CN104906114A - Metformin-gliquidone compound sustained-release capsule and preparation method thereof - Google Patents

Metformin-gliquidone compound sustained-release capsule and preparation method thereof Download PDF

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CN104906114A
CN104906114A CN 201510337942 CN201510337942A CN104906114A CN 104906114 A CN104906114 A CN 104906114A CN 201510337942 CN201510337942 CN 201510337942 CN 201510337942 A CN201510337942 A CN 201510337942A CN 104906114 A CN104906114 A CN 104906114A
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metformin
parts
gliquidone
pellets
preparation
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CN 201510337942
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夏征梅
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青岛海之星生物科技有限公司
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Abstract

The invention discloses a metformin-gliquidone compound sustained-release capsule and a preparation method thereof. The metformin-gliquidone compound sustained-release capsule comprises the following components in parts by weight: 30-35 parts of metformin, 1-3 parts of gliquidone, 20-25 parts of microcrystalline cellulose pills, 0.5-1 part of glyceride, 0.5-0.8 part of polyethylene glycol and 4-6 parts of ethyl cellulose. The preparation method of the metformin-gliquidone compound sustained-release capsule comprises the steps of material preparation, preparation of metformin drug-containing pellets, preparation of metformin sustained-release pellets, preparation of gliquidone drug-containing pellets, preparation of gliquidone sustained-release pellets and capsule filling. The effective medical components, namely metformin and gliquidone, of the metformin-gliquidone compound sustained-release capsule have a good synergistic effect; the contents of the effective medical components are high; the consumption of the effective medical components and pharmaceutical adjuvants is low; and metformin and gliquidone can be released enduringly and slowly, and the plasma concentration is stable and has small fluctuation, so that the administration frequency is reduced and the patient compliance is improved.

Description

一种二甲双胍格列喹酮复方缓释胶囊及制备方法 Gliquidone one kind of metformin sustained release capsules and preparation method of Compound

技术领域 FIELD

[0001] 本发明属于医药技术领域,具体讲是一种二甲双胍格列喹酮复方缓释胶囊及制备方法。 [0001] The present invention belongs to the technical field of medicine, specifically a compound of metformin gliquidone sustained release capsules, and method of preparation.

背景技术 Background technique

[0002] 二甲双胍降糖效果准确,和磺脲类降糖类药比无低血糖反应,对肥胖和不肥胖的非胰岛素依赖型糖尿病人(NIDDM)均有效,对单纯饮食治疗无效者单独用本品,可降低其基础血糖浓度彡20% (-般为2mmol/L或36mg/dl)。 [0002] The hypoglycemic effect accurate metformin, sulfonylurea drugs and non-specific hypoglycemia, are effective for obesity and obesity are not non-insulin dependent diabetes (of NIDDM), of ineffective dietary treatment alone present alone products, can reduce the blood glucose concentration San basis of 20% (- generally of 2mmol / L or 36mg / dl). 可改善口服或静脉葡萄糖耐量试验, 其降糖作用与用药前血糖浓度、年龄、病程、体重和基础胰岛素水平均无关,首选用于单纯饮食控制及体育锻炼治疗无效的II型糖尿病,特别是肥胖的II型糖尿病。 Can improve oral or intravenous glucose tolerance test, its hypoglycemic effect and blood sugar levels before treatment, age, disease duration, body weight and basal insulin levels were unrelated, the first choice for the simple diet and physical exercise ineffective treatment of type II diabetes, especially obesity type II diabetes. 与胰岛素合同, 可减少胰岛素用量,防止低血糖发生,与磺酰脲类降血糖药合用,具有协同作用。 Insulin and contract, can reduce the amount of insulin to prevent hypoglycemia, hypoglycemic sulfonylurea drug combination, have a synergistic effect. 药效学包括:①促进周围组织细胞(肌肉等)对葡萄糖的利用;②抑制肝糖原异生作用,因此降低肝糖输出;③抑制肠壁细胞摄取葡萄糖,与胰岛素作用不同,即本品无促使脂肪合成的作用, 对正常人无明显降血糖作用,因此,一般不引起低血糖。 Pharmacodynamic include: ① promote surrounding tissue (muscle) glucose utilization; ② suppress of hepatic gluconeogenesis, reduce hepatic glucose output and therefore; ③ inhibition of intestinal glucose uptake by cells with different insulin, i.e., the product promote fat synthesis had no effect on the normal no significant hypoglycemic effect, and therefore generally do not cause hypoglycemia. 药动学包括:口服2h后血药浓度达到高峰,药物聚集在肠壁,为血浆浓度的10-100倍,肾脏、肝脏和唾液的浓度为血浆浓度的2倍以上,不与血浆蛋白结合,以原形随尿液排泄,清除半衰期为I. 7-4. 5h,12h内90%被清除。 Pharmacokinetics comprising: orally 2h after the peak plasma concentration, the drug accumulation in the intestinal wall, the plasma concentration of 10 to 100 times, kidney, liver and salivary concentration is at least twice the plasma concentration, is not bound to plasma proteins, prototype with the urine, elimination half-life I. 7-4. 5h, 90% is cleared within 12h. 患者用药期间体重通常减轻、血浆胆固醇、甘油三酯和前e脂蛋白水平可降低,外周葡萄糖代谢能得到改善。 Weight usually reduce the patient during treatment, plasma cholesterol, triglycerides and lipoprotein levels can be reduced before e, the peripheral glucose metabolism can be improved. 速释制剂口服一日3次。 Immediate release formulations for oral three times a day.

[0003] 格列喹酮系第二代口服磺脲类降糖药,为高活性亲胰岛e细胞剂,与胰岛e细胞膜上的特异性受体结合,可诱导产生适量胰岛素,以降低血糖浓度。 [0003] gliquidone the second generation of oral sulfonylurea drugs, e islet cell an active agent is a high affinity, with binding to specific receptors on cell membranes e islets, can induce an appropriate amount of insulin to lower blood glucose concentration . 药效学包括:①促进胰腺胰岛e细胞分泌胰岛素,先决条件是胰岛e细胞还有一定的合成和分泌胰岛素的功能; ②通过增加门静脉胰岛素水平或对肝脏直接作用,抑制肝糖原分解和糖原异生作用,肝生成和输出葡萄糖减少;③也可能增加胰外组织对胰岛素的敏感性和糖的利用。 Pharmacodynamic include: ① from pancreatic islet cells secrete insulin e, there are certain prerequisites that synthesize and secrete insulin e islet cells; ② insulin levels by increasing the portal vein or direct effect on the liver, inhibition of glycogen breakdown and sugar gluconeogenesis action, reduce hepatic glucose output and to generate; ③ and may also increase the sensitivity of tissues to insulin using trypsin outer sugar. 药动学包括: ①口服格列喹酮2-2. 5h后达到最高血药浓度,很快即被完全吸收。 Pharmacokinetics comprising:. ① after oral gliquidone 2-2 5h maximum blood concentration, was soon completely absorbed. ②血浆半衰期为I. 5h, 代谢完全,其代谢产物不具有降血糖作用,代谢产物绝大部分经胆道消化系统排泄。 ② plasma half-life I. 5h, completely metabolized, and its metabolites have no hypoglycemic effect, most of the metabolites by biliary excretion of the digestive system. 适用于单用饮食控制疗效不满意的轻、中度非胰岛素依赖型糖尿病,病人胰岛B细胞有一定的分泌胰岛素功能,并且无严重的并发症。 Suitable diet alone unsatisfactory efficacy of mild to moderate non-insulin dependent diabetes mellitus, patients with a certain islet B cells secrete insulin function, and no serious complications. 本品作用温和,可根据患者的病情调整剂量,较少发生低血糖反应。 This product is a moderate effect, the dose may be adjusted according to the disease of the patient, less hypoglycemia reaction. 在治疗早期以促进内源性胰岛素分泌为主,经一段时间治疗后其主要作用在于改善周围组织对胰岛素的敏感性。 In order to facilitate the treatment of early main endogenous insulin secretion, its main function over a period of time after treatment is to improve the sensitivity of peripheral tissues to insulin. 它是目前磺脲类口服降血糖药中唯一不受肾功能影响的药物,故可用于肾功能受损的糖尿病患者。 It is sulfonylurea oral hypoglycemic agents are not the only drug on renal function, it can be used in diabetic patients with impaired renal function. 速释制剂口服一日3次。 Immediate release formulations for oral three times a day.

[0004] 糖尿病是一种由于胰岛素分泌缺陷和/或胰岛素作用障碍所致的以高血糖为特征的代谢疾病。 [0004] Diabetes mellitus is a due to the defects in insulin secretion and / or insulin-induced disorder characterized by hyperglycemia metabolic disorder. 持续高血糖与长期代谢紊乱等可导致全身组织器官,特别是眼、肾、心血管及神经系统的损害及其功能障碍和衰竭。 Long-term sustained high blood sugar and metabolic disorders can lead to body tissues and organs, especially the damage and dysfunction of the eye, kidney, cardiovascular and nervous system and failure. 严重者可引起失水,电解质紊乱和酸碱平衡失调等急性并发症酮症酸中毒和高渗昏迷。 Severe cases can cause dehydration, electrolyte imbalance and acid-base balance disorders and other complications of acute ketoacidosis and hyperosmolar coma. 糖尿病一旦确诊,即应对病人进行糖尿病教育,包括糖尿病的一般知识、自我血糖和尿糖的检测。 Once diagnosed with diabetes, it shall be patient diabetes education, diabetes including general knowledge, self-detect blood sugar and urine sugar. 降糖药物的用法,不良反应的观察和处理等, 以及各种并发症的表现及防治。 , As well as performance and prevention of complications of the use of hypoglycemic drugs, observation and treatment of adverse reactions and so on. 糖尿病目前不能根治,一旦患有糖尿病需要终生服药,因此如何降低服药量及服药次数以便提高病人的依从性是目前急需解决的问题。 At present no cure for diabetes, once suffering from diabetes need lifelong medication, how to reduce the amount of medication and the number of medication in order to improve patient compliance is urgently needed to solve the problem.

发明内容 SUMMARY

[0005] 为减少糖尿病人的服药量及服药次数,本发明提供了一种二甲双胍格列喹酮复方缓释胶囊,该复方缓释胶囊协同效果好,口服后在消化道内按程序释放药物,稳定而持久的保持人体内的有效血药浓度,减少病人每天的服药量及服药次数,提高了病人的依从性。 [0005] To reduce the amount of medication in people with diabetes and the number of medication, the present invention provides a compound of metformin gliquidone sustained release capsules, sustained release capsules good synergistic effect of the compound, according to the procedure to release the drug in the digestive tract after oral administration, stability and permanent maintaining effective blood concentration in the human body, reducing the amount of medication a patient per day and the number of medication, improved patient compliance.

[0006] 本发明目的是由以下技术方案实现的: [0006] The object of the present invention is achieved by the following technical solution:

[0007] -种二甲双胍格列喹酮缓释胶囊,该复方缓释胶囊的组分及重量份数包括:二甲双胍30~35份、格列喹酮1~3份、微晶纤维素丸20~25份、甘油酯0. 5~1份、聚乙二醇0. 5~0. 8份、乙基纤维素4~6份。 [0007] - metformin species gliquidone sustained release capsules, and the weight of component parts of the compound of sustained release capsules comprising: 30 to 35 parts by metformin, gliquidone 1 to 3 parts of microcrystalline cellulose pills ~ 20 25 parts of glycerol 0.5 to 1 parts of polyethylene glycol 0.5 - 0.8 parts of 4 to 6 parts of ethyl cellulose.

[0008] 进一步的,一种二甲双胍格列喹酮复方缓释胶囊,该复方缓释胶囊的组分及重量份数包括:二甲双胍33份、格列喹酮2份、微晶纤维素丸22份、甘油酯0. 8份、聚乙二醇0. 7 份、乙基纤维素5份。 [0008] Further, a method of metformin gliquidone compound sustained release capsules, and the weight of component parts of the compound of sustained release capsules comprising: 33 parts metformin, gliquidone 2 parts, 22 parts of microcrystalline cellulose pills , 0.8 parts glycerol, 0.7 parts of polyethylene glycol, 5 parts of ethyl cellulose.

[0009] 进一步的,一种二甲双胍格列喹酮复方缓释胶囊,该复方缓释胶囊的组分及重量份数包括:二甲双胍30份、格列喹酮1份、微晶纤维素丸20份、甘油酯0. 5份、聚乙二醇0. 5 份、乙基纤维素4份。 [0009] Further, a method of metformin gliquidone compound sustained release capsules, and the weight of component parts of the compound of sustained release capsules comprising: 30 parts of metformin, gliquidone parts 1, 20 parts of microcrystalline cellulose pills , 0.5 parts glycerol, 0.5 parts of polyethylene glycol, 4 parts of ethyl cellulose.

[0010] 进一步的,一种二甲双胍格列喹酮复方缓释胶囊,该复方缓释胶囊的组分及重量份数包括:二甲双胍35份、格列喹酮3份、微晶纤维素丸25份、甘油酯1份、聚乙二醇0. 8 份、乙基纤维素6份。 [0010] Further, a method of metformin gliquidone compound sustained release capsules, and the weight of component parts of the compound of sustained release capsules comprising: 35 parts of metformin, gliquidone 3 parts, 25 parts of microcrystalline cellulose pills , 1 part of glycerol, 0.8 parts of polyethylene glycol, 6 parts of ethyl cellulose.

[0011] 本发明还提供了一种二甲双胍格列喹酮复方缓释胶囊的制备方法,其制备步骤包括: [0011] The present invention further provides a method for preparing a compound of metformin gliquidone ER, which preparation step comprises:

[0012] 1)备料,按照所需组分及重量份数备料; [0012] 1) preparation, preparation according to the desired component and by weight;

[0013] 2)二甲双胍含药微丸的制备,采用流化床底喷上药工艺,用质量浓度为65%~ 70%的酒精溶解二甲双胍制备二甲双胍的饱和溶液,得含药溶液,将微晶纤维素丸总量的十分之九放入流化床内,将含药溶液喷至空白丸芯上,制成含药丸芯; [0013] 2) Preparation of drug-containing pellets metformin, fluidized bed bottom-spray process of the drug, a saturated solution prepared dissolving metformin metformin the mass concentration of 65% to 70% alcohol, to obtain a solution containing the drug, microcrystalline nine-tenths of the total amount of cellulose pellets into the fluidized bed, the drug-containing solution was sprayed onto the non-pareil seeds made of pills containing core;

[0014] 3)二甲双胍缓释微丸的制备:采用稳定的流化床底喷包衣工艺,将甘油酯、聚乙二醇、乙基纤维素总量的十分之九用质量浓度为70%~80%的酒精溶解,得包衣溶液,酒精的用量为甘油酯、聚乙二醇、乙基纤维素所用重量的12倍,将包衣溶液喷至步骤2)所得含药丸芯上,制成缓释微丸; Preparation of [0014] 3) metformin sustained release pellets: The stable fluidized bed bottom spray coating process, glycerides, polyethylene glycols, nine-tenths of the total amount of the mass concentration of ethylcellulose 70 % to 80% alcohol was dissolved to obtain a coating solution, an amount of alcohol esters, polyethylene glycols, ethyl cellulose with 12 times the weight of the coating solution was sprayed to step 2) the resulting pellets containing the core, sustained release pellets;

[0015] 4)格列喹酮含药微丸的制备,采用流化床底喷上药工艺,用质量浓度为85%~ 90 %的酒精溶解格列喹酮制备格列喹酮的饱和溶液,得含药溶液,将微晶纤维素丸总量的十分之一放入流化床内,将含药溶液喷至空白丸芯上,制成含药丸芯; [0015] 4) Preparation of gliquidone drug-containing pellets using a fluidized bed bottom-spray process of the drug, with the mass concentration of the saturated solution was prepared dissolving gliquidone gliquidone 85% to 90% alcohol inside to give a solution containing the drug, the tenth of microcrystalline cellulose pellets into a fluidized bed, the drug-containing solution sprayed onto the non-pareil seeds made of pills containing core;

[0016] 5)格列喹酮缓释微丸的制备:采用稳定的流化床底喷包衣工艺,将甘油酯、聚乙二醇、乙基纤维素总量的十分之一用质量浓度为70%~80%的酒精溶解,得包衣溶液,酒精的用量为甘油酯、聚乙二醇、乙基纤维素所用重量的12倍,将包衣溶液喷至步骤2)所得含药丸芯上,制成缓释微丸; Gliquidone preparation of sustained release pellets [0016] 5): A stable fluidized bed bottom spray coating process, glycerides, polyethylene glycols, with one-tenth of the total mass of ethylcellulose concentration of 70% to 80% alcohol was dissolved to obtain a coating solution, an amount of alcohol esters, polyethylene glycols, ethyl cellulose with 12 times the weight of the coating solution was sprayed to step 2) containing pills obtained core, sustained release pellets;

[0017] 6)装囊:将步骤3)所得二甲双胍缓释微丸及步骤5)所得格列喹酮缓释微丸混合均匀,通过装囊机装囊,规格为0.5~LOg/粒。 [0017] 6) balloon loaded: the step 3), and the resulting pellets Metformin Step 5) The obtained sustained-release pellets gliquidone uniformly mixed by means capsule capsule machine installed, specifications for 0.5 ~ LOg / grain.

[0018] 6、根据权利要求5所述的一种二甲双胍格列喹酮复方缓释胶囊的制备方法,其特征在于,二甲双胍含药微丸的制备工艺参数为:进风温度为55~60°C,物料温度为45~ 50°C,供液转速为50rpm,风机频率为25Hz,雾化压力为0. 15Mpa;二甲双胍缓释微丸的制备工艺参数为:进风温度为45~55°C,物料温度为35~45°C,供液转速为65rpm,风机频率为25Hz,雾化压力为0• 12Mpa。 [0018] 6. A 5 metformin glibenclamide preparation of sustained release capsules methaqualone compound as claimed in claim, characterized in that the process parameters of metformin drug-containing pellets: inlet air temperature is 55 ~ 60 ° C, the mass temperature 45 ~ 50 ° C, liquid feed speed of 50rpm, the fan frequency is 25Hz, atomization pressure of 0. 15Mpa; sustained-release pellets metformin process parameters were: inlet air temperature is 45 ~ 55 ° C , the material temperature is 35 ~ 45 ° C, the liquid supply speed of 65 rpm, the fan frequency is 25Hz, atomization pressure of 0 • 12Mpa.

[0019] 7、根据权利要求5所述的一种二甲双胍格列喹酮复方缓释胶囊的制备方法,其特征在于,格列喹酮含药微丸的制备工艺参数为:进风温度为50~55°C,物料温度为40~ 45°C,供液转速为55rpm,风机频率为25Hz,雾化压力为0. 13Mpa;二甲双胍缓释微丸的制备工艺参数为:进风温度为45~55°C,物料温度为35~45°C,供液转速为65rpm,风机频率为25Hz,雾化压力为0• 12Mpa。 [0019] 7. An metformin glibenclamide 5 Preparation of sustained release capsules quinolin-one compound as claimed in claim, characterized in that the process parameters gliquidone drug-containing pellets are: inlet air temperature of 50 ~ 55 ° C, the mass temperature 40 ~ 45 ° C, liquid feed speed of 55rpm, the fan frequency is 25Hz, atomization pressure of 0. 13Mpa; sustained-release pellets metformin process parameters were: inlet air temperature of 45 ~ 55 ° C, the mass temperature 35 ~ 45 ° C, liquid feed speed of 65rpm, the fan frequency is 25Hz, atomization pressure of 0 • 12Mpa.

[0020] 本发明的有益效果: [0020] Advantageous effects of the invention:

[0021] 1)为了更好的治疗II型糖尿病,本发明经过筛选采用二甲双胍、格列喹酮作为有效药物成分制成复方缓释胶囊。 [0021] 1) In order to better treatment of type II diabetes, the present inventors have screened metformin, gliquidone compound as an active pharmaceutical ingredient prepared sustained release capsules. 本复方缓释胶囊的有效药物成分二甲双胍、格列喹酮协同作用效果好,有效药物成分及药用辅料用量少,药物有效成分含量高,速释制剂用量每日为二甲双胍30mg/kg、格列喹酮3mg/kg,复方缓释制剂每日为二甲双胍24mg/kg、格列喹酮2. 4mg/kg。 This compound sustained active pharmaceutical ingredient metformin capsules, gliquidone synergistic effect, active pharmaceutical ingredients and pharmaceutically acceptable excipients with less high content of pharmaceutical active ingredients, the amount of fast-release formulation of metformin daily 30mg / kg, grid gliquidone 3mg / kg, a daily sustained release formulation of compound metformin 24mg / kg, gliquidone 2. 4mg / kg. 本复方缓释胶囊使二甲双胍、格列喹酮能够在体内实现持久、缓慢的释放药物, 血药浓度平稳,波动小,从而降低给药频率,提高患者依从性。 This compound metformin sustained release capsules, gliquidone lasting can be achieved in vivo, slow release of the drug, stable blood concentration, small fluctuations, thereby reducing the frequency of dosing, improving patient compliance. 通过控制有效药物成分在血液中的浓度以便维持药效,减少药物释放达峰次数,对患者的脏器还有一定保护。 By controlling the effective drug concentration in the blood in order to maintain the effect and reduces the drug release peak times, there is a certain organ of the patient protection. 本发明工艺简单,重现性好,易于工业化生产;成本低,有利于降低产品价格。 This process is simple, reproducible, easy to industrial production; low cost, help reduce prices.

[0022] 2)本发明的复方缓释胶囊在药用辅料、微晶纤维素丸、甘油酯、聚乙二醇、乙基纤维素的种类及用量选择方面,保证有效药物成分二甲双胍、格列喹酮能在体内实现持久、缓慢释放的同时,胶囊内填充物的均匀度好。 [0022] 2) sustained release capsule of Compound of the present invention is selected in type and amount of pharmaceutical excipients, microcrystalline cellulose pills, glycerol, polyethylene glycols, ethyl cellulose in order to ensure the effective pharmaceutical ingredient metformin, glibenclamide methaqualone lasting in the body can be achieved, while slow release, good uniformity of the capsule filling.

[0023] 3)本发明工艺的选择保证有效药物成分二甲双胍、格列喹酮能在体内实现持久、 缓慢释放的同时,胶囊内填充物的均匀度好。 Select [0023] 3) of the present invention, the process to ensure the effective pharmaceutical ingredient metformin, gliquidone lasting in the body can be achieved, while slow release, good uniformity of the capsule filling.

具体实施方式 detailed description

[0024] 根据下述实施例,可以更好地理解本发明。 [0024] The following examples, the present invention may be better understood. 然而,本领域的技术人员容易理解,实施例所描述的具体的物料配比、工艺条件及其结果仅用于说明本发明而不应当也不会限制权利要求书中所详细描述的本发明。 However, those skilled in the art will readily appreciate the specific materials described embodiments ratio, the process conditions and the results of the present invention are for illustration only and should not be described in detail without restricting the claims of the present invention.

[0025] 实施例1 [0025] Example 1

[0026] 一种二甲双胍格列喹酮复方缓释胶囊,该复方缓释胶囊的组分及重量份数包括: 二甲双胍33份、格列喹酮2份、微晶纤维素丸22份、甘油酯0. 8份、聚乙二醇0. 7份、乙基纤维素5份。 [0026] A compound of metformin gliquidone sustained release capsules, and the weight of component parts of the compound of sustained release capsules comprising: 33 parts metformin, gliquidone 2 parts, 22 parts of microcrystalline cellulose pills, glycerol 0.8 parts, 0.7 parts of polyethylene glycol, 5 parts of ethyl cellulose.

[0027] 一种二甲双胍格列喹酮复方缓释胶囊的制备方法,其制备步骤包括: [0027] A method for preparing the compound of metformin gliquidone ER, which preparation step comprises:

[0028] 1)备料,按照所需组分及重量份数备料; [0028] 1) preparation, preparation according to the desired component and by weight;

[0029] 2)二甲双胍含药微丸的制备,采用流化床底喷上药工艺,用质量浓度为65 %的酒精溶解二甲双胍制备二甲双胍的饱和溶液,得含药溶液,将微晶纤维素丸总量的十分之九放入流化床内,将含药溶液喷至空白丸芯上,制成含药丸芯;工艺参数为:进风温度为55~ 60°C,物料温度为45~50°C,供液转速为50rpm,风机频率为25Hz,雾化压力为0• 15Mpa; [0029] 2) Preparation of Metformin drug-containing pellets using a fluidized bed bottom-spray process drug, the mass concentration of 65% by a saturated solution of the alcohol prepared dissolving metformin metformin to obtain a solution containing the drug, microcrystalline cellulose pellets Add nine-tenths of the total amount of the fluidized bed, the drug-containing solution was sprayed onto the non-pareil seeds made of pills containing core; process parameters were: inlet air temperature is 55 ~ 60 ° C, the mass temperature 45 - 50 ° C, liquid feed speed of 50rpm, the fan frequency is 25Hz, atomization pressure of 0 • 15Mpa;

[0030] 3)二甲双胍缓释微丸的制备:采用稳定的流化床底喷包衣工艺,将甘油酯、聚乙二醇、乙基纤维素总量的十分之九用质量浓度为70%的酒精溶解,得包衣溶液,酒精的用量为甘油酯、聚乙二醇、乙基纤维素所用重量的12倍,将包衣溶液喷至步骤2)所得含药丸芯上,制成缓释微丸;工艺参数为:进风温度为45~55°C,物料温度为35~45°C,供液转速为65rpm,风机频率为25Hz,雾化压力为0• 12Mpa; Preparation of [0030] 3) metformin sustained release pellets: The stable fluidized bed bottom spray coating process, glycerides, polyethylene glycols, nine-tenths of the total amount of the mass concentration of ethylcellulose 70 % alcohol was dissolved to obtain a coating solution, an amount of alcohol esters, polyethylene glycols, ethyl cellulose with 12 times the weight of the coating solution was sprayed to step 2) containing the obtained core pellets, made slow release pellets; process parameters were: inlet air temperature is 45 ~ 55 ° C, the mass temperature 35 ~ 45 ° C, liquid feed speed of 65rpm, the fan frequency is 25Hz, atomization pressure of 0 • 12Mpa;

[0031] 4)格列喹酮含药微丸的制备,采用流化床底喷上药工艺,用质量浓度为85 %的酒精溶解格列喹酮制备格列喹酮的饱和溶液,得含药溶液,将微晶纤维素丸总量的十分之一放入流化床内,将含药溶液喷至空白丸芯上,制成含药丸芯;工艺参数为:进风温度为50~ 55°C,物料温度为40~45°C,供液转速为55rpm,风机频率为25Hz,雾化压力为0• 13Mpa; [0031] 4) Preparation of gliquidone drug-containing pellets using a fluidized bed bottom-spray process of the drug, with the mass concentration of 85% alcohol solution prepared by dissolving a saturated gliquidone of gliquidone give containing drug solution, a tenth of microcrystalline cellulose pellets into the fluidized bed, the drug-containing solution was sprayed onto the non-pareil seeds made of pills containing core; process parameters were: inlet air temperature of 50 to 55 ° C, the mass temperature 40 ~ 45 ° C, liquid feed speed of 55rpm, the fan frequency is 25Hz, atomization pressure of 0 • 13Mpa;

[0032] 5)格列喹酮缓释微丸的制备:采用稳定的流化床底喷包衣工艺,将甘油酯、聚乙二醇、乙基纤维素总量的十分之一用质量浓度为70%的酒精溶解,得包衣溶液,酒精的用量为甘油酯、聚乙二醇、乙基纤维素所用重量的12倍,将包衣溶液喷至步骤2)所得含药丸芯上,制成缓释微丸;工艺参数为:进风温度为45~55°C,物料温度为35~45°C,供液转速为65rpm,风机频率为25Hz,雾化压力为0• 12Mpa; Gliquidone preparation of sustained release pellets [0032] 5): A stable fluidized bed bottom spray coating process, glycerides, polyethylene glycols, with one-tenth of the total mass of ethylcellulose alcohol concentration of 70% was dissolved to obtain a coating solution, an amount of alcohol esters, polyethylene glycols, ethyl cellulose with 12 times the weight of the coating solution was sprayed to step 2) the resulting pellets containing the core, sustained release pellets; process parameters were: inlet air temperature is 45 ~ 55 ° C, the mass temperature 35 ~ 45 ° C, liquid feed speed of 65rpm, the fan frequency is 25Hz, atomization pressure of 0 • 12Mpa;

[0033] 6)装囊:将步骤3)所得二甲双胍缓释微丸及步骤5)所得格列喹酮缓释微丸混合均匀,通过装囊机装囊,规格为0. 5g/粒。 [0033] 6) balloon loaded: the step 3), and the resulting pellets Metformin Step 5) The obtained sustained-release pellets gliquidone uniformly mixed by means capsule capsule machine installed, specifications of 0. 5g / grain.

[0034] 使用方法:每日2次,每次1-2粒,或根据病情轻重情况遵医嘱。 [0034] Usage: 2 times a day, 1-2 capsules, according to the severity or compliance situation.

[0035] 贮藏:遮光、密封保存。 [0035] Storage: shading, sealed and stored.

[0036] 实施例2 [0036] Example 2

[0037] 一种二甲双胍格列喹酮复方缓释胶囊,该复方缓释胶囊的组分及重量份数包括: 二甲双胍30份、格列喹酮1份、微晶纤维素丸20份、甘油酯0. 5份、聚乙二醇0. 5份、乙基纤维素4份。 [0037] A compound of metformin gliquidone sustained release capsules, and the weight of component parts of the compound of sustained release capsules comprising: 30 parts of metformin, gliquidone parts 1, 20 parts of microcrystalline cellulose pills, glyceryl 0.5 parts, 0.5 parts of polyethylene glycol, 4 parts of ethyl cellulose.

[0038] 一种二甲双胍格列喹酮复方缓释胶囊的制备方法,其制备步骤包括: [0038] A method for preparing the compound of metformin gliquidone ER, which preparation step comprises:

[0039] 1)备料,按照所需组分及重量份数备料; [0039] 1) preparation, preparation according to the desired component and by weight;

[0040] 2)二甲双胍含药微丸的制备,采用流化床底喷上药工艺,用质量浓度为70%的酒精溶解二甲双胍制备二甲双胍的饱和溶液,得含药溶液,将微晶纤维素丸总量的十分之九放入流化床内,将含药溶液喷至空白丸芯上,制成含药丸芯;工艺参数为:进风温度为55~ 60°C,物料温度为45~50°C,供液转速为50rpm,风机频率为25Hz,雾化压力为0• 15Mpa; [0041] 3)二甲双胍缓释微丸的制备:采用稳定的流化床底喷包衣工艺,将甘油酯、聚乙二醇、乙基纤维素总量的十分之九用质量浓度为80%的酒精溶解,得包衣溶液,酒精的用量为甘油酯、聚乙二醇、乙基纤维素所用重量的12倍,将包衣溶液喷至步骤2)所得含药丸芯上,制成缓释微丸;工艺参数为:进风温度为45~55°C,物料温度为35~45°C,供液转速为65rpm,风机频率为25Hz,雾化压力为0• 12Mpa; [0040] 2) Preparation of Metformin drug-containing pellets using a fluidized bed bottom-spray process drug, the mass concentration of a saturated solution of 70% ethanol was prepared dissolving metformin metformin to obtain a solution containing the drug, microcrystalline cellulose pellets Add nine-tenths of the total amount of the fluidized bed, the drug-containing solution was sprayed onto the non-pareil seeds made of pills containing core; process parameters were: inlet air temperature is 55 ~ 60 ° C, the mass temperature 45 - 50 ° C, the liquid supply speed of 50 rpm is, the fan frequency is 25Hz, atomization pressure of 0 • 15Mpa; preparation [0041] 3) metformin sustained release pellets: the stable fluidized bed bottom spray coating process, glycerin esters, polyethylene glycol, nine-tenths of the total amount of the mass concentration of 80% ethyl cellulose dissolved in ethanol to give a coating solution, an amount of alcohol esters, polyethylene glycols, ethylcellulose used 12 times the weight of the coating solution was sprayed to step 2) the resultant core-containing pills, sustained release pellets; process parameters were: inlet air temperature is 45 ~ 55 ° C, the mass temperature 35 ~ 45 ° C, the liquid supply speed of 65rpm, the fan frequency is 25Hz, atomization pressure of 0 • 12Mpa;

[0042] 4)格列喹酮含药微丸的制备,采用流化床底喷上药工艺,用质量浓度为90%的酒精溶解格列喹酮制备格列喹酮的饱和溶液,得含药溶液,将微晶纤维素丸总量的十分之一放入流化床内,将含药溶液喷至空白丸芯上,制成含药丸芯;工艺参数为:进风温度为50~ 55°C,物料温度为40~45°C,供液转速为55rpm,风机频率为25Hz,雾化压力为0• 13Mpa; [0042] 4) Preparation of gliquidone drug-containing pellets using a fluidized bed bottom-spray process of the drug, with the mass concentration of 90% alcohol solution prepared by dissolving a saturated gliquidone of gliquidone give containing drug solution, a tenth of microcrystalline cellulose pellets into the fluidized bed, the drug-containing solution was sprayed onto the non-pareil seeds made of pills containing core; process parameters were: inlet air temperature of 50 to 55 ° C, the mass temperature 40 ~ 45 ° C, liquid feed speed of 55rpm, the fan frequency is 25Hz, atomization pressure of 0 • 13Mpa;

[0043] 5)格列喹酮缓释微丸的制备:采用稳定的流化床底喷包衣工艺,将甘油酯、聚乙二醇、乙基纤维素总量的十分之一用质量浓度为80%的酒精溶解,得包衣溶液,酒精的用量为甘油酯、聚乙二醇、乙基纤维素所用重量的12倍,将包衣溶液喷至步骤2)所得含药丸芯上,制成缓释微丸;工艺参数为:进风温度为45~55°C,物料温度为35~45°C,供液转速为65rpm,风机频率为25Hz,雾化压力为0• 12Mpa; Gliquidone preparation of sustained release pellets [0043] 5): A stable fluidized bed bottom spray coating process, glycerides, polyethylene glycols, with one-tenth of the total mass of ethylcellulose concentration of 80% alcohol was dissolved to obtain a coating solution, an amount of alcohol esters, polyethylene glycols, ethyl cellulose with 12 times the weight of the coating solution was sprayed to step 2) the resulting pellets containing the core, sustained release pellets; process parameters were: inlet air temperature is 45 ~ 55 ° C, the mass temperature 35 ~ 45 ° C, liquid feed speed of 65rpm, the fan frequency is 25Hz, atomization pressure of 0 • 12Mpa;

[0044] 6)装囊:将步骤3)所得二甲双胍缓释微丸及步骤5)所得格列喹酮缓释微丸混合均匀,通过装囊机装囊,规格为0.Sg/粒。 [0044] 6) balloon loaded: the step 3), and the resulting pellets Metformin Step 5) The obtained sustained-release pellets gliquidone uniformly mixed by means capsule capsule machine installed, specifications for 0.Sg/ grains.

[0045] 使用方法:每日2次,每次1-2粒,或根据病情轻重情况遵医嘱。 [0045] Usage: 2 times a day, 1-2 capsules, according to the severity or compliance situation.

[0046] 贮藏:遮光、密封保存。 [0046] Storage: shading, sealed and stored.

[0047] 实施例3 [0047] Example 3

[0048] 一种二甲双胍格列喹酮复方缓释胶囊,该复方缓释胶囊的组分及重量份数包括: 二甲双胍35份、格列喹酮3份、微晶纤维素丸25份、甘油酯1份、聚乙二醇0. 8份、乙基纤维素6份。 [0048] A compound of metformin gliquidone sustained release capsules, and the weight of component parts of the compound of sustained release capsules comprising: 35 parts of metformin, gliquidone 3 parts, 25 parts of microcrystalline cellulose pills, glycerol parts of 1, 0.8 parts of polyethylene glycol, 6 parts of ethyl cellulose.

[0049] 一种二甲双胍格列喹酮复方缓释胶囊的制备方法,其制备步骤包括: [0049] A method for preparing the compound of metformin gliquidone ER, which preparation step comprises:

[0050] 1)备料,按照所需组分及重量份数备料; [0050] 1) preparation, preparation according to the desired component and by weight;

[0051] 2)二甲双胍含药微丸的制备,采用流化床底喷上药工艺,用质量浓度为68 %的酒精溶解二甲双胍制备二甲双胍的饱和溶液,得含药溶液,将微晶纤维素丸总量的十分之九放入流化床内,将含药溶液喷至空白丸芯上,制成含药丸芯;工艺参数为:进风温度为55~ 60°C,物料温度为45~50°C,供液转速为50rpm,风机频率为25Hz,雾化压力为0• 15Mpa; [0051] 2) Preparation of Metformin drug-containing pellets using a fluidized bed bottom-spray process drug, the mass concentration of a saturated solution of 68% ethanol was prepared dissolving metformin metformin to obtain a solution containing the drug, microcrystalline cellulose pellets Add nine-tenths of the total amount of the fluidized bed, the drug-containing solution was sprayed onto the non-pareil seeds made of pills containing core; process parameters were: inlet air temperature is 55 ~ 60 ° C, the mass temperature 45 - 50 ° C, liquid feed speed of 50rpm, the fan frequency is 25Hz, atomization pressure of 0 • 15Mpa;

[0052] 3)二甲双胍缓释微丸的制备:采用稳定的流化床底喷包衣工艺,将甘油酯、聚乙二醇、乙基纤维素总量的十分之九用质量浓度为75%的酒精溶解,得包衣溶液,酒精的用量为甘油酯、聚乙二醇、乙基纤维素所用重量的12倍,将包衣溶液喷至步骤2)所得含药丸芯上,制成缓释微丸;工艺参数为:进风温度为45~55°C,物料温度为35~45°C,供液转速为65rpm,风机频率为25Hz,雾化压力为0• 12Mpa; Preparation of [0052] 3) metformin sustained release pellets: The stable fluidized bed bottom spray coating process, glycerides, polyethylene glycols, nine-tenths of the total amount of the mass concentration of ethylcellulose 75 % alcohol was dissolved to obtain a coating solution, an amount of alcohol esters, polyethylene glycols, ethyl cellulose with 12 times the weight of the coating solution was sprayed to step 2) containing the obtained core pellets, made slow release pellets; process parameters were: inlet air temperature is 45 ~ 55 ° C, the mass temperature 35 ~ 45 ° C, liquid feed speed of 65rpm, the fan frequency is 25Hz, atomization pressure of 0 • 12Mpa;

[0053] 4)格列喹酮含药微丸的制备,采用流化床底喷上药工艺,用质量浓度为88%的酒精溶解格列喹酮制备格列喹酮的饱和溶液,得含药溶液,将微晶纤维素丸总量的十分之一放入流化床内,将含药溶液喷至空白丸芯上,制成含药丸芯;工艺参数为:进风温度为50~ 55°C,物料温度为40~45°C,供液转速为55rpm,风机频率为25Hz,雾化压力为0• 13Mpa; [0053] 4) Preparation of gliquidone drug-containing pellets using a fluidized bed bottom-spray process of the drug, with the mass concentration of 88% ethanol was dissolved saturated solution prepared gliquidone of gliquidone give containing drug solution, a tenth of microcrystalline cellulose pellets into the fluidized bed, the drug-containing solution was sprayed onto the non-pareil seeds made of pills containing core; process parameters were: inlet air temperature of 50 to 55 ° C, the mass temperature 40 ~ 45 ° C, liquid feed speed of 55rpm, the fan frequency is 25Hz, atomization pressure of 0 • 13Mpa;

[0054] 5)格列喹酮缓释微丸的制备:采用稳定的流化床底喷包衣工艺,将甘油酯、聚乙二醇、乙基纤维素总量的十分之一用质量浓度为75%的酒精溶解,得包衣溶液,酒精的用量为甘油酯、聚乙二醇、乙基纤维素所用重量的12倍,将包衣溶液喷至步骤2)所得含药丸芯上,制成缓释微丸;工艺参数为:进风温度为45~55°C,物料温度为35~45°C,供液转速为65rpm,风机频率为25Hz,雾化压力为0• 12Mpa; Gliquidone preparation of sustained release pellets [0054] 5): A stable fluidized bed bottom spray coating process, glycerides, polyethylene glycols, with one-tenth of the total mass of ethylcellulose concentration of 75% alcohol was dissolved to obtain a coating solution, an amount of alcohol esters, polyethylene glycols, ethyl cellulose with 12 times the weight of the coating solution was sprayed to step 2) the resulting pellets containing the core, sustained release pellets; process parameters were: inlet air temperature is 45 ~ 55 ° C, the mass temperature 35 ~ 45 ° C, liquid feed speed of 65rpm, the fan frequency is 25Hz, atomization pressure of 0 • 12Mpa;

[0055] 6)装囊:将步骤3)所得二甲双胍缓释微丸及步骤5)所得格列喹酮缓释微丸混合均匀,通过装囊机装囊,规格为I.Og/粒。 [0055] 6) balloon loaded: the step 3), and the resulting pellets Metformin Step 5) The obtained sustained-release pellets gliquidone uniformly mixed by means capsule capsule machine installed, specifications for I.Og / grain.

[0056] 使用方法:每日2次,每次1-2粒,或根据病情轻重情况遵医嘱。 [0056] Usage: 2 times a day, 1-2 capsules, according to the severity or compliance situation.

[0057] 贮藏:遮光、密封保存。 [0057] Storage: shading, sealed and stored.

[0058] 实施例4 [0058] Example 4

[0059] 本发明的释放度检查 [0059] Release of the present invention to check

[0060] 按照中国药典2010版二部附录XD释放度测定法第一法,采用溶出度测定法的装置,以水为释放介质,分别测定实施例1-3所制得样品的释放度。 [0060] According to Chinese Pharmacopoeia 2010 edition Appendix XD release assay a first method, using the apparatus of the dissolution assay, with water as release medium, release were determined in the samples prepared in Example 1-3. 各样品均在lh、2h、8h、 12h取样,通过HPLC检测,二甲双胍释放度(%)结果见表1,格列喹酮释放度(%)结果见表2。 In each of the samples lh, 2h, 8h, 12h sampling, detected by HPLC, (%) release of metformin results in Table 1, (%) gliquidone release results in Table 2.

[0061] 表I [0061] TABLE I

[0062] [0062]

Figure CN104906114AD00091

[0065] 结论:本发明的二甲双胍格列喹酮复方缓释胶囊体外释放度结果表明该复方缓释胶囊具有缓慢释放药物,药物浓度平稳,波动小的特点。 [0065] Conclusion: Compound methaqualone sustained release capsules results of in vitro release of metformin glibenclamide indicates that the compound of the present invention has the characteristics of slow release capsules release the drug, the drug concentration stable, small fluctuations.

[0066] 实施例5 [0066] Example 5

[0067] 本发明的药效分析 [0067] Pharmacodynamic Analysis of the invention

[0068] 将Wistar大鼠共20只禁食12h,按60mg/kg体重腹腔注射链尿霉素(STZ)I次,并给予高热量饲料饲养12周,成功制备II型糖尿病动物模型,具有超重、糖耐量减低、血脂升高、血清胰岛素升高及胰岛素受体结合力降低伴胰岛素抵抗的特点,类似于II型糖尿病病人的临床特征。 [0068] 20 Wistar rats were fasted for 12h, according to 60mg / kg body weight by intraperitoneal injection of adriamycin urinary chain (STZ) I times, and high-calorie diet feeding for 12 weeks animal models of type II diabetes successfully prepared, having overweight , impaired glucose tolerance, elevated blood lipids, elevated serum insulin and decreased insulin receptor binding capacity characteristics with insulin resistance, type II diabetes patients with clinical features similar. 将II型糖尿病鼠随机平均分为2组,分别为阳性对照组、试验组。 The type II diabetic mice were randomly divided into 2 groups, namely the positive control group, the test group. 阳性对照组单方单剂量灌胃给药二甲双胍速释制剂,1日3次,1次10mg/kg,格列喹酮速释制剂,1日3次,1次lmg/kg。 Positive control group unilateral single dose of immediate release formulations of metformin oral administration, three times a day, once 10mg / kg, gliquidone immediate release formulation three times a day, 1 lmg / kg. 试验组复方单剂量灌胃给药1日2次,1次剂量为二甲双胍12mg/kg、格列喹酮I. 2mg/kg。 Single dose of the test compound group oral administration twice per day, a dose of Metformin 12mg / kg, gliquidone I. 2mg / kg. 每日早晨取血测空腹血糖值,连续检测10天。 Every morning fasting blood glucose level is continuously detected for 10 days.

[0069] 血糖检测:尾静脉取血,3000rpmXlOmin,分离血清,用葡萄糖氧化酶法测定血糖值,平均血糖值结果见表3。 [0069] The blood glucose monitoring: Tail vein blood, 3000rpmXlOmin, separation of serum glucose value was measured using glucose oxidase method, average blood glucose level results in Table 3.

[0070] 表3 [0070] TABLE 3

[0071] [0071]

Figure CN104906114AD00092

[0072] 结论:本发明的复方缓释胶囊有效药物用量每日为二甲双胍24mg/kg、格列喹酮2. 4mg/kg,少于阳性对照组有效药物用量每日为二甲双胍30mg/kg、格列喹酮3mg/kg。 [0072] Conclusion: Compound effective amount of drug release capsules of the present invention is metformin daily 24mg / kg, gliquidone 2. 4mg / kg, positive control group is less than the effective daily dosage of the drug metformin 30mg / kg, grid gliquidone 3mg / kg. 治疗效果方面,本发明的复方缓释胶囊降糖效果更快,优于对照组。 Therapeutic effect, sustained release capsules of Compound hypoglycemic effects of the present invention is faster than the control group. 说明本发明的二甲双胍格列喹酮复方缓释胶囊具有良好的缓释效果和药效。 DESCRIPTION metformin gliquidone sustained release capsule of Compound of the present invention have good efficacy and sustained release effect.

[0073] 本发明经过筛选采用二甲双胍、格列喹酮作为有效药物成分制成复方缓释胶囊。 [0073] The present inventors have screened metformin, gliquidone compound as an active pharmaceutical ingredient prepared sustained release capsules. 本复方缓释胶囊的有效药物成分二甲双胍、格列喹酮协同作用效果好,有效药物成分及药用辅料用量少,药物有效成分含量高。 Pharmaceutical active ingredient compound of the present sustained release capsules metformin, gliquidone synergistic effect, active pharmaceutical ingredients and pharmaceutically acceptable excipients with less high content of pharmaceutical active ingredients. 本复方缓释胶囊使二甲双胍、格列喹酮能够在体内实现持久、缓慢的释放药物,血药浓度平稳,波动小,从而降低给药频率,提高患者依从性。 This compound metformin sustained release capsules, gliquidone lasting can be achieved in vivo, slow release of the drug, stable blood concentration, small fluctuations, thereby reducing the frequency of dosing, improving patient compliance. 通过控制有效药物成分在血液中的浓度以便维持药效,减少药物释放达峰次数,对患者的脏器还有一定保护。 By controlling the effective drug concentration in the blood in order to maintain the effect and reduces the drug release peak times, there is a certain organ of the patient protection. 本发明工艺简单,重现性好,易于工业化生产;成本低,有利于降低产品价格。 This process is simple, reproducible, easy to industrial production; low cost, help reduce prices.

[0074] 以上所述的实施例仅仅是对本发明的优选实施方式进行描述,并非对本发明的范围进行限定,在不脱离本发明设计精神的前提下,本领域普通技术人员对本发明的技术方案作出的各种变形和改进,均应落入本发明权利要求书确定的保护范围内。 Example [0074] The above are merely preferred embodiments of the present invention will be described, not the scope of the present invention are defined, those of ordinary skill in the art to make technical solution of the present invention without departing from the spirit of the design of the present invention. various changes and modifications shall fall within the claims of the invention within the scope of protection determined.

Claims (7)

  1. 1. 一种二甲双胍格列喹酮复方缓释胶囊,其特征在于,该复方缓释胶囊的组分及重量份数包括:二甲双胍30~35份、格列喹酮1~3份、微晶纤维素丸20~25份、甘油酯0. 5~ 1份、聚乙二醇0. 5~0. 8份、乙基纤维素4~6份。 A compound of metformin gliquidone sustained release capsules, characterized in that the component parts and the weight of the compound of sustained release capsules comprising: 30 to 35 parts by metformin, gliquidone 1 to 3 parts of microcrystalline cellulose 20 to 25 parts hormone pellets, 0.5 to 1 parts of glycerol, polyethylene glycol 0.5 - 0.8 parts of 4 to 6 parts of ethyl cellulose.
  2. 2. -种二甲双胍格列喹酮复方缓释胶囊,其特征在于,该复方缓释胶囊的组分及重量份数包括:二甲双胍33份、格列喹酮2份、微晶纤维素丸22份、甘油酯0. 8份、聚乙二醇0. 7 份、乙基纤维素5份。 2. - Species metformin gliquidone compound sustained-release capsules, characterized in that the components and parts by weight of the compound sustained-release capsules comprising: 33 parts metformin, gliquidone 2 parts, 22 parts of microcrystalline cellulose pills , 0.8 parts glycerol, 0.7 parts of polyethylene glycol, 5 parts of ethyl cellulose.
  3. 3. -种二甲双胍格列喹酮复方缓释胶囊,其特征在于,该复方缓释胶囊的组分及重量份数包括:二甲双胍30份、格列喹酮1份、微晶纤维素丸20份、甘油酯0. 5份、聚乙二醇0. 5 份、乙基纤维素4份。 3 - Species metformin gliquidone compound sustained-release capsules, characterized in that the components and parts by weight of the compound sustained-release capsules comprising: 30 parts of metformin, gliquidone parts 1, 20 parts of microcrystalline cellulose pills , 0.5 parts glycerol, 0.5 parts of polyethylene glycol, 4 parts of ethyl cellulose.
  4. 4. 一种二甲双胍格列喹酮复方缓释胶囊,其特征在于,该复方缓释胶囊的组分及重量份数包括:二甲双胍35份、格列喹酮3份、微晶纤维素丸25份、甘油酯1份、聚乙二醇0. 8 份、乙基纤维素6份。 4. A compound of metformin gliquidone sustained release capsules, characterized in that the component parts and the weight of the compound of sustained release capsules comprising: 35 parts of metformin, gliquidone 3 parts, 25 parts of microcrystalline cellulose pills , 1 part of glycerol, 0.8 parts of polyethylene glycol, 6 parts of ethyl cellulose.
  5. 5. 根据权利要求1-4任一项所述的一种二甲双胍格列喹酮复方缓释胶囊的制备方法, 其特征在于,其制备步骤包括: 1) 备料,按照所需组分及重量份数备料; 2) 二甲双胍含药微丸的制备,采用流化床底喷上药工艺,用质量浓度为65%~70%的酒精溶解二甲双胍制备二甲双胍的饱和溶液,得含药溶液,将微晶纤维素丸总量的十分之九放入流化床内,将含药溶液喷至空白丸芯上,制成含药丸芯; 3) 二甲双胍缓释微丸的制备:采用稳定的流化床底喷包衣工艺,将甘油酯、聚乙二醇、 乙基纤维素总量的十分之九用质量浓度为70%~80%的酒精溶解,得包衣溶液,酒精的用量为甘油酯、聚乙二醇、乙基纤维素所用重量的12倍,将包衣溶液喷至步骤2)所得含药丸芯上,制成缓释微丸; 4) 格列喹酮含药微丸的制备,采用流化床底喷上药工艺,用质量浓度为85%~90%的酒精溶解格 The preparation method of any of claims 1-4 metformin gliquidone compound as claimed in claim sustained release capsules, wherein the preparation step comprises: 1) preparation according to desired components and parts by weight stock number; 2) preparation of drug-containing pellets metformin, fluidized bed bottom-spray process of the drug, with the mass concentration of 65% to 70% of the saturated ethanol solution prepared dissolving metformin metformin to obtain a solution containing the drug, microcrystalline nine-tenths of the total amount of cellulose pellets into the fluidized bed, the drug-containing solution was sprayed onto the non-pareil seeds, pellets made containing core; 3) preparation of sustained release pellets metformin: a stable fluidized bed bottom spray coating process, glycerides, polyethylene glycols, ethylcellulose total nine-tenths of the mass concentration of 70% to 80% alcohol was dissolved to obtain a coating solution, the amount of alcohol is glycerol preparation 4) gliquidone drug-containing pellets;, polyethylene glycol, ethylcellulose with 12 times the weight of the coating solution was sprayed to step 2) the obtained core containing the pills, sustained release pellets , using a fluidized bed bottom-spray process of the drug, with the mass concentration of 85% to 90% alcohol was dissolved grid 列喹酮制备格列喹酮的饱和溶液,得含药溶液,将微晶纤维素丸总量的十分之一放入流化床内,将含药溶液喷至空白丸芯上,制成含药丸芯; 5) 格列喹酮缓释微丸的制备:采用稳定的流化床底喷包衣工艺,将甘油酯、聚乙二醇、 乙基纤维素总量的十分之一用质量浓度为70%~80%的酒精溶解,得包衣溶液,酒精的用量为甘油酯、聚乙二醇、乙基纤维素所用重量的12倍,将包衣溶液喷至步骤2)所得含药丸芯上,制成缓释微丸; 6) 装囊:将步骤3)所得二甲双胍缓释微丸及步骤5)所得格列喹酮缓释微丸混合均匀,通过装囊机装囊,规格为0.5~LOg/粒。 A saturated solution prepared gliquidone gliquidone is to give drug-containing solution, one tenth of the total microcrystalline cellulose pellets into the fluidized bed, the drug-containing solution sprayed onto the non-pareil seeds made pellets containing the core; 5) preparation of gliquidone sustained-release pellets: the stable fluidized bed bottom spray coating process, glycerides, polyethylene glycols, with one-tenth of the total amount of ethylcellulose mass concentration of 70% to 80% alcohol was dissolved to obtain a coating solution, an amount of alcohol esters, polyethylene glycols, ethyl cellulose with 12 times the weight of the coating solution was sprayed to step 2) obtained containing the core pills, sustained release pellets; 6) is mounted capsule: the step 3), and the resulting pellets metformin step 5) the obtained sustained-release pellets gliquidone uniformly mixed by means Nikkiso bladder balloon, specifications of 0.5 ~ LOg / grain.
  6. 6. 根据权利要求5所述的一种二甲双胍格列喹酮复方缓释胶囊的制备方法,其特征在于,二甲双胍含药微丸的制备工艺参数为:进风温度为55~60°C,物料温度为45~50°C, 供液转速为50rpm,风机频率为25Hz,雾化压力为0. 15Mpa;二甲双胍缓释微丸的制备工艺参数为:进风温度为45~55 °C,物料温度为35~45°C,供液转速为65rpm,风机频率为25Hz,雾化压力为0• 12Mpa。 6. According to one of the metformin glibenclamide 5 Preparation of sustained release capsules quinolin-one compound as claimed in claim, wherein the preparation containing the drug metformin pellets were: inlet air temperature is 55 ~ 60 ° C, the material temperature is 45 ~ 50 ° C, liquid feed speed of 50rpm, the fan frequency is 25Hz, atomization pressure of 0. 15Mpa; metformin preparation of sustained release pellets: inlet air temperature is 45 ~ 55 ° C, the material temperature is 35 ~ 45 ° C, liquid feed speed of 65rpm, the fan frequency is 25Hz, atomization pressure of 0 • 12Mpa.
  7. 7. 根据权利要求5所述的一种二甲双胍格列喹酮复方缓释胶囊的制备方法,其特征在于,格列喹酮含药微丸的制备工艺参数为:进风温度为50~55°C,物料温度为40~45°C, 供液转速为55rpm,风机频率为25Hz,雾化压力为0. 13Mpa;二甲双胍缓释微丸的制备工艺 7. The metformin glibenclamide 5 Preparation of sustained release capsules quinolin-one compound as claimed in claim, characterized in that the process parameters gliquidone drug-containing pellets are: inlet air temperature is 50 ~ 55 ° C, the mass temperature 40 ~ 45 ° C, liquid feed speed of 55rpm, the fan frequency is 25Hz, atomization pressure of 0. 13Mpa; metformin preparation of pellets
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105832708A (en) * 2016-05-26 2016-08-10 江西京通美联药业有限公司 Sustained-release preparation for treating diabetes and preparation method thereof
CN106214667A (en) * 2016-08-31 2016-12-14 聊城大学 Felodipine isosorbide dinitrate compound sustained-release capsules and preparation method

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1451385A (en) * 2002-04-18 2003-10-29 谢理峰 Oral compound hypoglycemic medicine
CN1635894A (en) * 2001-09-28 2005-07-06 太阳医药工业有限公司 Dosage form for treatment of diabetes mellitus
CN101897696A (en) * 2009-05-27 2010-12-01 北京奥萨医药研究中心有限公司;深圳奥萨医药有限公司 Sugar-lowering drug composition and application thereof
CN103142552A (en) * 2013-02-22 2013-06-12 广州科的信医药技术有限公司 Lovastatin enteric coated sustained-release pellet capsule and preparation method thereof
CN104173272A (en) * 2013-05-27 2014-12-03 无锡杰西医药科技有限公司 Sustained release preparation of isothiocyanate compound

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1635894A (en) * 2001-09-28 2005-07-06 太阳医药工业有限公司 Dosage form for treatment of diabetes mellitus
CN1451385A (en) * 2002-04-18 2003-10-29 谢理峰 Oral compound hypoglycemic medicine
CN101897696A (en) * 2009-05-27 2010-12-01 北京奥萨医药研究中心有限公司;深圳奥萨医药有限公司 Sugar-lowering drug composition and application thereof
CN103142552A (en) * 2013-02-22 2013-06-12 广州科的信医药技术有限公司 Lovastatin enteric coated sustained-release pellet capsule and preparation method thereof
CN104173272A (en) * 2013-05-27 2014-12-03 无锡杰西医药科技有限公司 Sustained release preparation of isothiocyanate compound

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105832708A (en) * 2016-05-26 2016-08-10 江西京通美联药业有限公司 Sustained-release preparation for treating diabetes and preparation method thereof
CN106214667A (en) * 2016-08-31 2016-12-14 聊城大学 Felodipine isosorbide dinitrate compound sustained-release capsules and preparation method

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