CN112516096A - 一种酚咖滴丸及其制备方法 - Google Patents

一种酚咖滴丸及其制备方法 Download PDF

Info

Publication number
CN112516096A
CN112516096A CN202011463546.2A CN202011463546A CN112516096A CN 112516096 A CN112516096 A CN 112516096A CN 202011463546 A CN202011463546 A CN 202011463546A CN 112516096 A CN112516096 A CN 112516096A
Authority
CN
China
Prior art keywords
caffeine
paracetamol
inclusion
inclusion compound
pill
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.)
Withdrawn
Application number
CN202011463546.2A
Other languages
English (en)
Inventor
陈阳生
臧云龙
沈鑫
孙桂玉
刘晓霞
王明刚
刘振玉
刘薇
张丽敏
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Affiliated Hospital of University of Qingdao
CP Pharmaceutical Qingdao Co Ltd
Original Assignee
Affiliated Hospital of University of Qingdao
CP Pharmaceutical Qingdao Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Affiliated Hospital of University of Qingdao, CP Pharmaceutical Qingdao Co Ltd filed Critical Affiliated Hospital of University of Qingdao
Priority to CN202011463546.2A priority Critical patent/CN112516096A/zh
Publication of CN112516096A publication Critical patent/CN112516096A/zh
Withdrawn legal-status Critical Current

Links

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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
    • 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
    • A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Pain & Pain Management (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Rheumatology (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

本发明公开了一种酚咖滴丸及其制备方法，本发明的酚咖滴丸由酚咖包合物、基质和稳定剂组成，所述包合物包括对乙酰氨基酚、咖啡因和包合材料。本发明滴丸圆整度好，药物溶出迅速，生物利用度高，生产工艺简单，所得产品质量稳定，适合大规模生产。

Description

一种酚咖滴丸及其制备方法
技术领域
本发明涉及一种西药制剂技术，尤其涉及一种酚咖滴丸，本发明还涉及该滴丸的制备方法，属医药技术领域。
背景技术
酚咖药物制剂的有效成分为对乙酰氨基酚和咖啡因，用于普通感冒或流行性感冒引起的发热。也用于缓解轻至中度疼痛，如头痛、偏头痛、牙痛、神经痛、肌肉痛、痛经及关节痛等。对乙酰氨基酚能抑制前列腺素的合成而产生解热镇痛作用；咖啡因为中枢兴奋药，由于它能够收缩脑血管，减轻其搏动的幅度，故与解热镇痛药配伍能增强镇痛效果。
目前，市面上只有普通片剂和颗粒剂销售，无法满足广大患者多元化的用药需求，且普通口服制剂生物利用度低。
滴丸使用设备简单，工艺条件易于控制；制剂质量稳定，计量准确；基质容纳液态药物量大，可使液态药物固化；用固体分散技术制备的滴丸具有吸收迅速、生物利用度高。包合物具有以下优点：掩盖不良臭味，降低药物刺激性，增加药物溶出度与生物利用度，并提高药物稳定性。
发明内容
为了解决现有对乙酰氨基酚、咖啡因复合制剂稳定性差，生物利用度低的缺点，研发一种质量稳定的滴丸，本发明通过大量试验对辅料筛选和工艺优化，提供一种酚咖滴丸。先将对乙酰氨基酚、咖啡因制备成包合物，然后再制备成滴丸，将包合与滴丸技术合二为一，发挥两方面的优点。该滴丸质量稳定，生物利用度高。
为实现上述目的，本发明采取的技术方案是：
一种酚咖滴丸，包括对乙酰氨基酚、咖啡因、包合材料、基质、稳定剂、冷凝液，其特征在于，按重量百分比记，各组分含量为：
对乙酰氨基酚 25%
咖啡因 3.25%
包合材料 10-20%
基质 40-60%
稳定剂 1-5%
冷凝液 适量。
优选地，按重量百分比记，各组分含量为：
对乙酰氨基酚 25%
咖啡因 3.25%
包合材料 15%
基质 55%
稳定剂 1.75%
冷凝液 适量。
其中，所述包合材料为β-环糊精；所述基质为聚乙二醇6000、泊洛沙姆或硬脂酸中的一种或几种；所述稳定剂为磷酸二氢钠和磷酸氢二钠；所述冷凝液为液体石蜡。
其中，所述基质优选为聚乙二醇6000、泊洛沙姆；优选地，聚乙二醇6000、泊洛沙姆的重量比为1：1。
本发明的酚咖滴丸可以按下述方法制备：
(1)用80%乙醇为介质，按比例溶解对乙酰氨基酚、咖啡因和包合材料，将所得溶液经微孔滤膜过滤至澄清，从混合物中分离酚咖包合物，并将酚咖包合物粉碎过100-200目筛；
(2)将基质和稳定剂研磨混合均匀，在水溶上加热熔融，并混匀；
(3)将步骤（1）配好的酚咖包合物加入在步骤（2）制备好的熔融物中，混匀，倾入斜液槽中，保持温度65-75℃10分钟；
(4)将上述药液滴入0-20℃的冷凝液中形成滴丸，吸附冷凝液，干燥滴丸，即得。
本发明涉及的酚咖滴丸具有以下有益效果：
(1)质量稳定，增加药物溶出度和生物利用度，提高药物稳定性；
(2)所选辅料常见，生产工艺简单，所得产品圆整度好，质量稳定，适合大规模生产。
具体实施方式
下面结合实施例对本发明的具体实施方式作进一步描述，但这些实施例仅是范例性的，并不对本发明的范围构成任何限制。本领域技术人员应该理解的是，在不偏离本发明的精神和范围下可以对本发明技术方案的细节和形式进行修改或替换，但这些修改和替换均落入本发明的保护范围内。
一种酚咖滴丸的制备方法，包括以下步骤：
(1)用80%乙醇为介质，按比例溶解对乙酰氨基酚、咖啡因和包合材料，将所得溶液经微孔滤膜过滤至澄清，从混合物中分离酚咖包合物，并将酚咖包合物粉碎过100-200目筛；
(2)将基质和稳定剂研磨混合均匀，在水溶上加热熔融，并混匀；
(3)将步骤（1）配好的酚咖包合物加入在步骤（2）制备好的熔融物中，混匀，倾入斜液槽中，保持温度65-75℃10分钟；
(4)将上述药液滴入0-20℃的冷凝液中形成滴丸，吸附冷凝液，干燥滴丸，即得。
实施例1-6 酚咖滴丸的制备
按下述处方中的原辅料，按上述制备方法，制得酚咖滴丸。其中，“/”代表未使用。
Figure 562156DEST_PATH_IMAGE001
试验例1 实施例1-6所得酚咖滴丸的光滑圆整率及溶散时限测定
根据《中国药典》2015年版四部通则0108规定的方法检测所制备的滴丸的光滑圆整率和溶散时限，测定结果见表1。
Figure 820837DEST_PATH_IMAGE002
从表1可以看出，实施例5的酚咖滴丸光滑圆整率和溶散时限更佳，说明使用聚乙二醇6000和泊洛沙姆作为包衣的基质，且重量比为1：1时，所制成的酚咖滴丸效果优异。
实施例7-11 酚咖滴丸的制备
按下述处方中的原辅料，按上述制备方法，制得酚咖滴丸。
Figure 87870DEST_PATH_IMAGE003
试验例2 实施例7-11所得的酚咖滴丸光滑圆整率及溶散时限测定
测定方法同试验例1，测定结果见表2。
Figure 224453DEST_PATH_IMAGE004
从表2可知，实施例9的酚咖滴丸光滑圆整率和溶散时限更佳，说明当基质聚乙二醇6000与泊洛沙姆的重量之比为1:1时，所制得的酚咖滴丸相对于非此特定比例的滴丸具有更加优异的效果。

Claims (3)

1.一种酚咖滴丸，由酚咖包合物、基质和稳定剂组成，所述包合物包括对乙酰氨基酚、咖啡因和包合材料，其特征在于，按重量百分比记，各组分含量为：
对乙酰氨基酚 25%
咖啡因 3.25%
包合材料 15%
基质 55%
稳定剂 1.75%
冷凝液 适量。
2.按照权利要求1所述的酚咖滴丸，其特征在于所述包合材料为β-环糊精；所述基质为聚乙二醇6000、泊洛沙姆，且重量比为1：1；所述稳定剂为磷酸二氢钠和磷酸氢二钠；所述冷凝液为液体石蜡。
3.制备权利要求1所述的酚咖滴丸的方法，包括以下步骤：
(1)用80%乙醇为介质，按比例溶解对乙酰氨基酚、咖啡因和包合材料，将所得溶液经微孔滤膜过滤至澄清，从混合物中分离酚咖包合物，并将酚咖包合物粉碎过100-200目筛；
(2)将基质和稳定剂研磨混合均匀，在水溶上加热熔融，并混匀；
(3)将步骤（1）配好的酚咖包合物加入在步骤（2）制备好的熔融物中，混匀，倾入斜液槽中，保持温度65-75℃10分钟；
(4)将上述药液滴入0-20℃的冷凝液中形成滴丸，吸附冷凝液，干燥滴丸，即得。
CN202011463546.2A 2020-12-14 2020-12-14 一种酚咖滴丸及其制备方法 Withdrawn CN112516096A (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202011463546.2A CN112516096A (zh) 2020-12-14 2020-12-14 一种酚咖滴丸及其制备方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202011463546.2A CN112516096A (zh) 2020-12-14 2020-12-14 一种酚咖滴丸及其制备方法

Publications (1)

Publication Number Publication Date
CN112516096A true CN112516096A (zh) 2021-03-19

Family

ID=74999336

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202011463546.2A Withdrawn CN112516096A (zh) 2020-12-14 2020-12-14 一种酚咖滴丸及其制备方法

Country Status (1)

Country Link
CN (1) CN112516096A (zh)

Similar Documents

Publication Publication Date Title
CN102274200B (zh) 双氯芬酸钠缓释片及其制备工艺
CN101982179B (zh) 一种小儿氨酚黄那敏颗粒
CN114288257B (zh) 一种马来酸氟伏沙明片剂及其制备方法
CN110037994A (zh) 一种布洛芬速释缓释双层片及其制备方法
CA1261268A (en) Theophylline sustained release formulation
CN109925287A (zh) 一种盐酸赛庚啶片剂及其制备方法
CN112516096A (zh) 一种酚咖滴丸及其制备方法
CN107157943B (zh) 一种托匹司他制剂及其制备方法
CN108524458A (zh) 药物及其制备方法
CN105693793B (zh) 一种利巴韦林化合物及其药物组合物
CN112716956B (zh) 治疗感冒的日用型复方制剂及其制备方法
CN108295035A (zh) 盐酸丙卡特罗片及其制备方法
CN110907583B (zh) 一种洛索洛芬或其钠盐中有关物质的分离方法
CN104414988B (zh) 一种达沙替尼片剂及其制备工艺
CN115192652A (zh) 一种万应颗粒及其制备方法
CN102846572A (zh) 双氯芬酸钠缓释片及其制备方法
CN102643214B (zh) 伏立诺他ⅰ晶形大晶粒的制备方法及制剂
CN111700867B (zh) 一种去氢骆驼蓬碱胃肠道黏附片及其制备方法
CN116803378B (zh) 一种格列齐特缓释片剂及其制备方法
CN104306352A (zh) 一种光甘草定微囊及其制备方法
CN100364506C (zh) 一种用于治疗支气管炎的滴丸及其制备方法
CN108904465A (zh) 一种布洛芬药物制剂组合物及其制备方法
CN110898017A (zh) 一种琥珀酸呋罗曲坦滴丸及其制备方法
CN103494818A (zh) 一种烟酸辛伐他汀缓释片及其制备方法
CN112999170B (zh) 一种布洛芬载薄荷脑复合颗粒及其制备方法

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
WW01 Invention patent application withdrawn after publication

Application publication date: 20210319

WW01 Invention patent application withdrawn after publication