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WO2010010689A1 - Préparation liquide pour lentilles de contact - Google Patents

Préparation liquide pour lentilles de contact Download PDF

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Publication number
WO2010010689A1
WO2010010689A1 PCT/JP2009/003417 JP2009003417W WO2010010689A1 WO 2010010689 A1 WO2010010689 A1 WO 2010010689A1 JP 2009003417 W JP2009003417 W JP 2009003417W WO 2010010689 A1 WO2010010689 A1 WO 2010010689A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
contact lens
solution
cyclodextrin
agent
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.)
Ceased
Application number
PCT/JP2009/003417
Other languages
English (en)
Japanese (ja)
Inventor
谷川定康
塚本桂史
伊藤一作
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Menicon Co Ltd
Original Assignee
Menicon Co Ltd
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 Menicon Co Ltd filed Critical Menicon Co Ltd
Priority to JP2010501316A priority Critical patent/JP4751482B2/ja
Publication of WO2010010689A1 publication Critical patent/WO2010010689A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/40—Cyclodextrins; Derivatives thereof
    • 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
    • A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6949—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • A61K47/6951—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G83/00—Macromolecular compounds not provided for in groups C08G2/00 - C08G81/00
    • C08G83/007—Polyrotaxanes; Polycatenanes
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L71/00—Compositions of polyethers obtained by reactions forming an ether link in the main chain; Compositions of derivatives of such polymers
    • C08L71/02—Polyalkylene oxides

Definitions

  • the present invention relates to a liquid agent for contact lenses, and in particular, a drug component contained in a liquid medium is sufficiently exerted by inclusion of the drug component in pores of a compound such as cyclodextrin.
  • the present invention relates to a liquid agent for contact lenses that can advantageously solve the problem that it cannot be performed.
  • ophthalmic compositions such as liquids for contact lenses
  • prevention of adsorption of drug components to contact lenses and containers improvement of solubility, reduction of bitterness, relaxation of irritation, thickening and moisturizing of liquids
  • cyclodextrins are often included.
  • an eye drop containing a preservative having a cationic group eye drop for contact lens
  • cyclodextrins ethylenediaminetetraacetic acid or a salt thereof
  • boric acid And / or borax boric acid And / or borax
  • various components generally contained in the eye drop for example, an antiallergic agent, as a drug component other than the above-mentioned preservative in the eye drop
  • chemical ingredients such as anti-inflammatory agents, vasoconstrictors, and refreshing agents, these chemical ingredients are also included in the cyclodextrin pores, similar to the preservatives described above.
  • the ophthalmic composition containing a compound having a cyclic or cylindrical molecular structure such as cyclodextrin and capable of including other compounds (drug components) together with the drug component.
  • a compound having a cyclic or cylindrical molecular structure such as cyclodextrin and capable of including other compounds (drug components) together with the drug component.
  • drug components are included in the pores of the cyclic or cylindrical molecular structure of such a compound, so that the drug action inherent to these drug components cannot be fully exhibited. It was something that existed.
  • the present invention has been made in the background of such circumstances, and the problem to be solved thereof is to form a ring or cylinder such as cyclodextrin together with a drug component in a liquid medium. It is an object of the present invention to provide a contact lens solution capable of advantageously exerting the drug action of a drug component even if it is a contact lens solution containing a compound having a molecular structure.
  • the present inventors have a cyclic or cylindrical molecular structure together with a drug component and include other compounds (drug components).
  • a compound (compound B) having a chain molecular structure and capable of being included in the compound A to the liquid medium containing the compound (compound A) that can be contacted, It has been found that the problem can be advantageously solved.
  • the compound A contains a compound A having a cyclic or cylindrical molecular structure together with a drug component.
  • the gist of the liquid agent for contact lenses is characterized in that the liquid medium further contains a compound B having a chain molecular structure and capable of being included in the compound A.
  • the inclusion compound formed by inclusion of the compound B with the compound A in the liquid medium is a pseudorotaxane. It has a structure or pseudopolyrotaxane structure.
  • the compound A and the compound B are contained in a weight ratio of 1000: 1 to 1: 1000, According to another preferred embodiment, the compound A is contained at a concentration of 0.001 to 20.0 w / w%.
  • the compound B is a water-soluble polymer having a weight average molecular weight of 500 or more, more preferably polyethylene glycol.
  • the compound A having a cyclic or cylindrical molecular structure is a cyclodextrin.
  • the compound A is ⁇ -cyclodextrin
  • the compound B is polyethylene glycol having a weight average molecular weight of 6000
  • the compound A is In addition to ⁇ -cyclodextrin, the compound B is polyethylene glycol having a weight average molecular weight of 600.
  • the drug component is an antiallergic agent, an anti-inflammatory agent, a vasoconstrictor, a refreshing agent, an antiseptic / bactericidal agent, and a focus control. It is at least one selected from a function improving agent, an intraocular pressure-lowering agent, vitamins, an antibacterial agent (antibiotic) and a surfactant.
  • the present invention includes a predetermined drug component, compound A having a cyclic or cylindrical molecular structure, and compound B having a chain molecular structure and capable of being included in the compound A.
  • compound B is included in the compound A to form a pseudorotaxane structure or a pseudopolyrotaxane structure, thereby controlling the drug action of the drug component, This is the gist.
  • the liquid medium contains Compound A having a cyclic or cylindrical molecular structure and Compound B having a chain molecular structure and capable of being included in the Compound A.
  • the chain portion of the compound B enters the pores of the cyclic or cylindrical structure of the compound to form an inclusion compound exhibiting a pseudorotaxane structure or a pseudopolyrotaxane structure.
  • a gist of the method is also characterized by reducing toxicity.
  • the compound B is more preferably polyethylene glycol or polyoxyethylene polyoxypropylene glycol.
  • a chain molecule is further contained in a liquid medium containing a compound A having a cyclic or cylindrical molecular structure together with a predetermined drug component. Since the compound B having a structure and capable of being included in the compound A is contained, the compound B can be competitively or exchanged with the drug component in the pores of the compound A. So that the drug action of the drug component can be advantageously controlled, so that the drug effect of the drug component cannot be fully exerted, It can be effectively suppressed or prevented.
  • an advantageous effect realized by incorporating a compound A having a cyclic or cylindrical molecular structure together with a drug component in a liquid medium for example, the effect of suppressing the adsorption of drug components to contact lenses and containers, the effect of improving the solubility of poorly soluble substances, the effect of reducing bitterness, the effect of reducing irritation, and the effect of suppressing the decrease in viscosity have the chain molecular structure.
  • the presence of the compound B which can be included in the compound A is not lost at all, and those effects can also be enjoyed advantageously.
  • the liquid agent for contact lenses according to the present invention further comprises a compound having a chain molecular structure in a liquid medium containing a compound A having a cyclic or cylindrical molecular structure together with a predetermined drug component.
  • Compound B which can be included in A, is contained, and as the drug component there are known various drug components that have been conventionally incorporated in contact lens solutions (here, Can be used, and is not limited in any way, but particularly those that can be included in the compound A are preferably used (inclusion” includes those in which the drug component or compound B penetrates compound A. The same shall apply hereinafter.
  • drug components include antiallergic agents, anti-inflammatory agents, vasoconstrictors, refreshing agents, antiseptics / bactericides, focus control function improving agents, intraocular pressure-lowering agents, vitamins, antibacterial agents ( Antibiotics) and surfactants can be exemplified.
  • the antiallergic agent is a component used for the treatment of hay fever, allergic conjunctivitis, and the like, specifically, mast cells such as cromoglycic acid and tranilast.
  • Stabilizers and antihistamines such as chlorpheniramine maleate, diphenhydramine hydrochloride, amlexanox, ibudilast, tranilast, pemirolast potassium, emedastine fumarate, olopatadine hydrochloride, ebastine, acitazanolast, levocabastine, cetirizine hydrochloride, etc.
  • it is generally used at a concentration of about 0.00001 to 5 w / w%.
  • the anti-inflammatory agent is a component used for suppressing inflammation in the eye caused by stress or wearing of a contact lens, regardless of whether it is steroidal or non-steroidal, for example,
  • glycyrrhizic acid and salts thereof ⁇ -aminocaproic acid, allantoin, sodium azulenesulfonate, berberine chloride, berberine sulfate, zinc sulfate, zinc lactate, lysozyme, fluorometholone, etc., generally about 0.0001 to 10 w / w%, More preferably, it is used at a concentration of about 0.001 to 5 w / w%.
  • the above-mentioned vasoconstrictor is a component that acts on the scleral blood vessels in the eyeball, eliminates redness of the eye and has the effect of restoring eye strain, and includes, for example, epinephrine, hydrochloric acid Examples include epinephrine, ephedrine hydrochloride, naphazoline hydrochloride, naphazoline nitrate, phenylephrine hydrochloride, tetrahydrozoline hydrochloride, and the like.
  • the content in the liquid for contact lenses is preferably about 0.0001 to 1 w / w%, more preferably 0.0003 to 0.1 w / w%.
  • the refreshing agent is one that is included for the purpose of giving a refreshing feeling to the eyes or eliminating the feeling of foreign objects and itching when wearing contact lenses, For example, fennel oil, d-camphor, dl-camphor, cool mint no.
  • examples of the antiseptic / disinfectant include sorbic acid, potassium sorbate, benzoic acid or a salt thereof, ethyl paraoxybenzoate, butyl paraoxybenzoate, propyl paraoxybenzoate, methyl paraoxybenzoate, chlorobutanol, chloride
  • Polyquaterniums such as benzalkonium, polyhexamethylene biguanide (PHMB; polyhexanide hydrochloride), alkyldiaminoethylglycine hydrochloride, cetylpyridinium chloride (CPC), chlorhexidine, alexidine, chlorpheniramine or its salts, allantoin, polydronium chloride, etc.
  • sorbic acid, potassium sorbate, benzalkonium chloride, polyhexamethylene biguanide, alkyldiaminoethylglycol hydrochloride Emissions, chloride Poridoroniumu is, adverse effects on standard contact lens from where very small, in particular, is preferably employed.
  • These preservatives are generally used at a concentration of about 0.00001 to 1 w / w%.
  • antibacterial agents include sulfamethoxazole, sulfamethoxazole sodium, sulfisoxazole, sulfisomidine sodium and other sulfa drugs, and ofloxacin, norfloxacin, levofloxacin, gatifloxacin, moxifloxacin New quinolone antibacterial agents such as syn, tosufloxacin, lomefloxacin, ciprofloxacin, aminoglycoside antibacterial agents such as tobramycin, gentamicin, micronomycin, dibekacin, sisomycin, tetracycline antibacterial agents such as tetracycline and minocycline, macrolides such as erythromycin And chloramphenicol antibacterial agents such as chloramphenicol, and cephem antibacterial agents such as cefmenoxime.
  • vitamin A including retinol palmitate, ⁇ -carotene, etc.
  • vitamin B 2 flavin adenine nucleotide etc.
  • vitamin B 6 pyridoxine hydrochloride etc.
  • vitamin B 12 cyanocobalamin
  • vitamin C ascorbic acid etc.
  • vitamin Es acetic acid-d- ⁇ -tocopherol etc.
  • examples of the focus control function improving agent include neostigmine methyl sulfate.
  • intraocular pressure-lowering agent examples include betaxolol, timolol, dipivefrin, carteolol, latanoprost, tafluprost, travoprost, nipradilol, levobunolol and the like.
  • any of conventionally known anionic surfactants, nonionic surfactants, amphoteric surfactants and cationic surfactants can be appropriately employed.
  • the surfactant include polyglycerin fatty acid ester, polyoxyethylene-polyoxypropylene ethylenediamine, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene alkylphenyl ether formaldehyde condensate, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl Phenyl ether, polyoxyethylene glycerin fatty acid ester, polyoxyethylene sorbite fatty acid ester, polyoxyethylene castor oil, polyoxyethylene sterol, polyoxyethylene hydrogenated sterol, polio Siethylene fatty acid ester, polyoxyethylene-polyoxypropylene alkyl ether, polyoxyethylene lanolin alcohol, polyoxyethylene alkylamine, polyoxyethylene alkylamide, polyoxyethylene alkyl ether phosphoric acid, polyoxyethylene-poly
  • a thickener in addition to such drug components, as in the conventional contact lens solution, a thickener, a chelating agent, a tonicity adjusting agent, a buffering agent, a corneal epithelium.
  • Pharmaceutical components such as a disorder treatment agent, a solubilizing agent, fats and oils, and amino acids may be contained.
  • the above thickener is contained in order to adjust the viscosity of the liquid agent for contact lenses.
  • polysaccharides such as alginic acid, chitosan and salts thereof, hyaluronic acid (salt), chondroitin
  • Various gums such as mucopolysaccharides such as sulfuric acid (salt), heteropolysaccharides, polyvinyl alcohol (fully saponified and partially saponified), poly (meth) acrylic acid, poly-N-vinylpyrrolidone, poly Synthetic organic polymer compounds such as acrylamide and copolymer 845 (copolymer of polyvinylpyrrolidone and dimethylaminoethyl methacrylate), hydroxyethylcellulose, hydroxypropylmethylcellulose 2208, hydroxypropylmethylcellulose 2906, hydroxypropylmethylcellulose 2910, carboxymethylcellulose, methyl Cellulose derivatives such as cellulose, starch derivatives and the like are used at a concentration of
  • the chelating agent is a component for preventing deposition or adsorption of calcium or the like in tears on contact lenses, particularly soft contact lenses, and includes, for example, ethylenediaminetetraacetic acid (EDTA) and salts thereof, such as In general, ethylenediaminetetraacetic acid ⁇ disodium (EDTA ⁇ 2Na), ethylenediaminetetraacetic acid ⁇ trisodium (EDTA ⁇ 3Na) and the like are used at a concentration of about 0.001 to 0.5 w / w%.
  • the tonicity adjusting agent adjusts the osmotic pressure of the liquid for contact lenses to a value close to the osmotic pressure of tears to prevent eye irritation, contact lens standard changes, eye disorders
  • inorganic salts such as sodium chloride and potassium chloride
  • sugars such as glucose, dextran, trehalose and derivatives thereof
  • sugar alcohols such as xylitol, erythritol
  • At least one or more compounds selected from the group consisting of polyhydric alcohols such as propylene glycol and glycerin or ethers or esters thereof are usually in an osmotic pressure ratio with respect to physiological saline (where the osmotic pressure of physiological saline is 1).
  • An amount in the range of about 0.5 to 2.0, preferably in the range of about 0.6 to 1.6 Oite, it is allowed to contain.
  • the above-mentioned buffering agent may cause eye irritation or eye damage by adjusting the pH value of the liquid for contact lenses to about 3.5 to 9.0, particularly biologically safe pH.
  • carboxylic acids such as phosphoric acid, boric acid, citric acid and acetic acid
  • acids such as oxycarboxylic acid, and salts thereof (for example, sodium salts)
  • Good-Buffer, Tris (hydroxymethyl) aminomethane (TRIS), bis (2-hydroxyethyl) iminotris (hydroxymethyl) methane (Bis-Tris), sodium hydrogen carbonate, aminoethylsulfonic acid, glycine, arginine, Amino acids such as glutamic acid are contained at a concentration that gives a pH value within the above-described range.
  • the therapeutic agent for corneal epithelial disorder is a drug component for treating corneal epithelial disorder caused by dry eye, trauma, drug, etc., and examples thereof include hyaluronic acid and its salt, chondroitin sulfate and its salt, etc. Is generally used at a concentration of about 0.001 to 1 w / w%.
  • the solubilizing agent is a drug component for improving the solubility of a hardly soluble substance such as a water-insoluble drug, and for example, a lower or higher alcohol such as ethanol, isopropanol, oleyl alcohol, lauryl alcohol, etc. Can be mentioned.
  • fats and oils are components blended for the purpose of reducing friction on the ocular surface and supplementing the tear oil layer.
  • amino acids used in the present invention include aspartic acid and salts thereof, tranexamic acid, L-cysteine, alanine, lysine, anserine, carnosine and the like, and vitamins include vitamin A (palmitic acid). retinol, beta-containing carotene), vitamin B 2 (flavin adenine nucleotide sodium, etc.), B 6 (pyridoxine hydrochloride, etc.), B 12 (cyanocobalamin and the like), vitamin C (ascorbic acid), acetic acid d-alpha-tocopherol Vitamin E, panthenol and the like.
  • vitamins include vitamin A (palmitic acid). retinol, beta-containing carotene), vitamin B 2 (flavin adenine nucleotide sodium, etc.), B 6 (pyridoxine hydrochloride, etc.), B 12 (cyanocobalamin and the like), vitamin C (ascorbic acid), acetic acid d-alpha-
  • the sulfa drug is a component mainly used as an antibacterial agent, and examples thereof include sulfamethoxazole, sulfamethoxazole sodium, sulfisoxazole, and sulfisomidine sodium.
  • antibacterial agents in addition to the sulfa drugs described above, antibacterial agents such as ofloxacin and new quinolone antibacterial agents can also be used.
  • contact lens solution according to the present invention in addition to the above-described components, if necessary, one kind of various pharmaceutical components conventionally used in contact lens solutions. Even if two or more kinds are contained, there is no problem.
  • a drug component is highly safe to the living body, is ophthalmically acceptable, and does not adversely affect the shape and physical properties of the contact lens. It is desirable to be used within a quantitative range that satisfies the above.
  • the above-described pharmaceutical components are contained in a liquid medium alone or in combination of two or more.
  • a liquid medium It is not necessary that all drug components to be contained can be included in the compound A having a cyclic or cylindrical molecular structure described later, and at least one of these drug components is a compound described later. If it is included in A, the above-described effects of the present invention can be fully enjoyed. Therefore, in the contact lens solution according to the present invention, it is included in the compound A. There can be no adverse drug component present in the liquid medium.
  • a compound having a cyclic or cylindrical molecular structure (compound A) is contained in the liquid medium together with the drug components as described above.
  • compound A is ophthalmically acceptable, and is particularly capable of inclusion of at least one drug component and compound B having a chain molecular structure described later. It is not limited, and any of various compounds having a cyclic or cylindrical molecular structure can be employed.
  • Examples of such compound B include cyclodextrins having a structure in which a number of D-glucopyranose groups are cyclized in a crown shape by ⁇ 1 ⁇ 4 glycosidic bonds, and crown ethers that are cyclic polyethers, Examples thereof include carbon nanotubes that are tubular (tubular) carbon molecules, and calixarenes that are cyclic compounds obtained by reacting formaldehyde with a phenol derivative.
  • the safety to the living body is high, and a moisturizing effect and a thickening effect can be imparted to the liquid agent for contact lenses.
  • Cyclodextrins are preferably used because the following excellent effects can be advantageously achieved by enclosing various drug components.
  • the drug component when such a cyclodextrin is contained in a liquid medium together with the drug component, the drug component is included in the pores of the cyclodextrin, thereby causing undesirable adsorption and action of the drug component. This is advantageously suppressed. Specifically, when a drug component is included in the pores of cyclodextrins, the adsorption or action of the drug component on contact lenses, formulation containers, biological tissues, etc. is advantageously suppressed. .
  • cyclodextrins are not particularly limited in the present invention.
  • glucose polymerization such as ⁇ -cyclodextrin, ⁇ -cyclodextrin, ⁇ -cyclodextrin, ⁇ -cyclodextrin, etc.
  • Degree: 6-9 cyclodextrins can be used.
  • methylated cyclodextrin, hydroxyethylated cyclodextrin, maltosyl- ⁇ -cyclodextrin, hydroxyethyl- ⁇ -cyclodextrin, triacetyl- ⁇ -Cyclodextrin derivatives such as cyclodextrin and hydroxypropylated cyclodextrin, and cyclodextrin multimers such as cyclodextrin dimer are appropriately used.
  • ⁇ -cyclodextrin, ⁇ -cyclodextrin, and ⁇ -cyclodextrin are preferably used because of the low toxicity of the inclusion compound with the polyoxyethylene derivative described later.
  • the content of the compound A having a cyclic or cylindrical molecular structure as described above in the contact lens solution is not particularly limited in the present invention. Is preferably used at a concentration such that it can be advantageously controlled, generally at a concentration of about 0.001 to 20.0 w / w%, more preferably at a concentration of about 0.005 to 5.0 w / w%. Will be used.
  • a concentration such that it can be advantageously controlled, generally at a concentration of about 0.001 to 20.0 w / w%, more preferably at a concentration of about 0.005 to 5.0 w / w%.
  • the content of Compound A is too large, the osmotic pressure increases, which may cause problems of solubility and eye irritation.
  • the content of Compound A is too small, the above-mentioned book There is a possibility that the effects of the invention cannot be fully enjoyed.
  • the compound B which has a chain molecular structure and can be included in the compound A It is contained.
  • the contact lens solution according to the present invention further has a chain molecular structure in the liquid medium containing the compound A having a cyclic or cylindrical molecular structure together with the drug component.
  • the compound B that can be included in the compound A is contained, in the pores of the compound (compound A) having a cyclic or cylindrical molecular structure such as cyclodextrin, Competitively or in exchange with various drug components, Compound B having a chain molecular structure comes to be included, and thereby, the drug action of each drug component is respectively It can be used advantageously.
  • the conventional liquid medicine for contact lenses when compound A having a cyclic or cylindrical molecular structure is contained in a liquid medium together with various drug components, various liquid substances contained in the liquid medium are included.
  • the drug component can be encapsulated in the ring or cylinder (in the vacancies) of the compound A having a cyclic or cylindrical molecular structure.
  • the drug effect inherent to the drug component cannot be sufficiently exhibited.
  • a chain molecular structure is further provided in addition to the drug component and the compound having a cyclic or cylindrical molecular structure (compound A) in the liquid medium.
  • the compound (compound B) that can be included in the compound A is contained in the pores of the compound A, the compound B is competitively or exchanged with the drug component.
  • inclusion of the drug component to compound A is advantageously controlled, so that the drug action of such drug component is advantageously and effectively controlled. Therefore, the drug effect can be exerted advantageously. That is, in the contact lens solution according to the present invention, the drug action of a drug component such as a preservative can be reduced even in the presence of a cyclic or cylindrical molecular structure (compound A) such as cyclodextrin. This can be advantageously prevented.
  • the pores of Compound A having a cyclic or cylindrical molecular structure are competitive with the above-described drug components.
  • the drug component is pushed out from the pores of the compound A.
  • an advantageous effect realized by including a compound having a cyclic or cylindrical molecular structure (compound A) such as cyclodextrin together with a drug component for example, adsorption of a bactericide to a contact lens, a container or the like Suppression effect, solubility improvement effect of poorly soluble substances such as water-insoluble drugs, bitterness reduction effect such as antihistamines and anti-inflammatory agents, stimulant mitigation effect such as cooling agents, bactericides and antiseptics such as PHMB Drug corneal staining suppress or prophylactic effect due What like, without being loss, their effects, which may occur as it can be advantageously enjoyed.
  • compound A such as cyclodextrin
  • a drug component for example, adsorption of a bactericide to a contact lens, a container or the like Suppression effect, solubility improvement effect of poorly soluble substances such as water-insoluble drugs, bitterness reduction effect such as antihistamines and anti-inflammatory agents, stimulant mitigation effect such as cooling
  • the compound B is not particularly limited as long as it has a chain molecular structure and can be included in the compound A. Either a chain or a branched chain may be used, and various known compounds that are ophthalmically acceptable and have compatibility with contact lenses can be used as appropriate.
  • water-soluble polymers such as polyalkylene glycol such as polyethylene glycol (PEG), polyoxyethylene alkyl ether, Polyoxya such as polyoxyethylene alkyl ester and polyoxyethylene-polyoxypropylene block copolymer Killen derivatives advantageously used, among which, in the present invention, from where excellent inclusion against the aforementioned cyclodextrin, polyethylene glycol, more preferably used.
  • the molecular weight of such compound B is not particularly limited, but the inclusion compound with the above-mentioned cyclodextrins (compound A) can be formed advantageously and stably in a pharmaceutical manner.
  • the weight average molecular weight is preferably 500 or more, more preferably about 2000 to 40,000.
  • the weight average molecular weight of the compound B is too small, the inclusion compound of the compound B and the compound A may not be stably formed, and the treated contact lens is swollen thereby.
  • the standard of the contact lens may be changed.
  • the weight average molecular weight of the compound B is too large, the solubility of the compound B in the liquid medium may be deteriorated.
  • the content of such compound B in the liquid preparation for contact lens is not particularly limited in the present invention, but the drug action of the drug component can be advantageously exerted. It is desirable to use it at a concentration, and it is usually used at a concentration of about 0.001 to 10.0 w / w%, preferably at a concentration of about 0.005 to 5.0 w / w%.
  • the drug action of a drug ingredient can be controlled effectively. May be difficult.
  • the content of the compound B is too small, the effects as described above due to the addition and inclusion of the compound B may not be sufficiently enjoyed.
  • the ratio of the content of the compound A and the compound B in the contact lens solution according to the present invention is not particularly limited, but the drug action of the drug component coexisting in the solution is advantageously controlled. Therefore, the weight ratio is generally about 1000: 1 to 1: 1000, preferably about 500: 1 to 1: 500.
  • the contact lens solution according to the present invention comprises compound A and compound B as described above together with various drug components in a liquid medium.
  • the inclusion compound formed by the compound A and the compound B is a pseudorotaxane.
  • a (pseudorotaxane) structure or a pseudopolyrotaxane (pseudopolyrotaxane) structure will be exhibited.
  • the formation or release of the inclusion compound is easy, so that the drug action of the drug component can be controlled more advantageously.
  • a combination of Compound A and Compound B that forms such an inclusion compound having a pseudorotaxane structure or a pseudopolyrotaxane structure is preferably employed.
  • examples of such a combination of Compound A and Compound B include a combination of ⁇ -cyclodextrin (Compound A) and polyethylene glycol (Compound B) having a weight average molecular weight of 6000, ⁇ -cyclodextrin ( Examples include a combination of compound A) and polyethylene glycol having a weight average molecular weight of 600 (compound B).
  • the inclusion compound is formed by the compound A and the compound B, whereby the toxicity of the compound B can be effectively reduced.
  • the characteristics of the present invention can be found.
  • the above-described components that is, the predetermined drug component, Compound A and Compound B, are respectively contained in an appropriate liquid medium in the same manner as in the prior art.
  • the liquid medium used at that time will be carried out by adding it in an appropriate amount and dissolving and containing it. Any water-based solution can be used as long as it is highly safe to the living body and is sufficiently ophthalmically acceptable.
  • no special method is required, and each component can be added to the liquid medium in any order as in the case of preparing a normal aqueous solution. It can be easily obtained by dissolving.
  • the container to be filled is not limited at all, and a single layer or a multilayer structure of polyethylene terephthalate, polyethylene, polypropylene, polycarbonate or the like is appropriately selected.
  • the contact lens solution according to the present invention obtained as described above is not limited in any way.
  • the contact lens cleaning solution, the rinsing solution, the mounting solution, the storage solution, the protein removing agent or the As a multi-purpose solution, etc. as a contact lens packaging solution, an eyewash solution or an eye drop solution that can be used while wearing a contact lens, and a multi-purpose preparation that combines these functions (eg, eye drop solution, (Eye drops) can be prepared and used as appropriate.
  • the types of contact lenses are not limited in any way, and soft contact lenses (ionic) And non-ionic), hard contact lenses (including oxygen-permeable hard contact lenses), and hybrid contact lenses combining soft contact lenses and hard contact lenses.
  • It may be a contact lens made of silicone hydrogel.
  • contact lenses can be non-hydrous, low hydrous, and high hydrous, regardless of whether or not they are surface-treated.
  • disposable contact lenses typified by daily disposable contact lenses, regular exchange contact lenses, frequent exchange contact lenses, and conventional contact lenses that are used until the end of their lives are covered.
  • Such a contact lens may be an all day wear type or a continuous wear type.
  • benzalkonium chloride manufactured by Nacalai Tesque Co., Ltd.
  • ⁇ -cyclodextrin manufactured by Wako Pure Chemical Industries, Ltd.
  • weight average is used as compound B.
  • polyethylene glycol having a molecular weight of 6000 Macrogol 6000, manufactured by NOF Corporation
  • sodium hydrogen phosphate and sodium dihydrogen phosphate as buffering agents
  • -Test solution 2- Except for using 0.000025 w / v% of polyhexamethylene biguanide (polyhexanide hydrochloride, manufactured by Arch Chemicals Japan Co., Ltd.) instead of 0.01 w / v% of benzalkonium chloride as the drug component, A contact lens solution was prepared in the same manner as in Test solution 1. The prepared contact lens solution was evaluated for antiseptic effects in the same manner as described above. The obtained results are also shown in Table 1 below.
  • polyhexamethylene biguanide polyhexanide hydrochloride, manufactured by Arch Chemicals Japan Co., Ltd.
  • a contact lens solution was prepared in the same manner as in Test solution 1, except that the blending ratio of polyethylene glycol was changed to 0.25 w / v% instead of 1.5 w / v%.
  • the prepared contact lens solution was evaluated for antiseptic effects in the same manner as described above. The obtained results are also shown in Table 1 below.
  • a contact lens solution was prepared in the same manner as in the test solution 1, except that 0.83 w / v% of sodium chloride was used as the tonicity adjusting agent.
  • the prepared contact lens solution was evaluated for antiseptic effects in the same manner as described above. The obtained results are also shown in Table 1 below.
  • Comparative Solution 1 was prepared in the same manner as the sample solution 1 except that polyethylene glycol was not used at the blending ratio shown in Table 2 below. Further, Comparative Solution 2 was prepared in the same manner as in Test Solution 2, except that polyethylene glycol was not used, at the blending ratio shown in Table 2 below. And about the comparison liquid 1 and the comparison liquid 2, it evaluated the antiseptic effect similarly to the above. The obtained results are also shown in Table 2 below.
  • Comparative solution 3 was prepared in the same manner as test solution 1, except that ⁇ -cyclodextrin was not used. Further, Comparative Solution 4 was prepared in the same manner as Test Solution 1, except that ⁇ -cyclodextrin and polyethylene glycol were not used. And about the comparison liquid 3 and the comparison liquid 4, it carried out similarly to the above, and evaluated the antiseptic effect, respectively. The obtained results are shown together with the blending ratio in Table 2 below.
  • Comparative solution 5 was prepared in the same manner as test solution 2, except that ⁇ -cyclodextrin was not used. Further, Comparative Solution 6 was prepared in the same manner as Test Solution 2, except that ⁇ -cyclodextrin and polyethylene glycol were not used. And about the comparative liquid 5 and the comparative liquid 6, it carried out similarly to the above and evaluated the antiseptic effect. The obtained results are shown together with the blending ratio in Table 2 below.
  • the contact lens solutions (test solutions 1 to 4) according to the present invention have comparative solutions 3 and 5 that do not contain ⁇ -cyclodextrin, -It was found that it had an excellent antiseptic effect comparable to Comparative Solution 4 and Comparative Solution 6 which did not contain cyclodextrin and polyethylene glycol.
  • the conventional contact lens solution (Comparative Solution 1 and Comparative Solution 2) containing ⁇ -cyclodextrin and not containing polyethylene glycol which can be included in the ⁇ -cyclodextrin has a sufficient antiseptic effect. It was recognized that it was not.
  • ⁇ -cyclodextrin compound A in which the benzalkonium chloride and polyhexamethylene biguanide having antiseptic and disinfecting effects coexist in the contact lens solution in Comparative Solution 1 and Comparative Solution 2 is used.
  • the drug action could not be sufficiently exerted, whereas in the contact lens solution according to the present invention, such benzalkonium chloride or polyhexamethylene
  • the inclusion of biguanide in ⁇ -cyclodextrin (compound A) is considered to be the result of effective control by polyethylene glycol (compound B) coexisting in the liquid for contact lenses.
  • Comparative solution 7 As a pharmaceutical ingredient, 0.01 w / v% of benzalkonium chloride is used, 0.1 w / v% of ⁇ -cyclodextrin is used as Compound A, and 0.6 w / v of sodium hydrogen phosphate is used as a buffer. Comparative solution 7 was prepared using v% and 0.08 w / v% of sodium dihydrogen phosphate.
  • test solutions 1 and 3 and the comparative solution 7 which are contact lens solutions prepared as described above were evaluated for cytotoxicity as follows, respectively, and in the same manner as described above, the antiseptic effect ( Test bacteria: Pseudomonas aeruginosa) was evaluated. The results are also shown in Table 3 below together with the blending ratio.
  • a fresh medium (MEM solution supplemented with 5 vol% fetal calf serum) was injected into a multiplate for cell culture, and about 50 V79 cells (Chinese hamster lung-derived fibroblasts) were seeded there. Then, the multiplate was accommodated in a carbon dioxide culture apparatus maintained at 37 ° C., and cultured for about 24 hours at a carbon dioxide concentration of 5%. Thereafter, the culture solution in the well was removed, and the test solution 1, 3 and the comparison solution 7 that were prepared in the above were diluted 100 times with 5 vol% fetal calf serum-added MEM solution into the well. The aliquot was dispensed and kept in a carbon dioxide culture apparatus for 6-7 days.
  • the contact lens solution is removed from each well, the cells are fixed by adding ethanol for about 5 minutes, and then adding about 2 vol% Giemsa solution for about 30 minutes. Cells were stained. Then, the stained cells were observed with a stereomicroscope, and the number of colonies was counted with a colony in which 50 or more cells gathered as one colony.
  • a fresh medium (5 vol% fetal calf serum-added MEM solution) was injected into a cell culture multiplate, and about 50 V79 cells (Chinese hamster lung-derived fibroblasts) were seeded there. Thereafter, the cells were cultured in a carbon dioxide culture apparatus maintained at 37 ° C. for 1 week, and the number of colonies was measured by staining the medium after the culture.
  • Colony formation rate (%) [(Average number of colonies formed in the liquid for contact lenses) / (Average number of colonies formed with blanks)] ⁇ 100 (%) (Formula 1)
  • cytotoxicity was evaluated based on the following criteria.
  • Test Solution 1 and Test Solution 3 according to the present invention contain polyethylene glycol together with ⁇ -cyclodextrin, its cytotoxicity is low, and the eye It has been confirmed that the drug action (preservative effect) of the drug component (benzalkonium chloride) can be effectively exhibited.
  • the comparative solution 7 supplemented with EDTA or boric acid for the decrease in the antiseptic effect due to the addition of ⁇ -cyclodextrin has a sufficient antiseptic effect, but has a low colony formation rate and is highly toxic. It was recognized that there was.
  • Benzalkonium chloride adsorption test First, 2 mL of the contact lens solution prepared above was weighed into a glass vial, and one soft contact lens (1.DAY ACUVUE, manufactured by Johnson & Johnson Co., Ltd.) was immersed therein. Next, the glass vial in which the contact lens was immersed was shaken at room temperature for about 8 hours, and then the lens was taken out. And the light absorbency in 263 nm of the liquid agent for contact lenses before and behind immersion of a contact lens was measured, and the adsorption amount of benzalkonium chloride was computed according to the following formula 2.
  • Benzalkonium chloride adsorption ( ⁇ g) [(Absorbance of liquid for contact lens-Absorbance of liquid for contact lens after immersion) / (Absorbance of liquid for contact lens)] ⁇ 200 ( ⁇ g) (Formula 2)
  • -Comparison solution 9- A contact lens solution was prepared in the same manner as in Test Solution 4, except that ⁇ -cyclodextrin and polyethylene glycol were not used, and the amount of sodium chloride was 0.6 w / v%. The adjusted contact lens solution was subjected to a benzalkonium chloride adsorption test in the same manner as described above to calculate the amount of benzalkonium chloride adsorbed. The results are shown together with the blending ratio in Table 4 below.
  • Comparative Solution 9 containing no ⁇ -cyclodextrin and polyethylene glycol does not contain ⁇ -cyclodextrin, so that the antiseptic effect of benzalkonium chloride is sufficiently exhibited. Adsorbed in large amounts on contact lenses and was found to be inferior in eye safety.
  • -Test solution 5- chlorpheniramine maleate is used as the drug component (antihistamine), ⁇ -cyclodextrin (manufactured by Wako Pure Chemical Industries, Ltd.) is used as compound A, and compound B has a weight average molecular weight of 6000.
  • a contact lens solution (Test Solution 5) was prepared at a blending ratio shown in Table 5 below.
  • a HuMedia-EG2 culture solution manufactured by Kurashiki Boseki Co., Ltd.
  • was used in place of purified water for the following antihistamine activity test was used in place of purified water for the following antihistamine activity test.
  • antihistamine activity tests were done about this prepared contact lens solution. The results are shown in Table 5 below together with the blending ratio.
  • Comparative solution 10 and Comparative solution 11- A comparative solution 10 was prepared in the same manner as the test solution 5 except that polyethylene glycol was not used. Further, Comparative Solution 11 was prepared in the same manner as Test Solution 5, except that ⁇ -cyclodextrin was not used. And about the prepared comparison liquid 10 and the comparison liquid 11, it carried out similarly to the above, and performed the antihistamine activity test. The results are also shown in Table 5 below.
  • -Comparison solution 14 About 3,000 human umbilical cord-derived normal vascular endothelial cells (distributed from Human Science Research Resource Bank, resource number: IF050271, resource name: HUV-EC-C) in a 24-well plate for tissue culture (manufactured by Becton Dickinson, Japan) Seeds / cm 2 . Then, after culturing for 6 days using the HuMedia-EG2 culture solution and removing the culture solution, the HuMedia-EG2 culture solution was added as the comparison solution 14 and further cultured for 21 hours. The culture was performed under the conditions of temperature: 37 ° C. and CO 2 concentration: 5%. After completion of the culture, the concentration of interleukin-8 (IL-8) in the culture was measured by oxygen-linked immunosorbent assay (ELISA). The results are also shown in Table 5 below.
  • Comparative Solution 13 As is clear from the results of Table 5, in Comparative Solution 13, the production of interleukin-8 in the cells was enhanced by the addition of histamine, and the concentration of interleukin-8 in the culture solution was increased. . Further, in Comparative Solution 12 containing chlorpheniramine maleate, which is an antihistamine, chlorpheniramine maleate antagonized with histamine and suppressed the production of interleukin-8, resulting in a lower interleukin-8 concentration. It was. Further, in the comparative liquid 11 containing polyethylene glycol in addition to chlorpheniramine maleate, the concentration of interleukin-8 was lowered as in the comparative liquid 12.
  • the interleukin is compared with the comparative solution 12 which does not contain ⁇ -cyclodextrin. -8 concentration increased. This is presumably because chlorpheniramine maleate was included in the pores of ⁇ -cyclodextrin and its antihistaminic activity was suppressed. On the other hand, in the test solution 5 containing polyethylene glycol together with chlorpheniramine maleate and ⁇ -cyclodextrin, the interleukin-8 concentration was low.
  • chlorpheniramine maleate drug component
  • compound A ⁇ -cyclodextrin
  • compound B polyethylene glycol
  • -Test solution 6- Instead of 0.01 w / v% of benzalkonium chloride, 0.03 w / v% of chlorpheniramine maleate was used, and the blending ratio of polyethylene glycol was changed to 1.5 w / v%.
  • a contact lens solution (Test Solution 6) was prepared in the same manner as Test Solution 4, except that the concentration was 5 w / v%. The prepared contact lens solution was subjected to the following chlorpheniramine maleate adsorption test. The results are shown together with the blending ratio in Table 6 below.
  • Chlorpheniramine maleate adsorption [(Absorbance of liquid for contact lens-Absorbance of liquid for contact lens after immersion) / (Absorbance of liquid for contact lens)] ⁇ 600 ( ⁇ g) (Formula 3)
  • a comparative solution 15 was prepared in the same manner as the test solution 6 except that polyethylene glycol was not used.
  • a comparative solution 16 was prepared in the same manner as the test solution 6 except that ⁇ -cyclodextrin and polyethylene glycol were not used. And about the adjusted comparative liquid 15 and the comparative liquid 16, it carried out similarly to the above, the maleic acid chlorpheniramine adsorption test was done, and the maleic acid chlorpheniramine adsorption amount was computed. The results are also shown in Table 6 below.
  • test solutions 10 to 12 and 13 to 15 and the comparative solutions 18 and 19 were subjected to the cytotoxicity test described above, and the results are shown in Tables 8 and 9 below as colony formation rates. Also shown.
  • the cytotoxicity test was carried out using the test solution and the comparison solution as they were without diluting the test solutions 10 to 12, 13 to 15 and the comparison solutions 18 and 19 with 5 vol% fetal calf serum-added MEM solution.
  • any of the test solutions 10 to 12 and 13 to 15 As shown in Tables 8 and 9, as compared with the case of PEG alone (Comparative solutions 18 and 19), by allowing cyclodextrin to coexist with PEG, any of the test solutions 10 to 12 and 13 to 15 Also, the colony formation rate increased. Therefore, it is considered that PEG and cyclodextrin formed a pseudorotaxane or pseudopolyrotaxane structure, thereby reducing the cytotoxicity of PEG.
  • the reason why the colony formation rates are different in the test solutions 10 to 12 and 13 to 15 is that, similarly to the poloxamer, the ring size of each cyclodextrin is different and the formation rate of pseudorotaxane or pseudopolyrotaxane with PEG is different. Inferred.
  • PEG 600 is likely to form a pseudo-rotaxane or pseudo-polyrotaxane structure with ⁇ -cyclodextrin
  • PEG 6000 is likely to form a pseudo-rotaxane or pseudo-polyrotaxane structure with ⁇ -cyclodextrin.

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Abstract

La présente invention concerne une préparation liquide pour lentilles de contact qui contient un composé présentant une structure moléculaire cyclique ou tubulaire, telle de la cyclodextrine, ainsi qu'un composant médicamenteux dans un excipient liquide et qui peut avantageusement transmettre l'effet médicamenteux du composant médicamenteux. De plus, à un excipient liquide, contenant un composé (A) présentant une structure moléculaire cyclique ou tubulaire ainsi qu'un composant médicamenteux déterminé, est ajouté un composé (B) présentant une structure moléculaire en chaîne et pouvant être clathraté à l'intérieur du composé (A) de la manière précédemment décrite, de sorte que le composé (B) peut être simultanément clathraté avec le composant médicamenteux dans les pores cycliques ou tubulaires du composé (A). De ce fait, l'effet médicamenteux du composant médicamenteux peut avantageusement être régulé.
PCT/JP2009/003417 2008-07-22 2009-07-22 Préparation liquide pour lentilles de contact Ceased WO2010010689A1 (fr)

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JPWO2012005311A1 (ja) * 2010-07-06 2013-09-05 ロート製薬株式会社 コンタクトレンズケア用組成物
JP2016516068A (ja) * 2013-03-15 2016-06-02 エアーピオ セラピューティクス インコーポレイテッド 眼疾患を処置するための組成物、製剤、および方法
US10220048B2 (en) 2013-03-15 2019-03-05 Aerpio Therapeutics, Inc. Compositions and methods for treating ocular diseases
JP2019142833A (ja) * 2018-02-22 2019-08-29 優▲ニ▼康光學股▲フン▼有限公司 活性成分放出機能を有する水性組成物、及び反復利用可能なコンタクトレンズ製品
CN113527581A (zh) * 2020-04-13 2021-10-22 晶硕光学股份有限公司 水胶组成物及水胶镜片
TWI759050B (zh) * 2020-12-31 2022-03-21 財團法人工業技術研究院 具有緩釋特性的隱形眼鏡
JP2025003297A (ja) * 2023-06-21 2025-01-09 ペガヴィジョン コーポレーション 薬物組成物を含有するコンタクトレンズ及びその製造方法

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JPWO2012005311A1 (ja) * 2010-07-06 2013-09-05 ロート製薬株式会社 コンタクトレンズケア用組成物
JP7249374B2 (ja) 2013-03-15 2023-03-30 アイポイント ファーマシューティカルズ， インコーポレイテッド 眼疾患を処置するための組成物、製剤、および方法
JP2016516068A (ja) * 2013-03-15 2016-06-02 エアーピオ セラピューティクス インコーポレイテッド 眼疾患を処置するための組成物、製剤、および方法
US10220048B2 (en) 2013-03-15 2019-03-05 Aerpio Therapeutics, Inc. Compositions and methods for treating ocular diseases
JP2019218370A (ja) * 2013-03-15 2019-12-26 エアーピオ セラピューティクス インコーポレイテッド 眼疾患を処置するための組成物、製剤、および方法
JP2021100979A (ja) * 2013-03-15 2021-07-08 エアーピオ セラピューティクス インコーポレイテッド 眼疾患を処置するための組成物、製剤、および方法
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JP2019142833A (ja) * 2018-02-22 2019-08-29 優▲ニ▼康光學股▲フン▼有限公司 活性成分放出機能を有する水性組成物、及び反復利用可能なコンタクトレンズ製品
CN113527581A (zh) * 2020-04-13 2021-10-22 晶硕光学股份有限公司 水胶组成物及水胶镜片
JP7140869B2 (ja) 2020-04-13 2022-09-21 ペガヴィジョン コーポレーション ハイドロゲル組成物及びハイドロゲルレンズ
CN113527581B (zh) * 2020-04-13 2024-08-02 晶硕光学股份有限公司 水胶组成物及水胶镜片
JP2021169446A (ja) * 2020-04-13 2021-10-28 ペガヴィジョン コーポレーションPegavision Corporation ハイドロゲル組成物及びハイドロゲルレンズ
TWI759050B (zh) * 2020-12-31 2022-03-21 財團法人工業技術研究院 具有緩釋特性的隱形眼鏡
JP2025003297A (ja) * 2023-06-21 2025-01-09 ペガヴィジョン コーポレーション 薬物組成物を含有するコンタクトレンズ及びその製造方法

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