WO2023013628A1 - Composition de lavage oculaire - Google Patents

Composition de lavage oculaire Download PDF

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Publication number
WO2023013628A1
WO2023013628A1 PCT/JP2022/029621 JP2022029621W WO2023013628A1 WO 2023013628 A1 WO2023013628 A1 WO 2023013628A1 JP 2022029621 W JP2022029621 W JP 2022029621W WO 2023013628 A1 WO2023013628 A1 WO 2023013628A1
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Prior art keywords
salts
composition
present disclosure
acid
eye wash
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PCT/JP2022/029621
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English (en)
Japanese (ja)
Inventor
晃平 見目
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小林製薬株式会社
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Priority to CN202280053727.9A priority Critical patent/CN117835988A/zh
Publication of WO2023013628A1 publication Critical patent/WO2023013628A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4415—Pyridoxine, i.e. Vitamin B6
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/728—Hyaluronic acid
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • 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
    • 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 inventor aims to provide an eye wash composition that has excellent antiseptic properties while containing propylene glycol.
  • the present inventors have conducted intensive studies in view of the above problems, and have found that by using a combination of 0.01 w/v% or more of hyaluronic acid with propylene glycol in an eye wash composition, the antiseptic agent is not added. Nevertheless, the present inventors have found that antiseptic properties can be imparted to eye wash compositions despite the fact that propylene glycol is incorporated.
  • the present invention has been completed as a result of further studies based on this knowledge, and is described below. Section 1.
  • An eye wash composition excellent in antiseptic properties can be provided even if it does not contain an antiseptic selected from chlorobutanol and sorbic acids.
  • the present disclosure contains 0.01 w/v% or more of at least one selected from the group consisting of hyaluronic acid and salts thereof, and propylene glycol, quaternary ammonium salt preservatives, paraoxybenzoic acid esters, It includes preservative-free eye wash compositions selected from chlorobutanol and sorbic acids.
  • At least one selected from the group consisting of hyaluronic acid and salts thereof is a conventionally known substance, and as a salt of hyaluronic acid, preferably an alkali metal salt such as sodium salt. etc. are exemplified. These may be used individually by 1 type, and may be used in combination of 2 or more type.
  • component (A) is not limited as long as it is 0.01 w/v% or more in the eye wash composition of the present disclosure, preferably 0.01 to 0.08 w/v%, more preferably 0.01. ⁇ 0.02 w/v%, more preferably 0.015 to 0.02 w/v% is exemplified.
  • Propylene glycol (sometimes referred to as component (B)) is conventionally known.
  • the content of propylene glycol is not limited as long as the effects of the present disclosure can be obtained, but it is preferably 0.01 to 2 w/v%, more preferably 0.05 to 1.5 w/v% in the eye wash composition. , and more preferably 0.1 to 1 w/v%.
  • the content of propylene glycol is not limited as long as the effects of the present disclosure can be obtained, but is preferably 1 to 100 parts by mass, more preferably 10 to 100 parts by mass, per 1 part by mass of component (A) in the eye wash composition. 55 parts by mass, more preferably 20 to 50 parts by mass is exemplified.
  • the eye wash composition of the present disclosure does not contain a preservative selected from quaternary ammonium salt preservatives, paraoxybenzoic acid esters, chlorobutanol and sorbic acids.
  • the antiseptic is a conventionally known antiseptic in the fields of eye drops and eye washes.
  • quaternary ammonium preservatives include benzalkonium chloride and benzethonium chloride.
  • paraoxybenzoic acid esters include paraoxybenzoic acid esters such as methyl parahydroxybenzoate, propyl parahydroxybenzoate, and butyl parahydroxybenzoate, and salts of paraoxybenzoic acid esters (alkali metal salts such as sodium salts, etc.).
  • sorbic acids include sorbic acid, salts of sorbic acid (alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as calcium salts and magnesium salts, etc.), and the like.
  • the eyewash composition of the present disclosure may further contain at least one selected from the group consisting of edetic acid and salts thereof (sometimes referred to as component (C)).
  • Edetic acid is also known as ethylenediaminetetraacetic acid (EDTA).
  • Edetate salts include monosodium edetate, disodium edetate, trisodium edetate, tetrasodium edetate, dipotassium edetate, tripotassium edetate, and tetrapotassium edetate (including hydrates). be done. These may be used individually by 1 type, and may be used in combination of 2 or more type.
  • component (C) in the eyewash composition is 0.02 w/ v % or more, preferably 0.05 w/v % or more, more preferably 0.05 to 0.1 w/v %, still more preferably 0.05 to 0.08 w/v %.
  • the content of component (C) is not limited as long as the effects of the present disclosure can be obtained, but is preferably 1 to 8 parts by mass, more preferably 1 to 8 parts by mass per 1 part by mass of component (A) in the eye wash composition. Examples are 2 to 6 parts by mass, more preferably 2.5 to 5 parts by mass.
  • the eyewash composition of the present disclosure may further contain at least one selected from the group consisting of pyridoxine, chondroitin sulfate and salts thereof (sometimes referred to as component (D)).
  • Pyridoxine and its salts are known substances and are not limited, but examples of salts of pyridoxine include hydrochloride (pyridoxine hydrochloride) and inorganic acid salts such as phosphate.
  • Chondroitin sulfate is a mucopolysaccharide that has a structure in which sulfuric acid is ester-bonded to a sugar chain of repeating disaccharides of D-glucuronic acid and N-acetylgalactosamine.
  • chondroitin sulfate salts include, but are not limited to, alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as magnesium salts and calcium salts, and the like.
  • Examples of chondroitin sulfate salts which are not intended to limit the scope of the present invention, include sodium chondroitin sulfate and the like.
  • the chondroitin sulfate and salts thereof used in the present disclosure are not limited in this respect, but the molecular weight thereof is preferably exemplified by a weight-average molecular weight of about 05,000 to 45,000, more preferably 10,000 to 4,000. About 10,000, more preferably about 15,000 to 30,000 are exemplified. Weight average molecular weight is measured by gel filtration chromatography. Chondroitin sulfate and salts thereof are commercially available, for example, under the trade name of sodium chondroitin sulfate (manufactured by Seikagaku Corporation, weight average molecular weight: 20,000).
  • chondroitin sulfate and its salts may be used singly or in combination of two or more.
  • component (D) in the eye wash composition is preferably 0.5. 001 to 0.1 w/v%, more preferably 0.01 to 0.07 w/v%, and still more preferably 0.04 to 0.06 w/v%.
  • the content of component (D) is not limited as long as the effects of the present disclosure can be obtained, but is preferably 1 to 10 parts by mass, more preferably 2 parts by mass per 1 part by mass of component (A) in the eye wash composition. Up to 6 parts by mass, more preferably 2 to 4 parts by mass are exemplified.
  • At least one selected from the group consisting of pyridoxine and its salts is 0.008 to 0.01 w/v% in the eye wash composition, More preferably 0.001 to 0.01 w/v%, particularly preferably 0.005 to 0.01 w/v%.
  • At least one selected from the group consisting of chondroitin sulfate and salts thereof is 0.0055 to 0.05 w/v% in the eye wash composition. , more preferably 0.01 to 0.05 w/v%, particularly preferably 0.025 to 0.05 w/v%.
  • the eye wash composition of the present disclosure may further contain any other component acceptable for use in eye drops or eye wash.
  • Other ingredients include, but are not limited to, buffers, stabilizers, tonicity agents, solvents (such as water), pH adjusters, medicinal ingredients, cooling agents, stimulants, and thickeners. etc. are exemplified.
  • the other components may be appropriately selected according to the purpose, etc., as long as they do not interfere with the effects of the present disclosure, and may be used singly or in combination of two or more. , and the blending amount thereof may be appropriately determined.
  • the components (A) to (D) are also known as, for example, medicinal ingredients, stabilizers, thickeners, etc., depending on the component, but in the present disclosure, the components (A) to (D) are It is not included in any other component.
  • buffering agents such as boric acid and borax.
  • a buffering agent may be used individually by 1 type, and may be used in combination of 2 or more type.
  • boric acid the content of boric acid is not limited as long as it does not interfere with the effects of the present disclosure. exemplified, more preferably 0.5 to 2 w/v%.
  • borax the content of borax is not limited as long as it does not interfere with the effects of the present disclosure. exemplified, more preferably 0.005 to 0.05 w/v%.
  • the composition may or may not contain buffering agents other than boric acid and borax. Also, the composition may contain only one of boric acid and borax.
  • stabilizers include stabilizers such as polysorbate (polysorbate 80, polysorbate 60, etc.), polyoxyethylene (POE) hydrogenated castor oil (POE (80) hydrogenated castor oil, POE (60) hydrogenated castor oil,
  • POE polyoxypropylene glycol
  • the number in parentheses means the average number of added moles of ethylene oxide), POE polyoxypropylene glycol, trometamol and the like. These may be used individually by 1 type, and may be used in combination of 2 or more type.
  • the composition contains a stabilizer, its content is not limited as long as it does not interfere with the effects of the present disclosure, preferably 0.01 to 1 w / v% in the composition, more preferably 0.05 to 0.1 w/v% is exemplified.
  • composition when the composition contains a stabilizer, it may contain only one or only two selected from, for example, polysorbate, POE hydrogenated castor oil, POE polyoxypropylene glycol and trometamol. , polysorbate, it can also be prepared without POE hydrogenated castor oil, POE polyoxypropylene glycol and/or trometamol.
  • ingredients examples include amino acids, anti-inflammatory agents, vitamins, antihistamines, and the like. These may be used individually by 1 type, and may be used in combination of 2 or more type.
  • amino acids include amino acids such as glutamic acid and salts thereof and salts thereof; amino acid analogues such as taurine. These may be used individually by 1 type, and may be used in combination of 2 or more type.
  • the eyewash composition of the present disclosure can also be prepared without the amino acid and/or salt thereof.
  • amino acid as used herein means an amino acid having both an amino group and a carboxyl group and capable of becoming a structural unit of a protein, and includes, for example, L-aspartic acid.
  • the eyewash composition of the present disclosure can also be prepared without the amino acid analogue.
  • Non-limiting examples of anti-inflammatory agents include zinc sulfate, zinc lactate, epsilon-aminocaproic acid, allantoin, glycyrrhizic acid and its salts, azulenes (azulene, dimethylisopropylazulene, dimethylethylazulene, these salt etc.) and the like are exemplified. These may be used individually by 1 type, and may be used in combination of 2 or more type. While not limiting the disclosure, the composition preferably does not contain zinc sulfate and/or zinc lactate. The composition can also be prepared without epsilon-aminocaproic acid, allantoin, glycyrrhizic acid and salts thereof.
  • vitamins examples include vitamin A (retinol palmitate, retinol acetate, retinol, retinal, retinoic acid, etc.), vitamin B (flavin adenine dinucleotide, cyanocobalamin, etc.), vitamin E (acetic acid tocopherol, tocopherol succinate, tocopherol nicotinate, tocopherol linolenate, etc.). These may be used individually by 1 type, and may be used in combination of 2 or more type. While not limiting the disclosure, the composition may be prepared without at least one of the vitamins.
  • vitamin A retinol palmitate, retinol acetate, retinol, retinal, retinoic acid, etc.
  • vitamin B flavin adenine dinucleotide, cyanocobalamin, etc.
  • vitamin E acetic acid tocopherol, tocopherol succinate, tocopherol nicotinate, tocopherol linol
  • antihistamines include chlorpheniramine and its salts (chlorpheniramine maleate, etc.), diphenhydramine and its salts (diphenhydramine hydrochloride, etc.), and the like. These may be used individually by 1 type, and may be used in combination of 2 or more type. Compositions of the present disclosure may also be prepared without an antihistamine.
  • the content of the medicinal ingredient is not limited as long as it does not interfere with the effects of the present disclosure, and the content of the medicinal ingredient in the composition is preferably 0.05 to 0. .3 w/v%, more preferably 0.1 to 0.3 w/v%, and even more preferably 0.2 to 0.27 w/v%.
  • cooling agents such as menthol, camphor, and borneol.
  • a cooling agent may be used individually by 1 type, and may be used in combination of 2 or more types.
  • the compositions of the present disclosure may contain cooling agents or may be prepared without cooling agents.
  • compositions of the present disclosure may contain a stimulant or may be prepared without a stimulant.
  • Examples of other components include thickeners, such as alginic acid and salts thereof, hydroxyethylcellulose, methylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, polyethylene glycol, polyvinylpyrrolidone, polyvinyl alcohol, carboxyvinyl polymer, and these. Salt, glycerin and the like are exemplified. These may be used individually by 1 type, and may be used in combination of 2 or more type.
  • the eyewash composition of the present disclosure can also be prepared without these thickening agents.
  • the eye wash composition of the present disclosure can be produced by mixing the components (A) and (B), and optionally the components (C) and (D), and the other components.
  • the mixing is not limited as long as these components can be mixed, and may be mixed according to a normal procedure.
  • the pH of the eye wash composition of the present disclosure is not limited as long as it can be used as an eye drop or an eye wash. is pH 5.5 to 6, more preferably pH 5.5 to 5.8.
  • the form of the eye wash composition of the present disclosure is liquid at room temperature, and the method of use is not limited as long as the eye can be washed in the same manner as in conventionally known methods. used or used to wash the eyes with eye drops.
  • the eye wash composition of the present disclosure may be used with or without contact lenses.
  • Contact lenses may be either hard contact lenses or soft contact lenses.
  • the eye wash composition of the present disclosure is not limited as long as it can be used as described above. (including the cap).
  • the volume of the container is not limited, the volume is preferably 450 to 550 mL from the viewpoint of ease of use.
  • Eyewashing using an eyewash cup may follow a normal procedure.
  • an appropriate amount of the eyewash composition of the present disclosure is poured from the container into the eyewash cup, for example, 4 to 6 mL per eye at a time, and then the cup is poured. is pressed around the eye on one side to bring the eye wash composition in the cup into contact with the eye, and the eye is blinked several times.
  • the eyewash composition of the present disclosure when used for eyewash by eyedrops, it is usually housed in an eyedropper container for use.
  • the eye drop container is not limited as long as the composition can be accommodated and applied to the eye. and at least two of the caps are integrated) is exemplified.
  • the volume of the container is not limited, a volume of 8 to 20 mL is exemplified from the viewpoint of ease of use.
  • the eye wash by instillation may follow the usual method of use, and the eye wash composition of the present disclosure is used by instilling 4 to 6 drops per eye at a time.
  • the amount to be dropped per drop is also not limited, but preferably 35 to 40 ⁇ L is exemplified per drop.
  • the eye wash composition of the present disclosure hyaluronic acid and By using 0.01 w/v% or more of at least one selected from the group consisting of salts thereof in combination with propylene glycol, excellent antiseptic properties can be imparted to the eye wash composition. Further, by blending at least one selected from the group consisting of edetic acid and salts thereof, or blending at least one selected from the group consisting of pyridoxine, chondroitin sulfate and salts thereof, As shown in the examples, the eyewash composition can be provided with even better antiseptic properties, although no antiseptic is added. In addition, when the composition further contains the above-mentioned active ingredients and the like, useful effects based on the active ingredients and the like can also be obtained.
  • Test example 1 Preparation of eyewash composition
  • Each component was mixed according to the mixing ratio shown in Table 1 below, and the resulting mixture was passed through a sterilizing filter (Examples 1 to 5, Reference Examples, Comparative Examples 1 to 3).
  • the pH of each composition immediately after preparation was measured.
  • the pH was measured at room temperature (25° C.) using a desktop pH meter F-52 (manufactured by Horiba, Ltd.).
  • sodium chondroitin sulfate ester in the table a pharmacologically approved sodium chondroitin sulfate (weight average molecular weight: 20,000) was used.
  • a bacterial solution (1 ⁇ 10 8 cfu/mL) was prepared by suspending Candida albicans in sterilized physiological saline. 10 mL of each composition obtained as described above was inoculated with the bacterial solution at 1 ⁇ 10 6 cfu/mL and stored at 30° C. in the dark for 14 days. After storage, 0.1 mL of each composition inoculated with Candida was applied to a commercially available GPLP agar medium (GPLP agar medium "Daigo", manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) with a conlarge stick and cultured at 30 ° C. for 48 hours.
  • GPLP agar medium "Daigo" manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.
  • the antiseptic power of the eye wash composition was evaluated according to the following criteria. [Evaluation criteria] ⁇ : Survival rate decreased to 0.1% or less of the inoculated dose ⁇ : Survival rate decreased to 1% or less of the inoculated dose ⁇ : Survival rate decreased to 10% or less of the inoculated dose ⁇ : Does not meet the above ⁇ criteria
  • ⁇ Staphylococcus aureus> A bacterial solution (1 ⁇ 10 8 cfu/mL) was prepared by suspending Staphylococcus aureus in sterilized physiological saline. 10 mL of each composition obtained as described above was inoculated with the bacterial solution at 1 ⁇ 10 6 cfu/mL, and stored at 35° C. in the dark for 14 days. After storage, 0.1 mL of each composition inoculated with Staphylococcus aureus was applied to a commercially available SCDLP agar medium (SCDLP agar medium "Daigo", manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) with a conlarge stick, and kept at 35 ° C. for 48 hours.
  • SCDLP agar medium "Daigo manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.
  • the antiseptic power of the eye wash composition was evaluated according to the same criteria as described above.
  • the reference example containing benzalkonium chloride, which is an antiseptic, is a positive control in this test example.
  • Comparative Example 1 in which propylene glycol was added without benzalkonium chloride, the evaluation result was x, and the desired antiseptic power was not obtained.
  • Comparative Example 2 in which 0.01 w/v % sodium hyaluronate was added without benzalkonium chloride or propylene glycol, the evaluation result was ⁇ , and the desired antiseptic power was not obtained.
  • Comparative Example 3 in which 0.001 w/v% sodium hyaluronate and propylene glycol were blended without benzalkonium chloride, the evaluation result was ⁇ , and the desired antiseptic power was not obtained.
  • Example 1 in which 0.01 w/v% sodium hyaluronate and propylene glycol were blended without benzalkonium chloride, the evaluation result was ⁇ , and an improvement in antiseptic power was recognized. Also in Example 2 in which the content of sodium hyaluronate was increased in Example 1, the evaluation result was ⁇ , and an improvement in antiseptic power was recognized. From this, it was confirmed that the combination of 0.01 w/v% or more of sodium hyaluronate with propylene glycol, which surprisingly has poor antiseptic properties, can enhance the antiseptic properties of eye wash compositions.
  • Example 3 to 5 in which sodium edetate was further blended in Examples 1 and 2 Example 6 in which sodium chondroitin sulfate was further blended in Example 5, and pyridoxine hydrochloride in Example 6 were further blended.
  • Example 7 which was blended, the evaluation result was ⁇ or ⁇ , and an improvement in antiseptic power was recognized. Further, even when the pH of Examples 1 to 7 was 6.2, an improvement in antiseptic properties similar to that of Examples 1 to 7 was observed.
  • sodium hyaluronate is used in combination with propylene glycol, which has poor antiseptic properties, at 0.01 w/v% or more, and furthermore, sodium edetate, sodium chondroitin sulfate, and pyridoxine hydrochloride are used in combination. By doing so, it was confirmed that the antiseptic property of the eyewash composition can be enhanced.
  • the eyewash compositions of Examples 1 to 7 do not use a preservative such as benzalkonium chloride, which is likely to be adsorbed to contact lenses, the antiseptic properties of the eyewash compositions can be enhanced, and thus the eyes can be washed while the contact lenses are worn. It is possible to
  • An eye wash composition was prepared according to the blending ratio shown in Formulation Example Table 3, and the antiseptic power was evaluated in the same manner as in Test Examples. Improvement of antiseptic property was recognized to some extent.

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Abstract

Le problème décrit par la présente invention est de fournir une composition de lavage oculaire qui contient du propylène glycol mais présente néanmoins d'excellentes propriétés antiseptiques. La solution selon l'invention porte sur une composition de lavage oculaire qui contient 0,01 % en poids/volume ou davantage d'au moins un élément choisi dans le groupe constitué par l'acide hyaluronique et ses sels et le propylène glycol mais ne contient pas d'agent antiseptique choisi parmi des agents antiseptiques à base de sel d'ammonium quaternaire, des paraoxybenzoates, du chlorobutanol, de l'acide sorbique et leurs dérivés.
PCT/JP2022/029621 2021-08-03 2022-08-02 Composition de lavage oculaire WO2023013628A1 (fr)

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