CN114177182A - Application of sildenafil citrate/tadalafil/vardenafil in preparation of medicine for treating myopia - Google Patents
Application of sildenafil citrate/tadalafil/vardenafil in preparation of medicine for treating myopia Download PDFInfo
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- CN114177182A CN114177182A CN202111605127.2A CN202111605127A CN114177182A CN 114177182 A CN114177182 A CN 114177182A CN 202111605127 A CN202111605127 A CN 202111605127A CN 114177182 A CN114177182 A CN 114177182A
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- China
- Prior art keywords
- citrate
- vardenafil
- tadalafil
- myopia
- sildenafil citrate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 208000001491 myopia Diseases 0.000 title claims abstract description 53
- 230000004379 myopia Effects 0.000 title claims abstract description 50
- 239000003814 drug Substances 0.000 title claims abstract description 35
- 229960002639 sildenafil citrate Drugs 0.000 title claims abstract description 28
- DEIYFTQMQPDXOT-UHFFFAOYSA-N sildenafil citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 DEIYFTQMQPDXOT-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 229960000835 tadalafil Drugs 0.000 title claims abstract description 18
- IEHKWSGCTWLXFU-IIBYNOLFSA-N tadalafil Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C([C]4C=CC=CC4=N3)C[C@H]3N2C(=O)CN(C3=O)C)=C1 IEHKWSGCTWLXFU-IIBYNOLFSA-N 0.000 title claims abstract description 18
- SECKRCOLJRRGGV-UHFFFAOYSA-N Vardenafil Chemical compound CCCC1=NC(C)=C(C(N=2)=O)N1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(CC)CC1 SECKRCOLJRRGGV-UHFFFAOYSA-N 0.000 title claims abstract description 11
- 229960002381 vardenafil Drugs 0.000 title claims abstract description 11
- 238000002360 preparation method Methods 0.000 title abstract description 5
- 239000003889 eye drop Substances 0.000 claims abstract description 24
- 210000001508 eye Anatomy 0.000 claims abstract description 10
- KRRAUGJKMHOFMD-UHFFFAOYSA-N 2-[2-ethoxy-5-(4-ethylpiperazin-1-yl)sulfonylphenyl]-5-methyl-7-propyl-1h-imidazo[5,1-f][1,2,4]triazin-4-one;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.CCCC1=NC(C)=C(C(N=2)=O)N1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(CC)CC1 KRRAUGJKMHOFMD-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000007788 liquid Substances 0.000 claims abstract description 6
- 239000003755 preservative agent Substances 0.000 claims abstract description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 4
- 239000002671 adjuvant Substances 0.000 claims abstract description 3
- 239000002997 ophthalmic solution Substances 0.000 claims abstract 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 15
- -1 carboxybutyl Chemical group 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 7
- 229920001661 Chitosan Polymers 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 6
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 6
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 6
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 6
- 108010039918 Polylysine Proteins 0.000 claims description 5
- 229920002385 Sodium hyaluronate Polymers 0.000 claims description 5
- 229920000656 polylysine Polymers 0.000 claims description 5
- 230000002335 preservative effect Effects 0.000 claims description 5
- 229940010747 sodium hyaluronate Drugs 0.000 claims description 5
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 claims description 5
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 239000000022 bacteriostatic agent Substances 0.000 claims description 4
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 4
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 4
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 4
- 239000004327 boric acid Substances 0.000 claims description 4
- 235000010338 boric acid Nutrition 0.000 claims description 4
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 claims description 4
- 239000003623 enhancer Substances 0.000 claims description 4
- 230000003204 osmotic effect Effects 0.000 claims description 4
- 239000002504 physiological saline solution Substances 0.000 claims description 4
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 claims description 4
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 claims description 4
- 239000000243 solution Substances 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 3
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims description 2
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 claims description 2
- REPVLJRCJUVQFA-UHFFFAOYSA-N (-)-isopinocampheol Natural products C1C(O)C(C)C2C(C)(C)C1C2 REPVLJRCJUVQFA-UHFFFAOYSA-N 0.000 claims description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims 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 claims description 2
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 claims description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 2
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 2
- 229920001287 Chondroitin sulfate Polymers 0.000 claims 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 claims 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 claims description 2
- 239000011703 D-panthenol Substances 0.000 claims description 2
- SNPLKNRPJHDVJA-ZETCQYMHSA-N D-panthenol Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCCO SNPLKNRPJHDVJA-ZETCQYMHSA-N 0.000 claims description 2
- 235000004866 D-panthenol Nutrition 0.000 claims description 2
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 2
- 239000004698 Polyethylene Substances 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 2
- 229920002125 Sokalan® Polymers 0.000 claims description 2
- 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 claims description 2
- 229910021538 borax Inorganic materials 0.000 claims description 2
- 229940116229 borneol Drugs 0.000 claims description 2
- CKDOCTFBFTVPSN-UHFFFAOYSA-N borneol Natural products C1CC2(C)C(C)CC1C2(C)C CKDOCTFBFTVPSN-UHFFFAOYSA-N 0.000 claims description 2
- CDQSJQSWAWPGKG-UHFFFAOYSA-N butane-1,1-diol Chemical compound CCCC(O)O CDQSJQSWAWPGKG-UHFFFAOYSA-N 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 229960001631 carbomer Drugs 0.000 claims description 2
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 claims description 2
- 229960005091 chloramphenicol Drugs 0.000 claims description 2
- 229960004926 chlorobutanol Drugs 0.000 claims description 2
- 229940059329 chondroitin sulfate Drugs 0.000 claims description 2
- 229960003949 dexpanthenol Drugs 0.000 claims description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 2
- DTGKSKDOIYIVQL-UHFFFAOYSA-N dl-isoborneol Natural products C1CC2(C)C(O)CC1C2(C)C DTGKSKDOIYIVQL-UHFFFAOYSA-N 0.000 claims description 2
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 claims description 2
- 230000003203 everyday effect Effects 0.000 claims description 2
- 239000008103 glucose Substances 0.000 claims description 2
- 235000001727 glucose Nutrition 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 229920002674 hyaluronan Polymers 0.000 claims description 2
- 229960003160 hyaluronic acid Drugs 0.000 claims description 2
- 229940072106 hydroxystearate Drugs 0.000 claims description 2
- 229940041616 menthol Drugs 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
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- 235000019799 monosodium phosphate Nutrition 0.000 claims description 2
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 2
- YWFWDNVOPHGWMX-UHFFFAOYSA-N n,n-dimethyldodecan-1-amine Chemical class CCCCCCCCCCCCN(C)C YWFWDNVOPHGWMX-UHFFFAOYSA-N 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
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- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 2
- 229920000053 polysorbate 80 Polymers 0.000 claims description 2
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- 235000019422 polyvinyl alcohol Nutrition 0.000 claims description 2
- 239000004323 potassium nitrate Substances 0.000 claims description 2
- 235000010333 potassium nitrate Nutrition 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 235000002639 sodium chloride Nutrition 0.000 claims description 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 2
- 239000004317 sodium nitrate Substances 0.000 claims description 2
- 235000010344 sodium nitrate Nutrition 0.000 claims description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 2
- 235000011152 sodium sulphate Nutrition 0.000 claims description 2
- 239000004328 sodium tetraborate Substances 0.000 claims description 2
- 235000010339 sodium tetraborate Nutrition 0.000 claims description 2
- 239000004334 sorbic acid Substances 0.000 claims description 2
- 235000010199 sorbic acid Nutrition 0.000 claims description 2
- 229940075582 sorbic acid Drugs 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- 229960002920 sorbitol Drugs 0.000 claims description 2
- 239000004094 surface-active agent Substances 0.000 claims description 2
- 239000006196 drop Substances 0.000 claims 1
- 230000003020 moisturizing effect Effects 0.000 claims 1
- 239000002674 ointment Substances 0.000 claims 1
- BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 abstract description 20
- 229960003310 sildenafil Drugs 0.000 abstract description 10
- 229940079593 drug Drugs 0.000 abstract description 6
- 230000036770 blood supply Effects 0.000 abstract description 5
- 230000004308 accommodation Effects 0.000 abstract description 3
- 210000003161 choroid Anatomy 0.000 abstract description 3
- 230000001886 ciliary effect Effects 0.000 abstract description 3
- 210000003205 muscle Anatomy 0.000 abstract description 3
- 230000002829 reductive effect Effects 0.000 abstract description 3
- 210000001525 retina Anatomy 0.000 abstract description 3
- 210000003786 sclera Anatomy 0.000 abstract description 3
- 230000004323 axial length Effects 0.000 abstract description 2
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 210000005252 bulbus oculi Anatomy 0.000 abstract description 2
- 241000700198 Cavia Species 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 230000004438 eyesight Effects 0.000 description 6
- 229940012356 eye drops Drugs 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000001934 delay Effects 0.000 description 3
- 230000000979 retarding effect Effects 0.000 description 3
- 238000012795 verification Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 2
- 230000004423 myopia development Effects 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 1
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 1
- 206010013774 Dry eye Diseases 0.000 description 1
- ZTVIKZXZYLEVOL-MCOXGKPRSA-N Homatropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(O)C1=CC=CC=C1 ZTVIKZXZYLEVOL-MCOXGKPRSA-N 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 208000003464 asthenopia Diseases 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
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- 230000002708 enhancing effect Effects 0.000 description 1
- 229960000857 homatropine Drugs 0.000 description 1
- 230000004377 improving vision Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
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- 230000036961 partial effect Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000004436 pseudomyopia Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
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Images
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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/10—Ophthalmic agents for accommodation disorders, e.g. myopia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Abstract
The invention belongs to the technical field of new application of medicaments, and particularly relates to application of sildenafil citrate/tadalafil/vardenafil citrate in preparing medicaments for treating myopia. The application of sildenafil citrate, tadalafil and vardenafil in the preparation of the medicine for treating myopia is the content to be protected in focus, and the medicine is a liquid medicine, such as an eye drop. The invention also provides a medicament containing sildenafil, tadalafil and vardenafil for treating myopia. The above-mentioned drugs further include conventional adjuvants contained in ophthalmic solutions, such as preservatives, excipients and the like. The invention has the beneficial effects that: the sildenafil citrate, tadalafil and vardenafil citrate provided by the invention are applied to the treatment of myopia medicines, so that the blood supply of retina or choroid or ciliary muscle or sclera is effectively improved, the axial length of the inner wall of eyeball is reduced, or the accommodation capacity of the eye is enhanced, thereby achieving the purpose of treating myopia.
Description
Technical Field
The invention belongs to the technical field of new application of medicaments, and particularly relates to application of sildenafil citrate/tadalafil/vardenafil citrate in preparing medicaments for treating myopia.
Background
Until now, myopia does not have ideal retardation and treatment measures, and only can be removed by invasive operations such as laser myopia surgery and the like after adults. The incidence rate of myopia is higher and higher, the method becomes a serious social problem, a noninvasive and effective method for delaying myopia and even treating myopia is found, and the method has great social significance and economic significance.
CN105998020A discloses an eye drop capable of preventing myopia, which comprises homatropine, a preservative, a pH regulator, an isotonic regulator and a diluent, and the ratio of the components is as follows: a rear horse-made product: 0.01% -0.3%; preservative: 0.001% -0.05%; pH regulator: adjusting the pH value to 6.6-7.2; 1% -10% of an isoosmotic adjusting agent; diluting liquid: and (4) the balance. The eye drop can relieve the regulation muscle spasm in a short time and eliminate the pseudomyopia state by applying the low-concentration rear support to the eyes of a user before sleeping every day or every week when the user has eye fatigue or a myopia tendency, thereby achieving the purpose of preventing myopia.
The main effective component of the eye drop is the posterior aspects, but the specification does not give corresponding data to support whether the posterior aspects can effectively treat myopia. Therefore, without any data support, it is impossible to judge whether the eye drop is effective for preventing myopia.
The inventor consults other patent or journal literatures and finds that the eye drops have special effects on treating or preventing myopia. Therefore, if the eye drop can be invented, the eye drop can effectively prevent and treat myopia, the pain of a patient can be greatly relieved, the dry eye phenomenon caused by partial myopia operation can be avoided, and a fresh and bright world is provided for the patient.
Disclosure of Invention
In order to solve the technical problems, the invention provides a new application of sildenafil citrate/tadalafil citrate/vardenafil in preparing a medicine for treating myopia, and experiments show that the medicine has a remarkable curative effect on treating myopia.
The invention is mainly protected by the application of any one of sildenafil citrate, tadalafil and vardenafil citrate in preparing a medicament for treating myopia.
The medicine is preferably in liquid form, and is mainly used for improving and treating myopia by ophthalmic administration so as to achieve the purpose of recovering eyesight. Of course, the composition can also be any one of tablets, capsules, pills, granules, paste and decoction.
Preferably, the above-mentioned drug is an eye drop (eye drop).
The invention also provides a medicament containing any one of sildenafil citrate, tadalafil and vardenafil for treating myopia, which is also in the protection scope of the invention.
The above medicines also include conventional adjuvants contained in eye drops, such as antiseptic, excipient, moisture retention enhancer, osmotic pressure regulator, bacteriostatic agent, surfactant, and solubilizer;
the preservative is selected from: at least one of borneol, menthol, polylysine, chitosan, chlorobutanol, borax, dodecyl dimethyl ammonium salt, benzalkonium chloride, concentrated benzalkonium chloride solution 50 and sorbic acid;
the bacteriostatic agent is selected from any one of chloramphenicol, carboxybutyl chitosan, hydroxyethyl chitosan and the like;
the solubilizer is polyethylene glycol-15-hydroxystearate;
the moisture-keeping enhancer is at least one selected from sodium hyaluronate, propylene glycol, butanediol, sorbitol, chondroitin sulfate, hyaluronic acid, methylcellulose, D-panthenol, tween 80, polyvinyl alcohol, sodium carboxymethylcellulose, carbomer, polyoxyethylene 9-lauryl ether, polyoxyethylene 20-stearyl ether, glycerol, polyethylene pyrrolinone and boric acid;
the osmotic pressure regulator is at least one selected from sodium dihydrogen phosphate, sodium chloride, boric acid, potassium nitrate, glucose, sodium sulfate, disodium hydrogen phosphate, ethyl acetate and sodium nitrate;
of course, the conventional auxiliary materials are not limited to the above types, and may be other components beneficial to improve eyesight or improve the comfort of the myope. Such modifications are intended to fall within the scope of the present invention.
The medicine provided by the invention achieves the purpose of delaying or treating myopia by an eye administration mode, and provides a non-invasive mode for treating myopia.
The medicines sildenafil citrate, tadalafil and vardenafil provided by the invention have obvious effects in treating myopia, and the inventor analyzes that the medicines can reduce the myopia degree, possibly delays the myopia development and/or reduces the myopia degree and/or improves the vision through the following mechanisms:
(1) improving blood supply of retina, enhancing retina function, and improving vision;
(2) the blood supply of the choroid is improved, the choroid thickness is increased, and the axial length of the inner wall of the eyeball is reduced, namely the myopia degree is reduced;
(3) the blood supply of ciliary muscle which is responsible for the accommodation force in eyes is improved, the function of the ciliary muscle is enhanced, namely the accommodation force of the eyes is enhanced, and the vision is further improved;
(4) improves the blood supply of the sclera, changes the biomechanical strength of the sclera, delays the growth of the ocular axis and further delays the development of myopia.
Drawings
Fig. 1 is a diagram showing the verification of the anti-myopia effect of sildenafil citrate in guinea pigs in oral and eye drop modes.
Detailed Description
The present invention will now be further described with reference to specific embodiments in order to enable those skilled in the art to better understand the present invention.
Example 1
The sildenafil citrate is applied to the preparation of the myopia medicine, and the specific method comprises the following steps:
dissolving sildenafil citrate in physiological saline, keeping the concentration of sildenafil citrate about 0.7mg/mL, adding eye drop auxiliary materials, and uniformly mixing; then, the eye drops are dropped into eyes 1-3 times each time for 1-4 times a day.
The auxiliary materials of the eye drop are: 0.1% of sodium hyaluronate, 0.05% of sodium carboxymethylcellulose, 0.02% of glycerol and 0.01% of polylysine.
Example 2
The method for preparing the tadalafil applied to the preparation of the myopia medicine comprises the following steps:
dissolving sildenafil citrate in physiological saline, keeping the concentration of sildenafil citrate about 0.8mg/mL, adding eye drop auxiliary materials, and uniformly mixing; then, the eye drops are dropped into eyes 1-3 times each time for 1-4 times a day.
The auxiliary materials of the eye drop are: 0.1% of sodium hyaluronate, 0.02% of sodium carboxymethylcellulose, 0.03% of glycerol and 0.02% of polylysine.
Example 3
The method for preparing the medicine for treating the myopia by using the vardenafil comprises the following steps:
dissolving sildenafil citrate in physiological saline, keeping the concentration of sildenafil citrate about 0.6mg/mL, adding eye drop auxiliary materials, and uniformly mixing; then, the eye drops are dropped into eyes 1-3 times each time for 1-4 times a day.
The auxiliary materials of the eye drop are: 0.1% of sodium hyaluronate, 0.03% of sodium carboxymethylcellulose, 0.02% of sodium carboxymethylcellulose, 0.04% of glycerol and 0.01% of polylysine.
Example 4
4.1 verification of the anti-myopia Effect of oral sildenafil citrate on Guinea pigs
Sildenafil citrate is applied to a myopia experiment of 3-week-old guinea pigs, and the specific steps are as follows:
3 weeks old guinea pigs were orally administered sildenafil in an amount of 10mg per kg body weight once a day, and the refractive power was measured after 2, 4, 6, and 8 weeks after oral administration.
The diopters of the control group and the sildenafil oral group at week 8 were 1.63D and 1.82D, respectively, which were not statistically significant.
And covering the guinea pig with one eye to establish a form-deprivation type myopia model, wherein the diopters of the myopia model group and the oral sildenafil + myopia model group are respectively-3.61D and-1.56D at week 8, and the myopia degree of the later is obviously smaller than that of the former, so that the sildenafil has a retarding effect on myopia formation. As shown in figure 1.
4.2 verification of anti-myopia effect of sildenafil citrate by eye drop on guinea pigs
3-week-old guinea pigs were instilled with sildenafil solution (0.8 mg/ml) four times a day, and the refractive power was measured 2, 4, 6, and 8 weeks after instillation.
The diopters of the control group and the sildenafil eyedropper at week 8 were 1.63D and 2.31D, respectively, and the distance vision power of the latter was significantly greater than that of the former, demonstrating that sildenafil has a retarding effect on the reduction of distance vision, that is, a preventive effect on the formation of myopia.
Carrying out single-eye covering on guinea pigs, establishing a form-deprivation type myopia model, wherein the diopters of the myopia model group and the sildenafil eyespot + myopia model group are respectively-3.61D and 0.51D at week 8, and the myopia degree of the latter is obviously smaller than that of the former, thus proving that sildenafil has a retarding effect on myopia formation. As shown in figure 1.
Claims (10)
1. Application of sildenafil citrate/tadalafil/vardenafil in preparing medicine for treating myopia is provided.
2. The use of claim 1, wherein the medicament is any one of a liquid medicament, a tablet, a capsule, a pill, a granule, an ointment and a decoction.
3. The use of claim 1, wherein the medicament is an eye drop.
4. A medicine for treating myopia contains sildenafil citrate/tadalafil/vardenafil citrate.
5. The use of claim 1, wherein the medicament is an eye drop, and the medicament further comprises conventional excipients contained in ophthalmic solutions.
6. The use of claim 5, wherein the conventional adjuvant is at least one of a preservative, an excipient, a moisturizing enhancer, an osmotic pressure regulator, a bacteriostatic agent, a surfactant, and a solubilizing agent.
7. The use according to claim 6, wherein the preservative is selected from the group consisting of: at least one of borneol, menthol, polylysine, chitosan, chlorobutanol, borax, dodecyl dimethyl ammonium salt, benzalkonium chloride, concentrated benzalkonium chloride solution 50 and sorbic acid;
the bacteriostatic agent is selected from any one of chloramphenicol, carboxybutyl chitosan and hydroxyethyl chitosan;
the solubilizer is polyethylene glycol-15-hydroxystearate;
the moisture-keeping enhancer is at least one selected from sodium hyaluronate, propylene glycol, butanediol, sorbitol, chondroitin sulfate, hyaluronic acid, methylcellulose, D-panthenol, tween 80, polyvinyl alcohol, sodium carboxymethylcellulose, carbomer, polyoxyethylene 9-lauryl ether, polyoxyethylene 20-stearyl ether, glycerol, polyethylene pyrrolinone and boric acid;
the osmotic pressure regulator is at least one selected from sodium dihydrogen phosphate, sodium chloride, boric acid, potassium nitrate, glucose, sodium sulfate, disodium hydrogen phosphate, ethyl acetate, and sodium nitrate.
8. The use according to claim 1, wherein sildenafil citrate/tadalafil citrate/vardenafil citrate is dissolved for use.
9. The use of claim 1, wherein the sildenafil citrate/tadalafil citrate/vardenafil citrate is dissolved in a solution containing a physiological saline to form a liquid medicament for use.
10. The application method of the medicine containing sildenafil citrate/tadalafil/vardenafil for treating myopia is characterized in that: dripping the liquid medicine dissolved with sildenafil citrate/tadalafil/vardenafil in eyes for 1-4 times every day, and dripping 1-3 drops every time; or the sildenafil citrate is directly taken orally, and the dosage is 10 mg/kg.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001010406A2 (en) * | 1999-08-10 | 2001-02-15 | Board Of Regents, The University Of Texas System | Facilitating the preservation of sight by increasing optic nerve, choroidal and retinal blood flow |
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2021
- 2021-12-25 CN CN202111605127.2A patent/CN114177182A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001010406A2 (en) * | 1999-08-10 | 2001-02-15 | Board Of Regents, The University Of Texas System | Facilitating the preservation of sight by increasing optic nerve, choroidal and retinal blood flow |
Non-Patent Citations (2)
| Title |
|---|
| DAVID Y KIM等: "Measurement of choroidal perfusion and thickness following systemic sildenafil (Viagra(®) )", 《ACTA OPHTHALMOL》 * |
| 慕璟玉等: "近视的流行病学、病因学与发病机制研究现状", 《眼科新进展》 * |
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