CN101869710A - Antihypertensive medical composite - Google Patents
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- CN101869710A CN101869710A CN200910082591A CN200910082591A CN101869710A CN 101869710 A CN101869710 A CN 101869710A CN 200910082591 A CN200910082591 A CN 200910082591A CN 200910082591 A CN200910082591 A CN 200910082591A CN 101869710 A CN101869710 A CN 101869710A
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Abstract
The invention relates to an antihypertensive medical composite which is composed of 0.5-100mg of angiotensin converting enzyme inhibitor with curative dose, 4-800mg of AT1 receptor antagonist, 0.1-50mg of one or more of B-complex vitamins and pharmaceutically acceptable carrier in one tablet. The invention has the advantages that the medical composite can increase the curative effect of the antihypertensive medicine, improve the target organ protection function of the medicine and reduce the incidence rate of complications such as fundus hemorrhage, angina pectoris, myocardial infarction, brain stroke, heart failure and kidney failure. In addition, the antihypertensive medical composite can be used to ensure the patient to take the medicine conveniently and reduce medical expenses.
Description
Technical field
The present invention relates to a kind of prevention, treat and delay the pharmaceutical composition of hypertension and relevant disease thereof, especially a kind of pharmaceutical composition that contains angiotensin-convertion enzyme inhibitor, angiotensin ii receptor antagonist and vitamin B group.The invention belongs to pharmaceutical field.
Background technology
Hypertension is the most popular at present cardiovascular disease, and it also is the principal element that causes coronary heart disease, apoplexy, congestive heart failure and renal dysfunction simultaneously, and M ﹠ M has surpassed neoplastic disease and leapt to the first.Hypertension is 27.2% in China's prevalence, existing at present patient more than 1.3 hundred million, and the hypertension prevalence increases rapidly.Treatment hypertensive patient's main purpose is to reduce cardiovascular diseases's death and invalid total danger to greatest extent, medicine brings high blood pressure down and can reduce the M ﹠ M of cardiovascular complication effectively, prevents the generation and the development of apoplexy, coronary heart disease, heart failure and kidney disease.
The current medicine that is used for blood pressure lowering mainly contains: angiotensin converting enzyme inhibitor (ACEI), angiotensin ii receptor antagonist (AT
1RA), diuretic, beta-blocker, alpha-blocking agent and calcium antagonist etc.The hypertension drug treatment enters reinforcement, optimization, the simplification blood pressure lowering epoch of seeking best of breed.Most hyperpietics need two or more antihypertensive drug to come controlling blood pressure, two kinds of medicines can write out a prescription separately or for the compound preparation of fixed dosage (Chinese hypertension prevention and control guide Drafting Committee. Chinese hypertension prevention and control guide. the hypertension magazine, 2000:8 (1): 94-102,103-112).
Hypertensive treatment rate is respectively 28.2% and 59% in the China and the U.S., and control rate only is respectively 8.1% and 34%.As seen, the hypotensive effect of hypertensive Drug therapy still can not be fully up to expectations.In addition, to reach the target blood pressure be crucial though bring high blood pressure down, and target-organ protection is the final goal of hypertension therapeutic.
Angiotensin converting enzyme inhibitor (ACEI) is clinical the most frequently used medicine, mainly comprises: captopril (Captopril), enalapril (Enalapril), perindopril (Perindopril), cilazapril (Cilaza-pril), benazepril (Benazepril), ramipril (Ramipril), lisinopril (Lisinopril).ACEI mainly is by suppressing the activity of angiotensin converting enzyme (ACE), reduce the content of Angiotensin II and aldosterone, can reduce simultaneously the Kallidin I degraded, promote the release of prostaglandin, also can suppress ACE in local organization such as kidney, blood vessel wall and the brain, vasodilator reduces total peripheral resistance, bring high blood pressure down, be used for the treatment of essential hypertension.
ACEI depressor also has certain problem in clinical practice, at first its efficacy of antihypertensive treatment has certain limit, and lot of documents report total effective rate only is about 60%, 40% invalid or curative effect is not remarkable.Compare with other depressor; the target organ protection function of ACEI does not have clear superiority; ESC's hypertension therapeutic guide report in 2003; to comprising 46553 at random in 5 experimental studies of patient; the curative effect that compares ACEI and conventional medicament; evaluation index comprises general mortality rate, cardiovascular death rate, all cardiovascular events, myocardial infarction and heart failure, the result do not find ACEI aspect above-mentioned because old medicine.
Angiotensin-ii receptor (AT
1Receptor) antagonist is the most frequently used medicine of clinic control hypertension, comprise: irbesartan (Irbesartan), losartan (Losartan), valsartan (Valsartan), telmisartan (Telmisartan/Micardis, telmisartan), Candesartan (Candesartan, Kang Deshatan), eprosartan (Eprosartan, Eprosartan), Olmesartan (0lmesartan Medoxomil, olmesartan medoxomil), Tasosartan (Tasosartan/Verdia) etc.AT
1Receptor antagonist is mainly by specific inhibition Angiotensin II and AT
1The combination of receptor, thus the vasoconstriction of blocking-up Angiotensin II and aldosterone secretion reach the effect of blood pressure lowering and protection target organ.
AT
1There is certain problem in receptor antagonist in clinical practice.At first its efficacy of antihypertensive treatment has certain limit.Light to 3700 examples, in, the severe hypertension patient carries out at random, double blinding, multiple center clinical study, found that and take Losartan 50mg that effective percentage only is 41%-54%.Secondly; AT1 receptor antagonist target organ protection function is still limited; LIFE research (in November, 2003 AHA's academic conference report) is found; the therapeutic scheme that contains the angiotensin ii receptor antagonist losartan is compared with the therapeutic scheme that contains the beta-blocker atenolol, and the danger of two groups of crowd's myocardial infarctions and cardiovascular death there is no the significance difference.U.S.'s prevention, detection, assessment and the treatment hypertension whole nation the 7th report of joint committee (JNC7) be not also with the recommendation medicine of AT1 receptor antagonist as high-risk diseases such as myocardial infarction, coronary heart disease.In recent years studies show that the folic acid deficiency diet can cause rat hyperhomocysteinemiainjury and arterial injury, and (Xiao Chuanshi, hyperhomocysteinemiainjury influence the experimentation of left ventricular function for Gao Fen, Li Jing prunus mume (sieb.) sieb.et zucc., Chinese cardiovascular diseases's magazine, 2002; 30 (5): 312).Serum folic acid level and coronary heart disease have remarkable negative correlation, increase the folic acid intake and can reduce homocysteine level, reduce cardiovascular diseases's mortality rate, low serum folic acid level and dangerous relevant (the McCully KS.Homocysteine that raises of lethal coronary heart disease, vitamins, and prevention of vascular disease.Mil Med, 2004:169 (4): 325-9).
Summary of the invention
Technical problem to be solved by this invention is to overcome angiotensin converting enzyme inhibitor and AT
1The receptor agonist hypotensor above shortcomings provide a kind of and all are being better than angiotensin converting enzyme inhibitor or AT1 receptor antagonist aspect efficacy of antihypertensive treatment and the target-organ protection, and the pharmaceutical composition that toxicity does not increase.
For achieving the above object, the present invention is by the following technical solutions:
A kind of pharmaceutical composition is made up of angiotensin converting enzyme inhibitor, angiotensin ii receptor antagonist, one or more vitamin B group and the pharmaceutically acceptable carrier of treatment effective dose; Wherein the content of angiotensin converting enzyme inhibitor is 0.5-100mg, and the content of AT1 receptor antagonist is 4-800mg, and the content of vitamin B group is 0.1-50mg.
In the present invention, angiotensin converting enzyme inhibitor is selected from captopril (Captopril), enalapril (Enalapril), perindopril (Perindopril), cilazapril (Cilaza-pril), benazepril (Benazepril), ramipril (Ramipril), lisinopril (Lisinopril), quinapril (Quinapril), fosinopril (Fosinopril), delapril (Delapril), moexipril (Moexipril), spirapril (Spirapril), imidapril (Imidapril), trandolapril (Trandolapril), a kind of in the alacepril (Alacepril).As a kind of variation that can predict, above-mentioned substance can substitute with corresponding metabolite, esters or salt.
Angiotensin converting enzyme inhibitor and content are respectively: captopril (12.5-100mg), enalapril (2.5-40mg), perindopril (2-16mg), cilazapril (1.25-5mg), benazepril (2.5-40mg), ramipril (1.25-20mg), lisinopril (2.5-80mg), quinapril (5-80mg), fosinopril (10-80mg), delapril (15-120mg), moexipril (3.75-30mg), spirapril (3-30mg), imidapril (2.5-40mg), trandolapril (0.5-4mg), alacepril (12.5-100mg).The active metabolite of above-mentioned substance, esters or salt content are equal to corresponding above-mentioned substance content.
The better in the present invention content of these medicines is respectively: captopril (25-100mg), enalapril (5-40mg), perindopril (4-8mg), cilazapril (2.5-5mg), benazepril (5-40mg), ramipril (2.5-20mg), lisinopril (5-40mg), quinapril (10-40mg), fosinopril (10-40mg), delapril (15-60mg), moexipril (7.5-30mg), spirapril (3-15mg), imidapril (2.5-10mg), trandolapril (0.5-2mg), alacepril (25-100mg).The active metabolite of above-mentioned substance, esters or salt content are equal to corresponding above-mentioned substance content.
In the present invention, AT1 receptor antagonist and active metabolite thereof or salt are selected from losartan (Losartan), valsartan (Valsartan), irbesartan (Irbesartan, irbesartan, Irb), telmisartan (Telmisartan/Micardis, telmisartan), Candesartan (Candesartan, Kang Deshatan), eprosartan (Eprosartan, Eprosartan), Olmesartan (0lmesartan Medoxomil, olmesartan medoxomil), Tasosartan (Tasosartan/Verdia).As a kind of variation that can predict, above-mentioned substance can substitute with corresponding metabolite, esters or salt.
AT1 receptor antagonist and content are respectively: losartan (25-200mg), valsartan (40-320mg), irbesartan (75-600mg), telmisartan (20-160mg), Candesartan (4-64mg), eprosartan (200-800mg), Olmesartan (20-80mg), Tasosartan (10-300mg).The active metabolite of above-mentioned substance, esters or salt content are equal to corresponding above-mentioned substance content.
The better in the present invention content of these medicines is respectively: losartan (50-100mg), valsartan (80-160mg), irbesartan (150-300mg), telmisartan (20-80mg), Candesartan (8-32mg), eprosartan (400-800mg), Olmesartan (20-40mg), Tasosartan (25-300mg).The active metabolite of above-mentioned substance, esters or salt content are equal to corresponding above-mentioned substance content.
In the present invention, vitamin B group is selected from one or more in vitamin B6, vitamin B12, folic acid or the calcium leucovorin.
Described vitamin B6 comprises the derivant of pyridoxol, 2-methyl-3-hydroxy-4-formyl-5-hydroxymethylpyridine., pyridoxamine, pyridoxal 5-phosphate, phosphopyridoxamine and above-mentioned substance and can discharge/generate the material of this compounds in vivo.
Described vitamin B12 comprises the derivant of cobalamine, mecobalamin element, 5 ' deoxyadenosyl cobalamin, hydroxocobalamine, cyanocobalamin and other cobalamine and can discharge/generate the material of cobalamine in vivo.
Described folic acid class material comprises the active metabolite of folic acid, calcium leucovorin, L-methopterin, folate, folic acid or folate and can discharge/generate the material of folic acid in vivo.
Vitamin B group class material treatment effective dose in the present invention is respectively: the content of folic acid class material is 0.2-10mg, and vitamin B12 content is 0.1-2mg, and vitamin B6 content is 0.5-50mg.Its better treatment effective dose is respectively: folic acid class material 0.2-5mg, vitamin B12 0.25-2mg, vitamin B6 5-50mg.
The present invention is preferably by the component of the following content pharmaceutical composition as active component: wherein angiotensin converting enzyme inhibitor is selected from enalapril (5-40mg), perindopril (4-8mg), cilazapril (2.5-5mg), benazepril (5-40mg), ramipril (2.5-20mg), fosinopril (10-40mg), and the AT1 receptor antagonist is selected from losartan (50-100mg), valsartan (80-160mg), irbesartan (150-300mg), telmisartan (20-80mg), Candesartan (8-32mg); Vitamin B group class material be selected from folic acid class material (0.2-5mg), vitamin B12 (0.25-2mg) and vitamin B6 (5-50mg) neutralization-kind or several.
Described angiotensin converting enzyme inhibitor is selected from enalapril, and the AT1 receptor antagonist is selected from irbesartan, and vitamin B group is folic acid or calcium leucovorin; Wherein the content of angiotensin converting enzyme inhibitor is 5-40mg, and the content of AT1 receptor antagonist is 4-800mg, and the content of vitamin B group is 0.1-50mg.
Described angiotensin converting enzyme inhibitor is selected from enalapril, and the AT1 receptor antagonist is selected from irbesartan, and vitamin B group is a vitamin B6; Wherein the content of angiotensin converting enzyme inhibitor is 5-40mg, and the content of AT1 receptor antagonist is 150-300mg, and the content of vitamin B group is 5-50mg.
Described angiotensin converting enzyme inhibitor is selected from enalapril, and the AT1 receptor antagonist is selected from irbesartan, and vitamin B group is a vitamin B12; Wherein the content of angiotensin converting enzyme inhibitor is 5-40mg, and the content of AT1 receptor antagonist is 150-300mg, and the content of vitamin B group is 0.25-2mg.
Described angiotensin converting enzyme inhibitor is selected from enalapril, and the AT1 receptor antagonist is selected from valsartan, and vitamin B group is folic acid or calcium leucovorin; Wherein the content of angiotensin converting enzyme inhibitor is 5-40mg, and the content of AT1 receptor antagonist is 80-160mg, and the content of vitamin B group is 0.2-5mg.
Described angiotensin converting enzyme inhibitor is selected from enalapril, and the AT1 receptor antagonist is selected from valsartan, and vitamin B group is a vitamin B6; Wherein the content of angiotensin converting enzyme inhibitor is 5-40mg, and the content of AT1 receptor antagonist is 80-160mg, and the content of vitamin B group is 5-50mg.
Described angiotensin converting enzyme inhibitor is selected from enalapril, and the AT1 receptor antagonist is selected from valsartan, and vitamin B group is a vitamin B12; Wherein the content of angiotensin converting enzyme inhibitor is 5-40mg, and the content of AT1 receptor antagonist is 80-160mg, and the content of vitamin B group is 0.25-2mg.
Described angiotensin converting enzyme inhibitor is selected from enalapril, and the AT1 receptor antagonist is selected from losartan, and vitamin B group is folic acid or calcium leucovorin; Wherein the content of angiotensin converting enzyme inhibitor is 5-40mg, and the content of AT1 receptor antagonist is 50-100mg, and the content of vitamin B group is 0.2-5mg.
Described angiotensin converting enzyme inhibitor is selected from enalapril, and the AT1 receptor antagonist is selected from losartan, and vitamin B group is a vitamin B6; Wherein the content of angiotensin converting enzyme inhibitor is 5-40mg, and the content of AT1 receptor antagonist is 50-100mg, and the content of vitamin B group is 5-50mg.
Described angiotensin converting enzyme inhibitor is selected from enalapril, and the AT1 receptor antagonist is selected from losartan, and vitamin B group is a vitamin B12; Wherein the content of angiotensin converting enzyme inhibitor is 5-40mg, and the content of AT1 receptor antagonist is 50-100mg, and the content of vitamin B group is 0.25-2mg.
Described angiotensin converting enzyme inhibitor is selected from fosinopril, and the AT1 receptor antagonist is a valsartan, and vitamin B group is folic acid or calcium leucovorin; Wherein the content of angiotensin converting enzyme inhibitor is 10-40g, and the content 80-160mg of valsartan, the content of vitamin B group are 0.2-5mg.
Described angiotensin converting enzyme inhibitor is selected from fosinopril, and the AT1 receptor antagonist is a valsartan, and vitamin B group is a vitamin B6; Wherein the content of angiotensin converting enzyme inhibitor is 10-40mg, and the content 80-160mg of valsartan, the content of vitamin B group are 5-50mg.
Described angiotensin converting enzyme inhibitor is selected from fosinopril, and the AT1 receptor antagonist is a valsartan, and vitamin B group is a vitamin B12; Wherein the content of angiotensin converting enzyme inhibitor is 10-40mg, and the content 80-160mg of valsartan, the content of vitamin B group are 0.25-2mg.
Described angiotensin converting enzyme inhibitor is selected from benazepril, and the AT1 receptor antagonist is selected from irbesartan, and vitamin B group is folic acid or calcium leucovorin; Wherein the content of angiotensin converting enzyme inhibitor is 5-40mg, and the content of AT1 receptor antagonist is 150-300mg, and the content of vitamin B group is 0.2-5mg.
Described angiotensin converting enzyme inhibitor is selected from benazepril, and the AT1 receptor antagonist is selected from irbesartan, and vitamin B group is a vitamin B6; Wherein the content of angiotensin converting enzyme inhibitor is 5-40mg, and the content of AT1 receptor antagonist is 150-300mg, and the content of vitamin B group is 5-50mg.
Described angiotensin converting enzyme inhibitor is selected from benazepril, and the AT1 receptor antagonist is selected from irbesartan, and vitamin B group is a vitamin B12; Wherein the content of angiotensin converting enzyme inhibitor is 5-40mg, and the content of AT1 receptor antagonist is 150-300mg, and the content of vitamin B group is 0.25-2mg.
Described angiotensin converting enzyme inhibitor is selected from benazepril, and the AT1 receptor antagonist is selected from valsartan, and vitamin B group is folic acid or calcium leucovorin; Wherein the content of angiotensin converting enzyme inhibitor is 5-40mg, and the content of AT1 receptor antagonist is 80-160mg, and the content of vitamin B group is 0.2-5mg.
Described angiotensin converting enzyme inhibitor is selected from benazepril, and the AT1 receptor antagonist is selected from valsartan, and vitamin B group is a vitamin B6; Wherein the content of angiotensin converting enzyme inhibitor is 5-40mg, and the content of AT1 receptor antagonist is 80-160mg, and the content of vitamin B group is 5-50mg.
Described angiotensin converting enzyme inhibitor is selected from benazepril, and the AT1 receptor antagonist is selected from valsartan, and vitamin B group is a vitamin B12; Wherein the content of angiotensin converting enzyme inhibitor is 5-40mg, and the content of AT1 receptor antagonist is 80-160mg, and the content of vitamin B group is 0.25-2mg.
Described angiotensin converting enzyme inhibitor is selected from benazepril, and the AT1 receptor antagonist is selected from losartan, and vitamin B group is folic acid or calcium leucovorin; Wherein the content of angiotensin converting enzyme inhibitor is 5-40mg, and the content of AT1 receptor antagonist is 50-100mg, and the content of vitamin B group is 0.2-5mg.
Described angiotensin converting enzyme inhibitor is selected from benazepril, and the AT1 receptor antagonist is selected from losartan, and vitamin B group is a vitamin B6; Wherein the content of angiotensin converting enzyme inhibitor is 5-40mg, and the content of AT1 receptor antagonist is 50-100mg, and the content of vitamin B group is 5-50mg.
Described angiotensin converting enzyme inhibitor is selected from benazepril, and the AT1 receptor antagonist is selected from losartan, and vitamin B group is a vitamin B12; Wherein the content of angiotensin converting enzyme inhibitor is 5-40mg, and the content of AT1 receptor antagonist is 50-100mg, and the content of vitamin B group is 0.25-2mg.
Described angiotensin converting enzyme inhibitor is selected from fosinopril, and the AT1 receptor antagonist is a telmisartan, and vitamin B group is a folic acid; Wherein the content of angiotensin converting enzyme inhibitor is 10-40mg, and the content 20-80mg of telmisartan, the content of vitamin B group are 0.2-5mg.
Described angiotensin converting enzyme inhibitor is selected from lisinopril, and the AT1 receptor antagonist is a Candesartan, and vitamin B group is a folic acid; Wherein the content of angiotensin converting enzyme inhibitor is 5-40mg, and the content 8-32mg of Candesartan, the content of vitamin B group are 0.2-5mg.
Originally discover that the vitamin B group list when with angiotensin converting enzyme inhibitor, when the AT1 receptor antagonist share, can strengthen the hypotensive effect of medicine with slight hypotensive effect is arranged.Vitamin B group and angiotensin converting enzyme inhibitor, AT1 receptor antagonist share and can strengthen it causes target organ damage to hypertension protective effect.
Described pharmaceutical composition can be made into conventional tablet, conventional capsule, granule, slow releasing tablet, sublingual lozenge, oral cavity quick disintegrating slice, dispersible tablet, enteric coatel tablets, enteric coated capsule, delayed-release tablet, regularly/position releasing piece, slow releasing capsule, controlled release capsule, contain micropill or small pieces capsule, contain the dosage forms such as PH dependent form capsule, granule, oral liquid, membrane or patch of micropill or small pieces.
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition, can be made into common oral preparation, comprise conventional tablet, conventional capsule, granule etc., when making tablet described pharmaceutically acceptable carrier include help with reactive compound be mixed with the excipient of pharmaceutical formulation and accessory drugs such as starch, microcrystalline Cellulose, inorganic salts, sucrose, dextrin, lactose, Icing Sugar, glucose, sodium chloride, cysteine, citric acid and sodium sulfite etc.-kind or the compositions of several materials, belong to this area general knowledge.
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition, can be made into slow releasing tablet, comprise excipient and adjuvant etc.Described excipient and accessory drugs have comprised that the adjuvant of slow releasing function is solubility/insoluble salt and/or other adjuvant that plays slow releasing function of hypromellose and/or ethyl cellulose and/or polyacrylic resin class and/or polycarboxy ethene and/or alginic acid, the hypromellose employing includes the extensive stock of hydroxypropyl methylcellulose (HPMC) such as U.S. many elegant (Methocel) of all size, ethyl cellulose adopts the extensive stock that includes ethyl cellulose (EC), and the polyacrylic resin class adopts and includes polyacrylic resin II, the acrylic resin of III class or analog such as all size (Eudragit).Above-mentioned adjuvant is porogen, binding agent, lubricant, membrane material, solvent or other adjuvant, and porogen can adopt sucrose, mannitol, starch, Pulvis Talci, silicon dioxide etc.; Binding agent can adopt polyvinylpyrrolidone, hypromellose etc.; Wetting agent can adopt the ethanol-water solution of water, dehydrated alcohol, various concentration; Lubricant can adopt stearic acid, magnesium stearate, Pulvis Talci, starch, paraffin etc.; Solubilizing agent can be adopted tartaric acid, citric acid etc.; Emulsifying agent can adopt span80/span85 etc.; Membrane material can adopt polyvinyl alcohol, hydroxyl methylcellulose, hyetellose, hymetellose, methylcellulose etc.; Foaming agent can adopt basic magnesium carbonate, sodium bicarbonate etc.; Bleach activator can adopt hexadecanol, octadecanol, Cera Flava etc.; Solvent can adopt dehydrated alcohol, ethanol, water etc.
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition, can be made into controlled release tablet, comprise that active medicine has reached the adjuvant of controlled release effect.The above-mentioned adjuvant that plays the controlled release effect is polyoxyethylene and/or hypromellose and/or ethyl cellulose and/or sodium chloride and/or lactose and/or mannitol and/or fructose and/or glucose and/or sucrose/or low-substituted hydroxypropyl cellulose and/or cross-linking sodium carboxymethyl cellulose and/or crospolyvinylpyrrolidone and/or cellulose acetate.Above-mentioned adjuvant is pharmaceutical carrier, expanding material, permeation-promoter, solubilizing agent, binding agent, wetting agent, lubricant, coloring agent, porogen, membrane material, antiplastering aid, plasticizer, lucifuge agent, solvent.Pharmaceutical carrier, expanding material can adopt polyoxyethylene, hypromellose, ethyl cellulose, Glyceryl Behenate class etc.; Permeation-promoter can adopt sodium chloride, lactose, mannitol, fructose, glucose, sucrose etc.; But solubilizing agent can be adopted sodium lauryl sulphate poloxamer etc.; Binding agent can adopt polyvinylpyrrolidone, hypromellose etc.; Wetting agent can adopt the ethanol-water solution of water, dehydrated alcohol, various concentration; Lubricant can adopt stearic acid, magnesium stearate, Pulvis Talci, starch, paraffin etc.; Coloring agent can adopt iron oxide red, iron oxide yellow etc.; Porogen can adopt sucrose, mannitol, Polyethylene Glycol, titanium dioxide, Pulvis Talci, silicon dioxide etc.; Membrane material can adopt cellulose acetate, ethyl cellulose etc.; Solvent can adopt acetone, dehydrated alcohol, ethanol, water etc.
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition, can be made into sublingual lozenge, oral cavity quick disintegrating slice or dispersible tablet etc., comprise excipient and adjuvant etc.Described excipient and adjuvant have low substituted hydroxy-propyl methylcellulose, microcrystalline Cellulose, carboxymethyl starch sodium, cross-linked carboxymethyl cellulose sodium, crospolyvinylpyrrolidone, processing agar and mannitol, lactose etc.
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition; can be made into enteric coatel tablets or enteric coated capsule etc.; comprise excipient and adjuvant etc.; described excipient and adjuvant have starch; microcrystalline Cellulose; inorganic salts; hydroxypropyl emthylcellulose; ethyl cellulose; the polyacrylic resin class; polycarboxy ethene; the solubility of alginic acid/insoluble salt; octadecanol; stearic acid; sucrose; dextrin; lactose; Icing Sugar; glucose; sodium chloride; cysteine; the compositions of one or more materials of citric acid and sodium sulfite etc.; enteric-coating material comprises: Lac; the cellulose acetate phthalate ester; crylic acid resin (as Eudragit L and S type etc.); the polyvinyl acetate phthalic acid ester; phthalic acid hypromellose ester; succinic acid acetic acid hydroxypropyl methylcellulose, and plasticizer is (as diethyl phthalate; Polyethylene Glycol; propylene glycol; glycerol triacetate; dimethyl phthalate; dibutyl sebacate; triethyl citrate; tributyl citrate; CitroflexA-2; the acetylated monoglycerides of Oleum Ricini and percentage etc.) with various medicaments adjuvant such as porogen (as PEG6000 etc.).
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition; can be made into delayed-release tablet or timing (position) releasing piece; comprise excipient and adjuvant; described excipient and adjuvant have starch; microcrystalline Cellulose; inorganic salts; hydroxypropyl emthylcellulose; ethyl cellulose; the polyacrylic resin class; polycarboxy ethene; the solubility of alginic acid/insoluble salt; octadecanol; stearic acid; sucrose; dextrin; lactose; Icing Sugar; glucose; sodium chloride; cysteine; the compositions of one or more materials of citric acid and sodium sulfite etc.; described coating material that postpones release or regularly (position) release comprises: Lac; the cellulose acetate phthalate ester; ethyl cellulose; hydroxypropyl emthylcellulose; hydroxypropyl cellulose; crylic acid resin (as Eudragit L and S type etc.); the polyvinyl acetate phthalic acid ester; phthalic acid hypromellose ester; succinic acid acetic acid hydroxypropyl methylcellulose; hydroxypropylmethylcellulose acetate methylcellulose phthalate ester, and plasticizer is (as diethyl phthalate; Polyethylene Glycol; propylene glycol; glycerol triacetate; dimethyl phthalate; dibutyl sebacate; triethyl citrate; tributyl citrate; CitroflexA-2; acetylated monoglycerides of Oleum Ricini and percentage or the like) with various medicaments adjuvant such as porogen (as PEG6000 etc.).
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition; can be made into slow releasing capsule; controlled release capsule; the capsule that contains micropill or small pieces; contain the PH dependent form capsule of micropill or small pieces etc.; comprise excipient and adjuvant; described excipient and adjuvant have starch; microcrystalline Cellulose; inorganic salts; hydroxypropyl emthylcellulose; ethyl cellulose; the polyacrylic resin class; polycarboxy ethene; the solubility of alginic acid/insoluble salt; octadecanol; stearic acid; sucrose; dextrin; lactose; Icing Sugar; glucose; sodium chloride; cysteine; the compositions of one or more materials of citric acid and sodium sulfite etc., coating material comprises: Lac; cellulose acetate; the cellulose acetate phthalate ester; ethyl cellulose; hydroxypropyl emthylcellulose; hydroxypropyl cellulose; crylic acid resin (as Eudragit series); the polyvinyl acetate phthalic acid ester; phthalic acid hypromellose ester; succinic acid acetic acid hydroxypropyl methylcellulose; hydroxypropylmethylcellulose acetate methylcellulose phthalate ester; mono stearate glyceryl ester and plasticizer are (as diethyl phthalate; Polyethylene Glycol; propylene glycol; glycerol triacetate; dimethyl phthalate; dibutyl sebacate; triethyl citrate; tributyl citrate; CitroflexA-2; acetylated monoglycerides of Oleum Ricini and percentage or the like) with various medicaments adjuvant such as porogen (as PEG6000 etc.).
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition, can be made into dosage forms such as granule, oral liquid, membrane, patch.Make patch; described pharmaceutically acceptable carrier includes excipient and the accessory drugs that helps reactive compound is mixed with pharmaceutical formulation during membrane; as polyvinyl alcohol, Triafol T, ethylene-vinyl acetate copolymer, polyvinylpyrrolidone, polyacrylamide, polyisobutylene class pressure sensitive adhesive, crylic acid resin pressure sensitive adhesive, silicone pressure sensitive adhesive etc.; and polyvinyl fluoride, polyethylene, aluminium foil, polypropylene, polyester etc. be by lining material, the compositions of one or more materials of protecting film such as polyethylene, polystyrene, polypropylene etc.
Preparation of the present invention can use or use in turn with any order simultaneously, and is best to use simultaneously.Comprise in the above-mentioned use simultaneously that best uses with fixed combination with fixed combination and on-fixed combination.
Preparation of the present invention can be taken once or twice every day, perhaps with slow release or controlled release mode every day or every other day or at interval a few days take once, take once wherein preferred every day.
Described pharmaceutical composition can flexible using with " Combined drug box " form.Above-mentioned " Combined drug box " is a kind of case type container, the drug regimen of built-in multiple dosage form, and take description." Combined drug box " more is applicable to personalized medicine.
Pharmaceutical composition of the present invention is used for prevention, treats and delays hypertension and relevant disease thereof, the target organ damage that hypertension causes comprises left ventricular hypertrophy, angina pectoris, myocardial infarction, heart failure, optimum arteriolar nephrosclerosis, pernicious arteriolar nephrosclerosis, renal failure, retinal arteriosclerosis, hypertension retinopathy, apoplexy etc., and and the closely-related disease of hypertension, atherosclerosis, coronary heart disease, dissection of aorta and diabetes.
The invention has the beneficial effects as follows: the invention provides a kind of pharmaceutical composition; this pharmaceutical composition can improve the curative effect of depressor; the intensifier target organ protection, the incidence rate of complication such as minimizing retinal hemorrhage, angina pectoris, myocardial infarction, apoplexy, heart failure, renal failure.The patient is taken medicine conveniently, reduce medical expense.
The present invention will be further described below in conjunction with the specific embodiment, is not limitation of the invention, and the equal replacement of all any this areas of carrying out according to content of the present invention all belongs to protection scope of the present invention.
The specific embodiment
Embodiment 1: preparation of pharmaceutical compositions
Prescription
Enalapril maleate 5.0g
Irbesartan 150.0g
Folic acid 0.4g
Microcrystalline Cellulose 35.0g
Starch 45.0g
Carboxymethylstach sodium 5.0g
5% 30 POVIDONE K 30 BP/USP-30 QS
Magnesium stearate QS
Make 1000
Preparation technology:
(1) gets enalapril maleate, irbesartan, the folic acid of recipe quantity, cross behind 100 mesh sieves standby by equivalent incremental method mix homogeneously;
(2) other adjuvants are crossed behind 100 mesh sieves 75 ℃ of dryings 2 hours respectively;
(3) press behind the starch, microcrystalline Cellulose, carboxymethylstach sodium mixing of recipe quantity again and mixed crude drug equivalent incremental method mix homogeneously;
(4) add binding agent and make soft material in right amount, 24 mesh sieves are granulated, 20 mesh sieve granulate, 40-45 ℃ of drying;
(5) dried granule adds an amount of magnesium stearate mixing, tabletting behind the assay.
Embodiment 2: preparation of pharmaceutical compositions
Prescription
Enalapril maleate 5.0g
Irbesartan 150.0g
Folic acid 0.8g
Microcrystalline Cellulose 35.0g
Starch 45.0g
Carboxymethylstach sodium 5.0g
5% 30 POVIDONE K 30 BP/USP-30 QS
Magnesium stearate QS
Make 1000
Preparation technology:
(1) gets enalapril maleate, irbesartan, the folic acid of recipe quantity, cross behind 100 mesh sieves standby by equivalent incremental method mix homogeneously;
(2) other adjuvants are crossed behind 100 mesh sieves 75 ℃ of dryings 2 hours respectively;
(3) press behind the starch, microcrystalline Cellulose, carboxymethylstach sodium mixing of recipe quantity again and mixed crude drug equivalent incremental method mix homogeneously;
(4) add binding agent and make soft material in right amount, 24 mesh sieves are granulated, 20 mesh sieve granulate, 40-45 ℃ of drying;
(5) dried granule adds an amount of magnesium stearate mixing, tabletting behind the assay.
Embodiment 3: preparation of pharmaceutical compositions
Prescription
Fosinopril 10.0g
Valsartan 80.0g
Calcium leucovorin 5.0g
Starch 20.0g
Microcrystalline Cellulose 15.0g
Carboxymethylstach sodium 5.0g
Lactose 30.0g
Magnesium stearate QS
Make 1000
Preparation technology:
According to the prescription proportioning, get lactose, microcrystalline Cellulose, starch, carboxymethylstach sodium and in about 100 ℃, distinguish dry about 2 hours, cross 100 mesh sieves; After crude drug crossed 100 mesh sieves, with above-mentioned adjuvant by equivalent incremental method mix homogeneously, with No. 3 capsule fills.
Embodiment 4: preparation of pharmaceutical compositions
Hydrochloric acid benazepril 10.0g
Irbesartan 150.0g
Vitamin B6 5.0g
Starch 20.0g
Microcrystalline Cellulose 15.0g
Carboxymethylstach sodium 5.0g
Lactose 30.0g
Magnesium stearate QS
Make 1000
Preparation technology:
According to the prescription proportioning, get lactose, microcrystalline Cellulose, starch, carboxymethylstach sodium and in about 100 ℃, distinguish dry about 2 hours, cross 100 mesh sieves; After crude drug crossed 100 mesh sieves, with above-mentioned adjuvant by equivalent incremental method mix homogeneously, with No. 3 capsule fills.
Embodiment 5: enalapril+irbesartan+folic acid-collaborative hypotensive effect
Spontaneous hypertensive rat is available from Chinese Academy of Sciences's Shanghai Experimental Animal Center, and rat blood pressure raises after 6 ages in week, and 8-10 significantly raise after age in week, measured 1 week of rat blood pressure (the 1st, 6 day), and the rat of getting blood pressure stabilization is used for experiment.With the spontaneous hypertensive rat random packet, be respectively model group (giving solvent), enalapril group (0.5mg/kg), irbesartan group (20mg/kg), folic acid group (0.8mg/kg), enalapril+irbesartan+1 group of (0.5+10+0.2) mg/kg of folic acid, enalapril+irbesartan+2 groups of (0.5+10+0.4) mg/kg of folic acid, enalapril+irbesartan+3 groups of (0.5+10+0.8) mg/kg of folic acid, other establishes the normal control group.Gastric infusion, continuous two weeks.Measure before the administration respectively and administration after the different time blood pressure, calculate the blood pressure lowering percentage rate: (SBP
Before the administration-SBP
After the administration)/SBP
Before the administration* 100, the results are shown in Table 1.
Experimental example 6: the synergism of benazepril+irbesartan+folic acid-target organ protection function
With the narrow Wistar rat of 0.2mm silver brain clip left renal artery, 14-15 after week rat blood pressure raise to surpass 150mmHg above be hypertension animal model.Random packet, if model control group, benazepril group (0.5mg/kg), irbesartan group (20mg/kg), folic acid group (0.8mg/kg), benazepril+irbesartan+1 group of (0.5+10+0.2) mg/kg of folic acid, benazepril+irbesartan+2 groups of (0.5+10+0.4) mg/kg of folic acid, benazepril+irbesartan+3 groups of (0.5+10+0.8) mg/kg of folic acid, other gets 12 normal rats as the normal control group.Gastric infusion, is measured 24h urine α I microsphere egg respectively from, left chamber end diastolic pressure (LVEDP), isovolumic relaxation phase time constant (T), the heavy index (left ventricle mg/ body weight g) in chamber at continuous 13-15 week.The results are shown in Table 2.
Claims (9)
1. pharmaceutical composition is by angiotensin converting enzyme inhibitor, the AT of treatment effective dose
1In receptor antagonist, the vitamin B group one or more and pharmaceutically acceptable carrier are formed; Wherein the content of angiotensin converting enzyme inhibitor is 0.5-100mg, AT
1The content of receptor antagonist is 4-800mg, and the content of vitamin B group is 0.1-50mg.
2. pharmaceutical composition according to claim 1 is characterized in that: described angiotensin converting enzyme inhibitor is selected from captopril, enalapril, perindopril, cilazapril, benazepril, ramipril (Ramipril), lisinopril, quinapril, fosinopril, delapril, moexipril, spirapril, imidapril, trandolapril and alacepril.
3. pharmaceutical composition according to claim 2, it is characterized in that: the content of described captopril is 12.5-100mg, the content of enalapril is 2.5-40mg, the content of perindopril is 2-16mg, the content of cilazapril is 1.25-5mg, the content of benazepril is 2.5-40mg, the content of ramipril is 1.25-20mg, the content of lisinopril is 2.5-80mg, the content of quinapril is 5-80mg, the content of fosinopril is 10-80mg, and the content of delapril is 15-120mg, and the content of moexipril is 3.75-30mg, the content of spirapril is 3-30mg, the content of imidapril is 2.5-40mg, and the content of trandolapril is 0.5-4mg, and the content of alacepril is 12.5-100mg.
4. pharmaceutical composition according to claim 1 is characterized in that: described AT
1Receptor antagonist is selected from losartan, valsartan, irbesartan, telmisartan, Candesartan, eprosartan, Olmesartan and Tasosartan.
5. pharmaceutical composition according to claim 4, it is characterized in that: the content of described losartan is 25-200mg, the content of valsartan is 40-320mg, the content of irbesartan is 75-600mg, the content of telmisartan is 20-160mg, and the content of Candesartan is 4-64mg, and the content of eprosartan is 200-800mg, the content of Olmesartan is 20-80mg, and the content of Tasosartan is 0-300mg.
6. pharmaceutical composition according to claim 1 is characterized in that: described vitamin B group is selected from one or more in vitamin B6, vitamin B12, folic acid or the calcium leucovorin.
7. pharmaceutical composition according to claim 6 is characterized in that: the content of described folic acid class material is 0.2-10mg, and vitamin B12 content is 0.1-2mg, and vitamin B6 content is 0.5-50mg.
8. according to any one described pharmaceutical composition in the claim 1 to 7, it is characterized in that: described pharmaceutical composition can be made into conventional tablet, conventional capsule, granule, slow releasing tablet, sublingual lozenge, oral cavity quick disintegrating slice, dispersible tablet, enteric coatel tablets, enteric coated capsule, delayed-release tablet, regularly/dosage forms such as position releasing piece, slow releasing capsule, controlled release capsule, the PH dependent form capsule that contains micropill or small pieces, granule, oral liquid, membrane, patch.
9. according to any one described pharmaceutical composition in the claim 1 to 7, it is characterized in that: described pharmaceutical composition is used for the preparation prevention, treatment and delay hypertension and relevant disease thereof, the target organ damage that hypertension causes comprises left ventricular hypertrophy, angina pectoris, myocardial infarction, heart failure, optimum arteriolar nephrosclerosis, pernicious arteriolar nephrosclerosis, renal failure, retinal arteriosclerosis, the hypertension retinopathy, apoplexy etc., and and closely-related disease of hypertension such as atherosclerosis, coronary heart disease, purposes in the medicine of main Egyptian interlayer and diabetes.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910082591A CN101869710A (en) | 2009-04-24 | 2009-04-24 | Antihypertensive medical composite |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910082591A CN101869710A (en) | 2009-04-24 | 2009-04-24 | Antihypertensive medical composite |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101869710A true CN101869710A (en) | 2010-10-27 |
Family
ID=42994915
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200910082591A Pending CN101869710A (en) | 2009-04-24 | 2009-04-24 | Antihypertensive medical composite |
Country Status (1)
| Country | Link |
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| CN (1) | CN101869710A (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102641253A (en) * | 2012-05-07 | 2012-08-22 | 山东省医药工业研究所 | Valsartan sustained release tablet and preparation method thereof |
| CN110075304A (en) * | 2019-05-29 | 2019-08-02 | 四川大学华西医院 | A kind of medical composition and its use for treating osteoarthritis |
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| CN110075304A (en) * | 2019-05-29 | 2019-08-02 | 四川大学华西医院 | A kind of medical composition and its use for treating osteoarthritis |
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