CN105147678A - Oral medicine composition for treating obesity or vascular hypertension - Google Patents
Oral medicine composition for treating obesity or vascular hypertension Download PDFInfo
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- CN105147678A CN105147678A CN201510654984.XA CN201510654984A CN105147678A CN 105147678 A CN105147678 A CN 105147678A CN 201510654984 A CN201510654984 A CN 201510654984A CN 105147678 A CN105147678 A CN 105147678A
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Abstract
The invention discloses an oral medicine composition for treating obesity or vascular hypertension, and belongs to the field of medicine. The medicine composition comprises Orlistat or Cetilista and active ingredients of dipine medicine. In the medicine composition, the use amount of Orlistat or Cetilista and dipine medicine is greatly reduced; particularly, a sustained-release capsule prepared from the medicinal composition can achieve the treatment effect after being taken once a day only, so that the benefit/cost is increased, the patient compliance is improved, and the social value is higher.
Description
Technical field
The present invention relates to a kind of combination of oral medication being used for the treatment of obesity or vascular hypertension, belong to field of medicaments.
Background technology
" China's the first fat dying " has beaten alarm bell to us, existing society obesity has not belonged to fat person to be owned, as long as Body Mass Index reaches more than 24, all be referred to as obesity, it tangles the whole mankind just as " serious illness ", and obesity spreads in the developing country that developed country and economy develop rapidly and comes as pestilence, and sickness rate rises year by year, due to the raising of people's living standard and the change of diet structure, there is rejuvenation situation in obesity.For the treatment of this disease, the fat-reducing Western medicine prevailing in the market of the treatment for obesity divides two large classes: nervus centralis drugs with function and non-nervus centralis drugs with function.In China, the former with fenfluramine and sibutramine the most common, wherein fenfluramine is because of likely cardiac trigger valve disease, is just prohibited from using in the U.S. as far back as 1997.Sibutramine then can cause elevation of the blood pressure, increased heart rate.Therefore use the medicine of nervus centralis effect to follow the doctor's advice, want the fluctuation of periodic detection HRV index simultaneously, have the people of cardiovascular disease and apoplexy history more should be cautious use of.
The appetrol market of domestic market, the most remarkable with the development of orlistat and ATL-962, wherein orlistat is first and is a unique non-central nervous drugs, it is the up-to-date slimming medicine in international popular, this product is long-acting and potent specific gastrointestinal lipase inhibitor, it makes enzyme deactivation by forming covalent bond with the active ser position of gastric lipase in harmonization of the stomach small intestinal lumen and pancreatic lipase and plays therapeutical effect, the enzyme of inactivation can not by the fat in food, mainly triglyceride hydrolysis is absorbable free fatty and monoacylglycerol.Indigested triglyceride by body absorption, thus can not reduce energy intake, controls body weight.This medicine is without the need to playing drug effect by systemic Absorption.Orlistat suppresses fat absorption, and therefore may cause steatorrhea, another side effect that long-term taking orlistat may cause is fat-soluble avitaminosis.It is reported in the recent period, a large amount of take orlistat continuously liver parenchyma may be caused to damage.
ATL-962 is the up-to-date weight reducing medicine researched and developed by Alizyme, the efficacy and saferry of ATL-962 is confirmed, its effect is suitable with the similar medicine orlistat of Roche, but the toleration of ATL-962 is better, and later development trend will be more fierce, along with expanding economy, slimming medicine is relative to slimming health product, and curative effect is more definite, treats clearer, along with people are to improving constantly of requiring of quality of life, the market of appetrol also can be increasing.
Hypertension is called as " killer " in present one is also " affluenza ", present growth in the living standard, have stimulated the various desires of people greatly, especially appetite, irrational meals result in increasing of various index in blood vessel especially, cause the problem of a series of health subhealth state, such as hypertension, diabetes, obesity, wherein obesity is one of topmost disease caused in hypertension.Obesity has increased the weight of again the state of an illness of hypertension simultaneously.
The feature of Horizon class curative effect of medication: onset is rapid, powerful, efficacy of antihypertensive treatment and Amplitude of Hypotensive are comparatively strong, and curative effect and dose proportional, the individual variation of curative effect is less, has potentiation with the therapeutic alliance of other types depressor.Rarer contraindication except heart failure.Better to gerontal patient's antihypertensive effect, non-steroid stay body anti-inflammatory drug interference-free, also have remarkable hypotensive effect to alcoholic patient.Can be used for complication with diabetes, coronary heart disease and peripheral blood vessel patient, life-time service has study of anti-atherogenic effect.Untoward reaction causes increased heart rate, flush, headache, lower limbs edema.Non-dihydropyridine forbids nifedipine, nicardipine to heart failure, low atrionector function, heart-block person
Live about orlistat the use in conjunction of ATL-962 and Horizon class medicine, has no report in prior art.
Summary of the invention
In view of the deficiencies in the prior art, the object of the present invention is to provide a kind of novel combination of oral medication, for the first-line drug of hypertension, obese patient, especially the use of obesity-related hypertension patient, inventor proposes first and orlistat or ATL-962 and Horizon class medicine is prepared into pharmaceutical composition, and has filtered out the optimum dose proportion of front latter two medicine, by a large amount of animal experiment study, this pharmaceutical composition is evident in efficacy, demonstrates beyond thought technique effect.
In order to realize described object, creationary orlistat or ATL-962 and Horizon class medicine are prepared into pharmaceutical composition, performance orlistat is lost weight, the object of Horizon class medicine blood pressure lowering, by a large amount of animal model tests, present inventor filters out nifedipine in the hypertension drug of complexity or nicardipine is combined with orlistat or ATL-962, pay performing creative labour, in result unexpectedly, a kind of use in conjunction in orlistat or ATL-962 and nifedipine or nicardipine shows surprising synergism, the lasting medicine of use in conjunction two kinds of medicines plays a role stably, drug combination is obviously better than fat-reducing or the blood pressure lowering of same dosage single drug.
Described a kind of pharmaceutical composition for the treatment of hypertensive obesity patient can be ordinary tablet, slow releasing tablet, capsule, slow releasing capsule, dispersible tablet, granule, oral cavity disintegration tablet, is preferably, comprises slow releasing tablet, slow releasing capsule.
Through the experiment of continuous exploration, pharmaceutical composition of the present invention is made up of orlistat or ATL-962 and nifedipine or nicardipine and pharmaceutic adjuvant.Wherein, orlistat is 0.5-10:1 with the weight consumption ratio of nifedipine, and preferred ratio is orlistat is 1-4:1 with the weight consumption ratio of nifedipine, and most preferred orlistat is 3:1 with the weight consumption ratio of nifedipine; Orlistat is 0.5-6:1 with the weight consumption ratio of nicardipine, and preferred ratio is orlistat is 1-3:1 with the weight consumption ratio of nicardipine; Most preferred ratio is orlistat is 1.5:1 with the weight consumption ratio of nicardipine.Equally, ATL-962 is 0.8-12:1 with the weight consumption ratio of nifedipine, and preferred ratio is ATL-962 is 1-6:1 with the weight consumption ratio of nifedipine, and most preferred ATL-962 is 3.5:1 with the weight consumption ratio of nifedipine; ATL-962 is 1-7:1 with the weight consumption ratio of your card Horizon, and preferred ratio is ATL-962 is 1.5-2.5:1 with the weight consumption ratio of nicardipine; Most preferred ratio is ATL-962 is 2:1 with the weight consumption ratio of nicardipine.
Ratio through inventor's invention combination is screened, what deserves to be explained is, consumption per day nifedipine 15-60mg/d combines orlistat 30-120mg/d, and especially nifedipine 20mg/d associating orlistat 60mg/d therapeutic effect is best, there is obvious concertedness effect; Subsequently, the ratio of inventor to the combination medicine of nicardipine and orlistat is optimized screening, found that consumption per day nicardipine 20-60mg/d combines orlistat 40-160mg/d, especially nicardipine 40mg/d associating orlistat 60mg/d treatment is best.Consumption per day nifedipine 15-60mg/d combines ATL-962 50-180mg/d, and especially nifedipine 20mg/d associating ATL-962 70mg/d therapeutic effect is best, there is obvious concertedness effect; Subsequently, the ratio of inventor to the combination medicine of nicardipine and ATL-962 is optimized screening, found that consumption per day nicardipine 20-60mg/d combines ATL-962 60-200mg/d, especially nicardipine 40mg/d associating ATL-962 80mg/d treatment is best, above preferred ratio finds through animal model experiment, not only possess the long-term maintenance significantly hypertensive effect for the treatment of, also there is the object of significantly fat-reducing.
The present invention compared with prior art has beyond thought technique effect, is in particular in:
Compared with prior art, technique effect of the present invention has outstanding substantive distinguishing features and significant progress, is in particular in:
(1) combination that make use of orlistat and Horizon class medicine of the invention, especially the combination of nifedipine, nicardipine, over the course for the treatment of, merges the different appetrol of application mechanism of action and depressor, the effect that can reduce blood pressure and can lose weight, strengthens therapeutic effect.
(2) due to when forming immobilised compound, the dosage of each single medicine all has minimizing, especially the dosage of orlistat significantly reduces, thus the incidence rate of drug side effect reduces, benefit/expense the ratio for the treatment of is significantly improved, patient's curative compliance therefore increases greatly, and quality of life also just obviously improves.
(3) in zootype test, Horizon class medicine and orlistat or ATL-962 Synergistic treatment hypertensive obesity patient, in blood pressure statistics after body weight, medication, by biostatistics's angle analysis, compound recipe group of the present invention all has significant difference compared with model group, single dose group, other proportioning tests.
(4) drug combination of the present invention, production technology is comparatively simple, easy to operate, is applicable to suitability for industrialized production.
Specific embodiment
Embodiment 1: compound recipe orlistat/nifedipine tablets prescription (1000)
Preparation technology:
(1) granulate by orlistat, nifedipine, lactose respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85% alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate; after oven dry, cross 20 mesh sieve granulate, for subsequent use.
(2) tabletting is by the magnesium stearate of obtained granule and recipe quantity, and after mix homogeneously, tabletting, to obtain final product.
Embodiment 2: compound recipe orlistat/nifedipine tablets prescription (1000)
Preparation technology:
(1) granulate by orlistat, nifedipine, lactose respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85% alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate; after oven dry, cross 20 mesh sieve granulate, for subsequent use.
(2) tabletting is by the magnesium stearate of obtained granule and recipe quantity, and after mix homogeneously, tabletting, to obtain final product.
Embodiment 3: compound recipe orlistat/nifedipine tablets prescription (1000)
Preparation technology:
(1) granulate by orlistat, nifedipine, lactose respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85% alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate; after oven dry, cross 20 mesh sieve granulate, for subsequent use.
(3) tabletting is by the magnesium stearate of obtained granule and recipe quantity, and after mix homogeneously, tabletting, to obtain final product.
Embodiment 4: compound recipe orlistat/nifedipine tablets prescription (1000)
Preparation technology:
(1) granulate by orlistat, nifedipine, lactose respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85% alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate; after oven dry, cross 20 mesh sieve granulate, for subsequent use.
(4) tabletting is by the magnesium stearate of obtained granule and recipe quantity, and after mix homogeneously, tabletting, to obtain final product.
Embodiment 5: compound recipe orlistat/nifedipine tablets prescription (1000)
Preparation technology:
(1) granulate by orlistat, nifedipine, lactose respectively 80 orders sieve mixing after, together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose, mix, add 5%PVP85% alcoholic solution evenly and carry out wet granulation, take out granule 20 mesh sieves and carry out wet granulate, after oven dry, cross 20 mesh sieve granulate, for subsequent use;
(2) tabletting is by the magnesium stearate of obtained granule and recipe quantity, and after mix homogeneously, tabletting, to obtain final product.
Embodiment 6: compound recipe orlistat/nifedipine capsules prescription (1000)
Preparation technology:
Granulate by orlistat, nifedipine, lactose respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85% alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate, after oven dry, cross 20 mesh sieve granulate; incapsulate, to obtain final product.
Embodiment 7: compound recipe orlistat/nicardipine tablet prescription (1000)
Preparation technology:
(1) granulate by ATL-962, nicardipine, lactose respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85% alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate; after oven dry, cross 20 mesh sieve granulate, for subsequent use.
(2) tabletting is by the magnesium stearate of obtained granule and recipe quantity, and after mix homogeneously, tabletting, to obtain final product.
Embodiment 8: compound recipe orlistat/nicardipine capsule prescription (1000)
Preparation technology:
Granulate by ATL-962, nicardipine, lactose respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85% alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate; after oven dry, cross 20 mesh sieve granulate, incapsulate.
Embodiment 9: compound recipe orlistat/nicardipine tablet prescription (1000)
Preparation technology:
(1) granulate by ATL-962, nicardipine, lactose respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85% alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate; after oven dry, cross 20 mesh sieve granulate, for subsequent use.
(2) tabletting is by the magnesium stearate of obtained granule and recipe quantity, and after mix homogeneously, tabletting, to obtain final product.
Embodiment 10: compound recipe orlistat/nicardipine tablet prescription (1000)
Preparation technology:
(1) granulate by ATL-962, nicardipine, lactose respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85 alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate; after oven dry, cross 20 mesh sieve granulate, for subsequent use.
(2) tabletting is by the magnesium stearate of obtained granule and recipe quantity, and after mix homogeneously, tabletting, to obtain final product.
Embodiment 11: compound recipe orlistat/nicardipine tablet prescription (1000)
Preparation technology:
(1) granulate by ATL-962, nicardipine, lactose respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85% alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate; after oven dry, cross 20 mesh sieve granulate, for subsequent use.
(2) tabletting is by the magnesium stearate of obtained granule and recipe quantity, and after mix homogeneously, tabletting, to obtain final product.
Embodiment 12: compound recipe orlistat/nicardipine tablet prescription (1000)
Preparation technology:
(1) granulate by ATL-962, nicardipine, starch respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85% alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate; after oven dry, cross 20 mesh sieve granulate, for subsequent use.
(2) tabletting is by the magnesium stearate of obtained granule and recipe quantity, and after mix homogeneously, tabletting, to obtain final product.
Embodiment 13: compound recipe ATL-962/nifedipine tablets prescription (1000)
Preparation technology:
(1) granulate by ATL-962, nifedipine, lactose respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85 alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate; after oven dry, cross 20 mesh sieve granulate, for subsequent use.
(2) tabletting is by the magnesium stearate of obtained granule and recipe quantity, and after mix homogeneously, tabletting, to obtain final product.
Embodiment 14: compound recipe ATL-962/nifedipine tablets prescription (1000)
Preparation technology:
(1) granulate by ATL-962, nifedipine, lactose respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85% alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate; after oven dry, cross 20 mesh sieve granulate, for subsequent use.
(5) tabletting is by the magnesium stearate of obtained granule and recipe quantity, and after mix homogeneously, tabletting, to obtain final product.
Embodiment 15: compound recipe ATL-962/nifedipine tablets prescription (1000)
Preparation technology:
(1) granulate by ATL-962, nifedipine, lactose respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85% alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate; after oven dry, cross 20 mesh sieve granulate, for subsequent use.
(6) tabletting is by the magnesium stearate of obtained granule and recipe quantity, and after mix homogeneously, tabletting, to obtain final product.
Embodiment 16: compound recipe ATL-962/nifedipine tablets prescription (1000)
Preparation technology:
(1) granulate by ATL-962, nifedipine, lactose respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85% alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate; after oven dry, cross 20 mesh sieve granulate, for subsequent use.
(7) tabletting is by the magnesium stearate of obtained granule and recipe quantity, and after mix homogeneously, tabletting, to obtain final product.
Embodiment 17: compound recipe ATL-962/nifedipine tablets prescription (1000)
Preparation technology:
(1) granulate by ATL-962, nifedipine, lactose respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85% alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate; after oven dry, cross 20 mesh sieve granulate, for subsequent use.
(8) tabletting is by the magnesium stearate of obtained granule and recipe quantity, and after mix homogeneously, tabletting, to obtain final product.
Embodiment 18: compound recipe ATL-962/nifedipine capsules prescription (1000)
Preparation technology:
Granulate by ATL-962, nifedipine, lactose respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85% alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate, after oven dry, cross 20 mesh sieve granulate; incapsulate, to obtain final product.
Embodiment 19: compound recipe ATL-962/nicardipine tablet prescription (1000)
Preparation technology:
(1) granulate by ATL-962, nicardipine, lactose respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85% alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate; after oven dry, cross 20 mesh sieve granulate, for subsequent use.
(2) tabletting is by the magnesium stearate of obtained granule and recipe quantity, and after mix homogeneously, tabletting, to obtain final product.
Embodiment 20: compound recipe ATL-962/nicardipine capsule prescription (1000)
Preparation technology:
(1) granulate by ATL-962, nicardipine, lactose respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85% alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate; after oven dry, cross 20 mesh sieve granulate, incapsulate.
Embodiment 21: compound recipe ATL-962/nicardipine tablet prescription (1000)
Preparation technology:
(1) granulate by ATL-962, nicardipine, mannitol respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85% alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate; after oven dry, cross 20 mesh sieve granulate, for subsequent use.
(2) tabletting is by the magnesium stearate of obtained granule and recipe quantity, and after mix homogeneously, tabletting, to obtain final product.
Embodiment 22: compound recipe ATL-962/nicardipine tablet prescription (1000)
Preparation technology:
(1) granulate by ATL-962, nicardipine, lactose respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85% alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate; after oven dry, cross 20 mesh sieve granulate, for subsequent use.
(2) tabletting is by the magnesium stearate of obtained granule and recipe quantity, and after mix homogeneously, tabletting, to obtain final product.
Embodiment 23: compound recipe ATL-962/nicardipine tablet prescription (1000)
Preparation technology:
(1) granulate by ATL-962, nicardipine, lactose respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85% alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate; after oven dry, cross 20 mesh sieve granulate, for subsequent use.
(2) tabletting is by the magnesium stearate of obtained granule and recipe quantity, and after mix homogeneously, tabletting, to obtain final product.
Embodiment 24: compound recipe ATL-962/nicardipine tablet prescription (1000)
Preparation technology:
(1) granulate by ATL-962, nicardipine, lactose respectively 80 orders sieve mixing after; together mixer-granulator is put into hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose; mix; add 5%PVP85 alcoholic solution evenly and carry out wet granulation; take out granule 20 mesh sieves and carry out wet granulate; after oven dry, cross 20 mesh sieve granulate, for subsequent use.
(2) tabletting is by the magnesium stearate of obtained granule and recipe quantity, and after mix homogeneously, tabletting, to obtain final product.
Embodiment 25: compound recipe ATL-962/nicardipine prescription (1000)
Preparation technology:
(1) ATL-962 of recipe quantity, metoprolol, sorbitol, lactose, microcrystalline Cellulose mix homogeneously is taken;
(2) be separately incorporated in mixed-powder by appropriate 5%PVP alcoholic solution, mix homogeneously, soft material processed, makes wet grain by 18 mesh sieves, 50 DEG C of dryings, and dry granular moisture should control below 1.0%, incapsulates and get final product.
Above embodiment 1-25 is through long term test, and find efficacy stability, the content of related substance is all 1%, and especially embodiment 5, embodiment 6, embodiment 8, embodiment 12, embodiment 17, embodiment 18 are below 0.5%, is applicable to long term storage.
Embodiment 26: compound recipe is on the impact of obesity mice
1. the preparation of animal model
Normal diet group in 5 week age (normal group) 20,5 week age Kunming rat, original hypertensive rat 141, male, body weight 140-160g, nutrient fodder (nutrition group), water taken the photograph by two groups of all free diet.After 90 days (modeling phases), the rat that in nutrient fodder group, body weight exceedes general food group average weight 25% is hypertensive obesity rat model, removes 1 through screening.Wherein, nutrient fodder is prepared according to the following formulation: maltodextrin 20%, casein 20%, Adeps Sus domestica 20%, sucrose 10%, milk powder 10%, Semen arachidis hypogaeae 8%, egg 12%, Oleum Sesami 1%, Sal 2%.
2. grouping and administration
140 rats are divided into 7 groups at random, wherein rat model is divided into following 7 groups at random: model group, orlistat group, amlodipine group, compound recipe be group, compound recipe 2. group, compound recipe 3. group, compound recipe 4. group 1., amount to 8 groups with normal group group, gavage gives tested material, as table 1:
The grouping of table 1 laboratory animal and administrations
Except normal group, during administration other group still feed with the present invention configuration nutrient fodder, often organize 20, every day is administered once, during administration still feed with feedstuff of the present invention, every day gavage three times, respectively in 8:00,16:00,24:00 gavage, week for 7 weeks.
3. Testing index
(1) comparison of the body weight of different group is as table 2;
(2) blood pressure: with RBP-1 type rat blood pressure instrument Timing measurement rat systolic pressure.The results are shown in Table 3.
The comparison of the body weight after the different group of table 27 weeks
Compare with model group, * P < 0.05; Compare with model group, * * P < 0.01;
Compare with orlistat group,
■p < 0.05; Compare with orlistat group,
■ ■p < 0.01;
With compound recipe 1. group compare, P < 0.05; With compound recipe 1. group compare,
☆ ☆p < 0.01;
Compared with compound recipe 2. group,
#p < 0.05; With compound recipe 2. group compare,
##p < 0.01.
The comparison (mmHg) of table 3 each group blood pressure before and after treating
Compare with model group, * P < 0.05; Compare with model group, * * P < 0.01;
Compare with orlistat group,
■p < 0.05; Compare with orlistat group,
■ ■p < 0.01;
Compare with amlodipine group,
★p < 0.05; Compare with amlodipine group,
★ ★p < 0.01;
With compound recipe 1. group compare,
☆p < 0.05; With compound recipe 1. group compare,
☆ ☆p < 0.01;
Compared with compound recipe 2. group,
#p < 0.05; With compound recipe 2. group compare,
##p < 0.01.
Can be known by table 1, table 2, table 3, compound recipe of the present invention 3., 4. group, be obviously better than model group, orlistat group, amlodipine group, compound recipe 1. group, compound recipe 2. group at body weight, blood pressure; Compound recipe 1. group is by 15mgkg
-1d
-1orlistat+5mgkg
-1d
-1valsartan forms, and body weight control and blood pressure regulating are starkly lower than compound recipe group of the present invention, and the ratio that 2. compound recipe is organized is not the ratio that the present invention limits, and effect is also starkly lower than of the present invention group.
Embodiment 27: compound recipe is on the impact of obesity mice
1. the preparation of animal model
Normal diet group in 5 week age (normal group) 20,5 week age Kunming rat, original hypertensive rat 141, male, body weight 140-160g, nutrient fodder (nutrition group), water taken the photograph by two groups of all free diet.After 90 days (modeling phases), the rat that in nutrient fodder group, body weight exceedes general food group average weight 25% is hypertensive obesity rat model, removes 1 through screening.Wherein, nutrient fodder is prepared according to the following formulation: maltodextrin 20%, casein 20%, Adeps Sus domestica 20%, sucrose 10%, milk powder 10%, Semen arachidis hypogaeae 8%, egg 12%, Oleum Sesami 1%, Sal 2%.
2. grouping and administration
Rat is divided into 7 groups, wherein rat model is divided into following 7 groups at random: model group, orlistat group, nicardipine group, compound recipe be group, compound recipe 2. group, compound recipe 3. group, compound recipe 4. group 1., and amount to 8 groups with general food group, gavage gives tested material, as table 4:
The grouping of table 4 laboratory animal and administration
Except normal group, during administration other group still feed with the present invention configuration nutrient fodder, often organize 20, every day is administered once, during administration still feed with feedstuff of the present invention, every day gavage three times, respectively in 8:00,16:00,24:00 gavage, week for 7 weeks.
3. Testing index
(1) comparison of the body weight of different group is as table 5;
(2) blood pressure: with RBP-1 type rat blood pressure instrument Timing measurement rat systolic pressure.The results are shown in Table 6.
The comparison of the body weight after the different group of table 57 weeks
Compare with model group, * P < 0.05; Compare with model group, * * P < 0.01;
Compare with orlistat group,
■p < 0.05; Compare with orlistat group,
■ ■p < 0.01;
With compound recipe 1. group compare, P < 0.05; With compound recipe 1. group compare,
☆ ☆p < 0.01;
Compared with compound recipe 2. group,
#p < 0.05; With compound recipe 2. group compare,
##p < 0.01.
The comparison (mmHg) of table 6 each group blood pressure before and after treating
Compare with model group, * P < 0.05; Compare with model group, * * P < 0.01;
Compare with orlistat group,
■p < 0.05; Compare with orlistat group,
■ ■p < 0.01;
Compare with nicardipine group,
★p < 0.05; Compare with nicardipine group,
★ ★p < 0.01;
With compound recipe 1. group compare,
☆p < 0.05; 1. compare with compound recipe group,
☆ ☆p < 0.01;
Compared with compound recipe 2. group,
#p < 0.05; 1. compare with compound recipe group,
##p < 0.01.
Can be known by table 4, table 5, table 6, compound recipe of the present invention 3., 4. group, be obviously better than model group, orlistat group, nicardipine group, compound recipe 1. group, compound recipe 2. group at body weight, blood pressure, compound recipe 1. group is by 15mgkg
-1d
-1orlistat+10mgkg
-1d
-1captopril forms, and body weight control and blood pressure regulating are starkly lower than compound recipe group of the present invention, and the ratio that 2. compound recipe is organized is not the ratio that the present invention limits, and effect is also starkly lower than of the present invention group.
Embodiment 28: compound recipe is on the impact of obesity mice
1. the preparation of animal model
Normal diet group in 5 week age (normal group) 20,5 week age Kunming rat, original hypertensive rat 141, male, body weight 140-160g, nutrient fodder (nutrition group), water taken the photograph by two groups of all free diet.After 90 days (modeling phases), the rat that in nutrient fodder group, body weight exceedes general food group average weight 25% is hypertensive obesity rat model, removes 1 through screening.Wherein, nutrient fodder is prepared according to the following formulation: maltodextrin 20%, casein 20%, Adeps Sus domestica 20%, sucrose 10%, milk powder 10%, Semen arachidis hypogaeae 8%, egg 12%, Oleum Sesami 1%, Sal 2%.
2. grouping and administration
Rat is divided into 7 groups, wherein rat model is divided into following 7 groups at random: model group, ATL-962 group, amlodipine group, compound recipe be group, compound recipe 2. group, compound recipe 3. group, compound recipe 4. group 1., and amount to 8 groups with general food group, gavage gives tested material, as table 7:
The grouping of table 7 laboratory animal and administration
Except normal group, during administration other group still feed with the present invention configuration nutrient fodder, often organize 20, every day is administered once, during administration still feed with feedstuff of the present invention, every day gavage three times, respectively in 8:00,16:00,24:00 gavage, week for 7 weeks.
3. Testing index
(1) comparison of the body weight of different group is as table 8;
(2) blood pressure: with RBP-1 type rat blood pressure instrument Timing measurement rat systolic pressure.The results are shown in Table 9.
The comparison of the body weight after the different group of table 87 weeks
Compare with model group, * P < 0.05; Compare with model group, * * P < 0.01;
Compare with ATL-962 group,
■p < 0.05; Compare with ATL-962 group,
■ ■p < 0.01;
With compound recipe 1. group compare, P < 0.05; With compound recipe 1. group compare,
☆ ☆p < 0.01;
Compared with compound recipe 2. group,
#p < 0.05; With compound recipe 2. group compare,
##p < 0.01.
The comparison (mmHg) of table 9 each group blood pressure before and after treating
Compare with model group, * P < 0.05; Compare with model group, * * P < 0.01;
Compare with ATL-962 group,
■p < 0.05; Compare with ATL-962 group,
■ ■p < 0.01;
Compare with amlodipine group,
★p < 0.05; Compare with amlodipine group,
★ ★p < 0.01;
With compound recipe 1. group compare, P < 0.05; With compound recipe 1. group compare,
☆ ☆p < 0.01;
Compared with compound recipe 2. group,
#p < 0.05; With compound recipe 2. group compare,
##p < 0.01.
Can be known by table 7, table 8, table 9, compound recipe of the present invention 3., 4. group, be obviously better than model group, ATL-962 group, amlodipine group, compound recipe 1. group, compound recipe 2. group at body weight, blood pressure, compound recipe 1. group is by 15mgkg
-1d
-1aTL-962+5mgkg
-1d
-1valsartan forms, and body weight control and blood pressure regulating are starkly lower than compound recipe group of the present invention, and the ratio that 2. compound recipe is organized is not the ratio that the present invention limits, and effect is also starkly lower than of the present invention group.
Embodiment 29: compound recipe is on the impact of obesity mice
1. the preparation of animal model
Normal diet group in 5 week age (normal group) 20,5 week age Kunming rat, original hypertensive rat 141, male, body weight 140-160g, nutrient fodder (nutrition group), water taken the photograph by two groups of all free diet.After 90 days (modeling phases), the rat that in nutrient fodder group, body weight exceedes general food group average weight 25% is hypertensive obesity rat model, removes 1 through screening.Wherein, nutrient fodder is prepared according to the following formulation: maltodextrin 20%, casein 20%, Adeps Sus domestica 20%, sucrose 10%, milk powder 10%, Semen arachidis hypogaeae 8%, egg 12%, Oleum Sesami 1%, Sal 2%.
2. grouping and administration
Rat is divided into 7 groups, wherein rat model is divided into following 7 groups at random: model group, ATL-962 group, nicardipine group, compound recipe be group, compound recipe 2. group, compound recipe 3. group, compound recipe 4. group 1., and amount to 8 groups with normal group, gavage gives tested material, as table 10:
The grouping of table 10 laboratory animal and administration
Except normal group, during administration other group still feed with the present invention configuration nutrient fodder, often organize 20, every day is administered once, during administration still feed with feedstuff of the present invention, every day gavage three times, respectively in 8:00,16:00,24:00 gavage, week for 7 weeks.
3. Testing index
(1) comparison of the body weight of different group is as table 11;
(2) blood pressure: with RBP-1 type rat blood pressure instrument Timing measurement rat systolic pressure.The results are shown in Table 12.
The comparison of the body weight after the different group of table 11 7 weeks
Compare with model group, * P < 0.05; Compare with model group, * * P < 0.01;
Compare with ATL-962 group,
■p < 0.05; Compare with ATL-962 group,
■ ■p < 0.01;
With compound recipe 1. group compare, P < 0.05; With compound recipe 1. group compare,
☆ ☆p < 0.01;
Compared with compound recipe 2. group,
#p < 0.05; With compound recipe 2. group compare,
##p < 0.01.
The comparison (mmHg) of table 12 each group blood pressure before and after treating
Compare with model group, * P < 0.05; Compare with model group, * * P < 0.01;
Compare with ATL-962 group,
■p < 0.05; Compare with ATL-962 group,
■ ■p < 0.01;
Compare with nicardipine group,
★p < 0.05; Compare with nicardipine group,
★ ★p < 0.01;
With compound recipe 1. group compare,
☆p < 0.05; 1. compare with compound recipe group,
☆ ☆p < 0.01;
Compared with compound recipe 2. group,
#p < 0.05; 1. compare with compound recipe group,
##p < 0.01.
Can be known by table 10, table 11, table 12, compound recipe of the present invention 3., 4. group, be obviously better than model group, ATL-962 group, nicardipine group, compound recipe 1. group, compound recipe 2. group at body weight, blood pressure, compound recipe 1. group is by 15mgkg
-1d
-1aTL-962+10mgkg
-1d
-1captopril forms, and body weight control and blood pressure regulating are starkly lower than compound recipe group of the present invention, and the ratio that 2. compound recipe is organized is not the ratio that the present invention limits, and effect is also starkly lower than of the present invention group.
Claims (10)
1. be used for the treatment of a combination of oral medication for obesity or vascular hypertension, it is characterized in that, the active component of described pharmaceutical composition contains:
1) amlodipine or nicardipine one, and;
2) one of orlistat or ATL-962.
2. combination of oral medication according to claim 1, is characterized in that: described orlistat is 0.5-10:1 with the weight consumption ratio of amlodipine.
3. combination of oral medication according to claim 1, is characterized in that: described orlistat is 1-4:1 with the weight consumption ratio of amlodipine.
4. combination of oral medication according to claim 1, is characterized in that: described orlistat is 0.5-6:1 with the weight consumption ratio of nicardipine.
5. combination of oral medication according to claim 1, is characterized in that: described orlistat is 1-3:1 with the weight consumption ratio of nicardipine.
6. combination of oral medication according to claim 1, is characterized in that: described ATL-962 is 0.5-10:1 with the weight consumption ratio of amlodipine.
7. combination of oral medication according to claim 1, is characterized in that: described ATL-962 is 1-4:1 with the weight consumption ratio of amlodipine.
8. combination of oral medication according to claim 1, is characterized in that: described ATL-962 is 0.5-6:1 with the weight consumption ratio of nicardipine.
9. combination of oral medication according to claim 1, is characterized in that: described ATL-962 is 1.5: 1 with the weight consumption ratio of nicardipine.
10. combination of oral medication according to claim 1, is characterized in that: described orlistat is 3: 1 with the weight consumption ratio of amlodipine; Described orlistat is 1.5: 1 with the weight consumption ratio of nicardipine; Described ATL-962 is 3: 1 with the weight consumption ratio of amlodipine; Described ATL-962 is 1-3:1 with the weight consumption ratio of nicardipine.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107669673A (en) * | 2017-10-26 | 2018-02-09 | 郭裴哲 | A kind of medicine for treating obesity-related hypertension patient and preparation method thereof |
| CN107753482A (en) * | 2017-10-26 | 2018-03-06 | 郭裴哲 | A kind of drug compound preparation for treating obesity-related hypertension patient and preparation method thereof |
| CN107753471A (en) * | 2017-10-26 | 2018-03-06 | 郭裴哲 | A kind of pharmaceutical composition for treating obesity-related hypertension patient and preparation method thereof |
-
2015
- 2015-10-11 CN CN201510654984.XA patent/CN105147678A/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| S.N. KOVAL等: "Effect of amlodipine and orlistat combination on metabolic and endothelium-dependend vasoactive factors in hypertensive patients with obesity", 《HYPERTENSION》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107669673A (en) * | 2017-10-26 | 2018-02-09 | 郭裴哲 | A kind of medicine for treating obesity-related hypertension patient and preparation method thereof |
| CN107753482A (en) * | 2017-10-26 | 2018-03-06 | 郭裴哲 | A kind of drug compound preparation for treating obesity-related hypertension patient and preparation method thereof |
| CN107753471A (en) * | 2017-10-26 | 2018-03-06 | 郭裴哲 | A kind of pharmaceutical composition for treating obesity-related hypertension patient and preparation method thereof |
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Application publication date: 20151216 |