CN112716922A - 一种具有治疗骨质疏松症的米诺膦酸贴剂的制备方法 - Google Patents
一种具有治疗骨质疏松症的米诺膦酸贴剂的制备方法 Download PDFInfo
- Publication number
- CN112716922A CN112716922A CN202110252330.XA CN202110252330A CN112716922A CN 112716922 A CN112716922 A CN 112716922A CN 202110252330 A CN202110252330 A CN 202110252330A CN 112716922 A CN112716922 A CN 112716922A
- Authority
- CN
- China
- Prior art keywords
- patch
- minodronate
- osteoporosis
- acid
- treatment
- 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
- VMMKGHQPQIEGSQ-UHFFFAOYSA-N minodronic acid Chemical compound C1=CC=CN2C(CC(O)(P(O)(O)=O)P(O)(O)=O)=CN=C21 VMMKGHQPQIEGSQ-UHFFFAOYSA-N 0.000 title claims abstract description 44
- 229950011129 minodronic acid Drugs 0.000 title claims abstract description 44
- 208000001132 Osteoporosis Diseases 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title abstract description 12
- 239000004820 Pressure-sensitive adhesive Substances 0.000 claims abstract description 9
- 239000003623 enhancer Substances 0.000 claims abstract description 9
- -1 tackifier Substances 0.000 claims abstract description 9
- 238000005520 cutting process Methods 0.000 claims abstract description 8
- 238000001035 drying Methods 0.000 claims abstract description 8
- 238000004806 packaging method and process Methods 0.000 claims abstract description 8
- 239000004014 plasticizer Substances 0.000 claims abstract description 8
- 239000003755 preservative agent Substances 0.000 claims abstract description 8
- 230000002335 preservative effect Effects 0.000 claims abstract description 8
- 239000011248 coating agent Substances 0.000 claims abstract description 7
- 238000000576 coating method Methods 0.000 claims abstract description 7
- RSWGJHLUYNHPMX-UHFFFAOYSA-N Abietic-Saeure Natural products C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 claims description 8
- KHPCPRHQVVSZAH-HUOMCSJISA-N Rosin Natural products O(C/C=C/c1ccccc1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 KHPCPRHQVVSZAH-HUOMCSJISA-N 0.000 claims description 8
- 239000004745 nonwoven fabric Substances 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- KHPCPRHQVVSZAH-UHFFFAOYSA-N trans-cinnamyl beta-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OCC=CC1=CC=CC=C1 KHPCPRHQVVSZAH-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- 229920006267 polyester film Polymers 0.000 claims description 7
- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 6
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims description 6
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 229920000058 polyacrylate Polymers 0.000 claims description 6
- 229920005989 resin Polymers 0.000 claims description 6
- 239000011347 resin Substances 0.000 claims description 6
- 229920002545 silicone oil Polymers 0.000 claims description 6
- 239000011975 tartaric acid Substances 0.000 claims description 6
- 235000002906 tartaric acid Nutrition 0.000 claims description 6
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- 229920002367 Polyisobutene Polymers 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- DNTGGZPQPQTDQF-XBXARRHUSA-N crotamiton Chemical compound C/C=C/C(=O)N(CC)C1=CC=CC=C1C DNTGGZPQPQTDQF-XBXARRHUSA-N 0.000 claims description 4
- 229960003338 crotamiton Drugs 0.000 claims description 4
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 claims description 2
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 claims description 2
- HBTAOSGHCXUEKI-UHFFFAOYSA-N 4-chloro-n,n-dimethyl-3-nitrobenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 HBTAOSGHCXUEKI-UHFFFAOYSA-N 0.000 claims description 2
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 claims description 2
- 239000005711 Benzoic acid Substances 0.000 claims description 2
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 2
- 239000013032 Hydrocarbon resin Substances 0.000 claims description 2
- 125000002723 alicyclic group Chemical group 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 235000010233 benzoic acid Nutrition 0.000 claims description 2
- 229960004365 benzoic acid Drugs 0.000 claims description 2
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- 229940031578 diisopropyl adipate Drugs 0.000 claims description 2
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 claims description 2
- 229920006270 hydrocarbon resin Polymers 0.000 claims description 2
- 229940074928 isopropyl myristate Drugs 0.000 claims description 2
- 229940057995 liquid paraffin Drugs 0.000 claims description 2
- 229940041616 menthol Drugs 0.000 claims description 2
- 229920001296 polysiloxane Polymers 0.000 claims description 2
- 229920000346 polystyrene-polyisoprene block-polystyrene Polymers 0.000 claims description 2
- 235000010241 potassium sorbate Nutrition 0.000 claims description 2
- 239000004302 potassium sorbate Substances 0.000 claims description 2
- 229940069338 potassium sorbate Drugs 0.000 claims description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 claims description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 2
- 235000010234 sodium benzoate Nutrition 0.000 claims description 2
- 239000004299 sodium benzoate Substances 0.000 claims description 2
- 229960003885 sodium benzoate Drugs 0.000 claims description 2
- 235000010199 sorbic acid Nutrition 0.000 claims description 2
- 239000004334 sorbic acid Substances 0.000 claims description 2
- 229940075582 sorbic acid Drugs 0.000 claims description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims 1
- 206010041235 Snoring Diseases 0.000 claims 1
- 125000005498 phthalate group Chemical class 0.000 claims 1
- 239000010410 layer Substances 0.000 abstract description 13
- 230000000694 effects Effects 0.000 abstract description 6
- 239000011241 protective layer Substances 0.000 abstract description 2
- 238000003723 Smelting Methods 0.000 abstract 1
- 238000010579 first pass effect Methods 0.000 abstract 1
- 230000002496 gastric effect Effects 0.000 abstract 1
- 210000004185 liver Anatomy 0.000 abstract 1
- 238000002156 mixing Methods 0.000 abstract 1
- 239000007935 oral tablet Substances 0.000 abstract 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- 239000003814 drug Substances 0.000 description 8
- 210000000988 bone and bone Anatomy 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 238000012377 drug delivery Methods 0.000 description 6
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 5
- 206010039984 Senile osteoporosis Diseases 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 3
- 206010017076 Fracture Diseases 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 210000002997 osteoclast Anatomy 0.000 description 2
- 229920000728 polyester Polymers 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 208000010392 Bone Fractures Diseases 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 238000007923 drug release testing Methods 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical class OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 1
- ZDCHZHDOCCIZIY-UHFFFAOYSA-N phthalic acid;propane-1,2,3-triol Chemical compound OCC(O)CO.OC(=O)C1=CC=CC=C1C(O)=O ZDCHZHDOCCIZIY-UHFFFAOYSA-N 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 208000001685 postmenopausal osteoporosis Diseases 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000008539 xiaoyao Substances 0.000 description 1
Classifications
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Dermatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明公开了一种米诺膦酸贴剂的制备及其应用于老年人骨质疏松症的治疗。所述贴剂包括以下组分：米诺膦酸、压敏胶、透皮促进剂、增粘剂、防腐剂、增塑剂以及pH调节剂。所述贴剂的制备方法为将上述组分在一定温度下进行熔炼混合后得到含量均匀的膏体，随后将其均匀的涂抹在背衬层上，再贴上保护层进行干燥、裁切、包装得到贴剂。本发明的优势在于，米诺膦酸贴剂相比于口服片剂，可以不经过肝脏的首过效应，用于骨质疏松症的治疗具有安全性高、胃肠道副作用少、给药方便等特点。
Description
技术领域
本发明涉及药物制剂领域，具体涉及一种米诺膦酸贴剂的制备及应用。
背景技术
骨质疏松症(包括绝经期后骨质疏松和老年性骨质疏松)是一种以骨量减少、骨组织微细结构退化(松质骨骨小梁变细、断裂，数量减少；皮质骨多孔、变薄)为特征的，以致骨的脆性增加，骨折危险性增加的全身性的老年性骨骼疾病。调查表明，目前全世界约有2亿人患骨质疏松症，其发病率已跃居常见病、多发病的第七位，我国老年人中患病比例占一半以上。绝经后的女性骨质疏松的发病率更高，我国60岁以上女性的骨质疏松症发病率高达70％，我国已将它列为三大重点攻关研究的老年性疾病之一。
米诺膦酸是一种含氮的二碳酸盐化合物，通过抑制破骨细胞内的焦磷酸法尼酯合成酶，抑制破骨细胞的骨吸收功能，进而使骨代谢循环减退，从而达到治疗骨质疏松症的目的。米诺膦酸片由日本小野药品工业株式会社和日本Astellas制药株式会社共同开发，于2009年1月在日本首次获准上市，迄今未在国内上市。2020年12月江苏天士力帝益药业有限公司首仿米诺膦酸片在中国上市。口服米诺膦酸片每日一次，每次1mg，服药后至少30分钟内不可横卧，且主要不良反应为胃腹部不适（3.2%）、腹痛（2.4%）、血钙减少 (2.0%)及胃炎（1.4%）。为减轻这些副作用及服药后不可横卧的缺点，开发了由皮肤吸收药物的制剂，即透皮贴剂。
贴剂具有使用方便，贴敷舒适，对皮肤无刺激性，缓慢递送药物，可长期起效，无痛给药，患者可自行给药等特点，对于老年人骨质疏松患者具有更好的用药顺应性。
发明内容
有鉴于此，本发明的主要目的在于提供一种使用方便、副反应小、效果明显、可长时间起效的米诺膦酸贴剂，以用于老年人骨质疏松患者的治疗。本发明的技术方案如下：
治疗老年人骨质疏松的贴剂，包括以下组分：米诺膦酸、压敏胶、透皮促进剂、增粘剂、防腐剂、增塑剂以及pH调节剂。
制备方法为：将上述组分在一定温度下进行熔炼混合后得到含量均匀的膏体，随后将其均匀的涂抹在背衬层上，再贴上保护层进行干燥、裁切、包装得到贴剂。
进一步，所述米诺膦酸的含量为膏体总重量的2.0%-10%。
进一步，所述压敏胶为聚硅氧烷、聚丙烯酸酯、聚异丁烯、苯乙烯-异戊二烯-苯乙烯嵌段共聚物中至少一种，含量为膏体总重量的20%-45%。
进一步，所述透皮促进剂为丙二醇、氮酮、薄荷醇、克罗米通、肉豆蔻酸异丙酯、己二酸二异丙酯中至少一种，含量为膏体总重量的1.0%-5.0%。
进一步，所述增粘剂为脂环族饱和烃树脂、松香和氢化松香树脂中至少一种，含量为膏体总重量的10%-30%。
进一步，所述防腐剂选自二丁基羟基甲苯、苯甲酸、苯甲酸钠、山梨酸、山梨酸钾中至少一种，含量为膏体总重量的1.0%-5.0%。
进一步，所述增塑剂选自液体石蜡、邻苯二甲酸酯类、邻苯二甲酸酣类中至少一种，含量为膏体总重量的10%-30%。
进一步，所述pH调节剂选自酒石酸、磷酸、盐酸、硫酸、二乙胺、二乙醇胺中至少一种，含量为膏体总重量的1.0%-5.0%。
所述背衬层包括但不限于无纺布、聚酯无纺布、聚乙烯膜、铝箔中的一种。
所述保护膜包括但不限于涂有石蜡或二甲基硅油的PET聚酯膜、聚丙烯膜、聚乙烯膜、纸-聚酯复合膜中的一种。
米诺磷酸贴剂的制备工艺如下：
A. 将处方量的压敏胶、增粘剂、增塑剂以及防腐剂在40-60 ℃下，搅拌40-60 min得到均匀膏体，作为A相。
B. 40-60 ℃下将处方量的米诺膦酸、pH调节剂以及透皮促进剂加入到A相，并搅拌均匀，得到B相。
C. 以无纺布作为背衬层，涂二甲基硅油的PET聚酯膜作为防粘层，将B相进行涂布、干燥、裁切、包装等工序，得米诺膦酸贴剂。
所述米诺膦酸贴剂可用于老年人骨质疏松症的治疗。
本发明的优势在于：
基于以上，本发明所提供的米诺膦酸贴剂具有使用方便，贴敷舒适，对皮肤无刺激性，缓慢递送药物，可长期起效，无痛给药，患者可自行给药等特点，对于老年人患者具有更好的用药顺应性。
具体实施方式
所举实施例是为了更好地对本发明的内容进行说明，但并不是本发明的内容仅限于所举实施例。所以熟悉本领域的技术人员根据上述发明内容对实施方案进行非本质的改进和调整，仍属于本发明的保护范围。
实施例1 ：
处方组成：
制备工艺：
A. 将处方量的聚丙烯酸酯、氢化松香树脂、甘油以及二丁基羟基甲苯在40-60 ℃下，搅拌40-60 min得到均匀膏体，作为A相。
B. 40-60 ℃下将处方量的米诺膦酸、酒石酸以及L-薄荷醇加入到A相，并搅拌均匀，得到B相。
C. 以无纺布作为背衬层，涂二甲基硅油的PET聚酯膜作为防粘层，将B相进行涂布、干燥、裁切、包装等工序，得米诺膦酸贴剂。
实施例2：
处方组成：
制备工艺：
A. 将处方量的聚丙烯酸酯、聚异丁烯、氢化松香树脂、甘油以及二丁基羟基甲苯在40-60 ℃下，搅拌40-60 min得到均匀膏体，作为A相。
B. 40-60 ℃下将处方量的米诺膦酸、酒石酸以及L-薄荷醇加入到A相，并搅拌均匀，得到B相。
C. 以无纺布作为背衬层，涂二甲基硅油的PET聚酯膜作为防粘层，将B相进行涂布、干燥、裁切、包装等工序，得米诺膦酸贴剂。
实施例3 ：
处方组成：
制备工艺：
A. 将处方量的聚丙烯酸酯、氢化松香树脂、甘油以及二丁基羟基甲苯在40-60 ℃下，搅拌40-60 min得到均匀膏体，作为A相。
B. 40-60 ℃下将处方量的米诺膦酸、酒石酸、L-薄荷醇以及克罗米通加入到A相，并搅拌均匀，得到B相。
C. 以无纺布作为背衬层，涂二甲基硅油的PET聚酯膜作为防粘层，将B相进行涂布、干燥、裁切、包装等工序，得米诺膦酸贴剂。
实施例4：
处方组成：
制备工艺：
A. 将处方量的聚丙烯酸酯、聚异丁烯、氢化松香树脂、甘油以及二丁基羟基甲苯在40-60 ℃下，搅拌40-60 min得到均匀膏体，作为A相。
B. 40-60 ℃下将处方量的米诺膦酸、酒石酸、L-薄荷醇以及克罗米通加入到A相，并搅拌均匀，得到B相。
C. 以无纺布作为背衬层，涂二甲基硅油的PET聚酯膜作为防粘层，将B相进行涂布、干燥、裁切、包装等工序，得米诺膦酸贴剂。
实施例5：米诺膦酸贴剂的药物释放试验
使用实施例1-4制备的米诺膦酸贴剂，来进行药物对pH 7.4磷酸缓冲液的释放试验，求出来自米诺膦酸贴剂的药物释放速率。其结果示于下表：
| 实施例 | 24小时后的释放率（%） |
| 实施例1 | 83.3 |
| 实施例2 | 87.4 |
| 实施例3 | 90.1 |
| 实施例4 | 93.5 |
从以上实验结果可知，使用两种不同的压敏胶或透皮促进剂可提高药物从基质的释放性。
实施例6：米诺膦酸贴剂的体外透皮试验
使用实施例1-4制备的米诺膦酸贴剂，来进行使用了取自大鼠腹部的皮肤的体外透过试验。 其结果示于下表：
| 实施例 | 24小时累积透过量（nmol/cm<sup>2</sup>） |
| 实施例1 | 178.45 |
| 实施例2 | 258.32 |
| 实施例3 | 297.16 |
| 实施例4 | 321.37 |
从上表所示的结果可知， 实施例 2～4 与实施例 1比较， 药物释放性、透皮吸收性 ( 累积透过量 ) 明显优异。
以上所述实施例仅表达了本发明的几种实施方式，其描述较为具体和详细，但并不能因此而理解为对发明专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。因此，本发明专利的保护范围应以所附权利要求为准。
Claims (9)
1.治疗成人骨质疏松症的米诺膦酸贴剂，其特征在于，包括以下组分：米诺膦酸、压敏胶、透皮促进剂、增粘剂、防腐剂、增塑剂以及pH调节剂。
2.根据权利要求1所述治疗成人骨质疏松症的米诺膦酸贴剂，其特征在于，所述压敏胶为聚硅氧烷、聚丙烯酸酯、聚异丁烯、苯乙烯-异戊二烯-苯乙烯嵌段共聚物中至少一种。
3.根据权利要求1-2所述治疗成人骨质疏松症的米诺膦酸贴剂，其特征在于，所述透皮促进剂为丙二醇、氮酮、薄荷醇、克罗米通、肉豆蔻酸异丙酯、己二酸二异丙酯中至少一种。
4.根据权利要求1-3所述治疗成人骨质疏松症的米诺膦酸贴剂，其特征在于，所述增粘剂为脂环族饱和烃树脂、松香和氢化松香树脂中至少一种。
5.根据权利要求1-4所述治疗成人骨质疏松症的米诺膦酸贴剂，其特征在于，所述防腐剂选自二丁基羟基甲苯、苯甲酸、苯甲酸钠、山梨酸、山梨酸钾中至少一种。
6.根据权利要求1-5所述治疗成人骨质疏松症的米诺膦酸贴剂，其特征在于，所述增塑剂选自液体石蜡、邻苯二甲酸酯类、邻苯二甲酸酣类中至少一种。
7.根据权利要求1-6所述治疗成人骨质疏松症的米诺膦酸贴剂，其特征在于，所述pH调节剂选自酒石酸、磷酸、盐酸、硫酸、二乙胺、二乙醇胺中至少一种。
8.根据权利要求1-7所述治疗成人骨质疏松症的米诺膦酸贴剂，所述贴剂的制备工艺包括以下步骤：
A. 将处方量的压敏胶、增粘剂、增塑剂以及防腐剂在40-60 ℃下，搅拌40-60 min得到均匀膏体，作为A相；
B. 40-60 ℃下将处方量的米诺膦酸、pH调节剂以及透皮促进剂加入到A相，并搅拌均匀，得到B相；
C. 以无纺布作为背衬层，涂二甲基硅油的PET聚酯膜作为防粘层，将B相进行涂布、干燥、裁切、包装等工序，得米诺膦酸贴剂。
9.根据权利要求1-8所述的贴剂，其特征在于，所述贴剂可用于治疗成人骨质疏松症。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110252330.XA CN112716922A (zh) | 2021-03-09 | 2021-03-09 | 一种具有治疗骨质疏松症的米诺膦酸贴剂的制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110252330.XA CN112716922A (zh) | 2021-03-09 | 2021-03-09 | 一种具有治疗骨质疏松症的米诺膦酸贴剂的制备方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112716922A true CN112716922A (zh) | 2021-04-30 |
Family
ID=75595865
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110252330.XA Pending CN112716922A (zh) | 2021-03-09 | 2021-03-09 | 一种具有治疗骨质疏松症的米诺膦酸贴剂的制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112716922A (zh) |
-
2021
- 2021-03-09 CN CN202110252330.XA patent/CN112716922A/zh active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2062575B1 (en) | Adhesive preparation comprising desglymidodrine | |
| NO303262B1 (no) | FremgangsmÕte for fremstilling av et faststoffmatrikssystem for transdermal medikamentavlevering | |
| EP2491924B1 (en) | Water-based paste containing diclofenac sodium | |
| TW201431554A (zh) | 左炔諾孕酮（ｌｅｖｏｎｏｒｇｅｓｔｒｅｌ）及乙烯雌二醇之經皮藥物遞送系統 | |
| KR101766495B1 (ko) | 펜타닐 함유 외용 첩부제 | |
| US8852628B1 (en) | Transdermal drug delivery system for diclofenac | |
| JP5576573B2 (ja) | 貼付剤 | |
| TWI520733B (zh) | Contains lidocaine gel preparations | |
| JPH0662401B2 (ja) | ケトプロフエン含有パツプ剤 | |
| US20100215721A1 (en) | Poultice and process for producing the poultice | |
| WO2021098791A1 (zh) | 一种含有美金刚的透皮贴剂 | |
| EP0735867B1 (en) | Transdermal delivery device containing an estrogen | |
| CN112716922A (zh) | 一种具有治疗骨质疏松症的米诺膦酸贴剂的制备方法 | |
| WO2014068600A1 (en) | Stable transdermal pharmaceutical drug delivery system comprising diclofenac | |
| WO2024067722A1 (zh) | 含有秋水仙碱的贴剂及其制备方法和应用 | |
| EP2926814B1 (en) | Ropinirole-containing adhesive patch | |
| CN109481423B (zh) | 一种双氯芬酸盐透皮贴剂及其制备方法 | |
| JP2018524348A (ja) | レボノルゲストレルおよびエチニルエストラジオールのための経皮的薬物送達システム | |
| ES2969286T3 (es) | Sistema terapéutico transdérmico para la administración de escopolamina sin membrana | |
| JP7220473B2 (ja) | 経皮投与製剤 | |
| JPH1112163A (ja) | 貼付剤 | |
| EP4434525A1 (en) | Adhesive patch containing selexipag as active ingredient | |
| CN117899056A (zh) | 含利多卡因的透皮贴剂及其制备方法和用途 | |
| JPH06211696A (ja) | エペリゾンまたはトルペリゾン経皮吸収製剤 | |
| JP2024011413A (ja) | 経皮投与製剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20210430 |