CN101869572A - Composition containing biguanide antidiabetic medicament and ACEI (Angiotensin-Converting Enzyme Inhibitors) medicament and applications thereof - Google Patents
Composition containing biguanide antidiabetic medicament and ACEI (Angiotensin-Converting Enzyme Inhibitors) medicament and applications thereof Download PDFInfo
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- CN101869572A CN101869572A CN200910082592A CN200910082592A CN101869572A CN 101869572 A CN101869572 A CN 101869572A CN 200910082592 A CN200910082592 A CN 200910082592A CN 200910082592 A CN200910082592 A CN 200910082592A CN 101869572 A CN101869572 A CN 101869572A
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Abstract
The invention relates to a medicament composition containing biguanide antidiabetic medicament, ACEI (Angiotensin-Converting Enzyme Inhibitors) medicament and a pharmaceutically acceptable carrier. The invention also relates to the applications of the medicament composition in the preparation of medicaments for preventing or treating diabetes mellitus with hypertension. The implementation of the invention provides the medicament composition with specific applications, and the medicament composition not only has a precise curative effect, but also can improve the compliance of patients. The patients can take the medicament conveniently, and the medical expense is reduced. The invention has a better market prospect, and belongs to the field of pharmacy.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition that contains biguanide antidiabetic medicament and Puli's hypotensor thing, and this pharmaceutical composition is used for preventing or treating the purposes of the medicine of Diabetes with Hypertension in preparation.The invention belongs to pharmaceutical field.
Background technology
Diabetes be because insulin secretion and (or) defective causes is the metabolic disease of feature with the blood sugar increasing in effect.The diabetics of long-term poor blood glucose control, the various organs that can occur together, especially eye, the heart, blood vessel, kidney, nervous lesion or organ dysfunction are incomplete or depleted, cause maimed person or premature death.In recent years, raising along with countries in the world The development in society and economy and resident living level, the sickness rate and the prevalence of diabetes raise year by year, become the great social problem that threatens people ' s health, cause national governments, hygiene department and numerous medical personnels' concern and attention.
Hypertension is modal cardiovascular diseases, is the great public health problem in the global range.China's national hypertension sampling survey in 1991, the hypertension prevalence is 11.26% more than 15 years old, and investigation shows that hyperpietic's prevalence is ascendant trend year by year along with the change of China's resident living mode and the raising of average expected life-span.According to another updated statistics, at present the hypertensive prevalence of China has risen to 11.68%, and target organ damages such as the heart of hypertension secondary, brain, kidney especially have a strong impact on patient's life-span and quality of life, have become the disease of serious threat human health and life.
According to statistics, but the diabetes patient has complicated hypertensions more than half.In case morbidity, then the sickness rate of complication such as apoplexy, coronary heart disease, renal failure, retinopathy, diabetic foot obviously raises, and serious symptom, and prognosis is dangerous, has become the lethal major reason of diabetes.
The mechanism of action of biguanide antidiabetic medicament be by the glyconeogenesis that suppresses liver and intestinal wall to the absorption of glucose, strengthen peripheral tissues's ingestion of glucose and anerobic glycolysis, suppress Tissue respiration, generate lactic acid.Biguanide antidiabetic medicament does not stimulate insulin secretion, but can strengthen insulin and receptors bind and effect, and certain insulin-sensitizing effect is arranged.
Puli's hypotensor thing is angiotensin-convertion enzyme inhibitor (ACEI) class medicine just, angiotensin converting enzyme (ACE) is an important step in Re-A-A (RAS) system, and there is extremely important meaning in this system to the adjusting of blood pressure.The main effect of ACE is angiotensin I to be converted into have the vasoactive Angiotensin II that contracts strongly; ACE can also catalysis has the Kallidin I hydrolysis of short vasorelaxation action in addition.And the main pharmacological action of ACEI is to suppress the ACE activity, reduces the generation of Angiotensin II, reduces the hydrolysis of Kallidin I, causes vasodilation, hypovolemia, blood pressure drops.Puli's hypotensor thing all has tangible hypotensive effect to multiple hypertension, and can improve the cardiac function of patients with congestive heart failure.The clinical all kinds vascular hypertension that is applicable to is especially effective to the invalid serious hypertension of routine treatment.
In existing patent and scientific and technical literature, the pharmaceutical composition that we still do not have discovery to unite biguanide antidiabetic medicament and Puli's hypotensor thing in clinical and preclinical study is used to prevent or treat the report of Diabetes with Hypertension.
Summary of the invention
Order of the present invention provides the pharmaceutical composition of a kind of effective prevention or treatment Diabetes with Hypertension, and this pharmaceutical composition contains acceptable carrier on biguanide antidiabetic medicament and Puli's hypotensor thing and the pharmaceutics.Another object of the present invention provides the pharmaceutical composition that contains acceptable carrier on biguanide antidiabetic medicament and Puli's hypotensor thing and the pharmaceutics is used for preventing or treating the medicine of Diabetes with Hypertension in preparation purposes.
For realizing above-mentioned purpose of the present invention, the present invention by the following technical solutions:
A kind of pharmaceutical composition contains a kind of and pharmaceutically suitable carrier in Puli's hypotensor thing of a kind of, the medicinal content in the biguanide antidiabetic medicament of medicinal content.
In pharmaceutical composition provided by the invention, except that biguanide antidiabetic medicament chemical compound itself, can also be selected from the active metabolite or its esters of biguanide antidiabetic medicament chemical compound.Biguanide antidiabetic medicament comprises phenformin (phenformin), metformin (metformin), buformin (bufonamin) etc.Wherein, phenformin content is 25mg-200mg, and metformin content is 250mg-1500mg.
In pharmaceutical composition provided by the invention, described Puli's hypotensor thing comprises enalapril (enalapril), benazepril (benazepril), captopril (captopril), lisinopril (lisinopril), ramipril (ramipril), fosinopril (fosinopril), cilazapril (cilazapril), perindopril (perindopril), quinapril (quinapril), trandolapril (trandolapril), delapril (delapril), imidapril (imidapril), temocapril (temocapril), spirapril (spirapril), moexipril (moexipril) and alacepril (alacepril) and metabolite or salt apoplexy due to endogenous wind a kind of.
Research by experiment, the content of Puli's hypotensor thing is respectively: enalapril 2.5mg～40mg, benazepril 2.5mg～40mg, ramipril 1.25mg～20mg, fosinopril 10mg～80mg, lisinopril 2.5mg～80mg, captopril 12.5mg～100mg, quinapril 5mg～80mg, cilazapril 1.2mg～5mg, perindopril 2mg～16mg, delapril 15mg～120mg, moexipril 3.75mg～30mg, trandolapril 0.5mg～4mg, imidapril 2.5mg～40mg, spirapril 3mg～30mg, alacepril 12.5mg～100mg, the active metabolite of above-mentioned substance or salt content can be tried to achieve according to of equal value conversion of above-mentioned substance.
The better in the present invention treatment effective dose of above-mentioned Puli's hypotensor thing is respectively: enalapril 5mg～40mg, benazepril 5mg～40mg, ramipril 2.5mg～20mg, fosinopril 10mg～40mg, lisinopril 5mg～40mg, captopril 25mg～100mg, quinapril 10mg～40mg, cilazapril 2.5mg～5mg, perindopril 4mg～8mg, delapril 15mg～60mg, moexipril 7.5mg～30mg, trandolapril 0.5mg～2mg, imidapril 2.5mg～10mg, spirapril 3mg～15mg, alacepril 25mg～100mg, the active metabolite of above-mentioned substance or salt content can be tried to achieve according to of equal value conversion of above-mentioned substance.
In the pharmaceutical composition provided by the invention, biguanide antidiabetic medicament is a phenformin, and content is 25mg-200mg; Puli's hypotensor thing is an enalapril, and content is 5mg-40mg.
In the pharmaceutical composition provided by the invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's hypotensor thing is an enalapril, and content is 5mg-40mg.
In the pharmaceutical composition provided by the invention, biguanide antidiabetic medicament is a phenformin, and content is 25mg-200mg; Puli's hypotensor thing is a perindopril, and content is 4mg-8mg.
In the pharmaceutical composition provided by the invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's hypotensor thing is a perindopril, and content is 4mg-8mg.
In the pharmaceutical composition provided by the invention, biguanide antidiabetic medicament is a phenformin, and content is 25mg-200mg; Puli's hypotensor thing is a lisinopril, and content is 5mg-40mg.
In the pharmaceutical composition provided by the invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's hypotensor thing is a lisinopril, and content is 5mg-40mg.
In the pharmaceutical composition provided by the invention, biguanide antidiabetic medicament is a phenformin, and content is 25mg-200mg; Puli's hypotensor thing is an imidapril, and content is 2.5mg-10mg.
In the pharmaceutical composition provided by the invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's hypotensor thing is an imidapril, and content is 2.5mg-10mg.
In the pharmaceutical composition provided by the invention, biguanide antidiabetic medicament is a phenformin, and content is 25mg-200mg; Puli's hypotensor thing is a benazepril, and content is 5mg-40mg.
In the pharmaceutical composition provided by the invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's hypotensor thing is a benazepril, and content is 5mg-40mg.
In the pharmaceutical composition provided by the present invention, biguanide antidiabetic medicament is a phenformin, and content is 25mg-200mg; Puli's hypotensor thing is a captopril, and content is 25mg-100mg.
In the pharmaceutical composition provided by the present invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's hypotensor thing is a captopril, and content is 25mg-100mg.
In the pharmaceutical composition provided by the present invention, biguanide antidiabetic medicament is a phenformin, and content is 25mg-200mg; Puli's hypotensor thing is a moexipril, and content is 7.5mg-30mg.
In the pharmaceutical composition provided by the present invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's class medicine is a moexipril, and content is 7.5mg-130mg.
In the pharmaceutical composition provided by the present invention, biguanide antidiabetic medicament is a phenformin, and content is 25mg-200mg; Puli's hypotensor thing is a quinapril, and content is 10mg-40mg.
In the pharmaceutical composition provided by the present invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's hypotensor thing is a quinapril, and content is 10mg-40mg.
In the pharmaceutical composition provided by the present invention, biguanide antidiabetic medicament is a phenformin, and content is 25mg-200mg; Puli's hypotensor thing is a trandolapril, and content is 0.5mg-2mg.
In the pharmaceutical composition provided by the present invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's hypotensor thing is a trandolapril, and content is 0.5mg-2mg.
In the pharmaceutical composition provided by the present invention, biguanide antidiabetic medicament is a phenformin, and content is 25mg-200mg; Puli's hypotensor thing is a cilazapril, and content is 2.5mg-5mg.
In the pharmaceutical composition provided by the present invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's hypotensor thing is a cilazapril, and content is 2.5mg-5mg.
In the pharmaceutical composition provided by the present invention, biguanide antidiabetic medicament is a phenformin, and content is 25mg-200mg; Puli's hypotensor thing is a fosinopril, and content is 10mg-40mg.
In the pharmaceutical composition provided by the present invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's hypotensor thing is a fosinopril, and content is 10mg-40mg.
In the pharmaceutical composition provided by the present invention, biguanide antidiabetic medicament is a phenformin, and content is 25mg-200mg; Puli's hypotensor thing is a ramipril, and content is 2.5mg-20mg.
In the pharmaceutical composition provided by the present invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's hypotensor thing is a ramipril, and content is 2.5mg-20mg.
Term " medicinal content " is meant that the clinician grants content of medicines according to the diseased individuals degree that is in a bad way to diseased individuals in order to reach the purpose of effective control or treatment disease.Be to be understood that the medicinal content of medicine provided by the invention is not limitation of the present invention, but to of the present invention preferred, generally, in this content 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 content or medicinal content range can with mammal, as rat, mice etc., converting is fit to medicinal content or the content range that corresponding animal is suitable for to draw.
According to the present invention, the active component in the pharmaceutical composition is the solvent in the compositions, and one of them active component comes from a kind of in the biguanide antidiabetic medicament, and active component comes from a kind of in Puli's hypotensor thing; 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 biguanide antidiabetic medicament, the pharmaceutical composition of Puli's hypotensor thing 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 content form, and take description." Combined drug box " more is applicable to personalized medicine.
Another object of the present invention provides the pharmaceutical composition that contains acceptable carrier on biguanide antidiabetic medicament and Puli's hypotensor thing and the pharmaceutics is used for preventing or treating the medicine of Diabetes with Hypertension in preparation purposes.
In purposes of the present invention, described biguanide antidiabetic medicament comprises phenformin (phenformin), metformin (metformin), buformin (bufonamin) etc.Wherein, phenformin content is 25mg-200mg, and metformin content is 250mg-1500mg; Described Puli's hypotensor thing comprises enalapril (enalapril), benazepril (benazepril), captopril (captopril), lisinopril (lisinopril), ramipril (ramipril), fosinopril (fosinopril), cilazapril (cilazapril), perindopril (perindopril), quinapril (quinapril), trandolapril (trandolapril), delapril (delapril), imidapril (imidapril), temocapril (temocapril), spirapril (spirapril), moexipril (moexipril) and alacepril (alacepril) and metabolite or salt apoplexy due to endogenous wind a kind of.Wherein, enalapril content is 5mg～40mg, benazepril content is 5mg～40mg, ramipril content is 2.5mg～20mg, fosinopril content is 10mg～40mg, lisinopril content is 5mg～40mg, captopril content is 25mg～100mg, quinapril content is 10mg～40mg, cilazapril content is 2.5mg～5mg, perindopril content is 4mg～8mg, delapril content is 15mg～60mg, moexipril content is 7.5mg～30mg, trandolapril content is 0.5mg～2mg, imidapril content is 2.5mg～10mg, spirapril content is 3mg～15mg, alacepril content is 25mg～100mg, and the active metabolite of above-mentioned substance or salt content can be tried to achieve according to of equal value conversion of above-mentioned substance.
In purposes of the present invention, biguanide antidiabetic medicament is a phenformin, and content is 25mg-200mg; Puli's hypotensor thing is an enalapril, and content is 5mg-40mg.
In purposes of the present invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's hypotensor thing is an enalapril, and content is 5mg-40mg.
In purposes of the present invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's hypotensor thing is a perindopril, and content is 4mg-8mg.
In purposes of the present invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's hypotensor thing is a lisinopril, and content is 5mg-40mg.
In purposes of the present invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's hypotensor thing is an imidapril, and content is 2.5mg-10mg.
In purposes of the present invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's hypotensor thing is a benazepril, and content is 5mg-40mg.
In purposes of the present invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's hypotensor thing is a captopril, and content is 25mg-100mg.
In purposes of the present invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's class medicine is a moexipril, and content is 7.5mg-130mg.
In purposes of the present invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's hypotensor thing is a quinapril, and content is 10mg-40mg.
In purposes of the present invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's hypotensor thing is a trandolapril, and content is 0.5mg-2mg.
In purposes of the present invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's hypotensor thing is a cilazapril, and content is 2.5mg-5mg.
In purposes of the present invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's hypotensor thing is a fosinopril, and content is 10mg-40mg.
In purposes of the present invention, biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; Puli's hypotensor thing is a ramipril, and content is 2.5mg-20mg.
The medicine that pharmaceutical composition provided by the invention is made has the effect of obvious treatment Diabetes with Hypertension, therefore is the medicine of anti-diabetic complicated hypertension preferably.
In clinical practice or the scientific research document of having delivered, we do not find as yet that biguanide antidiabetic medicament, Puli's hypotensor thing are united and are used for therapy on Diabetes with Hypertension.In experiment, we find, the medicine that the compositions of biguanide antidiabetic medicament provided by the invention, Puli's hypotensor thing is made has excellent curative to prevention or treatment Diabetes with Hypertension.
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 1～8: the preparation (1000 amounts) of the compound recipe benazepril biguanide sheet of different content proportioning
Table 1 embodiment 1～8 tablet formulation is formed
Preparation technology:
(1) takes by weighing benazepril, the biguanide antidiabetic medicament of recipe quantity according to table 1, cross behind 100 mesh sieves standby by equivalent incremental method mix homogeneously;
(2) other adjuvants are crossed behind 100 mesh sieves standby respectively;
(3) take by weighing after the pregelatinized Starch, microcrystalline Cellulose, carboxymethylstach sodium mixing of recipe quantity again and mixed crude drug equivalent incremental method mix homogeneously;
(4) add suitable amount of adhesive system soft material, 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 9～30: the preparation of compound metformin Puli sheet (1000 amounts)
Table 2 embodiment 9～30 tablet formulations are formed
Continuous table 2 embodiment 9～30 tablet formulations are formed
Preparation technology:
(1) takes by weighing metformin hydrochloride and Puli's hypotensor thing of recipe quantity according to table 2, cross behind 100 mesh sieves standby by equivalent incremental method mix homogeneously;
(2) other adjuvants are crossed behind 100 mesh sieves standby respectively;
(3) take by weighing after the pregelatinized Starch, microcrystalline Cellulose, carboxymethylstach sodium mixing of recipe quantity again and mixed crude drug equivalent incremental method mix homogeneously;
(4) add suitable amount of adhesive system soft material, 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 31-42: the capsular preparation of compound recipe phenformin Puli (1000 amounts)
Table 3 embodiment 31～42 capsules prescription is formed
Preparation technology:
(1) takes by weighing phenformin hydrochloride and Puli's hypotensor thing of recipe quantity according to table 3, cross behind 100 mesh sieves standby by equivalent incremental method mix homogeneously;
(2) other adjuvants are crossed behind 100 mesh sieves standby respectively;
(3) take by weighing behind the pregelatinized Starch of recipe quantity and the carboxymethylstach sodium mixing again and mixed crude drug equivalent incremental method mix homogeneously;
(4) add suitable amount of adhesive system soft material, 24 mesh sieves are granulated, 20 mesh sieve granulate, 40～45 ℃ of dryings;
(5) dried granule adds an amount of magnesium stearate mixing, filled capsules behind the assay.
Embodiment 43～64: the preparation of compound metformin Puli granule (1000 bags of amounts)
Table 4 embodiment 43～64 granules prescription is formed
Continuous table 4 embodiment 43～64 granules prescription is formed
Preparation technology:
(1) takes by weighing metformin hydrochloride and Puli's hypotensor thing of recipe quantity according to table 4, cross behind 100 mesh sieves standby by equivalent incremental method mix homogeneously;
(2) other adjuvants are crossed behind 100 mesh sieves standby respectively;
(3) take by weighing behind lactose, pregelatinized Starch, carboxymethylstach sodium and the aspartame mixing of recipe quantity again and mixed crude drug equivalent incremental method mix homogeneously;
(4) add suitable amount of adhesive system soft material, 24 mesh sieves are granulated, 40～45 ℃ of dryings;
(5) 20 mesh sieve granulate remove fine powder with 80 mesh sieves sieve then;
(6) dried granule adds an amount of magnesium stearate mixing, packs behind the assay.
Embodiment 65～67: the preparation of compound metformin Puli slow releasing tablet (1000 amounts)
Table 5 embodiment 65～67 sustained-release tablet recipes are formed
Preparation technology:
(1) takes by weighing metformin hydrochloride and Puli's hypotensor thing of recipe quantity according to table 5, cross behind 100 mesh sieves standby by equivalent incremental method mix homogeneously;
(2) other adjuvants are crossed behind 100 mesh sieves standby respectively;
(3) take by weighing behind HPMC K15M, pregelatinized Starch, lactose and the 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 (the appearance agent is a dehydrated alcohol) and make soft material in right amount, 24 mesh sieves are granulated, 40～45 ℃ of dryings;
(5) dried granule adds an amount of magnesium stearate mixing, tabletting behind the assay.
Embodiment 68: the collaborative effect to Diabetes with Hypertension rat blood pressure and blood glucose of enalapril+metformin hydrochloride
80 of healthy 2 months aged Wistar rats, male and female half and half, average weight (201.2 ± 18.5) g.Adaptability is measured blood pressure with arteria caudalis pulse pressure method after raising for 1 week, and the tail vein is got the hematometry fasting glucose, and randomly draws 10 as the normal control group, the feed normal feedstuff.All the other each Mus from the tail vein injection streptozotocin (STZ, 25mg/kg).Glucose tolerances are measured in two week backs, select wherein impaired glucose tolerance, and 53 of the rats of hypertension are as the Diabetes with Hypertension animal pattern, and randomly draw 40 and be divided into 4 groups at random, and promptly model control group is 10, the high caloric diet of feeding; 10 of metformin hydrochloride groups, the feed high caloric diet, metformin hydrochloride 50mg/kg irritates stomach, 1 time/day; 10 of enalapril groups, the feed high caloric diet, enalapril 1mg/kg irritates stomach, 1 time/day; Enalapril+metformin hydrochloride group, 10, the feed high caloric diet, enalapril 1mg/kg+ metformin hydrochloride 50mg/kg irritates stomach, 1 time/day.Each organizes the administration cycle is 60d, and after administration the 20th, 40 and measure fasting glucose and blood pressure during 60d.
The statistical method data are used
Expression is relatively adopted variance analysis between each group, and P＜0.05 is for significant difference occurring.
Experimental result shows, administration the 60th day, and normal control group fasting glucose, pressure value do not have significant change; There were significant differences than normal matched group for model control group fasting glucose, blood pressure; Metformin hydrochloride group and enalapril+metformin group fasting blood sugar obviously reduces (P＜0.01 or P＜0.05), with model control group significant difference is arranged relatively, and enalapril+metformin group is than metformin group difference more remarkable (P＜0.05); Enalapril group and enalapril+metformin group blood pressure obviously reduces (P＜0.01 or P＜0.05), with model control group significant difference is arranged relatively, and enalapril+metformin group is than enalapril difference more remarkable (P＜0.05).
Claims (10)
1. pharmaceutical composition, contain:
1) a kind of in the biguanide antidiabetic medicament;
2) a kind of in Puli's hypotensor thing;
3) pharmaceutically suitable carrier.
2. the described compositions of claim 1, it is characterized in that: described biguanide antidiabetic medicament comprises metformin and phenformin.
3. the described compositions of claim 2, it is characterized in that: the content of described metformin is 250mg-1500mg, the content of described phenformin is 25mg-200mg.
4. the described compositions of claim 1, it is characterized in that: described Puli's hypotensor thing comprises enalapril, captopril, lisinopril, perindopril, imidapril, benazepril, ramipril, moexipril, quinapril, trandolapril, cilazapril, fosinopril.
5. the described compositions of claim 4, it is characterized in that: the content of described enalapril is 5mg-40mg, the content of captopril is 25mg-50mg, the content of lisinopril is 10mg-20mg, the content of perindopril is 4mg-8mg, the content of imidapril is 5mg-10mg, the content of benazepril is 5mg-20mg, the content of ramipril is 2.5mg-5mg, the content of moexipril is 7.5mg-15mg, the content of quinapril is 10mg-20mg, the content of trandolapril is 1mg-2mg, the content of cilazapril is 2.5mg-5mg, the content of fosinopril is 10mg-20mg.
6. the described compositions of claim 1, it is characterized in that: described biguanide antidiabetic medicament is a metformin, content is 250mg-1500mg; Described Puli's hypotensor thing is an enalapril, and content is 5mg-40mg.
7. the described compositions of claim 1, it is characterized in that: described biguanide antidiabetic medicament is a metformin, content is 250mg-1500mg; Described Puli's hypotensor thing is a lisinopril, and content is 5mg-40mg.
8. the described compositions of claim 1, it is characterized in that: described biguanide antidiabetic medicament is a metformin, content is 250mg-1500mg; Described Puli's hypotensor thing is a fosinopril, and content is 10mg-40mg.
9. the pharmacy dosage form of any one described compositions comprises conventional tablet, slow releasing tablet, controlled release tablet, granule, conventional capsule, slow releasing capsule, controlled release capsule in the claim 1 to 8.
10. any one described compositions is used for preventing or treating the purposes of the medicine of Diabetes with Hypertension in the claim 1 to 9 in preparation.
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|---|---|---|---|
| CN200910082592A CN101869572A (en) | 2009-04-24 | 2009-04-24 | Composition containing biguanide antidiabetic medicament and ACEI (Angiotensin-Converting Enzyme Inhibitors) medicament and applications thereof |
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| CN200910082592A CN101869572A (en) | 2009-04-24 | 2009-04-24 | Composition containing biguanide antidiabetic medicament and ACEI (Angiotensin-Converting Enzyme Inhibitors) medicament and applications thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107184952A (en) * | 2017-06-13 | 2017-09-22 | 江苏黄河药业股份有限公司 | A kind of lisinopril compound preparation and preparation method thereof |
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|---|---|---|---|---|
| CN1583173A (en) * | 2004-06-06 | 2005-02-23 | 李军生 | Serial medicines for hypertension and method for research, application and production |
| CN1602960A (en) * | 2004-07-23 | 2005-04-06 | 海南国栋药物研究所有限公司 | Mixture for preventing and treating metabolic syndrome like cerebrovascular and cardiovascular disease |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107184952A (en) * | 2017-06-13 | 2017-09-22 | 江苏黄河药业股份有限公司 | A kind of lisinopril compound preparation and preparation method thereof |
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