+

WO1999026637A1 - Preparation et composition ophtalmiques - Google Patents

Preparation et composition ophtalmiques Download PDF

Info

Publication number
WO1999026637A1
WO1999026637A1 PCT/JP1998/005299 JP9805299W WO9926637A1 WO 1999026637 A1 WO1999026637 A1 WO 1999026637A1 JP 9805299 W JP9805299 W JP 9805299W WO 9926637 A1 WO9926637 A1 WO 9926637A1
Authority
WO
WIPO (PCT)
Prior art keywords
ophthalmic
meta
group
polymer
monomer
Prior art date
Application number
PCT/JP1998/005299
Other languages
English (en)
Japanese (ja)
Inventor
Tsuyoshi Miyazaki
Nobuharu Nakada
Ryota Ando
Nobuo Nakabayashi
Kazuhiko Ishihara
Original Assignee
Nof Corporation
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Nof Corporation filed Critical Nof Corporation
Publication of WO1999026637A1 publication Critical patent/WO1999026637A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F30/00—Homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and containing phosphorus, selenium, tellurium or a metal
    • C08F30/02—Homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and containing phosphorus, selenium, tellurium or a metal containing phosphorus

Definitions

  • the present invention relates to an ophthalmic agent that can be used for alleviating symptoms such as discomfort when using a dry eye contact lens, and an ophthalmic composition containing the ophthalmic agent.
  • Japanese Patent Application Laid-Open No. Hei 9-152828 describes sodium hyanorenoate. Is disclosed as an ophthalmic drug.
  • Japanese Patent Application Laid-Open No. 4-182022 discloses chondroitin sodium sodium as an ophthalmic drug.
  • a polymer obtained by polymerizing methacryloyloxylexylphosphorylcholin (hereinafter abbreviated as MPC) is coated on the surface of an article to form
  • Japanese Patent Application Laid-Open No. H05-43031 discloses that a polymer comprising 2-methacrylo-leinoleoxy phosphorylcoline is prepared by applying a composition containing the same to the skin. It discloses that a film that protects the stratum corneum is formed to exhibit an excellent moisturizing effect. However, it has not been known to use this polymer as an ophthalmic drug.
  • the purpose of the present invention is to provide the cornea and the like with sufficient water retention and dry eye.
  • allergy such as hay fever
  • feeling of feeling at the time of wearing a contact lens or the like and dry eyes.
  • R 1 R 2 and R 3 are the same or different groups and are each a hydrogen atom or an alkynole group having 1 to 4 carbon atoms, and m represents an integer of 2 to 4).
  • An ophthalmic agent consisting essentially of a polymer having a styrene-like group in the side chain is provided.
  • the polymer has the following general formula (2):
  • R 1 R 2 and R 3 are the same or different groups and represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms;
  • R 4 represents a hydrogen atom or a methyl group;
  • R 5 is a group represented by 1 (BO) n—B— (where B is an alkylene group having 2 to 12 carbon atoms, and n is 0 to 10) Indicates an integer.
  • m represents an integer of 2 to 4.
  • the above ophthalmology which is a homopolymer of a phosphorylcholine-like group-containing monomer represented by the formula: or a copolymer of the monomer and another monomer copolymerizable with the monomer. An agent is provided.
  • the phosphorylcholine-like group-containing monomer is represented by the following formula (3):
  • the polymer has the following general formula (4):
  • R 1 R 2 and R 3 are the same or different groups and Represents an atom or an alkyl group having 1 to 4 carbon atoms
  • R 4 represents a hydrogen atom or a methyl group
  • R 5 represents a group represented by one (B B) n—B —
  • B represents an alkylene group having 2 to 12 carbon atoms
  • n represents an integer of 0 to 10
  • m represents an integer of 2 to 4.
  • the above-mentioned ophthalmic preparation comprising the structural unit (a) represented by the formula (1), wherein the ratio of the structural unit (a) to the total of all the structural units is 10 to 100 mol%.
  • the structural unit (a) is represented by the following formula (5):
  • the weight-average molecular weight of the polymer is from 1,000 to 10,0,000,000, and the ophthalmic agent is provided.
  • an ophthalmic composition comprising the ophthalmic agent.
  • the ophthalmic composition wherein the content of the ophthalmic agent is from 0.000 :! to 40% by weight.
  • the ophthalmic composition having a pH of 3.0 to 9.0 and a physiological saline osmotic pressure ratio of 0.5 to 2.3. .
  • the ophthalmic composition further including a substance having another pharmacological action in addition to the ophthalmic agent.
  • the ophthalmic agent of the present invention is substantially composed of a polymer having a phosphorylcholine-like group represented by the general formula (1) in the side chain (hereinafter, abbreviated as PC-1 polymer). You.
  • R ′, R 2 and R 3 are the same or different and represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and m represents an integer of 2 to 4. It is difficult to obtain a raw material that gives R 1 R 2 and R 3 having 5 or more carbon atoms, and it is difficult to synthesize a material having m of 1 or 5 or more.
  • PC-1 polymer a monomer having a phosphorylcholine analogous group represented by the general formula (2) (hereinafter, abbreviated as PC-1 monomer) or Or phosphorylcholine such as maleic acid, fumaric acid, or itaconic acid having a phosphorylcholine analogous group represented by the above general formula (1) in the side chain. Homopolymerization of similar group-containing monomer And copolymers of these monomers and other monomers copolymerizable therewith.
  • PC-1 monomer a monomer having a phosphorylcholine analogous group represented by the general formula (2)
  • phosphorylcholine such as maleic acid, fumaric acid, or itaconic acid having a phosphorylcholine analogous group represented by the above general formula (1) in the side chain.
  • PC-1 monomer examples include, for example, 2— (meta) ataryloyloxitytil-12,1 (trimethylammonio) ethinolefos, 3— (Meta) acryloyloxy mouth mouth pill 1-2,-(trimethinoleammonio) ethyl phosphate, 41 (meta) atarilo oxybutyl-2 '-(trimethinole butyl) Ammonio) ethylphosphate, 5 — (meta) aryloyloxypentyl 1-2,1 (trimethylammonio) ethylphosphate, 2 — (meta) acryloyl Noreki Shechiru 2, 1 (triethylammonio) ethyl phosphate, 3 — (meta) acryloinorekipropiryl 1, 2 (triethylammonio) etinolejos (Meth) acryloyloxybutyl-2,1
  • Styrene monomers such as styrene, methinorestyrene, and chlorostyrene
  • bierester monomers such as vinyl acetate, vinyl propionate, and vinyl bivalate Body: Methinole (meta) acrylate, ethyl (meta) acrylate, n-butyl (meta) acrylate, t-butyl (meta) acrylate , 2 —ethylhexyl (meta) atalylate, dodecyl (meta) atalylate, stearyl (meta) atalylate, 2 — hydroxyxethyl (meta) acrylate (Meta) acrylate esters such as acrylates and benzyl (meta) acrylates; (meta) atalynoleamides, N, N — dimethyl (meta) acrylamide, N, N — dimethyl (Meth)
  • the structural unit (a) is a structural unit represented by the general formula (4)
  • the structural unit (b) examples of the polymer include a polymer having a structural unit other than the structural unit represented by the general formula (4).
  • the structural unit (a) specifically, for example, a structural unit obtained by polymerizing those listed as specific examples of the PC-1 monomer, preferably, a compound represented by the formula (1)
  • the structural unit represented by 5) can be mentioned.
  • the structural unit (b) specifically includes, for example, a polymer obtained by polymerizing various monomers listed above as other monomers copolymerizable with PC-1. Examples of the structural units include, but are preferably, methyl (meth) acrylate, butyl (meth) acrylate, and 2-ethylhexyl (meth) acrylate. Relate and the structural unit obtained by polymerizing a monomer selected from the group consisting of 2-hydroxyl (meth) acrylate and mixtures thereof may be mentioned. it can.
  • the content of constituent units that put the ophthalmic preparation of the present invention (a) and the structural unit (b) is a proportion of the structural unit against the total of the structural units (a) and the structural unit (b) (a) Te, and preferred rather than the 1 0-1 0 0 molar%, rather than the preferred Ri good is Ru can and child to 3 0-9 5 mol 0/0.
  • an ophthalmic agent having high water retention derived from a phosphorylcholine-like group, high antifouling property against proteins, and the like can be obtained. It can be.
  • the molecular weight of the polymer constituting the ophthalmic preparation of the present invention is preferably as a weight average molecular weight, more preferably from 1,000 to 10,000, 0000, 0000, and still more preferably.
  • the force S is desirably 5, 000 to 2, 0000, 0000.
  • the ophthalmic preparation of the present invention comprises a monomer component such as the above-mentioned monomer having a phosphorylcholine analogous group and another monomer copolymerizable therewith, such as a PC_1 monomer.
  • a monomer component such as the above-mentioned monomer having a phosphorylcholine analogous group and another monomer copolymerizable therewith, such as a PC_1 monomer.
  • a radical polymerization initiator under degassing conditions, or in the presence of an inert gas such as nitrogen gas, argon gas, helium gas, or carbon dioxide gas or in an atmosphere.
  • an inert gas such as nitrogen gas, argon gas, helium gas, or carbon dioxide gas or in an atmosphere.
  • the compound can be produced by polymerization in a solvent such as methanol or ethanol by heating or irradiation with light.
  • the polymerization initiator is not particularly limited, and a usual radical polymerization initiator and the like can be used.
  • benzoic peroxide ⁇ Diisopropinole noreoxy sizzle carbonate, t-butyl hexolenoxie 2 — ethynol hexanoate, t butyl phenol phenol phenolate, t — butyl phenol Organic peroxides such as norexigisobutyrate; 2-cyano 2-propylazoformamide, 1,1-azobis (cyclohexane 11 ), 2,2, -azobis (2-amidinopropane) dihydrochloride, 2,2, -azobis (2-methylbutyronitrile), 2, 2,-azo Bisisobutyronitrile, 2, 2'-azobis (2,4-dimethylsilyl relonitrile), 2,2,1 azobis (4—methoxy 1, 2,4-dimethylsilyl rilonitrile), 4,4,4
  • the charge ratio of the monomer having a similar group to a phosphorinolecholine such as a PC-1 monomer and the other monomer copolymerizable therewith are preferably in the form of a monomer ratio. It can be 10:90 to: 100: 0, more preferably 30:70 to 95: 5. Further, the charge ratio of the polymerization initiator at the time of performing the polymerization is preferably 0.00000 to 10% by weight, more preferably 0.001 to 10% by weight, based on the total amount of the monomer components. Preferably, it can be 0.0001 to 5% by weight.
  • the polymerization temperature is from _10 to 150 ° (preferably from 0 to 100 ° C.
  • the polymerization time is from 30 minutes to 100 hours, preferably from 10 minutes to 100 hours. It can be 1 to 24 hours.
  • the ophthalmic composition of the present invention contains the ophthalmic agent.
  • the content ratio of the ophthalmic agent in the ophthalmic composition of the present invention is 0.0001 to 40% by weight, preferably 0.001 to 10% by weight, More preferably, it is 0.01 to 5% by weight.
  • the content ratio of the ophthalmic agent in the ophthalmic composition of the present invention is 0.0001 to 40% by weight, preferably 0.001 to 10% by weight, More preferably, it is 0.01 to 5% by weight.
  • the pH and the osmotic pressure of the ophthalmic composition of the present invention are not particularly limited, but in the case of a liquid preparation as an ophthalmic solution, the pH is from 3.0 to 9.0. It is particularly preferable that the osmotic pressure is 0.5 to 2.3 as an osmotic pressure ratio to physiological saline. By setting the pH and the osmotic pressure within these ranges, an ophthalmic composition that does not irritate the eyes when applied can be preferably obtained.
  • the dosage form of the ophthalmic composition of the present invention is not particularly limited, and examples thereof include liquid dosage forms dissolved, suspended, and emulsified in a medium such as water, and ointment dosage forms.
  • the ophthalmic composition of the present invention may further comprise, as necessary, an osmotic pressure adjusting agent, a pH adjusting agent, a viscosity adjusting agent, a stabilizing agent, a preservative, or other components in addition to the ophthalmic agent, which is an essential component. It can contain substances that have pharmacological effects.
  • Examples of the osmotic pressure adjusting agent or pH adjusting agent include sodium chloride, potassium chloride, calcium chloride, sodium hydrogencarbonate, sodium carbonate, magnesium sulfate, and the like.
  • Examples of the viscosity modifier include polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), methylcellulose, canoleboxyl, phenolic alcohol, and hydrazine.
  • Examples of the preservative include, but are not particularly limited to, parahydroxybenzoic acid esters such as methylparaben and ethylparaben, and invertible stones such as benzalkonium chloride and chlorhexidine dalconate. Specimens, chlorobutanol, phenol, ethyl alcohol, etc., sodium hydroxide, sodium dehydroacetate, sorbic acid, sorbic acid A preferable example is a nursery.
  • the other pharmacologically active substance is not particularly limited as long as it is a component that exhibits an effective action in the treatment of ophthalmic diseases, for example, 2. Standards for approval of manufacturing (import) of general drugs 2.
  • Anti-inflammatory agents such as teams; anti-histamines such as diphenhydramine hydrochloride and chlorpheniramine maleate; flavinade N, N-nucleotide natrimodium, cyanocovalamine, retinol acetate, retinol panolemitinitate, pyridoxine hydrochloride Cornea such as non -pentanol, calcium pantothenate, sodium nontothenate, sodium chondroitin sulfate Therapeutic agents: epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, tetrahydrozolin hydrochloride, naphazolin hydrochloride, nafa nitrate Vasoconstrictors such as zoline, phenylephrine hydrochloride
  • Bacterial agents including refreshing agents such as menthol, bonore neo-ole, camphor, and coconut oil; pilocarpine hydrochloride, pilocarinolepine, sari Physiotinamine, tinolenate, etinolefoline benzoate, benzoyl benzoate, phenol benzoate, iodicothiophyte, dimethyl bromide.
  • Miotic agents such as gumin and quinolone, and green tea, such as timolol maleate, fenolol hydrochloride, and carteol hydrochloride.
  • Ocular hypertension treatment drugs pentorate for hydrochloride, pin for hydrobromide, and atropine sulfate , Mydriatics such as phenylephrine hydrochloride, tropicamide, epipinephrine, hydrogen tartrate and epinefin, etc.; Cataract remedies such as gin, gnoretathione, pyrenoxine, sodium pentacecilsulfonate; perokinase, ⁇ -ki Enzyme preparations such as motripsin; antiseptic astringents such as silver nitrate; sulfa agents such as sulfisoxazonole; kufenramenikonore, Eris Romanisin, lactobionic acid Mycin, Hydroxoxytratracycline, Canamycin Sulfate, Becanamicin Sulfate, Gentamycin Sulfate, Genbramycin Sulfate Such as mysin, shiso-
  • Antibiotics Hydrochlorizon acetate, prednisolone acetate, dexamethasone phosphinate phosphate, dexamethasone sodium, toxin Adrenal cortical hormones such as riamsinolone acetonide, phenolic methrone, etc .; idoxperidine, aciclovinole etc.
  • Antiviral agent Others Zinc sulfate, water-soluble azulene, lysozyme chloride chromoglyme sodium, hydrochloride Shibu-pro-force, polyolefin polymethyl glycine, polyvinyl alcohol, iodine, indonemethine, heat Sodium sodium luonate, ofloxacin, tranilast, etorahydrazon hydrochloride, neostigmine methyl sulfate, a Mineoethylsnolephonic acid, betamethasone phosphinate, and mixtures thereof can be used.
  • a disposable type having a capacity of 0.5 to 3 ml, which is filled in an aseptic condition and sealed in a sealed state without adding a preservative. It is conceivable that a preservative is added to the ophthalmic composition, and a predetermined container is filled under aseptic conditions.
  • the ophthalmic composition of the present invention when it is prepared as an ointment, it may contain an ointment base in addition to the above-mentioned various components.
  • the ointment base include, but are not particularly limited to, petrolatum, liquid paraffin, polyethylene, or a mixture thereof.
  • Oil-based base Emulsified base obtained by emulsifying an oil phase and an aqueous phase with a surfactant or the like; Hydroxypropyl propylmethyl cellulose, Canoleboxime cellulose Cellulose, Polyethylene Water-soluble bases such as lenglycol are preferred.
  • the ophthalmic composition of the present invention can be used as eye drops, artificial tears, eyewashes, ointments and the like.
  • the ophthalmic composition of the present invention When used as eye drops or artificial tears, it can be used by instilling it directly into the eye. In this case, it is preferable to use the naked eye, but it is hard contact lenses, oxygen permeable hard contact lenses, and non-hydrous soft contacts. The eye may be instilled while wearing a lens or a hydrated soft contact lens.
  • the number of administrations and the amount of administration are not particularly limited, but, for example, as in the case of ordinary eye drops, 1 to 12 times a day and 1 to 1 time a day. 6 drops can be applied.
  • the ophthalmic composition of the present invention When the ophthalmic composition of the present invention is used as an eyewash, the ophthalmic composition of the present invention is transferred to an appropriately sized force, and the eyelids are repeatedly opened and closed. It can be used by returning it. In addition, eyes can be washed by directly pouring the ophthalmic composition of the present invention from a container into the eyes.
  • the ophthalmic composition of the present invention improves the water retentivity of the surface of the cornea, conjunctiva, etc., so that it can be used for allergic diseases such as dry eye, hay fever, and contact lenses. It can be used to treat or alleviate symptoms such as dry eyes. In addition, It can also be used for the purpose of preventing protein stains and the like from adhering to the contact lens when using a contact lens.
  • the ophthalmic agent of the present invention is made of a polymer having a specific side chain, it provides sufficient water retention to the cornea, and is suitable for dry eye, pollen allergy, etc., or contact lens. It is useful as an ophthalmological agent that can treat or alleviate symptoms such as a feeling of sensation of the eyes, dry eyes, etc. when wearing eyewear.
  • the ophthalmic composition of the present invention contains the above-mentioned specific ophthalmic agent, it imparts sufficient water retention to the cornea, and is used for allergic diseases such as dry eye and hay fever, or when wearing a contact lens. It is useful as an ophthalmic composition capable of treating or alleviating symptoms such as dry feeling and dry feeling in the eyes.
  • Example 1 was repeated except that 1.0 g of the MPC polymer synthesized and purified in Synthesis Example 1 and 99 g of purified water were replaced with the types and amounts of the polymer and purified water shown in Table 2. The same procedure as described above was performed to obtain eye drops.
  • Synthesis 1 to Synthesis 7 indicate that the polymers synthesized and purified in Synthesis Examples 1 to 7, respectively, were used.
  • Example 8 used the polymer obtained in Synthesis Example 2
  • Example 9 used the polymer obtained in Synthesis Example 7
  • Example 10 used the polymer obtained in Synthesis Examples 1 and 3
  • Example 11 used the polymer obtained in Synthesis Examples 1 and 3.
  • the polymers obtained in Synthetic Examples 2 and 4 and the polymers obtained in Synthetic Examples 2 and 5 in Example 12 were used in the amounts shown in Table 3, respectively, and further, sodium chloride and potassium chloride were used.
  • calcium chloride were used in the amounts shown in Table 3 and dissolved in purified water to prepare eye drops whose pH and osmotic pressure ratio were adjusted. Table 3 shows the results.
  • Example 5 200 ⁇ g of the ophthalmic solution prepared in Example 5 was applied to a commercially available acrylic plate (size: 40 mm long ⁇ 10 mm wide ⁇ lmm thick) by spraying, and immediately physiological saline was applied. Washed with water 10 Om1. Using a dynamic contact angle meter (Oriental Industrial Co., Ltd .; DCA-10), this was repeatedly immersed in 20 Om1 distilled water 50 times and pulled up. Returned. As a result of measuring the advancing contact angle during this immersion, the average value of 50 measurements was 23.5 ⁇ 1.8 degrees.
  • the ophthalmic composition of the present invention can impart water retention to the surface of an acryl plate.
  • the water retention provided on the acrylic plate surface was soaked 50 times. It was confirmed that it was stable even after repeated lifting operations.
  • Example 13 The same operation as in Example 13 was carried out except that the eye drops were not applied, and the advancing contact angle of the acrylic plate not treated with the eye drops was measured. As a result, 89.0 ⁇ 2.2 was obtained. It was a degree.
  • Example 13 From the results of Example 13 and Comparative Examples 1 to 4, the ophthalmic composition of the present invention was found to contain sodium hyaluronate, sodium chondroitin sulfate or polyvinylpyrrolidone. It can be seen that higher water retention can be imparted when these are applied as compared to conventional ophthalmic drugs containing don.
  • Example 8 or 9 In five naked human subjects, one or two drops of the eye drops prepared in Example 8 or 9 were instilled into the right eye, and artificial tears (trade name, “Santen Soft Santana”) were instilled into the left eye. A), one or two drops of Santen Pharmaceutical Co., Ltd.). After 1 minute, stain the tears in the right eye with 1% Fluorescein Trium, blink several times, and keep the eyelids open, slit lamps and cobalt filters. Using a microscope, the time to liquid layer disruption (BUT) until the dark portion appeared in the stained tear film was measured. After each measurement, the right eye was washed with artificial tears for the next measurement. The measurement was performed three times and the average was calculated. Table 4 shows the results. Comparative Example 5
  • Example 14 As an eye drop, instead of the eye drop prepared in Example 8 or 9, The same operation was performed as in Example 14 except that "Santen Hia Lein 0.1" (trade name, containing 0.1% by weight of sodium hyaluronate) was used. The BUT was measured for. Table 4 shows the results. Table 4
  • Example 14 the eye drops prepared in Example 8 were used for subjects A, B, and C, and the eye drops prepared in Example 9 were used for subjects D and E, respectively.
  • Example 14 In addition, in Example 14 and Comparative Examples 5 and 6, none of the subjects showed any reaction that was considered to be a side effect such as hyperemia.
  • Example 15 in the same manner as in Example 14, in Comparative Example 7 in the same manner as in Comparative Example 5, and in Comparative Example 8 in the same manner as in Comparative Example 6.
  • Table 5 Note that none of the subjects showed any reaction that was considered to be a side effect as compared to when wearing contact lenses before instillation.
  • Example 15 the eye drops prepared in Example 8 were used for subjects A, B, and C, and the eye drops prepared in Example 9 were used for subjects D and E, respectively.
  • the ophthalmic composition of the present invention showed that both the naked eye and the contact lens wearing eye had artificial tears and hyaluronan. It can be seen that the effect of extending BUT is higher than that of sodium phosphate. Therefore, the ophthalmic composition of the present invention has a higher effect of stabilizing the tear film as compared with artificial tears and sodium hyaluronate, and thus keeps water in the cornea and the like. The results show that it is highly effective and is effective in alleviating and treating symptoms such as dry eyes and dry eyes.
  • the MPC polymer synthesized and purified in Synthesis Example 1 2.0 g, etolahydrazoline hydrochloride 0.02 g, chloronoferene maleate 0.01 g, 0.05 g of neostigmine thiosulfate, 1.0 g of ipsilon ( ⁇ -) aminocaproic acid, 0.05 g of benzalkonium chloride, chloronodalonic acid Take 0.05 g of hexidine and 0.5 g of boric acid, add purified water to make a total of 100 g, and divide this with a 0.2 ⁇ membrane finolator. Bacterial treatment and eye drops It was prepared.
  • An eye drop was obtained in the same manner as in Example 16 except that the kinds and amounts of the polymers, drug components and other components shown in Tables 6 to 10 were used.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Cette invention a trait à une préparation ophtalmique, essentiellement composée d'un polymère possédant un groupe du type phosphorylcholine, représenté par la formule générale (1), sur la chaîne latérale, ainsi qu'à une composition ophtalmique contenant cette préparation. Dans cette formule générale (1), R?1, R2 et R3¿ sont identiques ou différents et chacun d'eux représente un hydrogène ou un alkyle comportant de 1 à 4 atomes de carbone, m représentant un nombre entier d'une valeur comprise entre 2 et 4.
PCT/JP1998/005299 1997-11-26 1998-11-25 Preparation et composition ophtalmiques WO1999026637A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP32457197 1997-11-26
JP9/324571 1997-11-26

Publications (1)

Publication Number Publication Date
WO1999026637A1 true WO1999026637A1 (fr) 1999-06-03

Family

ID=18167307

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1998/005299 WO1999026637A1 (fr) 1997-11-26 1998-11-25 Preparation et composition ophtalmiques

Country Status (1)

Country Link
WO (1) WO1999026637A1 (fr)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001002563A (ja) * 1999-06-17 2001-01-09 Tomey Corp 点眼剤
JP2001158750A (ja) * 1999-12-02 2001-06-12 Lion Corp 眼科用組成物及び抗アレルギー薬の持続性向上方法
WO2005065733A1 (fr) * 2003-12-26 2005-07-21 Hoya Corporation Implant intraoculaire, son procede de production, et prevention de la cataracte secondaire
US7192771B2 (en) 2000-08-30 2007-03-20 North Carolina State University Plant promoter sequence
JP2007530733A (ja) * 2004-03-22 2007-11-01 アドヴァンスド カーディオヴァスキュラー システムズ， インコーポレイテッド ホスホリルコリンコーティング組成物
JP2008189677A (ja) * 2008-03-10 2008-08-21 Rohto Pharmaceut Co Ltd 洗浄剤
JP2008273959A (ja) * 2007-04-04 2008-11-13 Taisho Pharmaceutical Co Ltd 点眼剤
JP2011075943A (ja) * 2009-09-30 2011-04-14 Rohto Pharmaceutical Co Ltd 眼科組成物
JP2011093898A (ja) * 2009-09-30 2011-05-12 Rohto Pharmaceutical Co Ltd 眼科組成物
JP2015034166A (ja) * 2014-10-15 2015-02-19 ロート製薬株式会社 眼科組成物
WO2017110874A1 (fr) * 2015-12-22 2017-06-29 日油株式会社 Stabilisateur de la couche lipidique du film lacrymal et gouttes ophtalmiques comprenant ce dernier
CN116284548A (zh) * 2023-05-24 2023-06-23 广东工业大学 一种具有多重自翻转的磷酸胆碱四元共聚物及其制备方法和应用
JP7552318B2 (ja) 2019-12-09 2024-09-18 日油株式会社 ソフトコンタクトレンズ用花粉吸着抑制剤及び花粉タンパク吸着抑制剤の製造方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH07166154A (ja) * 1993-12-10 1995-06-27 Nippon Oil & Fats Co Ltd コンタクトレンズ用溶液
JPH10324634A (ja) * 1997-03-28 1998-12-08 Rohto Pharmaceut Co Ltd リン脂質類似重合体を含有する眼科用医薬組成物

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH07166154A (ja) * 1993-12-10 1995-06-27 Nippon Oil & Fats Co Ltd コンタクトレンズ用溶液
JPH10324634A (ja) * 1997-03-28 1998-12-08 Rohto Pharmaceut Co Ltd リン脂質類似重合体を含有する眼科用医薬組成物

Cited By (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001002563A (ja) * 1999-06-17 2001-01-09 Tomey Corp 点眼剤
JP4605837B2 (ja) * 1999-06-17 2011-01-05 株式会社メニコンネクト 点眼剤
JP2001158750A (ja) * 1999-12-02 2001-06-12 Lion Corp 眼科用組成物及び抗アレルギー薬の持続性向上方法
US7192771B2 (en) 2000-08-30 2007-03-20 North Carolina State University Plant promoter sequence
WO2005065733A1 (fr) * 2003-12-26 2005-07-21 Hoya Corporation Implant intraoculaire, son procede de production, et prevention de la cataracte secondaire
JP2007530733A (ja) * 2004-03-22 2007-11-01 アドヴァンスド カーディオヴァスキュラー システムズ， インコーポレイテッド ホスホリルコリンコーティング組成物
US9468706B2 (en) 2004-03-22 2016-10-18 Abbott Cardiovascular Systems Inc. Phosphoryl choline coating compositions
JP2008273959A (ja) * 2007-04-04 2008-11-13 Taisho Pharmaceutical Co Ltd 点眼剤
JP2008189677A (ja) * 2008-03-10 2008-08-21 Rohto Pharmaceut Co Ltd 洗浄剤
JP2016145249A (ja) * 2009-09-30 2016-08-12 ロート製薬株式会社 眼科組成物
JP2015025011A (ja) * 2009-09-30 2015-02-05 ロート製薬株式会社 眼科組成物
JP2011093898A (ja) * 2009-09-30 2011-05-12 Rohto Pharmaceutical Co Ltd 眼科組成物
JP2011075943A (ja) * 2009-09-30 2011-04-14 Rohto Pharmaceutical Co Ltd 眼科組成物
JP2019043970A (ja) * 2009-09-30 2019-03-22 ロート製薬株式会社 眼科組成物
JP2017160274A (ja) * 2009-09-30 2017-09-14 ロート製薬株式会社 眼科組成物
JP2015034166A (ja) * 2014-10-15 2015-02-19 ロート製薬株式会社 眼科組成物
CN108289908A (zh) * 2015-12-22 2018-07-17 日油株式会社 泪液油层稳定剂及含有该泪液油层稳定剂的滴眼剂
JPWO2017110874A1 (ja) * 2015-12-22 2018-11-15 日油株式会社 涙液油層安定化剤およびこれを含有する点眼剤
WO2017110874A1 (fr) * 2015-12-22 2017-06-29 日油株式会社 Stabilisateur de la couche lipidique du film lacrymal et gouttes ophtalmiques comprenant ce dernier
US10391119B2 (en) 2015-12-22 2019-08-27 Nof Corporation Lacrimal oily layer stabilizer and eye drops comprising same
TWI759276B (zh) * 2015-12-22 2022-04-01 日商日油股份有限公司 淚液油層穩定劑及含有該淚液油層穩定劑的滴眼劑
JP7552318B2 (ja) 2019-12-09 2024-09-18 日油株式会社 ソフトコンタクトレンズ用花粉吸着抑制剤及び花粉タンパク吸着抑制剤の製造方法
CN116284548A (zh) * 2023-05-24 2023-06-23 广东工业大学 一种具有多重自翻转的磷酸胆碱四元共聚物及其制备方法和应用
CN116284548B (zh) * 2023-05-24 2023-08-11 广东工业大学 一种具有多重自翻转的磷酸胆碱四元共聚物及其制备方法和应用

Similar Documents

Publication Publication Date Title
Nanjawade et al. RETRACTED: In situ-forming hydrogels for sustained ophthalmic drug delivery
CA2216417C (fr) Emission controlee de medicaments myotiques et mydriatiques dans la chambre anterieure
JP4309974B2 (ja) 眼科用製剤
JP6359586B2 (ja) 眼科組成物
WO1999026637A1 (fr) Preparation et composition ophtalmiques
TW201636026A (zh) 滴眼劑及其所包含之共聚物之用途
JP2017206547A (ja) 眼科用組成物
TWI812881B (zh) 濕包裝軟性水凝膠眼睛插入物
JPH07503974A (ja) ｐＨ感受性の可逆的にゲル化する浸蝕性ドラッグデリバリーシステム
JPH10324634A (ja) リン脂質類似重合体を含有する眼科用医薬組成物
JP7218689B2 (ja) 点眼剤
CN114080226A (zh) 眼用组合物
Polat et al. Development of besifloxacin HCL loaded ocular in situ gels; in vitro characterization study
JP2016026150A (ja) リン脂質類似重合体を含有する眼科用医薬組成物
EP3936113A1 (fr) Microsphères dégradables hydrophiles pour administration de travoprost
JPH11246416A (ja) 点鼻用添加剤及び点鼻薬
WO2023205695A1 (fr) Compositions de crème topique ophtalmique
JP2008094857A (ja) リン脂質類似重合体を含有する眼科用医薬組成物
Severian Drug-Loaded Ophthalmic Prostheses
JP2005314336A (ja) 外皮用殺菌剤配合組成物及び、皮膚刺激緩和方法
Prasad et al. International Journal Pharmaceutica
Lane et al. Cataract surgery
Sarvaiya Polymeric Hydrogels for Controlled Drug Delivery to the Eye
JP2019219621A (ja) コンタクトレンズ用溶液
MXPA99008634A (en) Controlled release of pharmaceuticals in the anterior chamber of the eye

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): JP US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

Ref document number: 2000521839

Format of ref document f/p: F

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载