TR201714097A2 - İvermekti̇n topi̇k formülasyon - Google Patents
İvermekti̇n topi̇k formülasyon Download PDFInfo
- Publication number
- TR201714097A2 TR201714097A2 TR2017/14097A TR201714097A TR201714097A2 TR 201714097 A2 TR201714097 A2 TR 201714097A2 TR 2017/14097 A TR2017/14097 A TR 2017/14097A TR 201714097 A TR201714097 A TR 201714097A TR 201714097 A2 TR201714097 A2 TR 201714097A2
- Authority
- TR
- Turkey
- Prior art keywords
- topical formulation
- ivermectin
- formulation according
- formulation
- amount
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title description 24
- 238000009472 formulation Methods 0.000 title description 17
- SPBDXSGPUHCETR-JFUDTMANSA-N 8883yp2r6d Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O[C@@H]([C@@H](C)CC4)C(C)C)O3)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1C[C@H](C)[C@@H]([C@@H](C)CC)O[C@@]21O[C@H](C\C=C(C)\[C@@H](O[C@@H]1O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C1)[C@@H](C)\C=C\C=C/1[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\1)O)C[C@H]4C2 SPBDXSGPUHCETR-JFUDTMANSA-N 0.000 claims abstract description 33
- AZSNMRSAGSSBNP-UHFFFAOYSA-N 22,23-dihydroavermectin B1a Natural products C1CC(C)C(C(C)CC)OC21OC(CC=C(C)C(OC1OC(C)C(OC3OC(C)C(O)C(OC)C3)C(OC)C1)C(C)C=CC=C1C3(C(C(=O)O4)C=C(C)C(O)C3OC1)O)CC4C2 AZSNMRSAGSSBNP-UHFFFAOYSA-N 0.000 claims abstract description 30
- 229960002418 ivermectin Drugs 0.000 claims abstract description 30
- 239000012049 topical pharmaceutical composition Substances 0.000 claims abstract description 12
- 201000004700 rosacea Diseases 0.000 claims abstract description 9
- 241001303601 Rosacea Species 0.000 claims abstract description 8
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims description 15
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 claims description 14
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 8
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 claims description 8
- 229960000541 cetyl alcohol Drugs 0.000 claims description 7
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 claims description 7
- 239000003871 white petrolatum Substances 0.000 claims description 7
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 6
- 235000019271 petrolatum Nutrition 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 229940057917 medium chain triglycerides Drugs 0.000 claims description 4
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 claims description 4
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 claims description 4
- 229960002216 methylparaben Drugs 0.000 claims description 4
- 239000003755 preservative agent Substances 0.000 claims description 4
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 claims description 4
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 claims description 4
- 229960003415 propylparaben Drugs 0.000 claims description 4
- 239000004408 titanium dioxide Substances 0.000 claims description 3
- 230000000845 anti-microbial effect Effects 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims 2
- 230000008719 thickening Effects 0.000 claims 2
- 239000004615 ingredient Substances 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 abstract description 2
- 239000004480 active ingredient Substances 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 230000000699 topical effect Effects 0.000 description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 239000012535 impurity Substances 0.000 description 6
- 239000006071 cream Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000002335 preservative effect Effects 0.000 description 3
- 239000002562 thickening agent Substances 0.000 description 3
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 239000005660 Abamectin Substances 0.000 description 2
- 241000238876 Acari Species 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000002141 anti-parasite Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000003883 ointment base Substances 0.000 description 2
- 244000045947 parasite Species 0.000 description 2
- 229960005323 phenoxyethanol Drugs 0.000 description 2
- 229940118786 soolantra Drugs 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- VARHUCVRRNANBD-PVVXTEPVSA-N 22,23-dihydroavermectin B1b Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O[C@@H]([C@@H](C)CC4)C(C)C)O3)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C VARHUCVRRNANBD-PVVXTEPVSA-N 0.000 description 1
- IBSREHMXUMOFBB-JFUDTMANSA-N 5u8924t11h Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O3)C=C[C@H](C)[C@@H](C(C)C)O4)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 IBSREHMXUMOFBB-JFUDTMANSA-N 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 241001465677 Ancylostomatoidea Species 0.000 description 1
- 241000244203 Caenorhabditis elegans Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- YASYEJJMZJALEJ-UHFFFAOYSA-N Citric acid monohydrate Chemical compound O.OC(=O)CC(O)(C(O)=O)CC(O)=O YASYEJJMZJALEJ-UHFFFAOYSA-N 0.000 description 1
- 241000255925 Diptera Species 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 241001674048 Phthiraptera Species 0.000 description 1
- 229920002669 Polyoxyl 20 Cetostearyl Ether Polymers 0.000 description 1
- 241000258242 Siphonaptera Species 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
- 229950008167 abamectin Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 208000009736 adult acne Diseases 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 229940082500 cetostearyl alcohol Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960002303 citric acid monohydrate Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 229940008099 dimethicone Drugs 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 229940124274 edetate disodium Drugs 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 210000001061 forehead Anatomy 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000008309 hydrophilic cream Substances 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
- 229940075495 isopropyl palmitate Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 238000010525 oxidative degradation reaction Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 229940095050 propylene Drugs 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- KANINNSSRWMGIP-UHFFFAOYSA-M sodium;butyl 4-hydroxybenzoate;dodecyl sulfate;hexadecan-1-ol;methyl 4-hydroxybenzoate;octadecan-1-ol;propane-1,2-diol;propyl 4-hydroxybenzoate Chemical compound [Na+].CC(O)CO.COC(=O)C1=CC=C(O)C=C1.CCCOC(=O)C1=CC=C(O)C=C1.CCCCOC(=O)C1=CC=C(O)C=C1.CCCCCCCCCCCCCCCCO.CCCCCCCCCCCCOS([O-])(=O)=O.CCCCCCCCCCCCCCCCCCO KANINNSSRWMGIP-UHFFFAOYSA-M 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- 229940100617 topical lotion Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Classifications
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
Abstract
Mevcut buluş, rosacea tedavisinde kullanım için ivermektin topik formülasyonu ile ilgilidir. İvermektin hidrolitik stabilitesini iyileştirmek için etkin madde yağ fazında olacak şekilde formüle edilmiştir.
Description
TARIFNAME
IVERMEKTIN TOPIK FORMULASYON
Mevcut bulus, topikal yolla uygulanan ivermektin formülasyonuna ve bu formülasyonun
hazirlanmasina yönelik islemlere iliskindir.
açiklanmistir.
dihydro C-07681 olup, kimyasal yapisi asagida gösterilmistir (I):
Component Bia R = CH20H3
Component B1,, R = CH3
Avermektinlerin biri olan Abamektin bilesiginin semi-sentetik türevidir. ivermektin, 22,23-
dihydroavermectin B1a ve 22,23-dihydroavermectin B1b karisimi olup, en az %80 oraninda
içerdigi belirtilmektedir (Merck Index 13).
Makrosiklik Iakton halkasi tasiyan ivermektin, güçlü antiparaziter aktiviteye sahiptir ve
veteriner hekimlikte, iç parazitlere [yuvarlak solucan, kancali kurt] ve dis parazitlere [bit, pire,
kene, akar ve sineklere] karsi etkinligi kanitlanmis ve veteriner saglik 'ürünleri pazarinda
büyük 'öneme sahip bir antiparaziter etkin maddedir.
Ivermektinin suda çözünürlügü zayif oldugundan oral biyoyararlanimi oldukça düsüktür. Oral
ve topikal uygulamalarda düsük biyoyararlanimin daha düsük etkinlige neden oldugu
düsünülmektedir. Ancak ivermektin subkutan olarak uygulandiginda gastrointestinal
bariyerlerden etkilenmeden ve karacigerde ilk geçis etkisine ugramadan biyoyararlanimi
artmasi sözkonusu olmaktadir.
Piyasada mevcut olan SOOLANTRA krem %1 oraninda ivermektin içerir. Hidrofilik krem olup,
yardimci madde olarak carbomer copolymer type B, cetyl alcohol, citric acid monohydrate,
dimethicone, edetate disodium, glycerin, isopropyl palmitate, methylparaben, oleyl alcohol,
phenoxyethanol, polyoxyl 20 cetostearyl ether, propylene glycol, propylparaben, purified
water, sodium hydroxide, sorbitan monostearate ve stearyl alcohol içerir. SOOLANTRA krem
rosacea'nin enflamatör Iezyonlarinin tedavisinde kullanilir.
Rosacea yüzde kizariklik ve sisme sikayetleri ile seyreden yaygin bir deri hastaligidir. Siklikla
eriskin aknesi olarak bilinir. Hastalarda yanak, alin, çene ve burunda kizarikliklar görülür.
Bazen kulaklar, sirt ve gögüste hastaliktan etkilenebilir. Hastalik ilerlediginde küçük kilcal
damar genislemeleri ve üzerinde sivilce benzeri küçük kirmizi kabartilar meydana gelir.
Hastalik ilk basladiginda kendiliginden iyilesip tekrar edebilir. Nadiren kendiliginden
gerileyebilen hastalik, genellikle yillarca sürer ve tedavi edilmezse kötülesir.
EP Rosacea tedavisi için ivermektin içeren bir topikal farmas'otik
formülasyonla ilgilidir. Bilesim emülsiyon formunda olup, yag fazi, en az bir yüzey aktif
madde-emülsiyonlastirici, çözücülerin ve/veya pro-penetre edici maddelerin bir karisimi ve su
içerir. Çözücü ve/veya pro-penetre edici madde olarak propilen glikol, etanol, isopropilalkol,
butanol, N-metiI-2-pirolidon veya DMSO, polisorbat 80, fenoksietanolden seçilen ve propilen
glikol içeren maddeler belirtilmistir.
U rosacea tedavisinde oral veya topik yolla ivermektin kullanimini
U Rosacea tedavisinde ivermektin kullanimini kapsar. %0.075 ivermektin
içeren krem formu belirtilmistir.
cetaphil içinde hazirlanmis ivermektin (%0.05-8) topical losyon ile ilgilidir.
WOO ivermektin gibi az çözünen ilaçlarin emülsiyonlari ile ilgilidir.
Formülasyon bir emülsifyan, bir yag fazi ve su içerir. Yag fazi “polarite modifikasyon ajani”
olarak polisorbat içerir.
W bir yag asiti ve bir sulu surfaktan ile birlikte opsiyonel olarak
kosolvan içeren ivermektin kompozisyonu ile iliskilidir.
EP3019174 A1 (Galderma) Papulopustular Rosacea tedavisinde topical ivermektin kullanimi
ile ilgilidir.
Bulusun açiklamasi
Mevcut bulus, rosacea tedavisinde ivermektin kullanimini saglayan topikal formda ivermektin
içeren farmasötik bilesimle ve formülasyonun hazirlanmasina iliskilidir. Topikal formülasyonlar
krem, merhem, pat, losyon gibi cilt yoluyla kullanilan formülasyonlardir.
Bulus konusu bilesim agirlikça %1 (m/m) oraninda ivermektin içerir.
B1b (H2b1b) %20'den azdir (m/m).
Asagidaki sonuçlarda görülebilecegi zorlastirilmis bozundurma çalismalari neticesinde
ivermektin etkin maddesi asidik ve bazik kosullarda büyük miktarlarda bozunmaya
ugramaktadir.
Ortam Bozunma miktari %
Baslangiç 2.537
Asit Bozundurma 12.133
Baz Bozundurma 14.856
OksidatifBozundurma 1.728
Bulus konusu bilesim daha stabil ivermektin topik kompozisyon eldesi için ivermektinin yag
fazinda oldugu formülasyonla ilgilidir. ivermektin asit ve baz ortamda sulu çözelti içerisinde
bozunmaya yatkin oldugundan, etkin maddenin yag fazinda muhafaza edilmesinin su fazi
içerinde muhafaza edilmesinden daha stabil olacagi öngörülmektedir. Böylece ivermektin
hidrolitik stabilitesi probleminin üstesinden gelmek için ivermektin yag fazinda olacak sekilde
formüle edilmistir.
Formülasyonda yag fazi olarak hidrokarbon esasli merhem bazlari kullanimi öngörülmüstür.
Bu grup merhem bazlari suda çözünmez, su ile yikanmaz ve su içermez. Su absorbe
etmezler, yumusatici (emollient) ve oklusiv özelliktedir. Oleajinöz (yagli) olduklarindan
hidrolize yatkin ilaçlar için sivag olarak uygundur. Formülasyon için bu amaçla beyaz vazelin
(white petrolatum) seçilmistir. Formülasyon agirlikça (m/m) %50 ila 75, tercihen % 55 ila 65
beyaz vazelin içerir.
Formülasyonda kivam arttirici olarak setil alkol (setostearil alkol) ve stearil alkol kullanilmistir.
Formülasyonda toplam setil alkol ve stearil alkol miktari agirlikça (m/m) %5 ila 15, tercihen
Formülasyonda çözücü olarak orta zincirli trigliseridler, antimikrobik koruyucu olarak metal
paraben ve propel paraben seçilmistir. Formülasyonda orta zincirli trigliseridler miktari
Titan dioksit boyar madde olarak kullanilmistir.
Ornekler:
Ivermektin merhem asagidaki formülasyonda hazirlanmistir:
Bilesenler Miktar(glt'ilip) Miktar Islev
Setil alkol 1,20 4,00 Kivam arttirici ajan
Stearil alkol 0,90 3,00 Kivam arttirici ajan
Beyaz vazelin 18,36 61,20 Sivag
Metil paraben 0,06 0,20 Koruyucu
Propilparaben 0,03 0,10 Koruyucu
Titanyumdioksit 0,75 2,50 Boyar Madde
Toplam 30,00 100,00
Emülsiyon formundaki referans ürün ve yukaridaki formülasyonda hazirlanmis yag bazli test
sonunda safsizlik profilleri açisindan asagidaki kosullarda test edilmislerdir.
Kromatografik Kosullar (Chromatographic Conditions)
Cihaz: HPLC
Kolon: Kromasil
Akis Hizi:
Dalga Boyu: UV, 254 nm
Enjeksiyon Hacmi: 20 ul
Standart için Enjeksiyon Süresi: 40 dakika
Numuneler için Enjeksiyon Süresi: 60 dakika
Kolon Sicakligi: 25°C
Tray Sicakligi: 20°C
Çözücü: Metanol
Test kromatograminda ivermektin olarak H2b1b ve H2b1a piklerinin toplami göz önüne
alinmistir. Alikonma zamani
1.3 -1.5 dk.arasindaki impüritelerin toplami toplam bilinen
impL'irite , ivermektin (H2b1b ve H2b1a) ve bilinen impuriteler disindaki impuritelere ait pikler
toplam bilinmeyen safsizlik olarak tanimlanmaktadir.
Tablo 1a- Test ürünü baslangiç degerleri
Bilinmeyen 0,855
Tablo 1b- Test `ürünü 80°C 2. Gün degerleri
Bilinmeyen 0,850
Tablo 1c- Test ürünü 80°C 10. Gün degerleri
Bilinmeyen 0,929
Tablo 1d- Test ürünü 40°C 1 Ay @gelen (Numune 1)
Bilinmeyen 1,025
Tablo 1e- Test ürünü 40°C 1 Ay degerleri (Numune 2)
Bilinmeyen 1,106
Tablo 281- Referans ürün baslangiç de`erleri
Bilinmeyen 2,118
Tablo 2b- Referans ürün 80°C 2. Gün degerleri
Bilinmeyen 2,367
Tablo 20- Referans 'ürün 80°C 10. Gün degerleri
Bilinmeyen 4,008
Tablo 2d- Referans ürün 40°C 1 Ay degerleri(Numune 1)
Bilinmeyen 2,596
Tablo 2e- Referans ürün 40°C 1 Ay degerleri (Numune 2)
Bilinmeyen 2,596
Tablo 3a. Test ve referans ürünlerin 80°C kosullarinda karsilastirilmasi
Baslangiç 80°C 2 Gün 80°C 10 Gün
Tablo 3b. Test ve referans ürünlerin 40°C kosullarinda karsilastirilmasi
Baslangiç 40°C 1 AY
Test Referans Test1 Referans1 Test2 ReferansZ
Yukaridaki sonuçlardan görüldügü gibi test ürünün bilinen ve bilinmeyen safsizliklara
bozunmasi referans ürüne göre daha düsük olup, yag fazinda hazirlanan ivermektin topikal
preparat, emülsiyon formuna göre daha stabil bulunmustur.
Claims (10)
- Ivermektin içeren topik formülasyon olup, sivag olarak beyaz vazelin içerir.
- Istem 1`e göre topik formülasyon olup, beyaz vazelin miktari agirlikça (m/m) %50 ila 75, tercihen % 55 ila 65'tir.
- Istem 1 ila 2'nin herhangi birine göre topik formülasyon olup, en az bir kivam arttirici bilesik içerir.
- Istem 3'e göre topik formülasyon olup, kivam arttirici bilesik setil alkol ve stearil alkoldür.
- Istem 4'e göre topik formülasyon olup, toplam setil alkol ve stearil alkol miktari agirlikça (m/m) %5 ila 15, tercihen %5 ila 10'dur.
- Istem 1 ila 5'in herhangi birine göre topik formülasyon olup, çözücü olarak orta zincirli trigliseridler içerir.
- Istem öiya göre topik formülasyon olup, orta zincirli trigliseridler miktari agirlikça (m/m)
- Istem 1 ila ?inin herhangi birine göre topik formülasyon olup, antimikrobik koruyucu olarak metil paraben ve propil paraben içerir.
- Rosacea tedavisinde kullanim için önceki istemlerin herhangi birine göre hazirlanmis topik formülasyon.
- 10- Istem 9`a göre topik formülasyon asagidaki maddeleri içerir: Bilesenler Miktar(glt'üp) Miktar Setil alkol 1,20 4,00 Stearil alkol 0,90 3,00 Beyaz vazelin 18,36 61,20 Metil paraben 0,06 0,20 Propilparaben 0,03 0,10 Titanyumdioksit 0,75 2,50 Toplam 30,00 100,00
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2017/14097A TR201714097A2 (tr) | 2017-09-22 | 2017-09-22 | İvermekti̇n topi̇k formülasyon |
| PCT/TR2018/050519 WO2019059872A2 (en) | 2017-09-22 | 2018-09-22 | TOPICAL FORMULATION OF IVERMECTINE |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2017/14097A TR201714097A2 (tr) | 2017-09-22 | 2017-09-22 | İvermekti̇n topi̇k formülasyon |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TR201714097A2 true TR201714097A2 (tr) | 2018-10-22 |
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| Application Number | Title | Priority Date | Filing Date |
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| TR2017/14097A TR201714097A2 (tr) | 2017-09-22 | 2017-09-22 | İvermekti̇n topi̇k formülasyon |
Country Status (2)
| Country | Link |
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| TR (1) | TR201714097A2 (tr) |
| WO (1) | WO2019059872A2 (tr) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2854074B1 (fr) * | 2003-04-24 | 2007-11-23 | Galderma Res & Dev | Utilisation de l'ivermectine pour le traitement de desordres dermatologiques |
| US20160303152A1 (en) * | 2015-04-15 | 2016-10-20 | Gavis Pharmaceuticals | Topical Composition of Ivermectin |
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- 2017-09-22 TR TR2017/14097A patent/TR201714097A2/tr unknown
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Also Published As
| Publication number | Publication date |
|---|---|
| WO2019059872A2 (en) | 2019-03-28 |
| WO2019059872A3 (en) | 2019-06-20 |
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