate, conjugated estrogens, ethinylestradiol, nilestriol, the female alcohol of hexene, chlorotrianisene, estriol etc.), progestogen (progesterone, medroxyprogesterone, megestrol, chlormadinone, hydroxyprogesterone, norethindrone, norgestrel, gestrinone etc.), male's androgen (Testosterone Propionate, methyltestosterone, nandrolone phenylpropionate, danazol etc.), phytoestrogen (soybean isoflavone, daidzin etc.).Wherein estradiol dosage is from 0.1-50mg; 17 β estradiol dosage are from 0.1-50mg; Estradiol benzoate dosage is from 0.1-50mg; Estradiol valerate dosage is from 0.1-50mg; Estradiol cypionate dosage is from 0.1-50mg; Conjugated estrogens dosage is from 0.05-50mg; Ethinylestradiol dosage is from 0.1-1000ug; Nilestriol dosage is from 0.1-50mg; The female pure dosage of hexene is from 0.1-50mg; Chlorotrianisene dosage is from 0.1-50mg; Estriol dosage is from 0.1-100mg; Progesterone dosage is from 0.1-100mg; Medroxyprogesterone dosage is from 0.1-1000mg; Megestrol dosage is from 0.1-50mg; Chlormadinone dosage is from 0.01-50mg; Hydroxyprogesterone dosage is from 0.1-1000mg; Norethindrone dosage is from 0.05-100mg; Norgestrel dosage is from 0.1-100mg; Gestrinone dosage is from 0.1-50mg; Testosterone Propionate dosage is from 0.5-500mg; Methyltestosterone dosage is from 0.1-100mg; Nandrolone phenylpropionate dosage is from 0.1-200mg; Danazol dosage is from 1-1000mg; Soybean isoflavone dosage is from 0.1-1000mg; Daidzin dosage is from 0.1-1000mg etc.And according to different crowd, by various dose, ratio, independent and/or co-formulated.
4. according to claim 1,2 described compound mediciness, wherein blood fat reducing class comprises statins (lovastatin, simvastatin, pravastatin, atorvastatin, fluvastatin, simvastatin etc.), the special class medicine of shellfish (fenofibrate, gemfibrozil, bezafibrate, chlorine Bei Te, acipimox, probucol, lipanthyl etc.), plant class (Monas cuspurpureus Went etc.).Wherein lovastatin dosage is from 0.1-200mg; Simvastatin is from 0.1-200mg; Pravastatin dosage is from 0.1-200mg; Atorvastatin dosage is from 0.1-200mg; Fluvastatin dosage is from 0.1-200mg; Simvastatin dosage is from 0.1-200mg; Fenofibrate dosage is from 1-2000mg; Gemfibrozil dosage is from 1-2000mg; Bezafibrate dosage is from 1-2000mg; The special dosage of chlorine shellfish is from 1-2000mg; Acipimox dosage is from 1-2000mg; Probucol dosage is from 1-2000mg; Lipanthyl dosage is from 1-500mg; Monas cuspurpureus Went dosage is from 1-3000mg.And according to different crowd, by various dose, ratio, independent and/or co-formulated.
5. according to claim 1,2 described compound mediciness, wherein blood pressure lowering class comprises beta-blocker (metoprolol, bisoprolol, atenolol, Propranolol, carvedilol, timolol, labetalol, dilevalol, celiprolol, amosulalol, Almarl etc.), calcium antagonist (nifedipine, amlodipine, diltiazem, felodipine, Isradipine, nicardipine, the Mi Baifu Horizon, verapamil, nisoldipine, lacidipine etc.), angiotensin receptor blocker (losartan, valsartan, irbesartan, Candesartan, eprosartan, Tasosartan, telmisartan etc.).Angiotensin transaminase inhibitor (captopril, enalapril, benazepril, lisinopril, ramipril, fosinopril, cilazapril, perindopril, quinapril, trandolapril, delapril, Imidapril etc.).Wherein metoprolol dosage is from 0.1-500mg; Bisoprolol dosage is from 0.1-100mg; Atenolol dosage is from 0.1-100mg; Propranolol dosage is from 0.1-100mg; Carvedilol dosage is from 0.1-100mg; Timolol dosage is from 0.1-100mg; Labetalol dosage is from 0.1-100mg; Dilevalol dosage is from 0.1-100mg; Celiprolol dosage is from 0.1-100mg; Amosulalol dosage is from 0.1-100mg; Almarl dosage is from 0.1-100mg; Nifedipine dosage from 0.1-200mg. amlodipine dosage from 0.1-100mg; Diltiazem dosage is from 0.1-200mg; Felodipine dosage is from 0.1-100mg; Isradipine dosage is from 0.1-100mg; Nitrendipine dosage is from 0.1-200mg; Nicardipine dosage is from 0.1-200mg; Nisoldipine dosage is from 0.1-200mg; Mi Baifu Horizon dosage is from 0.1-100mg; Verapamil dosage is from 0.1-200mg; Lacidipine dosage is from 0.1-100mg; Captopril dosage is from 0.1-200mg; Enalapril dosage is from 0.1-100mg; Benazepril dosage is from 0.1-100mg; Lisinopril dosage is from 0.1-100mg; Ramipril dosage is from 0.1-100mg; Fosinopril dosage is from 0.1-100mg; Cilazapril dosage is from 0.1-100mg; Perindopril dosage is from 0.1-100mg; Quinapril dosage is from 0.1-100mg; Trandolapril dosage is from 0.1-100mg; Delapril dosage is from 0.1-100mg; Imidapril dosage is from 0.1-100mg etc.And according to different crowd, by various dose, ratio, independent and/or co-formulated.
6. according to claim 1,2 described compound mediciness, wherein anticoagulant comprises aspirin, warfarin etc.Wherein aspirin dosage is from 10-500mg.Warfarin is from 0.1-10mg.And according to different crowd, by various dose, ratio, independent and/or co-formulated.
7. according to claim 1,2 described compound mediciness is characterized in that: get principal agent and filler, disintegrating agent, surfactant, cosolvent, binding agent mixes, and guiding humid medium system soft material is granulated, dry, granulate adds lubricant, tabletting, make oral ordinary tablet, should oral ordinary tablet bag film-coat or enteric coating can further make Film coated tablets or enteric coatel tablets; Get principal agent and filler, binding agent mixes, and guiding humid medium system soft material is granulated, drying, and granulate adds correctives, lubricant, tabletting is made Sublingual tablet.Get principal agent and filler, disintegrating agent helps and collapses agent, surfactant, and surfactant mixes, and adds correctives, lubricant, tabletting is made dispersible tablet, oral cavity disintegration tablet; Get principal agent and slow release and/or rapid release and/or controlled-release material and mix, guiding humid medium system soft material is granulated, drying, and granulate adds lubricant, and tabletting is made slow releasing tablet, fast-release tablet, controlled release tablet.
8. according to claim 1,2 described compound mediciness is characterized in that: get principal agent and filler, disintegrating agent, surfactant, cosolvent, binding agent mixes, guiding humid medium system soft material, granulate, be filled into Capsules, make hard capsule, the capsule of preparation is handled with the coating enteric material, can further be made enteric coated capsule; Get principal agent and slow release and/or rapid release and/or controlled-release material and make one or more slow release and/or rapid release and/or controlled release piller, fill separately or mixing back filling Capsules, make slow release and/or quick-release capsules or controlled release capsule.
9. according to claim 1,2 described polypharmaceutic adjuvants: filler is arranged, binding agent, surfactant, wetting agent, wetting agent, disintegrating agent, help and collapse agent, suspending agent, fluidizer, lubricant, correctives, adsorbent, suspensoid, coating material, coating material, slow-release material, rapid release material, controlled-release material etc.
10. filler according to claim 9 includes but not limited to lactose, sucrose, glucose, mannitol, sorbitol, calcium sulfate, calcium gluconate, calcium hydrogen phosphate, calcium carbonate, starch, carboxymethyl starch, pregelatinized Starch, microcrystalline Cellulose etc.Binding agent includes but not limited to starch, pregelatinized Starch, gelatin, dextrin, maltodextrin, sucrose, arabic gum, polyvinylpyrrolidone, various viscosity methylcellulose, low viscosity carboxymethyl cellulose, various viscosity ethyl celluloses, various viscosity polyvinyl alcohol, polyethylene glycol 6000, the following hydroxypropyl emthylcellulose of 5MPAS etc.Disintegrating agent includes but not limited to starch, pregelatinized Starch, microcrystalline Cellulose, alginic acid, pure lignocellulose, carboxymethyl starch sodium, guar gum, crospolyvinylpyrrolidone, ion exchange resin, methylcellulose, sodium carboxymethyl cellulose etc.; Lubricant includes but not limited to magnesium stearate, calcium stearate, zinc stearate, Pulvis Talci, glyceryl monostearate, polyethylene glycol 6000, Polyethylene Glycol 8000, sodium benzoate, adipic acid, fumaric acid, boric acid, sodium chloride, triacetyl glycerine, polyoxyethylene monostearate, single Laurel sucrose acid ester, sodium chloride, sodium laurylsulfate, magnesium laurylsulfate etc.; Surfactant comprises but is not limited to sodium lauryl sulphate, smelting Luo Shamu, Tween 80, bromination hexadecane trimethylamine, sodium laurylsulfate, stearyl alcohol semi-annular jade pendant acid sodium, polyoxyethylene high fatty alcohol, sucrose fat, sorbitol fatty ester, soybean phospholipid etc.; Correctives includes but not limited to steviosin, fructose, glucose, high fructose syrup, Mel, aspartame, protein sugar, xylitol, mannitol essence, Fructus Citri tangerinae essence, Herba Menthae essence, Fructus Foeniculi, vanillin, Fructus Citri Limoniae essence, cherry essence, rose essence etc.Coating material includes but not limited to cellulose and derivatives class thereof, crylic acid resin, ethene polymers etc.Coating material includes but not limited to gelatin, arabic gum, carboxymethyl cellulose, polyvinyl alcohol, polyacrylic acid, hydroxyethyl-cellulose, polylactic acid, ethyl cellulose, polyethylene, polyamide, stearic acid, celluloid, tristerin, Lac, Cellulose Acetate Phthalate; Slow release, rapid release, controlled release matrix material include but not limited to that babassu is cured, castor oil hydrogenated, Semen Ricini is cured, and hydrogenated castor is cured, hydrogenated soya phosphatide, Lac, gelatin, sodium alginate, chitosan, amylopectin, agar, carrageenin, guar gum, cellulose derivative, crylic acid resin, polyethylene kind, macromolecular material etc.
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| CN 200510200832 CN1824312A (en) | 2005-12-19 | 2005-12-19 | Compound medicine for preventing and treating cardio vascular cerebral vascular disease and its application |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102370648A (en) * | 2010-08-10 | 2012-03-14 | 山东新时代药业有限公司 | Medicinal composition and its application |
| CN102526469A (en) * | 2012-02-16 | 2012-07-04 | 罗群 | Compound medicament for rehabilitation after myocardial infarction and preparation method thereof |
| WO2013084089A1 (en) * | 2011-12-09 | 2013-06-13 | Wockhardt Limited | Methods for treating cardiovascular disorder |
| CN106390094A (en) * | 2016-11-11 | 2017-02-15 | 上海雅本化学有限公司 | Trandolapril-containing pharmaceutical composition and preparation method thereof |
-
2005
- 2005-12-19 CN CN 200510200832 patent/CN1824312A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102370648A (en) * | 2010-08-10 | 2012-03-14 | 山东新时代药业有限公司 | Medicinal composition and its application |
| WO2013084089A1 (en) * | 2011-12-09 | 2013-06-13 | Wockhardt Limited | Methods for treating cardiovascular disorder |
| CN104114163A (en) * | 2011-12-09 | 2014-10-22 | 沃克哈特有限公司 | Methods for treating cardiovascular disorder |
| JP2015500276A (en) * | 2011-12-09 | 2015-01-05 | ウォックハート リミテッド | Methods for treating cardiovascular disorders |
| CN102526469A (en) * | 2012-02-16 | 2012-07-04 | 罗群 | Compound medicament for rehabilitation after myocardial infarction and preparation method thereof |
| CN106390094A (en) * | 2016-11-11 | 2017-02-15 | 上海雅本化学有限公司 | Trandolapril-containing pharmaceutical composition and preparation method thereof |
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