TR201602638A1 - OPHTHALMIC PHARMACEUTICAL COMPOSITIONS - Google Patents
OPHTHALMIC PHARMACEUTICAL COMPOSITIONS Download PDFInfo
- Publication number
- TR201602638A1 TR201602638A1 TR2016/02638A TR201602638A TR201602638A1 TR 201602638 A1 TR201602638 A1 TR 201602638A1 TR 2016/02638 A TR2016/02638 A TR 2016/02638A TR 201602638 A TR201602638 A TR 201602638A TR 201602638 A1 TR201602638 A1 TR 201602638A1
- Authority
- TR
- Turkey
- Prior art keywords
- pharmaceutical composition
- feature
- specified
- ophthalmic
- pharmaceutically acceptable
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 22
- 238000011282 treatment Methods 0.000 claims abstract description 18
- 230000001506 immunosuppresive effect Effects 0.000 claims abstract description 12
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 11
- 229920001184 polypeptide Polymers 0.000 claims abstract description 10
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 10
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 10
- 206010061218 Inflammation Diseases 0.000 claims abstract description 8
- 230000004054 inflammatory process Effects 0.000 claims abstract description 8
- 239000004480 active ingredient Substances 0.000 claims abstract description 6
- 230000000069 prophylactic effect Effects 0.000 claims abstract description 5
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 5
- 208000003556 Dry Eye Syndromes Diseases 0.000 claims description 16
- 206010013774 Dry eye Diseases 0.000 claims description 15
- -1 Abetimus Chemical compound 0.000 claims description 11
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 9
- 108010036949 Cyclosporine Proteins 0.000 claims description 9
- 229930182912 cyclosporin Natural products 0.000 claims description 9
- 239000000839 emulsion Substances 0.000 claims description 9
- 229960001265 ciclosporin Drugs 0.000 claims description 8
- 230000001965 increasing effect Effects 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 230000004489 tear production Effects 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 239000002552 dosage form Substances 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 239000002674 ointment Substances 0.000 claims description 4
- 239000000725 suspension Substances 0.000 claims description 4
- 208000009319 Keratoconjunctivitis Sicca Diseases 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 239000000243 solution Substances 0.000 claims description 3
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 claims description 2
- 229960001683 abetimus Drugs 0.000 claims description 2
- 239000006071 cream Substances 0.000 claims description 2
- 239000000499 gel Substances 0.000 claims description 2
- 229940040145 liniment Drugs 0.000 claims description 2
- 239000000865 liniment Substances 0.000 claims description 2
- 239000006193 liquid solution Substances 0.000 claims description 2
- 239000006210 lotion Substances 0.000 claims description 2
- KASDHRXLYQOAKZ-ZPSXYTITSA-N pimecrolimus Chemical compound C/C([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@@H](OC)C[C@@H](C)C/C(C)=C/[C@H](C(C[C@H](O)[C@H]1C)=O)CC)=C\[C@@H]1CC[C@@H](Cl)[C@H](OC)C1 KASDHRXLYQOAKZ-ZPSXYTITSA-N 0.000 claims description 2
- 229960005330 pimecrolimus Drugs 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 239000003755 preservative agent Substances 0.000 claims description 2
- 229960001967 tacrolimus Drugs 0.000 claims description 2
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 claims description 2
- 229960002706 gusperimus Drugs 0.000 claims 1
- IDINUJSAMVOPCM-UHFFFAOYSA-N gusperimus Chemical compound NCCCNCCCCNC(=O)C(O)NC(=O)CCCCCCN=C(N)N IDINUJSAMVOPCM-UHFFFAOYSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 12
- 239000013543 active substance Substances 0.000 abstract description 6
- 230000002708 enhancing effect Effects 0.000 abstract description 2
- 206010023332 keratitis Diseases 0.000 abstract description 2
- 201000010666 keratoconjunctivitis Diseases 0.000 abstract description 2
- 230000015572 biosynthetic process Effects 0.000 abstract 2
- 239000003795 chemical substances by application Substances 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 239000002202 Polyethylene glycol Substances 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 235000002639 sodium chloride Nutrition 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 4
- 229920001213 Polysorbate 20 Polymers 0.000 description 4
- 229920001219 Polysorbate 40 Polymers 0.000 description 4
- 229920001214 Polysorbate 60 Polymers 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000004359 castor oil Substances 0.000 description 4
- 235000019438 castor oil Nutrition 0.000 description 4
- 238000003745 diagnosis Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 4
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 229960001484 edetic acid Drugs 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920000136 polysorbate Polymers 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 235000011069 sorbitan monooleate Nutrition 0.000 description 3
- 239000001593 sorbitan monooleate Substances 0.000 description 3
- 229940035049 sorbitan monooleate Drugs 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 239000012929 tonicity agent Substances 0.000 description 3
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- 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 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 235000019483 Peanut oil Nutrition 0.000 description 2
- DLRVVLDZNNYCBX-UHFFFAOYSA-N Polydextrose Polymers OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(O)O1 DLRVVLDZNNYCBX-UHFFFAOYSA-N 0.000 description 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- IYFATESGLOUGBX-YVNJGZBMSA-N Sorbitan monopalmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O IYFATESGLOUGBX-YVNJGZBMSA-N 0.000 description 2
- 239000004147 Sorbitan trioleate Substances 0.000 description 2
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 206010047571 Visual impairment Diseases 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 229960001631 carbomer Drugs 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000003002 pH adjusting agent Substances 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 239000000312 peanut oil Substances 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 description 2
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 description 2
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 2
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 2
- 229940068977 polysorbate 20 Drugs 0.000 description 2
- 229940101027 polysorbate 40 Drugs 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 229940068965 polysorbates Drugs 0.000 description 2
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
- 229940069328 povidone Drugs 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 235000019337 sorbitan trioleate Nutrition 0.000 description 2
- 229960000391 sorbitan trioleate Drugs 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 208000029257 vision disease Diseases 0.000 description 2
- 230000004393 visual impairment Effects 0.000 description 2
- 229920001285 xanthan gum Polymers 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- FDCJDKXCCYFOCV-UHFFFAOYSA-N 1-hexadecoxyhexadecane Chemical compound CCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCC FDCJDKXCCYFOCV-UHFFFAOYSA-N 0.000 description 1
- 239000000263 2,3-dihydroxypropyl (Z)-octadec-9-enoate Substances 0.000 description 1
- FKOKUHFZNIUSLW-UHFFFAOYSA-N 2-Hydroxypropyl stearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(C)O FKOKUHFZNIUSLW-UHFFFAOYSA-N 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- RZRNAYUHWVFMIP-GDCKJWNLSA-N 3-oleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-GDCKJWNLSA-N 0.000 description 1
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 208000034309 Bacterial disease carrier Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- 108010072220 Cyclophilin A Proteins 0.000 description 1
- 108010048028 Cyclophilin D Proteins 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 108010036941 Cyclosporins Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- FPVVYTCTZKCSOJ-UHFFFAOYSA-N Ethylene glycol distearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCOC(=O)CCCCCCCCCCCCCCCCC FPVVYTCTZKCSOJ-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 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 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- 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 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 102100034539 Peptidyl-prolyl cis-trans isomerase A Human genes 0.000 description 1
- 102100034943 Peptidyl-prolyl cis-trans isomerase F, mitochondrial Human genes 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 229920001100 Polydextrose Polymers 0.000 description 1
- 229920002675 Polyoxyl Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 206010067171 Regurgitation Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 239000004288 Sodium dehydroacetate Substances 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
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 description 1
- XLLNINGEDIOQGQ-UHFFFAOYSA-N [acetyloxy(hydroxy)phosphoryl] acetate Chemical compound CC(=O)OP(O)(=O)OC(C)=O XLLNINGEDIOQGQ-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 229940099583 aluminum starch octenylsuccinate Drugs 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 229940101006 anhydrous sodium sulfite Drugs 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 238000011861 anti-inflammatory therapy Methods 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000000607 artificial tear Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 239000010836 blood and blood product Substances 0.000 description 1
- 229940125691 blood product Drugs 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 229960001777 castor oil Drugs 0.000 description 1
- 230000006727 cell loss Effects 0.000 description 1
- 229940081733 cetearyl alcohol Drugs 0.000 description 1
- 229940082500 cetostearyl alcohol Drugs 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000019504 cigarettes Nutrition 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 210000000795 conjunctiva Anatomy 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 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 1
- 238000011161 development Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 238000002405 diagnostic procedure Methods 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
- AMTWCFIAVKBGOD-UHFFFAOYSA-N dioxosilane;methoxy-dimethyl-trimethylsilyloxysilane Chemical compound O=[Si]=O.CO[Si](C)(C)O[Si](C)(C)C AMTWCFIAVKBGOD-UHFFFAOYSA-N 0.000 description 1
- SIGAZICKKNXYRV-XXAVUKJNSA-L disodium 4-[[(Z)-octadec-9-enoyl]amino]oxy-4-oxo-3-sulfonatobutanoate Chemical compound [Na+].[Na+].CCCCCCCC\C=C/CCCCCCCC(=O)NOC(=O)C(S([O-])(=O)=O)CC([O-])=O SIGAZICKKNXYRV-XXAVUKJNSA-L 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 230000004090 etiopathogenesis 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
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 235000021588 free fatty acids Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 229940075529 glyceryl stearate Drugs 0.000 description 1
- 229940100608 glycol distearate Drugs 0.000 description 1
- 210000002175 goblet cell Anatomy 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 230000002727 hyperosmolar Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 210000004561 lacrimal apparatus Anatomy 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 210000004175 meibomian gland Anatomy 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 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
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 238000010422 painting Methods 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 description 1
- 229960003330 pentetic acid Drugs 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920001987 poloxamine Polymers 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 235000013856 polydextrose Nutrition 0.000 description 1
- 239000001259 polydextrose Substances 0.000 description 1
- 229940035035 polydextrose Drugs 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 229920000259 polyoxyethylene lauryl ether Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000003441 saturated fatty acids Nutrition 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229940083037 simethicone Drugs 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 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 1
- 229940079839 sodium dehydroacetate Drugs 0.000 description 1
- 235000019259 sodium dehydroacetate Nutrition 0.000 description 1
- 229940023144 sodium glycolate Drugs 0.000 description 1
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
- JAJWGJBVLPIOOH-IZYKLYLVSA-M sodium taurocholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 JAJWGJBVLPIOOH-IZYKLYLVSA-M 0.000 description 1
- DSOWAKKSGYUMTF-GZOLSCHFSA-M sodium;(1e)-1-(6-methyl-2,4-dioxopyran-3-ylidene)ethanolate Chemical compound [Na+].C\C([O-])=C1/C(=O)OC(C)=CC1=O DSOWAKKSGYUMTF-GZOLSCHFSA-M 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 235000011071 sorbitan monopalmitate Nutrition 0.000 description 1
- 239000001570 sorbitan monopalmitate Substances 0.000 description 1
- 229940031953 sorbitan monopalmitate Drugs 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 229950003429 sorbitan palmitate Drugs 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 229940114926 stearate Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000004488 tear evaporation Effects 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 description 1
- 229960004418 trolamine Drugs 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 229940045860 white wax Drugs 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 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 description 1
- 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 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Mevcut buluş, keratokonjunktivitis sikka ile ilişkili oküler enflamasyona bağlı olarak gözyaşı yapımının baskılandığı öngörülen hastalarda gözyaşı yapımının artırılmasında profilaktik ve/veya semptomatik ve/veya terapötik tedavisinde kullanılmak üzere siklik bir polipeptit olan immünosüpresif özellikteki uygun etken maddeyi ve/veya farmasötik olarak kabul edilebilir türevlerini içeren farmasötik bileşim/ler ile ilgilidir.The present invention relates to a pharmaceutical composition comprising an immunosuppressive active agent and / or a pharmaceutically acceptable active ingredient comprising a cyclic polypeptide suitable for use in prophylactic and / or symptomatic and / or therapeutic treatment for enhancing tear formation in patients predicted to suppress tear formation due to ocular inflammation associated with keratoconjunctivitis cycka. composition (s).
Description
TARIFNAME OFTALMIK FARMASÖTIK BILESIMLER BULUSUN ILGILI OLDUGU ALAN Mevcut bulus, keratokonjunktivitis sikka ile iliskili oküler enflamasyona bagli olarak gözyasi yapiminin baskilandigi öngörülen hastalarda gözyasi yapiminin artirilmasinda profilaktik ve/veya semptomatik ve/veya terapötik tedavisinde kullanilmak üzere siklik bir polipeptit olan immünosüpresit` özellikteki uygun etken maddeyi ve/veya farmasötik olarak kabul edilebilir türevlerini içeren farmasötik bilesim/ler ile ilgilidir. DESCRIPTION OPHTHALMIC PHARMACEUTICAL COMPOSITIONS FIELD OF THE INVENTION The present invention is related to ocular inflammation associated with keratoconjunctivitis sicca. in increasing tear production in patients who are predicted to have suppressed tear production. cyclic therapy for use in the prophylactic and/or symptomatic and/or therapeutic treatment the appropriate active substance with immunosuppressive properties, which is a polypeptide, and/or pharmaceutically relates to pharmaceutical composition(s) containing acceptable derivatives.
Mevcut bulus; siklik bir polipeptit olan immünosüpresif özellikteki etken maddenin ve/veya farmasötik olarak kabul edilebilir türevleri oldugu ve uygun farmasötik formlarda etken madde olarak kullanildigi farmasötik bilesimler ile ilgilidir. The present invention; The active substance with immunosuppressive properties, which is a cyclic polypeptide and/or pharmaceutically acceptable derivatives and in suitable pharmaceutical forms relates to pharmaceutical compositions in which it is used as an active ingredient.
Formül 1: Ayrica bulus, Siklosporin ve/veya farmasötik olarak kabul edilebilir türevlerini içeren farmasötik bilesiinlerin oftalmik, oral ve parenteral uygulama için uygun olan formülasyonlarini ve profilaktik, semptomatik veya terapötik kullanimlarini da kapsamaktadir. ÖNCEKI TEKNIK (TEKNIGIN BILINEN DURUMU) Kuru göz sendromu, oküler yüzey hasari ile birlikte görme bozuklugu ile sonuçlanabilen gözyasi filmi ve oküler yüzeyin multifaktoriyel bir hastaligidir. Bu tabloya artmis gözyasi osmolaritesi ve oküler yüzey inflamasyonu eslik etmektedir. Kuru göz hastaliginin her bir formu farkli tedavi protokolü gerektirmektedir ve dogru taniyi koymak bu nedenle çok önemlidir. Hastaligin tedavisinde kuru göze neden olan faktörlerin ortaya çikarilmasi ve semptomlari arttiran durumlarin engellenmesi önemlidir. Tedavi, medikal, anti-inflamatuar tedavi, kan ürünleri ile tedavi, girisimsel tedaviler, cerrahi tedavi ve halen gelistirilmekte Kuru göz sendromuna (KGS) neden olan faktörlerin ortaya çikarilmasi kuru göz tedavisinde çok önemlidir ve ilk basamaktir. Kuru göz hastalarinda gerek altta yatan nedenlere, gerek hastaligin kendisine ve gerekse komplikasyonlara yönelik tedaviler esas tedavi yöntemlerini olusturmaktadir. ” grubunun tanimladigi sekilde kuru göz aslinda “Oküler yüzey hasari ile birlikte rahatsizlik hissi, görme bozuklugu ve stabil olmayan gözyasi film tabakasina neden olan gözyasi ve oküler yüzeyin multifaktoriyel disfonksiyonu” olarak belirtilmistir. Bu nedenle etyolojiye baktigimizda aslinda birçok farkli mekanizmanin rol oynadigini görmekte ve tedavi planlarken de bu mekanizmalar göz önünde bulundurulmaktadir. Uzun yillardir devam eden arastirmalara ragmen kuru göz tanisi ve tedavisi halen zorluk tasimaktadir. Tanida semptomlarin ayrintili degerlendirilmesi ve tanisal testlerin uygun kombinasyonlari ile hastaya yaklasilmasi çok önemlidir. Tedavinin basarisini, konulan taninin dogrulugu ve olgularin kuru göz etyopatogenezine göre uygun siniflandirilmasi belirlemektedir (Akova Genel ve koruyucu önlemler: - Göz kirpma sayisinin arttirilmasi: Çalisma ortami nedeniyle veya ekstrapiramidal sistem hastaliklari (Parkinson hastaligi) olan kisilerde gözlerini sikica kapatip açmalari lipid salinimini stimüle ederek gözyasi buharlasmasini arttiracaktir.Formula 1: In addition, the invention includes Cyclosporine and/or its pharmaceutically acceptable derivatives. suitable for ophthalmic, oral and parenteral administration of pharmaceutical compounds formulations and their prophylactic, symptomatic or therapeutic use. covers. PRIOR ART (KNOWN STATE OF THE ART) Dry eye syndrome can result in visual impairment with ocular surface damage. It is a multifactorial disease of the tear film and ocular surface. Increased tears for this painting osmolarity and ocular surface inflammation. Dry eye disease form requires a different treatment protocol and making the correct diagnosis is therefore very important. is important. In the treatment of the disease, revealing the factors that cause dry eye and It is important to prevent situations that increase symptoms. Treatment, medical, anti-inflammatory treatment, treatment with blood products, interventional treatments, surgical treatment and still under development. Revealing the factors that cause dry eye syndrome (KGS) dry eye It is very important in the treatment and is the first step. In dry eye patients, both the underlying Treatments for the causes, both the disease itself and the complications, are essential. form treatment methods. ” group, dry eye is actually “Discomfort with ocular surface damage. sensation, visual impairment, and unstable tear film causing multifactorial dysfunction of the ocular surface. Therefore, the etiology When we look at it, we actually see that many different mechanisms play a role and the treatment These mechanisms are taken into account when planning. continue for many years Despite the researches, the diagnosis and treatment of dry eye is still difficult. in diagnosis detailed assessment of symptoms and appropriate combinations of diagnostic tests. Approaching the patient is very important. The success of the treatment, the accuracy of the diagnosis and It determines the appropriate classification of the cases according to the etiopathogenesis of dry eye (Akova General and protective measures: - Increasing the number of blinks: due to the working environment or the extrapyramidal system In people with diseases (Parkinson's disease), closing and opening their eyes tightly It will increase tear evaporation by stimulating its release.
-Ortamdaki nemin arttirilmasi: Cihazlar ile ortam nemi arttirilabilir. -Increasing the humidity in the environment: The ambient humidity can be increased with the devices.
-Ortam isisinin ayarlanmasi: Kenari kapali olan gözlükler ile ortam isisi ve nemi arttirilabilir.-Adjusting the ambient temperature: Ambient temperature and humidity with closed-sided glasses can be increased.
-Ortamdaki hava sirkülasyonunun degistirilmesi.-Changing the air circulation in the environment.
-Ortam isiklandirmasiz Floresan isik ve yogun günesli ortam semptomlari arttirmaktadir. -Çalisma ortaminda ekran ile iliskinin düzenlenmesi: Bilgisayar ekrani 10-15 derece asagida olacak sekilde ayarlanmalidir (Sheedy ve ark., 2003).-Without ambient lighting Fluorescent light and intense sun increase symptoms. -Regulation of the relationship with the screen in the working environment: The computer screen is 10-15 degrees It should be set as below (Sheedy et al., 2003).
-Ortamdaki sigara dumaninin ve tozun azaltilmasi (Altinörs ve ark., 2006). -Reducing cigarette smoke and dust in the environment (Altinörs et al., 2006).
-Kafein ve alkol aliminin düzenlenmesi: Sempatik-parasempatik sistem uyarinin degismesi sonucu gözyasi etkilenmektedir.-Regulation of caffeine and alcohol intake: Change of sympathetic-parasympathetic system stimulus As a result, tears are affected.
-Sivi aliminin arttirilmasi. -Increasing fluid intake.
-Gözyasina etkili sistemik ve lokal ilaçlarin alimina yönelik uyari ve tedbirler (ß-Blokör, antihistaminikler, antihipertansifler, antiandrojenler, östrojen gibi). -Warnings and precautions for the intake of systemic and local drugs effective on tears (ß-Blocker, such as antihistamines, antihypertensives, antiandrogens, estrogen).
-Sicak kompres uygulamasi: Meibomian fonksiyonlari düzenlenmis olur (Craig ve ark., 1997).-Hot compress application: Meibomian functions are regulated (Craig et al., 1997).
-Buhar tedavisi: Bu amaçla kullanilan gözlükler mevcuttur. -Steam therapy: There are glasses used for this purpose.
Kuru göz patogenezinde inflamasyonun öneminin farkedilmesi ile yeni tedavi yaklasimlari gündeme gelmistir. 19987de Stem ve arkadaslarinin ileri sürdügü gözyasi fonksiyonel ünitesi kuru göz patogenezindeki intlamasyon modelini destekler niteliktedir (Stem ve ark., 1998). Hiperosmolar gözyasi intlamatuar medyatörlerin salinimi ve inflamatuar kaskadin aktive olmasi ile yüzey epitelini hasara ugratabilir ve goblet hücre kaybi ile müsin üretiminde azalmaya neden olabilir (Djalilian ve ark., 2005). Suni gözyasi preparatina ragmen konjonktivadaki hipereminin, komeadaki boyanmanin ve iritasyon sikayetlerinin devain ettigi olgular antiintlamatuar tedavi için adaydirlar. New treatment approaches with the recognition of the importance of inflammation in the pathogenesis of dry eye has come to the fore. In 1998, Stem et al. suggested that the tear is functional. unit supports the inflamation model in the pathogenesis of dry eye (Stem and et al., 1998). Hyperosmolar tear release of inflammatory mediators and inflammatory With the activation of the cascade, it can damage the surface epithelium and cause goblet cell loss. may cause a decrease in mucin production (Djalilian et al., 2005). artificial tear hyperemia in the conjunctiva, staining and irritation in the comea Cases with persistent complaints are candidates for anti-inflammatory therapy.
Siklosporinin en belirgin 2 etkisi T lenfosit aktivasyonunu baskilamak ve çesitli hücre tiplerinde apoptozisi önlemektir. Bu etkileri sitoplazmada bulunan siklof'ilin A ve D denilen iki sitoplazmik protein yardimi ile olusturmaktadir. Siklofilin A ile Cs A”nin birlesmesi ile T lenfosit aktivasyonu sirasinda özellikle IL-2 salinimi önlenmis olur ve hücresel bagisiklik cevabi baskilanir. Siklofilin D”nin Cs A ile birlesmesi sonucu hücrede apoptozis baskilanir. Cs A°nin konjonktiva epitelinde apoptozisi azalttigi farelerdeki kuru göz modelinde gösterilmistir (Strong ve ark., 2005). Yapilan çok merkezli 877 olguyu içeren bir Faz III çalismasinda %0,05 ve %0,1”lik Cs A kullanimi karsilastirilmis ve 6 aylik tedavi sonrasinda her iki doz grubunda belirgin olarak gözyasi fonksiyonlarinda ve subjektif sikayetlerde düzelme olmustur (Sall ve ark., 2000). Bir baska çalismada da aköz yetmezlik ile birlikte olan kuru göz olgularinda topikal Cs A uygulamasinin azalmis goblet hücre sayisinda ve bu hücrelerden salgilanan TGF,de artisa neden oldugu saptanmistir (Pflugfelder ve ark., 2008). Topikal siklosporin A kuru gözün yarattigi inflamasyonu baskilamanin yanisira meibomian bezlerinin salgi kanallarini tikayan tikayan meibum içindeki serbest yag asitlerinin polar lipidlere dönüstürülmesinden kaynaklanan inflamasyonu, bakteri kolonizasyonunun ürettigi bakteri lipazlarini da baskilamaktadir (Perry ve ark., 2006). The two most prominent effects of cyclosporine are suppressing T lymphocyte activation and inhibiting various cell types. types to prevent apoptosis. These effects are caused by cyclophililine A and D in the cytoplasm. It is formed with the help of two cytoplasmic proteins called of cyclophilin A and Cs A IL-2 release is prevented during T lymphocyte activation and the cellular immune response is suppressed. As a result of the combination of cyclophilin D with Cs A, apoptosis is suppressed. Dry mice in which Cs A decreased apoptosis in the conjunctival epithelium. shown in the eye model (Strong et al., 2005). Multicenter 877 cases were performed. The use of 0.05% and 0.1% Cs A was compared in a Phase III study involving 6 After one month of treatment, there was significant improvement in tear function and in both dose groups. subjective complaints improved (Sall et al., 2000). In another study, aqueous Decreased goblet effect of topical Cs A application in dry eye cases with regurgitation It has been determined that it causes an increase in the number of cells and TGF secreted from these cells. (Pflugfelder et al., 2008). Topical cyclosporine A for inflammation of dry eye In addition to suppression, the meibum that blocks the secretory ducts of the meibomian glands resulting from the conversion of free fatty acids into polar lipids. It also suppresses inflammation and bacterial lipases produced by bacterial colonization. (Perry et al., 2006).
Siklosporinler, birçok farmakolojik özellige sahip polar olmayan, halkali oligopeptitlerin bir sinifindandir. Bunlar özellikle, bagisiklik bastirici ( immünosüpresif) ve iltihap önleyici (antienflamatuvar) etkinlikleriyle taninir ve diger yandan, bagisiklik (immün) kökenli kuru keratokonjonktivit hastalarinda, gözyasi bezi tarafindan gözyasi salgilanmasini arttirmalari ya da eski durumuna getirmeleri bakimindan etkilidirler. Cyclosporins are non-polar, cyclic oligopeptides with many pharmacological properties. is from a class. These are particularly immunosuppressive (immunosuppressive) and anti-inflammatory known for its (anti-inflammatory) activities and, on the other hand, increase tear secretion by the lacrimal gland in patients with keratoconjunctivitis or they are effective in reinstatement.
W08901772 nolu patent belgesinde Siklosporin ve bir dolgu maddesi içeren, gözyasi bezlerindeki bir bozukluk nedeniyle gözyasi eksikliginden sikayetçi hastalarda gözyasi üretimini arttirmaya yönelik, haricen kullanilan bir göz bilesiminden bahsedilmektedir. Özellikle sözü edilen dolgu maddeleri zeytin yagi, yerfistigi yagi, hintyagi, polioksietilenlenmis hint yagi, mineral yaglar, vazelinler, dimetilsülfoksit, bir alkol, lipozomlar, silisyum yaglari yada bunlarin karisimlaridir.In the patent document W08901772, teardrop containing Cyclosporine and a filler Tears in patients who complain of a lack of tears due to a disorder in their glands An externally used eye compound is mentioned to increase its production. Particularly mentioned fillers are olive oil, peanut oil, castor oil, polyoxyethyleneated castor oil, mineral oils, petrolatum, dimethylsulfoxide, an alcohol, liposomes are silicon oils or their mixtures.
BULUSUN AÇIKLAMASI Mevcut bulus, keratokonjunktivitis sikka ile iliskili Oküler enflamasyona bagli olarak gözyasi yapiminin baskilandigi öngörülen hastalarda gözyasi yapiminin artirilmasinda profilaktik ve/veya seinptomatik ve/veya terapötik tedavisinde kullanilmak üzere siklik bir polipeptit olan immünosüpresif özellikteki uygun etken maddeyi ve/veya farmasötik olarak kabul edilebilir türevlerini içeren farmasötik bilesim/ ler ile ilgilidir. DESCRIPTION OF THE INVENTION The present invention is related to Ocular inflammation associated with keratoconjunctivitis sicca. in increasing tear production in patients who are predicted to have suppressed tear production. cyclic therapy for use in the prophylactic and/or symptomatic and/or therapeutic treatment the appropriate active substance with immunosuppressive properties, which is a polypeptide, and/or pharmaceutically relates to pharmaceutical composition(s) containing acceptable derivatives.
Mevcut bulusun bir diger yönü; oftalmik kullanilmak üzere siklik bir polipeptit olan immünosüpresif özellikteki uygun etken maddeyi ve/veya farmasötik olarak kabul edilebilir türevlerini ve farmasötik olarak kabul edilebilir yardimci maddeleri içeren farmasötik bilesimler ile ilgilidir. Another aspect of the present invention is; a cyclic polypeptide for ophthalmic use Accept the appropriate active substance with immunosuppressive properties and/or pharmaceutical containing derivatives and pharmaceutically acceptable excipients. relates to pharmaceutical compositions.
Bulusta siklik bir polipeptit olan immünosüpresif özellikteki uygun etken madde bunlarla sinirli olmamakla birlikte, Takrolimus, Siklosporin, Pimekrolimus, Abetimus, Gusperiinus ve/veya farmasötik olarak kabul edilebilir türevlerinin arasindan tercihen Siklosporin olarak seçilir. In the invention, the appropriate active substance with immunosuppressive properties, which is a cyclic polypeptide, but not limited to Tacrolimus, Cyclosporine, Pimecrolimus, Abetimus, Gusperiinus and/or pharmaceutically acceptable derivatives, preferably Cyclosporine is selected as.
Bulusta “farmasötik olarak kabul edilebilir türevleri” terimi ile farmasötik olarak kabul edilebilir uygun tuzlar, esterler, solvatlar, hidratlar, kompleksler, polimorflar, enantiyomerler, önilaçlar, asit adisyon tuzlari, analoglar, izomerler, rasematlar, ainidler, enantiyomer tuzlari, bazik tuzlar, konjugeler, tautomerler, anhidratlar, anhidritler, bazlar, asitler, eterler, kristal ve amorf formlar veya serbest formlarindan bir veya daha fazlasi ifade edilmektedir. In the invention, the term "pharmaceutically acceptable derivatives" is defined as pharmaceutically acceptable. Suitable salts, esters, solvates, hydrates, complexes, polymorphs, enantiomers, prodrugs, acid addition salts, analogs, isomers, racemates, ainides, enantiomer salts, basic salts, conjugates, tautomers, anhydrates, anhydrides, bases, one or more of acids, ethers, crystalline and amorphous forms or free forms is expressed.
Oftalinik uygulama için hazirlanan farmasötik bilesim/ler damla (solüsyon, süspansiyon), krem, jel, merhem, losyon, liniment (sivi merhem), solüsyon, süspansiyon, emülsiyon (su/yag, yag/su) ve sivi çözelti gibi dozaj formlarinda olabilir. Pharmaceutical composition(s) prepared for ophthalmic administration, drop (solution, suspension), cream, gel, ointment, lotion, liniment (liquid ointment), solution, suspension, emulsion It can be in dosage forms such as (water/oil, oil/water) and liquid solution.
Bulusta oftalmik uygulama için hazirlanan farmasötik bilesim/ler tercihen farmasötik emülsiyon formundadir. Oftalmik emülsiyon tek kullanimlik flakon/lar halinde ve/veya veya çoklu kullanima uygun olacak sekilde hazirlanir. The pharmaceutical composition(s) prepared for ophthalmic administration in the invention is preferably pharmaceutical in emulsion form. Ophthalmic emulsion in single-use vials/s and/or or prepared to be suitable for multiple uses.
Bulusta kullanilan oftalmik uygulamaya yönelik farmasötik formülasyon; uygun etken madde/ler yaninda en az bir çözünürlük arttirici ajan, en az bir tonisite ajani, en az bir Viskozite arttirici ajan, en az bir pH ayarlayici ajan, en az bir stabilizör, en az bir emülgatör ve tasiyicinin da dahil oldugu gruptan seçilen bir veya daha fazla yardimci madde içerebilen bir bilesimi tanimlar. Pharmaceutical formulation for ophthalmic administration used in the invention; appropriate factor In addition to the substance/s, at least one solubilizing agent, at least one tonicity agent, at least one Viscosity increasing agent, at least one pH adjusting agent, at least one stabilizer, at least one emulsifier and one or more excipients selected from the group that includes the carrier Defines a composition that can contain
Bulusta “çözünürlük arttirici ajan” ilacin sudaki çözünürlügünü ve göz içerisine ilacin absorbsiyonunu arttirir, aköz stabiliteyi iyilestirir, lokal irritasyonu azaltirlar. Bu nedenle bulusta çözünürlük arttirici ajan olarak; hidroksi propil betasiklodesktrin gibi siklo dekstrinler, polietoksillenmis hint yagi, yerfistigi yagi, mineral yaglar, vazelinler, dimetilsülfoksit, hintyagi, povidon kullanilabilir. In the invention, “solubility enhancing agent” means the solubility of the drug in water and the injection into the eye. They increase absorption, improve aqueous stability, reduce local irritation. Because as a solubilizing agent in the invention; cyclone, such as hydroxypropyl betacyclodesktrin dextrins, polyethoxylated castor oil, peanut oil, mineral oils, petroleum jelly, dimethylsulfoxide, castor oil, povidone can be used.
Bulusta “tonisite ajani” terimi, standart referans madde ile ayni osmotik basinca sahip maddeleri ifade etmektedir. Tonisite ajani olarak; sodyum klorür, mannitol, sorbitol, gliserin (gliserol), borik asit, potasyum nitrat, glukoz veya bunlarin karisimlari kullanilabilir. In the invention, the term "tonicity agent" means having the same osmotic pressure as the standard reference substance. means items. As a tonicity agent; sodium chloride, mannitol, sorbitol, glycerin (glycerol), boric acid, potassium nitrate, glucose or mixtures thereof can be used.
Bulusta “Viskozite ajani” terimi, sivinin kalinligini arttirarak yavas akmasini saglayan bir ajan veya ajan karisimini belirtmektedir. Viskozite ajani olarak karbomer, ksantam gami, guar gam, acacia, povidon, aljinik asit, etilselüloz, jelatin, hidroksietil selüloz, hidroksipropil selüloz, poliVinil pirolidon, hidroksi propil metil selüloz (HPMC), polidekstroz, karragenan, metil selüloz, sukroz, sorbitol, ksilitol, hidroksipropil metilselüloz, polivinil alkol, ketearil alkol, kolloidal silikon dioksit ve bunlarin karisimlari kullanilabilir. In the invention, the term “viscosity agent” is a liquid that increases the thickness of the liquid and makes it flow slowly. denotes an agent or a mixture of agents. Carbomer, xantham gum as viscosity agent, guar gum, acacia, povidone, alginic acid, ethylcellulose, gelatin, hydroxyethyl cellulose, hydroxypropyl cellulose, polyVinyl pyrrolidone, hydroxy propyl methyl cellulose (HPMC), polydextrose, carrageenan, methyl cellulose, sucrose, sorbitol, xylitol, hydroxypropyl methylcellulose, polyvinyl alcohol, ketaryl alcohol, colloidal silicon dioxide and mixtures thereof can be used.
Bulusta pH ayarlayici ajan olarak; sülfürik asit, sodyum hidroksit, hidroklorik asit, sodyum klorit, asetik asit, borik asit, anhidröz sodyum sülfit, sodyum sitrat, sodyum karbonat veya bunlarin karisimlari kullanilabilir.As a pH adjusting agent in the invention; sulfuric acid, sodium hydroxide, hydrochloric acid, sodium chloride, acetic acid, boric acid, anhydrous sodium sulfite, sodium citrate, sodium carbonate or mixtures of these can be used.
Bulusta “stabilizör” terimi; eklendiginde kristallenmeyi ya da faz ayrimini önleyen maddeler olarak ifade edilmektedir. Stabilizör olarak benzoik asit, edetik asit, salisilik asit, sorbik asit, sodyum dehidroasetat, tokoferol, butillenmis hidroksianisol, butillenmis hidroksitoluen, propilgallat, kastor yagi, oleil alkol, poloksamer ve poloksaminler (polioksietilen ve polioksipropilen blok kopolimeri), ksantan zamki, sorbitan yag asitlerinin etoksillenmis esterleri, sorbitan trioleat, sorbitan monooleat, sorbitaii monolaurat; polioksietilen (20) sorbitan monolaurat (polisorbat 20), polioksietilen (20) sorbitan monopalmitat (polisorbat 40), polioksietilen (20) sorbitan monostearat (polisorbat 60), polioksietilen (20) sorbitan moiiooleat (polisorbat 80) gibi polisorbatlar, etoksillenmis mono- ve digliseritler, etoksillenmis lipidler, etoksillenmis yag alkolleri veya yag asitleri, diasetil fosfat, fosfatidil gliserol, doymus veya doymamis yag asitleri, sodyum kolat, sodyum glikolat, sodyum taurokolat, paraoksibenzoik asit, etilen diamin tetraasetik asit (EDTA), dietilen triamin penta asetik asit veya bunlarin karisimlari kullanilabilir. The term "stabilizer" in the invention; prevents crystallization or phase separation when added referred to as items. Benzoic acid, edetic acid, salicylic acid as stabilizer, sorbic acid, sodium dehydroacetate, tocopherol, butylated hydroxyanisole, butylated hydroxytoluene, propylgallate, castor oil, oleyl alcohol, poloxamer and poloxamines (polyoxyethylene and polyoxypropylene block copolymer), xanthan gum, sorbitan oil ethoxylated esters of acids, sorbitan trioleate, sorbitan monooleate, sorbitaii monolaurate; polyoxyethylene (20) sorbitan monolaurate (polysorbate 20), polyoxyethylene (20) sorbitan monopalmitate (polysorbate 40), polyoxyethylene (20) sorbitan monostearate (polysorbate) 60), polysorbates such as polyoxyethylene (20) sorbitan moiooleate (polysorbate 80), ethoxylated mono- and diglycerides, ethoxylated lipids, ethoxylated fatty alcohols or fatty acids, diacetyl phosphate, phosphatidyl glycerol, saturated or unsaturated fatty acids, sodium cholate, sodium glycolate, sodium taurocholate, paraoxybenzoic acid, ethylene diamine tetraacetic acid (EDTA), diethylene triamine penta acetic acid or mixtures thereof can be used.
Bulusta “emülgatör” terimi, birbiri içerisinde karismayan iki sivi faz arasinda homojen dagilimi saglayan maddeler olarak ifade edilmektedir. Emülgatör olarak polietilen glikol stearat, polisorbat, poligliseril oleat, polioksietilen lauril eter, etoksilleiimis lariolin, stearil alkol, setostearil alkol, inakrogol setostearil, gliseril monostearat, setil alkol, polioksietilen lauril alkol, polioksi etilen sorbitan monostearat, polioksietilen stearat, sorbitan monostearat, propilen glikol stearat, alüminyum nisasta oktenilsuksinat, amonyum hidroksit, beyaz bir balmumu, sentetik bir balmumu, karbomer, setearil alkol, siklometikoii, digliseritler, dimetikon, disodyum monooleamido sülfosüksinat, pentaeritritol, gliseritler, gliseril monooleat, gliseril stearat, laiiolin, magnezyum hidrojene stearat, mineral yag, monogliseridler, polietilen glikol, polietilen glikol distearat, polietilen glikol monosetil eter, polietilen glikol monostearat, polioksietilen glikol, polioksil setostearil eter, polioksi] stearat, simetikon, sorbitan monolaurat, sorbitan monooleat, sorbitan monopalmitat, sorbitan palmitat, stearik asit, trietanolamin veya sodyum laurii sülfat veya bunlarin karisimlari kullanilabilir. In the invention, the term "emulsifier" means homogeneous between two immiscible liquid phases. are expressed as substances that provide dispersion. Polyethylene glycol as emulsifier stearate, polysorbate, polyglyceryl oleate, polyoxyethylene lauryl ether, ethoxylated lariolin, stearyl alcohol, cetostearyl alcohol, inacrogol cetostearyl, glyceryl monostearate, cetyl alcohol, polyoxyethylene lauryl alcohol, polyoxy ethylene sorbitan monostearate, polyoxyethylene stearate, sorbitan monostearate, propylene glycol stearate, aluminum starch octenylsuccinate, ammonium hydroxide, a white wax, a synthetic wax, carbomer, cetearyl alcohol, cyclomethicoii, diglycerides, dimethicone, disodium monooleamido sulfosuccinate, pentaerythritol, glycerides, glyceryl monooleate, glyceryl stearate, laiiolin, magnesium hydrogenated stearate, mineral oil, monoglycerides, polyethylene glycol, polyethylene glycol distearate, polyethylene glycol monocetyl ether, polyethylene glycol monostearate, polyoxyethylene glycol, polyoxyl cetostearyl ether, polyoxy] stearate, simethicone, sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate, sorbitan palmitate, stearic acid, triethanolamine or sodium laurii sulfates or their mixtures can be used.
Bulusta tasiyici olarak; sorbitan trioleat, sorbitan monooleat, sorbitaii monolaurat; polioksietilen (20) sorbitan monolaurat (polisorbat 20), polioksietilen (20) sorbitan monopalmitat (polisorbat 40), polioksietilen (20) sorbitan monostearat (polisorbat 60), polioksietilen (20) sorbitan monooleat (polisorbat 80) gibi polisorbatlar, saf su, enjeksiyonluk su, fizyolojik serum, sterilize damitilmis su gibi uygun sulu çözeltiler kullanilabilir.As a carrier in the invention; sorbitan trioleate, sorbitan monooleate, sorbitaii monolaurate; polyoxyethylene (20) sorbitan monolaurate (polysorbate 20), polyoxyethylene (20) sorbitan monopalmitate (polysorbate 40), polyoxyethylene (20) sorbitan monostearate (polysorbate 60), polysorbates such as polyoxyethylene (20) sorbitan monooleate (polysorbate 80), purified water, suitable aqueous solutions such as water for injections, physiological saline, sterilized distilled water can be used.
Bulus esas olarak oftalmik kullanilmak üzere siklik bir polipeptit olan immünosüpresif özellikteki uygun etken maddeyi ve/veya farmasötik olarak kabul edilebilir türevlerini ve farmasötik olarak kabul edilebilir uygun yardimci maddeleri içeren farmasötik bilesim/lerin hazirlanmasi ile ilgilidir. Bulusun farmasötik bilesimlerinin oftalmik emülsiyon formunda olmasi temeldir. Bulusun bir diger özelligi hazirlanan farmasötik oftalmik emülsiyonun koruyucu içermemesidir. Böylece Siklosporin ve/Veya farmasötik olarak kabul edilebilir türevlerini ve farmasötik olarak kabul edilebilir uygun yardimci maddeleri içeren farmasötik dozaj form/lari tahris edici özelliklerinin düsük olmasi, çabuk etki etmesi, gözde kuruluk yapmamasi, kullanimlarinin daha kolay olmasi gibi üstünlüklere sahiptir ve bu farmasötik bilesimler fiziksel ve kimyasal kararlilik açisindan oldukça stabil bir davranis sergilemistir.The invention is primarily an immunosuppressive, a cyclic polypeptide for ophthalmic use. appropriate active ingredient and/or pharmaceutically acceptable derivatives, and pharmaceutical containing suitable pharmaceutically acceptable excipients relates to the preparation of the composition(s). The ophthalmic compositions of the pharmaceutical compositions of the invention It is essential that it be in emulsion form. Another feature of the invention is the prepared pharmaceutical The ophthalmic emulsion does not contain preservatives. Thus, Cyclosporine and/or pharmaceutical acceptable derivatives and suitable pharmaceutically acceptable excipients. Pharmaceutical dosage form/s containing substances have low irritant properties, It has advantages such as being effective, not drying in the eyes, being easier to use. and these pharmaceutical compositions are quite stable in terms of physical and chemical stability. exhibited a behavior.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2016/02638A TR201602638A1 (en) | 2016-02-29 | 2016-02-29 | OPHTHALMIC PHARMACEUTICAL COMPOSITIONS |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2016/02638A TR201602638A1 (en) | 2016-02-29 | 2016-02-29 | OPHTHALMIC PHARMACEUTICAL COMPOSITIONS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TR201602638A1 true TR201602638A1 (en) | 2017-09-21 |
Family
ID=63832112
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TR2016/02638A TR201602638A1 (en) | 2016-02-29 | 2016-02-29 | OPHTHALMIC PHARMACEUTICAL COMPOSITIONS |
Country Status (1)
| Country | Link |
|---|---|
| TR (1) | TR201602638A1 (en) |
-
2016
- 2016-02-29 TR TR2016/02638A patent/TR201602638A1/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3518921B1 (en) | Compositions comprising a cannabinoid receptor binding ligand | |
| US20220079925A1 (en) | Compositions comprising tacrolimus for the treatment of intraocular inflammatory eye diseases | |
| ES2784229T3 (en) | Compositions and procedures for the treatment of eye inflammation and pain | |
| AU2017384650B2 (en) | Ophthalmic composition for treatment of dry eye disease | |
| DK2512515T3 (en) | PHARMACEUTICAL COMPOSITION FOR TREATMENT OF DRY EYES | |
| JP6824270B2 (en) | PEGylated lipid nanoparticles with bioactive lipophilic compounds | |
| US11759472B2 (en) | Compositions and methods of use for treating aberrant inflammation in peri-ocular secretory glands or at the ocular surface | |
| US20210052737A1 (en) | Ophthalmic formulation | |
| EA034839B1 (en) | Ophthalmic solution | |
| US11839616B2 (en) | Ocular pharmaceutical compositions | |
| US20230372360A1 (en) | Compositions and methods of use for treating aberrant inflammation in peri-ocular secretory glands or at the ocular surface | |
| US20170065611A1 (en) | Topical formulations and uses thereof | |
| BR112021015737A2 (en) | 4-(7-HYDROXY-2-ISOPROPYL-4-OXO-4H-QUINAZOLIN-3-YL)-BENZONITRILE FORMULATIONS | |
| TR201602638A1 (en) | OPHTHALMIC PHARMACEUTICAL COMPOSITIONS | |
| US20220226426A1 (en) | Ophthalmic composition for the treatment of ocular allergy | |
| JP7332602B2 (en) | Transdermal drug delivery system and method of use | |
| BR112021015998A2 (en) | METHODS TO TREAT OCULAR SURFACE PAIN | |
| TR201612233A1 (en) | OPHTHALMIC PHARMACEUTICAL COMPOSITIONS | |
| TR201604731A1 (en) | OPHTHALMIC PHARMACEUTICAL COMPOSITIONS | |
| JP2023518179A (en) | Use of anti-aging glycopeptides for the treatment of dry eye disease, retinal degenerative disease, or ocular inflammation | |
| OA19529A (en) | Compositions and methods for treating aberrant inflammation in peri - ocular secretory glands or at the ocular surface. | |
| Al-Saedi | Formulation and in vitro evaluation of cyclosporine A inserts prepared using HPMC for treating dry eye disease |