CN114712324B - 一种羟苯磺酸钙胶囊及其制备方法 - Google Patents
一种羟苯磺酸钙胶囊及其制备方法 Download PDFInfo
- Publication number
- CN114712324B CN114712324B CN202210484431.4A CN202210484431A CN114712324B CN 114712324 B CN114712324 B CN 114712324B CN 202210484431 A CN202210484431 A CN 202210484431A CN 114712324 B CN114712324 B CN 114712324B
- Authority
- CN
- China
- Prior art keywords
- calcium dobesilate
- capsules
- dried powder
- acerola cherry
- 100rpm
- 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.)
- Active
Links
- QGNBTYAQAPLTMX-UHFFFAOYSA-L calcium dobesilate Chemical compound [Ca+2].OC1=CC=C(O)C(S([O-])(=O)=O)=C1.OC1=CC=C(O)C(S([O-])(=O)=O)=C1 QGNBTYAQAPLTMX-UHFFFAOYSA-L 0.000 title claims abstract description 78
- 229960005438 calcium dobesilate Drugs 0.000 title claims abstract description 78
- 239000002775 capsule Substances 0.000 title claims abstract description 55
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 36
- WVXRAFOPTSTNLL-NKWVEPMBSA-N 2',3'-dideoxyadenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1CC[C@@H](CO)O1 WVXRAFOPTSTNLL-NKWVEPMBSA-N 0.000 claims abstract description 32
- 240000003394 Malpighia glabra Species 0.000 claims abstract description 32
- 235000014837 Malpighia glabra Nutrition 0.000 claims abstract description 32
- 241000167854 Bourreria succulenta Species 0.000 claims abstract description 30
- 235000019693 cherries Nutrition 0.000 claims abstract description 30
- 239000000843 powder Substances 0.000 claims abstract description 27
- 239000002245 particle Substances 0.000 claims abstract description 24
- 229920002261 Corn starch Polymers 0.000 claims abstract description 18
- 229920000881 Modified starch Polymers 0.000 claims abstract description 18
- 239000008120 corn starch Substances 0.000 claims abstract description 18
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 18
- 238000011049 filling Methods 0.000 claims description 15
- 239000000463 material Substances 0.000 claims description 15
- 238000002156 mixing Methods 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- 238000005303 weighing Methods 0.000 claims description 10
- 235000020985 whole grains Nutrition 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 6
- 238000007599 discharging Methods 0.000 claims description 5
- 238000005429 filling process Methods 0.000 claims description 5
- 238000005469 granulation Methods 0.000 claims description 5
- 230000003179 granulation Effects 0.000 claims description 5
- 238000011068 loading method Methods 0.000 claims description 5
- 238000005259 measurement Methods 0.000 claims description 5
- 238000007873 sieving Methods 0.000 claims description 5
- 235000013399 edible fruits Nutrition 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- 235000011389 fruit/vegetable juice Nutrition 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 238000009777 vacuum freeze-drying Methods 0.000 claims description 4
- 235000013339 cereals Nutrition 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 238000005070 sampling Methods 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 abstract description 7
- 238000002474 experimental method Methods 0.000 abstract description 4
- 230000000857 drug effect Effects 0.000 abstract description 2
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 6
- 229910052782 aluminium Inorganic materials 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 239000004033 plastic Substances 0.000 description 5
- 238000004806 packaging method and process Methods 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 239000008176 lyophilized powder Substances 0.000 description 2
- 230000004089 microcirculation Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- IKQCSJBQLWJEPU-UHFFFAOYSA-N 2,5-dihydroxybenzenesulfonic acid Chemical compound OC1=CC=C(O)C(S(O)(=O)=O)=C1 IKQCSJBQLWJEPU-UHFFFAOYSA-N 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 101800004538 Bradykinin Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
- 108010003272 Hyaluronate lyase Proteins 0.000 description 1
- 102000001974 Hyaluronidases Human genes 0.000 description 1
- 102100035792 Kininogen-1 Human genes 0.000 description 1
- 229920001328 Polyvinylidene chloride Polymers 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 206010046996 Varicose vein Diseases 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004155 blood-retinal barrier Anatomy 0.000 description 1
- 230000004378 blood-retinal barrier Effects 0.000 description 1
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 230000004856 capillary permeability Effects 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 230000001434 glomerular Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 229960002773 hyaluronidase Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 239000005033 polyvinylidene chloride Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 208000027185 varicose disease Diseases 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000011249 vascular protecting agent Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
- A61K36/736—Prunus, e.g. plum, cherry, peach, apricot or almond
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1664—Compounds of unknown constitution, e.g. material from plants or animals
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Heart & Thoracic Surgery (AREA)
- Botany (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Zoology (AREA)
- Dermatology (AREA)
- Rheumatology (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明属于药物制剂领域，具体涉及一种羟苯磺酸钙胶囊及其制备方法。所述的羟苯磺酸钙胶囊，每1000粒胶囊含有以下重量的组分：羟苯磺酸钙500g，针叶樱桃冻干粉20‑30g，硬脂酸镁1‑10g，玉米淀粉1‑5g，预胶化淀粉10‑20g。本发明制备的羟苯磺酸钙胶囊，稳定性实验显示，颗粒性状和有效成分含量可以在较长时间内保持稳定，有利于药效的稳定发挥。
Description
技术领域
本发明属于药物制剂领域，具体涉及一种羟苯磺酸钙胶囊及其制备方法。
背景技术
羟苯磺酸钙，中文别名2，5-二羟基苯磺酸钙，英文名称Calcium Dobesilate，其为白色或类白色吸湿性粉末，无臭，味苦，遇光易变质，有吸湿性。本品极易溶于水，易溶于乙醇或丙酮，极微溶于氯仿或乙醚。是一种口服血管保护剂，它通过抑制血管活性物质(组织胺、5-羟色胺、缓激肽、透明质酸酶、前列腺素)引起的高通透作用，从而改善基底膜胶原的生物合成。对微血管循环障碍(毛细血管循环障碍)引起的多种疾病均有疗效。羟苯磺酸钙的治疗作用是多方面的。通过降低毛细血管的通透性、稳定血-视网膜屏障，可以降低视网膜血液外渗，保持血液的正常稀释度。通过降低大分子血浆蛋白和降低红细胞刚性和凝聚性，可改善血液循环：通过降低血小板的高凝聚性，可防止缺血发生。临床用于治疗：糖尿病引起的视网膜病变；微循环障碍引起的心、脑、肾疾病，如肾小球动脉硬化症等；降低血液粘稠度；防止微血栓形成；四肢麻木、疼痛，皮肤瘙痒；静脉曲张等综合症。
胶囊剂是羟苯磺酸钙一种常见的剂型。但是，由于羟苯磺酸钙结构中有2个酚羟基，因此其具有引湿性、光不稳定性和易氧化等特点，不利于羟苯磺酸钙胶囊的长期稳定性，极大地影响了羟苯磺酸钙的贮存和临床使用。
发明内容
为了克服上述问题，本申请提供了一种羟苯磺酸钙胶囊及其制备方法。
本发明的技术方案是这样实现的：
一种羟苯磺酸钙胶囊，每1000粒胶囊含有以下重量的组分：羟苯磺酸钙500g，针叶樱桃冻干粉20-30g，硬脂酸镁1-10g，玉米淀粉1-5g，预胶化淀粉10-20g。
进一步，所述的针叶樱桃冻干粉的制备方法为：取针叶樱桃果实，去核，压榨出果汁，过滤除去不溶物，真空冷冻干燥即得针叶樱桃冻干粉。
进一步，所述的羟苯磺酸钙胶囊，每1000粒胶囊含有以下重量的组分：羟苯磺酸钙500g，针叶樱桃冻干粉25g，硬脂酸镁4.4g，玉米淀粉3g，预胶化淀粉20g。
一种羟苯磺酸钙胶囊的制备方法，包括以下步骤：
(1)羟苯磺酸钙、针叶樱桃冻干粉和玉米淀粉、预胶化淀粉过50-80目筛，称量备料；硬脂酸镁称量备料；
(2)依次将硬脂酸镁、玉米淀粉、预胶化淀粉、针叶樱桃冻干粉和羟苯磺酸钙加入混合机中，混合；混合结束后出料；
(3)将混合的物料送入干法制粒机制粒，得到羟苯磺酸钙颗粒；测定羟苯磺酸钙含量；
(4)根据羟苯磺酸钙颗粒中含量测定结果调节装量范围，将羟苯磺酸钙颗粒填充入空心胶囊中，即可。
进一步，所述的步骤(2)中，采用万向运动混合机，设定频率32Hz，混合时间：10分钟。
进一步，所述步骤(3)，干法制粒机工艺参数设定如下：送料转速：25.00-30.00rpm，压轮转速：8-12rpm，辊压压力：8.0-10.0Mpa，破碎转速：100rpm，整粒1转速：80-100rpm，筛网孔径Φ2.0mm；整粒2转速：80-100rpm，筛网孔径Φ1.0mm。
进一步，所述的步骤(3)干法制粒机工艺参数设定如下：送料转速：25.00rpm，压轮转速：8rpm，辊压压力：9.09Mpa，破碎转速：100rpm，整粒1转速：100rpm，筛网孔径Φ2.0mm；整粒2转速：100rpm，筛网孔径Φ1.0mm。
进一步，所述的步骤(4)采用胶囊填充机填充胶囊，设定填充速度为1500-2100粒/分。
进一步，所述步骤(4)在填充过程中每20分钟取样1次，检测粒重差异。
有益效果：
本发明制备的羟苯磺酸钙胶囊各项指标均达到了羟苯磺酸钙胶囊的制备标准。稳定性实验显示，其颗粒性状和有效成分含量可以在较长时间内保持稳定，稳定性大大提高，有利于药效的稳定发挥。有效成分含量保持稳定也延长了胶囊剂的有效期，对于药品的储藏和使用具有重要意义。
具体实施方式
下面结合具体的实施方式对本发明作进一步的说明，以更好地理解本发明。
实施例1
一种羟苯磺酸钙胶囊，每1000粒胶囊含有以下重量的组分：羟苯磺酸钙500g，针叶樱桃冻干粉20g，硬脂酸镁10g，玉米淀粉1g，预胶化淀粉10g。
其中，所述的针叶樱桃冻干粉的制备方法为：取针叶樱桃果实，去核，压榨出果汁，过滤除去不溶物，真空冷冻干燥即得针叶樱桃冻干粉。
一种羟苯磺酸钙胶囊的制备方法，包括以下步骤：
(1)羟苯磺酸钙、针叶樱桃冻干粉和玉米淀粉、预胶化淀粉过50目筛，称量备料；硬脂酸镁称量备料；
(2)依次将硬脂酸镁、玉米淀粉、预胶化淀粉、针叶樱桃冻干粉和羟苯磺酸钙加入万向运动混合机混合，设定频率32Hz，混合时间：10分钟；混合结束后出料；
(3)将混合的物料送入干法制粒机制粒，得到羟苯磺酸钙颗粒；测定羟苯磺酸钙含量；干法制粒机工艺参数设定如下：送料转速：25.00rpm，压轮转速：8rpm，辊压压力：8.0Mpa，破碎转速：100rpm，整粒1转速：80rpm，筛网孔径Φ2.0mm；整粒2转速：80rpm，筛网孔径Φ1.0mm；
(4)根据羟苯磺酸钙颗粒中含量测定结果调节装量范围，将羟苯磺酸钙颗粒和空心胶囊分别加入胶囊填充机中，设定填充速度为1500粒/分进行填充。在填充过程中每20分钟取样1次，检测粒重差异，粒重差异控制在±5.0％。
实施例2
一种羟苯磺酸钙胶囊，每1000粒胶囊含有以下重量的组分：羟苯磺酸钙500g，针叶樱桃冻干粉25g，硬脂酸镁4.4g，玉米淀粉3g，预胶化淀粉20g。
一种羟苯磺酸钙胶囊的制备方法，包括以下步骤：
(1)羟苯磺酸钙、针叶樱桃冻干粉和玉米淀粉过60目筛，称量备料；硬脂酸镁称量备料；
(2)依次将硬脂酸镁、玉米淀粉、预胶化淀粉、针叶樱桃冻干粉和羟苯磺酸钙加入万向运动混合机混合，设定频率32Hz，混合时间：10分钟；混合结束后出料；
(3)将混合的物料送入干法制粒机制粒，得到羟苯磺酸钙颗粒；测定羟苯磺酸钙含量；干法制粒机工艺参数设定如下：送料转速：25.00rpm，压轮转速：8rpm，辊压压力：9.09Mpa，破碎转速：100rpm，整粒1转速：100rpm，筛网孔径Φ2.0mm；整粒2转速：100rpm，筛网孔径Φ1.0mm；
(4)根据羟苯磺酸钙颗粒中含量测定结果调节装量范围，将羟苯磺酸钙颗粒和空心胶囊分别加入胶囊填充机中，设定填充速度为2000粒/分进行填充。在填充过程中每20分钟取样1次，检测粒重差异，粒重差异控制在±5.0％。
实施例3
一种羟苯磺酸钙胶囊，每1000粒胶囊含有以下重量的组分：羟苯磺酸钙500g，针叶樱桃冻干粉30g，硬脂酸镁1g，玉米淀粉5g，预胶化淀粉10g。
其中，所述的针叶樱桃冻干粉的制备方法为：取针叶樱桃果实，去核，压榨出果汁，过滤除去不溶物，真空冷冻干燥即得针叶樱桃冻干粉。
一种羟苯磺酸钙胶囊的制备方法，包括以下步骤：
(1)羟苯磺酸钙、针叶樱桃冻干粉和玉米淀粉、预胶化淀粉过80目筛，称量备料；硬脂酸镁称量备料；
(2)依次将硬脂酸镁、玉米淀粉、预胶化淀粉、针叶樱桃冻干粉和羟苯磺酸钙加入万向运动混合机混合，设定频率32Hz，混合时间：10分钟；混合结束后出料；
(3)将混合的物料送入干法制粒机制粒，得到羟苯磺酸钙颗粒；测定羟苯磺酸钙含量；干法制粒机工艺参数设定如下：送料转速：30.00rpm，压轮转速：12rpm，辊压压力：10.0Mpa，破碎转速：100rpm，整粒1转速：100rpm，筛网孔径Φ2.0mm；整粒2转速：100rpm，筛网孔径Φ1.0mm；
(4)根据羟苯磺酸钙颗粒中含量测定结果调节装量范围，将羟苯磺酸钙颗粒和空心胶囊分别加入胶囊填充机中，设定填充速度为2100粒/分进行填充。在填充过程中每20分钟取样1次，检测粒重差异，粒重差异控制在±5.0％。
上述实施例中制得的羟苯磺酸钙，可以采用铝塑包装，设定铝塑包装机工艺参数，成型温度80-100℃，热封温度165-185℃，压缩空气≥0.4Mpa，内包装为PVDC和铝箔。将铝塑合格的羟苯磺酸钙胶囊按上述工艺参数进行包装，12粒/板。
本发明制得的羟苯磺酸钙胶囊质量检查
分别取本发明3个实施例制得的羟苯磺酸钙胶囊，按照《中华人民共和国药典(2020版)》中关于羟苯磺酸钙胶囊的质量标准以及各项指标的检测方法，对上述产品进行检验，具体结果如下。
表1羟苯磺酸钙胶囊质量检查结果
由表1可知，本申请3个实施例制备的羟苯磺酸钙胶囊均均符合羟苯磺酸钙胶囊的质量要求。
不同方法制得的羟苯磺酸钙胶囊性能比较
分别取3个实施例中制得的羟苯磺酸钙胶囊，进行铝塑包装，在温度40℃±2℃，相对湿度75％±5％的条件下放置6个月。在实验期间，分别于第0个月、1个月、2个月、3个月和6个月末各取样一次。对比例1配方中去掉针叶樱桃冻干粉，对比例2配方中去掉针叶樱桃冻干粉和预胶化淀粉。对比例1-2均按照实施例2的制备方法制备胶囊，并且进行铝塑包装。每个处理组设置3个平行实验。其结果如表2所示。
表2内容物外观性状考察结果
表3有效成分含量考察结果(％)
| 第0个月 | 第1个月 | 第2个月 | 第3个月 | 第6个月 | |
| 实施例1 | 99.98 | 99.98 | 99.97 | 99.95 | 99.80 |
| 实施例2 | 100.30 | 100.22 | 100.25 | 99.97 | 99.92 |
| 实施例3 | 99.71 | 99.71 | 99.70 | 99.65 | 99.54 |
| 对比例1 | 99.92 | 98.34 | 96.05 | 94.01 | 93.02 |
| 对比例2 | 100.23 | 98.12 | 92.10 | 87.43 | 79.31 |
由表2和表3可以看出，本发明3个实施例中所述的羟苯磺酸钙胶囊，在温度40℃±2℃，相对湿度75％±5％的条件下放置6个月仍可以保持均匀的颗粒状，并且有效成分含量保持在99％以上，符合药品标准。而对比例1、2在实验过程中出现了不同程度的结块或变色情况，有效成分含量也有不同程度的下降，实验结束时，有效成分含量均达不到羟苯磺酸钙胶囊的质量标准。
以上对本发明的具体实施例进行了详细描述，但其只是作为范例，本发明并不限制于以上描述的具体实施例。对于本领域技术人员而言，任何对本发明进行的等同修改和替代也都在本发明的范畴之中。因此，在不脱离本发明的精神和范围下所作的均等变换和修改，都应涵盖在本发明的范围内。
Claims (8)
1.一种羟苯磺酸钙胶囊，其特征在于，每1000粒胶囊含有以下重量的组分：羟苯磺酸钙500g，针叶樱桃冻干粉20-30g，硬脂酸镁1-10g，玉米淀粉1-5g，预胶化淀粉10-20g；所述的针叶樱桃冻干粉的制备方法为：取针叶樱桃果实，去核，压榨出果汁，过滤除去不溶物，真空冷冻干燥即得针叶樱桃冻干粉。
2.如权利要求1所述的一种羟苯磺酸钙胶囊，其特征在于，所述的羟苯磺酸钙胶囊，每1000粒胶囊含有以下重量的组分：羟苯磺酸钙500g，针叶樱桃冻干粉25g，硬脂酸镁4.4g，玉米淀粉3g，预胶化淀粉20g。
3.一种如权利要求1或2所述的羟苯磺酸钙胶囊的制备方法，其特征在于，包括以下步骤：
（1）羟苯磺酸钙、针叶樱桃冻干粉和玉米淀粉、预胶化淀粉过50-80目筛，称量备料；硬脂酸镁称量备料；
（2）依次将硬脂酸镁、玉米淀粉、预胶化淀粉、针叶樱桃冻干粉和羟苯磺酸钙加入混合机中，混合；混合结束后出料；
（3）将混合的物料送入干法制粒机制粒，得到羟苯磺酸钙颗粒；测定羟苯磺酸钙含量；
（4）根据羟苯磺酸钙颗粒中含量测定结果调节装量范围，将羟苯磺酸钙颗粒填充入空心胶囊中，即可。
4.如权利要求3所述的一种羟苯磺酸钙胶囊的制备方法，其特征在于，所述的步骤（2）中，采用万向运动混合机，设定频率32Hz，混合时间：10分钟。
5.如权利要求4所述的一种羟苯磺酸钙胶囊的制备方法，其特征在于，所述步骤（3），干法制粒机工艺参数设定如下：送料转速：25.00-30.00rpm，压轮转速：8-12rpm，辊压压力：8.0-10.0Mpa，破碎转速：100rpm，整粒1转速：80-100rpm，筛网孔径Φ2.0mm；整粒2转速：80-100rpm，筛网孔径Φ1.0mm。
6.如权利要求3所述的一种羟苯磺酸钙胶囊的制备方法，其特征在于，所述的步骤（3）干法制粒机工艺参数设定如下：送料转速：25.00rpm，压轮转速：8rpm，辊压压力：9.09Mpa，破碎转速：100rpm，整粒1转速：100rpm，筛网孔径Φ2.0mm；整粒2转速： 100rpm，筛网孔径Φ1.0mm。
7.如权利要求3所述的一种羟苯磺酸钙胶囊的制备方法，其特征在于，所述的步骤（4）采用胶囊填充机填充胶囊，设定填充速度为1500-2100粒/分。
8.如权利要求3所述的一种羟苯磺酸钙胶囊的制备方法，其特征在于，所述步骤（4）在填充过程中每20分钟取样1次，检测粒重差异。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210484431.4A CN114712324B (zh) | 2022-05-06 | 2022-05-06 | 一种羟苯磺酸钙胶囊及其制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210484431.4A CN114712324B (zh) | 2022-05-06 | 2022-05-06 | 一种羟苯磺酸钙胶囊及其制备方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114712324A CN114712324A (zh) | 2022-07-08 |
| CN114712324B true CN114712324B (zh) | 2024-04-16 |
Family
ID=82232169
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210484431.4A Active CN114712324B (zh) | 2022-05-06 | 2022-05-06 | 一种羟苯磺酸钙胶囊及其制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114712324B (zh) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2208498A1 (en) * | 2007-09-07 | 2010-07-21 | World Trade Import-Export, WTIE A.G. | Pharmaceutical composition combining various venotonic and vasoprotective agents for the treatment of chronic venous insufficiency |
| CN103271896A (zh) * | 2012-03-14 | 2013-09-04 | 南京先宇科技有限公司 | 一种稳定的羟苯磺酸钙制备方法 |
-
2022
- 2022-05-06 CN CN202210484431.4A patent/CN114712324B/zh active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2208498A1 (en) * | 2007-09-07 | 2010-07-21 | World Trade Import-Export, WTIE A.G. | Pharmaceutical composition combining various venotonic and vasoprotective agents for the treatment of chronic venous insufficiency |
| CN103271896A (zh) * | 2012-03-14 | 2013-09-04 | 南京先宇科技有限公司 | 一种稳定的羟苯磺酸钙制备方法 |
Non-Patent Citations (2)
| Title |
|---|
| 常映明.《抗衰老漫谈：点燃生日蛋糕上的第120根蜡烛》.中国医药科技出版社,2017,第112-113页. * |
| 徐晖.《药用高分子材料学》.中国医药科技出版社,2019,第91-92页. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114712324A (zh) | 2022-07-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6419958B2 (en) | Extended release formulation of venlafaxine hydrochloride | |
| NO320355B1 (no) | Innkapslet eller belagt blanding med forlenget frigjoring | |
| CN104719910B (zh) | 具有热稳定性的egcg固体分散体组合物及其制备方法和应用 | |
| DE4221880A1 (de) | Feste und flüssige Lösungen von schwer wasserlöslichen Arzneistoffen | |
| CN104587260B (zh) | 竹叶黄酮和壳寡糖的组合物，其制备方法和应用 | |
| EP3996695A1 (en) | Cannabidiol orally disintegrating tablets | |
| CN110559269A (zh) | 一种单硝酸异山梨酯片剂及其质量检测方法 | |
| EP2612659B1 (en) | Panaxatriol saponins enteric pellet, capsule comprising same and method for preparing same | |
| CN102600132A (zh) | 一种含氨磺必利的口服制剂 | |
| CN114712324B (zh) | 一种羟苯磺酸钙胶囊及其制备方法 | |
| CN104784197A (zh) | EGCG与β-葡聚糖的组合物及其制备方法和药物应用 | |
| CN113795252B (zh) | 含硝羟喹啉的药物组合物、硝羟喹啉口服固体片剂及其制备方法和用途 | |
| CN104922143A (zh) | Egcg与壳寡糖的组合物及其制备方法和应用 | |
| CN114432424B (zh) | 一种稳定的铝塑包装去氨加压素片剂 | |
| CN115364166B (zh) | 一种提升工艺稳定性以及产品品质的维脂康胶囊的制备方法 | |
| CN111297918A (zh) | Egcg与蛹虫草提取物的组合物及其制备方法和应用 | |
| CN1857285A (zh) | 一种用于治疗心脑血管疾病的胶囊及其制备方法和应用 | |
| US7115283B2 (en) | Preparations for sustained release of nutraceuticals and methods of controllably releasing nutraceuticals | |
| CN111150713B (zh) | 一种吲达帕胺胶囊及其制备方法 | |
| CN109771596B (zh) | 一种抗菌消炎胶囊及其制备方法 | |
| Romas et al. | The Development of Granules Based on Arginine and Ginseng | |
| CN105343723A (zh) | 一种桔远止咳微囊的制备方法 | |
| CN115581681A (zh) | 一种新型羟苯磺酸钙胶囊剂及其制备方法 | |
| CN115400181B (zh) | 一种低含水量裸花紫珠胶囊制剂的制备方法 | |
| CN105582546A (zh) | 一种恩替卡韦磷脂复合物和甘草酸二铵的复方肠溶片剂 |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |