CN101574331A - Lappaconitine transdermal patch and preparation method thereof - Google Patents
Lappaconitine transdermal patch and preparation method thereof Download PDFInfo
- Publication number
- CN101574331A CN101574331A CNA2009101189289A CN200910118928A CN101574331A CN 101574331 A CN101574331 A CN 101574331A CN A2009101189289 A CNA2009101189289 A CN A2009101189289A CN 200910118928 A CN200910118928 A CN 200910118928A CN 101574331 A CN101574331 A CN 101574331A
- Authority
- CN
- China
- Prior art keywords
- lappaconitine
- transdermal patch
- layer
- sensitive adhesive
- pressure sensitive
- 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
- NWBWCXBPKTTZNQ-UHFFFAOYSA-N (16S)-4-(N-Acetyl-anthraniloyloxy)-20-aethyl-1alpha,14alpha,16-trimethoxy-aconitan-8,9-diol Natural products C1CC(OC)C2(C3C4)C5CC(C(C6)OC)C(OC)C5(O)C6(O)C4C2N(CC)CC31OC(=O)C1=CC=CC=C1NC(C)=O NWBWCXBPKTTZNQ-UHFFFAOYSA-N 0.000 title claims abstract description 82
- NWBWCXBPKTTZNQ-QOQRDJBUSA-N y4m5974f7z Chemical compound O([C@]12CN([C@@H]3[C@H]4[C@]5(O)[C@@]6(O)[C@@H](OC)[C@@H]([C@H](C5)OC)C[C@H]6[C@@]3([C@@H]1C4)[C@@H](OC)CC2)CC)C(=O)C1=CC=CC=C1N=C(C)O NWBWCXBPKTTZNQ-QOQRDJBUSA-N 0.000 title claims abstract description 82
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 239000003814 drug Substances 0.000 claims abstract description 58
- 239000004820 Pressure-sensitive adhesive Substances 0.000 claims abstract description 42
- 229940079593 drug Drugs 0.000 claims abstract description 37
- 239000002994 raw material Substances 0.000 claims abstract description 19
- 230000003110 anti-inflammatory effect Effects 0.000 claims abstract description 12
- 239000010410 layer Substances 0.000 claims description 71
- 239000011241 protective layer Substances 0.000 claims description 31
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 30
- 238000010521 absorption reaction Methods 0.000 claims description 23
- -1 polysiloxanes Polymers 0.000 claims description 22
- 239000003623 enhancer Substances 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 239000011505 plaster Substances 0.000 claims description 18
- 238000001816 cooling Methods 0.000 claims description 17
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 15
- 238000005516 engineering process Methods 0.000 claims description 15
- 238000002156 mixing Methods 0.000 claims description 15
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 14
- 238000007766 curtain coating Methods 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 13
- 229920002367 Polyisobutene Polymers 0.000 claims description 11
- 239000006184 cosolvent Substances 0.000 claims description 11
- 239000004014 plasticizer Substances 0.000 claims description 11
- 244000147568 Laurus nobilis Species 0.000 claims description 10
- 235000017858 Laurus nobilis Nutrition 0.000 claims description 10
- 235000005212 Terminalia tomentosa Nutrition 0.000 claims description 10
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims description 10
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 10
- 239000000194 fatty acid Substances 0.000 claims description 10
- 229930195729 fatty acid Natural products 0.000 claims description 10
- 150000002576 ketones Chemical class 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 239000000284 extract Substances 0.000 claims description 9
- 229920001296 polysiloxane Polymers 0.000 claims description 9
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 8
- 150000004665 fatty acids Chemical class 0.000 claims description 8
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 claims description 8
- NOOLISFMXDJSKH-UHFFFAOYSA-N p-menthan-3-ol Chemical compound CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 6
- 229940044949 eucalyptus oil Drugs 0.000 claims description 6
- 239000010642 eucalyptus oil Substances 0.000 claims description 6
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 5
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 5
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 5
- 239000005642 Oleic acid Substances 0.000 claims description 5
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 5
- 244000173166 Pyrus ussuriensis Species 0.000 claims description 5
- 235000011572 Pyrus ussuriensis Nutrition 0.000 claims description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 5
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 5
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 5
- 229950008882 polysorbate Drugs 0.000 claims description 5
- 229920000136 polysorbate Polymers 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 239000011787 zinc oxide Substances 0.000 claims description 5
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 claims description 4
- 229920001971 elastomer Polymers 0.000 claims description 4
- 229960001047 methyl salicylate Drugs 0.000 claims description 4
- 239000003921 oil Substances 0.000 claims description 4
- 210000000582 semen Anatomy 0.000 claims description 4
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims description 3
- 239000005995 Aluminium silicate Substances 0.000 claims description 3
- DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 claims description 3
- 235000012211 aluminium silicate Nutrition 0.000 claims description 3
- 125000005456 glyceride group Chemical group 0.000 claims description 3
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 claims description 3
- 239000004408 titanium dioxide Substances 0.000 claims description 3
- 230000001760 anti-analgesic effect Effects 0.000 claims 3
- 230000000694 effects Effects 0.000 abstract description 17
- 238000010579 first pass effect Methods 0.000 abstract description 3
- 230000036592 analgesia Effects 0.000 abstract description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract description 2
- 230000002045 lasting effect Effects 0.000 abstract description 2
- 210000004185 liver Anatomy 0.000 abstract description 2
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 abstract 2
- 206010061623 Adverse drug reaction Diseases 0.000 abstract 1
- 206010070863 Toxicity to various agents Diseases 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 19
- 239000000243 solution Substances 0.000 description 18
- 208000002193 Pain Diseases 0.000 description 13
- 230000036407 pain Effects 0.000 description 13
- 241000699670 Mus sp. Species 0.000 description 12
- 239000007924 injection Substances 0.000 description 11
- 238000002347 injection Methods 0.000 description 11
- 239000000047 product Substances 0.000 description 9
- QUSPUZQKMRMVFL-UHFFFAOYSA-N 2-(benzenesulfonamido)-4-methylsulfanylbutanoic acid Chemical compound CSCCC(C(O)=O)NS(=O)(=O)C1=CC=CC=C1 QUSPUZQKMRMVFL-UHFFFAOYSA-N 0.000 description 8
- 230000000202 analgesic effect Effects 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 7
- 238000013270 controlled release Methods 0.000 description 7
- 230000001276 controlling effect Effects 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- 239000003182 parenteral nutrition solution Substances 0.000 description 6
- 230000008961 swelling Effects 0.000 description 6
- 239000000853 adhesive Substances 0.000 description 5
- 230000001070 adhesive effect Effects 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 238000000576 coating method Methods 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 241000196324 Embryophyta Species 0.000 description 4
- 238000012449 Kunming mouse Methods 0.000 description 4
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 229960001340 histamine Drugs 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000004856 capillary permeability Effects 0.000 description 3
- 230000003203 everyday effect Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 238000007619 statistical method Methods 0.000 description 3
- 229940126680 traditional chinese medicines Drugs 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 206010014025 Ear swelling Diseases 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 240000001307 Myosotis scorpioides Species 0.000 description 2
- 241000053227 Themus Species 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 210000005069 ears Anatomy 0.000 description 2
- 238000000556 factor analysis Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000003292 glue Substances 0.000 description 2
- 229960001660 histamine phosphate Drugs 0.000 description 2
- ZHIBQGJKHVBLJJ-UHFFFAOYSA-N histamine phosphate Chemical compound OP(O)(O)=O.OP(O)(O)=O.NCCC1=CNC=N1 ZHIBQGJKHVBLJJ-UHFFFAOYSA-N 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 1
- 240000006409 Acacia auriculiformis Species 0.000 description 1
- 241000227129 Aconitum Species 0.000 description 1
- 241001586439 Aconitum sinomontanum Species 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- COXVTLYNGOIATD-HVMBLDELSA-N CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O Chemical compound CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O COXVTLYNGOIATD-HVMBLDELSA-N 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 206010015719 Exsanguination Diseases 0.000 description 1
- 244000283207 Indigofera tinctoria Species 0.000 description 1
- 206010022086 Injection site pain Diseases 0.000 description 1
- 101100293261 Mus musculus Naa15 gene Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 208000000114 Pain Threshold Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000010513 Stupor Diseases 0.000 description 1
- 206010053615 Thermal burn Diseases 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000001741 anti-phlogistic effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229940025250 camphora Drugs 0.000 description 1
- 239000010238 camphora Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 229960003699 evans blue Drugs 0.000 description 1
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 230000003760 hair shine Effects 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000004084 narcotic analgesic agent Substances 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000037040 pain threshold Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920006264 polyurethane film Polymers 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012109 statistical procedure Methods 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229940117958 vinyl acetate Drugs 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a lappaconitine transdermal patch and preparation method thereof. The patch comprises a back sheet, a drug storing layer and a protection layer, wherein, the drug storing layer is composed of the raw materials of lappaconitine and pressure sensitive adhesive, or a right amount of transdermal accelerant is added to finally prepare lappaconitine transdermal patch. The lappaconitine transdermal patch of the invention has the advantages of convenient use, high bioavailability and lasting action, avoids first-pass effect of liver as well as damage to gastrointestinal tract, reduces drug toxicity and side effect, improves bioavailability of drug and safety of treatment, and has obvious effect on anti-inflammatory and analgesia.
Description
Technical field
The present invention relates to a kind of percutaneous plaster and preparation method thereof, particularly a kind of Lappaconitine transdermal patch and preparation method thereof.
Background technology
Pain is modal multiple common symptoms in the medical research clinical disease, and this difficult problem is a great challenge to research worker and doctor.The medicine of nowadays treating pain is based on Western medicine, mainly be divided into non_steroidal anti_inflammatory drug and narcosis analgesic two classes, in this two classes medicine, though anaesthetic analgesic effect is strong, but the side effect of self is big, addiction is arranged, though and the non-steroidal anti-inflammatory analgesic does not have the so big side effect of narcotic analgesic medicine, the untoward reaction of reverse side such as many gastrointestinal tract is also arranged.Medical domain is also constantly being sought the good and anti-inflammation analgesia medicine of side effect minimum of analgesic effect.
Lappaconitine molecular formula lappaconitine hydrobromide molecular formula
Lappaconitine is alkaloid---the Lappaconitine that extracts from Ranunculaceae aconitum plant Aconitum sinomontanum Nakai (Aconitum sinomoutanumNakai), at present the hydrobromate that is mainly lappaconitine that uses clinically.The lappaconitine hydrobromide molecular weight is 683.64, fusing point is 217~221 ℃, be dissolved in methanol, be slightly soluble in water and ethanol, be insoluble in organic solvents such as chloroform, its preparation type is mainly oral formulations and injection, the oral formulations bioavailability is lower, half-life is shorter, needs long-time oral administration, and has the medicine first pass effect; Injection administration inconvenience, pain during injection, prescription is relatively stricter, and improper use is easily caused danger; Lappaconitine hydrobromide ester dissolubility is low, is unfavorable for making paster; Lappaconitine is compared with lappaconitine hydrobromide and has been omitted salify technology, can reduce cost from producing.
Summary of the invention
The objective of the invention is to disclose a kind of Lappaconitine transdermal patch; Another object of the present invention is to disclose the preparation method of this paster.
The objective of the invention is to be achieved through the following technical solutions:
Percutaneous plaster of the present invention comprises backing layer, drug storehouse layer and protective layer, and wherein the raw material of drug storehouse layer consists of:
Lappaconitine: 0.1-2 weight portion
Percutaneous absorption enhancer: 0.1-2 weight portion
Pressure sensitive adhesive: 5-15 weight portion.
Percutaneous plaster of the present invention comprises backing layer, drug storehouse layer and protective layer, and wherein the raw material of drug storehouse layer composition is preferably:
Lappaconitine: 0.5 weight portion
Percutaneous absorption enhancer: 1 weight portion
Pressure sensitive adhesive: 10 weight portions.
Percutaneous plaster of the present invention comprises backing layer, drug storehouse layer and protective layer, and wherein the raw material of drug storehouse layer composition is preferably:
Or lappaconitine: 1 weight portion
Percutaneous absorption enhancer: 0.5 weight portion
Pressure sensitive adhesive: 12 weight portions.
Percutaneous plaster of the present invention comprises backing layer, drug storehouse layer and protective layer, and wherein the raw material of drug storehouse layer composition is preferably:
Or lappaconitine: 1.5 weight portions
Percutaneous absorption enhancer: 1.5 weight portions
Pressure sensitive adhesive: 8 weight portions.
Also can add cosolvent and/or plasticizer in the drug storehouse layer raw material of the invention described above percutaneous plaster, wherein the amount of cosolvent or plasticizer be the amount of amount, Percutaneous absorption enhancer of lappaconitine and pressure sensitive adhesive amount total amount 1-5 doubly.
Also can add cosolvent and/or plasticizer in the drug storehouse layer raw material of the invention described above percutaneous plaster, wherein the amount of cosolvent or plasticizer all is preferably 3 times of total amount of the amount of the amount of amount, Percutaneous absorption enhancer of lappaconitine and pressure sensitive adhesive.
The preparation method of percutaneous plaster of the present invention:
Get the raw material mixing and stirring of above-mentioned drug storehouse layer; Adopt curtain coating technology that said mixture is coated on the backing layer to solvent and volatilize, protective layer on the cooling bonnet, Lappaconitine transdermal patch; Or said mixture is coated on the backing layer, protective layer on the cooling bonnet, Lappaconitine transdermal patch.
Paster of the present invention comprises backing layer, drug storehouse layer and protective layer, it is characterized in that wherein Percutaneous absorption enhancer is meant Laurel nitrogen
In ketone, Mentholum, Borneolum Syntheticum, eucalyptus oil, Fructus Zanthoxyli oil, Oleum Bulbus Allii and Rhizoma Chuanxiong extract, Semen Myristicae extract, propylene glycol, methyl salicylate or the oleic acid one or more.
Paster of the present invention comprises backing layer, drug storehouse layer and protective layer, it is characterized in that wherein pressure sensitive adhesive is meant acrylate pressure sensitive adhesive, Polyisobutylene PSA, polysiloxanes pressure sensitive adhesive or thermo-elasto-plasticity rubber.
Paster of the present invention, Laurel nitrogen
Ketone is by one or more replacements in Mentholum, Borneolum Syntheticum, eucalyptus oil, Fructus Zanthoxyli oil, Oleum Bulbus Allii and Rhizoma Chuanxiong extract, Semen Myristicae extract, propylene glycol, methyl salicylate or the oleic acid; Acrylate pressure sensitive adhesive is replaced by Polyisobutylene PSA, polysiloxanes pressure sensitive adhesive or thermo-elasto-plasticity rubber.
Paster of the present invention, cosolvent is smooth by the fatty acid Pyrusussuriensis, in the polyoxyethylene aliphatic alcohol ether, Polysorbate, fatty glyceride, polyoxyethylene fatty acid ester one or more are united use.
Paster of the present invention, plasticizer is united use by in Kaolin, zinc oxide, titanium dioxide, kieselguhr, glycerol, the propylene glycol one or more.
Wherein, the backing layer of paster of the present invention is that polyurethane film, vinylacetate film, polychloroethylene film are made according to common process; The protective layer of paster is the polyethylene film that common process is made.
The invention provides a kind of easy to use, bioavailability is high, effect persistent " Gaowujiasu " picking and preparation method thereof.Experiment and clinical research show that lappaconitine has antiinflammatory, analgesic effect." Gaowujiasu " picking of the present invention is that glue mixes the type transdermal patch, compares with film controlling type percutaneous plaster in the prior art, and structure is simpler, and cost is lower, and the production cycle is shorter, is easier to produce; In addition, contain controlled release layer in the prior art film controlling type percutaneous plaster, Lappaconitine transdermal patch of the present invention has been removed controlled release layer, the Transdermal absorption result of the test shows: drug transdermal assimilation effect of the present invention is better than prior art film controlling type percutaneous plaster, illustrated that simultaneously lappaconitine makes the paster agent, because the lappaconitine molecular weight is relatively large, release-controlled film is relatively poor to the controlled-release effect of paster, and this curative effect to paster can produce certain influence.Lappaconitine transdermal patch of the present invention is by with lappaconitine and adjuvant rational proportion, guaranteed that not only paster has significant analgesic activity, and reduced the toxic and side effects of medicine, blood drug level is stable, lasting, avoided " first pass effect " and the gastrointestinal of liver to destroy, improved the safety of bioavailability of medicament and treatment, avoid occurring the film controlling type percutaneous plaster and the danger that reasons such as release-controlled film breaks cause occurs, and medication is convenient, no pain, and is remarkable at antiinflammatory, ease pain effect.
Description of drawings
Fig. 1: the different transdermal enhancer Transdermal absorption of " Gaowujiasu " picking curve.
Fig. 2: dissimilar paster Transdermal absorption effect comparison diagrams.
Following experimental example and embodiment are used for further specifying but are not limited to the present invention.
Experimental example 1
The " Gaowujiasu " picking anti-inflammatory of the embodiment of the invention 1 preparation, the pharmacodynamics test of analgesic activity
One, antiinflammatory action test
(1) paraxylene causes the effect of mice auricle swelling (mouse ear swelling test)
1, material
1.1 reagent and apparatus
Dimethylbenzene (analyze pure, Xi'an chemical reagent factory, lot number: 070922); Electron portable balance (model: YB1201, Haikang, Shanghai Electronic Instruments Plant, precision 0.01g); Card punch (specification: 6mm); Tweezers; Syringe (specification: 1ml); The gavage syringe needle; Psychrometer; Picric acid; Microsyringe (Shanghai Medicine Laser Instrument Plant, 50 μ L).
1.2 medicine
" Gaowujiasu " picking; The negative control product are not for containing the paster (self-control) of medicine; Lappaconitine parenteral solution (Gansu Xin Lan pharmaceutcal corporation, Ltd, authentication code: the accurate word H62020888 of traditional Chinese medicines, lot number: 20080201).
1.3 animal used as test
The healthy adult Kunming mouse, male and female half and half, (Lanzhou Institute of Biological Products's Experimental Animal Center provides body weight (20 ± 2) g, the quality certification number: the moving word 14-001 of doctor).
2, grouping and method
Get body weight (20 ± 2) g Kunming mouse, male, be divided at random 5 groups, every group 10, be made as respectively Lappaconitine parenteral solution (0.8mg/kg) control group (I), model control group (paster that does not contain medicine) (II), " Gaowujiasu " picking low dose group (1mg/ subsides) (III), in the " Gaowujiasu " picking dosage group (2mg/ subsides) (IV), " Gaowujiasu " picking high dose group (4mg/ subsides) (V). I group injection Lappaconitine parenteral solution 0.8mg/kg, II~V organizes every group of mouse and pastes corresponding tested material, successive administration 3 days, every day 1 time. The last administration is thrown off tested material after half an hour, with the auris dextra wiped clean, gets dimethylbenzene 0.02mL/ only in mouse right ear before and after two sided coatings with microsyringe with warm water, and every each 0.01mL brings out mouse ear and swells, and left ear is not done any processing. Put to death animal after causing scorching 1h, cut ears along the auricle baseline, lay round auricle, scales/electronic balance weighing with 6mm diameter card punch at same position. Take left and right sides auricle weight difference as swelling, obtain swelling inhibiting rate (%), the antiinflammatory action of comparative drug. Each is organized under mouse the same terms and feeds, freely ingests, and drinking-water, room temperature is controlled at (20 ± 1) ℃, humidity about 60%.
Swelling inhibiting rate (%)=(control group swelling-be subjected to reagent group swelling)/control group swelling * 100%.
3, statistical analysis
(x ± s) expression adopts the SPSS11.5 statistical software to carry out data and processes all data with mean ± standard deviation. Carry out one-way analysis of variance, check with LSD when variance has homogeneous, heterogeneity of variance Dunnett ' s T3 check is carried out comparing between each group. P<0.05 or P<0.01 expression difference has conspicuousness.
4, result
Mouse auricle edema method does not need special equipment, and method is easy, instant effect, and dosage is few, and is copied into the power height. Be applicable to the conventional screening of anti-inflammatory agent. This experimental result shows, " Gaowujiasu " picking can significantly suppress the mice caused by dimethylbenzene xylene ear swelling, inhibiting rate is respectively: " Gaowujiasu " picking low dose group (1mg/ subsides) (III) is 13.07%, dosage group (2mg/ subsides) (IV) is 17.03% in the " Gaowujiasu " picking, " Gaowujiasu " picking high dose group (4mg/ subsides) is 36.93% (suitable with the inhibiting rate of Lappaconitine parenteral solution group, the inhibiting rate of Lappaconitine parenteral solution group is 37.77%) (V). Dosage group in the " Gaowujiasu " picking (2mg/ subsides) (IV) (V) compares with model control group with " Gaowujiasu " picking high dose group (4mg/ subsides), difference has conspicuousness (P<0.05 or P<0.01), " Gaowujiasu " picking low dose group (1mg/ subsides) (III) compares with model control group, no significant difference (P>0.05), as shown in table 1, the middle and high dosage of prompting " Gaowujiasu " picking has antiinflammatory action, and antiphlogistic effects has dose dependent.
Table 1 " Gaowujiasu " picking paraxylene causes the impact (x ± s) of mice ear
Annotate: compare with model control group,*P<0.05,
**P<0.01
(2) histamine is caused the impact that the mouse capillary permeability increases
1, test material
1.1 medicine and reagent
" Gaowujiasu " picking; The negative control product are not for containing the paster (self-control) of medicine; Lappaconitine parenteral solution (Gansu Xin Lan pharmaceutcal corporation, Ltd, authentication code: the accurate word H62020888 of traditional Chinese medicines, lot number: 20080201); Histamine phosphate (Histamine diphosphate), Shanghai Biochemical Research institute of Chinese Academy of Sciences product; Evans blue, Switzerland's import packing, the Solution on Chemical Reagents in Shanghai purchasing and supply station provides.
1.2 instrument
72-1 type spectrophotometer (Shanghai the 3rd analytical instrument factory product); LD5-2 type centrifuge (Beijing Medical Centrifugal Machine Factory's product); Electron portable balance (model: YB1201, Haikang, Shanghai Electronic Instruments Plant, precision 0.01g); Grainer; Card punch (specification: 2cm).
1.3 animal used as test
The healthy adult Kunming mouse, (Lanzhou Institute of Biological Products's Experimental Animal Center provides body weight (20 ± 2) g, the quality certification number: the moving word 14-001 of doctor).
2, method
Get 50 of mices, male and female half and half, be divided into 5 groups at random, every group 10, be made as respectively lappaconitine hydrobromide injection (0.8mg/kg) matched group (I), model control group (paster that does not contain medicine) (II), " Gaowujiasu " picking low dose group (1mg/ subsides) (III), in the " Gaowujiasu " picking dosage group (2mg/ subsides) (IV), " Gaowujiasu " picking high dose group (4mg/ subsides) (V).I group injection lappaconitine hydrobromide injection 0.8mg/kg sloughs the about 3cm of mouse back with depilator before other treated animal test
2Hair, II~V organizes the right hind of every group of mice by 1cm
2/ only paste and tried thing accordingly, successive administration 6 days, every day 2 times.30min after the last administration throws off and is tried thing, will paste medicine position wiped clean with warm water, at mouse back center subcutaneous injection 0.1% histamine phosphate 0.1mL, tail vein injection 1%Evans indigo plant 5mlkg immediately
-1Behind the 20min, the sacrificed by exsanguination mice peels off skin of back, lays the skin speckle of the position, deep of dyeing with the card punch of diameter 2cm, shred then, soak at twice with 7: 3 acetone and normal saline mixed solution 4mL, each 2h merges immersion, add above-mentioned mixed liquor to 5mL, insulation is hatched 36h until the blue complete obiteration of skin in 60 ℃ of calorstats.Then with 2000rmin
-1Centrifugal 5min gets supernatant, with 72-1 type spectrophotometer colorimetric under the 610nm wavelength, measures the filtrate absorbance.Measured absorbance is carried out statistical procedures.
3, statistical analysis
(x ± s) expression adopts the SPSS11.5 statistical software to carry out date processing to all data with mean ± standard deviation.Carry out one factor analysis of variance, check with LSD when variance has homogeneous, heterogeneity of variance Dunnett ' s T3 check is carried out comparing between each group.P<0.05 or P<0.01 expression difference has significance.
4, result
During acute inflammation,, blood vessel-the organize change of barrier function, plasma protein accelerate along with penetrating extravascular tissue speed.This law causes on the scorching basis at the applied chemistry medium, and the dyestuff of quiet notes doses is simultaneously measured the dyestuff of local inflammation intralesional, the variation that can quantitatively and accurately record vascular permeability subsequently.
This result of the test shows that the mice capillary permeability increase that " Gaowujiasu " picking causes histamine has obvious suppression effect (P<0.05 or P<0.01), sees Table 2, has antiinflammatory action preferably.
Table 2 " Gaowujiasu " picking causes the influence that the mice capillary permeability increases (x ± s) to histamine
Compare with the model control group group,
*P<0.05,
*P<0.01
Two, analgesic activity test
The effect of whipping (tail-flick test) due to radiant heat (radiant heat) stimulated
1, test material
1.1 medicine
" Gaowujiasu " picking; The negative control product are not for containing the paster (self-control) of medicine; Lappaconitine hydrobromide injection (Gansu Xin Lan pharmaceutcal corporation, Ltd, authentication code: the accurate word H62020888 of traditional Chinese medicines, lot number: 20080201).
1.2 instrument
SW-200 photo-thermal tail pain tester; The portable balance of electronics (model: YB1201, Haikang, Shanghai Electronic Instruments Plant, precision 0.01g).
1.3 laboratory animal
The healthy adult Kunming mouse, (Lanzhou Institute of Biological Products's Experimental Animal Center provides body weight (20 ± 2) g, the quality certification number: the moving word 14-001 of doctor).
2, method
Mice is divided into 5 groups at random, every group 12, be made as respectively: lappaconitine hydrobromide injection (0.8mg/kg) matched group (I), blank group (paster that does not contain medicine) (II), " Gaowujiasu " picking low dose group (1mg/ subsides) (III), in the " Gaowujiasu " picking dosage group (2mg/ subsides) (IV), " Gaowujiasu " picking high dose group (4mg/ subsides) (V).During test, animal is put in the Mus tube, tail falls in outside the tube down naturally, uses manual time-keeping, to start (tail flick latency incubation period that photo-thermal to the time that the Mus tail is swung rapidly is the whipping reaction, TFL) as the threshold of pain, regulating load voltage makes basic threshold of pain TFL (pain threshold before the administration) comparatively sensitive for the stimulus intensity of 2-4s to about the 20V, and survey earlier is 3 times during on-test, each 5min at interval, getting its average is the basic threshold of pain.For preventing skin scald, illumination deadline, 10s exceeded.I group injection lappaconitine hydrobromide injection 0.8mg/kg, II~V organizes every group of mice by 1cm
2/ only paste and tried thing accordingly, successive administration 4 days, every day 1 time.30min surveys its threshold of pain after the last administration.Calculate threshold of pain raising rate %.
Threshold of pain raising rate %=(TFL-basis TFL after the administration)/basic TFL * 100%
3, statistical analysis
(x ± s) expression adopts the SPSS11.5 statistical software to carry out date processing to all data with mean ± standard deviation.Carry out one factor analysis of variance, check with LSD when variance has homogeneous, heterogeneity of variance Dunnett ' s T3 check is carried out comparing between each group.P<0.05 or P<0.01 expression difference has significance.This group self cross-reference adopts Paired-Samples T Test check.
4, result
The result shows: dosage group in the " Gaowujiasu " picking (2mg/ subsides) (IV) (V) can obviously improve the threshold of pain that radiant heat shines mice with " Gaowujiasu " picking high dose group (4mg/ subsides), with before the administration of this group and the blank group relatively all difference significance (P<0.05 or P<0.01) is arranged, see Table 3.
Table 3 " Gaowujiasu " picking stimulates the influence cause pain (x ± s) to the mice radiant heat
Compare with the blank group,
*P<0.05,
*P<0.01
It is relatively preceding with the treatment of this group,
#P<0.05,
##P<0.01
The screening experiment of experimental example 2 various adjuvants
1, the selection of adhesive test:
Take by weighing lappaconitine, through method adding transdermal enhancer and the different adhesive of embodiment 1, mixing, coating, drying cuts, and measures and holds viscous force (the results are shown in Table 4).
The various adhesive of table 4 hold the viscous force correction data
Experimental result shows that acrylate pressure sensitive adhesive, Polyisobutylene PSA, these three kinds of raw materials of polysiloxanes pressure sensitive adhesive all can be used as the adhesive in the paster preparation process of the present invention, and with the increase of its consumption, and it is bigger to hold viscous force intensity.
2, the selection of transdermal enhancer test:
Take by weighing lappaconitine, method through embodiment 1 adds adhesive, adds the transdermal enhancer of various dose and kind again, adds acrylate pressure sensitive adhesive 80%, mixing, coating, drying cuts, measure drug transdermal absorbing state (the results are shown in accompanying drawing 1), experimental result shows that these three kinds of raw materials of azone, Camphora and oleic acid all can be used as the transdermal enhancer in the paster preparation process of the present invention, and its skin transit dose all can reach requirement.
The comparative experiments of experimental example 3 different percutaneous plaster types
Membrane controlled release type percutaneous drug administration preparation " Gaowujiasu " picking includes protective layer, pressure-sensitive adhesive layer, controlled release layer, drug storehouse storage glue-line and backing layer in the prior art, totally five layers." Gaowujiasu " picking of the present invention is compared with it, and the present invention is simple in structure, and easily with production, the two has essential distinction, and is specific as follows:
The present invention | Prior art | |
Patch type | Glue mixes type | Film controlling type |
Structure | Totally three layers of backing layer, pressure-sensitive adhesive layer, protective layers, simple in structure | Totally five layers of protective layer, pressure-sensitive adhesive layer, controlled release layer, drug storehouse storage glue-line and backing layer, complex structure |
Curative effect | Significantly | More remarkable |
Production equipment | Easily produce, production equipment is simple | Be difficult for producing the production equipment complexity |
Production cycle | Once coating is with short production cycle | Need repeatedly coating, the production cycle is long |
Safety | Safe | Safety is low, release-controlled film easily break (as the Durogesic incident) |
The test of experimental example 4 Transdermal absorption
Lappaconitine transdermal patch of the present invention and prior art film controlling type percutaneous plaster (No. 92100233.5 patents) have been carried out the Transdermal absorption test, the result shows: the Transdermal absorption effect of Lappaconitine transdermal patch of the present invention obviously is better than prior art (seeing accompanying drawing 2), also illustrated when lappaconitine is made the film controlling type percutaneous plaster simultaneously, because molecular weight is relatively large, release-controlled film is relatively poor to the controlled-release effect of paster, and this also is a Lappaconitine transdermal patch Transdermal absorption obvious results reason of the present invention.
Following embodiment all can realize the beneficial effect of experimental example of the present invention.
The specific embodiment
Embodiment 1: " Gaowujiasu " picking
Acrylate pressure sensitive adhesive: 10kg;
Get lappaconitine 0.5kg, add acrylate pressure sensitive adhesive 10kg and Laurel nitrogen
Ketone 1kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology, above-mentioned solution coat on backing layer, is volatilized to solvent, protective layer on the cooling bonnet must " Gaowujiasu " picking.
Embodiment 2: " Gaowujiasu " picking
Lappaconitine: 1kg Mentholum: 0.5kg
Polyisobutylene PSA: 12kg;
Get lappaconitine 1kg, add Polyisobutylene PSA 12kg and Mentholum 0.5kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology, above-mentioned solution coat on backing layer, is volatilized to solvent, protective layer on the cooling bonnet must " Gaowujiasu " picking.
Embodiment 3: " Gaowujiasu " picking
Lappaconitine: 1.5kg Percutaneous absorption enhancer: 1.5kg
Polysiloxanes pressure sensitive adhesive: 8kg;
Get lappaconitine 1.5kg, add polysiloxanes pressure sensitive adhesive 8kg and propylene glycol 1.5kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology, above-mentioned solution coat on backing layer, is volatilized to solvent, protective layer on the cooling bonnet must " Gaowujiasu " picking.
Embodiment 4: " Gaowujiasu " picking
Lappaconitine: 1kg acrylate pressure sensitive adhesive 10kg
Polyoxyethylene fatty acid ester: 44kg;
Get lappaconitine 1kg, add acrylate pressure sensitive adhesive 10kg and polyoxyethylene fatty acid ester 44kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology, above-mentioned solution coat on backing layer, is volatilized to solvent, protective layer on the cooling bonnet must " Gaowujiasu " picking.
Embodiment 5: " Gaowujiasu " picking
Lappaconitine: 0.4kg Polysorbate: 0.2kg
Polysiloxanes pressure sensitive adhesive: 10kg propylene glycol: 20kg;
Get lappaconitine 0.4kg, add polysiloxanes pressure sensitive adhesive 10kg, Polysorbate 0.2kg and propylene glycol 20kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology, above-mentioned solution coat on backing layer, is volatilized to solvent, protective layer on the cooling bonnet must " Gaowujiasu " picking.
Embodiment 6: " Gaowujiasu " picking
Acrylate pressure sensitive adhesive: 2kg kieselguhr: 9kg
Glycerol: 3kg;
Get lappaconitine 0.8kg, add acrylate pressure sensitive adhesive 2kg, Laurel nitrogen
Ketone 0.2kg, kieselguhr 9kg and glycerol 3kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology above-mentioned solution coat on backing layer, volatilize to solvent, protective layer on the cooling bonnet must " Gaowujiasu " picking.
Embodiment 7: " Gaowujiasu " picking
Acrylate pressure sensitive adhesive: 10kg;
Get lappaconitine 1.2kg, add acrylate pressure sensitive adhesive 10kg and Laurel nitrogen
Ketone 0.4kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology above-mentioned solution coat on backing layer, volatilize to solvent, protective layer on the cooling bonnet must " Gaowujiasu " picking.
Embodiment 8: " Gaowujiasu " picking
Lappaconitine: 0.11kg Mentholum: 1.8kg
Polyisobutylene PSA: 14kg;
Get lappaconitine 0.11kg, add Polyisobutylene PSA 14kg and Mentholum 1.8kg, the dissolving mixing is prepared into solution; Adopt curtain coating technology above-mentioned solution coat on backing layer, volatilize to solvent, protective layer on the cooling bonnet must " Gaowujiasu " picking.
Embodiment 9: " Gaowujiasu " picking
Lappaconitine: 1.8kg eucalyptus oil: 0.2kg
Polyisobutylene PSA: 5kg fatty acid Pyrusussuriensis is smooth: 21kg
Zinc oxide: 14kg;
Get lappaconitine 1.8kg, pulverizing adds Polyisobutylene PSA 5kg, eucalyptus oil 0.3kg, the smooth 21kg of fatty acid Pyrusussuriensis and zinc oxide 14kg, mixing and stirring again; Adopt curtain coating technology that said mixture is coated on the backing layer, volatilize to solvent, protective layer on the cooling bonnet, " Gaowujiasu " picking.
Claims (16)
1, a kind of Lappaconitine transdermal patch is formed by three layers, comprises backing layer, drug storehouse layer and protective layer, it is characterized in that the raw material of drug storehouse layer consists of:
Lappaconitine: 0.1-2 weight portion
Percutaneous absorption enhancer: 0.1-2 weight portion
Pressure sensitive adhesive: 5-15 weight portion.
2, Lappaconitine transdermal patch as claimed in claim 1 is formed by three layers, comprises backing layer, drug storehouse layer and protective layer, it is characterized in that the raw material of drug storehouse layer consists of:
Lappaconitine: 0.5 weight portion
Percutaneous absorption enhancer: 1 weight portion
Pressure sensitive adhesive: 10 weight portions.
3, Lappaconitine transdermal patch as claimed in claim 1 is formed by three layers, comprises backing layer, drug storehouse layer and protective layer, it is characterized in that the raw material of drug storehouse layer consists of:
Lappaconitine: 1 weight portion
Percutaneous absorption enhancer: 0.5 weight portion
Pressure sensitive adhesive: 12 weight portions.
4, Lappaconitine transdermal patch as claimed in claim 1 is formed by three layers, comprises backing layer, drug storehouse layer and protective layer, it is characterized in that the raw material of drug storehouse layer consists of:
Lappaconitine: 1.5 weight portions
Percutaneous absorption enhancer: 1.5 weight portions
Pressure sensitive adhesive: 8 weight portions.
5, as the arbitrary described Lappaconitine transdermal patch of claim 1-4, it is characterized in that also adding in the drug storehouse layer raw material cosolvent and/or plasticizer, the amount of cosolvent or plasticizer be the amount of the amount of lappaconitine, Percutaneous absorption enhancer and pressure sensitive adhesive amount total amount 1-5 doubly.
6, Lappaconitine transdermal patch as claimed in claim 5, it is characterized in that also adding in the drug storehouse layer raw material cosolvent and/or plasticizer, the amount of cosolvent or plasticizer is 3 times of total amount of the amount of the amount of the amount of lappaconitine, Percutaneous absorption enhancer and pressure sensitive adhesive.
7, as claim 1-4 or 6 arbitrary described Lappaconitine transdermal patch, it is characterized in that wherein Percutaneous absorption enhancer is meant Laurel nitrogen
In ketone, Mentholum, Borneolum Syntheticum, eucalyptus oil, Fructus Zanthoxyli oil, Oleum Bulbus Allii and Rhizoma Chuanxiong extract, Semen Myristicae extract, propylene glycol, methyl salicylate or the oleic acid one or more; Pressure sensitive adhesive is meant acrylate pressure sensitive adhesive, Polyisobutylene PSA, polysiloxanes pressure sensitive adhesive or thermo-elasto-plasticity rubber.
8, as the arbitrary described Lappaconitine transdermal patch of claim 5, it is characterized in that wherein Percutaneous absorption enhancer is meant Laurel nitrogen
In ketone, Mentholum, Borneolum Syntheticum, eucalyptus oil, Fructus Zanthoxyli oil, Oleum Bulbus Allii and Rhizoma Chuanxiong extract, Semen Myristicae extract, propylene glycol, methyl salicylate or the oleic acid one or more; Pressure sensitive adhesive is meant acrylate pressure sensitive adhesive, Polyisobutylene PSA, polysiloxanes pressure sensitive adhesive or thermo-elasto-plasticity rubber.
9, Lappaconitine transdermal patch as claimed in claim 5 is characterized in that wherein cosolvent is: the fatty acid Pyrusussuriensis is smooth, in polyoxyethylene aliphatic alcohol ether, Polysorbate, fatty glyceride or the polyoxyethylene fatty acid ester one or more are united use; Plasticizer is: one or more in Kaolin, zinc oxide, titanium dioxide, kieselguhr, glycerol or the propylene glycol are united use.
10, Lappaconitine transdermal patch as claimed in claim 6 is characterized in that wherein cosolvent is: the fatty acid Pyrusussuriensis is smooth, in polyoxyethylene aliphatic alcohol ether, Polysorbate, fatty glyceride or the polyoxyethylene fatty acid ester one or more are united use; Plasticizer is: one or more in Kaolin, zinc oxide, titanium dioxide, kieselguhr, glycerol or the propylene glycol are united use.
11, as claim 1-4 or 6 or the preparation method of the arbitrary described Lappaconitine transdermal patch of 8-10, it is characterized in that this method is:
Get the raw material mixing and stirring of drug storehouse layer; Adopt curtain coating technology that said mixture is coated on the backing layer to solvent and volatilize, protective layer on the cooling bonnet, Lappaconitine transdermal patch; Or said mixture is coated on the backing layer, protective layer on the cooling bonnet, Lappaconitine transdermal patch.
12, the preparation method of Lappaconitine transdermal patch as claimed in claim 5 is characterized in that this method is:
Get the raw material mixing and stirring of drug storehouse layer; Adopt curtain coating technology that said mixture is coated on the backing layer to solvent and volatilize, protective layer on the cooling bonnet, Lappaconitine transdermal patch; Or said mixture is coated on the backing layer, protective layer on the cooling bonnet, Lappaconitine transdermal patch.
13, the preparation method of Lappaconitine transdermal patch as claimed in claim 7 is characterized in that this method is:
Get the raw material mixing and stirring of drug storehouse layer; Adopt curtain coating technology that said mixture is coated on the backing layer to solvent and volatilize, protective layer on the cooling bonnet, Lappaconitine transdermal patch; Or said mixture is coated on the backing layer, protective layer on the cooling bonnet, Lappaconitine transdermal patch.
14, as claim 1-4 6 or the arbitrary described percutaneous plaster of 8-10 have application in the medicine of anti-inflammatory and analgesic effect in preparation.
15, percutaneous plaster as claimed in claim 5 has application in the medicine of anti-inflammatory and analgesic effect in preparation.
16, percutaneous plaster as claimed in claim 7 has application in the medicine of anti-inflammatory and analgesic effect in preparation.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNA2009101189289A CN101574331A (en) | 2009-01-08 | 2009-03-06 | Lappaconitine transdermal patch and preparation method thereof |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN200910076270 | 2009-01-08 | ||
CN200910076270.X | 2009-01-08 | ||
CNA2009101189289A CN101574331A (en) | 2009-01-08 | 2009-03-06 | Lappaconitine transdermal patch and preparation method thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
CN101574331A true CN101574331A (en) | 2009-11-11 |
Family
ID=41269498
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNA2009101189289A Pending CN101574331A (en) | 2009-01-08 | 2009-03-06 | Lappaconitine transdermal patch and preparation method thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN101574331A (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102178658A (en) * | 2011-05-03 | 2011-09-14 | 中国人民解放军第三军医大学第二附属医院 | Lappaconitine hydrobromide orally disintegrating tablets and preparation method thereof |
CN108543076A (en) * | 2018-07-13 | 2018-09-18 | 邛崃市医疗中心医院 | Prevent the external medicine preparation of rheumatoid arthritis |
CN112007592A (en) * | 2020-09-03 | 2020-12-01 | 中科芯云微电子科技有限公司 | Acid colloid for eliminating photoetching layout and protecting intellectual property of integrated circuit and application thereof |
-
2009
- 2009-03-06 CN CNA2009101189289A patent/CN101574331A/en active Pending
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102178658A (en) * | 2011-05-03 | 2011-09-14 | 中国人民解放军第三军医大学第二附属医院 | Lappaconitine hydrobromide orally disintegrating tablets and preparation method thereof |
CN102178658B (en) * | 2011-05-03 | 2013-04-10 | 中国人民解放军第三军医大学第二附属医院 | Lappaconitine hydrobromide orally disintegrating tablets and preparation method thereof |
CN108543076A (en) * | 2018-07-13 | 2018-09-18 | 邛崃市医疗中心医院 | Prevent the external medicine preparation of rheumatoid arthritis |
CN112007592A (en) * | 2020-09-03 | 2020-12-01 | 中科芯云微电子科技有限公司 | Acid colloid for eliminating photoetching layout and protecting intellectual property of integrated circuit and application thereof |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN102284012B (en) | A kind of gel patch containing curcumin and bletilla striata gum and preparation method thereof | |
Shu et al. | Polyvinylpyrrolidone microneedles for localized delivery of sinomenine hydrochloride: preparation, release behavior of in vitro & in vivo, and penetration mechanism | |
CN101932305A (en) | Transcutaneous pharmaceutical compositions containing a steroid hormone | |
Yuniarsih et al. | Evaluation of Wound‐Healing Activity of Hydrogel Extract of Sansevieria trifasciata Leaves (Asparagaceae) | |
CN106620445B (en) | Skin-care microemulsion gel and preparation method thereof | |
CZ2015272A3 (en) | Polymeric film containing photosensitizers and use thereof | |
CN101574331A (en) | Lappaconitine transdermal patch and preparation method thereof | |
CN101518531B (en) | Analgesic anti-inflammatory composite medicament and method for preparing same | |
CN102133175B (en) | Amygdalin gel and preparation method and medicinal application thereof | |
CN107456386A (en) | The acupuncture needle of a kind of anti-inflammatory analgesic and can packing type field operation quick needle insertion device | |
CN101669986A (en) | Compound gel preparation containing sophora alopecuroide oil | |
CN101618030B (en) | Triptolide transdermal patch and preparation method thereof | |
CN112891325A (en) | Preparation and application of ketorolac patch | |
CN101703492B (en) | Tetrahydropalmatine transdermal patch and preparation method thereof | |
WO2014199455A1 (en) | Percutaneous absorption type patch memantine preparation | |
CN105797100B (en) | Pressure-sensitive sticker of promoting blood circulation and stopping pain and preparation method thereof | |
CN101623286B (en) | Transdermal administration composite containing cucurbitacin-type active ingredient | |
CN102940684A (en) | Traditional Chinese medicine composition containing illicium henryi and preparation method thereof | |
CN114588108A (en) | Oil-soluble solution containing insect-resistant agent and preparation method and application thereof | |
CN111298075B (en) | Traditional Chinese medicine composition and preparation method and application thereof | |
CN101904831B (en) | Application of alkannin and compositions thereof | |
CN101417019A (en) | External medicine composition with anti-inflammation, detumescence and pain-easing function | |
CN101485645B (en) | Elemene transdermal agent and preparation method thereof | |
CN103054879B (en) | Norethisterone acetate-containing compound estradiol transdermal sustained release preparation and preparation method thereof | |
CN104274494A (en) | America periplaneta external preparation and preparation method thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C12 | Rejection of a patent application after its publication | ||
RJ01 | Rejection of invention patent application after publication |
Open date: 20091111 |