CN1972708A - 用于局部治疗的组合物 - Google Patents
用于局部治疗的组合物 Download PDFInfo
- Publication number
- CN1972708A CN1972708A CNA2005800203645A CN200580020364A CN1972708A CN 1972708 A CN1972708 A CN 1972708A CN A2005800203645 A CNA2005800203645 A CN A2005800203645A CN 200580020364 A CN200580020364 A CN 200580020364A CN 1972708 A CN1972708 A CN 1972708A
- Authority
- CN
- China
- Prior art keywords
- compositions
- mixture
- enzyme
- antibacterium
- fatty acid
- 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 129
- 230000000699 topical effect Effects 0.000 title claims abstract description 14
- 102000004190 Enzymes Human genes 0.000 claims abstract description 40
- 108090000790 Enzymes Proteins 0.000 claims abstract description 40
- 201000004624 Dermatitis Diseases 0.000 claims abstract description 23
- 208000010668 atopic eczema Diseases 0.000 claims abstract description 23
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 19
- 229930195729 fatty acid Natural products 0.000 claims abstract description 19
- 239000000194 fatty acid Substances 0.000 claims abstract description 19
- 150000004665 fatty acids Chemical class 0.000 claims abstract description 19
- 201000004681 Psoriasis Diseases 0.000 claims abstract description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 12
- 229940088598 enzyme Drugs 0.000 claims description 39
- 210000003491 skin Anatomy 0.000 claims description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 26
- 239000000839 emulsion Substances 0.000 claims description 22
- 238000002360 preparation method Methods 0.000 claims description 22
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 20
- 239000003921 oil Substances 0.000 claims description 20
- 235000019198 oils Nutrition 0.000 claims description 20
- NBGQZFQREPIKMG-PONOSELZSA-N Boswellic acid Chemical compound C1C[C@@H](O)[C@](C)(C(O)=O)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C NBGQZFQREPIKMG-PONOSELZSA-N 0.000 claims description 16
- NBGQZFQREPIKMG-UHFFFAOYSA-N 3beta-hydroxy-beta-boswellic acid Natural products C1CC(O)C(C)(C(O)=O)C2CCC3(C)C4(C)CCC5(C)CCC(C)C(C)C5C4=CCC3C21C NBGQZFQREPIKMG-UHFFFAOYSA-N 0.000 claims description 15
- 239000006071 cream Substances 0.000 claims description 13
- 239000000758 substrate Substances 0.000 claims description 13
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 12
- 230000000694 effects Effects 0.000 claims description 11
- 241000124008 Mammalia Species 0.000 claims description 10
- 210000004027 cell Anatomy 0.000 claims description 10
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 10
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 9
- 230000001185 psoriatic effect Effects 0.000 claims description 9
- 108010023244 Lactoperoxidase Proteins 0.000 claims description 8
- 102000045576 Lactoperoxidases Human genes 0.000 claims description 8
- 239000004902 Softening Agent Substances 0.000 claims description 8
- 229940057428 lactoperoxidase Drugs 0.000 claims description 8
- 108010015776 Glucose oxidase Proteins 0.000 claims description 7
- 239000004366 Glucose oxidase Substances 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 229940116332 glucose oxidase Drugs 0.000 claims description 7
- 235000019420 glucose oxidase Nutrition 0.000 claims description 7
- 210000002510 keratinocyte Anatomy 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 230000001225 therapeutic effect Effects 0.000 claims description 5
- 239000000080 wetting agent Substances 0.000 claims description 5
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 4
- 239000003242 anti bacterial agent Substances 0.000 claims description 4
- 239000008103 glucose Substances 0.000 claims description 4
- VGTPCRGMBIAPIM-UHFFFAOYSA-M sodium thiocyanate Chemical compound [Na+].[S-]C#N VGTPCRGMBIAPIM-UHFFFAOYSA-M 0.000 claims description 4
- 235000012424 soybean oil Nutrition 0.000 claims description 4
- 239000003549 soybean oil Substances 0.000 claims description 4
- 241000167854 Bourreria succulenta Species 0.000 claims description 3
- 235000019485 Safflower oil Nutrition 0.000 claims description 3
- 241001233037 catfish Species 0.000 claims description 3
- 230000010261 cell growth Effects 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 235000019693 cherries Nutrition 0.000 claims description 3
- 230000012010 growth Effects 0.000 claims description 3
- 150000002632 lipids Chemical class 0.000 claims description 3
- 235000005713 safflower oil Nutrition 0.000 claims description 3
- 239000003813 safflower oil Substances 0.000 claims description 3
- 210000000582 semen Anatomy 0.000 claims description 3
- 230000008859 change Effects 0.000 claims description 2
- 150000004671 saturated fatty acids Chemical class 0.000 claims description 2
- 208000017520 skin disease Diseases 0.000 abstract description 9
- 208000024891 symptom Diseases 0.000 abstract description 6
- 239000002253 acid Substances 0.000 abstract description 4
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 3
- 230000007774 longterm Effects 0.000 abstract description 2
- 150000007513 acids Chemical class 0.000 abstract 1
- 230000003822 cell turnover Effects 0.000 abstract 1
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 14
- 235000020778 linoleic acid Nutrition 0.000 description 14
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 14
- 230000008569 process Effects 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 239000012071 phase Substances 0.000 description 9
- 206010048768 Dermatosis Diseases 0.000 description 8
- -1 as Oleum helianthi Substances 0.000 description 8
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 8
- 230000003110 anti-inflammatory effect Effects 0.000 description 7
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 6
- 230000036541 health Effects 0.000 description 6
- 240000007551 Boswellia serrata Species 0.000 description 5
- 238000003745 diagnosis Methods 0.000 description 5
- 241000717739 Boswellia sacra Species 0.000 description 4
- 235000012035 Boswellia serrata Nutrition 0.000 description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
- 239000004863 Frankincense Substances 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 4
- 208000003251 Pruritus Diseases 0.000 description 4
- 230000000845 anti-microbial effect Effects 0.000 description 4
- 230000008030 elimination Effects 0.000 description 4
- 238000003379 elimination reaction Methods 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 239000004310 lactic acid Substances 0.000 description 4
- 235000014655 lactic acid Nutrition 0.000 description 4
- 239000000600 sorbitol Substances 0.000 description 4
- 235000015112 vegetable and seed oil Nutrition 0.000 description 4
- 239000008158 vegetable oil Substances 0.000 description 4
- 241000233866 Fungi Species 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 230000007803 itching Effects 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 239000001509 sodium citrate Substances 0.000 description 3
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 3
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 241001608538 Boswellia Species 0.000 description 2
- 235000018062 Boswellia Nutrition 0.000 description 2
- 206010013786 Dry skin Diseases 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 2
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 2
- 206010037888 Rash pustular Diseases 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 229930003427 Vitamin E Natural products 0.000 description 2
- 230000002421 anti-septic effect Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000003139 buffering effect Effects 0.000 description 2
- 229960001631 carbomer Drugs 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000037336 dry skin Effects 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 206010020718 hyperplasia Diseases 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 150000002978 peroxides Chemical class 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- GBROPGWFBFCKAG-UHFFFAOYSA-N picene Chemical compound C1=CC2=C3C=CC=CC3=CC=C2C2=C1C1=CC=CC=C1C=C2 GBROPGWFBFCKAG-UHFFFAOYSA-N 0.000 description 2
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 description 2
- 208000029561 pustule Diseases 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000001540 sodium lactate Substances 0.000 description 2
- 229940005581 sodium lactate Drugs 0.000 description 2
- 235000011088 sodium lactate Nutrition 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 229930003799 tocopherol Natural products 0.000 description 2
- 235000010384 tocopherol Nutrition 0.000 description 2
- 229960001295 tocopherol Drugs 0.000 description 2
- 239000011732 tocopherol Substances 0.000 description 2
- 235000019165 vitamin E Nutrition 0.000 description 2
- 239000011709 vitamin E Substances 0.000 description 2
- 229940046009 vitamin E Drugs 0.000 description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical class C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- DBHODFSFBXJZNY-UHFFFAOYSA-N 2,4-dichlorobenzyl alcohol Chemical compound OCC1=CC=C(Cl)C=C1Cl DBHODFSFBXJZNY-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 235000007173 Abies balsamea Nutrition 0.000 description 1
- 206010063409 Acarodermatitis Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 239000004857 Balsam Substances 0.000 description 1
- 241000252203 Clupea harengus Species 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 206010061619 Deformity Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 206010016936 Folliculitis Diseases 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 244000018716 Impatiens biflora Species 0.000 description 1
- 206010021531 Impetigo Diseases 0.000 description 1
- 102000010445 Lactoferrin Human genes 0.000 description 1
- 108010063045 Lactoferrin Proteins 0.000 description 1
- 102000003820 Lipoxygenases Human genes 0.000 description 1
- 108090000128 Lipoxygenases Proteins 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- 201000011152 Pemphigus Diseases 0.000 description 1
- 235000019484 Rapeseed oil Nutrition 0.000 description 1
- 241000447727 Scabies Species 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- 208000002474 Tinea Diseases 0.000 description 1
- 241000130764 Tinea Species 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 235000021324 borage oil Nutrition 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000032798 delamination Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 235000004626 essential fatty acids Nutrition 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- FMMOOAYVCKXGMF-MURFETPASA-N ethyl linoleate Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OCC FMMOOAYVCKXGMF-MURFETPASA-N 0.000 description 1
- 229940031016 ethyl linoleate Drugs 0.000 description 1
- 238000004299 exfoliation Methods 0.000 description 1
- 210000004905 finger nail Anatomy 0.000 description 1
- 235000021323 fish oil Nutrition 0.000 description 1
- 210000003953 foreskin Anatomy 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 235000021474 generally recognized As safe (food) Nutrition 0.000 description 1
- 235000021473 generally recognized as safe (food ingredients) Nutrition 0.000 description 1
- 235000019514 herring Nutrition 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- ICIWUVCWSCSTAQ-UHFFFAOYSA-M iodate Chemical compound [O-]I(=O)=O ICIWUVCWSCSTAQ-UHFFFAOYSA-M 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
- 229940006461 iodide ion Drugs 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 229940078795 lactoferrin Drugs 0.000 description 1
- 235000021242 lactoferrin Nutrition 0.000 description 1
- FMMOOAYVCKXGMF-UHFFFAOYSA-N linoleic acid ethyl ester Natural products CCCCCC=CCC=CCCCCCCCC(=O)OCC FMMOOAYVCKXGMF-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 201000001976 pemphigus vulgaris Diseases 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000009118 salvage therapy Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 208000005687 scabies Diseases 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229940100615 topical ointment Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/201—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/04—Sulfur, selenium or tellurium; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/18—Iodine; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/286—Carthamus (distaff thistle)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/40—Transferrins, e.g. lactoferrins, ovotransferrins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/44—Oxidoreductases (1)
- A61K38/443—Oxidoreductases (1) acting on CH-OH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/54—Mixtures of enzymes or proenzymes covered by more than a single one of groups A61K38/44 - A61K38/46 or A61K38/51 - A61K38/53
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Mycology (AREA)
- Alternative & Traditional Medicine (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Dermatology (AREA)
- Zoology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Cosmetics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
公开了用于哺乳类动物皮肤的局部治疗,尤其是人类皮肤局部治疗的组合物,该组合物减轻许多皮肤疾病的疾病症状并且在许多种情况下,提供长期的治愈。所述的组合物包括一种或多种乳香酸和/或具有至少18个碳原子链长并且含有至少两个不饱和键的脂肪酸和基于酶的抗细菌***的混合物。组合物将选择性地降低细胞的更新并且可以用于湿疹和/或银屑病的治疗。
Description
本发明涉及用于哺乳类动物皮肤尤其人类皮肤局部治疗的组合物。
现存的持久的皮肤疾病极其抵抗补救的治疗。尤其是湿疹和银屑病,以及其他皮肤疾病如小脓疱疹,寻常型天疱疮,Roscicea毛囊炎是造成患者不舒服和外貌损伤的原因。包括忌食和药物局部应用的补救治疗在很多种情况下提供了缓解但是很少有长期提高。
本发明的主要优势是提供用于治疗银屑病,湿疹和其它令人不愉快的皮肤疾病的组合物,该组合物相对简单并且具有廉价的设计和操作。所述的组合物没有不理想的副作用,有效治疗病症并且能够提供不理想皮肤疾病的病愈。
本发明进一步的优点是提供治疗银屑病或其它令人不愉快的皮肤疾病的方法,该方法降低和/或消除皮肤的“痒感”,这种“痒感”是这类皮肤疾病常见的症状/病情。
本发明提供用于皮肤表面局部应用的组合物,该组合物解除上面疾病的痛苦症状并且在很多种情况下,提供长期的痊愈。
根据本发明,提供一种局部应用于哺乳类动物皮肤的组合物,该组合物包括一种或多种乳香酸和基于酶的抗细菌***的混合物。
本发明也提供了一种局部应用于哺乳类动物皮肤的组合物,该组合物包括具有至少18个碳原子的链长并且包括至少两个不饱和键的脂肪酸和基于酶的抗细菌***的混合物。
本发明进一步提供了一种局部应用于哺乳类动物皮肤的组合物,该组合物包括一种或多种乳香酸,具有至少18个碳原子的链长并且包括至少两个不饱和键的脂肪酸和基于酶的抗细菌***的混合物。
基于酶的抗细菌***优选含有一种或多种酶,缓冲液和底物的混合物,其把氧气转化为具有抗细菌作用的氧化物。抗细菌剂选择性地抑制高生长的角质化细胞而并不影响细胞的正常生长。所述的主要的酶优选乳过氧化物酶和葡糖氧化酶,伴随着葡萄糖作为底物并且混合物缓冲至pH为5到6.5的范围,最优选5.3到5.6的范围。优选通过与碘化钾和硫氰酸钠的混合物混合而活化基于酶的抗细菌***。
脂肪酸或脂肪酸混合物为或者饱和的或者不饱和的,并且包含8到28个碳原子。优选地,用于局部应用的组合物为膏乳剂,包含以重量计5到40%的辛酰癸酰甘油三酯,向日葵油,红花油,大豆油,玉米油,晚樱油,鲱鱼或鲔鱼的精炼油和其它油作为载体。用于局部应用的组合物也可包含以重量计2到20%的甘油,丙二醇或其它有增加湿度性质的湿润剂。所述组合物的脂类成分优选地制备一种在水性乳液中的不连续相,所述水性乳液中水包含以重量计15到85%的乳液。
根据本发明,组合物将选择性地降低细胞更新并且降低皮肤的发炎。这样的组合物可以治愈或减轻银屑病的症状。它们也可以治愈或减轻银屑病关节炎和关节炎的症状。
虽然可以许多不同的形式体现本发明,但现在描述本发明特殊的优选的实施方案。用于治疗银屑病或其他皮肤疾病如干燥皮肤,湿疹,发瘁的皮肤,红皮肤,发痒的湿疹,发炎的皮肤,和/或龟裂皮肤的方法包括局部软膏的应用,为了治疗令人不愉快的皮肤状况,软膏至少每天一次并且优选每天两次用于个体皮肤的感染区域。
一种用于局部治疗因银屑病或其他皮肤疾病如干燥皮肤,湿疹,发痒的皮肤,红皮肤,发痒的湿疹,发炎的皮肤,和/或龟裂皮肤而痛苦的人的皮肤部位的组合物,这种组合物包含四种主要成分:
I选择性抗炎剂,该抗炎剂对湿疹和银屑病有特异性,它减少发炎并且允许所有其他生物途径正常延续,
II防止感染的抗微生物剂,
III减缓过度的细胞更新的抗-过度增生的细胞剂,和
IV一种或多种使皮肤感染区域恢复到正常状况的化合物。
全部的I到IV成分都包含在药学上可接受的载体中。组合物可以和其它成分混合,制备有助于在皮肤上应用及有助于应用后保留的液态,凝胶或膏乳剂形式。
优选的抗炎剂为自然生成并且基于:
A包括乳香酸的印乳香提取物,已知该提取物是天然的抗炎剂,选择性地抑制白三(leuketrine)(身体产生的促炎细胞因子)形成。
B聚不饱和脂肪酸或它们的酯,也称为具有至少18个碳原子链长的必需脂肪酸,例如,亚油酸(lipoleic acid)和/或其酯。
乳香酸(A)是天然的物质,它是从印乳香植物和其它乳香属种类如乳香树的树脂中得到。树脂可以乳香和乳香(olibanuma)的名字获得并且因为其芳香性质被应用。在树脂中发现的乳香酸基于一个二萘品苯苉核并且以大量的异构体存在。天然混合物可包括核取代的成分。混合酸可以市售获得。分离不同的天然乳香酸成分的方法在EP-A-0755940中描述。已经发现乳香酸为脂肪氧合酶抑制剂。
脂肪酸(B)有两个不饱和键并且可为纯的化合物或为商品油,如向日葵油,大豆油,油菜籽油,琉璃苣油,和其它植物油或鱼油如鲔鱼或鲱鱼油。
具有多于18个碳原子的链长的脂肪酸是众所周知的。许多天然地以游离态或更通常地以甘油三酯的形式存在。酯化的酸通过水解作用轻易地释放。脂肪酸以许多异构体存在,直链,支链,并且可包含一个或多个不饱和的键。这样的脂肪酸可以市售获得。
优选的抗细菌***以商品名“Myavert-C”和“Biovert”销售。这些***是天然酶,缓冲液和底物的混合物,其把氧气,可能为大气的,转化为有抗细菌作用的氧化物。应用的主要酶为乳过氧化物酶和葡糖氧化酶。葡萄糖作为底物存在并且混合物缓冲至pH为5.0到6.5范围,优选5.3到5.6范围。通过与含有碘化钾和硫氰酸钠的混合物混合而活化抗细菌***。所述酶的氧化使碘离子变成碘酸根并且使硫氰酸根离子变成次硫氰酸根。氧化的离子通过选择性地氧化细菌和真菌细胞壁而杀死细菌和真菌。
在WO-A-91/11105中描述这些成分的混合物的抗细菌作用。其他基于酶的抗细菌***,如乳铁蛋白,在本发明组合物中细菌和真菌的控制方面也有效。
已经发现,在本发明组合物中应用的乳香酸和酶***的混合物并且还有基于聚不饱和脂肪酸和/或它们的酯如亚油酸或亚油酸乙酯等抗炎剂和抗微生物剂化合物,如葡糖氧化酶和乳过氧化物酶等的混合物,选择性地减缓SVK-14细胞(起源于人类新生儿的过度增生的***的永久角质化细胞系)的更新但是对正常细胞没有影响。这种作用战胜了银屑病。
众所周知的增湿剂,软化剂和湿润剂可作为皮肤的恢复者应用。优选的化合物基于纯的亚油酸或富含亚油酸的植物油。
本发明一种优选形式的组合物包含在药学上可接受的载体中的抗炎剂,亚油酸,和基于酶的抗微生物***。
由于不饱和亚油酸(纯的或作为植物油的部分)在暴露到空气中时不稳定并且易于降解,主要被氧化,为醛或醇衍生物。为了防止这样的降解大多数市售获得的植物油和纯化的亚油酸包含作为抗氧化剂的生育酚(维生素E)。本发明组合物中生育酚的存在对亚油酸减缓角质化细胞的细胞更新能力有不利的影响。本发明组合物中应用的亚油酸本质上应该无任何抗氧化剂。
基于酶的抗微生物***(Myavert C)通过与可获得的氧气反应生成过氧化物开始起作用,生成的过氧化物反过来被乳过氧化物酶消耗,生成破坏细菌和真菌的活性物质。本发明组合物中酶的存在看起来好像使亚油酸稳定,因为酶消除了氧气并且因此防止了亚油酸的氧化。
本发明组合物中的亚油酸显示5个方面的作用:
1.它作为抗炎剂;
2.它选择性地降低角质化细胞的细胞更新;
3.它软化硬的皮肤表面;
4.它作为增湿剂和软化剂以及
5.它帮助角质层恢复到正常因此它可完成其屏障功能(防止水分丢失,化学药品和微生物的进入)。
本发明组合物中的基于酶的抗细菌***“Myavert C”的全部功能为:
1.消除密闭***(例如,管内或瓶内的膏)中的氧气并且因此使亚油酸稳定;
2.作为防腐剂使产物稳定;
3.在使用的时候破坏皮肤表面的抗-微生物和
4.选择性地降低角质化细胞的细胞更新。
本发明的局部组合物是在药学上可接受的载体中被提供应用并且该组合物可以呈现溶液,膏,软膏,乳剂或香膏或本领域众所周知的其他形式中的任一形式,并且优选的载体形式是水包油乳膏。
根据本发明下表列出了优选的组合物/载体的成分。可代替的载体在本领域众所周知并且基于GRAS(一般认为是安全的)的成分能够取代下面给出的基础。
组分的功能和范围
成分 | 功能 | 范围,%w/w |
水 | 载体相 | 20-80 |
Permulen TR2 NF(卡波姆) | 乳化剂 | 最高达2 |
乳酸 | PH缓冲 | 最高达5 |
卡波伯980NF | 增稠剂 | 最高达2 |
甘油 | 湿润剂 | 最高达20 |
辛酰/癸酰甘油三酯 | 药学上的溶剂,乳香增溶剂 | 最高达80 |
乳香 | 抗炎剂 | 最高达25 |
油酸 | 最高达25 | |
向日葵油 | 软化剂 | 最高达25 |
聚氧乙烯山梨糖醇单油酸酯 | 表面活性剂 | 最高达10 |
2,4-二氯苯甲醇 | 抗真菌剂 | 最高达2 |
乳酸钠 | PH缓冲 | 最高达5 |
Myavert C | 防腐剂和抗细菌剂 | 最高达25 |
制剂
下表给出制剂的例子。
成分 | 6A | 6B | 44 | 15A6 | 15B6%w/w | 18A | 18B | 20A | 20B |
水I | 13.60 | 17.60 | 13.20 | 13.20 | 24.55 | 28.55 | 5.15 | 5.88 | |
乳酸(90%) | 0.25 | 0.25 | 0.25 | 0.25 | 0.25 | 0.20 | 0.24 | ||
柠檬酸 | - | - | 0.15 | 0.15 | |||||
Pemulen TR2NF(3.0%溶液) | 13.70 | 13.70 | 13.70 | 15.00 | 15.00 | 13.70 | 13.70 | 15.00 | 17.66 |
卡波伯900NF(2.0%溶液) | 20.40 | 20.40 | 20.04 | 17.50 | 17.50 | 20.40 | 20.04 | 15.00 | 17.66 |
甘油 | 5.00 | 5.00 | 5.00 | 5.00 | 5.00 | 4.00 | 4.00 | 4.00 | 4.71 |
辛酰/癸酰甘油三酯 | 36.00 | 36.00 | 36.00 | 24.00 | 24.00 | 16.00 | 16.00 | 25.00 | 29.43 |
有全部乳香酸异构体的印乳香 | 4.00 | 4.00 | - | 4.00 | 15.00 | ||||
向日葵油 | - | 16.50 | 12.00 | 12.00 | 12.00 | 14.12 | |||
亚油酸-92.6%活性水平(有-50ppm天然维生素E) | 20.00 | 16.50 | - | ||||||
SurfacareT80(聚氧乙烯山梨糖醇单油酸酯) | 0.30 | 0.30 | 0.30 | 0.30 | 0.30 | 0.25 | 0.25 | 0.40 | 0.47 |
Myacide SP) | 0.15 | 0.15 | 0.15 | 0.15 | 0.15 | 0.15 | 0.15 | 0.15 | 0.15 |
(2,4-二氯苯甲醇)水II | 2.00 | 2.00 | 2.00 | 2.00 | 2.00 | 2.00 | 2.00 | 2.35 | |
乳酸钠(60%) | 2.00 | 2.00 | 2.00 | 2.50 | 2.50 | 2.00 | 2.35 | ||
柠檬酸钠 | - | - | - | 1.25 | 1.25 | ||||
TEA(50%溶液) | - | 1.00 | 1.00 | 1.50 | 2.30 | ||||
Myavert C部分1 | 2.00 | 2.00 | - | 2.00 | 2.00 | 1.00 | 1.00 | 2.00 | 2.00 |
水III | 0.50 | 0.50 | - | 0.50 | 0.50 | 0.50 | 0.50 | 0.50 | 0.59 |
MyavertC部分2 | 0.10 | 0.10 | - | 0.10 | 0.10 | 0.05 | 0.05 | 0.10 | 0.10 |
总计 | 100.00 | 100.00 | 100.00 | 100.00 | 100.00 | 100.00 | 100.00 | 100.00 | 100.00 |
制剂的典型过程
上面的制剂可利用下面描述的冷过程制备。
阶段 | 操作 |
1 | 按生产商描述的操作过程制备3.0%的Premulen TR2 NF溶液 |
2 | 按生产商描述的操作过程制备2.0%的卡波伯980 NF溶液 |
3 | 将乳香酸和辛酰/癸酰甘油三酯混合并加热到115-120℃。在此温度加热30分钟然后冷却至室温。在过程4整个操作过程中的混合物温度必须维持在22-24℃ |
4 | 向合适的有锚式搅拌机和匀浆器的混合容器内,添加乳酸和水1并且搅拌5分钟。 |
5 | 添加第1阶段制备的Premulen TR2 NF溶液并且搅拌20分钟。 |
6 | 添加第2阶段制备的卡渡姆908 NF溶液并且搅拌20分钟。 |
7 | 添加甘油,搅拌20分钟。(水相) |
8 | 在22-24℃,向第3阶段制备的印乳香和辛酰/癸酰甘油三酯的溶液中添加亚油酸和/或向日葵油,聚氧乙烯山梨糖醇单油酸酯和2,4-二氯苯甲醇并且搅拌30分钟(油相) |
9 | 确保油相的温度比水相的温度高大约2℃。 |
10 | 将油相加入到水相中,迅速搅拌5分钟以上并且继续搅拌15分钟以制备水包油的乳膏。 |
11 | 必要时冷却乳剂至温度在22-24℃之间。 |
12 | 将柠檬酸钠溶解在水2中,并且添加到主要乳剂中迅速搅拌混合;搅拌5分钟。 |
13 | 检验pH |
14 | 减缓搅拌器至缓和搅拌并且用TEA(50%)调pH值至5.4-5.6,在此pH时搅拌20分钟。 |
15 | 添加MyavertC部分1并且搅拌15分钟。 |
16 | 将Myavert C部分2溶解在水3中,并且添加到乳剂中搅拌15分钟。 |
17 | 检验并记录最终的pH和乳剂的粘度(详细说明pH=5.4-5.6并且粘度=20,0000-80,000cps) |
包含印乳香的组合物也可以利用下面描述的热过程制备。
阶段 | 操作 |
1 | 按生产商描述的操作过程制备3.0%的Premulen TR2 NF溶液 |
2 | 按生产商描述的操作过程制备2.0%的卡波伯980NF溶液 |
3 | 将乳香酸和辛酰/癸酰甘油三酯混合并加热到115-120℃。在此温度加热30分钟然后冷却至82-84℃。 |
4 | 向合适的有锚式搅拌机和匀浆器的混合容器内,添加乳酸和水1并且搅拌5分钟 |
5 | 添加第1阶段制备的Premulen TR2NF溶液并且搅拌20分钟 |
6 | 添加第2阶段制备的卡波姆980NF溶液并且搅拌20分钟 |
7 | 添加甘油,搅拌20分钟然后升高温度至80-82℃(水相) |
8 | 在82-84℃,向第3阶段制备的乳香酸和辛酰/癸酰甘油三酯的溶液中添加亚油酸和/或向日葵油,聚氧乙烯山梨糖醇单油酸酯和2,4-二氯苯甲醇并且搅拌30分钟(油相) |
9 | 确保油相的温度比水相的温度高大约2℃ |
10 | 将油相加入到水相中,迅速搅拌5分钟以上并且继续搅拌15分钟以制备水包油的乳膏 |
11 | 开始冷却乳剂 |
12 | 将柠檬酸钠溶解在水2中,并且在45-50℃添加到主要乳剂中迅速搅拌混合;搅拌5分钟 |
13 | 检验pH |
14 | 减缓搅拌器至缓和搅拌并且在40-45℃用TEA(50%)调pH值至5.4-5.6并且搅拌20分钟 |
15 | 添加Myavert到C部分1并且搅拌15分钟 |
16 | 将Myavert C部分2溶解在水3中,并且添加到乳剂中搅拌15分钟 |
17 | 检验并记录最终的pH和乳剂的粘度(详细说明pH=5.4-5.6并且粘度=20,000-80,000cps) |
临床试验
制剂18A和19B
一个两岁半的患有异位性湿疹的男孩(患者No.1/98),湿疹覆盖体表的18%以上。他患湿疹已经两个星期并且没有治疗。很明显湿疹是细菌感染诱导的。以一种固定的方式对患者感染的皮肤区域应用湿疹膏18A。3天后,红和疼痛消退。两个月后,皮肤瘙瘁消失并且在两个半月之内克服了所有湿疹的症状,使皮肤恢复到正常健康状况。患者至少三年(这是他最后一次作检查的时间点)没有患湿疹。
22例患者用膏18A治疗并且22例用膏18B治疗。两种膏在患者身上都克服了湿疹,并且膏18A在两周之内在平均克服湿疹方面给出比较快速的响应,而18B则需要3到4周。与用18B治疗的患者相比,用18A治疗的患者湿疹的复发率比较低。
15A和15B膏制剂在银屑病治疗方面的效果的试点研究临床结果
为了确定最佳制剂的全部功效及其防治银屑病的性能,利用挑选出来的膏(15A-94%的15%=14.1%)有效的亚油酸和基于酶的抗细菌***与(15B)仅仅在软化剂基质中的基于酶的抗细菌***比较,进行了临床试验。
以调查表,并且在那里可能以照相的方式记录信息。在应用命名为或者15A或者15B的两种局部膏中的一种进行治疗的患者的第一次会诊过程中,处方指导每天应用膏两次,直到疾患消除后两个星期。15A是在软化剂基质中的亚油酸(14.1%)和基于酶的抗细菌***。15B是仅仅在软化剂基质中的基于酶的抗细菌***。随着并且当病人返回到诊所时,以调查表、记录和照相的方式记录临床状态中的进展。
从就诊皮肤科门诊被诊断患有银屑病并且通过组织检查确认的患者中招募两位男性和四位女性参与者。招募了各式各样的参与者(N)。按几年内银屑病覆盖身体面积的百分比记录参与者银屑病状况的年限和以前持续时间。数据标记为;(A)1%或更少,(B)1-5%,(C)10%,(D)10-18%和(E)大于18%。‘银屑病的类型’记录为斑块,红皮病型,点滴型(点滴),倒转型,脓疱型,头皮型,指甲癣,银屑病性关节炎,其它在第一次就诊和或紧接着的组织检查明确的)类型。通过圈出受影响的区域和‘损伤部位’标志‘身体地图’,‘身体地图’被明确指定和标记为,(0)很好,(1)轻微的,(2)中等的,(3)中等到严重,和(4)严重。征得患者的同意,也以照相的方式记录损伤。视觉检查的真菌感染的存在被标记为或者‘是’,‘不是’或者‘不知道’,标记的‘损伤部位’也被应用于评价特征‘表皮脱落/起鳞’,‘痛’,‘红和疼痛’,‘瘙痒’,和‘脓疱’,收集每一个参与者的详细的人口统计资料。对治疗响应的测量被记录为所有损伤从身体所有部位消除需要的天数,命名为‘消除的’。提高,‘消除’,和缓和的数据在下表描述。
应用15A和15B治疗的参与者的提高和清除
应用15A治疗的参与者 | |||||||
参与者号码 | 观察的提高 | 消除 | 消除后的缓和 | 全部 | 最后纪录的就诊 | ||
天 | 天数 | 天数 | 就诊天数 | 就诊天数 | 天数 | ||
1 | 21,35,63,91,119 | 147 | 51 | 2 | 9 | 198 | |
3 | 4和72 | 72 | - | - | 3 | 72 | |
4 | 7,14,和44 | 44 | - | - | 4 | 44 | |
5 | 14 | 30 | - | - | 3 | 30 | |
6 | 24 | 56 | - | - | 3 | 47 | |
应用15B治疗的参与者 | |||||||
2 | 24和40 | 40 | - | - | 3 | 40 |
权利要求书(按照条约第19条的修改)
1.一种局部应用于哺乳类动物皮肤的组合物,其包括一种或多种乳香酸和基于酶的抗细菌***的混合物。
2.一种局部应用于哺乳类动物皮肤的组合物,其包括具有至少18个碳原子的链长并且含有至少两个不饱和键的脂肪酸和包括至少两种酶的基于酶的抗细菌***的混合物。
3.如权利要求2所述的组合物,其中所述的基于酶的抗细菌***包括乳过氧化物酶和葡糖氧化酶。
4.如权利要求3所述的组合物,其中所述的乳过氧化物酶和葡糖氧化酶的量占所述组合物重量的0.05到0.10%。
5.一种局部应用于哺乳类动物皮肤的组合物,其包括一种或多种乳香酸,基于酶的抗细菌***和具有至少18个碳原子的链长并且含有至少两个不饱和键的脂肪酸。
6.一种局部应用的组合物,其包括在软化剂基质中的基于酶的抗细菌***。
7.如前述任一项权利要求所述的组合物,其中所述基于酶的抗细菌***是至少两种酶,缓冲液和底物的混合物,该混合物把氧气转变为具有抗细菌作用的氧化物。
8.如权利要求7所述的组合物,其中所述的抗细菌剂选择性地抑制高生长角质化细胞而不影响细胞的正常生长。
9.如权利要求7或8所述的组合物,其中所述的主要的酶是乳过氧化物酶和葡糖氧化酶,其带有葡萄糖作为底物存在并且所述混合物被缓冲至pH在5到6.5的范围。
10.如权利要求9所述的组合物,其中所述的混合物被缓冲至pH在5.3到5.6的范围。
11.如前述任一项权利要求所述的组合物,其中所述基于酶的抗细菌***通过与碘化钾和硫氰酸钠的混合物混合而被活化。
12.如前述任一项权利要求所述的组合物,其中或者是饱和的脂肪酸或者是不饱和的脂肪酸并且包含8到28个碳原子的脂肪酸或脂肪酸的混合物作为运送剂存在。
13.如前述任一项权利要求所述的组合物,其中所述的组合物为局部应用的膏乳剂形式,包括以重量计5到40%的作为载体的向日葵油,红花油,大豆油,玉米油,晚樱油,精炼的鲱鱼或鲔鱼油和其它任一种油。
14.如前述任一项权利要求所述的组合物,其包括以重量计10到80%的辛酰/癸酰甘油三酯。
15.如前述任一项权利要求所述的组合物,其包括以重量计2到20%的甘油,丙二醇和其它有增加湿度性质的湿润剂。
16.如权利要求10到12所述的组合物,其中所述的脂类成分制备一种在水性乳液中的不连续相,在所述水性乳液中水包含以重量计15到85%的乳液。
17.如权利要求1至6中所述的组合物,其将选择性地降低细胞的更新。
18.如前述任一项权利要求所述的组合物在治疗中的应用。
19.如权利要求1所述的组合物在制备治疗湿疹和银屑病的药物中的应用。
20.如权利要求2至4所述的组合物在制备治疗银屑病的药物中的应用。
21.如权利要求5所述的组合物在制备联合治疗银屑病和湿疹的药物中的应用。
22.一种如前所述的1到17任一项权利要求所述的组合物的制备方法。
23.一种治疗银屑病的方法,其包括对需要其的患者给药有效量的根据权利要求1到17任一项权利要求所述的组合物。
24.一种治疗湿疹的方法,其包括对需要其的患者给药有效量的根据权利要求1到17任一项权利要求所述的组合物。
Claims (22)
1.一种局部应用于哺乳类动物皮肤的组合物,其包括一种或多种乳香酸和基于酶的抗细菌***的混合物。
2.一种局部应用于哺乳类动物皮肤的组合物,其包括具有至少18个碳原子的链长并且含有至少两个不饱和键的脂肪酸和基于酶的抗细菌***的混合物。
3.一种局部应用于哺乳类动物皮肤的组合物,其包括一种或多种乳香酸,基于酶的抗细菌***和具有至少18个碳原子的链长并且含有至少两个不饱和键的脂肪酸的混合物。
4.一种局部应用的组合物,其包括在软化剂基质中的基于酶的抗细菌***。
5.如前述任一项权利要求所述的组合物,其中所述基于酶的抗细菌***是一种或多种酶,缓冲液和底物的混合物,该混合物把氧气转变为具有抗细菌作用的氧化物。
6.如权利要求5所述的组合物,其中所述的抗细菌剂选择性地抑制高生长角质化细胞而不影响细胞的正常生长。
7.如权利要求6所述的组合物,其中所述的主要的酶是乳过氧化物酶和葡糖氧化酶,其带有葡萄糖作为底物存在并且所述混合物被缓冲至pH在5到6.5的范围。
8.如权利要求7所述的组合物,其中所述的混合物被缓冲至pH在5.3到5.6的范围。
9.如前述任一项权利要求所述的组合物,其中所述基于酶的抗细菌***通过与碘化钾和硫氰酸钠的混合物混合而被活化。
10.如前述任一项权利要求所述的组合物,其中或者是饱和的脂肪酸或者是不饱和的脂肪酸并且包含8到28个碳原子的脂肪酸或脂肪酸的混合物作为运送剂存在。
11.如前述任一项权利要求所述的组合物,其中所述的组合物为局部应用的膏乳剂形式,包括以重量计5到40%的作为载体的向日葵油,红花油,大豆油,玉米油,晚樱油,精炼的鲱鱼或鲔鱼油和其它任一种油。
12.如前述任一项权利要求所述的组合物,其包括以重量计10到80%的辛酰/癸酰甘油三酯。
13.如前述任一项权利要求所述的组合物,其包括以重量计2到20%的甘油,丙二醇和其它有增加湿度性质的湿润剂。
14.如权利要求8到10所述的组合物,其中所述的脂类成分制备一种在水性乳液中的不连续相,在所述水性乳液中水包含以重量计15到85%的乳液。
15.如权利要求1、2、3或4中所述的组合物,其将选择性地降低细胞的更新。
16.如前述任一项权利要求所述的组合物在治疗中的应用。
17.如权利要求1所述的组合物在制备治疗湿疹和银屑病的药物中的应用。
18.如权利要求2所述的组合物在制备治疗银屑病的药物中的应用。
19.如权利要求3所述的一种组合物在制备联合治疗银屑病和湿疹的药物中的应用。
20.一种如前述的1到15任一项权利要求所述的组合物的制备方法。
21.一种治疗银屑病的方法,其包括对需要其的患者给药有效量的根据权利要求1到15任一项权利要求所述的组合物。
22.一种治疗湿疹的方法,其包括对需要的患者给药有效量的根据权利要求1到15任一项权利要求所述的组合物。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB0413954.9A GB0413954D0 (en) | 2004-06-22 | 2004-06-22 | Compositions for topical treatment |
GB0413954.9 | 2004-06-22 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN1972708A true CN1972708A (zh) | 2007-05-30 |
Family
ID=32799947
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNA2005800203645A Pending CN1972708A (zh) | 2004-06-22 | 2005-06-16 | 用于局部治疗的组合物 |
Country Status (15)
Country | Link |
---|---|
US (1) | US20070253943A1 (zh) |
EP (1) | EP1776128B1 (zh) |
JP (1) | JP2008503558A (zh) |
KR (1) | KR20070040369A (zh) |
CN (1) | CN1972708A (zh) |
AU (1) | AU2005256908A1 (zh) |
BR (1) | BRPI0511355A (zh) |
CA (1) | CA2571444A1 (zh) |
EA (1) | EA011723B1 (zh) |
GB (5) | GB0413954D0 (zh) |
IL (1) | IL180091A0 (zh) |
IN (1) | IN2006DE07403A (zh) |
MX (1) | MXPA06014787A (zh) |
WO (1) | WO2006000867A1 (zh) |
ZA (1) | ZA200700012B (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101721340B (zh) * | 2009-10-23 | 2012-02-15 | 无限极(中国)有限公司 | 一种用于延缓肌肤衰老的化妆品组合物 |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ITVR20080125A1 (it) * | 2008-11-13 | 2010-05-14 | Phytonature Sas Di Masini Dr Antoni O E C | Nuova forma di preparazione ed utilizzo della boswellia serrata |
WO2010106417A2 (en) * | 2009-03-16 | 2010-09-23 | Himalaya Global Holdings Ltd. | Herbal personal care formulations and method of preparing the same |
US20130004477A1 (en) * | 2009-10-26 | 2013-01-03 | Zhe Lu | Methods for Treating Inflammation and Oxidative Stress Related Diseases |
PL2366408T3 (pl) * | 2010-03-01 | 2013-01-31 | Salvat Lab Sa | Klarowne roztwory wodne acetonidu fluocinolonu do leczenia zapalenia uszu |
EP2444081B1 (en) * | 2010-10-19 | 2015-04-08 | Parenteral, A.S. | A composition for the treatment of inflammatory diseases comprising boswellic acids and cannabidiol |
WO2012177825A1 (en) | 2011-06-21 | 2012-12-27 | Bvw Holding Ag | Medical device comprising boswellic acid |
ITUA20162425A1 (it) * | 2016-04-08 | 2017-10-08 | Medivis S R L | Composizione oftalmica che comprende PVP-I |
US9975917B1 (en) | 2017-09-20 | 2018-05-22 | King Saud University | Pentacyclic triterpenoidal derivatives |
GB2584647A (en) * | 2019-06-06 | 2020-12-16 | Boston Healthcare Ltd | Skin treatment composition |
BE1028576B1 (fr) * | 2021-12-30 | 2023-08-17 | Dyna S A R L | Composition comprenant au moins un acide boswellique et/ou au moins un extrait végétal comprenant au moins un acide boswellique pour utilisation topique dans le traitement des maladies inflammatoires de la peau |
WO2023187598A1 (en) * | 2022-03-27 | 2023-10-05 | Biblical Lands Ltd | Compositions and methods |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9002422D0 (en) | 1990-02-03 | 1990-04-04 | Boots Co Plc | Anti-microbial compositions |
GB9127062D0 (en) * | 1991-12-20 | 1992-02-19 | Unilever Plc | Lip treatment composition |
FR2685202B1 (fr) * | 1991-12-24 | 1995-03-24 | Sederma Sa | Nouvelle methode de traitement pharmaceutique et cosmetique pour la regulation de la seborrhee, de l'acne et de la flore cutanee. |
DE4201903B4 (de) | 1992-01-24 | 2004-04-15 | Hermann P.T. Prof. Dr.Med. Ammon | Pharmazeutische Verwendung von Boswelliasäuren |
JP3746081B2 (ja) | 1994-02-24 | 2006-02-15 | 森永乳業株式会社 | 動物皮膚病治療剤 |
JP3888707B2 (ja) * | 1996-01-22 | 2007-03-07 | 森永乳業株式会社 | 血管新生病治療剤 |
NO301635B1 (no) * | 1996-07-29 | 1997-11-24 | Bjoern Gunnar Risa | Oppspolingsanordning, særlig for oppspoling av lastestropper |
US5972355A (en) * | 1997-09-30 | 1999-10-26 | E-L Management Corp. | Stable compositions containing biologically active components |
EP1121021A1 (en) | 1998-10-15 | 2001-08-08 | Dsm N.V. | Antimicrobial enzymes in animal feed |
GB9906914D0 (en) * | 1999-03-26 | 1999-05-19 | Quest Int | Compositions containing boswellia extracts |
EP1173162A1 (en) * | 1999-04-30 | 2002-01-23 | Sabinsa Corporation | Compositions of boswellic acids derived from boswellia serrata gum resin, for treating lymphoproliferative and autoimmune conditions |
US6214339B1 (en) * | 2000-01-12 | 2001-04-10 | Michael A. Pellico | Di-enzymatic treatment of outer ear infection in dogs and cats |
WO2001074327A1 (en) * | 2000-04-04 | 2001-10-11 | Color Access, Inc. | Composition for improving skin lipid barrier function |
GB0100643D0 (en) * | 2001-01-10 | 2001-02-21 | Basf Ag | Liquid antimicrobial compositions |
WO2002085921A2 (de) * | 2001-03-01 | 2002-10-31 | Johann Jauch | Einfaches verfahren zur synthese von boswelliasäuren und derivaten davon |
NL1018421C1 (nl) * | 2001-06-29 | 2003-01-07 | Sara Lee De Nv | Mondverzorgingsmiddel. |
JP2003089629A (ja) * | 2001-09-18 | 2003-03-28 | Kakunai Juyotai Kenkyusho:Kk | 新規化粧品、新規外用剤及び新規浴剤の製造方法 |
US20030211995A1 (en) | 2001-12-21 | 2003-11-13 | Kokai-Kun John Fitzgerald | Methods and formulations for eradicating or alleviating staphylococcal nasal colonization using lysostaphin |
US20040082504A1 (en) * | 2002-05-10 | 2004-04-29 | Atul Varadhachary | Intratumorally administered lactoferrin in the treatment of malignant neoplasms and other hyperproliferative diseases |
US20040214750A1 (en) * | 2003-04-28 | 2004-10-28 | Georgiades Izolda M. | Medicaments for healing skin conditions in humans |
US20070264222A1 (en) * | 2006-05-10 | 2007-11-15 | Biohealth Advance, Llc | Enhanced protection against skin injury in humans |
-
2004
- 2004-06-22 GB GBGB0413954.9A patent/GB0413954D0/en not_active Ceased
-
2005
- 2005-06-16 WO PCT/IB2005/001692 patent/WO2006000867A1/en active Application Filing
- 2005-06-16 CA CA002571444A patent/CA2571444A1/en not_active Abandoned
- 2005-06-16 GB GB0625339A patent/GB2430884B/en not_active Expired - Fee Related
- 2005-06-16 AU AU2005256908A patent/AU2005256908A1/en not_active Abandoned
- 2005-06-16 EA EA200700044A patent/EA011723B1/ru not_active IP Right Cessation
- 2005-06-16 CN CNA2005800203645A patent/CN1972708A/zh active Pending
- 2005-06-16 GB GB0820552A patent/GB2451597B/en not_active Expired - Fee Related
- 2005-06-16 KR KR1020077000578A patent/KR20070040369A/ko not_active Application Discontinuation
- 2005-06-16 US US11/570,806 patent/US20070253943A1/en not_active Abandoned
- 2005-06-16 MX MXPA06014787A patent/MXPA06014787A/es not_active Application Discontinuation
- 2005-06-16 EP EP05753109.7A patent/EP1776128B1/en active Active
- 2005-06-16 BR BRPI0511355-5A patent/BRPI0511355A/pt not_active IP Right Cessation
- 2005-06-16 GB GB0800351A patent/GB2445674B/en not_active Expired - Fee Related
- 2005-06-16 JP JP2007517511A patent/JP2008503558A/ja active Pending
-
2006
- 2006-12-07 IN IN7403DE2006 patent/IN2006DE07403A/en unknown
- 2006-12-14 IL IL180091A patent/IL180091A0/en unknown
-
2007
- 2007-01-02 ZA ZA200700012A patent/ZA200700012B/en unknown
-
2008
- 2008-10-01 GB GBGB0817929.3A patent/GB0817929D0/en not_active Ceased
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101721340B (zh) * | 2009-10-23 | 2012-02-15 | 无限极(中国)有限公司 | 一种用于延缓肌肤衰老的化妆品组合物 |
Also Published As
Publication number | Publication date |
---|---|
GB2430884A (en) | 2007-04-11 |
KR20070040369A (ko) | 2007-04-16 |
GB2451597B (en) | 2009-03-25 |
WO2006000867B1 (en) | 2006-05-18 |
GB0413954D0 (en) | 2004-07-28 |
IN2006DE07403A (zh) | 2007-08-31 |
GB0820552D0 (en) | 2008-12-17 |
AU2005256908A1 (en) | 2006-01-05 |
US20070253943A1 (en) | 2007-11-01 |
BRPI0511355A (pt) | 2007-12-04 |
CA2571444A1 (en) | 2006-01-05 |
ZA200700012B (en) | 2008-04-30 |
WO2006000867A1 (en) | 2006-01-05 |
EP1776128A1 (en) | 2007-04-25 |
EP1776128B1 (en) | 2018-02-14 |
GB0625339D0 (en) | 2007-02-07 |
MXPA06014787A (es) | 2007-03-12 |
GB0800351D0 (en) | 2008-02-20 |
GB2445674B (en) | 2009-02-18 |
GB2445674A (en) | 2008-07-16 |
JP2008503558A (ja) | 2008-02-07 |
EA011723B1 (ru) | 2009-04-28 |
IL180091A0 (en) | 2007-07-04 |
GB0817929D0 (en) | 2008-11-05 |
GB2451597A (en) | 2009-02-04 |
EA200700044A1 (ru) | 2007-08-31 |
GB2430884B (en) | 2008-03-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1972708A (zh) | 用于局部治疗的组合物 | |
Bassett et al. | A comparative study of tea‐tree oil versus benzoylperoxide in the treatment of acne | |
CA3018969C (en) | Apremilast pharmaceutical compositions | |
JP2017226664A (ja) | Dgla、15−ohepaおよび/または15−hetreを含む医薬組成物、ならびにその使用方法 | |
KR20110096054A (ko) | 과불화탄소 겔 배합물 | |
US8603542B2 (en) | Veterinary topical agent | |
EP1625844A1 (en) | The composition for external use by percutaneous administration | |
CN101474284B (zh) | 一种治疗真菌性皮肤病的外用药 | |
CN107519236A (zh) | 一种治疗灰指甲的外用药剂 | |
US6589568B2 (en) | Therapeutic body lotion containing alkali metal hypohalite | |
JPH02500106A (ja) | 鱗屑形成性皮膚病用サリチル酸含有薬剤 | |
CN102526056B (zh) | 一种伏立康唑滴耳液及其制备方法和用途 | |
CN105832764A (zh) | 一种治疗***湿疹的软膏剂及其制备方法 | |
CN105168360A (zh) | 一种治疗痤疮、粉刺的植物提取物复方擦剂及其制备方法 | |
CN110063925A (zh) | 一种祛痘组合物及其制备方法 | |
CN105434431B (zh) | 一种多功能外用抗菌制剂及其制备方法和应用 | |
US5576005A (en) | Effectiveness of wart removal by compositions including propolis | |
CN113413331B (zh) | 祛痘组合物及其制剂和用途 | |
KR20180135169A (ko) | 퀘르세틴 및 비타민 d를 함유하는 여드름 피부 개선용 조성물 | |
US11318182B1 (en) | Plant extract for skin infections | |
JP2002332237A (ja) | 皮膚外用剤 | |
EP4346864A1 (en) | Method for the treatment of microbial overgrowth, imbalance and infections | |
EP1982694B1 (en) | Anti-oedema composition | |
CN1617709A (zh) | 克拉霉素的稳定局部制剂 | |
CN111686131A (zh) | 一种肛裂蛋黄霜及其制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1100904 Country of ref document: HK |
|
C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
WD01 | Invention patent application deemed withdrawn after publication | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: WD Ref document number: 1100904 Country of ref document: HK |