CN101057973A - Alcohol-free transdermal analgesic composition and processes for manufacture and use thereof - Google Patents
Alcohol-free transdermal analgesic composition and processes for manufacture and use thereof Download PDFInfo
- Publication number
- CN101057973A CN101057973A CNA2006101453767A CN200610145376A CN101057973A CN 101057973 A CN101057973 A CN 101057973A CN A2006101453767 A CNA2006101453767 A CN A2006101453767A CN 200610145376 A CN200610145376 A CN 200610145376A CN 101057973 A CN101057973 A CN 101057973A
- Authority
- CN
- China
- Prior art keywords
- effective dose
- composition
- inflammation
- patient body
- compositions
- 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
- 239000000203 mixture Substances 0.000 title claims abstract description 50
- 230000000202 analgesic effect Effects 0.000 title claims abstract description 28
- 238000000034 method Methods 0.000 title claims abstract description 12
- 238000004519 manufacturing process Methods 0.000 title 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims abstract description 8
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 8
- 239000000194 fatty acid Substances 0.000 claims abstract description 8
- 229930195729 fatty acid Natural products 0.000 claims abstract description 8
- 229960001680 ibuprofen Drugs 0.000 claims abstract description 8
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 6
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims abstract description 5
- 208000002193 Pain Diseases 0.000 claims description 20
- 230000036407 pain Effects 0.000 claims description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- 206010061218 Inflammation Diseases 0.000 claims description 17
- 230000004054 inflammatory process Effects 0.000 claims description 16
- HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 9
- 239000003349 gelling agent Substances 0.000 claims description 9
- -1 tetradecane ester Chemical class 0.000 claims description 8
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 claims description 5
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 4
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical group CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 4
- VZWGRQBCURJOMT-UHFFFAOYSA-N Dodecyl acetate Chemical compound CCCCCCCCCCCCOC(C)=O VZWGRQBCURJOMT-UHFFFAOYSA-N 0.000 claims description 4
- FLIACVVOZYBSBS-UHFFFAOYSA-N Methyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC FLIACVVOZYBSBS-UHFFFAOYSA-N 0.000 claims description 4
- HPEUJPJOZXNMSJ-UHFFFAOYSA-N Methyl stearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC HPEUJPJOZXNMSJ-UHFFFAOYSA-N 0.000 claims description 4
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 4
- 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 4
- QSQLTHHMFHEFIY-UHFFFAOYSA-N methyl behenate Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OC QSQLTHHMFHEFIY-UHFFFAOYSA-N 0.000 claims description 4
- UQDUPQYQJKYHQI-UHFFFAOYSA-N methyl laurate Chemical compound CCCCCCCCCCCC(=O)OC UQDUPQYQJKYHQI-UHFFFAOYSA-N 0.000 claims description 4
- ZAZKJZBWRNNLDS-UHFFFAOYSA-N methyl tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OC ZAZKJZBWRNNLDS-UHFFFAOYSA-N 0.000 claims description 4
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims description 4
- RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 claims description 3
- SBDNJUWAMKYJOX-UHFFFAOYSA-N Meclofenamic Acid Chemical compound CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C(O)=O)=C1Cl SBDNJUWAMKYJOX-UHFFFAOYSA-N 0.000 claims description 3
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 claims description 3
- 239000000679 carrageenan Substances 0.000 claims description 3
- 235000010418 carrageenan Nutrition 0.000 claims description 3
- 229920001525 carrageenan Polymers 0.000 claims description 3
- 229940113118 carrageenan Drugs 0.000 claims description 3
- 229960001259 diclofenac Drugs 0.000 claims description 3
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 claims description 3
- 229960001419 fenoprofen Drugs 0.000 claims description 3
- 229960002390 flurbiprofen Drugs 0.000 claims description 3
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 claims description 3
- 229960000905 indomethacin Drugs 0.000 claims description 3
- 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 3
- 229960000991 ketoprofen Drugs 0.000 claims description 3
- 229960002009 naproxen Drugs 0.000 claims description 3
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 claims description 3
- 229960000894 sulindac Drugs 0.000 claims description 3
- 229960001017 tolmetin Drugs 0.000 claims description 3
- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 claims description 3
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 claims description 3
- QMMJWQMCMRUYTG-UHFFFAOYSA-N 1,2,4,5-tetrachloro-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=C(Cl)C(Cl)=CC(Cl)=C1Cl QMMJWQMCMRUYTG-UHFFFAOYSA-N 0.000 claims description 2
- FLPJVCMIKUWSDR-UHFFFAOYSA-N 2-(4-formylphenoxy)acetamide Chemical compound NC(=O)COC1=CC=C(C=O)C=C1 FLPJVCMIKUWSDR-UHFFFAOYSA-N 0.000 claims description 2
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 claims description 2
- 229920001817 Agar Polymers 0.000 claims description 2
- 239000005698 Dodecyl acetate Substances 0.000 claims description 2
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 claims description 2
- 108010010803 Gelatin Proteins 0.000 claims description 2
- 229920002907 Guar gum Polymers 0.000 claims description 2
- 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 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 2
- 239000004698 Polyethylene Substances 0.000 claims description 2
- 229920002472 Starch Polymers 0.000 claims description 2
- BGHCVCJVXZWKCC-UHFFFAOYSA-N Tetradecane Natural products CCCCCCCCCCCCCC BGHCVCJVXZWKCC-UHFFFAOYSA-N 0.000 claims description 2
- 239000008272 agar Substances 0.000 claims description 2
- 235000010419 agar Nutrition 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 239000001913 cellulose Substances 0.000 claims description 2
- 229920002678 cellulose Polymers 0.000 claims description 2
- 229940074979 cetyl palmitate Drugs 0.000 claims description 2
- 239000003246 corticosteroid Substances 0.000 claims description 2
- CAMHHLOGFDZBBG-UHFFFAOYSA-N epoxidized methyl oleate Natural products CCCCCCCCC1OC1CCCCCCCC(=O)OC CAMHHLOGFDZBBG-UHFFFAOYSA-N 0.000 claims description 2
- FMMOOAYVCKXGMF-MURFETPASA-N ethyl linoleate Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OCC FMMOOAYVCKXGMF-MURFETPASA-N 0.000 claims description 2
- 229940031016 ethyl linoleate Drugs 0.000 claims description 2
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 claims description 2
- 229940093471 ethyl oleate Drugs 0.000 claims description 2
- 239000000499 gel Substances 0.000 claims description 2
- 239000008273 gelatin Substances 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- 235000011852 gelatine desserts Nutrition 0.000 claims description 2
- 239000000665 guar gum Substances 0.000 claims description 2
- 235000010417 guar gum Nutrition 0.000 claims description 2
- 229960002154 guar gum Drugs 0.000 claims description 2
- 235000008216 herbs Nutrition 0.000 claims description 2
- PXDJXZJSCPSGGI-UHFFFAOYSA-N hexadecanoic acid hexadecyl ester Natural products CCCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC PXDJXZJSCPSGGI-UHFFFAOYSA-N 0.000 claims description 2
- 229920013821 hydroxy alkyl cellulose Polymers 0.000 claims description 2
- FMMOOAYVCKXGMF-UHFFFAOYSA-N linoleic acid ethyl ester Natural products CCCCCC=CCC=CCCCCCCCC(=O)OCC FMMOOAYVCKXGMF-UHFFFAOYSA-N 0.000 claims description 2
- 229960003803 meclofenamic acid Drugs 0.000 claims description 2
- 229960000485 methotrexate Drugs 0.000 claims description 2
- WIBFFTLQMKKBLZ-SEYXRHQNSA-N n-butyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCCCC WIBFFTLQMKKBLZ-SEYXRHQNSA-N 0.000 claims description 2
- 229960005489 paracetamol Drugs 0.000 claims description 2
- 229920000573 polyethylene Polymers 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 239000008107 starch Substances 0.000 claims description 2
- 235000019698 starch Nutrition 0.000 claims description 2
- 239000000230 xanthan gum Substances 0.000 claims description 2
- 229920001285 xanthan gum Polymers 0.000 claims description 2
- 235000010493 xanthan gum Nutrition 0.000 claims description 2
- 229940082509 xanthan gum Drugs 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims 8
- 235000010980 cellulose Nutrition 0.000 claims 1
- 239000008240 homogeneous mixture Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 abstract description 8
- 239000003795 chemical substances by application Substances 0.000 abstract description 5
- 239000003995 emulsifying agent Substances 0.000 abstract description 4
- 239000010776 emu oil Substances 0.000 abstract 1
- 239000004615 ingredient Substances 0.000 abstract 1
- 238000013271 transdermal drug delivery Methods 0.000 abstract 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 15
- 238000012377 drug delivery Methods 0.000 description 10
- 239000003814 drug Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 241000271571 Dromaius novaehollandiae Species 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 241000237536 Mytilus edulis Species 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000002500 effect on skin Effects 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 230000035515 penetration Effects 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- KBKGPMDADJLBEM-UHFFFAOYSA-N 1-(4-pentylphenyl)ethanone Chemical compound CCCCCC1=CC=C(C(C)=O)C=C1 KBKGPMDADJLBEM-UHFFFAOYSA-N 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 230000037324 pain perception Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000037317 transdermal delivery Effects 0.000 description 2
- DWHIUNMOTRUVPG-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCO DWHIUNMOTRUVPG-UHFFFAOYSA-N 0.000 description 1
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- WEEGYLXZBRQIMU-UHFFFAOYSA-N Eucalyptol Chemical compound C1CC2CCC1(C)OC2(C)C WEEGYLXZBRQIMU-UHFFFAOYSA-N 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 206010031009 Oral pain Diseases 0.000 description 1
- 241001537211 Perna canaliculus Species 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 206010040943 Skin Ulcer Diseases 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 229960000458 allantoin Drugs 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- ALYNCZNDIQEVRV-UHFFFAOYSA-N aniline-p-carboxylic acid Natural products NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000003356 anti-rheumatic effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003435 antirheumatic agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 159000000032 aromatic acids Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 229960002504 capsaicin Drugs 0.000 description 1
- 235000017663 capsaicin Nutrition 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229960005233 cineole Drugs 0.000 description 1
- RKHQGWMMUURILY-UHRZLXHJSA-N cortivazol Chemical class C([C@H]1[C@@H]2C[C@H]([C@]([C@@]2(C)C[C@H](O)[C@@H]1[C@@]1(C)C2)(O)C(=O)COC(C)=O)C)=C(C)C1=CC1=C2C=NN1C1=CC=CC=C1 RKHQGWMMUURILY-UHRZLXHJSA-N 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 229940031674 laureth-7 Drugs 0.000 description 1
- 210000003041 ligament Anatomy 0.000 description 1
- 229940087305 limonene Drugs 0.000 description 1
- 235000001510 limonene Nutrition 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 229940013798 meclofenamate Drugs 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
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 235000020638 mussel Nutrition 0.000 description 1
- 229940090008 naprosyn Drugs 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 231100000075 skin burn Toxicity 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 230000008417 skin turnover Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to a transdermal drug delivery system composition containing a water-based excipient, including emu oil, at least one fatty acid alkyl ester, polyethylene glycol, at least one gelating agent/emulsifier and at least one analgesic ingredient, such as ibuprofen, and the invention further relates to a preparation and an application method.
Description
The cross reference of related application
The application is the partial continuous application of U.S. Patent application 10/412,626 co-pending when submitting on April 11st, 2003, and its content is hereby incorporated by.
Technical field
The present invention relates to be used for percutaneous dosing with the bonded analgesic composition of percutaneous drug delivery system that does not have alcohol with and methods for making and using same.
Background technology
Disease treatment often need be taken in a large amount of drug components.Especially, to there being the active component of certain level in the treatment of pain requirement blood samples of patients, its concentration is enough to keep pain relieving or antiinflammatory effect.In order to realize this point, the patient must take in a large amount of tablets, capsule or analog every day for several times.This therapy usually is difficult to keep, and is because active component, relevant with gastrointestinal stimulation as aspirin and triethanolamine Salicylate or NSAIDs such as ibuprofen (ibuprofen), naproxen (naprosyn) etc.The stimulation of even now may only cause chronic indigestion, and in some cases, stimulation can promptly cause spontaneous gastrorrhagia, and this may bring life danger.
Another problem relevant with oral drug therapy is must possess significant concentration level in order effectively to treat the periphery of pain or inflammation in the blood.These levels often such as the fruit medicine more accurately during the specific site of targeting pain or wound necessary level much higher.Therefore needing can the tip administration and can local ease the pain and the transdermal analgesic prescription of inflammation.
Prior art
United States Patent (USP) 6,416,772 have instructed the local skin anaesthetic composition that eases the pain, and said composition contains the alcohol of about 57-91wt%; The glycerol of about 1-12wt%; The analgesic of about 2-28wt%, this analgesic comprises salicylic derivant; The dimethyl sulfone of about 0.02-5wt%; And Dromaius novaehollandiae (Emu) oil of about 0.01-3wt%.This component produces percutaneous pain when analgesic is applied directly to afflicted areas.
Alcohol, preferred alcohol or isopropyl alcohol according to announcement, are effectively to dissolve analgesic that it can be absorbed by skin is necessary.Secondly, need the stabilizing agent of glycerol, thus the sale effect duration that alcohol can the appreciable impact component as aspirin, triethanolamine Salicylate or other analgesic.It is essential that glycerol also is considered to abundant dispersion analgesic, so needn't rock or stir component before use the part.Introduce dimethyl sulfone and fat of Oromaius norvaehollandeae and be considered to help to quicken the absorption of skin component, and because the feature that eases the pain of itself, they make analgesic more effective, have improved the effect of component.
The compositions that this patent can effectively ease the pain when instruction is not used for the regional tip of various trigger point, uncomfortable real sensation.In addition, ' 772 patent need be used alcohol when percutaneous dosing, and alcohol causes the degraded of analgesic, needs glycerol to stop the alcohol degraded as stabilizing agent thus.
United States Patent (USP) 6,346,278 have instructed lipid-soluble extract with blue or green limit mussel (Perna canaliculus) or Mytilus edulis (Mytilus edulis) as the active component in the compositions that is applicable to percutaneous dosing, said composition comprises ointment or lotion base material or excipient, can comprise that skin penetration enhancer is to assist the administration of active component.Suitable base material or excipient are oil, as olive oil or fat of Oromaius norvaehollandeae, and can be separately or with penetrating agent such as eucalyptole or limonene administration.
United States Patent (USP) 6,444,234 have instructed a kind of pharmaceutical composition that contains alcohol, carry out the percutaneous dosing of medicine or other active agent by the topical to the skin of people or other animal.The method of preparing these components is based on transdermal delivery system (TDS), this system's Chinese medicine modified and specific solvent and solvent and solute dressing agent and skin combination of stabilizers formation mixture true solution, this method makes medicine by fast Absorption, shift and, simultaneously skin irritation and/or immunoreation are minimized by skin arrival fatty tissue or vascular system.Analgesic such as ibuprofen and analog thereof, MSM and fat of Oromaius norvaehollandeae are considered to and can be used in combination with transdermal delivery system.
United States Patent (USP) 6,528,040 has instructed the prescription based on fat of Oromaius norvaehollandeae as analgesic, anesthetis and pruritus.Prescription contains 0.01 to 13wt% Arrcostab; And 20 to 70wt% fat of Oromaius norvaehollandeae; 10 to 33wt% benzyl alcohol; 10 to 33% Benzoinum; 0.2 allantoin to 2wt%; 0.25 to the nipagin of 1.25wt% and 0.01 to 0.30wt% propyl parabene.This prescription can be made into spraying or percutaneous prescription, can be used to treat chronic skin ulcer and burn wound.
United States Patent (USP) 5,885,597 have instructed a kind of local prescription that is used to alleviate the patient suffering, and this prescription basic composition is the combination of at least a corticoid class analgesic of effective dose, at least a aromatic acid class analgesic and at least a para-aminobenzoic acid ester type local anesthetic; With the capsaicin compositions of the raising pain relief effect of effective dose, and at least a phospholipid of its skin turn-over capacity of the raising of effective dose and at least a polyoxyethylene polyoxypropylene copolymer.
U.S. Patent application 20030031724 has been instructed from Dromaius novaehollandiae, the cost-effective component that Dromiceiusnovaehollandiae derives or prepares, and this component can be used as the intravital antiinflammatory of patient.This application is not imagined MSM or analgesic in the percutaneous dosing environmental applications.
U.S. Patent application 20010033838 has been instructed fat of Oromaius norvaehollandeae and various fraction thereof the carrier as antifungal, antibacterium and antiviral drugs and preparation.This application has instructed being used in combination of MSM and fat of Oromaius norvaehollandeae, but when the needs percutaneous dosing, fat of Oromaius norvaehollandeae is substituted by liposome component or oiliness percutaneous composition.
Summary of the invention
Research has shown when NSAIDs and nutrient during by orally ingestible, has had only 5% arrival to need their areas of inflammation.This is to wherein much resetting and abandoning because of stomach, liver and digestive system.
The invention discloses a kind of percutaneous drug delivery set of systems compound that comprises water base excipient, comprise at least a fatty acid alkyl esters, Polyethylene Glycol-8 (PEG-8), fat of Oromaius norvaehollandeae and gellant with 13 to 30 six carbon atoms.
The example of suitable fatty acid alkyl esters comprises, but be not limited to methyl laurate, methyl myristate, methyl hexadecanoate, methyl stearate, methyl behenate, ethyl oleate, Ethyl linoleate, butyl oleate, butyl stearate, isopropyl myristate, isopropyl palmitate, dodecyl acetate, sad tetradecane ester, cetyl palmitate and stearic stearolactone.
Above-mentioned fatty acid alkyl esters promotes chemical combination and can add in the prescription that its amount is the about 31.0wt% of about 0.001-of compositions, preferably approximately 3wt%.
Can be used for suitable gelling/emulsifying agent of the present invention and comprise guar gum, xanthan gum, carrageenan (carrageenan), cellulose, hydroxy alkyl cellulose, carboxycellulose sodium, SEPIGEL 305, gelatin, agar, starch or analog.SEPIGEL 305 is trade marks, and (Fairfield NJ) makes by Seppic company.SEPIGEL 305 is a kind of gelling/emulsifying agents, comprises about 40% polyacrylamide, about 15% C
13-C
14Isoparaffin and about 5% laureth-7 and suitable quantity of water.
Add gelling/emulsifying agent reaching required viscosity in this prescription, its amount can be about 0.001 to about 31.0wt%, preferably approximately 3wt%.
The preferred Polyethylene Glycol that uses among the present invention is that (trade mark PROTACHEM400 is by Protameen Chemical, Inc. for PEG-8, Totawa, NJ makes), its addition in this prescription be compositions about 0.001 to approximately to about 31.0wt%, preferably approximately 3wt%.In this prescription, add fat of Oromaius norvaehollandeae and promote the absorption of said composition in skin.Fat of Oromaius norvaehollandeae the amount in the present invention prescription of can adding is about 0.001 to about 31.0wt%.
In a preferred implementation, the present invention openly comprises the percutaneous drug delivery set of systems compound of water base excipient, comprise fat of Oromaius norvaehollandeae (U.S.), isopropyl palmitate (trade mark PROTACHEMIPP, by Protameen Chemical, Inc., Totawa, NJ makes), PEG-8, dimethyl sulfone (MSM) and SEPIGEL 305 (by the sale of Seppic company).
In this water base excipient, add analgesic, be example with the ibuprofen but be not limited thereto.
According to the present invention, analgesic composition should be understood that to comprise any can minimizing or the pharmaceutical composition of prevent irritation, inflammation etc.These compositionss include but not limited to gentle analgesic such as aspirin and acetaminophen, and NSAIDS (non-steroid anti-inflammation drugs) is as indometacin (Indomethacin), ibuprofen, naproxen, fenoprofen (Fenoprofen), tolmetin (Tolmetin), sulindac (Sulindac), meclofenamic acid (Meclofenamate), ketoprofen (Ketoprofen), Luo Xika (Proxicam), flurbiprofen (Flurbiprofen) and diclofenac (Diclofenac) and various DMARDS (amelioration of disease antirheumatic) are as corticosteroid, methotrexate and analog.
In addition, percutaneous drug delivery of the present invention system can add any can minimizing or the allopathy of prevent irritation, inflammation etc. with chemical compound or medical herbs chemical compound.Specifically, all percutaneous dosings less than the chemical compound of insulin molecule size can be used for compositions of the present invention.In addition, all nanotechnology products well known in the prior art can join in the present composition and not deviate from the scope of the invention.
Opposite with the agent of use oral pain alleviating, local cream of the present invention has some benefits.
These benefits comprise:
1) uses the more active component of a small amount of;
2) avoid liver metabolism;
3) avoid the degraded of active component in gastrointestinal tract;
4) avoid gastrointestinal is stimulated.
Percutaneous drug delivery system in this explanation does not contain alcohol, does not therefore have the problem of the effect duration shortening relevant with the prior art formula that contains alcohol.Because do not use alcohol, the existence of glycerol is optional equally.Therefore, provide a kind of percutaneous drug delivery system of no alcohol of uniqueness, this system has improved the penetration to skin, become thus replace capsule and tablet safer, effect rapidly and the method that is easy to realize.
In the various experiments of between prior art formula and the present invention's prescription, carrying out, have been found that current disclosed prescription needn't directly be used in the pain perception source.Correspondingly, compositions can be applied to various trigger point, pain perception point tip still will be realized alleviating of pain.
Trigger point be intramuscular stress over-drastic fibre bundle, they since the injured tuberosity and do not have elasticity of becoming can not shrink or unfold.Trigger point has multiple inducement, as overuse, injured, disease or or even daily pressure.Intramuscular trigger point shortens and tension muscle, stretch tendon and ligament and reduce intramuscular blood circulation singularly.When muscle was strained, muscle lacked oxygen, and human body discharges the chemical compound that triggers pain.Thus, the present inventor has been found that the percutaneous drug delivery system that will comprise the local analgesia agent is used for these trigger point and will reduces or remove pain in the relevant range of health.
Therefore, the purpose of this invention is to provide not containing of a kind of percutaneous dosing that is used for analgesic composition of fast skin drug-supplying system alcohol, cream, said composition can effectively be treated arthralgia and stiff.
Another object of the present invention provides analgesic composition, and when being applied to the terminal in uncomfortable impression source, said composition can systematicness ease the pain and/or the discomfort of inflammation.
Another purpose of the present invention provides a kind of method for preparing the percutaneous drug delivery system.
A further object of the present invention provides the prescription that is used for skin that a kind of effective minimizing prostaglandin produces.
In conjunction with appended accompanying drawing, by illustration of the present invention and embodiment, specific implementations, other purpose of the present invention and benefit are conspicuous according to following explanation.
The specific embodiment
The percutaneous drug delivery system that can improve dermal osmosis power in order to simplify the operation is necessary to understand the parameter that influences this phenomenon.
Influence the various factors of dermal osmosis power:
1) oil-soluble (J Pharm Sci " Linear relationships between lipophiliccharacter and biological activity of drugs. " 1972 Jan; 61 (1): 1-19) oil-soluble of material (lipotropy) is good more, and dermal osmosis power is strong more;
2) molecular weight (molecule is more little, easy more infiltration);
3) penetration of cream, gel and liquid is better than solid;
4) penetration enhancers improves local absorption (Targeted drug delivery tothe skin and deeper tissues:role of physiology, the solute structure and disease of lipophilic substance; Clin Exp Pharmacol Physiol 1997 Nov; 24 (11): 874-9).
Embodiment 1
This paper provides indefiniteness explanation embodiment; Following just embodiment and can not independently represent notion of the present invention disclosed herein.
According to preferred implementation of the present invention, the batching of excipient base material has following composition:
| Component | Amount (wt%) |
| U.S. fat of Oromaius norvaehollandeae isopropyl palmitate PEG-8 SEPIGEL 305 dimethyl sulfone water (deionized water) | ～3％ ～3％ ～4％ ～3％ *～0.75% surplus |
(
*Gelling if desired additionally increases by 1%)
Preparation steps:
At least a active component such as ibuprofen are added in the above-mentioned excipient.In this embodiment, expection adds about 10% active component.
1, active component is weighed, and uses mortar that it is fully mixed;
2, measure U.S.'s fat of Oromaius norvaehollandeae of 3%, add high-speed mixing device;
3, active component is added fat of Oromaius norvaehollandeae.Mixing enters oil until all powder.Mixture will be very dry;
4, measure isopropyl palmitate and PEG-8, add the fat of Oromaius norvaehollandeae mixture;
5, mix half an hour;
6, add sterilized water, mixed 5 minutes, scraping mixes vessel wall once in a while;
7, the SEPICEL 305 of adding 3% mixes 5 minutes (if the denseness of also not realizing ideal, the SEPIGEL 305 of increase by 1% is until obtaining ideal denseness).
All patents and the publication mentioned in this description have illustrative for those skilled in the art in the invention.Quoted by reference with same degree in these all patents and publication, illustrated by reference respectively specially as each publication and quote.
Illustrated that particular form of the present invention, the present invention are not limited in the particular form of this description and demonstration or the arrangement of each several part although be understood that.In the case without departing from the scope of the present invention, it is apparent to one skilled in the art to carry out various modifications, and should not think that the present invention is subjected in the description showing and the restriction of the content of explanation.
One of ordinary skill in the art will readily recognize that the present invention is very suitable for realizing goal of the invention, obtain to mention and itself inherent result and benefit.Any chemical compound, method, step and technology in this explanation are the representatives of current preferred specific embodiments, be intended to the explanation and scope is not limited.That those skilled in the art will carry out that spirit of the present invention comprised and by variation and other application of the scope definition of claims.Although the present invention is illustrated in conjunction with specific preferred specific embodiments, be understood that the present invention who declares should not be subjected to the improper restriction of these specific specific embodiments.In fact, conspicuous to those skilled in the art should be within the scope of the appended claims to carrying out various modifications that described pattern of the present invention carries out.
Claims (10)
- One kind reduce and/or prevention patient body in the analgesic composition of no alcohol of inflammation, comprising:The gellant of at least a fatty acid alkyl esters of the fat of Oromaius norvaehollandeae of effective dose, effective dose, the Polyethylene Glycol of effective dose, gelling effective dose, the pain relieving composition of effective dose and the sterilized water of enough supplying 100%.
- 2. the compositions of inflammation in minimizing as claimed in claim 1 and/or the prevention patient body, wherein said fatty acid alkyl esters comprises that at least one is selected from the composition in methyl laurate, methyl myristate, methyl hexadecanoate, methyl stearate, methyl behenate, ethyl oleate, Ethyl linoleate, butyl oleate, butyl stearate, isopropyl myristate, isopropyl palmitate, dodecyl acetate, sad tetradecane ester, cetyl palmitate and the stearic stearolactone.
- 3. the compositions of inflammation in minimizing as claimed in claim 1 and/or the prevention patient body, wherein said pain relieving composition comprises that at least one is selected from the composition of aspirin and acetaminophen, indometacin, ibuprofen, naproxen, fenoprofen, tolmetin, sulindac, meclofenamic acid, ketoprofen, a Luo Xika, flurbiprofen, diclofenac, corticosteroid and methotrexate.
- 4. the compositions of inflammation in minimizing as claimed in claim 1 and/or the prevention patient body, wherein said gellant comprises that at least one is selected from the composition of guar gum, xanthan gum, carrageenan, cellulose, hydroxy alkyl cellulose, carboxycellulose sodium, SEPIGEL 305, gelatin, agar, starch or analog.
- 5. the compositions of inflammation in minimizing as claimed in claim 1 and/or the prevention patient body, wherein said Polyethylene Glycol is a Polyethylene Glycol-8.
- 6. the compositions of inflammation in minimizing as claimed in claim 1 and/or the prevention patient body also comprises the dimethyl sulfone of effective dose.
- 7. the compositions of inflammation in minimizing as claimed in claim 1 and/or the prevention patient body also comprises at least a composition that is selected from allopathy with chemical compound, medical herbs chemical compound or nanotechnology product of effective dose.
- One kind reduce and/or prevention patient body in the method for inflammation and pain, comprising:The position of pain and/or inflammation in the identification patient body;Discern the trigger point relevant with described position; AndWith analgesic composition at least one place of described position or described trigger point percutaneous dosing, described compositions basic composition is the fat of Oromaius norvaehollandeae of effective dose, at least a fatty acid alkyl esters of effective dose, the Polyethylene Glycol of effective dose, the dimethyl sulfone of effective dose, the gellant of gelling effective dose, the pain relieving composition of effective dose, and the sterilized water of enough supplying 100%;The treatment that realizes described pain and/or inflammation is thus alleviated.
- 9, a kind of preparation is effective to the method for analgesic composition of the no alcohol of percutaneous dosing, comprising:The described analgesic composition of effective dose is provided;The fat of Oromaius norvaehollandeae of effective dose is provided in high-speed mixing device;Described analgesic composition is added the component of also mixing in the described fat of Oromaius norvaehollandeae until the formation mix homogeneously;In described homogeneous mixture, add the Polyethylene Glycol of the fatty acid alkyl esters of effective dose and effective dose and mix the sufficiently long time;Add sterilized water and be mixed to even;At least a gellant that adds effective dose is mixed to evenly and is gel-like consistency; WithIf desired, add extra gellant, until the gel consistency of realizing ideal.
- 10. by the product of the described method of claim 9 preparation.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/407,387 US7291591B2 (en) | 2003-04-11 | 2006-04-18 | Alcohol-free transdermal insulin composition |
| US11/407,387 | 2006-04-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101057973A true CN101057973A (en) | 2007-10-24 |
Family
ID=38864376
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2006101453767A Pending CN101057973A (en) | 2006-04-18 | 2006-11-24 | Alcohol-free transdermal analgesic composition and processes for manufacture and use thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101057973A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101977598B (en) * | 2008-03-25 | 2012-07-18 | 帝国制药株式会社 | Water-based adhesive skin patch comprising ketoprofen lysine salt |
| CN103356700A (en) * | 2012-03-26 | 2013-10-23 | 朱晓明 | Joint maintaining ointment |
-
2006
- 2006-11-24 CN CNA2006101453767A patent/CN101057973A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101977598B (en) * | 2008-03-25 | 2012-07-18 | 帝国制药株式会社 | Water-based adhesive skin patch comprising ketoprofen lysine salt |
| CN103356700A (en) * | 2012-03-26 | 2013-10-23 | 朱晓明 | Joint maintaining ointment |
| CN103356700B (en) * | 2012-03-26 | 2014-10-29 | 朱晓明 | Joint maintaining ointment |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7052715B2 (en) | Alcohol-free transdermal analgesic composition and processes for manufacture and use thereof | |
| RU2467759C2 (en) | Composition for local use and its applications | |
| EP1248613B1 (en) | Clonidine preparations | |
| ES2318233T3 (en) | IMPROVEMENT SYSTEMS OF PENETRATION AND IRRITATION REDUCERS THAT INCLUDE TESTOSTERONE. | |
| EP1425381B1 (en) | Emu-based formulations for wound treatment related application information | |
| EP2373346B1 (en) | Ibuprofen for topical administration | |
| US7033998B2 (en) | Alcohol-free transdermal insulin composition and processes for manufacture and use thereof | |
| JP2003171301A (en) | Calmeggel as an adjunct in the treatment of periodontitis | |
| CN101790370A (en) | A novel non-aqueous topical solution of diclofenac and process for preparing the same | |
| CN114209688A (en) | Compositions, methods, and systems for treating skin conditions | |
| EP2588100A1 (en) | Topical pharmaceutical composition comprising flurbiprofen | |
| US20130209585A1 (en) | Topical NMDA Antagonist Formulations for the Treatment of Peripheral Neuropathy | |
| US20090082738A1 (en) | Natural Anti-Inflammatory Agents for Reducing Pain | |
| US7291591B2 (en) | Alcohol-free transdermal insulin composition | |
| TW200403077A (en) | Trans-dermal absorption preparation | |
| KR19990082461A (en) | How to treat drugs and organisms with drugs | |
| CN101057973A (en) | Alcohol-free transdermal analgesic composition and processes for manufacture and use thereof | |
| US20040121023A1 (en) | Composition to alleviate pain and topical method of applying same | |
| CN101036660A (en) | Estrogen gel medicine and preparation method thereof | |
| US6663874B2 (en) | Composition to alleviate pain and topical method of applying same | |
| RU2381810C1 (en) | Wound healing gel balm | |
| CN101057972A (en) | Alcohol-free transdermal analgesic composition and processes for manufacture and use thereof | |
| US20060263439A1 (en) | Alcohol-free transdermal analgesic composition and processes for manufacture and use thereof | |
| KR20230026449A (en) | Topical formulations of (1S)-1-phenyl-2-pyridin-2-yletanamine | |
| KR100347883B1 (en) | New pharmaceutical composition of gel preparation containing local anaesthetic agents |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |