WO2006062184A1 - 分子内にフッ素原子を有するプロスタグランジン含有製品 - Google Patents
分子内にフッ素原子を有するプロスタグランジン含有製品 Download PDFInfo
- Publication number
- WO2006062184A1 WO2006062184A1 PCT/JP2005/022618 JP2005022618W WO2006062184A1 WO 2006062184 A1 WO2006062184 A1 WO 2006062184A1 JP 2005022618 W JP2005022618 W JP 2005022618W WO 2006062184 A1 WO2006062184 A1 WO 2006062184A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- prostaglandin
- derivative
- fluorine atom
- molecule
- container
- Prior art date
Links
- 150000003180 prostaglandins Chemical class 0.000 title claims abstract description 72
- 125000001153 fluoro group Chemical group F* 0.000 title claims abstract description 35
- 229910052731 fluorine Inorganic materials 0.000 title claims abstract description 33
- 230000001954 sterilising effect Effects 0.000 claims abstract description 26
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims abstract description 25
- 238000004659 sterilization and disinfection Methods 0.000 claims abstract description 23
- 239000007788 liquid Substances 0.000 claims abstract description 22
- 238000002360 preparation method Methods 0.000 claims abstract description 15
- 239000011347 resin Substances 0.000 claims abstract description 15
- 229920005989 resin Polymers 0.000 claims abstract description 15
- -1 3 —Chlorophenoxy Chemical group 0.000 claims description 33
- 239000002997 ophthalmic solution Substances 0.000 claims description 31
- 229940054534 ophthalmic solution Drugs 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 13
- PXGPLTODNUVGFL-BRIYLRKRSA-N (E,Z)-(1R,2R,3R,5S)-7-(3,5-Dihydroxy-2-((3S)-(3-hydroxy-1-octenyl))cyclopentyl)-5-heptenoic acid Chemical class CCCCC[C@H](O)C=C[C@H]1[C@H](O)C[C@H](O)[C@@H]1CC=CCCCC(O)=O PXGPLTODNUVGFL-BRIYLRKRSA-N 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 10
- 239000007864 aqueous solution Substances 0.000 claims description 9
- 239000004698 Polyethylene Substances 0.000 claims description 8
- 229920000573 polyethylene Polymers 0.000 claims description 8
- 125000005907 alkyl ester group Chemical group 0.000 claims description 7
- 239000003889 eye drop Substances 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 claims description 6
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 6
- 239000005020 polyethylene terephthalate Substances 0.000 claims description 6
- 229920000139 polyethylene terephthalate Polymers 0.000 claims description 6
- PXGPLTODNUVGFL-UHFFFAOYSA-N prostaglandin F2alpha Natural products CCCCCC(O)C=CC1C(O)CC(O)C1CC=CCCCC(O)=O PXGPLTODNUVGFL-UHFFFAOYSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 abstract description 3
- 230000003247 decreasing effect Effects 0.000 abstract 2
- 239000007789 gas Substances 0.000 description 19
- 150000001875 compounds Chemical class 0.000 description 14
- 230000000052 comparative effect Effects 0.000 description 9
- 238000010894 electron beam technology Methods 0.000 description 8
- GGXICVAJURFBLW-CEYXHVGTSA-N latanoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1CC[C@@H](O)CCC1=CC=CC=C1 GGXICVAJURFBLW-CEYXHVGTSA-N 0.000 description 7
- 229960001160 latanoprost Drugs 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 229940012356 eye drops Drugs 0.000 description 4
- 238000004388 gamma ray sterilization Methods 0.000 description 4
- 229920001155 polypropylene Polymers 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 3
- 239000005977 Ethylene Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 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 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 229920005604 random copolymer Polymers 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 description 1
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920002701 Polyoxyl 40 Stearate Polymers 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 239000004283 Sodium sorbate Substances 0.000 description 1
- CPGKMLVTFNUAHL-UHFFFAOYSA-N [Ca].[Ca] Chemical compound [Ca].[Ca] CPGKMLVTFNUAHL-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229960002684 aminocaproic acid Drugs 0.000 description 1
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 229960003260 chlorhexidine Drugs 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- OKBPCTLSPGDQBO-UHFFFAOYSA-L disodium;dichloride Chemical compound [Na+].[Na+].[Cl-].[Cl-] OKBPCTLSPGDQBO-UHFFFAOYSA-L 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- HQQADJVZYDDRJT-UHFFFAOYSA-N ethene;prop-1-ene Chemical group C=C.CC=C HQQADJVZYDDRJT-UHFFFAOYSA-N 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 230000005251 gamma ray Effects 0.000 description 1
- 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 1
- 239000004519 grease Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229940099429 polyoxyl 40 stearate Drugs 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- ZDHURYWHEBEGHO-UHFFFAOYSA-N potassiopotassium Chemical compound [K].[K] ZDHURYWHEBEGHO-UHFFFAOYSA-N 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 229920005653 propylene-ethylene copolymer Polymers 0.000 description 1
- 125000003259 prostaglandin group Chemical class 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- LROWVYNUWKVTCU-STWYSWDKSA-M sodium sorbate Chemical compound [Na+].C\C=C\C=C\C([O-])=O LROWVYNUWKVTCU-STWYSWDKSA-M 0.000 description 1
- 235000019250 sodium sorbate Nutrition 0.000 description 1
- 239000004328 sodium tetraborate Substances 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 239000000243 solution 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
- 239000000126 substance Substances 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 239000000057 synthetic resin Substances 0.000 description 1
- KKEYFWRCBNTPAC-UHFFFAOYSA-M terephthalate(1-) Chemical compound OC(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-M 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000012929 tonicity agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
- A61L2/0082—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using chemical substances
- A61L2/0094—Gaseous substances
-
- 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
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
- A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
- A61L2/20—Gaseous substances, e.g. vapours
-
- 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
Definitions
- the present invention relates to a product stored in a sterilized resin container containing an aqueous solution containing a prostaglandin derivative having a fluorine atom in its molecule or a salt thereof, and sterilization is performed with ethylene oxide gas.
- the present invention relates to a prostaglandin-containing product and a method for producing the same, characterized in that a decrease in the content of the prostaglandin derivative in an aqueous liquid is suppressed.
- a container for storing an aqueous liquid agent a resin-made container molded with a synthetic resin such as polypropylene, propylene-ethylene copolymer, or polyethylene is used.
- aqueous liquids such as eye drops are directly administered to eyes, which are particularly sensitive organs in the human body, it is strictly required to maintain sterility until the time of eye drops. Therefore, containers for storing eye drops must be sterile and must be sterilized.
- Known methods for sterilizing the container include gamma ray sterilization, electron beam sterilization, ethylene oxide gas sterilization, hydrogen peroxide sterilization, and high-pressure steam sterilization.
- Patent Document 1 includes 13, 14 dihydro-1, 15 keto prostaglandin derivatives, and Patent Document 2, 13, 14-dihydro-17 Fuenolei 18, 19, 20 Trinore Prostag Langin F2 a derivative power
- Patent Document 3 discloses 15 deoxy 15 monofluoroprostaglandin F2
- Patent Document 4 discloses 15 deoxy-15,15 difluoroprostaglandin F2 ⁇ derivative. Yes.
- Patent Document 1 and Patent Document 2 are directed to prostaglandin derivatives that do not have a fluorine atom in the molecule, while Patent Documents 3 and 4 include intramolecular molecules. Prostaglandin derivatives having a fluorine atom are the target.
- Patent Document 1 Japanese Patent Laid-Open No. 2-108 Patent Document 2: Japanese Patent Publication No. 3-501025
- Patent Document 3 Japanese Patent Laid-Open No. 10-251225
- Patent Document 4 JP-A-11-71344
- the storage stability of the prostaglandin derivative is a prostaglandin derivative that does not have a fluorine atom in the molecule. 13, 14-dihydro-17-phenol-18, 19, 20 — Trinor monoprostaglandin F2 a isopropyl ester (latanoprost), for example, does not decrease the content of latanoprost over time, even if it is stored in a sterilized resin container sterilized by gamma rays or electron beams.
- a prostaglandin derivative having a fluorine atom in it has a peculiarity that its content rate is likely to decrease when stored in a sterilized container sterilized by gamma rays or electron beams!
- the present inventors have preserved an aqueous liquid containing a prostaglandin derivative having a fluorine atom in the molecule in a resin-made container treated with ethylene oxide. As a result, it was found that a decrease in the content of the prostaglandin derivative having a fluorine atom in the molecule in the aqueous liquid preparation can be remarkably suppressed, and the present invention has been completed.
- the present invention provides:
- the prostaglandin-containing product according to (1), wherein the aqueous liquid preparation is an ophthalmic solution (3)
- the prostaglandin derivative having a fluorine atom in the molecule is a prostaglandin F2a derivative having a fluorine atom in the molecule or a salt thereof, containing the prostaglandin described in (1) or (2) above Products,
- prostaglandin-containing product according to (3) wherein the prostaglandin F2 a derivative having a fluorine atom in the molecule is a prostaglandin F2 a derivative having a fluorine atom at the 15-position,
- 15 Deoxy-15,15 Difluoroprostaglandin F2 a derivative is 16 phenoxy-15 deoxy-15,15 difluoro 17, 18, 19, 20-tetranorprostaglandin F2 a, 16- (3 chlorophenoxy 15) 15 Deoxy 15, 15 Difluo 17, 17, 19, 20—Tetranorprostaglandin F2 a, 16 Phenoxy 15 —Deoxy 15, 15 Difluoro 13, 14 Dihydro 17, 18, 19, 20 —A prostaglandin-containing product according to (5), which is tetraprostaglandin F2a or an alkyl ester thereof,
- Prostaglandin derivatives with fluorine atoms in the molecule are 16-phenoxy 15-deoxy-15,15 difluoro-17, 18, 19, 20-tetranor prostaglandin F2 a, 16- (3-chlorophenoxy 15) 15 Deoxy 15, 15 Difluoro 17, 1 8, 19, 20—Tetranorprostaglandin F2 a, 16 Phenoxy 15 Deoxy 1 5, 15 Difunole 1 13, 14 Dihydro 17, 18, 19, 20-tetranoreprostaglandin F2a or an alkyl ester thereof, and the resin container is made of polypropylene, propylene ethylene copolymer, polyethylene or polyethylene terephthalate (1) or (2) Prostaglandin-containing products as described in
- (9) Contains a prostaglandin derivative having a fluorine atom in the molecule or a salt thereof
- the content of the prostaglandin derivative or its salt in the aqueous solution is reduced by sterilizing the container with ethylene oxide gas.
- a prostaglandin derivative having a fluorine atom in the molecule which is an active ingredient of a prostaglandin-containing product in the present invention (hereinafter referred to as the present prostaglandin derivative), contains a fluorine atom in the molecule.
- the present prostaglandin derivative contains a fluorine atom in the molecule.
- it is preferably a prostaglandin F2 a derivative containing a fluorine atom in the molecule, more preferably a prostaglandin F2 a derivative having a fluorine atom at the 15-position, and more preferably 15—Deoxy—15,15 Difluoroprostaglandin F2 a derivative.
- alkyl ester examples include lower alkyl esters such as methyl ester, ethino les ester, propino les ester, isopropino les ester, tert-butino ester, pentyl ester, and hexyl ester.
- the resin-made container sterilized with ethylene oxide gas is not particularly limited as long as it is a sterilized container sterilized with ethylene oxide gas.
- Ethylene oxide gas sterilization is not particularly limited as long as it is a sterilization method using ethylene oxide gas.
- the resin container may be exposed to ethylene oxide gas for a sufficient time to sterilize at a predetermined temperature and a predetermined humidity, sterilized, and then air-laid to remove the ethylene oxide gas.
- the sterilization temperature is a force that can be appropriately selected according to the characteristics of the grease container. 0-60 ° C.
- the relative humidity is 20 to 90%, preferably 30 to 80%.
- Examples of the material of the resin-made container include polypropylene, polypropylene-polyethylene copolymer, polyethylene, polyethylene terephthalate, polyvinyl chloride, acrylic resin, polystyrene, etc., preferably polypropylene, propylene-ethylene copolymer, polyethylene, Examples thereof include polyethylene terephthalate, and particularly preferred are polypropylene and propylene monoethylene copolymer.
- the propylene-ethylene copolymer is not particularly limited as long as it is a propylene polymer containing an ethylene component, but is preferably a propylene polymer containing 10 mol% or less of an ethylene component.
- the prostaglandin derivative is preferably present in a state of being dissolved in water in a container.
- the concentration of the prostaglandin derivative may be appropriately selected in consideration of the use of the aqueous liquid agent.
- the concentration of the present prostaglandin derivative in the ophthalmic solution is monkey force with a suitable Yichun selected depending on the target disease or condition, such as 0. 00005 ⁇ 0. 05 0/0 ( W / V) Power I like it!
- the content of the prostaglandin derivative refers to the concentration of the prostaglandin derivative present in the aqueous solution at the beginning of the production of the prostaglandin-containing product after a predetermined period of time.
- the ratio (%) of the concentration of the prostaglandin derivative present in the aqueous solution For example, when the prostaglandin derivative is dissolved in water, the concentration of the prostaglandin derivative dissolved in water is determined after a predetermined period of time. The percentage (%) of the concentration of the prostaglandin derivative present in the aqueous solution.
- the prostaglandin-containing product of the present invention is an ophthalmic solution
- a surfactant examples include polysorbate 80, polyoxyethylene hydrogenated castor oil 60, and polyoxyl 40 stearate.
- the antioxidant include ethylenediamine tetraacetic acid or a salt thereof, dibutylhydroxytoluene and the like.
- isotonic agents include sodium chloride sodium, potassium salt potassium, calcium salt calcium, glycerin, propylene glycol and the like.
- buffer examples include boric acid, borax, citrate, disodium hydrogen phosphate, and ⁇ -aminocaproic acid.
- Preservatives include salted benzalcoum and darco Examples include chlorhexidine acid, benzethonium chloride, sorbic acid, sodium sorbate, oxyethyl benzoate, and butyl oxybenzoate.
- the method for preparing the ophthalmic solution containing the prostaglandin derivative does not require any special technique or operation, and the ophthalmic solution can be prepared by a widely used method.
- the pH of the ophthalmic solution is preferably 3 to 8, particularly 4 to 7.
- the prostaglandin derivative is stored in a resin-made container obtained by sterilizing the aqueous liquid of the present invention with ethylene oxide, gamma ray sterilization and electron beam
- the decrease in the content of the present prostaglandin derivative in the aqueous liquid can be significantly suppressed as compared with the case where it is stored in a sterilized container treated with either sterilization.
- this prostaglandin derivative As a representative example of this prostaglandin derivative, 0.005% (WZV) of 16-phenoxy-15-deoxy-15,15-difluoro-17, 18, 19, 20-tetranorprostaglandin F2 a isopropyl ester (Hereinafter referred to as this compound). This compound is dissolved in purified water using 0.05% (WZV) of polysorbate 80 as a nonionic surfactant, and ethylenediamine tetraacetic acid (appropriate amount), concentrated glycerin (appropriate amount) and salt Additives commonly used in ophthalmic solutions such as -um (appropriate amount) were added to obtain ophthalmic solution 1 having an osmotic pressure of about 1 and a pH of about 6.
- latanoprost which is a prostaglandin derivative having no fluorine atom in the molecule, was used to obtain ophthalmic solution 2 by the same procedure as 1) ophthalmic solution 1 adjustment method.
- Ethylene oxide gas sterilization treatment (ethylene oxide concentration 20% (VZV), temperature 40 ° C, relative humidity 50%, sterilization for 3 hours) is performed on the resin container obtained in “2. Thereafter, the eye drop 1 obtained in “1. Preparation of eye drop” was placed in the same container.
- This ophthalmic solution container was stored at a temperature of 40 ° C and a relative humidity of 75% before the start of storage and for 30 days. After that, the concentration of this compound in the container was measured by high performance liquid chromatography and stored. The content ratio of the compound was calculated using the concentration at the start as a reference (100%). The results are shown in Table 1.
- the values in Table 1 are the average values of three cases.
- the content of this compound was calculated in the same manner as in Example 1, except that the ethylene oxide gas sterilization treatment was changed to gamma ray sterilization treatment (32 kGy).
- the content of this compound was calculated in the same manner as in Example 1, except that the ethylene oxide gas sterilization treatment was changed to electron beam sterilization treatment (23 kGy).
- the content ratio of the present compound was calculated in the same manner as in Example 1 except that a sterilized untreated container was used as the container.
- the content of latanobrost was calculated in the same manner as in Example 1 except that ophthalmic solution 1 was changed to ophthalmic solution 2 and ethylene oxide gas sterilization treatment was changed to gamma ray sterilization treatment (32 kGy).
- Comparative Example 6 The content of latanobrost was calculated in the same manner as in Example 1, except that ophthalmic solution 1 was changed to ophthalmic solution 2 and ethylene oxide gas sterilization treatment was changed to electron beam sterilization treatment (23 kGy).
- the content of latanobroast was calculated in the same manner as in Example 1, except that ophthalmic solution 1 was changed to ophthalmic solution 2 and a sterile untreated container was used as the container.
- an ophthalmic solution containing latanoprost which is a prostaglandin derivative having no fluorine atom in the molecule, in a container sterilized with gamma rays, electron beams or ethylene oxide gas. Even when the solution is stored, the content of latanoprost in the ophthalmic solution does not decrease, and the content of latanoprost in the ophthalmic solution is the same as when stored in a container that is not sterilized. It was about. Therefore, it was confirmed that an aqueous liquid preparation containing a prostaglandin derivative having no fluorine atom in the molecule such as latanoprost is stable even when stored in any sterilized container.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Ophthalmology & Optometry (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
- Apparatus For Disinfection Or Sterilisation (AREA)
- Packages (AREA)
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA2590277A CA2590277C (en) | 2004-12-09 | 2005-12-09 | Product containing prostaglandin having fluorine atom in its molecule |
ES05814731.5T ES2588581T3 (es) | 2004-12-09 | 2005-12-09 | Producto que contiene prostaglandina con átomo de flúor en su molécula |
US11/792,637 US20080139648A1 (en) | 2004-12-09 | 2005-12-09 | Product Containing Prostaglandin Having Fluorine Atom In Its Molecule |
KR1020077012095A KR101305649B1 (ko) | 2004-12-09 | 2005-12-09 | 분자 내에 불소 원자를 갖는 프로스타글란딘 함유 제품 |
EP05814731.5A EP1825855B1 (en) | 2004-12-09 | 2005-12-09 | Product containing prostaglandin having fluorine atom in molecule |
NO20073353A NO341174B1 (no) | 2004-12-09 | 2007-06-29 | Fluorholding prostaglandinprodukt og fremgangsmåte for fremstilling |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2004356969 | 2004-12-09 | ||
JP2004-356969 | 2004-12-09 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2006062184A1 true WO2006062184A1 (ja) | 2006-06-15 |
Family
ID=36578004
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2005/022618 WO2006062184A1 (ja) | 2004-12-09 | 2005-12-09 | 分子内にフッ素原子を有するプロスタグランジン含有製品 |
Country Status (10)
Country | Link |
---|---|
US (1) | US20080139648A1 (ja) |
EP (1) | EP1825855B1 (ja) |
JP (2) | JP2006187602A (ja) |
KR (1) | KR101305649B1 (ja) |
CN (2) | CN102526064A (ja) |
CA (1) | CA2590277C (ja) |
ES (1) | ES2588581T3 (ja) |
NO (1) | NO341174B1 (ja) |
RU (1) | RU2429849C2 (ja) |
WO (1) | WO2006062184A1 (ja) |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4753178B2 (ja) * | 2004-12-24 | 2011-08-24 | 参天製薬株式会社 | プロスタグランジンF2α誘導体含有製品 |
JP2008247828A (ja) * | 2007-03-30 | 2008-10-16 | Wakamoto Pharmaceut Co Ltd | ラタノプロストを含有する水性医薬組成物。 |
EP2127638A1 (en) | 2008-05-30 | 2009-12-02 | Santen Pharmaceutical Co., Ltd | Method and composition for treating ocular hypertension and glaucoma |
US9089720B2 (en) * | 2008-09-04 | 2015-07-28 | Santen Pharmaceutical Co., Ltd. | Hair growth promoting agent containing 15,15-difluoroprostaglandin F2α derivative as active ingredient |
RU2482851C2 (ru) * | 2009-02-20 | 2013-05-27 | Микро Лабс Лимитед | Хранение стабильного продукта простагландина |
EP2269575A1 (en) | 2009-06-30 | 2011-01-05 | Santen Pharmaceutical Co., Ltd | Method for improving bioavailability of latanoprost |
EP2979695B1 (en) | 2013-03-29 | 2018-08-01 | AskAt Inc. | Therapeutic agent for ocular disease |
WO2018235935A1 (ja) * | 2017-06-23 | 2018-12-27 | 参天製薬株式会社 | 水溶性粘稠化剤を含有する医薬組成物 |
JP7037349B2 (ja) * | 2017-06-23 | 2022-03-16 | 参天製薬株式会社 | 水溶性粘稠化剤を含有する医薬組成物 |
WO2019026992A1 (ja) | 2017-08-03 | 2019-02-07 | 参天製薬株式会社 | クロルヘキシジンを含有する医薬組成物 |
JP6855632B1 (ja) * | 2020-02-19 | 2021-04-07 | 千寿製薬株式会社 | 医薬製品 |
JP6798054B1 (ja) * | 2020-02-19 | 2020-12-09 | 千寿製薬株式会社 | 医薬製品 |
WO2022014707A1 (ja) | 2020-07-16 | 2022-01-20 | ラクオリア創薬株式会社 | 眼疾患の治療薬としてのtrpv4阻害薬 |
WO2024204749A1 (ja) * | 2023-03-31 | 2024-10-03 | ロート製薬株式会社 | 眼科組成物 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH1171344A (ja) * | 1996-12-26 | 1999-03-16 | Santen Pharmaceut Co Ltd | ジフルオロプロスタグランジン誘導体およびその用途 |
JP2004516099A (ja) * | 2000-12-22 | 2004-06-03 | ノバルティス アクチエンゲゼルシャフト | 医薬組成物の安定性の改善方法 |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4310543A (en) * | 1980-10-09 | 1982-01-12 | Hoffmann-La Roche Inc. | Prostaglandin compositions |
ATE82499T1 (de) * | 1987-09-18 | 1992-12-15 | R Tech Ueno Ltd | Okulare hypotensivagenzien. |
US5565492A (en) * | 1988-07-18 | 1996-10-15 | Alcon Laboratories, Inc. | Prostaglandin combinations in glaucoma therapy |
US5486540A (en) * | 1993-10-28 | 1996-01-23 | Allergan, Inc. | Cyclopentane heptanoic or heptenoic acid, 2-arylalkyl or arylalkenyl and derivatives as therapeutic agents |
US6235781B1 (en) * | 1998-07-14 | 2001-05-22 | Alcon Laboratories, Inc. | Prostaglandin product |
AU743607B2 (en) * | 1998-07-14 | 2002-01-31 | Alcon Laboratories, Inc. | Prostaglandin product |
US6440364B1 (en) * | 1999-02-16 | 2002-08-27 | Ethicon, Inc. | Method of degassing absorbable suture products |
JP2003500302A (ja) * | 1999-05-28 | 2003-01-07 | ノバルティス アクチエンゲゼルシャフト | 医薬品のパッケージおよびそのパッケージの滅菌方法 |
CA2422031C (en) * | 2000-09-13 | 2011-11-15 | Santen Pharmaceutical Co., Ltd. | Ophthalmic solutions comprising difluoroprostaglandin f2 alpha |
AU2002212234A1 (en) * | 2000-09-14 | 2002-03-26 | Novartis Ag | Stable ophthalmic preparation |
EP1666043B1 (en) * | 2003-07-31 | 2009-12-02 | Santen Pharmaceutical Co., Ltd. | Product containing prostaglandin |
JP4092507B2 (ja) * | 2003-07-31 | 2008-05-28 | 参天製薬株式会社 | プロスタグランジン含有製品 |
US20050049311A1 (en) * | 2003-09-03 | 2005-03-03 | Pharmacia & Upjohn Company | Medicinal products comprising prostaglandin compositions and methods of packaging such compositions |
-
2005
- 2005-12-09 CN CN201110396063XA patent/CN102526064A/zh active Pending
- 2005-12-09 JP JP2005355566A patent/JP2006187602A/ja active Pending
- 2005-12-09 US US11/792,637 patent/US20080139648A1/en not_active Abandoned
- 2005-12-09 CA CA2590277A patent/CA2590277C/en not_active Expired - Fee Related
- 2005-12-09 WO PCT/JP2005/022618 patent/WO2006062184A1/ja active Application Filing
- 2005-12-09 CN CNA2005800421480A patent/CN101072568A/zh active Pending
- 2005-12-09 EP EP05814731.5A patent/EP1825855B1/en active Active
- 2005-12-09 ES ES05814731.5T patent/ES2588581T3/es active Active
- 2005-12-09 RU RU2007125699/15A patent/RU2429849C2/ru active
- 2005-12-09 KR KR1020077012095A patent/KR101305649B1/ko active IP Right Grant
-
2007
- 2007-06-29 NO NO20073353A patent/NO341174B1/no not_active IP Right Cessation
-
2010
- 2010-12-20 JP JP2010283026A patent/JP5323040B2/ja active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH1171344A (ja) * | 1996-12-26 | 1999-03-16 | Santen Pharmaceut Co Ltd | ジフルオロプロスタグランジン誘導体およびその用途 |
JP2004516099A (ja) * | 2000-12-22 | 2004-06-03 | ノバルティス アクチエンゲゼルシャフト | 医薬組成物の安定性の改善方法 |
Also Published As
Publication number | Publication date |
---|---|
JP2011063625A (ja) | 2011-03-31 |
CN102526064A (zh) | 2012-07-04 |
RU2429849C2 (ru) | 2011-09-27 |
US20080139648A1 (en) | 2008-06-12 |
CA2590277A1 (en) | 2006-06-15 |
EP1825855A4 (en) | 2010-09-08 |
JP5323040B2 (ja) | 2013-10-23 |
RU2007125699A (ru) | 2009-01-20 |
KR101305649B1 (ko) | 2013-09-09 |
JP2006187602A (ja) | 2006-07-20 |
ES2588581T3 (es) | 2016-11-03 |
KR20070085523A (ko) | 2007-08-27 |
NO341174B1 (no) | 2017-09-04 |
CN101072568A (zh) | 2007-11-14 |
NO20073353L (no) | 2007-08-27 |
EP1825855B1 (en) | 2016-08-17 |
EP1825855A1 (en) | 2007-08-29 |
CA2590277C (en) | 2014-07-08 |
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