CN112274496A - Pressure-sensitive adhesive composition for transdermal patch, pressure-sensitive adhesive material and transdermal patch - Google Patents
Pressure-sensitive adhesive composition for transdermal patch, pressure-sensitive adhesive material and transdermal patch Download PDFInfo
- Publication number
- CN112274496A CN112274496A CN202011175102.9A CN202011175102A CN112274496A CN 112274496 A CN112274496 A CN 112274496A CN 202011175102 A CN202011175102 A CN 202011175102A CN 112274496 A CN112274496 A CN 112274496A
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- Prior art keywords
- component
- weight
- sensitive adhesive
- pressure
- acrylate
- Prior art date
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- 239000004820 Pressure-sensitive adhesive Substances 0.000 title claims abstract description 68
- 239000000203 mixture Substances 0.000 title claims abstract description 47
- 239000000463 material Substances 0.000 title claims abstract description 35
- 239000003814 drug Substances 0.000 claims abstract description 61
- 229940079593 drug Drugs 0.000 claims abstract description 57
- 150000001336 alkenes Chemical class 0.000 claims abstract description 37
- 229920001577 copolymer Polymers 0.000 claims abstract description 37
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims abstract description 29
- 229920000642 polymer Polymers 0.000 claims abstract description 29
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims abstract description 26
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims abstract description 22
- 150000002148 esters Chemical class 0.000 claims abstract description 20
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims abstract description 19
- 229920002635 polyurethane Polymers 0.000 claims abstract description 12
- 239000004814 polyurethane Substances 0.000 claims abstract description 12
- 229920002647 polyamide Polymers 0.000 claims abstract description 9
- 239000004952 Polyamide Substances 0.000 claims abstract description 7
- 229920000058 polyacrylate Polymers 0.000 claims description 19
- 239000003623 enhancer Substances 0.000 claims description 13
- 238000010521 absorption reaction Methods 0.000 claims description 12
- -1 polypropylene Polymers 0.000 claims description 11
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical compound C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 claims description 8
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 claims description 7
- CQEYYJKEWSMYFG-UHFFFAOYSA-N butyl acrylate Chemical compound CCCCOC(=O)C=C CQEYYJKEWSMYFG-UHFFFAOYSA-N 0.000 claims description 7
- GOXQRTZXKQZDDN-UHFFFAOYSA-N 2-Ethylhexyl acrylate Chemical compound CCCCC(CC)COC(=O)C=C GOXQRTZXKQZDDN-UHFFFAOYSA-N 0.000 claims description 6
- 229920002367 Polyisobutene Polymers 0.000 claims description 6
- QMMOXUPEWRXHJS-UHFFFAOYSA-N pentene-2 Natural products CCC=CC QMMOXUPEWRXHJS-UHFFFAOYSA-N 0.000 claims description 6
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 claims description 5
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims description 5
- 239000004743 Polypropylene Substances 0.000 claims description 5
- 150000001252 acrylic acid derivatives Chemical class 0.000 claims description 5
- 125000005396 acrylic acid ester group Chemical group 0.000 claims description 5
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 claims description 5
- 229920001155 polypropylene Polymers 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 4
- 239000005977 Ethylene Substances 0.000 claims description 4
- 239000012458 free base Substances 0.000 claims description 4
- VOZRXNHHFUQHIL-UHFFFAOYSA-N glycidyl methacrylate Chemical compound CC(=C)C(=O)OCC1CO1 VOZRXNHHFUQHIL-UHFFFAOYSA-N 0.000 claims description 4
- 239000000178 monomer Substances 0.000 claims description 4
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 4
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 4
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 claims description 3
- 229920000098 polyolefin Polymers 0.000 claims description 3
- 239000005062 Polybutadiene Substances 0.000 claims description 2
- ULQMPOIOSDXIGC-UHFFFAOYSA-N [2,2-dimethyl-3-(2-methylprop-2-enoyloxy)propyl] 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCC(C)(C)COC(=O)C(C)=C ULQMPOIOSDXIGC-UHFFFAOYSA-N 0.000 claims description 2
- 229920005680 ethylene-methyl methacrylate copolymer Polymers 0.000 claims description 2
- 229920002857 polybutadiene Polymers 0.000 claims description 2
- 239000010410 layer Substances 0.000 claims 3
- 239000012790 adhesive layer Substances 0.000 claims 1
- 230000000181 anti-adherent effect Effects 0.000 claims 1
- 239000012567 medical material Substances 0.000 abstract description 2
- 125000000524 functional group Chemical group 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
- 239000000654 additive Substances 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 210000003491 skin Anatomy 0.000 description 7
- 238000000034 method Methods 0.000 description 6
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 238000013268 sustained release Methods 0.000 description 5
- 239000012730 sustained-release form Substances 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 230000035515 penetration Effects 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000000853 adhesive Substances 0.000 description 3
- 230000001070 adhesive effect Effects 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000005538 encapsulation Methods 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000004014 plasticizer Substances 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 239000003349 gelling agent Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000002085 irritant Substances 0.000 description 2
- 239000002923 metal particle Substances 0.000 description 2
- 208000004296 neuralgia Diseases 0.000 description 2
- 208000021722 neuropathic pain Diseases 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 229920001485 poly(butyl acrylate) polymer Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 239000007939 sustained release tablet Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 239000005526 vasoconstrictor agent Substances 0.000 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 description 1
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 229920002126 Acrylic acid copolymer Polymers 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- LWZFANDGMFTDAV-BURFUSLBSA-N [(2r)-2-[(2r,3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O LWZFANDGMFTDAV-BURFUSLBSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 229940124532 absorption promoter Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229920006243 acrylic copolymer Polymers 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 235000021313 oleic acid Nutrition 0.000 description 1
- 239000002357 osmotic agent Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920000120 polyethyl acrylate Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 230000000379 polymerizing effect Effects 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 235000011067 sorbitan monolaureate Nutrition 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000003981 vehicle 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
- 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
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
- A61K9/7061—Polyacrylates
-
- 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
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
-
- 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
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
-
- 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
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
-
- 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
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7069—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
Landscapes
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pain & Pain Management (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to the field of medical materials, in particular to a pressure-sensitive adhesive composition for a transdermal patch, a pressure-sensitive adhesive material and a transdermal patch. Comprises a component A and a component B and/or a component C; wherein, the component A is one or more of C2-C6 olefin and polymer thereof, copolymer of C2-C6 olefin and C4-C10 ester and derivative thereof; the component B is one or more of polyurethane, polyamide and derivatives thereof; the component C is one or more of acrylic acid, acrylate, polymer taking acrylic acid and/or acrylate as main structural units and derivatives thereof; the total weight of the B component and/or the C component is 1 to 35 parts by weight with respect to 100 parts by weight of the A component. The transdermal patch of the present invention can release an effective dose of a drug for a long time and stably, and can achieve a relatively higher drug release amount based on a certain drug concentration.
Description
Technical Field
The invention relates to the field of medical materials, in particular to a pressure-sensitive adhesive composition for a transdermal patch, a pressure-sensitive adhesive material containing the pressure-sensitive adhesive composition or prepared from the pressure-sensitive adhesive composition, and the transdermal patch containing the pressure-sensitive adhesive material.
Background
Currently, many drugs are taken orally in only one mode, for example, the chronic pain treatment drug milobalin (miroalbin).
Mirobaline besylate tablets 2.5mg, 5mg, 10mg, 15mg (Tarlige) of the first three of Japanese drugs, Goujin, Sankyo, are currently approved in Japan for use in the treatment of Peripheral Neuropathic Pain (PNP) and intended for use in the treatment of central neuropathic pain. Typically, an adult patient has an initial dose of 5mg taken 2 times daily, followed by a gradual increase of 5mg up to 15mg at intervals of at least one week. The dosage can be adjusted between 10mg and 15mg according to age and symptoms, and is administered orally 2 times daily.
Japanese drug Enterprise's first three patents CN104334169A, CN107427483A and CN107405322A all protect a solid composition containing milopaline besylate, which are common oral sustained-release or immediate-release preparations. The prior art CN110917164A discloses a milpa besylate sustained release tablet and a preparation method thereof, the milpa besylate sustained release tablet prepared by the method has sustained release characteristics after being taken orally, can slowly release medicine within 24 hours, is beneficial to maintaining long-term and efficient blood concentration in vivo, and improves the treatment effect of the medicine.
The majority of drugs represented by milbelin are mainly used in the clinic by oral administration. The existing technology for prolonging the treatment effect of the milobalin adopts the sustained-release technology of oral administration, and the sustained-release effect can only reach 24 hours.
Although transdermal patches have been developed in recent years to replace oral administration or injection, the difficulty of delivering effective doses of drugs across the stratum corneum of the skin remains significant, and the permeation dose, stability and duration have been less than ideal. In this regard, the prior art has been largely investigated in the direction of finding more suitable absorption promoters and additives. However, the existing transdermal patches still have difficulty in achieving effective release with a long duration (up to 3-7 days), and new absorption enhancers may pose new risks to the human body.
Therefore, it is very important to develop a new transdermal patch of a drug which is safer to human body and can be released stably for a long time.
Disclosure of Invention
The present invention is directed to overcoming the above-mentioned disadvantages of the prior art and providing a pressure-sensitive adhesive composition for a transdermal patch, a pressure-sensitive adhesive material containing the pressure-sensitive adhesive composition or prepared therefrom, and a transdermal patch containing the pressure-sensitive adhesive material. The transdermal patch of the present invention can release an effective dose of a drug for a long time and stably, and can achieve a relatively higher drug release amount based on a certain drug concentration.
In order to achieve the above object, the present invention provides in a first aspect a pressure-sensitive adhesive composition comprising an a-component and a B-component and/or a C-component; wherein the component A is one or more of C2-C6 olefin and polymer thereof, C2-C6 olefin and copolymer of C4-C10 ester and derivative thereof; the component B is one or more of polyurethane, polyamide and derivatives thereof; the component C is one or more of acrylic acid, acrylate, polymer taking acrylic acid and/or acrylate as main structural units and derivatives thereof; the total weight of the B component and/or the C component is 1 to 35 parts by weight with respect to 100 parts by weight of the A component.
The inventors of the present invention have surprisingly found that the composition of the pressure sensitive adhesive has a significant effect on the stability and durability of drug release. The inventor of the invention discovers through further research that the pressure-sensitive adhesive with a new component can generate good synergistic effect through the mutual matching of specific components, so that the stability and the durability of the drug release are prolonged under the condition that the total amount of the drug is not changed.
By the combination of the above specific components, the present invention has been able to achieve better effects than the prior art. To further achieve better stability and durability, one or more of the following preferred features may be further defined.
Preferably, the total weight of the B component and/or the C component is 5 to 20 parts by weight with respect to 100 parts by weight of the a component. In the calculation of the total weight, when "and/or" take "and" are used, it means that both of the B component and the C component are present, and when "or" is used, it means that only one of the B component or the C component is present.
In the present invention, the B component and the C component may not be present at the same time. The pressure-sensitive adhesive composition of the present invention may include an a-component and a B-component, or may include an a-component and a C-component, or may include an a-component, a B-component and a C-component.
According to a specific embodiment of the present invention, the pressure sensitive adhesive composition is a combination of an a-component and a B-component in an amount of 5 to 15 parts by weight, more preferably 8 to 12 parts by weight, relative to 100 parts by weight of the a-component.
According to another embodiment of the present invention, the pressure sensitive adhesive composition is a combination of the a-component and the C-component in an amount of 10 to 20 parts by weight, more preferably 12 to 18 parts by weight, relative to 100 parts by weight of the a-component.
According to another embodiment of the present invention, the pressure-sensitive adhesive composition is a combination of a component a, a component B and a component C, the amount of the component B being 1 to 10 parts by weight and the amount of the component C being 5 to 15 parts by weight, relative to 100 parts by weight of the component a; more preferably, the amount of the B component is 2 to 8 parts by weight and the amount of the C component is 5 to 15 parts by weight with respect to 100 parts by weight of the A component.
In the invention, the component A is one or more of C2-C6 olefin and polymer thereof, C2-C6 olefin and copolymer of C4-C10 ester and derivative thereof.
Preferably, the C2-C6 olefin is selected from one or more of ethylene, isobutylene, butadiene, propylene and 2-pentene.
Preferably, the polymer of the C2-C6 olefin is selected from one or more of polyisobutylene, polypropylene, polybutadiene and isobutylene-propylene copolymer (molar ratio is (50-80): 50-20)).
Preferably, the molecular weight of the polymer of C2 to C6 olefins is in the range of 10 to 100 ten thousand, more preferably in the range of 5 to 40 ten thousand.
According to a preferred embodiment, the polymer of olefins C2 to C6 is a polyisobutylene having a molecular weight of 20 to 40 ten thousand and a polypropylene having a molecular weight of 5 to 10 ten thousand in a weight ratio (55 to 70): (45-30).
Preferably, the C4-C10 ester is selected from one or more of butyl acrylate, 2-ethylhexyl acrylate, ethyl acrylate and methyl methacrylate.
Preferably, the molar ratio of the C2-C6 olefin monomer to the C4-C10 ester monomer in the copolymer of the C2-C6 olefin and the C4-C10 ester is (30-45): (70-55).
In the present invention, unless otherwise specified, the structure is (X1-Y1): the proportion formula of (X2-Y2) represents the proportion range of each component in the proportion formula, wherein the total amount of each substance in the proportion formula is 100 parts. For example (70-90): in (30-10), when the former takes 70, the latter can only take 30, but the latter is not still within the range of 10-30.
Preferably, the copolymer of the C2-C6 olefin and the C4-C10 ester is selected from one or more of ethylene-methyl methacrylate copolymer, isobutylene-butyl acrylate copolymer and propylene-ethyl acrylate copolymer.
According to a preferred embodiment of the present invention, the A component is composed of 3 to 8% by weight of a C2-C6 olefin, 10 to 25% by weight of a polymer of a C2-C6 olefin, and 70 to 85% by weight of a copolymer of a C2-C6 olefin and a C4-C10 ester, based on the total weight of the A component.
In the invention, the component A also contains derivatives.
In the above-described components and ratios, it is assumed that the component A does not contain a derivative, and when a derivative is contained, the above-described components and ratios are understood to be included in the derivative. For example, the foregoing embodiments are understood to mean that the A component is composed of 3 to 8% by weight, based on the total weight of the A component, of a C2-C6 olefin and its derivatives, 10 to 25% by weight of a polymer of a C2-C6 olefin and its derivatives, and 70 to 85% by weight of a copolymer of a C2-C6 olefin and a C4-C10 ester and its derivatives. The same explanation is also made for the following groups B and C, and the description is omitted.
According to a specific embodiment, the component a contains derivatives of the foregoing substances, which may be derivatives obtained by substituting functional groups such as halogen, hydroxyl, carboxyl, etc. which are conventional in the art, or derivatives obtained by modifying for medical purposes (for example, compounds bound to drugs, metal particles or other active molecules, etc., in which case, the weight of the bound macromolecular substances is not counted).
The molecular weight of the polymer in the A component is preferably in the range of 1 ten thousand to 60 ten thousand, more preferably in the range of 5 ten thousand to 20 ten thousand, unless otherwise specified.
In the present invention, the B component is a combination of one or more selected from the group consisting of polyurethane, polyamide, and derivatives thereof.
Preferably, the B component is composed of 60 to 80 weight percent of polyurethane and 40 to 20 weight percent of polyamide based on the total weight of the B component.
Preferably, the molecular weight of the polymer in the B component is preferably in the range of 1 ten thousand to 20 ten thousand, more preferably in the range of 1 ten thousand to 5 ten thousand.
In the present invention, the component B may further contain a derivative obtained by substituting a functional group such as halogen, hydroxyl, carboxyl, etc. which are conventional in the art, or a derivative obtained by modifying the functional group for medical purposes.
In the present invention, the C component is one or more selected from acrylic acid, acrylic esters, polymers having acrylic acid and/or acrylic esters as main structural units, and derivatives thereof.
In the present invention, the term "main structural unit" means that the structural unit occupies the largest number of all structural units constituting the polymer in the polymer. For example, when the polymer is formed by polymerizing the structural units I, II and III, the structural unit I is a main structural unit, meaning that the number of the structural unit I is larger than that of the structural units II and III, and the number of the structural unit I is preferably 50% or more, more preferably 70% or more, and still more preferably 90% or more of the total number of the structural units.
In the present invention, the polymer having acrylic acid and/or acrylic acid ester as a main structural unit includes polyacrylic acid (all of which are polymerized from acrylic acid), acrylic acid copolymer (all of which are polymerized from acrylic acid and a secondary structural unit), polyacrylate (all of which are polymerized from acrylic acid ester), and acrylate copolymer (all of which are polymerized from acrylic acid ester and a secondary structural unit).
Wherein the acrylic copolymer and the acrylate copolymer are composed of a main structural unit and an auxiliary structural unit, the main structural unit is acrylic acid and/or acrylate, and the auxiliary structural unit is preferably selected from one or more of acrylic acid, vinyl acetate, isobutene and butadiene. The proportions of the main structural elements and the auxiliary structural elements satisfy the foregoing description of the term "main structural element".
According to a preferred embodiment, the C component comprises at least polyacrylate, which constitutes 40 to 100 wt.%, more preferably 60 to 90 wt.%, of the total weight of the C component.
According to a preferred embodiment, the C-component comprises at least acrylates and polyacrylates, the total weight of the acrylates and polyacrylates representing 60 to 100 wt.%, more preferably 80 to 100 wt.%, of the total weight of the C-component. Preferably, the weight ratio of the acrylate to the polyacrylate is (0.1-0.8): 1, more preferably (0.2-0.45): 1.
in the present invention, the acrylate and the acrylate structural unit constituting the polyacrylate may be the same or different, each independently selected from, but not limited to, the following: butyl acrylate, glycidyl methacrylate, 2-ethylhexyl acrylate, ethyl acrylate, methyl methacrylate and neopentyl glycol dimethacrylate; more preferably from butyl acrylate, glycidyl methacrylate and 2-ethylhexyl acrylate. Wherein, the acrylate structural unit of the polyacrylate can be one or more of the above.
According to a preferred embodiment of the invention, the C component comprises acrylic acid, acrylates, polyacrylates and acrylate copolymers in the weight ratio (0.05-0.3): (0.2-0.45): 1: (0.1-0.3). The acrylate copolymer is preferably a vinyl acetate-acrylate copolymer, and more preferably the copolymerization molar ratio of the vinyl acetate to the acrylate is 5-15: 95-85.
In the above-described components and ratios, it is premised that no derivative is contained in the C component, and when a derivative is contained, the above-described components and ratios are understood to be included in the derivative. For example, the foregoing embodiments are understood to include combinations of acrylic acid and its derivatives, acrylates and their derivatives, polyacrylates and their derivatives, and acrylate copolymers and their derivatives.
In the present invention, the component C may further contain a derivative.
According to a particular embodiment, the derivative is a compound modified with a carboxyl function or a hydroxyl function. When the C component contains such a derivative, the content of the derivative may be up to 100%, that is, the C component may be entirely modified with a carboxyl functional group or a hydroxyl functional group. When the component C is divided into a carboxyl functional group modified component, a hydroxyl functional group modified component and a component which is not modified by a functional group, preferably, the compound of the carboxyl functional group modified component accounts for 10 to 80 percent of the molar amount of all the compounds of the component C, the compound of the hydroxyl functional group modified component accounts for 0 to 40 percent, and the component which is not modified by a functional group accounts for 10 to 90 percent; more preferably, the compound of the carboxyl functional group modification component accounts for 20 to 60% of the molar amount of all the compounds of the C component, the compound of the hydroxyl functional group modification component accounts for 10 to 30%, and the non-functional group modification component accounts for 30 to 70%.
The carboxyl functional group or the hydroxyl functional group may be modified based on (poly) acrylate, for example.
According to another embodiment, the derivatives may be modified for therapeutic purposes as is conventional in the art, for example by binding the compound to a drug, metal particles or other active molecules, etc.
Preferably, the molecular weight of the polymer contained in the C component is in the range of 5 to 150 ten thousand, more preferably in the range of 20 to 80 ten thousand.
In a second aspect, the present invention provides a pressure-sensitive adhesive material, wherein the pressure-sensitive adhesive material comprises a pressure-sensitive adhesive and a drug dispersed in the pressure-sensitive adhesive, and the pressure-sensitive adhesive comprises or is prepared from the pressure-sensitive adhesive composition of the first aspect.
The drug may be present in various forms conventionally used in transdermal patches in the art, such as a free acid, a free base, or a pharmacologically acceptable salt; preferably a free base or a pharmacologically acceptable salt. The pharmacologically acceptable salt may be selected from one or any combination of the following: hydrochloride, benzenesulfonate, sulfate, nitrate, tartrate and succinate.
In the invention, the drug may also be present at least partially in the form of coated particles after coating with the inclusion material.
According to a particular embodiment of the invention, the drug is milobalin free base or a pharmacologically acceptable salt thereof. It should be noted that although the purpose of the present application is to make a new type of milobalin transdermal patch, the present application has been mainly studied for milobalin and has achieved a good effect; it will be understood by those skilled in the art that the drug-loaded pressure sensitive adhesive and transdermal patch of the present invention can be used to load various drugs, not limited to milobaline, and those skilled in the art can predict that good results will be achieved when used with other drugs.
Preferably, the pressure-sensitive adhesive material further contains a percutaneous absorption enhancer. Preferably, the percutaneous absorption enhancer is contained in an amount of 2 to 15% by weight, more preferably 4 to 10% by weight, based on the total weight of the pressure-sensitive adhesive material.
In the present invention, the transdermal absorption enhancer may be a transdermal absorption enhancer conventionally used in a drug-loaded layer of a transdermal patch in the art, and may be, for example, one or more selected from alcohols, sulfoxides, terpenes, amines, amides, fatty acids and esters, amino acids and esters thereof, and phospholipid compounds; preferably, the percutaneous absorption enhancer is selected from one or more of span 80, tween 80, span 20, oleic acid, menthol, N-methylpyrrolidone and isopropyl myristate.
The pressure-sensitive adhesive material of the present invention may further contain other pharmaceutically acceptable materials or additives such as one or more of stabilizers, diluents, plasticizers, tackifiers, carriers, inert fillers, antioxidants, excipients, gelling agents, anti-irritants, vasoconstrictors and fillers, provided that these additives do not substantially affect the basic and unique characteristics of the main component.
In a third aspect, the present invention provides a transdermal patch, which comprises a backing layer, an anti-sticking layer and a drug-loaded layer disposed therebetween, wherein the drug-loaded layer is made of the pressure-sensitive adhesive material according to the second aspect of the present invention.
The pharmaceutical preparation and the pharmaceutical transdermal patch according to the present invention can realize a suitable transdermal flux that is long-lasting and stable in a small administration area; preferably, the thickness of the drug-loaded layer is 10-300 μm and the administration area of the drug transdermal patch is 3-100cm2(ii) a More preferably, the thickness of the drug-carrying layer is 15-250 μm and the administration area of the drug transdermal patch is 5-80cm2。
The material of the backing layer may be any material conventionally used in the art, and according to a preferred embodiment, the backing layer is polyurethane, polyethylene or EVA. The thickness of the backing layer may be as conventional in the art, e.g. 0.5-10 μm.
The material of the release layer may be a material conventionally used in the art, and according to a preferred embodiment, the release layer is a release film. The thickness of the release layer may be as conventional in the art, for example, 0.5 to 10 μm.
The transdermal patch of the present invention may also contain other pharmaceutically acceptable materials or additives such as diluents, skin irritation reducing agents, carriers or vehicles, excipients, plasticizers, emollients or other additives and mixtures thereof, provided that such additives do not materially affect the basic and unique characteristics of the main ingredient.
The transdermal patch of the present invention can be prepared by a method conventional in the art, for example, comprising the steps of:
(1) melting the pressure-sensitive adhesive composition of the first aspect at a first temperature and mixing with a drug and a percutaneous absorption enhancer at a second temperature to obtain a pressure-sensitive adhesive material;
(2) the pressure sensitive adhesive material is disposed between a release layer and a backing layer.
In step (1), the first temperature is preferably 150-. The first temperature allows the components of the pressure sensitive adhesive composition to melt.
In step (1), the second temperature is preferably 80 to 120 ℃, more preferably 85 to 95 ℃.
In step (1), the drug may be dissolved in the solvent and then mixed with the other components; the solvent may be selected, for example, from one or more of methanol, ethanol, propylene glycol, butylene glycol or n-butanol. The amount of the solvent is preferably 0.5 to 10 times the weight of the drug.
In step (2), preferably, the means for disposing the pressure-sensitive adhesive material between the release layer and the backing layer comprises: the pressure-sensitive adhesive material is applied to the release layer while it is hot (preferably 70-85 c) and, after cooling (preferably 10-50 c), is covered with a backing layer.
The material obtained after covering with the backing layer is punched to obtain the transdermal drug patch of the invention.
Through the technical scheme, compared with the prior art, the invention at least has the following advantages:
(1) compared with the traditional acrylic acid adhesive pressure-sensitive adhesive, the pressure-sensitive adhesive can promote the release of the medicine, and can release more medicines on the premise of the same total amount of the medicine;
(2) the transdermal patch containing the pressure-sensitive adhesive can ensure that the drug is released more stably, reduce the fluctuation of the blood concentration and better avoid the side effect caused by the fluctuation of the blood concentration;
(3) the transdermal patch containing the pressure-sensitive adhesive can enable the drug to be released more durably, and can realize the continuous administration of effective dose for a longer time (generally, the sustained administration can be realized for 7 days for the purpose of protecting the skin, and actually, the sustained administration can be realized for a longer time) on the premise of the same total amount of the drug.
The transdermal patch of the present invention can be used for indications of various corresponding drugs.
The endpoints of the ranges and any values disclosed herein are not limited to the precise range or value, and such ranges or values should be understood to encompass values close to those ranges or values. For ranges of values, between the endpoints of each of the ranges and the individual points, and between the individual points may be combined with each other to give one or more new ranges of values, and these ranges of values should be considered as specifically disclosed herein.
Detailed Description
The present invention will be described in detail below by way of examples. The described embodiments of the invention are only some, but not all embodiments of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Before the present disclosure and description are made, it is to be understood that this invention is not limited to the particular process and materials disclosed herein but, on the contrary, extends to equivalent processes and materials recognized by those skilled in the relevant art. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the present invention.
The singular forms "a", "an" and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a transdermal absorption enhancer" includes reference to one or more transdermal penetration enhancers and reference to "an adhesive" includes reference to one or more such adhesives.
The term "encapsulation" as used herein means that the drug is physically or chemically bound in one or more materials in a single molecule, multiple molecules, crystalline micronized or amorphous form, such as "encapsulation", "inclusion", "encapsulation", "adsorption", "dispersion", etc., to form a composition, thereby changing the physical or chemical properties of the drug itself.
The term "therapeutically effective" refers to the amount of a drug or the rate of administration required to produce the desired therapeutic result.
An "effective amount" of a drug or osmotic agent refers to a non-toxic but sufficient amount of the compound to provide the desired local or systemic effect. As used herein, an "effective amount" of a permeation enhancer refers to an amount selected to provide a desired increase in membrane permeability and, correspondingly, a desired depth of penetration, rate of administration, and amount of drug.
As used herein, "transdermal" or "transdermal" delivery refers to delivery of a drug by entering and through skin or mucosal tissue. Thus, the terms "transdermal" and "transmucosal" are used interchangeably unless specifically indicated otherwise. Likewise, the terms "skin", "dermis", "epidermis", "mucosa", etc. should be used interchangeably unless otherwise indicated.
The term "component" as used herein refers to an ingredient within the drug-loaded layer, including, but not limited to, drugs, additives, penetration enhancers, stabilizers, dyes, diluents, plasticizers, viscosity increasing agents, pigments, carriers, inert fillers, antioxidants, excipients, gelling agents, anti-irritants, vasoconstrictors, and the like, as defined above.
As used herein, "application site" refers to a site suitable for topical application, with or without mechanical sustained release devices, e.g., behind the ears, arms, back, chest, abdomen, legs, instep, etc.
The raw materials and reagents not specifically described in the following examples were all standard substances.
In the following examples, 1 part by weight means 1 mg.
The following group I examples are presented to illustrate the pressure sensitive adhesive compositions of the present invention and the compositions of each example are identified by the same reference numerals as the example.
Example I1
The component A (total 100 parts by weight) comprises:
C2-C6 olefin: 7 parts by weight of 2-pentene.
Polymers of C2-C6 olefins: 15 parts by weight in total, comprising 10 parts by weight of polyisobutylene having an average molecular weight of 28 ten thousand and 5 parts by weight of polypropylene having an average molecular weight of 8 ten thousand;
copolymers of C2-C6 olefins with C4-C10 esters: 78 parts by weight of a copolymer obtained by copolymerizing isobutylene and butyl acrylate in a molar ratio of 42:58, and having an average molecular weight of 32 ten thousand.
The component B (5 parts by weight in total) comprises:
polyurethane: 3.5 parts by weight, the average molecular weight is 3.8 ten thousand;
polyamide: 1.5 parts by weight, average molecular weight 2.2 ten thousand.
And the component C (the total weight is 10 parts) comprises the following components:
acrylic acid: 0.88 weight part;
acrylate ester: 2.06 parts by weight of 2-ethylhexyl acrylate;
polyacrylate: 5.88 parts by weight, 34 ten thousand of average molecular weight and polybutyl acrylate;
acrylate copolymer: 1.18 parts by weight, average molecular weight 51 ten thousand, butyl acrylate-vinyl acetate copolymer (structural unit molar ratio 88: 12).
Example I2
The component A (total 100 parts by weight) comprises:
C2-C6 olefin: 5 parts by weight of propylene.
Polymers of C2-C6 olefins: 25 parts by weight of an isobutylene-propylene copolymer (molar ratio 62:38) having an average molecular weight of 34 ten thousand;
copolymers of C2-C6 olefins with C4-C10 esters: 70 parts by weight of a copolymer obtained by copolymerizing ethylene and methyl methacrylate in a molar ratio of 31:69, and having an average molecular weight of 24 ten thousand.
The component B (total 8 parts by weight) comprises:
polyurethane: 6.4 parts by weight, the average molecular weight is 4.6 ten thousand;
polyamide: 1.6 parts by weight, average molecular weight 1.8 ten thousand.
And the component C (5 parts by weight in total) comprises:
acrylic acid: 0.31 part by weight;
acrylate ester: 0.63 part by weight of butyl acrylate;
polyacrylate: 3.13 parts by weight, average molecular weight 23 ten thousand, poly ethyl acrylate;
acrylate copolymer: 0.94 part by weight, an average molecular weight of 47 ten thousand, and an ethyl acrylate-isobutylene copolymer (molar ratio of structural units 85: 15).
Example I3
The component A (total 100 parts by weight) comprises:
C2-C6 olefin: 5 parts by weight of ethylene.
Polymers of C2-C6 olefins: 10 parts by weight of polyisobutylene with an average molecular weight of 22 ten thousand;
copolymers of C2-C6 olefins with C4-C10 esters: 85 parts by weight of a copolymer obtained by copolymerizing propylene and ethyl acrylate in a molar ratio of 36:64, and having an average molecular weight of 31 ten thousand.
The component B (total 2 parts by weight) comprises:
polyurethane: 1.2 parts by weight, the average molecular weight is 3.5 ten thousand;
polyamide: 0.8 parts by weight, average molecular weight 3.8 ten thousand.
And the component C (15 parts by weight in total) comprises:
acrylic acid: 2.43 parts by weight;
acrylate ester: 3.65 parts by weight of glycidyl methacrylate;
polyacrylate: 8.11 parts by weight, an average molecular weight of 45 ten thousand, polybutyl acrylate;
acrylate copolymer: 0.81 part by weight of acrylic acid-2-ethylhexyl ester-vinyl acetate copolymer (molar ratio of structural units is 80:20) with an average molecular weight of 56 ten thousand.
Example I4
A composition was prepared with reference to example I1, except that component B was not prepared but replaced with the same weight of component C (keeping the proportion of the interior of component C constant).
Example I5
A composition was prepared with reference to example I1, except that component C was not prepared and replaced with the same weight of component B (keeping the proportion of the interior of component B constant).
Example I6
Compositions were prepared with reference to example I1, except that the ratio between the ABC components was adjusted and the internal ratio of the components was kept constant, specifically, 100 parts by weight for the a component, 15 parts by weight for the B component, and 20 parts by weight for the C component.
Example I7
A composition was prepared by reference to example I1, except that the A component was provided as a single component, specifically 100 parts by weight of the same copolymer of a C2-C6 olefin and a C4-C10 ester as in example I1.
Example I8
A composition was prepared with reference to example I1, except that the B component was provided as a single component, specifically 5 parts by weight of the same polyurethane as in example I1.
Example I9
A composition was prepared with reference to example I1, except that the C component was provided as a single ingredient, specifically 10 parts by weight of the same polyacrylate as in example I1.
Comparative example ID1
A composition was prepared as described in example I1, except that only the A component was provided.
Comparative example ID2
A composition was prepared as described in example I1, except that only the C component was provided.
Comparative example ID3
A composition was prepared by referring to example I1, except that only the polyacrylate in the same C component as in example I1 was provided.
The following group II examples are presented to illustrate transdermal patches of the present invention.
Example II1
5g of the pressure-sensitive adhesive composition prepared in example I1 was mixed and heated to 163. + -. 2 ℃ and the temperature was adjusted to 90. + -. 5 ℃ after the components were completely melted, and stirred until the system was uniformly mixed, then 0.25g of the drug milobalin solution dissolved in 1.5g of absolute ethanol in advance and 0.4g of the percutaneous absorption enhancer (isopropyl myristate) were added and sufficiently mixed to obtain a drug-loaded layer material, which was coated on a release film (3M, hereinafter the same) while hot, cooled, covered with polyurethane (3M, hereinafter the same) as a backing material, and die-cut into a patch.
Examples II2-II9
Reference is made individually to example II1, except that examples II2-II9 each replace the pressure-sensitive adhesive composition prepared in example I1 with an identical mass of the pressure-sensitive adhesive composition prepared in examples I2-I9.
Comparative examples IID1-IID3
Reference was made to example II1, respectively, except that comparative examples ID1-ID3 replaced the pressure-sensitive adhesive composition prepared in example I1 with the pressure-sensitive adhesive composition prepared in comparative examples ID1-ID3, respectively, of the same quality.
Test example
The patches obtained in the above group II examples were tested in this group of test examples as follows:
the adopted external penetration absorption device is a horizontal diffusion pool, the effective area is 1.77 square centimeters, the used skin is the skin of a hair-removed pig, the patch is attached to one side of the horny layer of the skin in the experimental process, one side of the corium layer faces to the receiving pool, the volume of the receiving pool is 7.0ml, continuous magnetic stirring is carried out in the permeation process, the stirring speed is 800rpm, and the temperature of the receiving pool is maintained to be 32 ℃ by using peripheral circulating water bath.
The unit transdermal permeability (ug/cm) per day was measured by high performance liquid chromatography2Day), 10 tests per day were averaged and the results are reported in table 1; and 5-balance mean reduction (equal to (day 1 transdermal transmission-day 5 transdermal transmission) ÷ 5) and 7-balance mean reduction (equal to (day 1 transdermal transmission-day 7 transdermal transmission) ÷ 7) were calculated, the smaller the mean reduction, indicating more stable drug release, indicating greater stability.
TABLE 1
As can be seen from table 1, the transdermal patches made of the pressure-sensitive adhesive compositions of the examples of the present invention can release a greater cumulative amount of the drug at the same concentration of the drug in all the examples and comparative examples, and the release rate is stable, the fluctuation is small, and the duration can reach more than 7 days.
The preferred embodiments of the present invention have been described above in detail, but the present invention is not limited thereto. Within the scope of the technical idea of the invention, many simple modifications can be made to the technical solution of the invention, including combinations of various technical features in any other suitable way, and these simple modifications and combinations should also be regarded as the disclosure of the invention, and all fall within the scope of the invention.
Claims (10)
1. The pressure-sensitive adhesive composition is characterized by comprising a component A and a component B and/or a component C; wherein the component A is one or more of C2-C6 olefin and polymer thereof, C2-C6 olefin and copolymer of C4-C10 ester and derivative thereof; the component B is one or more of polyurethane, polyamide and derivatives thereof; the component C is one or more of acrylic acid, acrylate, polymer taking acrylic acid and/or acrylate as main structural units and derivatives thereof; the total weight of the B component and/or the C component is 1 to 35 parts by weight with respect to 100 parts by weight of the A component.
2. The pressure-sensitive adhesive composition according to claim 1, wherein the total weight of the B-component and/or the C-component is 5 to 20 parts by weight relative to 100 parts by weight of the a-component;
preferably, the pressure-sensitive adhesive composition is a combination of an a-component and a B-component in an amount of 5 to 15 parts by weight relative to 100 parts by weight of the a-component;
preferably, the pressure-sensitive adhesive composition is a combination of an a-component and a C-component in an amount of 10 to 20 parts by weight relative to 100 parts by weight of the a-component;
preferably, the pressure-sensitive adhesive composition is a combination of a component a, a component B and a component C, the amount of the component B being 1 to 10 parts by weight and the amount of the component C being 5 to 15 parts by weight with respect to 100 parts by weight of the component a.
3. The pressure sensitive adhesive composition of claim 1 or 2, wherein in the a component, the C2-C6 olefin is selected from one or more of ethylene, isobutylene, butadiene, propylene, and 2-pentene;
preferably, the polymer of the C2-C6 olefin is selected from one or more of polyisobutylene, polypropylene, polybutadiene, and isobutylene-propylene copolymer;
preferably, the polymer of C2-C6 olefin is polyisobutylene with a molecular weight of 20-40 ten thousand and polypropylene with a molecular weight of 5-10 ten thousand in a weight ratio (55-70): (45-30).
4. The pressure sensitive adhesive composition of any one of claims 1-3, wherein in the A component, the C4-C10 ester is selected from one or more of butyl acrylate, 2-ethylhexyl acrylate, ethyl acrylate, and methyl methacrylate;
preferably, the molar ratio of the C2-C6 olefin monomer to the C4-C10 ester monomer in the copolymer of the C2-C6 olefin and the C4-C10 ester is (30-45): (70-55);
preferably, the copolymer of the C2-C6 olefin and the C4-C10 ester is selected from one or more of ethylene-methyl methacrylate copolymer, isobutylene-butyl acrylate copolymer and propylene-ethyl acrylate copolymer.
5. The pressure-sensitive adhesive composition of claim 1 or 2, wherein the B component is composed of 60 to 80 wt% of polyurethane and 40 to 20 wt% of polyamide based on the total weight thereof;
preferably, the molecular weight of the polymer in the B component is in the range of 1 to 20 ten thousand.
6. The pressure-sensitive adhesive composition according to claim 1 or 2, wherein the C component comprises at least polyacrylate, which is 40 to 100 wt% of the total weight of the C component;
preferably, the C component at least comprises acrylate and polyacrylate, the total weight of the acrylate and the polyacrylate accounts for 60-100 wt% of the total weight of the C component, and the weight ratio of the acrylate to the polyacrylate is (0.1-0.8): 1;
preferably, the C component comprises acrylic acid, acrylates, polyacrylates and acrylate copolymers in a weight ratio (0.05-0.3): (0.2-0.45): 1: (0.1-0.3).
7. The pressure-sensitive adhesive composition according to claim 6, wherein the acrylate and the acrylate structural unit constituting the polymer having acrylate as a main structural unit are the same or different and are each independently selected from one or more of butyl acrylate, glycidyl methacrylate, 2-ethylhexyl acrylate, ethyl acrylate, methyl methacrylate and neopentyl glycol dimethacrylate;
preferably, the auxiliary structural unit in the polymer taking acrylic acid and/or acrylic acid ester as the main structural unit is selected from one or more of acrylic acid, vinyl acetate, isobutene and butadiene;
preferably, in the polymer having acrylic acid and/or acrylic acid ester as a main structural unit, the number of the main structural unit accounts for 70% or more of the total number of the structural units.
8. A pressure-sensitive adhesive material comprising a pressure-sensitive adhesive comprising or prepared from the pressure-sensitive adhesive composition of any one of claims 1 to 7 and a drug dispersed in the pressure-sensitive adhesive.
9. The pressure-sensitive adhesive material of claim 8, wherein the drug is milobalin free base or a pharmacologically acceptable salt thereof;
preferably, the pressure-sensitive adhesive material further comprises a percutaneous absorption enhancer, and the content of the percutaneous absorption enhancer is 2-15 wt% based on the total weight of the pressure-sensitive adhesive material.
10. A transdermal patch comprising a backing layer, an anti-adhesive layer and a drug-loaded layer disposed therebetween, wherein the drug-loaded layer is made of the pressure-sensitive adhesive material according to claim 8 or 9.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011175102.9A CN112274496A (en) | 2020-10-28 | 2020-10-28 | Pressure-sensitive adhesive composition for transdermal patch, pressure-sensitive adhesive material and transdermal patch |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011175102.9A CN112274496A (en) | 2020-10-28 | 2020-10-28 | Pressure-sensitive adhesive composition for transdermal patch, pressure-sensitive adhesive material and transdermal patch |
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| CN112274496A true CN112274496A (en) | 2021-01-29 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011175102.9A Pending CN112274496A (en) | 2020-10-28 | 2020-10-28 | Pressure-sensitive adhesive composition for transdermal patch, pressure-sensitive adhesive material and transdermal patch |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112985952A (en) * | 2021-02-20 | 2021-06-18 | 山东骏腾医疗科技有限公司 | Novel pathological sealing sheet material |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070098766A1 (en) * | 2003-06-24 | 2007-05-03 | Saitama Daiichi Pharmaceutical Co., Ltd. | Nonaqueous pressure-sensitive adhesive for medicinal tape preparation for percutaneous absorption, medicinal tape preparation for percutaneous asorption, and process for producing the same |
| JP2019131480A (en) * | 2018-01-29 | 2019-08-08 | 旭化成株式会社 | Percutaneous absorption promoter and percutaneous preparation |
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2020
- 2020-10-28 CN CN202011175102.9A patent/CN112274496A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070098766A1 (en) * | 2003-06-24 | 2007-05-03 | Saitama Daiichi Pharmaceutical Co., Ltd. | Nonaqueous pressure-sensitive adhesive for medicinal tape preparation for percutaneous absorption, medicinal tape preparation for percutaneous asorption, and process for producing the same |
| JP2019131480A (en) * | 2018-01-29 | 2019-08-08 | 旭化成株式会社 | Percutaneous absorption promoter and percutaneous preparation |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112985952A (en) * | 2021-02-20 | 2021-06-18 | 山东骏腾医疗科技有限公司 | Novel pathological sealing sheet material |
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