CN1628634A - Hydrophilic biological sticking gel pasting agent and preparation technique thereof - Google Patents
Hydrophilic biological sticking gel pasting agent and preparation technique thereof Download PDFInfo
- Publication number
- CN1628634A CN1628634A CN 200410040593 CN200410040593A CN1628634A CN 1628634 A CN1628634 A CN 1628634A CN 200410040593 CN200410040593 CN 200410040593 CN 200410040593 A CN200410040593 A CN 200410040593A CN 1628634 A CN1628634 A CN 1628634A
- Authority
- CN
- China
- Prior art keywords
- gel
- polyacrylic acid
- patch
- sodium
- linking agent
- 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.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 238000000034 method Methods 0.000 title claims abstract description 7
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 27
- 150000004676 glycans Chemical class 0.000 claims abstract description 25
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 25
- 239000005017 polysaccharide Substances 0.000 claims abstract description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 claims abstract description 17
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 claims abstract description 17
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 14
- 229920001184 polypeptide Polymers 0.000 claims abstract description 5
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 5
- 239000000499 gel Substances 0.000 claims description 139
- 229920002125 Sokalan® Polymers 0.000 claims description 51
- 239000004584 polyacrylic acid Substances 0.000 claims description 51
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 42
- 239000003814 drug Substances 0.000 claims description 42
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 41
- 239000011734 sodium Substances 0.000 claims description 41
- 229910052708 sodium Inorganic materials 0.000 claims description 41
- 239000003431 cross linking reagent Substances 0.000 claims description 38
- -1 is that 10-90 Substances 0.000 claims description 35
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 30
- 239000000758 substrate Substances 0.000 claims description 29
- 239000000227 bioadhesive Substances 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 23
- 108010010803 Gelatin Proteins 0.000 claims description 20
- 239000008273 gelatin Substances 0.000 claims description 20
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- 235000019322 gelatine Nutrition 0.000 claims description 20
- 235000011852 gelatine desserts Nutrition 0.000 claims description 20
- 239000000284 extract Substances 0.000 claims description 16
- 238000003756 stirring Methods 0.000 claims description 16
- 235000010603 pastilles Nutrition 0.000 claims description 15
- NOOLISFMXDJSKH-UHFFFAOYSA-N p-menthan-3-ol Chemical compound CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 14
- 230000008961 swelling Effects 0.000 claims description 14
- 229920006037 cross link polymer Polymers 0.000 claims description 13
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 claims description 12
- 239000000654 additive Substances 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 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 11
- 230000000996 additive effect Effects 0.000 claims description 11
- 239000000463 material Substances 0.000 claims description 11
- 230000000149 penetrating effect Effects 0.000 claims description 11
- 239000002904 solvent Substances 0.000 claims description 11
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 claims description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 10
- 239000010238 camphora Substances 0.000 claims description 10
- 229940025250 camphora Drugs 0.000 claims description 10
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical group COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 claims description 10
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- 239000002253 acid Substances 0.000 claims description 9
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- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 claims description 8
- 229960000991 ketoprofen Drugs 0.000 claims description 8
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 7
- LRWZZZWJMFNZIK-UHFFFAOYSA-N 2-chloro-3-methyloxirane Chemical compound CC1OC1Cl LRWZZZWJMFNZIK-UHFFFAOYSA-N 0.000 claims description 7
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 7
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 7
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- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 7
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- 235000010417 guar gum Nutrition 0.000 claims description 6
- 239000000665 guar gum Substances 0.000 claims description 6
- 229960002154 guar gum Drugs 0.000 claims description 6
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 claims description 6
- 229920001285 xanthan gum Polymers 0.000 claims description 6
- WEEGYLXZBRQIMU-UHFFFAOYSA-N 1,8-cineole Natural products C1CC2CCC1(C)OC2(C)C WEEGYLXZBRQIMU-UHFFFAOYSA-N 0.000 claims description 5
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 5
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 claims description 5
- 229920001817 Agar Polymers 0.000 claims description 5
- 239000004342 Benzoyl peroxide Substances 0.000 claims description 5
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims description 5
- 229920001661 Chitosan Polymers 0.000 claims description 5
- 102000008186 Collagen Human genes 0.000 claims description 5
- 108010035532 Collagen Proteins 0.000 claims description 5
- WEEGYLXZBRQIMU-WAAGHKOSSA-N Eucalyptol Chemical compound C1C[C@H]2CC[C@]1(C)OC2(C)C WEEGYLXZBRQIMU-WAAGHKOSSA-N 0.000 claims description 5
- 239000008272 agar Substances 0.000 claims description 5
- 235000010419 agar Nutrition 0.000 claims description 5
- 235000019400 benzoyl peroxide Nutrition 0.000 claims description 5
- 229960005233 cineole Drugs 0.000 claims description 5
- 239000006185 dispersion Substances 0.000 claims description 5
- 229960001047 methyl salicylate Drugs 0.000 claims description 5
- 239000004302 potassium sorbate Substances 0.000 claims description 5
- 235000010241 potassium sorbate Nutrition 0.000 claims description 5
- 229940069338 potassium sorbate Drugs 0.000 claims description 5
- 235000010413 sodium alginate Nutrition 0.000 claims description 5
- 239000000661 sodium alginate Substances 0.000 claims description 5
- 229940005550 sodium alginate Drugs 0.000 claims description 5
- 241000717739 Boswellia sacra Species 0.000 claims description 4
- 239000004863 Frankincense Substances 0.000 claims description 4
- 241001057584 Myrrha Species 0.000 claims description 4
- 230000002421 anti-septic effect Effects 0.000 claims description 4
- 229910021538 borax Inorganic materials 0.000 claims description 4
- 238000007796 conventional method Methods 0.000 claims description 4
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- 239000000049 pigment Substances 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 235000010339 sodium tetraborate Nutrition 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 claims description 4
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- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims description 3
- PPKXEPBICJTCRU-XMZRARIVSA-N (R,R)-tramadol hydrochloride Chemical compound Cl.COC1=CC=CC([C@]2(O)[C@H](CCCC2)CN(C)C)=C1 PPKXEPBICJTCRU-XMZRARIVSA-N 0.000 claims description 3
- LVYLCBNXHHHPSB-UHFFFAOYSA-N 2-hydroxyethyl salicylate Chemical compound OCCOC(=O)C1=CC=CC=C1O LVYLCBNXHHHPSB-UHFFFAOYSA-N 0.000 claims description 3
- RLFWWDJHLFCNIJ-UHFFFAOYSA-N Aminoantipyrine Natural products CN1C(C)=C(N)C(=O)N1C1=CC=CC=C1 RLFWWDJHLFCNIJ-UHFFFAOYSA-N 0.000 claims description 3
- RMMXTBMQSGEXHJ-UHFFFAOYSA-N Aminophenazone Chemical compound O=C1C(N(C)C)=C(C)N(C)N1C1=CC=CC=C1 RMMXTBMQSGEXHJ-UHFFFAOYSA-N 0.000 claims description 3
- 241000416162 Astragalus gummifer Species 0.000 claims description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical class [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- 229920000742 Cotton Polymers 0.000 claims description 3
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 3
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 claims description 3
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- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 3
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- HDERJYVLTPVNRI-UHFFFAOYSA-N ethene;ethenyl acetate Chemical group C=C.CC(=O)OC=C HDERJYVLTPVNRI-UHFFFAOYSA-N 0.000 description 2
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 2
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 2
- 239000010642 eucalyptus oil Substances 0.000 description 2
- 229940044949 eucalyptus oil Drugs 0.000 description 2
- IVLVTNPOHDFFCJ-UHFFFAOYSA-N fentanyl citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 IVLVTNPOHDFFCJ-UHFFFAOYSA-N 0.000 description 2
- 238000001879 gelation Methods 0.000 description 2
- 229940089161 ginsenoside Drugs 0.000 description 2
- 229930182494 ginsenoside Natural products 0.000 description 2
- 235000003642 hunger Nutrition 0.000 description 2
- 238000009413 insulation Methods 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- 230000002045 lasting effect Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 2
- 239000000347 magnesium hydroxide Substances 0.000 description 2
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 2
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000011505 plaster Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 2
- 229960003415 propylparaben Drugs 0.000 description 2
- SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical compound OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 239000000341 volatile oil Substances 0.000 description 2
- 238000003809 water extraction Methods 0.000 description 2
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241001489978 Eupolyphaga Species 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 239000004368 Modified starch Substances 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000035587 bioadhesion Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000000413 hydrolysate Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- WABPQHHGFIMREM-UHFFFAOYSA-N lead(0) Chemical compound [Pb] WABPQHHGFIMREM-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- BHTJEPVNHUUIPV-UHFFFAOYSA-N pentanedial;hydrate Chemical compound O.O=CCCCC=O BHTJEPVNHUUIPV-UHFFFAOYSA-N 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 230000036548 skin texture Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention discloses a hydrophilic biological sticking gel pasting agent and preparation technique thereof, wherein the agent is a medical biological material crosslinked from water-based biological polysaccharides, macromolecular polypeptides and skeleton type high molecular polymer sodium polyacrylate, the agent has biological adherence, biological compatibility, flexibility and cohesion.
Description
Technical field: the present invention relates to hydrophilic bioadhesive gel patch and preparation technology thereof, particularly medicine bioengineering new material and medicine percutaneous dosing novel form belong to the technical field of pharmaceutical preparation.
Background technology: patch is a kind of ancient and effective dosage form.By black plaster rubber cream, cataplasma extremely afterwards the earliest, technical development is constantly progressive.Because its determined curative effect, blood drug level is stable, is convenient to long term administration, and no liver first-pass effect and gastrointestinal tract zest are less to body injury, and more and more is subjected to patient's welcome.Yet because its defective has separately limited their development again.Easily be sticky with medicated clothing as black plaster, medicament active composition easily loses, the Plumbum preparatium accumulate poisoning; And the abietic resin in the rubber cream is big to skin irritation, and drug loading is few, and a large amount of easily volatilizations cause environmental pollution; Cataplasma can't keep the water content and the viscosity of substrate lastingly owing to be the simple mixing of water-soluble high-molecular material, and long-term shelf-stability is poor.Therefore, the development of adhesive substrate materials seems particularly important.
The patent of the hydrophilic high molecular material patch of having announced so far roughly is divided into three major types.
One class is to be the combination of skeleton with polyvinyl alcohol (PVA), adds modified starch as thickening agent more, cooperates binding agents such as vinyl acetate-ethylene copolymerization ester, adds penetrating agent such as azone and propylene glycol, ethanol, water equal solvent and mixes.This patch substrate does not pass through sufficient grafting and bonding, does not form network structure, use and storage in easy dry and lose viscosity.
One class is medicine directly to be added in the pressure sensitive adhesive that unsaturated carboxylic ester multiple copolymers such as vinyl acetate-ethylene make, adding the direct coating filmforms of composition such as penetrating agent again cuts and forms, its shortcoming is that the pharmaceutical pack capacitive is little, only be suitable for containing the patch of trace drug, and ionic medicine can destroy the structure of pressure sensitive adhesive and cause it to lose viscosity.
The another kind of patch that is commonly referred to as cataplasma, its substrate is generally that sodium polyacrylate, carboxymethyl cellulose, polyvinyl alcohol, polyvinylpyrrolidone, gelatin etc. add potter's clay after once crosslinked again, Kaolin is made, its shortcoming is that water content is little, biocompatibility and viscosity are all undesirable, and storage ability is poor.
Summary of the invention: the object of the present invention is to provide a kind of hydrophilic bioadhesive gel patch and preparation technology.The shortcoming of this patch substrate abandoning tradition patch substrate realizes the superiority of percutaneous dosing, be a kind of non-stimulated, do not have allergy, slow release long-acting, lasting adhere to, use comfortable, stick convenience, stable in properties, patch substrate of new generation with wide application prospect.
The present invention constitutes like this: hydrophilic bioadhesive gel patch, and it is made of backing layer, pastille high-molecular gel casing play and sealing coat, and pastille high-molecular gel casing play is made of substrate, active medicine and additive; Substrate is prepared into polyacrylic acid sodium gel, polysaccharide gel, peptide-based gel and multiple crosslinking agent, calculates in pastille high-molecular gel casing play the polyacrylic acid sodium gel according to components by weight percent and accounts for 10-90, polysaccharide gel and account for 1-30, peptide-based gel and account for that 5-50, multiple crosslinking agent account for 0.1-10, active medicine accounts for the 1-20 additive and accounts for 2-20.The polyacrylic acid sodium gel is that the polyacrylic acid of different molecular weight, sodium polyacrylate and polyacrylic acid crosslinked polymer are formulated in solvent according to a conventional method: in glycerol, propylene glycol, ethanol or the water, allotment is made.Wherein polyacrylic acid crosslinked polymer is polymethylacrylic acid, polyacrylate, poly-alkyl sucrose with polyacrylic acid crosslinked polymer, gathers one or more the mixture in alkyl tetramethylolmethane and polyacrylic acid crosslinked polymer, polymethacrylates, poly-methyl acrylate and the copolymer between them.Low-molecular polypropylene acid sodium molecule amount is 2.0 * 10
5～6.0 * 10
7Between, the high molecular weight sodium polyacrylate molecular weight is 1.0 * 10
8～5.0 * 10
10Between, calculate according to components by weight percent: low-molecular-weight sodium polyacrylate accounts for 5-45, high molecular weight sodium polyacrylate accounts for 5-45.
Active medicine is methyl salicylate, salicylic acid ethylene glycol, Mentholum, Camphora, Borneolum Syntheticum, diclofenac sodium, diclofenac ethylenediamine salt, ibuprofen, ketoprofen, piroxicam, fenbufen, indomethacin, tramadol hydrochloride, dipyrone, aminophenazone, fentanyl, Chinese medicine extract among the present invention.Preferred active medicine is: the extract of ketoprofen, diclofenac ethylenediamine-salt, Mentholum, Camphora, Borneolum Syntheticum and Flos Carthami, Sanguis Draxonis, Rhizoma Chuanxiong, Cortex Cinnamomi, Flos Caryophylli, Olibanum, Herba Asari, Myrrha, Radix Aconiti, Radix Aconiti Kusnezoffii.Polysaccharide among the present invention in the polysaccharide gel is chitosan, agar, sodium alginate, xanthan gum, Tragacanth, arabic gum, guar gum, SKGM, pectin according to conventional method and solvent: the gel that water, ethanol form; Polypeptide is gelatin, osseocolla, collagen protein and macromole aminoacid in the peptide-based gel.In substrate, its components by weight percent ratio of the polysaccharide gel of use and peptide-based gel is: polysaccharide gel: peptide-based gel=0.2～0.8: 1～1.2.Additive in the substrate is the transdermal penetrating agent: dimethyl sulfoxide, azone and derivant thereof, cithrol class, carbamide, squalane and derivant thereof; And natural percutaneous penetrating agent: Mentholum, Camphora, menthol, oleic acid, camphor oil, eucalyptol, Borneolum Syntheticum; Can also be drug solvent: glycerol, propylene glycol, ethanol, ethylene glycol, n-butyl alcohol; Also can be antiseptic: parabens, benzoate, potassium sorbate; Or other essence, pigment.
Its preparation technology: substrate preparation technology is made up of precrosslink, medicine dispersion, the ter procedure of reestablishing diplomatic relations, and at first, mixes the polyacrylic acid sodium gel that swelling is good under 30 ℃～70 ℃, and adding just, cross-linking agent carries out the precrosslink reaction; Secondly polysaccharide gel, peptide-based gel, active medicine and other additive are added mixing in the material of precrosslink under stirring state; Add the reestablish diplomatic relations connection reaction of last cross-linking agent at last, promptly make bioadhesive gel, it is evenly coated on the backing that non-woven fabrics, chemical fiber cloth or cotton make, cover to go up the sealing coat that polyurethane, polyester, polyethylene, polypropylene, silicone oil paper or aluminium foil and mutual complex thereof are made again, through cutting, molding and curing promptly.The first cross-linking agent that uses in the preparation process is metallic aluminium, magnesium, ferrum, silicon, the various inorganic salts of calcium, oxide, hydroxide; The end cross-linking agent is boric acid, sodium borate, benzoyl peroxide, epoxychloropropane, the organic aldehyde of carbon number below 10.Just the consumption of cross-linking agent is the 0.05%-5% of composition by weight, and last dosage of crosslinking agent is 0.05%-5%, and just cross-linking agent is used for precrosslink, and the last cross-linking agent connection that is used to reestablish diplomatic relations carries out in two steps, plays the composite crosslinking solidification jointly.
Further explain:
1, hydrophilic bioadhesive gel patch structure
This hydrophilic bioadhesive gel patch comprises backing layer, pastille high-molecular gel casing play, sealing coat three parts composition.
2, hydrophilic bioadhesive gel patch substrate prescription:
The pastille high-molecular gel casing play of this patch is that polyacrylic acid sodium gel, polysaccharide gel, peptide-based gel, pharmaceutical compositions and the additive cross-linking polymerization under the multiple crosslinking agent effect by possess hydrophilic property forms, and its prescription is as follows:
| Form | Components by weight percent |
| Low molecule (S) polyacrylic acid sodium gel | ????5-45 |
| Macromolecule (H) polyacrylic acid sodium gel | ????5-45 |
| Polysaccharide gel | ????1-30 |
| Peptide-based gel | ????5-50 |
| First cross-linking agent | ????0.05-5 |
| The end cross-linking agent | ????0.05-5 |
| Pharmaceutical compositions | ????1-20 |
| Penetrating agent | ????1-10 |
| Solvent | ????1-10 |
3, hydrophilic bioadhesive gel patch dispensing information
1. the acid of the low-molecular polypropylene in matrix formulations sodium gel is to add suitable moisture content swelling by dispersions such as sodium polyacrylate and suitable solvent such as glycerol, propylene glycol back to form, and low-molecular polypropylene acid sodium molecule amount is 2.0 * 10
5～6.0 * 10
7Between.The macromolecule polyacrylic acid sodium gel is to be formed by polyacrylic acid crosslinked polymer and suitable solvent such as dispersion swellings such as ethanol, water, it is polymethylacrylic acid, polyacrylate, poly-alkyl sucrose and polyacrylic acid crosslinked polymer, poly-alkyl tetramethylolmethane and polyacrylic acid crosslinked polymer, polymethacrylates, poly-methyl acrylate and the copolymer between them that polyacrylic acid closes linked polymer, from wherein selecting one or more, molecular weight is 1.0 * 10
8～5.0 * 10
10Between.The low-molecular polypropylene acid sodium degree of cross linking is lower, so its gel has good thixotropy and adhesiveness; And the high-molecular weight sodium polyacrylate degree of cross linking is higher, so very strong viscoelasticity and interior plasticity are arranged.Suitably the allotment of the low-molecular-weight of proportioning and high molecular can make the gel that makes that suitable gelation and cohesiveness are arranged, usually preferred weight component ratio is low-molecular-weight: high molecular=0.8-3: between 1, and polypropylene acid sodium gel accounts for 30～80% of substrate total amount and is advisable.
2. the polysaccharide gel in the matrix formulations can be the gel that chitosan, agar, sodium alginate, xanthan gum, Tragacanth, arabic gum, guar gum, SKGM and pectin and suitable solvent form, wherein preferred arabic gum, xanthan gum, guar gum.Can form interior hydrogen bond with carboxyl and the amido in the polyacrylic acid sodium gel because of it contains abundant hydroxyl, make substrate that good cohesiveness be arranged, make the medicine and the moisture content micromolecule that are contained in the macromolecular skeleton grid be difficult for dissipation.They still are good emulsifying agent and thickening agent simultaneously; Arabic glue as 1% just can make the Emulsion of generation highly stable; play the effect of 5%～8% conventional surfactant; when forming o/w Emulsion; the arabic gum hydrate molecule forms the absorption gel layer around each oil droplet; gel layer makes whole oil droplet all protected and be fixed on original position and reach the emulsifying thickening power because charge polarity repels mutually.
3. the peptide-based gel in the matrix formulations can be gelatin, osseocolla, collagen protein and macromole aminoacid, gelatin generally commonly used.Gelatin is the hydrolysate of collagen protein, during the molecule hydrolysis of collagen protein, triple helix shape peptide chain is taken apart mutually, and fracture is in various degree arranged, form the three-dimensional dispersed structure of coiled coil when it disperses in G ﹠ W, the polysaccharide gel that add this moment mutually combines with gelatin under cross-linking agent and hydrogen bond action, forms three-dimensional network structure, the molecular motion of gelatin is restricted, thereby viscoelasticity increases.But uncrosslinked " the glycopeptide chain " of the part of clamping therebetween then has good gelation, and be similar to skin texture, thus bonding with part skin under the effect of body temperature when sticking, so good biocompatibility is arranged.In general, when the polysaccharide gel ratio is higher, form more interior hydrogen bond in the substrate, gel elastomer and cohesiveness are good, viscosity is poor; When the peptide-based gel ratio was higher, the interior hydrogen bond that forms in the substrate was less and many with skin glycoprotein hydrogen bond action, so substrate has good viscosity, but cohesiveness is poor.So regulate the ratio of polysaccharide gel and peptide-based gel, substrate can have viscosity and cohesiveness preferably simultaneously.General ratio is: polysaccharide gel: peptide-based gel=0.2～0.8: 1～1.2 is advisable.
4. the multiple crosslinking agent in the matrix formulations comprises just cross-linking agent and last cross-linking agent, and first cross-linking agent is metallic aluminium, magnesium, ferrum, silicon, the various inorganic salts of calcium, oxide, hydroxide; The end cross-linking agent is boric acid, sodium borate, benzoyl peroxide, epoxychloropropane, the organic aldehyde of carbon number below 10.Just dosage of crosslinking agent is 0.05%-5%, and last dosage of crosslinking agent is 0.05%-5%, and just cross-linking agent is used for precrosslink, and the last cross-linking agent connection that is used to reestablish diplomatic relations carries out in two steps.Two step cross-linking reactions had both guaranteed medicine homodisperse when just crosslinked, were filled in the macromolecular skeleton, increased the denseness of substrate; Substrate and cross-linking agent react completely when having guaranteed to reestablish diplomatic relations connection again, increase gel elastomer and cohesiveness, and the ability of bound water significantly strengthens, and makes the patch that makes that good viscosity, cohesiveness, moisture retention, slow release effect be arranged, and quality keeps stable for a long time.
5. the active medicine in the matrix formulations can be a methyl salicylate, salicylic acid ethylene glycol, Mentholum, Camphora, Borneolum Syntheticum, diclofenac sodium, diclofenac ethylenediamine salt, piroxicam, ibuprofen, ketoprofen, fenbufen, tramadol hydrochloride, indomethacin, dipyrone, aminophenazone, fentanyl, Flos Carthami, Sanguis Draxonis, Rhizoma Chuanxiong, Cortex Cinnamomi, Flos Caryophylli, Olibanum, Herba Asari, Myrrha, Radix Aconiti, Radix Aconiti Kusnezoffii and other plant extract.Wherein preferred ketoprofen, diclofenac ethylenediamine salt, Mentholum, Borneolum Syntheticum and Chinese medicine extract.
6. the additive composition in the matrix formulations can be the transdermal penetrating agent, as: dimethyl sulfoxide, azone and derivant thereof, cithrol class, carbamide, squalane and derivant thereof; And natural percutaneous penetrating agent, as: Mentholum, Camphora, menthol, camphor oil, oleic acid, eucalyptol, Borneolum Syntheticum.Penetrating agent is selected according to the character that adds medicine: preferred azone of western medicine composition and oleic acid, preferred Mentholum of Chinese medicine extract and eucalyptol.Its consumption azone is suitably 1%-4%, and should with the glycerol adapted; Oleic acid is suitably 3%-8%, and should with the propylene glycol adapted; Mentholum and eucalyptol are suitably 1%-3%.
7. other additive in the matrix formulations can be drug solvent, as: glycerol, propylene glycol, ethanol, ethylene glycol, n-butyl alcohol etc.; Can be antiseptic, as: parabens, benzoate, potassium sorbate etc.; Also have other essence, pigment etc.
8. the backing layer of patch can be non-woven fabrics, and chemical fiber cloth, cotton, sealing coat are polyurethane, polyester, polyethylene, polypropylene, silicone oil paper, aluminium foil and mutual complex thereof.
4, hydrophilic bioadhesive gel patch preparation method of the present invention
1. gel is first crosslinked:
With the polyacrylic acid sodium gel that swelling is good, add the aqueous solution mixing of cross-linking agent just, 30 ℃～70 ℃ lasting stirring reactions 30～120 minutes add polysaccharide gel, peptide-based gel, mix homogeneously therebetween respectively.
2. medicine disperses and coats:
With behind the dissolution with solvents active pharmaceutical ingredients, in the gelinite in the adding 1., kept the equality of temperature stirring reaction 5～30 minutes earlier, medicine is dispersed in the gel.
3. the connection of reestablishing diplomatic relations of gel;
In the drug gel body that has made in 2., behind the additives such as adding penetrating agent, antiseptic, essence, pigment, the aqueous solution adding with last cross-linking agent is warming up to 50 ℃～70 ℃, and stirring reaction promptly got gel-type vehicle in 10～40 minutes.
4. patch preparation
3. the gel-type vehicle that makes in is coated on the backing while hot, covers isolating membrane, cut, pack, solidify promptly.
5, hydrophilic bioadhesive gel patch preparation process process conditions
1. temperature is controlled between 30 ℃～70 ℃, 40 ℃～60 ℃ of optimum ranges.Temperature is too high, reacts too fast, the crosslinking degree height; Temperature is low excessively, reacts slower, is difficult for machine-shaping.
2. must stir in the course of reaction, so need suitable mixing speed, strong excessively mechanical shear stress has bigger destruction to plasticity in the colloid.
3. production process needs to carry out in the clean environment more than 300,000 grades, and backing and sealing coat need be done can use after the aseptic process, and be contaminated to guarantee that substrate is difficult for.
The main difference of the present invention and prior art is:
1, matrix structure adopts is that carboxylic acid metal's salt and polysaccharide are closed in the poly-insatiable hunger of straight chain macromole, the polypeptides matter ternary is crosslinked, makes its structure to skin more similar, thereby has better biocompatibility.
2, the precrosslink of the present invention's employing and two step of the connection cross-linking methods of reestablishing diplomatic relations, wherein precrosslink guarantees that polymeric matrix has suitable viscosity and thixotropy, and the connection of reestablishing diplomatic relations can strengthen the viscosity and the cohesiveness of substrate, and water retaining capacity is strengthened, and drug release is stablized.
3, the present invention closes the combination of the suitable proportioning of carboxylate with the poly-insatiable hunger of different molecular weight, has improved the autohesion, cohesiveness of product, anti-physical and chemical performance such as ionic, makes that the adaptability to the embedding of heterogeneity medicine strengthens greatly.
Hydrophilic bioadhesive gel patch of the present invention is to be the gel skeleton material with combined sodium polyacrylate of different molecular weight and polyacrylic acid crosslinked polymer, owing to contain a large amount of carboxylic groups and bonding sodium ion in the sodium polyacrylate polymer architecture, therefore behind hydration, carboxylic ionsization, form center of positive charge and center of negative charge widely in polymer inside, because repulsive interaction between electric charge, impel sodium polyacrylate granule swelling, add that polyacrylic acid crosslinked polymer contains abundant carbonyl, hydroxyl, hydrophilic radicals such as amido, therefore with aqueous dispersion after, under the effect of first cross-linking agent, form an expansible three-dimensional netted gel rubber system of Ionized internally crosslinked very big limit.Polysaccharide gel that add this moment and the glycopeptide chain in the peptide-based gel in water fully swelling unfold, be easy under external force be dispersed in the netted gelinite of sodium polyacrylate, enrich on the sugar chain enrich on hydroxyl and the peptide chain peptide bond easier with sodium polyacrylate in a large amount of carboxyls form " interior hydrogen chain ", make polymer gel that extraordinary elasticity and pliability be arranged.Under the solution pervasion effect of solvent, be well-dispersed in the small molecule active medicine in the high molecular back bone network structure, again under last cross-linking agent effect, make the further cross-linking reaction of medicine-containing gel body generate macromole, the patch that makes at last just has suitable adhesiveness, cohesiveness and release effect.During with contact skin, owing to wherein contain polypeptides matter, the structural similarity with skin has excellent biological compatibility, can reach bioadhesion effect preferably.So this patch substrate can be used as bioadhesive material, slow controlled-release material and framework material, be widely used in the researching and producing of medicine and cosmetics, reached the purpose of inventing; Product has become one of medicine bioengineering new material and medicine patch developing direction.
The specific embodiment:
Embodiments of the invention 1
| Component | Components by weight percent |
| Low molecule (S) polyacrylic acid sodium gel (M=3 * 10 5) | ????5 |
| Macromolecule (H) polyacrylic acid sodium gel (M=3 * 10 9) | ????45 |
| The guar gum gel | ????20.5 |
| The gelatin glycerogel | ????16 |
| Six hydration aluminum chlorides | ????0.3 |
| Benzoyl peroxide | ????0.2 |
| Ketoprofen | ????3 |
| Oleum menthae | ????3 |
| Glycerol | ????2 |
| Nipagin ester propylene glycol liquid | ????1 |
| Purified water | ????4 |
Preparation:
1. with swelling is good S, H polyacrylic acid sodium gel mix homogeneously, get six hydration aluminum chloride aqueous solutions and add wherein, be warming up to 40 ℃, stirred 30 minutes, add guar gum, gelatin glycerogel, insulated and stirred 30 minutes.
2. stir evenly in the gel in adding glycerol, Oleum menthae, ketoprofen dissolving back 1., be warming up to 45 ℃, reacted 30 minutes.
3. in the pastille colloid in adding nipalgin propylene glycol liquid 2., add benzoyl peroxide liquid again after, be warming up to 50 ℃ of reactions 30 minutes, coating is while hot cut and is got final product.
Embodiments of the invention 2
| Component | Components by weight percent |
| Low molecule (S) polyacrylic acid sodium gel (M=6 * 10 5) | ????45 |
| Macromolecule (H) polyacrylic acid sodium gel (M=1 * 10 10) | ????5 |
| The Radix astragali glue | ????9.5 |
| The gelatin glycerogel | ????5 |
| Aluminium-magnesium silicate | ????0.2 |
| Epoxychloropropane | ????0.3 |
| The Chinese medicine fluid extract | ????20 |
| Oleic acid | ????4 |
| Propylene glycol | ????4 |
| Ethyl hydroxybenzoate | ????1 |
| Purified water | ????4 |
Preparation:
1. get each 20g such as Radix Aconiti, Radix Aconiti Kusnezoffii, Cortex Cinnamomi, Rhizoma Zingiberis Recens, Flos Carthami, Rhizoma Chuanxiong, Olibanum, Myrrha and be ground into coarse powder, extract twice with 70% reflow of alcohol, merge extractive liquid,, concentrating under reduced pressure become fluid extract (density is 1.05～1.15).
2. with swelling is good S, H polyacrylic acid sodium gel mix homogeneously, get the aluminium-magnesium silicate aqueous solution and add wherein, be warming up to 30 ℃, stirred 30 minutes, add Radix astragali glue, gelatin glycerogel, insulated and stirred 30 minutes.
3. with 1. stirring evenly behind middle fluid extract and propylene glycol, the oleic acid mixed solvent, stir evenly in the gel in the adding 2., be warming up to 45 ℃, reacted 30 minutes.
4. in the pastille colloid in adding ethyl hydroxybenzoate liquid 3., add epoxychloropropane liquid again after, be warming up to 50 ℃ of reactions 30 minutes, coating is while hot cut and is got final product.
Embodiments of the invention 3
| Component | Components by weight percent |
| Low molecule (S) polyacrylic acid sodium gel (M=2 * 10 5) | ????20 |
| Macromolecule (H) polyacrylic acid sodium gel (M=5 * 10 8) | ????12 |
| The xanthan glue | ????1 |
| The osseocolla glycerogel | ????36 |
| Ferric chloride (FeCl36H2O) | ????0.5 |
| Acetaldehyde | ????5 |
| The Chinese medicine fluid extract | ????8 |
| Azone | ????2 |
| Propylene glycol | ????6 |
| Propylparaben | ????0.5 |
| Purified water | ????8 |
Preparation:
1. get each 25g such as Herba Asari, Radix Aconiti Kusnezoffii, Caulis et folium gaultheriae yunnanensis, Flos Daturae, Flos Carthami and be ground into coarse powder, water extraction three times and pinching volatile oil, concentrating under reduced pressure becomes fluid extract (density is 1.05～1.20) again.
2. with swelling is good S, H polyacrylic acid sodium gel mix homogeneously, get ferric chloride (FeCl36H2O) solution and add wherein, be warming up to 45 ℃, stirred 20 minutes, add xanthan glue, osseocolla glycerogel, insulated and stirred 40 minutes.
3. with 1. stirring evenly after middle fluid extract and volatile oil, azone, the mixed with propylene glycol, stir evenly in the gel in the adding 2., be warming up to 50 ℃, reacted 30 minutes.
4. in the pastille colloid in adding propylparaben liquid 3., add acetaldehyde solution again after, be warming up to 55 ℃, react 30 minutes, be coated with while hot, cut and get final product.
Embodiments of the invention 4
| Component | Components by weight percent |
| Low molecule (S) polyacrylic acid sodium gel (M=7 * 10 5) | ????20 |
| Macromolecule (H) polyacrylic acid sodium gel (M=2 * 10 9) | ????40 |
| Sodium alginate gel | ????4.5 |
| The gelatin glycerogel | ????16 |
| Aluminum trichloride (anhydrous) | ????0.5 |
| Sodium borate | ????1.6 |
| Methyl salicylate | ????5 |
| Oleum Camphora | ????3 |
| Glycerol | ????2 |
| Cyanine liquid | ????2 |
| Purified water | ????5.4 |
Preparation:
1. with swelling is good S, H polyacrylic acid sodium gel mix homogeneously, get the aluminum trichloride (anhydrous) aqueous solution and add wherein, be warming up to 40 ℃, stirred 60 minutes, add sodium alginate gel, gelatin glycerogel, insulated and stirred 20 minutes.
2. stir evenly in the gel in adding glycerol, Oleum Camphora, methyl salicylate dissolving back 1., be warming up to 55 ℃, reacted 15 minutes.
3. in the pastille colloid in adding cyanine liquid 2., add dobell's solution again, be warming up to 60 ℃, react 10 minutes, be coated with while hot, cut and get final product.
Embodiments of the invention 5
| Component | Components by weight percent |
| Low molecule (S) polyacrylic acid sodium gel (M=8 * 10 6) | ????26 |
| Macromolecule (H) polyacrylic acid sodium gel (M=2 * 10 10) | ????10 |
| Chitosan gel rubber | ????30 |
| The gelatin glycerogel | ????8 |
| Anhydrous calcium chloride | ????4.5 |
| Salicylic aldehyde | ????2.0 |
| Diclofenac ethylenediamine salt | ????3.5 |
| Borneolum Syntheticum | ????1 |
| Dimethyl sulfoxide | ????2 |
| Marennin liquid | ????2 |
| Purified water | ????5.4 |
Preparation:
1. with swelling is good S, H polyacrylic acid sodium gel mix homogeneously, get the anhydrous calcium chloride aqueous solution and add wherein, be warming up to 40 ℃, stirred 25 minutes, add chitosan gel rubber, gelatin glycerogel, insulated and stirred 20 minutes.
2. stir evenly in the gel in adding dimethyl sulfoxide, Borneolum Syntheticum, diclofenac ethylenediamine salt dissolving back 1., insulation was reacted 20 minutes to 50 ℃.
3. in the pastille colloid in adding marennin liquid 2., add salicylic aldehyde liquid again after, be warming up to 55 ℃, react after 15 minutes, be coated with while hot, cut and get final product.
Embodiments of the invention 6
| Component | Components by weight percent |
| Low molecule (S) polyacrylic acid sodium gel (M=2 * 10 7) | ????30 |
| Macromolecule (H) polyacrylic acid sodium gel (M=5 * 10 8) | ????10 |
| The agar glue | ????25 |
| The gelatin glycerogel | ????5 |
| Magnesium hydroxide | ????0.1 |
| Epoxychloropropane | ????5 |
| The Chinese medicine fluid extract | ????15 |
| Azone | ????2 |
| Ethanol | ????1.5 |
| Potassium sorbate | ????2.9 |
| Purified water | ????3.5 |
Preparation:
1. get each 35g such as Rhizoma Chuanxiong, Lignum Sappan, Radix Et Rhizoma Rhei, Lignum Aquilariae Resinatum, Eupolyphaga Seu Steleophaga, be ground into coarse powder, water extraction three times, merge extractive liquid, concentrating under reduced pressure become fluid extract (density is 1.05～1.15).
2. with swelling is good S, H polyacrylic acid sodium gel mix homogeneously, get magnesium hydroxide aqueous solution and add wherein, be warming up to 40 ℃, stirred 90 minutes, add agar glue, gelatin glycerogel, insulated and stirred 20 minutes.
3. with 1. stirring evenly after middle fluid extract, azone, the ethanol mixing, stir evenly in the gel in the adding 2., be warming up to 50 ℃, reacted 25 minutes.
4. behind the pastille colloid in adding potassium sorbate 3., add epoxychloropropane after, be warming up to 70 ℃, react after 10 minutes, be coated with while hot, cut and get final product.
Embodiments of the invention 7
| Component | Components by weight percent |
| Low molecule (S) polyacrylic acid sodium gel (M=3 * 10 5) | ????30 |
| Macromolecule (H) polyacrylic acid sodium gel (M=3 * 10 9) | ????43 |
| The arabic gum gel | ????2 |
| The gelatin glycerogel | ????8 |
| Six hydration aluminum chlorides | ????0.4 |
| Glutaraldehyde | ????0.6 |
| The ginsenoside | ????1 |
| Eucalyptus oil | ????3 |
| Azone | ????2 |
| Cyanine liquid | ????2 |
| Purified water | ????5 |
Preparation:
1. with swelling is good S, H polyacrylic acid sodium gel mix homogeneously, get six hydration aluminum chloride aqueous solutions and add wherein, be warming up to 60 ℃, stirred 50 minutes, add arabic gum, gelatin glycerogel, insulated and stirred 20 minutes.
2. stir in the gel in adding ginsenoside, eucalyptus oil, azone dissolving back 1., insulation was reacted 20 minutes to 65 ℃.
3. behind the pastille colloid in adding cyanine liquid 2., the adding glutaraldehyde water solution is incubated 65 ℃, reacts after 15 minutes, is coated with while hot, cuts to get final product.
Claims (10)
1, a kind of hydrophilic bioadhesive gel patch, it is made of backing layer, pastille high-molecular gel casing play and sealing coat, and pastille high-molecular gel casing play is made of substrate, active medicine and additive; It is characterized in that: substrate is prepared into polyacrylic acid sodium gel, polysaccharide gel, peptide-based gel and multiple crosslinking agent, is that 10-90, polysaccharide gel are that 1-30, peptide-based gel are that 5-50, multiple crosslinking agent are that 0.1-10, active medicine are 2-20 for the 1-20 additive according to components by weight percent calculating polyacrylic acid sodium gel in pastille high-molecular gel casing play.
2, according to the described hydrophilic bioadhesive gel of claim 1 patch, it is characterized in that: the polyacrylic acid sodium gel is that the polyacrylic acid of different molecular weight, sodium polyacrylate and polyacrylic acid crosslinked polymer are formulated in solvent according to a conventional method: in glycerol, propylene glycol, ethanol or the water, allotment is made, and wherein low-molecular polypropylene acid sodium molecule amount is 2.0 * 10
5～6.0 * 10
7Between, the high molecular weight sodium polyacrylate molecular weight is 1.0 * 10
8～5.0 * 10
10Between, calculate according to components by weight percent: low-molecular-weight sodium polyacrylate accounts for 5-45, high molecular weight sodium polyacrylate accounts for 5-45.
3, according to claim 1 or 2 described hydrophilic bioadhesive gel patches, it is characterized in that: polyacrylic acid crosslinked polymer is polymethylacrylic acid, polyacrylate, poly-alkyl sucrose and polyacrylic acid crosslinked polymer, poly-alkyl tetramethylolmethane and polyacrylic acid crosslinked polymer, polymethacrylates, poly-methyl acrylate and the copolymer between them.
4, according to the described hydrophilic bioadhesive gel of claim 1 patch, it is characterized in that: active medicine is methyl salicylate, salicylic acid ethylene glycol, Mentholum, Camphora, Borneolum Syntheticum, diclofenac sodium, diclofenac ethylenediamine salt, ibuprofen, ketoprofen, piroxicam, fenbufen, indomethacin, tramadol hydrochloride, dipyrone, aminophenazone, fentanyl or Chinese medicine extract.
5, according to claim 1 or 4 described hydrophilic bioadhesive gel patches, it is characterized in that: preferred active medicine is: the extract of ketoprofen, diclofenac ethylenediamine-salt, Mentholum, Camphora, Borneolum Syntheticum and Flos Carthami, Sanguis Draxonis, Rhizoma Chuanxiong, Cortex Cinnamomi, Flos Caryophylli, Olibanum, Herba Asari, Myrrha, Radix Aconiti, Radix Aconiti Kusnezoffii.
6, according to the described hydrophilic bioadhesive gel of claim 1 patch, it is characterized in that: the polysaccharide in the polysaccharide gel is chitosan, agar, sodium alginate, xanthan gum, Tragacanth, arabic gum, guar gum, SKGM, pectin according to conventional method and solvent: the gel that water, ethanol form, polypeptide is gelatin, osseocolla, collagen protein and macromole aminoacid in the peptide-based gel.
7, according to the described hydrophilic bioadhesive gel of claim 1 patch, it is characterized in that: its components by weight percent ratio of polysaccharide gel that uses in the substrate and peptide-based gel is: polysaccharide gel: peptide-based gel=0.2～0.8: 1～1.2.
8, according to the described hydrophilic bioadhesive gel of claim 1 patch, it is characterized in that: the additive in the substrate is the transdermal penetrating agent: dimethyl sulfoxide, azone and derivant thereof, cithrol class, carbamide, squalane and derivant thereof; And natural percutaneous penetrating agent: Mentholum, Camphora, menthol, oleic acid, camphor oil, eucalyptol, Borneolum Syntheticum; Can also be drug solvent: glycerol, propylene glycol, ethanol, ethylene glycol, n-butyl alcohol; Also can be antiseptic: parabens, benzoate, potassium sorbate; Or other essence, pigment.
9, as the preparation technology of any described hydrophilic bioadhesive gel patch among the claim 1-8, it is characterized in that: substrate preparation technology is made up of precrosslink, medicine dispersion, the ter procedure of reestablishing diplomatic relations, at first, mix the polyacrylic acid sodium gel that swelling is good under 30 ℃～70 ℃, adding just, cross-linking agent carries out the precrosslink reaction; Secondly polysaccharide gel, peptide-based gel, active medicine and other additive are added mixing in the material of precrosslink under stirring state; Add the reestablish diplomatic relations connection reaction of last cross-linking agent at last, promptly make bioadhesive gel, it is evenly coated non-woven fabrics, on the backing that chemical fiber cloth or cotton are made, cover to go up the sealing coat that polyurethane, polyester, polyethylene, polypropylene, silicone oil paper or aluminium foil and mutual complex thereof are made again, through cutting, molding and curing promptly.
10, according to the preparation technology of the described hydrophilic bioadhesive gel of claim 9 patch, it is characterized in that: the first cross-linking agent that uses is metallic aluminium, magnesium, ferrum, silicon, the various inorganic salts of calcium, oxide, hydroxide; The end cross-linking agent is boric acid, sodium borate, benzoyl peroxide, epoxychloropropane, the organic aldehyde of carbon number below 10, component meter by weight, just the consumption of cross-linking agent is 0.05%-5%, the end dosage of crosslinking agent is 0.05%-5%, and just cross-linking agent is used for precrosslink, the end cross-linking agent connection that is used to reestablish diplomatic relations carries out in two steps, plays the composite crosslinking solidification jointly.
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|---|---|---|---|
| CNB2004100405930A CN1329022C (en) | 2004-08-31 | 2004-08-31 | Hydrophilic biological sticking gel pasting agent and preparation technique thereof |
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| CN1329022C CN1329022C (en) | 2007-08-01 |
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