CN101897685A - Composition containing sibutramine and fibrate lipid-lowering drugs - Google Patents
Composition containing sibutramine and fibrate lipid-lowering drugs Download PDFInfo
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- CN101897685A CN101897685A CN2009100862750A CN200910086275A CN101897685A CN 101897685 A CN101897685 A CN 101897685A CN 2009100862750 A CN2009100862750 A CN 2009100862750A CN 200910086275 A CN200910086275 A CN 200910086275A CN 101897685 A CN101897685 A CN 101897685A
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Abstract
The invention relates to a drug composition containing sibutramine hydrochloride, fibrate lipid-lowering drugs and a pharmaceutically acceptable carrier. The invention also relates to application of the drug composition to preparing the drugs for treating obesity associated with hyperlipidemia. The invention belongs to the pharmaceutical field.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition that contains sibutramine and fibrate lipid-lowering drugs, and this pharmaceutical composition is used for the treatment of purposes in the medicine that obesity merges hyperlipidemia in preparation.The invention belongs to pharmaceutical field.
Background technology
China's problem of obesity is severe day by day, overweight and fat crowd increases very fast, shows according to the related data of Chinese residents nutrition in 2004 and health survey, and China's overweight rate of being grown up is 22.8%, obesity rates is 7.1%, and estimated number is respectively more than 2.0 hundred million and 6,000 ten thousand.Overweight rate and obesity rates are grown up respectively up to 30.0% and 12.3% in the big city, the children obesity rate has reached 8.1%, compares with national nutrition survey data in 1992, and the overweight rate of being grown up rises 39%, obesity rates rises 97%, and fat prevalence still is fast rise trend.
Obesity be meant the body fat overheap and (or) distribute unusually, weight increase is a kind of multifactorial chronic metabolic disease.It is fat main cause that inherited genetic factors, high heat, high fat diet, physical exertion reduce.Obesity is normal assembles appearance with dyslipidemia, hypertension, type 2 diabetes mellitus etc.
Because fat and relevant disease healthhazard own, obesity can damage patient's physical and mental health, quality of life decline, life expectancy shortening, obesity becomes one of important worldwide health problem gradually.The China adult who announced in 2003 is overweight and obesity prevention and control guideline recommendation should be used the medicine loss of weight for the obesity that merges dyslipidemia, hypertension, hyperglycemia and fatty liver.
Sibutramine (Sibutramine) is that only two kinds of FDA (Food and Drug Adminstration) (FDA) approval can be used for one of medicine of bariatrician for a long time, its main mechanism is: suppress the reuptake of neurocyte to 5-hydroxy tryptamine, norepinephrine, can reduce beta-adrenaline binding ability and norepinephrine receptor stimulates the adenylate cyclase enzyme system.This is a kind of two-way function pattern, can reduce food-intake by increasing satietion; Simultaneously by inducing calorigenic action to increase energy expenditure.
Fibrate lipid-lowering drugs can quicken the decomposition of lipoprotein by strengthening the activity of lipoprotein lipase, also can reduce the synthetic of lipoprotein in the liver simultaneously, thus blood lipid regulation.
Still there is not at present the medicine that effective treatment of obesity merges hyperlipidemia clinically, in existing patent and scientific and technical literature, we do not have to find that the pharmaceutical composition of uniting sibutramine and fibrate lipid-lowering drugs in clinical and preclinical study is used for the treatment of the report that obesity merges hyperlipidemia yet.
Summary of the invention
The purpose of this invention is to provide the pharmaceutical composition that a kind of effective treatment of obesity merges hyperlipidemia, still do not have the problem that effective treatment of obesity merges the medicine of hyperlipidemia clinically to solve.Pharmaceutical composition provided by the invention contains acceptable carrier on sibutramine, fibrate lipid-lowering drugs and the pharmaceutics.
For realizing above-mentioned purpose of the present invention, the present invention by the following technical solutions:
A kind of pharmaceutical composition contains sibutramine or its officinal salt or the active metabolite of medicinal content, acceptable carrier on a kind of and pharmaceutics in the fibrate lipid-lowering drugs of medicinal content.
In pharmaceutical composition provided by the invention, sibutramine is as a kind of active component, becomes content of the present invention with acceptable carrier mutual group on fibrate lipid-lowering drugs and the pharmaceutics.Sibutramine can exist with the form of chemical compound, also can the medicinal precursor of sibutramine, forms such as sibutramine active metabolite or sibutramine salt exist.The preferred Sibutramine hydrochloride of the salt of sibutramine.As the equivalents of sibutramine, above-mentioned substance is also in the scope of protection of present invention.
In pharmaceutical composition provided by the invention, sibutramine content is 1～20mg, and preferred 5mg～15mg is more preferably 5mg～10mg.The content and the sibutramine content of the medicinal precursor of sibutramine, sibutramine active metabolite or sibutramine salt can be equal to conversion.
In pharmaceutical composition provided by the invention, fibrate lipid-lowering drugs comprises clofibrate, lifibrate, chlorine shellfish butanoic acid aluminum, simfibrate, bezafibrate, fenofibrate, ciprofibrate, clinofibrate, binifibrate, etofibrate, metibride, gemfibrozil, etofylline clofibrate, etofibrate, Ronifibrate, beclobrate, preferred bezafibrate, fenofibrate, gemfibrozil are more preferably fenofibrate.Will be appreciated that; above-mentioned explanation is not a limitation of the present invention; every is the chemical compound of active component with clofibrate, lifibrate, chlorine shellfish butanoic acid aluminum, simfibrate, bezafibrate, fenofibrate, ciprofibrate, clinofibrate, binifibrate, etofibrate, metibride, gemfibrozil, etofylline clofibrate, etofibrate, Ronifibrate or beclobrate; for example almufibrate, clofibrate magnesium, clofibrate calcium etc. all are the scope of protection of the invention.
In pharmaceutical composition provided by the invention, bezafibrate content is that 200mg～500mg, fenofibrate content are that 100mg～600mg, gemfibrozil content are that 300mg～1200mg, clofibrate content are that 200mg～1500mg, ciprofibrate content are 100mg～200mg, etofylline clofibrate 250mg～500mg, and the active metabolite of above-mentioned substance or salt product 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 fibrate is respectively: bezafibrate 200mg～400mg, fenofibrate 100mg～400mg, gemfibrozil 300mg～600mg, clofibrate 250mg～500mg, the active metabolite of above-mentioned substance or salt product can be tried to achieve according to of equal value conversion of above-mentioned substance.
In the pharmaceutical composition provided by the invention, the content of Sibutramine hydrochloride is 5mg～10mg; Fibrate lipid-lowering drugs is a fenofibrate, and content is 100mg～400mg.
In the pharmaceutical composition provided by the invention, the content of Sibutramine hydrochloride is 5mg～10mg; Fibrate lipid-lowering drugs is a clofibrate, and content is 250mg～500mg.
In the pharmaceutical composition provided by the invention, the content of Sibutramine hydrochloride is 5mg～10mg; Fibrate lipid-lowering drugs is a bezafibrate, and content is 200mg～400mg.
In the pharmaceutical composition provided by the invention, the content of Sibutramine hydrochloride is 5mg～10mg; Fibrate lipid-lowering drugs is a gemfibrozil, and content is 300mg～600mg.
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 is a Sibutramine hydrochloride, and active component comes from a kind of in the fibrate lipid-lowering drugs; 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 Sibutramine hydrochloride, the pharmaceutical composition of fibrate lipid-lowering drugs 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 or three every day, perhaps with slow release or controlled release mode every day or a few days takes once every other day or at interval.
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 sibutramine or its officinal salt or active metabolite and fibrate lipid-lowering drugs and the pharmaceutics and is used for the treatment of purposes in the medicine that obesity merges hyperlipidemia in preparation.
In purposes of the present invention, described sibutramine or its officinal salt or active metabolite are Sibutramine hydrochloride, and its content is 5mg～10mg; Described fibrate lipid-lowering drugs comprises clofibrate, lifibrate, chlorine shellfish butanoic acid aluminum, simfibrate, bezafibrate, fenofibrate, ciprofibrate, clinofibrate, binifibrate, etofibrate, metibride, gemfibrozil, etofylline clofibrate, etofibrate, Ronifibrate, beclobrate, preferred bezafibrate, fenofibrate, gemfibrozil are more preferably fenofibrate.Will be appreciated that; above-mentioned explanation is not a limitation of the present invention; every is the chemical compound of active component with clofibrate, lifibrate, chlorine shellfish butanoic acid aluminum, simfibrate, bezafibrate, fenofibrate, ciprofibrate, clinofibrate, binifibrate, etofibrate, metibride, gemfibrozil, etofylline clofibrate, etofibrate, Ronifibrate or beclobrate; for example almufibrate, clofibrate magnesium, clofibrate calcium etc. all are the scope of protection of the invention.
In purposes of the present invention, bezafibrate content is that 200mg～500mg, fenofibrate content are that 100mg～600mg, gemfibrozil content are that 300mg～1200mg, clofibrate content are that 200mg～1500mg, ciprofibrate content are 100mg～200mg, etofylline clofibrate 250mg～500mg, and the active metabolite of above-mentioned substance or salt product 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 fibrate is respectively: bezafibrate 200mg～400mg, fenofibrate 100mg～400mg, gemfibrozil 300mg～600mg, clofibrate 250mg～500mg, the active metabolite of above-mentioned substance or salt product can be tried to achieve according to of equal value conversion of above-mentioned substance.
In purposes of the present invention, the content of Sibutramine hydrochloride is 5mg～10mg; Fibrate lipid-lowering drugs is a fenofibrate, and content is 100mg～400mg.
In purposes of the present invention, the content of Sibutramine hydrochloride is 5mg～10mg; Fibrate lipid-lowering drugs is a clofibrate, and content is 250mg～500mg.
In purposes of the present invention, the content of Sibutramine hydrochloride is 5mg～10mg; Fibrate lipid-lowering drugs is a bezafibrate, and content is 200mg～400mg.
In purposes of the present invention, the content of Sibutramine hydrochloride is 5mg～10mg; Fibrate lipid-lowering drugs is a gemfibrozil, and content is 300mg～600mg.
The medicine that pharmaceutical composition provided by the invention is made has the effect that the obvious treatment obesity merges hyperlipidemia, therefore is the medicine that treatment of obesity preferably merges hyperlipidemia.
In clinical practice or the scientific research document of having delivered, we do not find as yet that Sibutramine hydrochloride, fibrate lipid-lowering drugs are united and are used for the treatment that obesity merges hyperlipidemia.In experiment, we find, the medicine that the compositions of Sibutramine hydrochloride provided by the invention, fibrate lipid-lowering drugs is made, and obesity is merged hyperlipidemia excellent curative.
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 1～4: the preparation of the compound hydrochloric acid sibutramine fenofibrate of different content proportioning (1000 amounts)
Table 1 embodiment 1～4 tablet formulation is formed
Preparation technology:
(1) takes by weighing the Sibutramine hydrochloride and the fenofibrate 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 5～16: the preparation (1000 amounts) of the special sheet of compound hydrochloric acid sibutramine shellfish
Table 2 embodiment 5～16 tablet formulations are formed
Continuous table 2 embodiment 5～16 tablet formulations are formed
Preparation technology:
(1) takes by weighing the Sibutramine hydrochloride and the fibrate 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 17～19: the special capsular preparation (1000 amounts) of compound hydrochloric acid sibutramine shellfish
Table 3 embodiment 17～19 capsules prescription is formed
Preparation technology:
(1) takes by weighing the Sibutramine hydrochloride and the fibrate 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 20～22: the preparation (1000 bags of amounts) of the special granule of compound hydrochloric acid sibutramine shellfish
Table 4 embodiment 20～22 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) it is standby that other adjuvants are crossed 100 mesh sieves 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 23～25: the preparation (1000 amounts) of the special slow releasing tablet of compound hydrochloric acid sibutramine shellfish
Preparation technology:
(1) takes by weighing the Sibutramine hydrochloride and the fibrate 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 (solvent 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.
Table 5 embodiment 23～25 sustained-release tablet recipes are formed
Embodiment 26: the collaborative effect that obesity is merged hyperlipemia rat obesity and blood fat of Sibutramine hydrochloride+fenofibrate
80 of fat Zecker rats, male and female half and half, adaptability is measured blood fat and is randomly drawed 10 as the normal control group, the feed normal feedstuff after raising a week.Select 43 of obviously unusual rats of blood fat and merge the high blood lipid model animal as fat, and randomly draw 40 and be divided into 4 groups at random, promptly model control group is 10, the high fat diet of feeding; 10 of Sibutramine hydrochloride groups, the high fat diet of feeding, Sibutramine hydrochloride 1mg/kg irritates stomach, 1 time/day; 10 of fenofibrate groups, the high fat diet of feeding, fenofibrate 30mg/kg irritates stomach, 1 time/day; 10 of Sibutramine hydrochloride+fenofibrate group, the high fat diet of feeding, Sibutramine hydrochloride 1mg/kg+ fenofibrate 30mg/kg irritates stomach, 1 time/day.Each organizes the administration cycle is 60d, and measures blood fat and Body Mass Index when younger brother 20,40 and 60d after administration.
Statistical method: data are represented with x ± s, relatively adopt 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 blood fat and Body Mass Index do not have significant change; There were significant differences for the normal matched group of model control group blood fat and Body Mass Index; Sibutramine hydrochloride and Sibutramine hydrochloride+fenofibrate group Body Mass Index obviously reduces (P＜0.01 or P＜0.05), with model control group significant difference is arranged relatively, and Sibutramine hydrochloride+fenofibrate group is than Sibutramine hydrochloride group difference more remarkable (P＜0.05); Fenofibrate group and Sibutramine hydrochloride+fenofibrate group blood fat obviously reduces (P＜0.01 or P＜0.05), with model control group significant difference is arranged relatively, and Sibutramine hydrochloride+fenofibrate group is than fenofibrate group difference more remarkable (P＜0.05).
Claims (10)
1. pharmaceutical composition, contain:
1) sibutramine of medicinal content;
2) a kind of in the fibrate lipid-lowering drugs of medicinal content;
3) acceptable carrier on the pharmaceutics.
2. the described compositions of claim 1, it is characterized in that: described fibrate lipid-lowering drugs is selected from fenofibrate, bezafibrate, clofibrate, gemfibrozil, lifibrate, chlorine shellfish butanoic acid aluminum, simfibrate, ciprofibrate, clinofibrate, binifibrate, etofibrate, metibride, etofylline clofibrate, etofibrate, Ronifibrate, a kind of in the beclobrate, wherein, bezafibrate content is 200mg～500mg, fenofibrate content is 100mg～600mg, gemfibrozil content is 300mg～1200mg, clofibrate content is 200mg～1500mg, ciprofibrate content is 100mg～200mg, etofylline clofibrate 250mg～500mg.
3. the described compositions of claim 2, it is characterized in that: described fibrate lipid-lowering drugs is selected from a kind of in bezafibrate, fenofibrate, gemfibrozil, the clofibrate, wherein, bezafibrate content is that 200mg～400mg, fenofibrate content are that 100mg～400mg, gemfibrozil content are that 300mg～600mg, clofibrate content are 250mg～500mg.
4. the described compositions of claim 1, it is characterized in that: described sibutramine content is 1mg～20mg, preferred 5mg～15mg is more preferably 10mg～15mg.
5. the described compositions of claim 1, it is characterized in that: described sibutramine content is 5mg～10mg; Described fibrate lipid-lowering drugs is a bezafibrate, and content is 200mg～400mg.
6. the described compositions of claim 1, it is characterized in that: described sibutramine content is 5mg～10mg; Described fibrate lipid-lowering drugs is a fenofibrate, and content is 100mg～400mg.
7. the described compositions of claim 1, it is characterized in that: described sibutramine content is 5mg～10mg; Described fibrate lipid-lowering drugs is a gemfibrozil, and content is 300mg～600mg.
8. the described compositions of claim 1, it is characterized in that: described sibutramine content is 5mg～10mg; Described fibrate lipid-lowering drugs is a clofibrate, and content is 250mg～500mg.
9. any one described compositions in the claim 1 to 8 is characterized in that, the pharmacy dosage form of described compositions comprises conventional tablet, slow releasing tablet, controlled release tablet, granule, conventional capsule, slow releasing capsule, controlled release capsule.
10. any one described compositions is used for the treatment of purposes in the medicine that obesity merges hyperlipidemia in preparation in the claim 1 to 9.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2009100862750A CN101897685A (en) | 2009-05-27 | 2009-05-27 | Composition containing sibutramine and fibrate lipid-lowering drugs |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2009100862750A CN101897685A (en) | 2009-05-27 | 2009-05-27 | Composition containing sibutramine and fibrate lipid-lowering drugs |
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| CN101897685A true CN101897685A (en) | 2010-12-01 |
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| CN2009100862750A Pending CN101897685A (en) | 2009-05-27 | 2009-05-27 | Composition containing sibutramine and fibrate lipid-lowering drugs |
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2009
- 2009-05-27 CN CN2009100862750A patent/CN101897685A/en active Pending
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Application publication date: 20101201 |