CN102908345A - Drug composition suitable for transdermal drug delivery and containing granisetron as well as preparation and application of same - Google Patents
Drug composition suitable for transdermal drug delivery and containing granisetron as well as preparation and application of same Download PDFInfo
- Publication number
- CN102908345A CN102908345A CN2011102235332A CN201110223533A CN102908345A CN 102908345 A CN102908345 A CN 102908345A CN 2011102235332 A CN2011102235332 A CN 2011102235332A CN 201110223533 A CN201110223533 A CN 201110223533A CN 102908345 A CN102908345 A CN 102908345A
- Authority
- CN
- China
- Prior art keywords
- methyl
- acrylamide
- granisetron
- component
- pharmaceutical composition
- 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
- MFWNKCLOYSRHCJ-BTTYYORXSA-N granisetron Chemical compound C1=CC=C2C(C(=O)N[C@H]3C[C@H]4CCC[C@@H](C3)N4C)=NN(C)C2=C1 MFWNKCLOYSRHCJ-BTTYYORXSA-N 0.000 title claims abstract description 54
- 229960003727 granisetron Drugs 0.000 title claims abstract description 50
- 239000000203 mixture Substances 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title claims description 16
- 239000003814 drug Substances 0.000 title abstract description 15
- 229940079593 drug Drugs 0.000 title abstract description 6
- 238000013271 transdermal drug delivery Methods 0.000 title 1
- 239000000178 monomer Substances 0.000 claims abstract description 28
- 239000004925 Acrylic resin Substances 0.000 claims abstract description 21
- 229920001577 copolymer Polymers 0.000 claims abstract description 16
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 claims abstract description 16
- YPHQUSNPXDGUHL-UHFFFAOYSA-N n-methylprop-2-enamide Chemical compound CNC(=O)C=C YPHQUSNPXDGUHL-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 12
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000001087 glyceryl triacetate Substances 0.000 claims abstract description 8
- 235000013773 glyceryl triacetate Nutrition 0.000 claims abstract description 8
- 229960002622 triacetin Drugs 0.000 claims abstract description 8
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims abstract description 5
- CERQOIWHTDAKMF-UHFFFAOYSA-N alpha-methacrylic acid Natural products CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 26
- 239000008194 pharmaceutical composition Substances 0.000 claims description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 17
- 230000000149 penetrating effect Effects 0.000 claims description 17
- 229920000058 polyacrylate Polymers 0.000 claims description 15
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 claims description 9
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 8
- 235000017858 Laurus nobilis Nutrition 0.000 claims description 7
- 244000125380 Terminalia tomentosa Species 0.000 claims description 7
- 235000005212 Terminalia tomentosa Nutrition 0.000 claims description 7
- -1 diamino ethyl Chemical group 0.000 claims description 7
- 150000002576 ketones Chemical class 0.000 claims description 7
- CQEYYJKEWSMYFG-UHFFFAOYSA-N butyl acrylate Chemical compound CCCCOC(=O)C=C CQEYYJKEWSMYFG-UHFFFAOYSA-N 0.000 claims description 6
- 238000007334 copolymerization reaction Methods 0.000 claims description 5
- 239000004148 curcumin Substances 0.000 claims description 5
- 239000010410 layer Substances 0.000 claims description 5
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 claims description 4
- 239000011241 protective layer Substances 0.000 claims description 4
- 238000005303 weighing Methods 0.000 claims description 4
- RQAVKYPVSDCFJQ-UHFFFAOYSA-N 2-methyl-n-(2-methylpropoxy)prop-2-enamide Chemical compound CC(C)CONC(=O)C(C)=C RQAVKYPVSDCFJQ-UHFFFAOYSA-N 0.000 claims description 2
- BQBYBPAPSIWHCE-UHFFFAOYSA-N 5-(dimethylamino)-2-methylpent-2-enoic acid Chemical compound CN(C)CCC=C(C)C(O)=O BQBYBPAPSIWHCE-UHFFFAOYSA-N 0.000 claims description 2
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 claims description 2
- FQPSGWSUVKBHSU-UHFFFAOYSA-N methacrylamide Chemical compound CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 claims description 2
- YHOSNAAUPKDRMI-UHFFFAOYSA-N n,n-di(propan-2-yl)prop-2-enamide Chemical compound CC(C)N(C(C)C)C(=O)C=C YHOSNAAUPKDRMI-UHFFFAOYSA-N 0.000 claims description 2
- UTSYWKJYFPPRAP-UHFFFAOYSA-N n-(butoxymethyl)prop-2-enamide Chemical compound CCCCOCNC(=O)C=C UTSYWKJYFPPRAP-UHFFFAOYSA-N 0.000 claims description 2
- QMQNMBYPQFQQPK-UHFFFAOYSA-N n-methoxyprop-2-enamide Chemical compound CONC(=O)C=C QMQNMBYPQFQQPK-UHFFFAOYSA-N 0.000 claims description 2
- 206010040880 Skin irritation Diseases 0.000 abstract description 8
- 230000004907 flux Effects 0.000 abstract description 8
- 231100000475 skin irritation Toxicity 0.000 abstract description 8
- 230000036556 skin irritation Effects 0.000 abstract description 8
- 230000000694 effects Effects 0.000 abstract description 5
- 239000004820 Pressure-sensitive adhesive Substances 0.000 abstract description 4
- 239000003961 penetration enhancing agent Substances 0.000 abstract description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 abstract 2
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 abstract 2
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 abstract 2
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 abstract 1
- 229920003134 Eudragit® polymer Polymers 0.000 abstract 1
- 229960004063 propylene glycol Drugs 0.000 abstract 1
- 230000000052 comparative effect Effects 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 239000011230 binding agent Substances 0.000 description 9
- 238000000034 method Methods 0.000 description 8
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 239000003292 glue Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 6
- 229940117958 vinyl acetate Drugs 0.000 description 6
- 239000004568 cement Substances 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 4
- 206010047700 Vomiting Diseases 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- 229920001971 elastomer Polymers 0.000 description 4
- 230000035515 penetration Effects 0.000 description 4
- 239000005060 rubber Substances 0.000 description 4
- 229920002799 BoPET Polymers 0.000 description 3
- 239000004821 Contact adhesive Substances 0.000 description 3
- 239000005041 Mylar™ Substances 0.000 description 3
- 230000001186 cumulative effect Effects 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 239000012790 adhesive layer Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 239000010408 film Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 238000007654 immersion Methods 0.000 description 2
- 239000003999 initiator Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229920001296 polysiloxane Polymers 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 229920003048 styrene butadiene rubber Polymers 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- 238000005491 wire drawing Methods 0.000 description 2
- JKNCOURZONDCGV-UHFFFAOYSA-N 2-(dimethylamino)ethyl 2-methylprop-2-enoate Chemical compound CN(C)CCOC(=O)C(C)=C JKNCOURZONDCGV-UHFFFAOYSA-N 0.000 description 1
- DEXFNLNNUZKHNO-UHFFFAOYSA-N 6-[3-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-3-oxopropyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)C(CCC1=CC2=C(NC(O2)=O)C=C1)=O DEXFNLNNUZKHNO-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- AXISYYRBXTVTFY-UHFFFAOYSA-N Isopropyl tetradecanoate Chemical class CCCCCCCCCCCCCC(=O)OC(C)C AXISYYRBXTVTFY-UHFFFAOYSA-N 0.000 description 1
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 229920002614 Polyether block amide Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 239000002174 Styrene-butadiene Substances 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 239000005030 aluminium foil Substances 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 230000003474 anti-emetic effect Effects 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- ONIHPYYWNBVMID-UHFFFAOYSA-N diethyl benzene-1,4-dicarboxylate Chemical compound CCOC(=O)C1=CC=C(C(=O)OCC)C=C1 ONIHPYYWNBVMID-UHFFFAOYSA-N 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 239000003845 household chemical Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 125000005397 methacrylic acid ester group Chemical group 0.000 description 1
- 229920003052 natural elastomer Polymers 0.000 description 1
- 229920001194 natural rubber Polymers 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000004745 nonwoven fabric Substances 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 229920003051 synthetic elastomer Polymers 0.000 description 1
- 239000005061 synthetic rubber Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000004017 vitrification Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention relates to a drug composition containing granisetron. The drug composition comprises a sodium polyacrylate pressure-sensitive adhesive (A), a polyacrylic resin (B), a penetration enhancer (C) and granisetron (D), wherein the sodium polyacrylate pressure-sensitive adhesive (A) is a (methyl) acrylate copolymer containing (methyl) acrylamide or N, N-substituted monomer thereof; the polyacrylic resin (B) is an Eudragit polyacrylic resin; and the penetration enhancer (C) is selected from isopropyl myristate, azone, glyceryl triacetate and 1, 2-propylene glycol as well a a mixture thereof. A granisetron transdermal patch containing the drug composition obtains satisfactory technical effects on mechanical property, skin irritation and the like; more importantly, the transdermal patch obtains considerable transdermal flux when the excellent performances are guaranteed.
Description
Technical field
The present invention relates to be suitable for the pharmaceutical composition that contains granisetron and preparation method thereof and application of transdermal administration.This pharmaceutical composition is combined by a certain percentage by special adhesive compositions, penetrating agent and granisetron.Contain the transdermal patch of this pharmaceutical composition when satisfying the requirements such as skin irritation and mechanical property, further improved the transdermal flux of granisetron.
Background technology
Granisetron is a kind of potent, high selectivity periphery and central nervous system's 5-hydroxy tryptamine (5-HT
3) receptor antagonist, by the 5-HT to small intestinal abdominal part centripetal nerve fiber and nucleus solitarius or vomiting chemoceptor trigger region
3The blocking effect of receptor suppresses the nausea and vomiting that antitumor drug and radiotherapy cause.At present, the route of administration that granisetron is commonly used clinically has vein, oral and rectally, but because the pain that intravenously administrable may bring, oral administration increases the weight of reaction and first pass effect for what suffer from that serious vomiting, nauseating patient bring, and the inconvenience of rectally, make people be more prone to seek a kind of easy to use, compliance is high, side effect is little, can keep the new granisetron form of administration of Cpss.
Chinese patent application CN 1747724A has described a kind of binding agent patch for the granisetron transdermal administration, and wherein binding agent is the acryloid cement that contains nonacid hydroxylic moiety.This application thinks that the binding agent that contains hydroxyl obviously is better than the electroneutral binding agent of non-nucleophilic, and this class binding agent mainly improves the transdermal flux of granisetron.It is favourable that any penetration enhancer is not used in this application instruction, can reduce zest and eliminating to the adverse effect of binding agent mechanics performance.
Chinese patent application CN 101180018A has described a kind of compositions for applied dermally antiemetic, and wherein the contact skin compositions comprises: the 1) 5-HT of emesis effective dose
3Receptor antagonist, 2) account for skin contacting adhesive layer 0.5%-15% weight penetration enhancers and, 3) binding agent.Described binding agent is selected from acrylic resin, vinylacetate, natural and synthetic rubber, ethylene vinyl acetate copolymer, polysiloxanes, polyacrylate, polyurethane, the polyether block amide copolymer of plasticising, the SBR styrene butadiene rubbers block copolymer of plasticising and their mixture.This application instruction is used medium but the penetration enhancers of the concentration of remarkable efficacy is arranged, and can obtain the benefit identical with CN 1747724A.
But, lack a kind of transdermal flux that can more effectively improve granisetron in the prior art, and take into account simultaneously even improve the transdermal patch that contains granisetron of skin irritation and mechanical property.
The inventor is by a large amount of experiments, the pharmaceutical composition of the present invention of finding to adopt the adhesive composition, transdermal penetration promoter and the granisetron that are comprised of the polyacrylate pressure-sensitive with particular functional group's monomer and polyacrylic resin to mix in specific proportions and preparing is as the transdermal patch of hypothallus, can significantly improve the transdermal flux of active medicine granisetron, and in skin irritation, the aspects such as mechanical property have improved premium properties.
Summary of the invention
Therefore, the invention provides a kind of pharmaceutical composition that contains granisetron, by (A) polyacrylate pressure-sensitive, (B) polyacrylic resin, (C) penetrating agent and (D) granisetron form, wherein said polyacrylate pressure-sensitive (A) is for containing (methyl) acrylamide or its N, (methyl) acrylate copolymer of N substituted monomer; Described polyacrylic resin (B) is Eudragit class polyacrylic resin, and described penetrating agent (C) is selected from isopropyl myristate, Laurel nitrogen
Ketone, glyceryl triacetate, 1,2-PD and composition thereof.
The present invention also provides the application of this pharmaceutical composition that contains granisetron aspect preparation granisetron transdermal patch.
The present invention also provides a kind of granisetron transdermal patch, its structure comprises backing layer, hypothallus and protective layer, described hypothallus by (A) polyacrylate pressure-sensitive, (B) polyacrylic resin, (C) penetrating agent and (D) granisetron form, wherein said polyacrylate pressure-sensitive (A) is for containing (methyl) acrylamide or its N, (methyl) acrylate copolymer of N substituted monomer; Described polyacrylic resin (B) is Eudragit class polyacrylic resin, and described penetrating agent (C) is selected from isopropyl myristate, Laurel nitrogen
Ketone, glyceryl triacetate, 1,2-PD and composition thereof.
Transdermal patch of the present invention, its Percutaneously absorbable can be excellent, and is little to skin irritation, and has enough adhesion strengths, and patch does not exist wire drawing, excessive glue etc. to be unfavorable for the phenomenon of using.
In pharmaceutical composition of the present invention, by the weighing scale of compositions, the shared weight ratio of preferred ingredient A and B is about 65%-95%, and the about 9-1 of A: B=; The shared weight ratio of component C is about 2%-15%; And the shared weight ratio of component D is about 3%-20%.
In a preferred embodiment of pharmaceutical composition of the present invention, by the weighing scale of compositions, the shared weight ratio of component A is about 60%-80%; The shared weight ratio of B component is about 9%-20%; The shared weight ratio of component C is about 6%-12%; And the shared weight ratio of component D is about 5%-13%.
The preferred embodiment of pharmaceutical composition according to the present invention wherein comprises: based on the composition total weight meter, what be about 60%-80% contains (methyl) acrylamide or its N, (methyl) acrylate copolymer of N substituted monomer, 9-20%'s
The granisetron alkali of the isopropyl myristate of RS100,6%-12% and 5%-13%.
Another preferred embodiment of pharmaceutical composition according to the present invention, wherein comprise: based on the composition total weight meter, what be about 60%-80% contains (methyl) acrylamide or its N, (methyl) acrylate copolymer of N substituted monomer, 9%-20%'s
RS100 and 6%-12% by Laurel nitrogen
The penetrating agent compositions that ketone, glyceryl triacetate and 1,2-PD combine and the granisetron alkali of 5%-13%.
On the other hand, in described granisetron transdermal patch of the present invention, component A and B shared weight ratio in hypothallus is about 65%-95%, wherein the about 9-1 of A: B=; Component C shared weight ratio in hypothallus is about 2%-15%; And component D shared weight ratio in hypothallus is about 3%-20%.
In the preferred embodiment of granisetron transdermal patch of the present invention, comprise in its hypothallus: by the hypothallus gross weight, be about the component A of 60%-80%; The B component that is about 9%-20%; The component C that is about 6%-12%; With the component D that is about 5%-13%.
The preferred embodiment of granisetron transdermal patch according to the present invention, comprise in its hypothallus: by the hypothallus gross weight, what be about 60%-80% contains (methyl) acrylamide or its N, (methyl) acrylate copolymer of N substituted monomer, 9-20%'s
The granisetron alkali of the isopropyl myristate of RS100,6%-12% and 5%-13%.
Another preferred embodiment of granisetron transdermal patch according to the present invention, comprise in its hypothallus: by the hypothallus gross weight, be about (methyl) acrylate copolymer that contains (methyl) acrylamide or its N, N substituted monomer, the 9%-20% of 60%-80%
RS100,6%-12% by Laurel nitrogen
The penetrating agent compositions that ketone, glyceryl triacetate and 1,2-PD combine and the granisetron alkali of 5%-13%.
In the present invention, described containing (methyl) acrylamide or its N, (methyl) acrylate copolymer of N substituted monomer [namely, polyacrylate pressure-sensitive (A)] be with (methyl) acrylic acid and/or (methyl) acrylate and comprise (methyl) acrylamide or its N, the N substituted monomer causes the polymer substance that copolymerization forms at interior functional monomer's free radical, and monomer whose is selected from (methyl) acrylic acid, (methyl) acrylic acid C
1-10Arrcostab, 2-EHA, vinyl acetate, α-methacrylic acid, acrylonitrile, Methacrylamide, acrylamide, isobutoxy Methacrylamide, methoxy acrylamide, diamino ethyl methacrylate, N-butoxymethyl acrylamide, dimethylaminoethyl methacrylic acid, diethyllaminoethyl methacrylate, diisopropyl acrylamide etc.
In the present invention, described containing (methyl) acrylamide or its N, (methyl) acrylate copolymer of N substituted monomer is preferably by acrylamide, butyl acrylate, 2-EHA, vinyl acetate and α-methacrylic acid monomer copolymerization form, the preferred acrylamide 1%-5% of the proportion of each monomer, butyl acrylate 30%-40%, 2-EHA 35%-50%, vinyl acetate 15%-25% and α-methacrylic acid O.5%-2%, acrylamide 3.3-4.3% particularly preferably, butyl acrylate 32.6-33.6%, 2-EHA 40.4-41.4%, vinyl acetate 20.5-21.5% and α-methacrylic acid are O.7-1.7%.
Polyacrylate pressure-sensitive of the present invention (A) has good pressure-sensitive and cohesive at normal temperatures, and lower vitrification point (55 ℃-15 ℃).Polyacrylate pressure-sensitive of the present invention is owing to introduce functional monomer's (methyl) acrylamide, makes and produced to a certain degree crosslinked between the copolymer molecule, and its cohesive strength and bond properties are improved significantly.
Described polyacrylate pressure-sensitive can adopt technology preparation known in the art, for example, according to conventional method (referring to Yang Yukun, " pressure sensitive adhesive goods technical manual ", Chemical Industry Press, in JIUYUE, 2004 is published, the 260-261 page or leaf), monomer and an amount of solvent beyond the functional monomer are added in the retort, initiator (for example benzoyl peroxide), functional monomer and an amount of solvent are added in the Dropping funnel, under blanket of nitrogen, begin heated and stirred, begin during to 72 ℃ to drip, close nitrogen.Keep reaction temperature at 72-78 ℃, the initiator dropping liquid dripped off in 3 hours, was incubated 2 hours again, and holding temperature is 75-80 ℃, the cooled and filtered discharging.
In the present invention, described " polyacrylic resin " refers to German Evonik Degussa company
(especially strange) E, L, S, RL, the model commodity such as RS, NE, and " the polyacrylic resin kind that two ones of Chinese pharmacopoeia 201O versions are recorded has the models (Lianyungang of Jiangsu Chinese system of weights iodine factory) such as polyacrylic resin II, III, IV.For example,
E is cationic dimethylaminoethyl methacrylate and the copolymer of two kinds of neutral methacrylic acid esters,
RL and RS contain the methacrylate of quaternary ammonium and the copolymer of acrylate and methacrylate.In the present invention, preferred
L100,
S100,
RL 1OO,
RS1OO,
E100,
L1OO-55,
E PO,
RL PO,
RS PO and composition thereof, especially preferred
RS 1OO or
E100.
The polyacrylate pressure-sensitive (A) of the present invention by will having particular functional group's monomer and polyacrylic resin (B) combination have contact adhesive composition than the high-mechanic capacity thereby form to penetrating agent.The preferred proportion of the two is the about 9-1 of A: B=in the present invention, such as the about 8-1.5 of A: B=or 7-2 etc.
In order to improve the transdermal flux of medicine, the common employing adds various penetrating agents in patch, but penetrating agent usually produces zest to skin, and the mechanical property meeting of patch is destroyed when adding a large amount of penetrating agent.In order to be provided at the good granisetron transdermal patch of balance between percutaneous rate and mechanical property and the skin irritation, the inventor passes through lot of experiments, filter out the penetrating agent that has the fabulous compatibility with contact adhesive composition of the present invention and active medicine granisetron, be selected from isopropyl myristate, Laurel nitrogen
Ketone, glyceryl triacetate, 1,2-PD or one or more the mixture in them.In transdermal patch of the present invention, the weight ratio of penetrating agent (C) in hypothallus is higher, and it is better that Percutaneously absorbable can become, but when weight ratio surpasses 15%, the cohesive strength of binding agent will reduce greatly, thereby the mechanical property of patch is affected adversely.
In granisetron patch of the present invention, backing layer is made of back lining materials well known to those skilled in the art such as aluminium foil, poly terephthalic acid diethylester, polyethylene or non-woven fabrics etc.
In granisetron patch of the present invention; the protective layer that is covered on the hypothallus is made of protective material well known to those skilled in the art; thin film such as polyester, polrvinyl chloride, polyethylene terephthalate etc.; perhaps said film is carried out conventional release coat and processes, be included in directly with film surface that hypothallus contacts on silicone coated resin or fluororesin etc.The protective layer preferred surface of transdermal patch of the present invention is coated with the mylar of fluororesin.
The pharmaceutical composition that the present invention contains granisetron can adopt technology preparation known in the art, for example in suitable container, the polyacrylic resin of formula ratio (for example is selected from
RS100,
E100 etc.) solvent (for example ethyl acetate) immersion with appropriate amount made it to dissolve fully in 2-3 hour, the granisetron, polyacrylate pressure-sensitive and the transdermal penetration promoter that add again formula ratio, add the solvent (such as ethyl acetate etc.) of appropriate amount to certain volume, stirring fully mixes each component, can make the pharmaceutical composition that contains granisetron that is the rubber cement shape.
The transdermal patch that the present invention contains granisetron can adopt technology preparation known in the art; for example the above-mentioned pharmaceutical composition rubber cement that contains granisetron for preparing is coated on the open and flat back lining materials by certain thickness; the preparation hypothallus; then under 60 ℃ of conditions dry 2-3 hour; remove volatile solvent; take out cooling, then the protective material layer is covered on the hypothallus, fill at last the patch that is cut into certain area and shape.
Compared with prior art, patch of the present invention has obviously improved the transdermal flux of granisetron, indicating and satisfying under the prerequisite of identical dosage, the more similar patch product of patch of the present invention can reduce the content of dispersion in the unit are, perhaps dwindles usable floor area under the prerequisite that keeps same units area medicine content.The former can save manufacturing cost, and latter can improve comfort and the compliance of patch user.Simultaneously, patch of the present invention is little to skin irritation, and has enough adhesion strengths, does not also exist wire drawing, excessive glue etc. to be unfavorable for the phenomenon of using.
Description of drawings
Fig. 1 shows the external 0-72 of granisetron hour transdermal cumulative release amount (mg/cm in embodiment 1 transdermal patch and comparative example 1 patch
2) curve chart.
The specific embodiment
Further illustrate the present invention below by embodiment, but embodiment does not constitute any limitation to the present invention.
I. transdermal patch preparation
Embodiment 1
In suitable container, be weighed into 1.47 grams
RS100 (German Evonik Degussa company produce), add again appropriate amount ethyl acetate (Beijing Yili Fine Chemicals Co., Ltd., chemical pure) immersion made it to dissolve fully in 2-3 hour, being weighed into 24.42 grams contains the polyacrylate pressure-sensitive of 30% solids content (its preparation method is seen: Yang Yukun again, " pressure sensitive adhesive goods technical manual ", Chemical Industry Press, in JIUYUE, 2004 is published, the 260-261 page or leaf), wherein used monomer and content thereof are respectively: acrylamide 3.8%, butyl acrylate 33.1%, 2-EHA 40.9%, vinyl acetate 21% and α-methacrylic acid 1.2%.Above monomer is all available from Beijing Yili Fine Chemicals Co., Ltd., be chemical pure), and then add 0.55 gram granisetron (Sinopharm Chuankang Pharmaceutical Co., Ltd.) and 1.04 gram isopropyl myristates (Fauna of Kunshan, Jiangsu city China new household chemicals company limited produce), add the ethyl acetate of appropriate amount to certain volume, stirring makes each component fully be mixed into the rubber cement shape.With the rubber cement for preparing by certain thickness be coated in open and flat mylar (
1109) on the back lining materials, the preparation hypothallus, then, under 60 ℃ of conditions dry 2-3 hour, make it dry after thickness be about 100 μ m.To scribble again the fluorine layer mylar (
1022) cover on this hypothallus, be die-cut at last the patch of certain area and shape, thereby make transdermal patch of the present invention.The granisetron medicament contg of this patch is about 0.66mg/cm
2, wherein the weight percentage of each component is as shown in table 1.
Embodiment 2
Adopt the method for embodiment 1, according to the weight percentage of each component in the hypothallus that provides in the table 1, the patch of Preparation Example 2.
Embodiment 3-6
Adopt the method for embodiment 1, according to the weight percentage of each component in the hypothallus that provides in the table 2, the patch of Preparation Example 3-6.
Comparative example 1
Be granisetron listing product
(STRAKAN LIMITED, specification is 34.3mg/52cm
2, namely granisetron content is 0.66mg/cm
2).
Comparative example 2-5
Patch according to the method for embodiment 1 makes does not wherein contain polyacrylic resin in comparative example 2 prescriptions, does not contain any penetrating agent in the comparative example 3, and the content of penetrating agent exceeds beyond the scope of the invention in the comparative example 4, and the contact adhesive that uses in the comparative example 5 is Duro-
87-2516 (production of national of the United States's starch company).
Table 1
Annotate: all to contain with comparative example 1 same amount be 0.66mg/cm for all embodiment and comparative example in the table 1
2Granisetron.
Table 2
II. transdermal patch performance test
1, the granisetron burst size is measured
According to " percutaneous drug administration preparation " (Liang Bingwen, Chinese Medicine science and technology publishing house, in JIUYUE, 1992 is published, 252 pages) method introduced carries out the transdermal test in vitro experiment, records the cumulative release amount (mg/cm of the patch 0-72 hour granisetron of embodiment and comparative example
2), wherein the cumulative release amount result of embodiment 1 and comparative example 1 is as shown in Figure 1.
2, to the evaluation of hot-fluid, cold flow
Adhesive-layer is made 30cm
2Disk test, hot-fluid is that paster was deposited 24 hours under 50 ℃ of temperature; Cold flow is with at ambient temperature seasoning 6 months of paster.Standards of grading are: 5-represents that the glue that overflows obviously appears in the edge, and 4-represents that the glue that overflows appears in the edge, and 3-represents that a small amount of glue that overflows appears in the edge, and 2-represents that the fragmentary glue that overflows appears in the edge, and 1-represents that the glue that overflows does not appear in the edge.。
3, hold the test of viscous forceCarry out according to GB/T4851-1998.
4, the test of initial bonding strengthCarry out (spin slope method) according to GB4852-84.
5, irritation test
[test carrier] Japan large ear rabbit (regular grade animal), 7～8 monthly ages.
The specimen of [sample size] each embodiment or comparative example patch is parallel selects 4 samples.
[test method] employing standard: pertinent regulations and content in " the medicine registration management way " that State Food and Drug Administration issues, " chemicals zest, anaphylaxis and the hemolytic investigative technique guideline ".
Each test sample adopts 4 Japan large ear rabbits., male and female half and half, all administration is 2 times, sticks continuously 7 days at every turn.Give animal 1 5cm at every turn
2Granisetron circular patch (content of dispersion 3.3mg).The all left side administrations of all animals, stick the granisetron transdermal patch, before animal note after at every turn dispelling old paster applies new paster, the last administration take off paster after the perusal record stick the position whether erythema, edema arranged, and mark, standards of grading are: 1) 0-0.49 is nonirritant, 2) 0.5-2.99 is slight zest; 3) 3.0-5.99 is the moderate zest, 4) 6.0-8.00 is strong and stimulating.As exist the persistency damage then to prolong the observation time limit, observe recovery situation and time that injured skin changes.
Above result of the test shows that transdermal patch of the present invention has all obtained gratifying technique effect in skin irritation, mechanical property as holding the aspects such as viscous force, initial bonding strength, cold flow, hot-fluid.Particularly importantly, when guaranteeing above-mentioned premium properties, compare with comparative example 1, granisetron transdermal patch of the present invention has obtained higher transdermal flux (result as shown in Figure 1), the transdermal effect that has shown patch of the present invention is better, the per area per time percutaneous rate of active medicine increases, residual quantity reduces, indicating under the prerequisite that satisfies identical dosage, the active medicine content of unit are can reduce, and this is being very favourable aspect preparation cost that reduces patch.Perhaps, under the identical prerequisite of guarantor unit's area medicine content, the less patch of usable floor area be can make, thereby comfort and the compliance of patch user improved.
Claims (9)
1. the pharmaceutical composition that contains granisetron, by (A) polyacrylate pressure-sensitive, (B) polyacrylic resin, (C) penetrating agent and (D) granisetron form, wherein said polyacrylate pressure-sensitive (A) is for containing (methyl) acrylamide or its N, (methyl) acrylate copolymer of N substituted monomer; Described polyacrylic resin (B) is Eudragit class polyacrylic resin, and described penetrating agent (C) is selected from isopropyl myristate, Laurel nitrogen
Ketone, glyceryl triacetate, 1,2-PD and composition thereof.
2. the pharmaceutical composition of claim 1 wherein, is pressed the weighing scale of compositions, and the shared weight ratio of component A and B is 65%-95%, and A: B=9-1; The shared weight ratio of component C is 2%-15%; And the shared weight ratio of component D is 3%-20%.
3. the pharmaceutical composition of claim 1 wherein, is pressed the weighing scale of compositions, and the shared weight ratio of component A is 60%-80%; The shared weight ratio of B component is 9%-20%; The shared weight ratio of component C is 6%-12%; And the shared weight ratio of component D is 5%-13%.
4. the pharmaceutical composition of claim 3, wherein component C is
RS100 or
E100, and/or component D is isopropyl myristate or Laurel nitrogen
The mixture of ketone, glyceryl triacetate and 1,2-PD.
5. each described pharmaceutical composition of claim 1 to 4, wherein said containing (methyl) acrylamide or its N, (methyl) acrylate copolymer of N substituted monomer forms by being selected from following monomer copolymerization: (methyl) acrylic acid, (methyl) acrylic acid C
1-10Arrcostab, 2-EHA, vinyl acetate, α-methacrylic acid, acrylonitrile, Methacrylamide, acrylamide, isobutoxy Methacrylamide, methoxy acrylamide, diamino ethyl methacrylate, N-butoxymethyl acrylamide, dimethylaminoethyl methacrylic acid, diethyllaminoethyl methacrylate and diisopropyl acrylamide; And/or described Eudragit class polyacrylic resin is selected from
L100,
S100,
RL 100,
RS100,
E100,
L100-55,
E PO,
RL PO,
RS PO and composition thereof.
6. pharmaceutical composition claimed in claim 5, wherein said containing (methyl) acrylamide or its N, (methyl) acrylate copolymer of N substituted monomer is formed by acrylamide, butyl acrylate, 2-EHA, vinyl acetate and α-methacrylic acid monomer copolymerization.
7. pharmaceutical composition claimed in claim 6, wherein said containing (methyl) acrylamide or its N, (methyl) acrylate copolymer of N substituted monomer is formed by 1%-5% acrylamide, 30%-40% butyl acrylate, 35%-50% 2-EHA, 15%-25% vinyl acetate and the copolymerization of 0.5%-2% α-methacrylic acid.
8. each the application of pharmaceutical composition aspect preparation granisetron transdermal patch of claim 1-7.
9. granisetron transdermal patch, its structure comprises backing layer, hypothallus and protective layer, it is characterized in that described hypothallus is made of each the pharmaceutical composition of claim 1-7.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610590115.XA CN106176742A (en) | 2011-08-01 | 2011-08-01 | Be suitable to the pharmaceutical composition containing granisetron and the preparation and application thereof of transdermal administration |
| CN2011102235332A CN102908345A (en) | 2011-08-01 | 2011-08-01 | Drug composition suitable for transdermal drug delivery and containing granisetron as well as preparation and application of same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011102235332A CN102908345A (en) | 2011-08-01 | 2011-08-01 | Drug composition suitable for transdermal drug delivery and containing granisetron as well as preparation and application of same |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610590115.XA Division CN106176742A (en) | 2011-08-01 | 2011-08-01 | Be suitable to the pharmaceutical composition containing granisetron and the preparation and application thereof of transdermal administration |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102908345A true CN102908345A (en) | 2013-02-06 |
Family
ID=47607084
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011102235332A Pending CN102908345A (en) | 2011-08-01 | 2011-08-01 | Drug composition suitable for transdermal drug delivery and containing granisetron as well as preparation and application of same |
| CN201610590115.XA Pending CN106176742A (en) | 2011-08-01 | 2011-08-01 | Be suitable to the pharmaceutical composition containing granisetron and the preparation and application thereof of transdermal administration |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610590115.XA Pending CN106176742A (en) | 2011-08-01 | 2011-08-01 | Be suitable to the pharmaceutical composition containing granisetron and the preparation and application thereof of transdermal administration |
Country Status (1)
| Country | Link |
|---|---|
| CN (2) | CN102908345A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109875982A (en) * | 2019-04-15 | 2019-06-14 | 广东红珊瑚药业有限公司 | Palonosetron transdermal patch and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101721394A (en) * | 2008-10-29 | 2010-06-09 | 大连理工大学 | Granisetron and/or hydrochloride patch thereof |
| CN102038664A (en) * | 2010-12-20 | 2011-05-04 | 蚌埠丰原涂山制药有限公司 | Scopolamine transdermal patch and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0302662D0 (en) * | 2003-02-05 | 2003-03-12 | Strakan Ltd | Transdermal granisetron |
-
2011
- 2011-08-01 CN CN2011102235332A patent/CN102908345A/en active Pending
- 2011-08-01 CN CN201610590115.XA patent/CN106176742A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101721394A (en) * | 2008-10-29 | 2010-06-09 | 大连理工大学 | Granisetron and/or hydrochloride patch thereof |
| CN102038664A (en) * | 2010-12-20 | 2011-05-04 | 蚌埠丰原涂山制药有限公司 | Scopolamine transdermal patch and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 周祥兴等: "包装用塑料制品的生产配方和生产工艺", 《包装用塑料制品的生产配方和生产工艺》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109875982A (en) * | 2019-04-15 | 2019-06-14 | 广东红珊瑚药业有限公司 | Palonosetron transdermal patch and preparation method thereof |
| CN109875982B (en) * | 2019-04-15 | 2022-05-20 | 广东红珊瑚药业有限公司 | Palonosetron transdermal patch and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106176742A (en) | 2016-12-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6895755B2 (en) | Methods for regulating the release of active agents in a transdermal delivery system | |
| EP3253840B1 (en) | Pressure-sensitive adhesives for transdermal drug delivery | |
| CN101899276B (en) | Amphiphilic hot-melt pressure sensitive adhesive and preparation method thereof | |
| US9585862B2 (en) | Patch containing rivastigmine | |
| ES2954087T3 (en) | Transdermal delivery system including an interface mediator | |
| WO2007035940A2 (en) | Transdermal norelgestromin delivery system | |
| HK1248265A1 (en) | Pressure-sensitive adhesives for transdermal drug delivery | |
| JPS63246327A (en) | Plasta containing etofenamate | |
| KR20120093239A (en) | Water-based paste containing diclofenac sodium | |
| ES2609247T3 (en) | Composition to improve transdermal absorption of a drug and prepared in patch | |
| WO2018026759A1 (en) | Pressure-sensitive adhesives for transdermal drug delivery | |
| KR101558043B1 (en) | Transdermal composition comprising rotigotine | |
| CN113648297B (en) | Pharmaceutical composition and patch containing flurbiprofen | |
| CN102908345A (en) | Drug composition suitable for transdermal drug delivery and containing granisetron as well as preparation and application of same | |
| WO2012090322A1 (en) | Patch | |
| CN108498491A (en) | A kind of transdermal oxybutynin absorption patch and its preparation and application | |
| CN101785864B (en) | Post-crosslinking hydrophilic patch substrate and preparation method thereof | |
| CN101612141B (en) | Buprenorphine patch | |
| CN112040936B (en) | Transdermal therapeutic system for transdermal administration of solifenacin | |
| JP5431969B2 (en) | Fentanyl-containing external patch | |
| CN104173322A (en) | Piroxicam-containing transdermal-absorption preparation and preparation method thereof | |
| TWI844643B (en) | A pharmaceutical composition that has excellent absorption by the organism and excellent chemical stability | |
| CN107456446A (en) | A kind of Pyridostigmine Bromide gel ointment and preparation method thereof | |
| CN102144991A (en) | Composition containing selegiline and transdermal patch containing composition | |
| CN100548302C (en) | The patch that contains estrogen |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| ASS | Succession or assignment of patent right |
Owner name: JIANGSU KANGBEIDE PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: HENAN KANGBEIDE PHARMACEUTICAL CO., LTD. BEIJING TECHNOLOGY DEVELOPMENT CENTER Effective date: 20130704 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 100000 HAIDIAN, BEIJING TO: 211500 NANJING, JIANGSU PROVINCE |
|
| TA01 | Transfer of patent application right |
Effective date of registration: 20130704 Address after: Zhongxin Road, Nanjing Industrial Development Zone along the Yangtze River in Jiangsu province 211500 Zhongshan science and Technology Park No. 709 Applicant after: JIANGSU KBD PHARMACEUTICAL CO., LTD. Address before: 100000 Beijing Haidian District Zizhuyuan Road No. 98 Building No. 116, No. 205 Applicant before: Henan Kangbeide Pharmaceutical Co.,Ltd. Beijing Technology Development Center |
|
| CB02 | Change of applicant information |
Address after: Zhongshan science and Technology Park, Zhongxin road along the Yangtze River Industrial Development Zone in Nanjing City, Jiangsu Province, No. 709 211500 Applicant after: Jiangsu Kang times pharmaceutical Limited by Share Ltd Address before: Zhongxin Road, Nanjing Industrial Development Zone along the Yangtze River in Jiangsu province 211500 Zhongshan science and Technology Park No. 709 Applicant before: JIANGSU KBD PHARMACEUTICAL CO., LTD. |
|
| COR | Change of bibliographic data | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20130206 |