CN101590084A - The pharmaceutical composition that contains angiotensin-convertion enzyme inhibitor, vitamin B group and Folium Ginkgo extract - Google Patents
The pharmaceutical composition that contains angiotensin-convertion enzyme inhibitor, vitamin B group and Folium Ginkgo extract Download PDFInfo
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Abstract
The present invention relates in the vitamin B group of a kind of, the pharmaceutical dosage in a kind of angiotensin-convertion enzyme inhibitor (ACEI) that contains pharmaceutical dosage and active metabolite or its officinal salt one or more, the Folium Ginkgo extract (GbE) of pharmaceutical dosage and the pharmaceutical composition of pharmaceutically suitable carrier.And this pharmaceutical composition is used for the treatment of, prevents in preparation or delays purposes in the medicine of apoplexy.The medicine that pharmaceutical composition provided by the invention is made is treating, preventing or delay to be better than simple antihypertensive drugs aspect the apoplexy disease, and more convenient patient is taken.The invention belongs to pharmaceutical field.
Description
Technical field
The present invention relates in the vitamin B group of a kind of angiotensin-convertion enzyme inhibitor that contains pharmaceutical dosage, pharmaceutical dosage one or more, the Folium Ginkgo extract of pharmaceutical dosage and the pharmaceutical composition of pharmaceutically suitable carrier, and this pharmaceutical composition is used for preventing, treating or delay the purposes of the medicine of apoplexy in preparation.The invention belongs to pharmaceutical field.
Background technology
In China, apoplexy is one of murderous main reason, also is to continue to disable and lose the main cause of self care ability.This just makes selects ideal antihypertensive drugs, further reduces apoplexy danger seem more important [model profit, the relation of control hypertension, hyperlipidemia and prevention of brain apoplexy, the medical officer people, 2004,47 (8): 479-481 in blood pressure lowering; Zhang Hongye etc., the perspective study of China's ten groups of crowd's apoplexy risk factor, Chinese chronic disease prevention and control, 1996,4 (4): 150-152].
The final purpose of hypertension prevention and control is control risk factor, protection target organ and improves patient's survival rate, and angiotensin-convertion enzyme inhibitor (ACEI) hypotensor has irreplaceable effect to this, be the most frequently used medicine of clinic control blood pressure.Enalapril (enalapril) is that a kind of nothing is dredged basic, long-acting, oral ACEI, and only need once oral every day, and common dose is 5-20mg, clinical be widely used in treatment gently, severe hypertension is sick.Other clinical ACEI commonly used also have: benazepril (benazepril), lisinopril (lisinopril), fosinopril (fosinopril), imidapril (imidapril), perindopril (perindopril), ramipril (ramipril), captopril (captopril) etc.
Also there is certain problem clinically in the ACEI antihypertensive drugs, and at first its efficacy of antihypertensive treatment has certain limit, and lot of documents report total effective rate only is about 50%～60%, 40%～50% invalid or curative effect is not remarkable.Compare with other depressor, the target organ protection function of ACEI depressor 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 mortality, all cardiovascular events, myocardial infarction and heart failure, and the result does not find that ACEI is better than old medicine aspect above-mentioned.
B supports one's family and have B1, B2, B6, B12, B4, folic acid, nicotinic acid, pantothenic acid and biotin etc.
Vitamin B12 is cobalamine again, participates in making the bone marrow erythrocyte, prevents and treats pernicious anemia.Folic acid is a kind of vitamin B group that extensively is present in the green vegetables, and chemical name is " pteroylglutamic acid ".Folic acid has important Nutrition to human body.Human (or other animal) can cause megaloblastic anemia and leukopenia as lacking folic acid.
Folium Ginkgo extract (GbE) is the dried leaves extract of Ginkgoaceae plant Ginkgo biloba (Ginkgo biloba L.).Make by modern extraction process,, inherent fragrance is arranged, bitter in the mouth for light yellowish brown flowable powder.Main chemism composition is total flavones and total lactone.Up to the present kind surplus the Folium Ginkgo extract of known its chemical constituent reaches 160.Mainly contain flavonoid, terpenoid, phenols, alkaloid, polyisoamylene, quininic acid, linoleic acid, boa oxalic acid, ascorbic acid, a-hexenoic aldehyde, Ginnol, bilobanone etc.
Summary of the invention
One of purpose of the present invention provides a kind of pharmaceutical composition, this pharmaceutical composition contain in the vitamin B group of a kind of, the pharmaceutical dosage in the angiotensin-convertion enzyme inhibitor (ACEI) of pharmaceutical dosage and active metabolite or its officinal salt one or more, Folium Ginkgo extract and pharmaceutically suitable carrier of pharmaceutical dosage.The medicine that pharmaceutical composition provided by the invention is made, on the basis of the hypertensive effective effect of treatment, the beneficial effect with certain prevention of brain apoplexy.
In clinical practice or the scientific research document of having delivered, we do not find that as yet ACEI class antihypertensive drug, vitamin B group and Folium Ginkgo extract unite the treatment that is used for cardiovascular disease.In experiment, we surprisingly find, the medicine that the compositions of the vitamin B group of ACEI class antihypertensive drug that contains pharmaceutical dosage provided by the invention and pharmaceutical dosage and the Folium Ginkgo extract of pharmaceutical dosage is made, except that hypertension is had the excellent curative, obvious prevention of brain apoplexy, thus the incidence rate of apoplexy reduced.The part Study results suggest of our ongoing pharmaceutical composition molecular biology mechanism of action: ACEI class antihypertensive drug merges the use in conjunction of vitamin B group and Folium Ginkgo extract, except that said composition produces the more stable effect that brings high blood pressure down, can also be by the generation of following effect prophylaxis of hypertension complication: 1. protect vascular endothelial cell, avoid glycosylation dead end product and LDL oxidation and modify the endothelial injury that causes; 2. activate anticoagulation system, increase the release of vessel dilator and platelet modifying factor, reduce thrombosis, strengthen being connected of endotheliocyte and tissue-type plasminogen activator (t-PA), further promote the function of fibrinolytic system.
For achieving the above object, the present invention is by the following technical solutions:
A kind of pharmaceutical composition, contain in the vitamin B group of a kind of, the pharmaceutical dosage in the angiotensin-convertion enzyme inhibitor (ACEI) of pharmaceutical dosage and active metabolite or its officinal salt one or more, Folium Ginkgo extract and pharmaceutically suitable carrier of pharmaceutical dosage.
According to the present invention, described angiotensin-convertion enzyme inhibitor and active metabolite thereof or its officinal salt comprise enalapril (enalapril), benazepril (benazepril), lisinopril (lisinopril), fosinopril (fosinopril), imidapril (imidapril), ramipril (ramipril), captopril (captopril), quinapril (quinapril), cilazapril (cilazpril), perindopril (perindopril), delapril (delapril), moexipril (moexipril), spirapril (spirapril), trandolapril (trandolapril) and alacepril (alacepril) and active metabolite or its officinal salt.
By experimental study, the content of ACEI is respectively: enalapril 2.5mg～40mg, benazepril 2.5mg～40mg, lisinopril 2.5mg～80mg, fosinopril 10mg～80mg, imidapril 2.5mg～40mg, ramipril 1.25mg～20mg, captopril 12.5mg～100mg, quinapril 5mg～80mg, cilazapril 1.25mg～5mg, perindopril 2mg～16mg, delapril 15mg～120mg, moexipril 3.75mg～30mg, spirapril 3mg～30mg, trandolapril 0.5mg～4mg, alacepril 12.5mg～100mg, the active metabolite of above-mentioned substance or salt content are equal to corresponding above-mentioned substance content.
The better in the present invention treatment effective dose of these medicines is respectively: enalapril 5mg～40mg, benazepril 5mg～40mg, lisinopril 5mg～40mg, fosinopril 10mg～40mg, imidapril 2.5mg～10mg, ramipril 2.5mg～20mg, captopril 25mg～100mg, quinapril 10mg～40mg, cilazapril 2.5mg～5mg, perindopril 4mg～8mg, delapril 15mg～60mg, moexipril 7.5mg～30mg, spirapril 3mg～15mg, trandolapril 0.5mg～2mg, alacepril 25mg～100mg, the active metabolite of above-mentioned substance or salt content are equal to corresponding above-mentioned substance content.
According to the present invention, described vitamin B group is selected from one or more in vitamin B6, vitamin B12 and the folic acid.Vitamin B6 among the present invention comprises the derivant of pyridoxol, 2-methyl-3-hydroxy-4-formyl-5-hydroxymethylpyridine., pyridoxamine, pyridoxin phosphate, pyridoxal 5-phosphate, phosphopyridoxamine and above-mentioned substance and metabolism and/or generate the material of this compounds in vivo, the preferred 2mg-50mg of the dosage of vitamin B6 among the present invention, the dosage of the vitamin B6 among the present invention can be replaced to produce equivalent effect with above-mentioned substance; Vitamin B12 among the present invention comprises the derivant of cobalamine, mecobalamin element, 5 '-deoxyadenosyl cobalamin, hydroxocobalamine, cyanocobalamin and above-mentioned substance and metabolism and/or generate the material of this compounds in vivo, the preferred 0.001mg-2mg of the dosage of vitamin B12 among the present invention, the dosage of the vitamin B12 among the present invention can be replaced to produce equivalent effect with above-mentioned substance; Folic acid comprises the active metabolite of folic acid, formyl tetrahydrofolic acid, L-methopterin, folic acid officinal salt, folic acid or folic acid officinal salt and metabolism and/or generate the material of folic acid in vivo, the preferred 0.1mg-5mg of the dosage of folic acid among the present invention, the dosage of the folic acid among the present invention can be replaced to produce equivalent effect with above-mentioned substance.
According to the present invention, described Folium Ginkgo extract (GbE) is the dried leaves extract of Ginkgoaceae plant Ginkgo biloba (Ginkgo biloba L.), extracts by the contemporary standard metallization processes to form, and for light yellowish brown flowable powder, inherent fragrance is arranged, bitter in the mouth.Main chemism composition is total flavones (account for 24%, mainly comprise kaempferol, Quercetin and 3 kinds of single flavone of isorhamnetin and derivant thereof) and total lactone (accounting for 6%).The preferred 40mg-240mg of the dosage of Folium Ginkgo extract among the present invention.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is an enalapril maleate, and content is the amount that is equivalent to the 5mg-40mg enalapril; Described vitamin B group is a folic acid, and content is 0.1mg-5mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is an enalapril maleate, and content is the amount that is equivalent to the 5mg-40mg enalapril; Described vitamin B group is a vitamin B6, and content is 2mg-50mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is an enalapril maleate, and content is the amount that is equivalent to the 5mg-40mg enalapril; Described vitamin B group is a vitamin B12, and content is 0.001mg-2mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is an enalaprilat, and content is the amount that is equivalent to the 5mg-40mg enalapril; Described vitamin B group is a folic acid, and content is 0.1mg-5mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is an enalaprilat, and content is the amount that is equivalent to the 5mg-40mg enalapril; Described vitamin B group is a vitamin B6, and content is 2mg-50mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is an enalaprilat, and content is the amount that is equivalent to the 5mg-40mg enalapril; Described vitamin B group is a vitamin B12, and content is 0.001mg-2mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a benazepril hydrochloride, and content is the amount that is equivalent to the 5mg-40mg benazepril; Described vitamin B group is a folic acid, and content is 0.1mg-5mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a benazepril hydrochloride, and content is the amount that is equivalent to the 5mg-40mg benazepril; Described vitamin B group is a vitamin B6, and content is 2mg-50mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a benazepril hydrochloride, and content is the amount that is equivalent to the 5mg-40mg benazepril; Described vitamin B group is a vitamin B12, and content is 0.001mg-2mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a benazeprilat, and content is the amount that is equivalent to the 5mg-40mg benazepril; Described vitamin B group is a folic acid, and content is 0.1mg-5mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a benazeprilat, and content is the amount that is equivalent to the 5mg-40mg benazepril; Described vitamin B group is a vitamin B6, and content is 2mg-50mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a benazeprilat, and content is the amount that is equivalent to the 5mg-40mg benazepril; Described vitamin B group is a vitamin B12, and content is 0.001mg-2mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a lisinopril, and content is 5mg-40mg; Described vitamin B group is a folic acid, and content is 0.1mg-5mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a lisinopril, and content is 5mg-40mg; Described vitamin B group is a vitamin B6, and content is 2mg-50mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a lisinopril, and content is 5mg-40mg; Described vitamin B group is a vitamin B12, and content is 0.001mg-2mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a fosinopril, and content is 10mg-40mg; Described vitamin B group is a folic acid, and content is 0.1mg-5mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a fosinopril, and content is 10mg-40mg; Described vitamin B group is a vitamin B6, and content is 2mg-50mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a fosinopril, and content is 10mg-40mg; Described vitamin B group is a vitamin B12, and content is 0.001mg-2mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is an imidapril, and content is 2.5mg-10mg; Described vitamin B group is a folic acid, and content is 0.1mg-5mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is an imidapril, and content is 2.5mg-10mg; Described vitamin B group is a vitamin B6, and content is 2mg-50mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is an imidapril, and content is 2.5mg-10mg; Described vitamin B group is a vitamin B12, and content is 0.001mg-2mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a ramipril, and content is 2.5mg-20mg; Described vitamin B group is a folic acid, and content is 0.1mg-5mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a ramipril, and content is 2.5mg-20mg; Described vitamin B group is a vitamin B6, and content is 2mg-50mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a ramipril, and content is 2.5mg-20mg; Described vitamin B group is a vitamin B12, and content is 0.001mg-2mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a captopril, and content is 25mg-100mg; Described vitamin B group is a folic acid, and content is 0.1mg-5mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a captopril, and content is 25mg-100mg; Described vitamin B group is a vitamin B6, and content is 2mg-50mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a captopril, and content is 25mg-100mg; Described vitamin B group is a vitamin B12, and content is 0.001mg-2mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a quinapril, and content is 10mg-40mg; Described vitamin B group is a folic acid, and content is 0.1mg-5mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a quinapril, and content is 10mg-40mg; Described vitamin B group is a vitamin B6, and content is 2mg-50mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a quinapril, and content is 10mg-40mg; Described vitamin B group is a vitamin B12, and content is 0.001mg-2mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a cilazapril, and content is 2.5mg-5mg; Described vitamin B group is a folic acid, and content is 0.1mg-5mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a cilazapril, and content is 2.5mg-5mg; Described vitamin B group is a vitamin B6, and content is 2mg-50mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a cilazapril, and content is 2.5mg-5mg; Described vitamin B group is a vitamin B12, and content is 0.001mg-2mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a perindopril, and content is 4mg-8mg; Described vitamin B group is a folic acid, and content is 0.1mg-5mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a perindopril, and content is 4mg-8mg; Described vitamin B group is a vitamin B6, and content is 2mg-50mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a perindopril, and content is 4mg-8mg; Described vitamin B group is a vitamin B12, and content is 0.001mg-2mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a delapril, and content is 15mg-60mg; Described vitamin B group is a folic acid, and content is 0.1mg-5mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a delapril, and content is 15mg-60mg; Described vitamin B group is a vitamin B6, and content is 2mg-50mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a delapril, and content is 15mg-60mg; Described vitamin B group is a vitamin B12, and content is 0.001mg-2mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a moexipril, and content is 7.5mg-30mg; Described vitamin B group is a folic acid, and content is 0.1mg-5mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a moexipril, and content is 7.5mg-30mg; Described vitamin B group is a vitamin B6, and content is 2mg-50mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a moexipril, and content is 7.5mg-30mg; Described vitamin B group is a vitamin B12, and content is 0.001mg-2mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a spirapril, and content is 3mg-15mg; Described vitamin B group is a folic acid, and content is 0.1mg-5mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a spirapril, and content is 3mg-15mg; Described vitamin B group is a vitamin B6, and content is 2mg-50mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a spirapril, and content is 3mg-15mg; Described vitamin B group is a vitamin B12, and content is 0.001mg-2mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a trandolapril, and content is 0.5mg-2mg; Described vitamin B group is a folic acid, and content is 0.1mg-5mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a trandolapril, and content is 0.5mg-2mg; Described vitamin B group is a vitamin B6, and content is 2mg-50mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is a trandolapril, and content is 0.5mg-2mg; Described vitamin B group is a vitamin B12, and content is 0.001mg-2mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is an alacepril, and content is 25mg-100mg; Described vitamin B group is a folic acid, and content is 0.1mg-5mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is an alacepril, and content is 25mg-100mg; Described vitamin B group is a vitamin B6, and content is 2mg-50mg; Described Folium Ginkgo extract content is 40mg-240mg.
In the pharmaceutical composition provided by the invention, described angiotensin-convertion enzyme inhibitor is an alacepril, and content is 25mg-100mg; Described vitamin B group is a vitamin B12, and content is 0.001mg-2mg; Described Folium Ginkgo extract content is 40mg-240mg.
According to the present invention, active component in the pharmaceutical composition is the solvent in the compositions, one of them active component comes from a kind of in the ACEI class antihypertensive drug, and an active component is from one or more vitamin B group, and an active component is from Folium Ginkgo extract.The dosage form of this pharmaceutical composition includes but not limited to conventional tablet, bilayer tablet, multilayer tablet, slow releasing tablet, the single chamber controlled release tablet, two chambers controlled release tablet, the pore type controlled release tablet, sublingual lozenge, oral cavity quick disintegrating slice, dispersible tablet, enteric coatel tablets, granule, pill, enteric coated capsule, delayed-release tablet, regularly/the position releasing piece, conventional capsule, slow releasing capsule, controlled release capsule, the capsule that contains micropill or small pieces, the pH dependent form capsule that contains micropill or small pieces, oral liquid, membrane or patch, what should particularly point out is to contain ACEI class antihypertensive drug, the pharmaceutical composition of vitamin B group and Folium Ginkgo extract is made tablet or capsule.
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition, can be made into common oral preparation, comprise conventional tablet, conventional capsule, granule etc., described pharmaceutically suitable carrier includes excipient and the accessory drugs that helps reactive compound is mixed with pharmaceutical formulation when making tablet, compositions as one or more materials of starch, microcrystalline Cellulose, inorganic salts, sucrose, dextrin, lactose, sodium chloride, citric acid and sodium sulfite etc. belongs to this area general knowledge.
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition, can be made into slow releasing preparation, comprise excipient and adjuvant etc.Described excipient and adjuvant have comprised that the adjuvant of slow releasing function is that the solubility/insoluble salt of hydroxypropyl methylcellulose and/or ethyl cellulose and/or polyacrylic resin class and/or polycarboxy ethene and/or alginic acid and/or ethyl cellulose and/or other play the adjuvant of slow releasing function, 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 polyacrylic resin adopts and includes polyacrylic resin II, the acrylic resin of III class or analog such as all size (Eudragit).
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition, can be made into controlled release preparation, 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, hydroxypropyl cellulose, methylcellulose, Glyceryl Behenate class etc.; Permeation-promoter can adopt sodium chloride, lactose, mannitol etc.; Solubilizing agent can be adopted sodium lauryl sulphate or poloxamer etc.; Binding agent can adopt polyvinylpyrrolidone, hypromellose, chitosan, sodium alginate, methylcellulose, ethyl cellulose, starch slurry, arabic gum, gelatin, sucrose, polyvinyl alcohol etc.; Wetting agent can adopt the ethanol-water solution of dehydrated alcohol, water, various concentration; Lubricant can adopt stearic acid, magnesium stearate, Pulvis Talci, starch, paraffin etc.; Coloring agent can adopt natural pigment such as carmine, amaranth, lemon yellow, bright orchid, indigo, brownish red ferrum oxide and synthetic dyestuff or the like; Porogen can adopt sucrose, mannitol, Polyethylene Glycol, titanium dioxide, Pulvis Talci, silicon dioxide etc.; Membrane material can adopt cellulose acetate, ethyl cellulose, hydroxypropyl emthylcellulose acetic acid succinate, beautiful jade Cellulose Acetate Phthalate, poly-phthalic acid vinyl acetate cellulose, hydroxypropyl cellulose, hydroxyethyl-cellulose etc.; Solvent can adopt acetone, dehydrated alcohol, ethanol, water etc.
Also contain the pharmaceutics acceptable carrier in the said 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 mannitol, sorbitol, maltose alcohol, low substituted hydroxy-propyl methylcellulose, microcrystalline Cellulose, carboxymethyl starch sodium, cross-linked carboxymethyl cellulose sodium, crospolyvinylpyrrolidone, processing agar, cyclodextrin, glycyrrhizic acid, stevioside, citric acid, Oleum menthae, eucalyptus oil, Oleum Caryophylli, Fructus Citri Limoniae oil, citrus seed oil and some other correctives that wraps up with microcapsule 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; 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 porogen various medicaments adjuvants such as (as PEG6000).
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; sodium chloride; cysteine; the compositions of one or more materials of citric acid and sodium sulfite etc., coating material 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; the polyvinyl acetate phthalic acid ester; 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 porogen various medicaments adjuvants such as (as PEG6000).
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition, can be made into dosage forms such as granule, oral liquid, membrane, patch.Described pharmaceutically acceptable carrier includes excipient and the adjuvant that helps reactive compound is mixed with pharmaceutical formulation when making the patch membrane; as polyvinyl alcohol, Triafol T, ethylene-vinyl acetate copolymer, polyvinylpyrrolidone, polyacrylamide, polybutene class pressure sensitive adhesive, crylic acid resin pressure sensitive adhesive, silicone pressure sensitive adhesive etc.; and back lining materials such as polrvinyl chloride, polyethylene, aluminium foil, polypropylene, polyester, 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 a few days takes once every other day or at interval.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.
Another object of the present invention provide in the vitamin B group of a kind of, the pharmaceutical dosage in the angiotensin-convertion enzyme inhibitor that contains pharmaceutical dosage and active metabolite or its officinal salt one or more, the pharmaceutical composition of the Folium Ginkgo extract of pharmaceutical dosage and pharmaceutically suitable carrier in the preparation prevention, treat or delay purposes in the medicine of apoplexy and risk factor thereof.
Among the present invention, term " pharmaceutical dosage " is meant that the clinician grants the dosage of medicine to diseased individuals according to the diseased individuals degree that is in a bad way in order to reach effective control or treatment disease purpose.Be to be understood that medicine pharmaceutical dosage provided by the invention is not a limitation of the present invention, but to of the present invention preferred, generally, in this dosage preferable range, this medicine can produce effective therapeutic effect to diseased individuals.Diseased individuals is meant the self-existent life entity of suffering from disease, and in the present invention, life entity refers to the mankind especially.Should be appreciated that in the prior art, human pharmaceutical use dosage or pharmaceutical dosage scope can with mammal, as rat, mice etc., converting is fit to pharmaceutical dosage or the dosage range that corresponding animal is suitable for to draw.
Among the present invention, the risk factor of apoplexy specifically comprises hypertension, diabetes, dyslipidemia, smoking, drinks, fat, lack physical training, cerebral arterial stenosis, heart change.Other risk factors have unreasonable use of anticoagulant behind artery dissection, patent foramen ovale, hyperhomocysteinemiainjury, high blood coagulation state, Cerebral Venous Sinus thrombosis, women's hormone replacement therapy, the cerebral thrombosis etc.
Advantage of the present invention is: the combined effect of angiotensin-convertion enzyme inhibitor, vitamin B group and Folium Ginkgo extract be not each active substance each self-applying simply add and, but in treatment, prevent or delay to have aspect apoplexy and the hazard factor thereof significant more effect.That is to say that angiotensin ii receptor antagonist, vitamin B group and Folium Ginkgo extract administering drug combinations have been obtained synergy.Therefore pharmaceutical composition provided by the invention has tangible prevention or delays apoplexy and the beneficial effect of hazard factor on the effective therapeutic effect that brings high blood pressure down, and is treatment preferably, prevents or delay the apoplexy medicine.
The present invention will be further described below in conjunction with the specific embodiment, is not limitation of the invention, all any this areas of carrying out according to content of the present invention be equal to replacement, all belong to protection scope of the present invention.
The specific embodiment
The consumption of the preparation process of following pharmaceutical preparation embodiment and used material of preparation or the used material of preparation is not limited to character express; all formulation methods that contains pharmaceutical composition provided by the invention; all belong to protection scope of the present invention; but concrete experimental technique reference drug preparation quick-reference book is as " pharmaceutical necessities is used and preparation ", " pharmaceutics ", " Biopharmaceutics and Pharmacokinetics " etc.
Embodiment 1～10: the preparation of the enalapril maleate/vitamin B group of different content proportioning/Folium Ginkgo (1000 amounts)
Make tablet according to the granule that prescription shown in the table 1 obtains.
Table 1 embodiment 1～10 tablet formulation is formed
Preparation method:
(1) enalapril maleate, vitamin B group and the Folium Ginkgo extract of getting recipe quantity crossed behind 100 mesh sieves standby by equivalent incremental method mix homogeneously respectively;
(2) with other adjuvant respectively at 70 ℃ of dry about 2h after, mistake 100 mesh sieves;
(3) get microcrystalline Cellulose, carboxymethylstach sodium, the starch mixing of recipe quantity, then with mixed crude drug by equivalent incremental method mix homogeneously;
(4) add 5% 30 POVIDONE K 30 BP/USP-3095% alcoholic solution and make soft material in right amount, 24 mesh sieves are granulated, 40 ℃ of dryings, and controlling particulate water content is 2-3%, 20 mesh sieve granulate;
(5) with dried granule and magnesium stearate mix homogeneously, tabletting behind the assay, aluminium-plastic bubble plate packing.
Embodiment 11～20: the preparation of the enalapril maleate/vitamin B group of different content proportioning/Folium Ginkgo capsule (1000 amounts)
Make capsule according to the granule that prescription shown in the table 2 obtains.
Table 2 embodiment 11～20 capsule prescriptions are formed
Preparation method:
(1) enalapril maleate, vitamin B group and the Folium Ginkgo extract of getting recipe quantity crossed behind 100 mesh sieves standby by equivalent incremental method mix homogeneously respectively;
(2) with other adjuvant respectively at 70 ℃ of dry about 2h after, mistake 100 mesh sieves;
(3) get microcrystalline Cellulose, carboxymethylstach sodium, lactose, the starch mixing of recipe quantity, then with mixed crude drug by equivalent incremental method mix homogeneously;
(4) add 5% 30 POVIDONE K 30 BP/USP-30,95% alcoholic solution and make soft material in right amount, 24 mesh sieves are granulated, 40 ℃ of dryings, and controlling particulate water content is 2-3%, 20 mesh sieve granulate;
(5) with dried granule and magnesium stearate mix homogeneously, the Capsules of packing into behind the assay, aluminium-plastic bubble plate packing.
Embodiment 21～29: the preparation of the benazepril hydrochloride/vitamin B group of different content proportioning/Folium Ginkgo
Preparation method is identical with embodiment 1, makes tablet according to the granule that prescription shown in the table 3 obtains.
Table 3 embodiment 21～29 tablet formulations are formed
Embodiment 30～38: the preparation of the benazepril hydrochloride/vitamin B group of different content proportioning/Folium Ginkgo capsule
Preparation method is identical with embodiment 11, makes capsule according to the granule that prescription shown in the table 4 obtains.
Table 4 embodiment 30～38 capsule prescriptions are formed
Embodiment 39～47: the preparation of the ACEI/B vitamin/Folium Ginkgo of different content proportioning
Preparation method is identical with embodiment 1, makes tablet according to the granule that prescription shown in the table 5 obtains.
Table 5 embodiment 39～47 tablet formulations are formed
Embodiment 48～50: preparation ACEI/ folic acid/Folium Ginkgo (1000 amounts)
Preparation method is identical with embodiment 1, makes tablet according to the granule that prescription shown in the table 6 obtains.
Table 6 embodiment 48～50 tablet formulations are formed
Preparation technology:
(1) ACEI, folic acid and the Folium Ginkgo extract that takes by weighing recipe quantity crossed behind 100 mesh sieves standby by equivalent incremental method mix homogeneously;
(2) other adjuvants are crossed behind 100 mesh sieves standby 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 5% 30 POVIDONE K 30 BP/USP 30 (solvent is 50% ethanol) and make soft material in right amount, 24 mesh sieves are granulated, 20 mesh sieve granulate, 40～45 ℃ of dryings;
(5) dried granule adds an amount of magnesium stearate mixing, tabletting behind the assay.
Embodiment 50～53: the preparation of benazepril hydrochloride/vitamin B group/Folium Ginkgo capsule
Make capsule according to the granule that prescription shown in the table 7 obtains.
Table 7 embodiment 50～53 capsule formulas are formed
Preparation method:
(1) benazepril hydrochloride, vitamin B group and the Folium Ginkgo extract of getting recipe quantity crossed behind 100 mesh sieves standby by equivalent incremental method mix homogeneously respectively;
(2) with other adjuvant respectively at 70 ℃ of dry about 2h after, mistake 100 mesh sieves;
(3) get microcrystalline Cellulose, carboxymethylstach sodium, lactose, the starch mixing of recipe quantity, then with mixed crude drug by equivalent incremental method mix homogeneously;
(4) add 5% 30 POVIDONE K 30 BP/USP-3095% alcoholic solution and make soft material in right amount, 24 mesh sieves are granulated, 40 ℃ of dryings, and controlling particulate water content is 2-3%, 20 mesh sieve granulate;
(5) with dried granule and magnesium stearate mix homogeneously, the Capsules of packing into behind the assay, aluminium-plastic bubble plate packing.
The preparation of embodiment 54～56:ACEI/ folic acid/gingko leaf slow-releasing table
Make slow releasing tablet according to the granule that prescription shown in the table 8 obtains.
Table 8 embodiment 54～56 slow releasing tablet prescriptions are formed
Preparation method:
(1) ACEI, folic acid and the Folium Ginkgo extract of getting recipe quantity crossed behind 100 mesh sieves standby by equivalent incremental method mix homogeneously respectively;
(2) get microcrystalline Cellulose, hydroxypropyl methylcellulose, carboxymethylstach sodium, the starch mixing of recipe quantity, then with mixed crude drug by equivalent incremental method mix homogeneously;
(3) add 5% 30 POVIDONE K 30 BP/USP-30 ethanol solution and make soft material in right amount, 24 mesh sieves are granulated, 40 ℃ of dryings, 20 mesh sieve granulate;
(5) with dried granule and magnesium stearate mix homogeneously, tabletting behind the assay, aluminium-plastic bubble plate packing.
Embodiment 57: enalapril maleate/folic acid/Folium Ginkgo extract is worked in coordination with hypotensive effect
With the narrow Wistar rat of 0.2mm silver brain clip left renal artery, it is the hypertension artery model that the back rat blood pressure rising of 8～10 weeks surpasses 140mmHg above.With the Hypertensive Rats random packet, be respectively model group (giving solvent), enalapril+folic acid group (1mg/kg+0.04mg/kg), 1 group of Folium Ginkgo extract (8mg/kg), 2 groups of Folium Ginkgo extract (24mg/kg), enalapril+folic acid+1 group of (1+0.04+8) mg/kg of Folium Ginkgo extract, enalapril+folic acid+2 groups of (1+0.04+24) mg/kg of Folium Ginkgo extract, other establishes the normal control group.Gastric infusion, continuous 8 weeks.Measure before the administration respectively and administration after the different time blood pressure, the results are shown in Table 9.
The result shows: compare with normal group, the model group rat blood pressure significantly raises, and shows the hypertension model establishment; Compare with model group, Folium Ginkgo extract group rat blood pressure slightly reduces, but statistics does not have significant difference; Enalapril+folic acid group rat blood pressure significantly reduces, with enalapril+folic acid group relatively, enalapril+folic acid+Folium Ginkgo extract group rat blood pressure further reduces, and statistics there were significant differences, there is certain dose-effect relationship in Folium Ginkgo extract.
Table 9 enalapril+folic acid+Folium Ginkgo extract is to the influence of renal hypertensive rat blood pressure (x ± s)
Compare ##P＜0.01 with normal control; Compare with model group: * * P＜0.01; Compare with enalapril folic acid group,
▲P＜0.05,
▲ ▲P＜0.01
Embodiment 58: quinapril/folic acid/ginkgo leaf extract composition is to the influence of apoplexy susceptible type spontaneous hypertensive rat (SHRsp) cerebrovascular structure
Male SHRsp is divided at random and is respectively model group (give equivalent solvent), quinapril+folic acid group (1mg/kg+0.04mg/kg), Folium Ginkgo extract 1 group of (8mg/kg), Folium Ginkgo extract 2 groups of (24mg/kg), quinapril+folic acid+1 group of Folium Ginkgo extract (1mg/kg+0.04mg/kg+8mg/kg) with 6 ages in week, quinapril+folic acid+2 groups of Folium Ginkgo extract (1mg/kg+0.04mg/kg+24mg/kg), every group 15, all raise high protein feed, drink 1.5%NaCl since the 8th age in week.Other gets 15 6 week male normal arterial pressure rats in age (WKY) as the normal control group, raises normal diet, the drink tap water.Gastric infusion, every day 1 time, continuous 18 weeks.
Every morning marks according to rat brain apoplexy clinical manifestation standards of grading: 1 minute: movable lacking-quantity of motion slightly reduces or is slight excited; 2 minutes: activity seldom-quantity of motion obviously reduce or excitation excited; 3 minutes: prostrate motionless-can not walk the melancholy symptom; 4 minutes: paralyse-can not stand any side or bilateral limb paralysis.
The back drug withdrawal of 18 weeks, row aorta intubate behind the rat anesthesia, the perfusion of 2.5% glutaraldehyde is fixing, broken end is got brain, separates skull base arterial ring and intraparenchymatous small artery of brain and arteriole, separates skull base arterial ring and intraparenchymatous small artery of brain and arteriole under operating microscope, 2.5% glutaraldehyde is fixed, Epon 812 embeddings, semithin section, Toluidine blue staining.Semithin section adopts CMIAS series 2 multi-functional true color pathological image analysis systems to measure the media thickness of blood vessel, tube chamber radius, middle film cross-sectional area, tube chamber cross-sectional area etc., calculates the ratio of media thickness/tube chamber radius, and 10 blood vessels are surveyed in every section.
All (x ± s) expression, with the analysis of SPSS statistical software, the relatively employing one factor analysis of variance of a plurality of sample averages, the q that relatively adopts in twos of a plurality of sample averages checks all data with (mean+SD).The results are shown in Table 10.
Table 10 is respectively organized rat brain tremulous pulse morphometric and stereologic analysis
Annotate: compare with the normal control group,
*P＜0.05,
*P＜0.01; Compare with model group,
##P＜0.01.
The scoring of normal control group apoplexy is (0.11 ± 0.09), model group apoplexy scoring (3.54 ± 0.51) significantly raises, compare with model group, quinapril+folic acid group (0.78 ± 0.17), 1 group of (0.83 ± 0.15), Folium Ginkgo extract 2 groups of (0.80 ± 0.14), quinapril+folic acid+Folium Ginkgo extract 1 group of (0.39 ± 0.25) and quinapril+folic acid of Folium Ginkgo extract+2 groups of (0.37 ± 0.22) apoplexy scorings of Folium Ginkgo extract significantly reduce; Compare with quinapril+folic acid group, quinapril+folic acid+Folium Ginkgo extract group rat brain apoplexy scoring further reduces, and significant difference is arranged.
Structure under the cerebral arteries light microscopic: normal control group middle cerebral artery structure is normal, and film obviously thickens in the model group middle cerebral artery, and quinapril+folic acid group, Folium Ginkgo extract group and quinapril+folic acid+Folium Ginkgo extract group does not all have obviously and thickens.
This research shows cerebrovascular om observation of SHRsp and morphometric and stereologic analysis result: the ratio of model group cerebral arteries media thickness/tube chamber radius is apparently higher than the normal control group; Quinapril+folic acid group, Folium Ginkgo extract group and quinapril+folic acid+Folium Ginkgo extract group all can significantly reduce the ratio and the apoplexy clinical manifestation scoring of SHRsp cerebral arteries media thickness/tube chamber radius, reduce apoplexy incidence rate and mortality rate, wherein with quinapril+folic acid+Folium Ginkgo extract group most pronounced effects.
Claims (12)
1. pharmaceutical composition, contain:
1) a kind of in the angiotensin-convertion enzyme inhibitor of pharmaceutical dosage and active metabolite thereof or its officinal salt;
2) one or more in the vitamin B group of pharmaceutical dosage;
3) Folium Ginkgo extract of pharmaceutical dosage;
4) pharmaceutically suitable carrier.
2. the pharmaceutical composition described in the claim 1 is characterized in that: described angiotensin-convertion enzyme inhibitor and active metabolite thereof or its officinal salt are selected from a kind of in enalapril, benazepril, lisinopril, fosinopril, imidapril, ramipril, captopril, quinapril, cilazapril, PERINDOPRIL, delapril, moexipril, spirapril, trandolapril and alacepril and active metabolite or its officinal salt; Described vitamin B group is selected from one or more in folic acid, vitamin B6, the vitamin B12; Described Folium Ginkgo extract is the dried leaves extract of Ginkgoaceae plant Ginkgo biloba, extracts by the contemporary standard metallization processes to form, and main chemism composition is that total flavones accounts for 24% and total lactone 6%.
3. the pharmaceutical composition described in the claim 2, it is characterized in that: the content that described enalapril content is 5mg-40mg, enalapril maleate or enalaprilat is that the amount, the benazepril content that are equivalent to the 5mg-40mg enalapril are that 5mg-40mg, benazepril hydrochloride content are that amount, the lisinopril content that is equivalent to the 5mg-40mg benazepril is that 5mg-40mg, fosinopril content are that 10mg-40mg, imidapril content are that 2.5mg-10mg, ramipril content are that 2.5mg-20mg, quinapril content are 10mg～40mg; The content of described folic acid is 0.1mg-5mg, and the content of vitamin B6 is 2mg-50mg, and the content of vitamin B12 is 0.001mg-2mg; The content of described Folium Ginkgo extract is 40mg-240mg.
4. the pharmaceutical composition described in the claim 1, it is characterized in that: described angiotensin-convertion enzyme inhibitor is enalapril maleate or enalaprilat, content is the amount that is equivalent to the 5mg-40mg enalapril; Described vitamin B group is a folic acid, and content is 0.1mg-5mg; Described Folium Ginkgo extract content is 40mg-240mg.
5. the pharmaceutical composition described in the claim 1, it is characterized in that: described angiotensin-convertion enzyme inhibitor is enalapril maleate or enalaprilat, content is the amount that is equivalent to the 5mg-40mg enalapril; Described vitamin B group is a vitamin B6, and content is 2mg-50mg; Described Folium Ginkgo extract content is 40mg-240mg.
6. the pharmaceutical composition described in the claim 1, it is characterized in that: described angiotensin-convertion enzyme inhibitor is enalapril maleate or enalaprilat, content is the amount that is equivalent to the 5mg-40mg enalapril; Described vitamin B group is a vitamin B12, and content is 0.001mg-2mg; Described Folium Ginkgo extract content is 40mg-240mg.
7. the pharmaceutical composition described in the claim 1, it is characterized in that: described angiotensin-convertion enzyme inhibitor is a benazepril hydrochloride, content is the amount that is equivalent to the 5mg-40mg benazepril; Described vitamin B group is a folic acid, and content is 0.1mg-5mg; Described Folium Ginkgo extract content is 40mg-240mg.
8. the pharmaceutical composition described in the claim 1, it is characterized in that: described angiotensin-convertion enzyme inhibitor is a benazepril hydrochloride, content is the amount that is equivalent to the 5mg-40mg benazepril; Described vitamin B group is a vitamin B6, and content is 2mg-50mg; Described Folium Ginkgo extract content is 40mg-240mg.
9. the pharmaceutical composition described in the claim 1, it is characterized in that: described angiotensin-convertion enzyme inhibitor is a benazepril hydrochloride, content is the amount that is equivalent to the 5mg-40mg benazepril; Described vitamin B group is a vitamin B12, and content is 0.001mg-2mg; Described Folium Ginkgo extract content is 40mg-240mg.
10. the pharmaceutical composition described in the claim 1, it is characterized in that: described angiotensin-convertion enzyme inhibitor is a quinapril, content is the amount that is equivalent to the 10mg-40mg benazepril; Described vitamin B group is a folic acid, and content is 0.1mg-5mg; Described Folium Ginkgo extract content is 40mg-240mg.
11. each described pharmaceutical composition in the claim 1 to 10, it is characterized in that: this pharmaceutical composition can be made into conventional tablet, slow releasing tablet, controlled release tablet, granule, conventional capsule, slow releasing capsule, controlled release capsule.
12. the purposes of each described pharmaceutical composition in the medicine for preparing treatment, prevents or delay apoplexy in the claim 1 to 11.
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| CN 200810113919 CN101590084B (en) | 2008-05-29 | 2008-05-29 | Pharmaceutical composition containing angiotensin converting enzyme inhibitors, B vitamins and ginkgo biloba extracts |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012073077A1 (en) * | 2010-12-03 | 2012-06-07 | Raouf Rekik | Folic acid - ramipril combination: cellprotective, neuroprotective and retinoprotective ophtalmologic compositions |
| CN107007838A (en) * | 2016-09-30 | 2017-08-04 | 南京优科制药有限公司 | A kind of pharmaceutical composition containing enalapril maleate, folic acid and sour stabilizer |
| CN114832111A (en) * | 2018-03-21 | 2022-08-02 | 成都百裕制药股份有限公司 | Pharmaceutical composition for preventing and/or treating hypertension |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1269529C (en) * | 2004-07-28 | 2006-08-16 | 安徽省生物医学研究所 | Medicinal composition contaniing angiotensin invertase inhibitor and vitamin B |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012073077A1 (en) * | 2010-12-03 | 2012-06-07 | Raouf Rekik | Folic acid - ramipril combination: cellprotective, neuroprotective and retinoprotective ophtalmologic compositions |
| CN103338758A (en) * | 2010-12-03 | 2013-10-02 | 拉乌夫·雷基克 | Folic acid - ramipril combination: cellprotective, neuroprotective and retinoprotective ophtalmologic compositions |
| RU2602738C2 (en) * | 2010-12-03 | 2016-11-20 | Рауф РЕКИК | Combination of folic acid and ramipril: cytoprotective, neuroprotective and retinoprotective ophthalmic compositions |
| AU2011334617B2 (en) * | 2010-12-03 | 2017-01-12 | Raouf Rekik | Folic acid - Ramipril combination: cellprotective, neuroprotective and retinoprotective ophtalmologic compositions |
| CN107007838A (en) * | 2016-09-30 | 2017-08-04 | 南京优科制药有限公司 | A kind of pharmaceutical composition containing enalapril maleate, folic acid and sour stabilizer |
| CN114832111A (en) * | 2018-03-21 | 2022-08-02 | 成都百裕制药股份有限公司 | Pharmaceutical composition for preventing and/or treating hypertension |
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