CN106236755A - 一种含有盐酸马尼地平和氢氯噻嗪的复方片剂及制备方法 - Google Patents
一种含有盐酸马尼地平和氢氯噻嗪的复方片剂及制备方法 Download PDFInfo
- Publication number
- CN106236755A CN106236755A CN201610745242.2A CN201610745242A CN106236755A CN 106236755 A CN106236755 A CN 106236755A CN 201610745242 A CN201610745242 A CN 201610745242A CN 106236755 A CN106236755 A CN 106236755A
- Authority
- CN
- China
- Prior art keywords
- hydrochlorothiazide
- compound tablet
- hydroxypropyl cellulose
- tablet
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 title claims abstract description 57
- 229960002003 hydrochlorothiazide Drugs 0.000 title claims abstract description 56
- XVIXARVAOCTOLU-BVNFUTIRSA-N chembl312176 Chemical compound CC=1N=C(C)C(=C(O)/OC)/C(C=2C=C(C=CC=2)[N+]([O-])=O)C=1C(=O)OCCN(CC1)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 XVIXARVAOCTOLU-BVNFUTIRSA-N 0.000 title claims abstract description 54
- 150000001875 compounds Chemical class 0.000 title claims abstract description 52
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 7
- 239000000470 constituent Substances 0.000 claims abstract description 3
- 239000004615 ingredient Substances 0.000 claims abstract description 3
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 28
- 239000002671 adjuvant Substances 0.000 claims description 16
- GUBGYTABKSRVRQ-QKKXKWKRSA-N lactose group Chemical group OC1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](O2)CO)[C@H](O1)CO GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 16
- 239000000463 material Substances 0.000 claims description 16
- 239000008187 granular material Substances 0.000 claims description 15
- 229920002472 Starch Polymers 0.000 claims description 14
- 239000008101 lactose Substances 0.000 claims description 14
- 235000019359 magnesium stearate Nutrition 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 14
- 239000008107 starch Substances 0.000 claims description 14
- 235000019698 starch Nutrition 0.000 claims description 14
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 13
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 13
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 13
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- 239000007864 aqueous solution Substances 0.000 claims description 10
- ANEBWFXPVPTEET-UHFFFAOYSA-N manidipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ANEBWFXPVPTEET-UHFFFAOYSA-N 0.000 claims description 10
- 229960003963 manidipine Drugs 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- 238000001035 drying Methods 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 239000002245 particle Substances 0.000 claims description 5
- 239000008213 purified water Substances 0.000 claims description 5
- 239000002994 raw material Substances 0.000 claims description 5
- 239000007779 soft material Substances 0.000 claims description 5
- 229910001220 stainless steel Inorganic materials 0.000 claims description 5
- 239000010935 stainless steel Substances 0.000 claims description 5
- 229940082195 hydrochlorothiazide 12.5 mg Drugs 0.000 claims description 4
- 230000003276 anti-hypertensive effect Effects 0.000 abstract description 4
- -1 CV-4093 forms compound Chemical class 0.000 abstract description 3
- 230000007423 decrease Effects 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 239000007916 tablet composition Substances 0.000 abstract description 2
- 230000036772 blood pressure Effects 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 6
- 206010020772 Hypertension Diseases 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000005457 optimization Methods 0.000 description 5
- 229940127291 Calcium channel antagonist Drugs 0.000 description 4
- 239000002220 antihypertensive agent Substances 0.000 description 3
- 229940127088 antihypertensive drug Drugs 0.000 description 3
- 210000002216 heart Anatomy 0.000 description 3
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 208000004880 Polyuria Diseases 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 229910001424 calcium ion Inorganic materials 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 208000010643 digestive system disease Diseases 0.000 description 2
- 230000035619 diuresis Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 208000018685 gastrointestinal system disease Diseases 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 210000002464 muscle smooth vascular Anatomy 0.000 description 2
- 238000011125 single therapy Methods 0.000 description 2
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010018366 Glomerulonephritis acute Diseases 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 206010029164 Nephrotic syndrome Diseases 0.000 description 1
- 206010033264 Ovarian hyperfunction Diseases 0.000 description 1
- KEGCMAVWPIBGJY-UHFFFAOYSA-N S1NC=CC=C1.[Cl] Chemical compound S1NC=CC=C1.[Cl] KEGCMAVWPIBGJY-UHFFFAOYSA-N 0.000 description 1
- 229940121792 Thiazide diuretic Drugs 0.000 description 1
- 231100000851 acute glomerulonephritis Toxicity 0.000 description 1
- 239000003470 adrenal cortex hormone Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004531 blood pressure lowering effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000007211 cardiovascular event Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 229940127292 dihydropyridine calcium channel blocker Drugs 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 201000006564 estrogen excess Diseases 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 229940082203 hydrochlorothiazide 15 mg Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000000297 inotrophic effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000010503 organ complication Effects 0.000 description 1
- 210000003540 papillary muscle Anatomy 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 210000005245 right atrium Anatomy 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000003451 thiazide diuretic agent Substances 0.000 description 1
- 230000032895 transmembrane transport Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/549—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及一种含有盐酸马尼地平和氢氯噻嗪的复方片剂及制备方法,该复方片剂以盐酸马尼地平和氢氯噻嗪为药物有效成分,复方片剂中药物有效成分含量比例为:盐酸马尼地平与氢氯噻嗪的质量比为1:2~1:3。本发明的复方片剂配方合理,减少了用药剂量,增强了降压效果,盐酸马尼地平与氢氯噻嗪组成复方,有很好的协同作用,且制备工艺简单易行,生产成本低,适合大规模的工业化生产。
Description
技术领域
本发明涉及医药技术领域,具体涉及一种含有盐酸马尼地平和氢氯噻嗪的复方片剂及制备方法。
背景技术
我国高血压的治疗面临着巨大的挑战,不仅患病人数众多,并且知晓率、治疗率、控制率仍然处于较低水平。必须采取积极、有效的降压治疗方案,以提高达标率,有效降低心血管事件的发生率和死亡率。降压达标是减少心脑血管病发生及死亡的关键,同时血压波动明显也是引起心、脑、肾等重要脏器并发症和较高致残、致死率的重要原因之一,因此要有效平稳降压,减少血压的波动。理想的降压药物,既要强效降压,又能长效平稳降压,有效保护靶器官功能。降压治疗的长期疗效是基于治疗方案的有效性、安全性以及患者的依从性,因此,治疗方案的实施以及血压达标已成为高血压治疗的重点。目前的降压药物治疗存在两种形式,即单药治疗和联合治疗。联合治疗的方式包括了单片复方制剂以及处方的多片药物联合。《中国高血压防治指南2010》指出,联合用药可以增加降压效果减少不良反应,在低剂量(有效治疗剂量在)单药治疗疗效不满意时,可以采用两种或多种降压药物联合治疗。对血压≥ 160/100mmHg(1mmHg=0.133kPa)或高危以上的高血压患者,起始即可采用小剂量两种药联合治疗,其中包括固定配比的单片复方制剂。
盐酸马尼地平是一种二氢吡啶钙拮抗剂(CCB),它能够抑制钙离子跨膜进入血管平滑肌和心肌。实验数据表明马尼地平与二氢吡啶及非二氢吡啶的结合位点均可结合。心肌和血管平滑肌的收缩过程依赖于细胞外钙离子通过离子通道进入细胞内来完成。马尼地平可选择性抑制钙离子跨膜转运,体外研究表明马尼地平具有高度的血管选择性,对心脏作用很小。以豚鼠的乳头肌和右心房作为实验标本,提示马尼地平的负性肌力作用和负性频率低于其他钙通道拮抗剂。马尼地平不影响血清钙的浓度。在生理酸碱度范围内,马尼地平是一种离子化的复合物,通过与钙通道受体在结合点缓慢的结合/分解实现其逐步起效的作用。马尼地平是一个外周动脉血管扩张剂,它直接作用于血管平滑肌,从而降低外周血管阻力和血压。
氢氯噻嗪是噻嗪类利尿剂的一种,主要适用于心原性水肿、肝原性水肿和肾性水肿:如肾病综合征、急性肾小球肾炎、慢性肾功能衰竭以及肾上腺皮质激素与雌激素过多引起的水肿,口服后利尿作用在2小时内发生,在第4小时时利尿作用最强,且持续6~12小时。临床验证它可以和其他降压药物联合应用,并且药代动力学研究显示,CCB与氢氯噻嗪联合应用时CCB的药代动力学特性并无改变,氢氯噻嗪的结果虽然不尽一致,但均不对耐受性产生影响。
发明内容
本发明的目的是为解决上述技术问题的不足,提供一种含有盐酸马尼地平和氢氯噻嗪的复方片剂及制备方法,制得的复方片剂稳定性以及药物溶出均较好,并且具有明显的降压效果。
本发明为解决上述技术问题的不足,所采用的技术方案是:一种含有盐酸马尼地平和氢氯噻嗪的复方片剂,该复方片剂以盐酸马尼地平和氢氯噻嗪为药物有效成分,复方片剂中药物有效成分含量比例为:盐酸马尼地平与氢氯噻嗪的质量比为1:2~1:3。
作为本发明一种含有盐酸马尼地平和氢氯噻嗪的复方片剂的进一步优化:复方片剂还包括辅料,辅料为乳糖、淀粉、低取代羟丙基纤维素、羟丙基纤维素以及硬脂酸镁。
作为本发明一种含有盐酸马尼地平和氢氯噻嗪的复方片剂的进一步优化:所述辅料中各成分占复方片剂的重量百分比为:乳糖35~45%,淀粉25~35%,低取代羟丙基纤维素8~12%,羟丙基纤维素2~5%以及硬脂酸镁1~2%。
作为本发明一种含有盐酸马尼地平和氢氯噻嗪的复方片剂的进一步优化:该复方片剂中盐酸马尼地平与氢氯噻嗪的质量比为1:2.5。
作为本发明一种含有盐酸马尼地平和氢氯噻嗪的复方片剂的进一步优化:每单位片剂中含盐酸马尼地平的重量为5mg,含氢氯噻嗪的重量为12.5mg。
作为本发明一种含有盐酸马尼地平和氢氯噻嗪的复方片剂的进一步优化:每单位片剂中各成分的含量为:盐酸马尼地平5mg、氢氯噻嗪12.5mg、乳糖43.76mg、淀粉32.82mg、低取代羟丙基纤维素10.95mg、羟丙基纤维素3.28mg、以及硬脂酸镁1.09mg。
上述一种含有盐酸马尼地平和氢氯噻嗪的复方片剂的制备方法,包括以下步骤:
(1)、按照上述重量百分比取各种原料,先将盐酸马尼地平和氢氯噻嗪分别过100目筛,并分别进行超微粉碎,控制盐酸马尼地平和氢氯噻嗪的粒径均为D90≤25μm,备用;
(2)、将乳糖、淀粉和低取代羟丙基纤维素混合后搅拌均匀,得到辅料备用;
(3)、将步骤(1)超微粉碎后的盐酸马尼地平和氢氯噻嗪加入到步骤(2)制得的辅料中,搅拌均匀,得到混合物料,备用;
(4)、将羟丙基纤维素溶于适量纯化水中,制得浓度为8%的水溶液,再将该水溶液加入到步骤(3)制得的混合物料中制软材,并将湿颗粒置于55℃~60℃温度下烘干,烘干后的干颗粒过20目不锈钢筛,完成整粒;
(5)、将硬脂酸镁加入到步骤(4)整粒后的物料中,进行总混,并进行压片,即得到复方片剂。
有益效果
本发明的复方片剂配方合理,减少了用药剂量,增强了降压效果,盐酸马尼地平与氢氯噻嗪组成复方,有很好的协同作用,与盐酸马尼地平或氢氯噻嗪单独用药相比,大幅度减少了每一种单药成分的剂量,取得了意想不到的结果;并且本发明的复方片剂对辅料也进行和筛选及组合,按照该处方制备的片剂具有良好的溶出度和稳定性;另外,本发明的片剂采用湿法制粒工艺制备,工艺简单易行,生产成本低,适合大规模的工业化生产。
具体实施方式
实施例1
一种含有盐酸马尼地平和氢氯噻嗪的复方片剂,每单位片剂中各成分的含量为:盐酸马尼地平5mg、氢氯噻嗪12.5mg、乳糖43.76mg、淀粉32.82mg、低取代羟丙基纤维素10.95mg、羟丙基纤维素3.28mg、以及硬脂酸镁1.09mg。
上述含有盐酸马尼地平和氢氯噻嗪的复方片剂的制备方法,包括以下步骤:
(1)、按照上述重量百分比取各种原料,先将盐酸马尼地平和氢氯噻嗪分别过100目筛,并分别进行超微粉碎,控制盐酸马尼地平和氢氯噻嗪的粒径均为D90≤25μm,备用;
(2)、将乳糖、淀粉和低取代羟丙基纤维素混合后搅拌均匀,得到辅料备用;
(3)、将步骤(1)超微粉碎后的盐酸马尼地平和氢氯噻嗪加入到步骤(2)制得的辅料中,搅拌均匀,得到混合物料,备用;
(4)、将羟丙基纤维素溶于适量纯化水中,制得浓度为8%的水溶液,再将该水溶液加入到步骤(3)制得的混合物料中制软材,并将湿颗粒置于55℃温度下烘干,烘干后的干颗粒过20目不锈钢筛,完成整粒;
(5)、将硬脂酸镁加入到步骤(4)整粒后的物料中,进行总混,并进行压片,即得到复方片剂。
实施例2
一种含有盐酸马尼地平和氢氯噻嗪的复方片剂,每单位片剂中各成分的含量为:盐酸马尼地平5mg、氢氯噻嗪10mg、乳糖41.86mg、淀粉36.42mg、低取代羟丙基纤维素11.75mg、羟丙基纤维素3.28mg、以及硬脂酸镁1.09mg。
上述含有盐酸马尼地平和氢氯噻嗪的复方片剂的制备方法,包括以下步骤:
(1)、按照上述重量百分比取各种原料,先将盐酸马尼地平和氢氯噻嗪分别过100目筛,并分别进行超微粉碎,控制盐酸马尼地平和氢氯噻嗪的粒径均为D90≤25μm,备用;
(2)、将乳糖、淀粉和低取代羟丙基纤维素混合后搅拌均匀,得到辅料备用;
(3)、将步骤(1)超微粉碎后的盐酸马尼地平和氢氯噻嗪加入到步骤(2)制得的辅料中,搅拌均匀,得到混合物料,备用;
(4)、将羟丙基纤维素溶于适量纯化水中,制得浓度为8%的水溶液,再将该水溶液加入到步骤(3)制得的混合物料中制软材,并将湿颗粒置于60℃温度下烘干,烘干后的干颗粒过20目不锈钢筛,完成整粒;
(5)、将硬脂酸镁加入到步骤(4)整粒后的物料中,进行总混,并进行压片,即得到复方片剂。
实施例3
一种含有盐酸马尼地平和氢氯噻嗪的复方片剂,每单位片剂中各成分的含量为:盐酸马尼地平5mg、氢氯噻嗪15mg、乳糖49.23mg、淀粉27.54mg、低取代羟丙基纤维素8.76mg、羟丙基纤维素2.78mg、以及硬脂酸镁1.09mg。
上述含有盐酸马尼地平和氢氯噻嗪的复方片剂的制备方法,包括以下步骤:
(1)、按照上述重量百分比取各种原料,先将盐酸马尼地平和氢氯噻嗪分别过100目筛,并分别进行超微粉碎,控制盐酸马尼地平和氢氯噻嗪的粒径均为D90≤25μm,备用;
(2)、将乳糖、淀粉和低取代羟丙基纤维素混合后搅拌均匀,得到辅料备用;
(3)、将步骤(1)超微粉碎后的盐酸马尼地平和氢氯噻嗪加入到步骤(2)制得的辅料中,搅拌均匀,得到混合物料,备用;
(4)、将羟丙基纤维素溶于适量纯化水中,制得浓度为8%的水溶液,再将该水溶液加入到步骤(3)制得的混合物料中制软材,并将湿颗粒置于60℃温度下烘干,烘干后的干颗粒过20目不锈钢筛,完成整粒;
(5)、将硬脂酸镁加入到步骤(4)整粒后的物料中,进行总混,并进行压片,即得到复方片剂。
本发明复方片剂的降血压效果试验
选择90例中重度患者,男性58人,女性42人,分三组,年龄50-80岁。
三组分别为:
①盐酸马尼地平组,5mg/片,口服,一日一次,一次一片,两周后效果不佳者改为一次2片
②氢氯噻嗪组,12.5mg/片,口服,一日一次,一次一片,两周后效果不佳者改为一次2片
③复方制剂组,盐酸马尼地平5mg+氢氯噻嗪12.5mg/片,口服,一日一次,一次一片。
3组比较
组别 | n | 显效 | 有效 | 无效 | 有效率(%) |
盐酸马尼地平 | 30 | 10 | 15 | 5 | 83.33 |
氢氯噻嗪 | 30 | 9 | 17 | 4 | 86.67 |
复方 | 30 | 22 | 8 | 0 | 100.0 |
治疗前后,P<0.05
3组治疗前后血压变化(+s)
治疗前后,P<0.05。
Claims (7)
1.一种含有盐酸马尼地平和氢氯噻嗪的复方片剂,其特征在于:该复方片剂以盐酸马尼地平和氢氯噻嗪为药物有效成分,复方片剂中药物有效成分含量比例为:盐酸马尼地平与氢氯噻嗪的质量比为1:2~1:3。
2.如权利要求1所述含有盐酸马尼地平和氢氯噻嗪的复方片剂,其特征在于:复方片剂还包括辅料,辅料为乳糖、淀粉、低取代羟丙基纤维素、羟丙基纤维素以及硬脂酸镁。
3.如权利要求2所述含有盐酸马尼地平和氢氯噻嗪的复方片剂,其特征在于:所述辅料中各成分占复方片剂的重量百分比为:乳糖35~45%,淀粉25~35%,低取代羟丙基纤维素8~12%,羟丙基纤维素2~5%以及硬脂酸镁1~2%。
4.如权利要求3所述含有盐酸马尼地平和氢氯噻嗪的复方片剂,其特征在于:该复方片剂中盐酸马尼地平与氢氯噻嗪的质量比为1:2.5。
5.如权利要求4所述含有盐酸马尼地平和氢氯噻嗪的复方片剂,其特征在于:每单位片剂中含盐酸马尼地平的重量为5mg,含氢氯噻嗪的重量为12.5mg。
6.如权利要求5所述含有盐酸马尼地平和氢氯噻嗪的复方片剂,其特征在于:每单位片剂中各成分的含量为:盐酸马尼地平5mg、氢氯噻嗪12.5mg、乳糖43.76mg、淀粉32.82mg、低取代羟丙基纤维素10.95mg、羟丙基纤维素3.28mg、以及硬脂酸镁1.09mg。
7.如权利要求3所述含有盐酸马尼地平和氢氯噻嗪的复方片剂的制备方法,其特征在于:包括以下步骤:
(1)、按照上述重量百分比取各种原料,先将盐酸马尼地平和氢氯噻嗪分别过100目筛,并分别进行超微粉碎,控制盐酸马尼地平和氢氯噻嗪的粒径均为D90≤25μm,备用;
(2)、将乳糖、淀粉和低取代羟丙基纤维素混合后搅拌均匀,得到辅料备用;
(3)、将步骤(1)超微粉碎后的盐酸马尼地平和氢氯噻嗪加入到步骤(2)制得的辅料中,搅拌均匀,得到混合物料,备用;
(4)、将羟丙基纤维素溶于适量纯化水中,制得浓度为8%的水溶液,再将该水溶液加入到步骤(3)制得的混合物料中制软材,并将湿颗粒置于55℃~60℃温度下烘干,烘干后的干颗粒过20目不锈钢筛,完成整粒;
(5)、将硬脂酸镁加入到步骤(4)整粒后的物料中,进行总混,并进行压片,即得到复方片剂。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610745242.2A CN106236755A (zh) | 2016-08-29 | 2016-08-29 | 一种含有盐酸马尼地平和氢氯噻嗪的复方片剂及制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610745242.2A CN106236755A (zh) | 2016-08-29 | 2016-08-29 | 一种含有盐酸马尼地平和氢氯噻嗪的复方片剂及制备方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN106236755A true CN106236755A (zh) | 2016-12-21 |
Family
ID=57596988
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610745242.2A Pending CN106236755A (zh) | 2016-08-29 | 2016-08-29 | 一种含有盐酸马尼地平和氢氯噻嗪的复方片剂及制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN106236755A (zh) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1225203A (zh) * | 1996-07-05 | 1999-08-04 | 西门子公司 | 输出电压与电源电压具有弱相关性的电压倍增装置 |
CN104490881A (zh) * | 2014-11-26 | 2015-04-08 | 许昌恒生制药有限公司 | 一种含有盐酸马尼地平和阿齐沙坦的片剂及其制备方法 |
-
2016
- 2016-08-29 CN CN201610745242.2A patent/CN106236755A/zh active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1225203A (zh) * | 1996-07-05 | 1999-08-04 | 西门子公司 | 输出电压与电源电压具有弱相关性的电压倍增装置 |
CN104490881A (zh) * | 2014-11-26 | 2015-04-08 | 许昌恒生制药有限公司 | 一种含有盐酸马尼地平和阿齐沙坦的片剂及其制备方法 |
Non-Patent Citations (2)
Title |
---|
胡定波等: "氨氯地平联合氢氯噻嗪或依那普利治疗老年高血压的效果", 《江苏医药》 * |
闫盈盈等: "马尼地平治疗高血压有效性与安全性的Meta分析", 《中国循证心血管医学杂志》 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN103655539B (zh) | 一种卡格列净的口服固体制剂及其制备方法 | |
CN105555276A (zh) | 作为治疗病毒性感染的药剂的贝前列素异构体 | |
CN104884051A (zh) | 包含吉格列汀和二甲双胍的组合药物及其制备方法 | |
EP2968176B1 (en) | Orally administrable compositions comprising calcium | |
CN103599140B (zh) | 银杏内酯控释片及制备方法 | |
CN106236755A (zh) | 一种含有盐酸马尼地平和氢氯噻嗪的复方片剂及制备方法 | |
WO2013189305A1 (zh) | 缬沙坦氨氯地平复方固体制剂及其制备方法 | |
CN102716128A (zh) | 一种治疗哮喘的药用组合物 | |
CN109288836B (zh) | 一种复方硫酸双肼屈嗪制剂及其制备方法和应用 | |
CN108853044B (zh) | 一种硝苯地平缓释片及其制备方法 | |
CN103565807A (zh) | 一种奥美沙坦酯氨氯地平药物组合物 | |
CN103006651B (zh) | 一种含奥美沙坦酯和氨氯地平的片剂及其制备方法 | |
CN103271907B (zh) | 一种小檗碱和二甲双胍的口服药物组合物及其制备方法 | |
CN102579453B (zh) | 一种治疗胃溃疡的复方制剂及其制备方法 | |
CN102228457A (zh) | 一种治疗糖尿病及其并发症的药物组合物 | |
CN101797253B (zh) | 一种岩白菜素、盐酸西替利嗪复方口服剂型 | |
CN107773559B (zh) | 吲哚啉酮类化合物在制备预防治疗肺纤维化的药物中的应用 | |
CN1660104A (zh) | 格列吡嗪肠溶片及其制备方法 | |
KR101816726B1 (ko) | 베포타스틴 함유 방출제어형 정제 | |
CN104721162A (zh) | 一种泼尼松口服脉冲片及其制备方法 | |
CN104337783B (zh) | 一种卡培他滨片剂及其制备方法 | |
CN105287550A (zh) | 一种缬沙坦/非洛地平复方制剂及其制备方法 | |
CN103006605A (zh) | 苄达赖氨酸缓释制剂和制备方法及其应用 | |
CN102526063A (zh) | 一种含有氯沙坦钾和氢氯噻嗪的复方制剂及其制备方法 | |
CN102755319B (zh) | 一种含有普拉格雷和卡维地洛的药物组合物及其用途 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20161221 |