CN117462490A - 一种阿莫罗芬搽剂 - Google Patents
一种阿莫罗芬搽剂 Download PDFInfo
- Publication number
- CN117462490A CN117462490A CN202311642653.5A CN202311642653A CN117462490A CN 117462490 A CN117462490 A CN 117462490A CN 202311642653 A CN202311642653 A CN 202311642653A CN 117462490 A CN117462490 A CN 117462490A
- Authority
- CN
- China
- Prior art keywords
- amorolfine
- liniment
- film forming
- forming agent
- nails
- 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
- MQHLMHIZUIDKOO-OKZBNKHCSA-N (2R,6S)-2,6-dimethyl-4-[(2S)-2-methyl-3-[4-(2-methylbutan-2-yl)phenyl]propyl]morpholine Chemical compound C1=CC(C(C)(C)CC)=CC=C1C[C@H](C)CN1C[C@@H](C)O[C@@H](C)C1 MQHLMHIZUIDKOO-OKZBNKHCSA-N 0.000 title claims abstract description 52
- 229960003204 amorolfine Drugs 0.000 title claims abstract description 52
- 239000000865 liniment Substances 0.000 title claims abstract description 38
- 229940040145 liniment Drugs 0.000 title claims abstract description 37
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 19
- 239000000203 mixture Substances 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 12
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 12
- 239000004014 plasticizer Substances 0.000 claims description 10
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 9
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 9
- -1 polydimethylsiloxane Polymers 0.000 claims description 8
- 239000002202 Polyethylene glycol Substances 0.000 claims description 6
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims description 6
- 229920001223 polyethylene glycol Polymers 0.000 claims description 6
- 239000001069 triethyl citrate Substances 0.000 claims description 6
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims description 6
- 235000013769 triethyl citrate Nutrition 0.000 claims description 6
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 5
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 5
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 5
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 5
- 229920001577 copolymer Polymers 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
- 229920001661 Chitosan Polymers 0.000 claims description 3
- 239000001856 Ethyl cellulose Substances 0.000 claims description 3
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 3
- 229920001249 ethyl cellulose Polymers 0.000 claims description 3
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 3
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 2
- 229940057917 medium chain triglycerides Drugs 0.000 claims description 2
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 18
- 238000005516 engineering process Methods 0.000 abstract description 9
- 229940079593 drug Drugs 0.000 abstract description 7
- 230000035699 permeability Effects 0.000 abstract description 3
- 239000002131 composite material Substances 0.000 abstract description 2
- 238000013461 design Methods 0.000 abstract description 2
- 230000000717 retained effect Effects 0.000 abstract description 2
- 210000000282 nail Anatomy 0.000 description 23
- 208000010195 Onychomycosis Diseases 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- 206010017533 Fungal infection Diseases 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 230000035515 penetration Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 229920003155 Eudragit® RL 100 Polymers 0.000 description 3
- 230000004888 barrier function Effects 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 210000000003 hoof Anatomy 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 201000005882 tinea unguium Diseases 0.000 description 3
- 239000004925 Acrylic resin Substances 0.000 description 2
- 229920000178 Acrylic resin Polymers 0.000 description 2
- 229920003159 Eudragit® RS 100 Polymers 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 208000031888 Mycoses Diseases 0.000 description 2
- 241000223238 Trichophyton Species 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 208000024386 fungal infectious disease Diseases 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- 241000223600 Alternaria Species 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 241000336315 Cistanche salsa Species 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 1
- 206010033372 Pain and discomfort Diseases 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 241001045770 Trichophyton mentagrophytes Species 0.000 description 1
- 241000223229 Trichophyton rubrum Species 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001857 anti-mycotic effect Effects 0.000 description 1
- 239000002543 antimycotic Substances 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000008576 chronic process Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 208000026721 nail disease Diseases 0.000 description 1
- 238000009782 nail-penetration test Methods 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 210000004906 toe nail Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 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
- A61K9/7015—Drug-containing film-forming compositions, e.g. spray-on
-
- 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
- A61K31/535—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 oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
-
- 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
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
- 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
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明是一种阿莫罗芬搽剂,采用复合成膜技术,同时在处方中使用亲脂性成膜剂和亲水性成膜剂,改良后的阿莫罗芬搽剂涂抹在指甲上后,实现即能长时间滞留在指甲上,也具备高渗透能力,增加药物的渗透速度和程度。本发明的优点:配方设计合理,在不改变药物剂量的前提下,通过对阿莫罗芬搽剂组合物进行优化,可增加阿莫罗芬的渗透速率和渗透量,并且不减少阿莫罗芬在指甲上的滞留时间,可提升药物的有效性和安全性,符合药物经济学的基本理论,可提升产品的临床价值。
Description
技术领域
本发明涉及的是一种阿莫罗芬搽剂,具体涉及一种延长在指甲上的滞留时间、提高渗透能力的阿莫罗芬搽剂。
背景技术
甲癣是指甲的真菌感染。最近对欧洲和美国人群的甲癣调查回顾发现,其平均患病率为4.3%。甲癣可引起疼痛和不适,并且可影响患者的生活质量,损害患者的心理和生理健康。指甲疾病可导致触觉功能受损或丧失,而趾甲疾病则妨碍行走、运动和穿鞋的舒适度。患者如不接受治疗,可传染给其他家庭成员,并且可能污染公共区域。甲的真菌感染可呈慢性过程,并对治疗产生抵抗,有16%-25%的患者经现有的治疗无法获得治愈。且就目前所知,感染无法自发性清除。
阿莫罗芬是局部外用抗真菌药,其活性成分为吗啉衍生物——阿莫罗芬。阿莫罗芬的抑菌作用主要是通过改变构成真菌细胞膜的脂类生物合成来实现的。阿莫罗芬为广谱高效抗真菌药,它的抗菌谱为:白色念珠菌及其他念珠菌种、红色毛癣菌、指(趾)间毛癣菌、须发毛癣菌及其他毛癣菌种、小孢子菌、帚霉菌、链格孢菌、分枝孢子菌等。
成膜技术是一种外用制剂技术,能够将产品长时间的滞留在靶部位,增加药物的作用时间,减少使用次数。是一种外用的缓释技术。目前成膜技术大多用于皮肤用制剂中。
《英国甲真菌病管理指南(2014年)》、《2021年版中国甲真菌病诊疗指南》均推荐阿莫罗芬搽剂作为甲真菌感染的一线治疗药物。阿莫罗芬搽剂可渗透甲板并在其中弥散,根除甲板内及甲板下的真菌。其中一种阿莫罗芬搽剂是由法国高德美制药公司开发的外用抗甲真菌药物。该阿莫罗芬搽剂的制剂技术采用了成膜技术,药物涂抹在指甲上,随着溶剂的挥发,高分子在指甲表面形成一层透明的薄膜,将药物包封在指甲表面,长效给药。通过使用成膜技术,阿莫罗芬能够在表面成膜,每周需要给药一到两次。
Mayur M Patel,Zeal M Vora等人研究了不同的成膜材料对于透甲的促渗透作用,其研究结果显示,亲水性成膜剂相比于亲脂性成膜剂,能够更好的促进药物的透甲。而亲脂性的成膜剂能够延长药物在靶部位的作用时间。相比透皮技术,透甲技术存在不同之处,指甲是由角蛋白(主要成分)、水分、细胞间质组成的;氨基酸的差异带来的屏障差异是巨大的。相比于角质层,指甲更像是一个亲水屏障。水溶性的药物能更好的渗透进入指甲体中。
高德美在开发阿莫罗芬搽剂时,选择的辅料为:季铵基甲基丙烯酸酯共聚物A型(丙烯酸树脂/EUDRAGIT RL100)(成膜材料)、三乙酸甘油酯(增塑剂)、乙酸丁酯(溶剂)、乙酸乙酯(溶剂)和无水乙醇(溶剂)。该处方中的成膜材料为EUDRAGIT RL100,而EUDRAGITRL100是一种亲脂性的高分子化合物,亲水性差,这使得阿莫罗芬搽剂在指甲上形成的是一种亲脂性的薄膜。该薄膜虽然能长时间的滞留在指甲表面,长效给药。但亲脂性的薄膜缺乏水合作用,会降低药物渗透进入指甲的速率和程度。限制了阿莫罗芬搽剂的药效,增加了真菌的存活概率。而对于甲真菌这种易复发的感染,临床上需要大剂量来完全杀死甲真菌,治疗的原则需要足量、足周期的治疗,降低复发率。
发明内容
本发明提出的是一种阿莫罗芬搽剂,其目的旨在克服现有技术存在的上述不足,提高阿莫罗芬的渗透量。
本发明的技术解决方案:一种阿莫罗芬搽剂,采用复合成膜技术,同时在处方中使用亲脂性成膜剂和亲水性成膜剂,改良后的阿莫罗芬搽剂涂抹在指甲上后,实现即能长时间滞留在指甲上,也具备高渗透能力,增加药物的渗透速度和程度。
具体的,包括以下组分:活性成分阿莫罗芬、亲水性成膜剂、亲脂性成膜剂、增塑剂、溶剂。
优选的,具体包括以重量百分比计的以下组分:阿莫罗芬5%、亲水性成膜剂5%、亲脂性成膜剂5%、增塑剂3%、溶剂82%。
优选的,所述的亲水性成膜剂为羟丙甲基纤维素(HPMC E4M,E15,E50M K4M等)、羟丙基纤维素(HPC LF、MF、HF等)、聚乙烯醇(聚乙烯醇聚乙二醇共聚物)、壳聚糖系列中的一种或多种混合。
具体优选为聚乙烯醇聚乙二醇共聚物。
优选的,所述的亲脂性成膜剂为丙烯酸树脂系列(Eudragit RS100、RL100、NE、RS300、S100等)、乙酰共聚物(Avalure AC118、AC120等)、乙基纤维素、聚二甲基硅氧烷(PDMS)系列中的一种或多种混合。
具体优选为聚二甲基硅氧烷(PDMS)。
优选的,所述的增塑剂为中链甘油三酸酯、柠檬酸三乙酯、醋酸三乙酯中的一种或多种混合。
具体优选为柠檬酸三乙酯。
优选的,所述的溶剂为乙醇、异丙醇中的一种或两种混合。
具体优选为乙醇。
本发明的优点:配方设计合理,在不改变药物剂量的前提下,通过对阿莫罗芬搽剂组合物进行优化,可增加阿莫罗芬的渗透速率和渗透量,并且不减少阿莫罗芬在指甲上的滞留时间,可提升药物的有效性和安全性,符合药物经济学的基本理论,可提升产品的临床价值。
实施方式
下面结合实施例和具体实施方式对本发明作进一步详细的说明。
一种阿莫罗芬搽剂,包括以下组分:活性成分阿莫罗芬、亲水性成膜剂、亲脂性成膜剂、增塑剂、溶剂。
溶剂的选择需要满足ICH Q3的要求,以降低药物的毒性和刺激性。对于成膜剂来说,需要溶剂满足:1.低毒、低刺激性;2.蒸气压高,常温下即可快速挥发;3.分子结构具有足够多的氧原子和氢原子,能够通过氢键和范德华力的作用,形成均匀的薄膜。满足上述条件的溶剂为小分子醇,包括但不限于乙醇、异丙醇中的一种或多种混合。
增塑剂可选包括但不限于中链甘油三酸酯、柠檬酸三乙酯、醋酸三乙酯中的一种或多种混合。
亲脂性成膜剂可选包括但不限于丙烯酸树脂系列(Eudragit RS100、RL100、NE、RS300、S100、dermacryl79等)、乙酰共聚物(Avalure AC118、AC120等)、乙基纤维素、聚二甲基硅氧烷(PDMS)系列中的一种或多种混合。
亲水性成膜剂可选包括但不限于羟丙甲基纤维素(HPMC E4M,E15,E50M K4M等)、羟丙基纤维素(HPC LF、 MF、HF等)、聚乙烯醇(聚乙烯醇聚乙二醇共聚物)、壳聚糖系列中的一种或多种混合。
实施例1
一种阿莫罗芬搽剂,组分如下表所示:
其中聚二甲基硅氧烷(PDMS)为亲脂性成膜剂,聚乙烯醇聚乙二醇共聚物为亲水性成膜剂,柠檬酸三乙酯为增塑剂,乙醇为溶剂。
制备方法为将上表所示原辅料依次溶解在溶剂中至澄清。
对比例1
一种阿莫罗芬搽剂,与实施例1区别在于组分包括重量百分比10%的聚乙烯醇聚乙二醇共聚物,不包括聚二甲基硅氧烷(PDMS)。
实施例2
将实施例1所得阿莫罗芬搽剂与市售高德美阿莫罗芬搽剂及对比例1所得阿莫罗芬搽剂进行透甲对比。
指甲模型采用牛蹄甲,牛蹄甲厚度控制在500±100μm。采用Franz扩散池的方法,以牛蹄甲(500±100μm)为渗透屏障,按10mg/cm2上药,上药量约17.7mg,接收液为生理盐水进行体外透甲试验,其中温度设置为32℃,转速600rpm,n=6,取样时间点为1d、2d、3d、4d、5d、6d、7d。
得到的结果见下表。
表1累积透甲量对比
表2指甲滞留量对比
从表1和表2的结果可知,相比于市售高德美阿莫罗芬搽剂和对比例1,本发明实施例1阿莫罗芬搽剂能显著提高阿莫罗芬的透甲渗透量以及指甲滞留量(p<0.05)。
以上所述的仅是本发明的优选实施方式,应当指出,对于本领域的普通技术人员来说,在不脱离本发明创造构思的前提下,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。
Claims (10)
1.一种阿莫罗芬搽剂,其特征在于,组分包括阿莫罗芬、亲水性成膜剂和亲脂性成膜剂。
2.如权利要求1所述的一种阿莫罗芬搽剂,其特征在于,以重量百分比计,组分包括阿莫罗芬5%、亲水性成膜剂5%和亲脂性成膜剂5%。
3.如权利要求2所述的一种阿莫罗芬搽剂,其特征在于,以重量百分比计,组分还包括增塑剂3%、溶剂82%。
4.如权利要求1-3任一项所述的一种阿莫罗芬搽剂,其特征在于,所述的亲水性成膜剂为羟丙甲基纤维素、羟丙基纤维素、聚乙烯醇、壳聚糖系列中的一种或多种混合。
5.如权利要求4所述的一种阿莫罗芬搽剂,其特征在于,所述的亲水性成膜剂为聚乙烯醇聚乙二醇共聚物。
6.如权利要求1-3任一项所述的一种阿莫罗芬搽剂,其特征在于,所述的亲脂性成膜剂为丙烯酸树脂系列、乙酰共聚物、乙基纤维素、聚二甲基硅氧烷系列中的一种或多种混合。
7.如权利要求6所述的一种阿莫罗芬搽剂,其特征在于,所述的亲脂性成膜剂为聚二甲基硅氧烷。
8.如权利要求3所述的一种阿莫罗芬搽剂,其特征在于,所述的增塑剂为中链甘油三酸酯、柠檬酸三乙酯、醋酸三乙酯中的一种或多种混合。
9.如权利要求8所述的一种阿莫罗芬搽剂,其特征在于,所述的增塑剂为柠檬酸三乙酯。
10.如权利要求3所述的一种阿莫罗芬搽剂,其特征在于,所述的溶剂为乙醇。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202311642653.5A CN117462490A (zh) | 2023-12-04 | 2023-12-04 | 一种阿莫罗芬搽剂 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202311642653.5A CN117462490A (zh) | 2023-12-04 | 2023-12-04 | 一种阿莫罗芬搽剂 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN117462490A true CN117462490A (zh) | 2024-01-30 |
Family
ID=89638039
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202311642653.5A Pending CN117462490A (zh) | 2023-12-04 | 2023-12-04 | 一种阿莫罗芬搽剂 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN117462490A (zh) |
-
2023
- 2023-12-04 CN CN202311642653.5A patent/CN117462490A/zh active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US7678366B2 (en) | Controlled delivery system of antifungal and keratolytic agents for local treatment of fungal infections of the nail and surrounding tissues | |
US6319509B1 (en) | Pharmaceutical composition | |
TWI232756B (en) | Nail lacquer composition for drug delivery | |
JP6307203B1 (ja) | 皮膚および爪の治療のための抗真菌組成物 | |
JP2010537988A5 (zh) | ||
JPH01501143A (ja) | 爪への薬物の施用のための皮膜形成性製剤用ヴェヒクル、これらのヴェヒクルを基にした薬剤組成物および同じものの使用法 | |
JP2007534764A (ja) | 抗真菌薬物送達 | |
EP1283708A2 (fr) | Utilisation de derives de biguanide pour fabriquer un medicament ayant un effet cicatrisant | |
EP2389938B1 (en) | Antifungal medicinal compositions | |
US20100168233A1 (en) | Terbinafine formulation | |
CN111741745A (zh) | 多用托拉塞米组合物 | |
JP2669951B2 (ja) | 麻薬性鎮痛剤を含有する経皮吸収組成物 | |
CN117462490A (zh) | 一种阿莫罗芬搽剂 | |
CN114129509B (zh) | 一种保湿性nmn亲水凝胶剂及其制备方法 | |
CN112263544B (zh) | 一种盐酸利多卡因凝胶及其制备方法 | |
Kishchenko et al. | Films in Russian medicine and cosmetology: development history, classification, technology | |
JP3657435B2 (ja) | 経皮吸収用組成物 | |
KR101690765B1 (ko) | 항진균성 활성물질을 포함하는 경피 제제 | |
KR101799008B1 (ko) | 케라틴 조직의 진균감염증 치료를 위한 약제학적 조성물 | |
CN113274500A (zh) | 神经激肽1受体抑制剂的外用制剂及其制备方法 | |
Shinde et al. | Recent updates on oral and dermal film-based formulations and their applications | |
US8257688B2 (en) | Controlled delivery system of antifungal and keratolytic agents for local treatment of fungal infections of the nail and surrounding tissues | |
CN114931564A (zh) | 一种长效抗真菌贴剂 | |
CN108355138A (zh) | 一种氮酮在药物透皮促渗中的应用 | |
RU2311186C1 (ru) | Биологически активный компонент, обладающий противогрибковым действием, и противогрибковый лечебно-косметический лак демиктен на его основе |
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 |