WO2015156321A1 - Composition ophtalmique - Google Patents

Composition ophtalmique Download PDF

Info

Publication number
WO2015156321A1
WO2015156321A1 PCT/JP2015/060989 JP2015060989W WO2015156321A1 WO 2015156321 A1 WO2015156321 A1 WO 2015156321A1 JP 2015060989 W JP2015060989 W JP 2015060989W WO 2015156321 A1 WO2015156321 A1 WO 2015156321A1
Authority
WO
WIPO (PCT)
Prior art keywords
ophthalmic composition
polysorbate
polydispersity
molecular weight
eye
Prior art date
Application number
PCT/JP2015/060989
Other languages
English (en)
Japanese (ja)
Inventor
昌志 伊藤
剛典 松本
千草 中塚
史恵 眺野
Original Assignee
ロート製薬株式会社
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
Priority claimed from JP2014110926A external-priority patent/JP5654704B1/ja
Priority claimed from JP2014204950A external-priority patent/JP2016053014A/ja
Application filed by ロート製薬株式会社 filed Critical ロート製薬株式会社
Priority to US15/302,636 priority Critical patent/US20170056335A1/en
Priority to CN201580016532.7A priority patent/CN106163565A/zh
Publication of WO2015156321A1 publication Critical patent/WO2015156321A1/fr

Links

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
    • A61K31/74—Synthetic polymeric materials
    • A61K31/765—Polymers containing oxygen
    • A61K31/77—Polymers containing oxygen of oxiranes

Definitions

  • the present invention relates to an ophthalmic composition.
  • the cornea is a tissue composed of five layers of the corneal epithelium, Bowman's membrane, corneal stroma, Descemet's membrane, and corneal endothelium in order from the outside, and is configured on the outermost surface of the eyeball (the outermost surface of the eyeball).
  • the cornea is easily invaded by various foreign substances such as antigens, microorganisms, and dust due to anatomical features that are in direct contact with the outside world. Cornea perception is one of the most sensitive perceptions of human pain.
  • Patent Document 1 As a countermeasure against the intrusion of such foreign matter, an eyewash containing a carboxyvinyl polymer and a monoterpene and removing a cosmetic or pollen from the eyeball or eyelid and using a single eyewash of 500 ⁇ L or more is seen.
  • Patent Document 1 An eyewash containing a carboxyvinyl polymer and a monoterpene and removing a cosmetic or pollen from the eyeball or eyelid and using a single eyewash of 500 ⁇ L or more is seen.
  • the present invention has been made in view of the above circumstances, and an object thereof is to provide an ophthalmic composition capable of improving the effect of suppressing the adsorption of foreign matter to the cornea and alleviating the feeling of foreign matter in the eye.
  • the ophthalmic composition in which the polydispersity of the component (A) in the ophthalmic composition is 1.00 to 1.26 suppresses the adsorption of foreign matter to the cornea and alleviates the feeling of foreign matter in the eye.
  • the inventors of the present invention are the first to focus on the polydispersity of polysorbate 80 in the ophthalmic composition with respect to the suppression of the foreign matter adsorption to the cornea and the influence on the foreign matter sensation of the eye. Based on these findings, the present inventors have completed the present invention.
  • the present invention provides an ophthalmic composition having the following aspect.
  • the details of the mechanism for suppressing the adsorption of foreign substances to the cornea or alleviating the feeling of foreign substances in the eyes by setting the polydispersity of polysorbate 80 within the following range have not been clarified.
  • One possible reason is that the micelle structure differs slightly from that of the agent, which affects the affinity between corneal epithelial cells and foreign substances.
  • the present invention provides the following [1] to [7].
  • Polysorbate 80; A cooling agent, An ophthalmic composition comprising: The polydispersity of the polysorbate 80 in the ophthalmic composition is 1.00 to 1.26, An ophthalmic composition wherein the refreshing agent comprises at least one selected from the group consisting of camphor, borneol and geraniol; [2] The ophthalmic composition according to the above [1], wherein the total content of the refreshing agent is 0.00005 to 0.5 w / v% based on the total amount of the ophthalmic composition; [3] The above [1] or [2], wherein the total content of the refreshing agent is 0.0001 to 100 parts by mass with respect to 1 part by mass of the polysorbate 80 contained in the ophthalmic composition.
  • the ophthalmic composition according to [4] The ophthalmic composition according to any one of the above [1] to [3], which is an eye drop; [5] The ophthalmic composition according to any one of [1] to [4], which is applied to a contact lens; [6] A foreign substance sensation relieving agent comprising the ophthalmic composition according to any one of [1] to [5] above; [7] A method of imparting a foreign substance easing effect to the ophthalmic composition, comprising blending polysorbate 80 and a refreshing agent in the ophthalmic composition, The polydispersity of the polysorbate 80 in the ophthalmic composition is 1.00 to 1.26, The method wherein the refreshing agent comprises at least one selected from the group consisting of camphor, borneol and geraniol.
  • the present invention also provides the following [P1] to [P7].
  • [P1] polysorbate 80; A cooling agent, An ophthalmic composition comprising: An ophthalmic composition having a polydispersity of the polysorbate 80 in the ophthalmic composition of 1.00 to 1.26;
  • [P3] The above [P1] or [P2], wherein the total content of the cooling agent is 0.0001 to 100 parts by mass with respect to 1 part by mass of the polysorbate 80 contained in the ophthalmic composition.
  • the ophthalmic composition according to [P4] The ophthalmic composition according to any one of the above [P1] to [P3], which is an eye drop;
  • [P5] The ophthalmic composition according to any one of the above [P1] to [P4], which is for a soft contact lens;
  • [P6] A foreign substance sensation relieving agent comprising the ophthalmic composition according to any one of [P1] to [P5] above;
  • [P7] A method of imparting a mitigating action of a foreign body sensation to an ophthalmic composition by blending polysorbate 80 and a refreshing agent, A method wherein the polydispersity of the polysorbate 80 in the ophthalmic composition is 1.00 to 1.26.
  • the present invention provides the following [P8] to [P16].
  • [P8] A method for alleviating ocular foreign body sensation, comprising a step of bringing an ophthalmic composition containing polysorbate 80 and a refreshing agent into contact with an eye of a subject or a contact lens, The method wherein the polydispersity of the polysorbate 80 in the ophthalmic composition is from 1.00 to 1.26;
  • the refreshing agent includes at least one selected from the group consisting of menthol, camphor, borneol and geraniol;
  • [P10] The method according to [P8] or [P9] above, wherein the subject is a human;
  • [P11] Use of polysorbate 80 and a refreshing agent for the manufacture of an ophthalmic composition that relieves ocular foreign body sensation, Use wherein the polydispersity of the polysorbate 80 in the ophthalmic composition is 1.00 to 1.26;
  • an ophthalmic composition capable of improving the effect of suppressing the adsorption of foreign matter to the cornea and alleviating the feeling of foreign matter in the eye.
  • an ophthalmic composition that reduces the adsorption of foreign matter such as air pollutants and cosmetics to the cornea to dust, pollen, eyes, and the like, and reduces the feeling of foreign matter in the eye.
  • the unit of content “%” means “w / v%” and is synonymous with “g / 100 mL”.
  • “foreign substance sensation” means subjective symptoms (discomfort, irritation) of the eyes which are caused by the adsorption of foreign substances to the cornea.
  • subjective symptoms include a subjective symptom in which something hits the eye when blinking, and a subjective symptom in which something is stuck in the eye.
  • the present inventors have focused on suppressing the adsorption of foreign matter to the cornea and improving subjective symptoms in order to alleviate the feeling of foreign matter in the eye.
  • suppressing the adsorption of foreign matter to the cornea has a preventive effect on the feeling of foreign matter in the eye.
  • the ophthalmic composition according to the present embodiment contains (A) polysorbate 80 and (B) a cooling agent, and includes the above-described ophthalmic composition.
  • Polysorbate 80 has a polydispersity of 1.00 to 1.26, and the cooling agent includes at least one selected from the group consisting of camphor, borneol and geraniol.
  • Another ophthalmic composition according to this embodiment contains (A) polysorbate 80 and (B) a refreshing agent, and the polydispersity of the polysorbate 80 in the ophthalmic composition is 1.00 to 1. 26.
  • the polysorbate 80 according to this embodiment (hereinafter sometimes simply referred to as “polysorbate 80”) is not particularly limited as long as the polydispersity is 1.00 to 1.26.
  • the polysorbate 80 can be obtained by measuring the polysorbate 80 obtained as a commercial product by the measurement method described later and selecting a polysorbate 80 having a polydispersity of 1.00 to 1.26.
  • a polysorbate 80 having a polydispersity of 1.00 to 1.26 can be obtained by further fractionating or purifying the polysorbate 80 obtained as a commercial product by a known method.
  • the method for fractionation or purification of the polysorbate 80 is not particularly limited, but purification using an ion exchange resin, activated carbon or adsorbent, steam deodorization, decolorization, dehydration and desolvation, filter filtration, cake filtration, centrifugation, sedimentation A method such as removal or a combination of two or more of these can be used. These fractionation or purification methods can be carried out if it is necessary to eliminate adverse effects on polydispersity measurement errors and the like.
  • fractionation methods of the polysorbate 80 include, for example, a membrane filtration method, a distillation method, an extraction method or washing with an organic solvent, a reprecipitation method, a liquid / liquid separation method, or two or more of these methods. A combined method is mentioned. Specific examples include the following membrane filtration methods.
  • the molecular weight and polydispersity of polysorbate 80 obtained as a commercial product are measured by the size exclusion chromatography (SEC) method described later, and an appropriate ultrafiltration membrane with a rejection rate close to 90% and a permeation flux is selected. .
  • a commercially available filtration membrane can be used (for example, UF disk PLBC Ultracell RC 3K NMWL (molecular weight cut-off 3 KDa, cellulose membrane) (manufactured by Millipore Corporation)).
  • a pressure of 0.5 to 200 Pa is applied according to the limit pressure of the filtration membrane.
  • Polysorbate 80 having a polydispersity of 1.00 to 1.26 can be obtained by fractionation based on the weight average molecular weight and the Z average molecular weight.
  • As other purification methods of the polysorbate 80 for example, crystallization, resin chromatography, a method of directly drying the reaction solution with a spray dryer and pulverizing, a method of removing by steam distillation, an organic solvent and water were used.
  • Examples include liquid-liquid extraction methods.
  • Specific examples of the purification method include the following methods. First, polysorbate 80 is dissolved in methanol, the molecular weight at the critical micelle concentration is measured by a light scattering method, and the fractional molecular weight of the ultrafiltration membrane is determined. Next, membrane filtration is performed under conditions of a flow rate of 0.5 to 10 ml / min and a pressure of 0.1 to 20 bar.
  • the production method of the polysorbate 80 is not particularly limited, but the polysorbate 80 having a polydispersity of 1.00 to 1.26 can be obtained by the following method. It is produced by adding ethylene oxide to a mixture obtained by partially esterifying sorbitol and / or sorbitol anhydride with a fatty acid mainly composed of oleic acid.
  • the ester reaction can be carried out with sorbitan and a fatty acid under a basic catalyst, under an inert gas stream, at normal pressure or under reduced pressure, usually at a temperature of 150 to 280 ° C. After the reaction, neutralization is performed by adding a small amount of acid sufficient to deactivate the basic catalyst.
  • the raw material sorbitol can be obtained by high-pressure hydrogen reduction of glucose, and a commercially available product may be used (for example, sorbitol D-70 (manufactured by Towa Kasei Kogyo Co., Ltd.), sorbitol S (Japan Kenken Chemical Co., Ltd.)). Sorbitan can be obtained by dehydrating cyclization of sorbitol, and commercially available products may be used (for example, those manufactured by Toei Chemical Co., Ltd.). Commercially available sorbitan oleate can also be used.
  • the step of adding ethylene oxide to sorbitan fatty acid ester uses a catalyst such as an alkali metal catalyst and fatty acid soap.
  • the manufactured polysorbate 80 can be filtered.
  • Basic catalysts in the ester reaction include alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and lithium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, alkali metal hydrogen carbonates, alkali metals, alkaline earths.
  • Alkaline compounds such as alkali metals, alkaline earth metal oxides, alkaline earth metal hydroxides, other metals, oxides thereof, and mixtures thereof, and phosphorous acid (salts) and / or hypophosphorous acid (Salt).
  • nitrogen or argon can be used as the inert gas used.
  • Examples of the metal catalyst for adding ethylene oxide to the product after the ester reaction include potassium hydroxide, sodium hydroxide, sodium methylate and the like.
  • Polysorbate 80 having a polydispersity of 1.00 to 1.26 can be obtained by further fractionating or purifying the polysorbate 80 thus obtained by a known method.
  • a polysorbate 80 having a polydispersity of 1.00 to 1.26 can be prepared by mixing two or more polysorbates 80 having different polydispersities.
  • the ophthalmic composition according to this embodiment has a polysorbate 80 having a polydispersity of 1.00 to 1.26 obtained as a commercially available product, and a polydispersity of 1.
  • Manufactured by a method comprising a step of blending polysorbate 80 having a polydispersity of 00 to 1.26 or polysorbate 80 having a polydispersity of 1.00 to 1.26 manufactured by the above-described manufacturing method with a cooling agent. Also good. You may manufacture by the method including the process of mix
  • the polydispersity of polysorbate 80 is 1.00 to 1.26, preferably 1.00 to 1.23, more preferably 1.00 to 1.21, and 1.00 to 1 Even more preferably, .19.
  • the weight average molecular weight of polysorbate 80 is not particularly limited, but is preferably in the range of 1200 to 3200, more preferably 1300 to 3000.
  • the Z-average molecular weight of polysorbate 80 is not particularly limited, but is preferably in the range of 1300 to 3500, more preferably 1400 to 3300.
  • the polydispersity of polysorbate 80 is defined as M z / M w .
  • M z represents the Z average molecular weight
  • M w represents the weight average molecular weight.
  • the molecular weight measurement method various molecular weight measurement methods such as liquid chromatography, ultracentrifugation, light scattering method, and intrinsic viscosity method are known. Depending on the measurement method, the type of average molecular weight obtained such as weight average molecular weight, Z average molecular weight or the like, or the measurable molecular weight range is different.
  • the weight average molecular weight, Z average molecular weight and polydispersity defined by the present invention are measured by size exclusion chromatography (SEC).
  • SEC size exclusion chromatography
  • the SEC method can measure a weight average molecular weight, a Z average molecular weight, and a polydispersity, and is easy to operate. Therefore, the SEC method is most widely used for measuring high molecular compounds, oligomers, and the like.
  • the SEC method uses a column packed with a gel with pores, and has a mechanism that separates when the elution time differs due to the difference in the moving distance in the column depending on the molecular size of the molecules in the sample solution.
  • Have. Average molecular weights such as M z and M w are calculated based on a calibration curve prepared with a standard substance having a known molecular weight.
  • the Z average molecular weight, weight average molecular weight and polydispersity obtained by the SEC method are relative values obtained by performing molecular weight calibration using a standard substance, the same standard substance can be used. Can only be obtained. Therefore, the SEC method of the present invention is defined as using polyethylene oxide and polyethylene glycol as standard substances as described later.
  • the Z average molecular weight, the weight average molecular weight and the polydispersity obtained by the SEC method are relative values, it is also important to set conditions for separating the test components and preparing a calibration curve.
  • the present inventors have intensively studied the measurement conditions of the SEC method in order to increase the accuracy of calculation of the Z average molecular weight, weight average molecular weight and polydispersity of polysorbate 80.
  • the weight average molecular weight, Z average molecular weight, and polydispersity of polysorbate 80 in the ophthalmic composition are measured as follows.
  • Polyethylene oxide (Tosoh Corporation) and polyethylene glycol (Wako Pure Chemical Industries, Ltd.) having a molecular weight of several hundred thousand to several hundreds are used as standard substances.
  • Polyethylene oxide and polyethylene glycol as standard substances have three types with molecular weights of several hundred thousand, two types with molecular weights of tens of thousands, two types with molecular weights of thousands, and molecular weights of hundreds. It is preferable to use one type.
  • polyethylene oxide having molecular weights of 580000, 255000, 146000, 44900, and 27000, and polyethylene glycol having molecular weights of 8000, 1000, and 600, respectively, are used.
  • the molecular weight is 580000, 146000, 27000, 1000, and the molecular weight is 255000, 44900, 8000, 600, respectively, and they are combined so that the elution positions do not overlap.
  • An aqueous solution with a standard substance concentration of 0.1 w / v% is prepared and used as a standard solution.
  • concentration of the standard substance is very important for suppressing the relative standard deviation of the Z average molecular weight, the weight average molecular weight, and the polydispersity.
  • a standard solution of 1.0 mL is accurately taken, and a solution obtained by accurately adding 4.0 mL of methanol is used as a calibration curve solution.
  • Preparation of sample solution 4). Take 1.0 mL of the test solution accurately, and accurately add 4.0 mL of methanol as the sample solution. (Measurement by liquid chromatograph) 5.
  • Each calibration curve solution and sample solution are measured by a liquid chromatograph (Agilent 1200 series, manufactured by Agilent Technologies). 6). The columns are manufactured by Tosoh Corporation.
  • TSK-Gel ⁇ -4000 (exclusion limit molecular weight of about 400,000) and TSK-Gel ⁇ -2500 (exclusion limit molecular weight of about 5000) filled with hydrophilic vinyl polymer (both columns have an inner diameter of 7.8 mm, 300 mm long) are connected and installed one by one in this order.
  • the column temperature is 40.0 ° C. It is very important to keep 40.0 ° C. constant in order to suppress the relative standard deviation of Z average molecular weight, weight average molecular weight, and polydispersity. 7).
  • As the eluent a mixed solution in which the volume of methanol is 4.0 times the 0.10 mol / L sodium chloride aqueous solution is prepared for each measurement and used.
  • the inclusion of sodium chloride in the eluent to suppress the interaction between sample molecules or between the sample molecules and the filler is very important for suppressing the relative standard deviation of the Z average molecular weight, weight average molecular weight and polydispersity. It is. 8).
  • the flow rate is 0.5 mL / min. 9.
  • the injection volume is 50 ⁇ L. Filter through 0.45 ⁇ m filter prior to injection. 10.
  • the calibration curve solution and the sample solution were measured in this order, and the analysis cycle was 60 minutes for the calibration curve solution and 90 minutes for the sample solution. It is very important to continuously measure the calibration curve solution and the sample solution without interrupting the measurement in order to suppress the relative standard deviation of the Z average molecular weight, the weight average molecular weight, and the polydispersity. 11.
  • the detector is a differential refractive index detector, and the detector temperature is 35.0 ° C. (Calculation of Z average molecular weight, weight average molecular weight and polydispersity) 12
  • the obtained chromatogram is analyzed by an SEC analyzer, and the Z-average molecular weight and the weight-average molecular weight are calculated for the range sandwiched between the chromatogram curve and the baseline.
  • the elution time and molecular weight value of each peak are plotted from the calibration curve solution, approximated by a linear equation to obtain a calibration curve, and the correlation coefficient is 0.99 or more.
  • the obtained peaks are vertically divided at intervals of 0.1 minutes or more and less than 0.001 minutes to calculate the average molecular weight. 13.
  • the polydispersity is calculated from the formula of Mz / Mw . 4. above. Measure the sample solution of the process indicated by 3 times, and adopt the average value of the Z average molecular weight, weight average molecular weight or polydispersity obtained in each as the Z average molecular weight, weight average molecular weight or polydispersity of the present application, respectively. To do.
  • the relative standard deviation of the average molecular weight in the generally known SEC method is calculated by the following formulas A and B and is about 4 to 5%. Since the relative standard deviation of polydispersity is less than 5% under the above SEC measurement conditions, it can be said that the measurement conditions are appropriate.
  • the polydispersity in the present application is measured and calculated so that the relative standard deviation is less than 5%. When the above-mentioned reagents, columns, liquid chromatographs and the like are not available, measurements can be performed using alternatives equivalent to these. However, it is necessary to measure so that the relative standard deviation of polydispersity is less than 5%. When the relative standard deviation is 5% or more, it is necessary to suppress the relative standard deviation within the examination range of the measurement conditions normally performed.
  • the content of the component (A) is not particularly limited, and is appropriately set according to the type and content of the component (B) to be used together.
  • the content of the component (A) is, for example, preferably 0.0001 to 8 w / v%, more preferably 0.0001 to 4 w / v%, based on the total amount of the ophthalmic composition, It is more preferably 0.0005 to 2 w / v%, and particularly preferably 0.01 to 1 w / v%.
  • the content of the component (A) is suitable from the viewpoint of the effect of suppressing the adsorption of foreign matter to the cornea or alleviating the feeling of foreign matter in the eye.
  • component (B) A component is a cooling agent.
  • component (B) one type may be used alone, or two or more types may be used in arbitrary combination.
  • the refreshing agent used in the ophthalmic composition according to the present embodiment is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable.
  • the refreshing agent include terpenoids, essential oils containing terpenoids (eg, eucalyptus oil, bergamot oil, peppermint oil, fennel oil, rose oil, cinnamon oil, spearmint oil, camphor oil, cool mint and mint oil).
  • terpenoids eg, eucalyptus oil, bergamot oil, peppermint oil, fennel oil, rose oil, cinnamon oil, spearmint oil, camphor oil, cool mint and mint oil.
  • terpenoids examples include menthol, menthone, camphor (also referred to as “camphor” or “camphor”), borneol (also referred to as “ryuuno” or “carp”), geraniol, nerol, cineol, citronellol, carvone, anethole, Examples include eugenol, limonene, linalool and linalyl acetate.
  • the terpenoid may be any of d-form, l-form and dl-form, and examples thereof include l-menthol, d-menthol, dl-menthol, dl-camphor, d-camphor, dl-borneol and d-borneol.
  • the refreshing agent preferably contains at least one selected from the group consisting of menthol, camphor, borneol and geraniol. It is particularly preferred to include at least one selected from the group consisting of, l-menthol, dl-camphor, d-camphor and d-borneol.
  • the content of the refreshing agent in the ophthalmic composition according to the present embodiment is not particularly limited, and is appropriately set according to the type of the refreshing agent, the type and content of the component (A) to be used together.
  • the content of the refreshing agent can be measured as a terpenoid.
  • the total content of the refreshing agent is 0.00005 to 0.5 w / v. %, More preferably 0.0001 to 0.3 w / v%, still more preferably 0.0005 to 0.2 w / v%, and 0.001 to 0.1 w / v. % Is particularly preferred.
  • the content of the refreshing agent is suitable from the viewpoint of the effect of suppressing the adsorption of foreign matter to the cornea or alleviating the feeling of foreign matter in the eye.
  • the content ratio of the refreshing agent relative to the component (A) is not particularly limited, and is appropriately set according to the type of the refreshing agent.
  • the content ratio of the refreshing agent to the component (A) is, for example, that the total content of the refreshing agent is 0.0001 to 100 with respect to 1 part by mass of the component (A) contained in the ophthalmic composition.
  • the amount is preferably part by mass, more preferably 0.001 to 80 parts by mass, still more preferably 0.005 to 60 parts by mass, and particularly preferably 0.01 to 50 parts by mass.
  • the content ratio of the refreshing agent relative to the component (A) is preferable from the viewpoint of the effect of suppressing the adsorption of foreign matter to the cornea or alleviating the feeling of foreign matter in the eye.
  • the ophthalmic composition according to the present embodiment preferably further contains a buffer. Thereby, the pH of the ophthalmic composition can be adjusted, and the effects of the present invention can be exhibited more remarkably.
  • the buffer is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable.
  • the buffer include borate buffer, phosphate buffer, carbonate buffer, citrate buffer, acetate buffer, tris buffer, aspartic acid, aspartate, edetate, and the like. These buffering agents may be used alone or in any combination of two or more.
  • the boric acid buffer include boric acid or a salt thereof (alkali metal borate, alkaline earth metal borate, etc.).
  • the phosphate buffer include phosphoric acid or a salt thereof (such as an alkali metal phosphate or an alkaline earth metal phosphate).
  • Examples of the carbonate buffer include carbonic acid or a salt thereof (an alkali metal carbonate, an alkaline earth metal carbonate, etc.).
  • Examples of the citrate buffer include citric acid or salts thereof (alkali metal citrate, alkaline earth metal citrate, etc.).
  • a borate or phosphate hydrate may be used as the borate buffer or phosphate buffer.
  • boric acid or a salt thereof sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.
  • a phosphate buffer phosphoric acid or a salt thereof Salt
  • sodium hydrogen phosphate sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, tripotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, etc.
  • a salt thereof sodium bicarbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium bicarbonate, magnesium carbonate, etc.
  • citric acid or a salt thereof sodium citrate, potassium citrate, citric acid, etc.
  • Acid calcium sodium dihydrogen citrate, disodium citrate, etc.
  • acetic acid Agents as, acetic acid or a salt thereof (ammonium acetate, potassium acetate, calcium acetate, sodium acetate,
  • boric acid buffering agents for example, a combination of boric acid and borax
  • phosphoric acid buffering agents for example, a combination of disodium hydrogen phosphate and sodium dihydrogen phosphate
  • a borate buffer is more preferable.
  • the content thereof includes the type of the buffering agent, the type and content of other blending components, the use of the ophthalmic composition, the formulation form, the method of use, etc. It is set appropriately according to As the content of the buffer, for example, based on the total amount of the ophthalmic composition, the total content of the buffer is preferably 0.001 to 15 w / v%, and 0.01 to 10 w / v%. Is more preferably 0.05 to 7.5 w / v%, and particularly preferably 0.1 to 5 w / v%.
  • the ophthalmic composition according to this embodiment preferably further contains a chelating agent.
  • the chelating agent is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable.
  • examples of chelating agents include ethylenediaminediacetic acid (EDDA), ethylenediaminetriacetic acid, ethylenediaminetetraacetic acid (edetic acid, EDTA), N- (2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA), and diethylenetriaminepentaacetic acid (DTPA).
  • EDDA ethylenediaminediacetic acid
  • EDTA ethylenediaminetriacetic acid
  • HEDTA ethylenediaminetetraacetic acid
  • DTPA diethylenetriaminepentaacetic acid
  • ethylenediaminetetraacetic acid is preferred.
  • These chelating agents may be used alone or in any combination of two or more.
  • the content depends on the type of chelating agent, the type and content of other blending components, the use of the ophthalmic composition, the dosage form, the method of use, etc. It is set accordingly.
  • the content of the chelating agent for example, the total content of the chelating agent is preferably 0.0001 to 2 w / v%, based on the total amount of the ophthalmic composition, and 0.0004 to 1.5 w / v. % Is more preferable, 0.0008 to 1 w / v% is further preferable, and 0.001 to 0.8 w / v% is particularly preferable.
  • the pH of the ophthalmic composition according to the present embodiment is not particularly limited as long as it is within a range that is pharmaceutically, pharmacologically (pharmaceutically), or physiologically acceptable.
  • the pH of the ophthalmic composition is in the range of 4.0 to 9.5, preferably 4.5 to 9.0, and more preferably 5.0 to 8.5. When the pH is in the above range, there is little irritation to the eye when the ophthalmic composition is used, and the adsorption of foreign matter to the cornea tends to be further suppressed to further alleviate the feeling of foreign matter in the eye.
  • the ophthalmic composition according to this embodiment preferably further contains an isotonic agent.
  • the isotonic agent is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable.
  • isotonic agents include disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, sodium hydrogen sulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, potassium acetate, acetic acid.
  • Sodium, sodium hydrogen carbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, glycerin, propylene glycol, polyethylene glycol, glucose, mannitol, sorbitol and the like can be mentioned.
  • isotonic agents glycerin, propylene glycol, polyethylene glycol, glucose, sodium chloride, potassium chloride, calcium chloride or magnesium chloride are preferable, sodium chloride, potassium chloride or propylene glycol is more preferable, and sodium chloride is particularly preferable.
  • These tonicity agents may be used alone or in any combination of two or more.
  • the content of the tonicity agent is appropriately set according to the type of tonicity agent, the type and content of other components, and the like.
  • the content of the tonicity agent for example, the total content of the tonicity agent is preferably 0.001 to 10 w / v% based on the total amount of the ophthalmic composition, and 0.01 to 5 w. / V% is more preferable, and 0.05 to 3 w / v% is still more preferable.
  • the osmotic pressure of the ophthalmic composition according to the present embodiment is not particularly limited as long as it is within a range acceptable for a living body.
  • the osmotic pressure ratio of the ophthalmic composition is, for example, preferably 0.5 to 5.0, more preferably 0.6 to 3.0, and further preferably 0.7 to 2.0. It is preferably 0.8 to 1.6.
  • the osmotic pressure can be adjusted by a method known in the art using an inorganic salt, a polyhydric alcohol, a sugar alcohol or a sugar.
  • the osmotic pressure ratio is the ratio of the osmotic pressure of the sample to 286 mOsm (0.9 w / v% sodium chloride aqueous solution) based on the 16th revised Japanese Pharmacopoeia. Measure with reference to (freezing point depression method).
  • sodium chloride Japanese Pharmacopoeia standard reagent
  • the ophthalmic composition according to this embodiment preferably further contains a thickener. Thereby, the viscosity of the ophthalmic composition can be adjusted, and the effect of the present application can be exhibited more remarkably.
  • polyvinyl alcohol completely saponified product or partially saponified product
  • polyvinylpyrrolidone K25, K30, K90 etc.
  • carboxyvinyl polymer cellulose derivative [methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxy Propylmethylcellulose (2208, 2906, 2910, etc.), carboxymethylcellulose, carboxyethylcellulose, nitrocellulose, or salts thereof]
  • polyethylene glycol Macrogol 300, Macrogol 400, Macrogol 1500, Macrogol 4000, Macrogol 6000, etc.
  • Sodium chondroitin sulfate, sodium hyaluronate, gum arabic, gellan gum, tragacanth, dextst (Eg 40, 70), glucose, sorbitol, etc. preferably polyvinyl alcohol (completely saponified or partially saponified), polyvinylpyrrolidone (K25,
  • polyvinylpyrrolidone hydroxyethylcellulose or hydroxypropylmethylcellulose is more preferred, and polyvinylpyrrolidone is particularly preferred.
  • These thickeners may be used alone or in any combination of two or more.
  • the content is suitably set according to the kind of thickener, the kind and content of other containing components, etc.
  • the content of the thickening agent for example, based on the total amount of the ophthalmic composition, the total content of the thickening agent is preferably 0.0001 to 5 w / v%, and 0.0005 to 3 w / v. % Is more preferable, 0.001 to 2 w / v% is further preferable, and 0.01 to 1 w / v% is particularly preferable.
  • the viscosity of the ophthalmic composition according to the present embodiment is not particularly limited as long as it is within a range acceptable for a living body.
  • the viscosity at 25 ° C. measured with a rotational viscometer (RE550 viscometer, manufactured by Toki Sangyo Co., Ltd., rotor: 1 ° 34 ′ ⁇ R24) is preferably 0.1 to 1000 mPa ⁇ s, for example, 0.5 More preferably, it is ⁇ 100 mPa ⁇ s, and further preferably 1 ⁇ 50 mPa ⁇ s.
  • the ophthalmic composition according to the present embodiment may contain an appropriate amount of various pharmacologically active components or physiologically active components in addition to the above components as long as the effects of the present invention are not hindered.
  • Such components are not particularly limited, and examples thereof include active ingredients in various pharmaceuticals described in the OTC Drug Manufacturing and Sales Approval Standards 2012 edition (supervised by the Japanese Society for Regulatory Science). Specifically, the following components are listed as components used in ophthalmic drugs.
  • Antiallergic agents cromoglycate, amlexanox, ibudilast, suplatast, pemirolast potassium, tranilast, olopatadine hydrochloride, levocabastine hydrochloride and acitazanolast.
  • Antihistamines chlorpheniramine maleate, diphenhydramine hydrochloride, ketotifen fumarate, etc.
  • Vasoconstrictor (decongestant) tetrahydrozoline hydrochloride, tetrahydrozoline nitrate, naphazoline hydrochloride, naphazoline nitrate, epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, phenylephrine hydrochloride, and dl-methylephedrine hydrochloride.
  • Anti-inflammatory agents pranoprofen, glycyrrhizic acid, allantoin, berberine sulfate, berberine chloride, azulenesulfonic acid, ⁇ -aminocaproic acid, zinc sulfate, zinc lactate, lysozyme, salicylic acid, tranexamic acid, licorice and salts thereof.
  • Eye muscle modulating agent For example, cholinesterase inhibitor having an active center similar to acetylcholine, specifically, neostigmine methyl sulfate, tropicamide, helenien, atropine sulfate and the like.
  • Bactericides Acrinol, cetylpyridinium, benzalkonium chloride, benzethonium chloride, chlorhexidine, polyhexamethylene biguanide, alkyldiaminoethylglycine hydrochloride and the like.
  • Amino acids glycine, alanine, ⁇ -aminobutyric acid, aspartic acid, potassium L-aspartate, glutamic acid, arginine, lysine, aminoethylsulfonic acid (taurine), chondroitin sulfate, sodium chondroitin sulfate, sodium hyaluronate and alginic acid.
  • Vitamins vitamin B 1 , vitamin B 2 (flavin adenine dinucleotide sodium), niacin (nicotinic acid and nicotinamide), pantothenic acid, panthenol, vitamin B 6 (pyridoxine, pyridoxal and pyridoxamine), biotin, folic acid, vitamin B 12 (cyanocobalamin, hydroxocobalamin, methylcobalamin and adenosylcobalamin), retinol acetate, retinol palmitate, tocopherol acetate and the like.
  • Other For example, sulfamethoxazole, sulfamethoxazole sodium and the like.
  • various additives are appropriately selected according to a conventional method according to the use or formulation form within a range that does not impair the effects of the invention, and one or more are selected.
  • An appropriate amount may be contained in combination.
  • these additives include various additives described in Pharmaceutical Additives Encyclopedia 2007 (edited by Japan Pharmaceutical Additives Association).
  • Typical additives include the following additives.
  • Carrier An aqueous carrier such as water or hydrous ethanol.
  • Sugars for example, glucose, cyclodextrin and the like.
  • Sugar alcohols For example, xylitol, sorbitol, mannitol and the like. These may be any of d-form, l-form and dl-form.
  • Nonionic surfactants monouraric acid POE (20) sorbitan (polysorbate 20), monopalmitic acid POE (20) sorbitan (polysorbate 40), monostearic acid POE (20) sorbitan (polysorbate 60) and tristearic acid POE ( 20) POE sorbitan fatty acid ester such as sorbitan (polysorbate 65); POE such as POE (40) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 40) and POE (60) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 60) Hardened castor oil; POE castor oil such as POE (10) castor oil (polyoxyethylene castor oil 10) and POE (35) castor oil (polyoxyethylene castor oil 35); POE alkyl ether such as POE (9) lauryl ether ; POE 20) POE-POP alkyl ethers such as POP (4) cetyl ether; POE (54) POP (39) glycol,
  • Amphoteric surfactants N- [2-[[2- (alkylamino) ethyl] amino] ethyl] glycine and its salts (also called alkyldiaminoethylglycine or alkylpolyaminoethylglycine) and the like.
  • Negative surfactant alkylbenzene sulfonate, alkyl sulfate, polyoxyethylene alkyl sulfate, ⁇ -sulfo fatty acid ester salt, ⁇ -olefin sulfonic acid and the like.
  • Positive surfactant benzalkonium chloride, benzethonium chloride, etc.
  • Antiseptics, bactericides or antibacterials for example, zinc chloride, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, chlorobutanol, sorbic acid, potassium sorbate, dehydroacetic acid Sodium, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguanide compounds (specifically, polyhexamethylene biguanide, polyhexanide hydrochloride, etc.), Glow Kill (trade name, manufactured by Rhodia).
  • zinc chloride alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, benzalkonium chloride, benzethonium chloride
  • Stabilizers trometamol, sodium formaldehyde sulfoxylate (Longalite), tocopherol, sodium pyrosulfite, monoethanolamine, aluminum monostearate, glyceryl monostearate, dibutylhydroxytoluene, sodium edetate, etc.
  • Base for example, octyldodecanol, titanium oxide, potassium bromide, paraffin, plastibase, lanolin, propylene glycol and the like.
  • the ophthalmic composition according to the present embodiment is prepared by adding the above components (A) and (B) and other components as necessary to the carrier so as to have a desired content.
  • the components can be dissolved or suspended in purified water, adjusted to a predetermined pH and osmotic pressure, and sterilized by filtration sterilization or the like.
  • the content of water in the ophthalmic composition according to this embodiment is preferably 85 w / v% or more, more preferably 90 w / v% or more, and 92 w / v based on the total amount of the ophthalmic composition. % Or more, more preferably 94 w / v% or more, and particularly preferably 96 w / v% or more.
  • water used in the ophthalmic composition water that is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable may be used. Specific examples of such water include distilled water, ordinary water. Examples thereof include water, purified water, sterilized purified water, water for injection, and distilled water for injection.
  • the ophthalmic composition according to the present embodiment is provided by being accommodated in an arbitrary container.
  • the container for storing the ophthalmic composition is not particularly limited, and may be made of glass or plastic, for example.
  • the plastic include, for example, polyethylene terephthalate, polyarylate, polyethylene naphthalate, polycarbonate, polyethylene, polytetrafluoroethylene, polypropylene, polybutylene terephthalate, polyimide, polymethylpentene, and copolymers of monomers constituting these, and these What mixed 2 or more types including a material is mentioned.
  • Polyethylene terephthalate is preferable.
  • the container for storing the ophthalmic composition may be a transparent container that can visually recognize the inside of the container, or an opaque container that is difficult to visually recognize the interior of the container.
  • a transparent container is preferable.
  • the “transparent container” includes both a colorless transparent container and a colored transparent container.
  • the ophthalmic composition may be housed and used in a multi-dose form that can be used repeatedly, for example, in a colored transparent plastic container, or may be housed and used in a single-use form.
  • the ophthalmic composition according to this embodiment can be used as a pharmaceutical preparation or a quasi-drug preparation, and is a so-called eye drop [however, the eye drop includes an eye drop that can be applied while wearing a contact lens. ] In addition to artificial tears and eye wash [however, eye wash contains eye wash that can be washed while wearing contact lenses. ], Contact lens composition [contact lens mounting solution, contact lens care composition (contact lens disinfectant, contact lens preservative, contact lens cleaning agent, contact lens cleaning preservative), etc.] .
  • Preferable examples of the present invention include eye drops, artificial tears, eye washes, and contact lens mounting liquids, and eye drops and artificial tears are particularly preferable examples.
  • the ophthalmic composition When used as a composition for contact lenses, it can be applied to all contact lenses including hard contact lenses and soft contact lenses, and can also be applied in a state of wearing on the contact lenses. is there.
  • the ophthalmic composition according to the present embodiment is also suitable for application to a contact lens from the viewpoint of suppressing the adsorption of foreign matter to the cornea due to compression or the like by wearing the contact lens or alleviating the feeling of foreign matter on the eye.
  • the ophthalmic composition is applicable to any contact lens as long as it is a known contact lens. From the viewpoint of a large lens diameter and a large contact area with the eye, it is particularly preferably applied to a soft contact lens.
  • Soft contact lenses SCL are classified by the method described in ISO18369-1: 2006 and ISO18369-1: AMENDENT1, for example.
  • the ophthalmic composition according to the present embodiment can not only improve the subjective symptoms themselves but also suppress the adsorption of foreign matters to the cornea in order to relieve the feeling of foreign matters in the eye.
  • the foreign body sensation means a subjective symptom (discomfort, irritation) of the eyes that is tingling or tingling. Foreign body sensations may be triggered by dry eyes, contact lens use, or allergic conjunctivitis. Foreign body sensation is further enhanced by accompanying inflammation.
  • the ophthalmic composition according to the present embodiment can be applied for the purpose of preventing or treating various symptoms accompanied by a foreign body sensation. From the viewpoint of suppressing the adsorption of foreign substances, it is suitable for foreign body sensations caused by allergic conjunctivitis, contact lens wearing, eye contact, etc. That is, the said ophthalmic composition is used suitably as a foreign material feeling mitigation agent.
  • the foreign substance sensation mitigating agent includes the ophthalmic composition.
  • the ophthalmic composition includes (A) polysorbate 80 and (B) a refreshing agent.
  • a way to The polydispersity of the polysorbate 80 in the ophthalmic composition is 1.00 to 1.26,
  • the present invention provides a method wherein the refreshing agent comprises at least one selected from the group consisting of camphor, borneol and geraniol.
  • (A) a polysorbate 80 and (B) a refreshing agent are blended to provide an ophthalmic composition with an alleviating effect on the foreign body sensation of the eye.
  • a method is provided wherein the polydispersity of the polysorbate 80 in the ophthalmic composition is 1.00 to 1.26.
  • a method for alleviating ocular foreign body sensation comprising the step of contacting an ophthalmic composition comprising polysorbate 80 and a refreshing agent to a subject's eye or contact lens.
  • a method is provided wherein the polydispersity of the polysorbate 80 in the ophthalmic composition is 1.00 to 1.26.
  • the object include mammals such as humans.
  • the combination of polysorbate 80 having a polydispersity of 1.00 to 1.26 in the ophthalmic composition and a cooling agent suppresses the adsorption of foreign substances to the cornea. By doing so, it is possible to further alleviate the feeling of foreign objects in the eye.
  • Test Example 1 Measurement of the amount of foreign matter adsorbed on corneal epithelial cells (1) Test method Test solutions A and B shown in Tables 2 and 3 using polysorbate 80 having different polydispersities shown in Table 1 respectively. And the polydispersity of polysorbate 80 in each test solution was measured. Thereafter, each test solution to which fluorescently labeled albumin (final concentration 0.2%) was added was added to the culture medium, and the influence on the foreign substance adsorption to the corneal epithelial cells was evaluated.
  • Human corneal epithelial cell line HCE-T (RIKEN BioResource Center, No. RCB2280) is cultured in each well so as to be 3.0 ⁇ 10 5 cells / well in a 48-well microplate (manufactured by Corning). 600 ⁇ L each of the medium was seeded and cultured at 37 ° C. under 5% CO 2 for 24 hours. After culturing, the culture medium was removed by suction, 200 ⁇ L of each test solution to which albumin (final concentration 0.2%) fluorescently labeled with fluorescein isothiocyanate (FITC) was added was placed and allowed to stand at room temperature for 60 minutes.
  • albumin final concentration 0.2%) fluorescently labeled with fluorescein isothiocyanate (FITC) was added was placed and allowed to stand at room temperature for 60 minutes.
  • the solution in the well was removed by suction, and 600 ⁇ L of phosphate buffer was added to each well.
  • 200 ⁇ L of a phosphate buffer solution was added, and a fluorescence plate reader (Fluoroskan Ascent CF, manufactured by MTX Labsystems) was used at an excitation wavelength of 495 nm / emission wavelength of 520 nm. The fluorescence value was measured. Based on a calibration curve between the amount of foreign matter (albumin amount) and fluorescence value prepared in advance, the obtained fluorescence value was converted into the amount of foreign matter. From the amount of foreign matter obtained, the foreign matter adsorption suppression rate (%) was calculated based on the formula (1).
  • Test Example 2 Sensory test: Effect of improving foreign body feeling (1) Test method Each eye drop was prepared according to the conventional method according to Table 5 below, and the polydispersity of polysorbate 80 in each eye drop was measured. Each eye drop was filled in a polyethylene terephthalate container. Eye drops that contain (A) polysorbate 80 and (B) l-menthol, and the polydispersity of polysorbate 80 in the eye drops is less than 1.21 for subjects who are usually aware of the foreign body sensation in the eyes. Examples 5 to 7) for the left eye, an eye drop containing (A) polysorbate 80 and (B) 1-menthol, and having a polydispersity of polysorbate 80 in the eye drop of 1.34 or more (Comparative Example 3) ) was administered to the right eye once.
  • Test Example 3 Effect of improving foreign body sensation (1) Test method Foreign matter of eye after instillation by the same method as in Test Example 2 except that each eye drop was prepared according to the conventional method according to Tables 7 and 8 below. The feeling was evaluated. In the tests of Comparative Example 4, Example 8, and Example 9, five contact lens non-wearers and five contact lens wearers were subjects. In other tests, 3 subjects who were not wearing contact lenses and 3 people who were wearing contact lenses were subjects. (2) Test results Tables 7 and 8 show the results.
  • Examples 8 to 15 comprising (A) polysorbate 80 and (B) a cooling agent (d-borneol, d-camphor or geraniol), and the polydispersity of polysorbate 80 in the eye drop is less than 1.34 It was confirmed that when an eye drop was used, a remarkable foreign matter sensation improving effect was exhibited.
  • a cooling agent d-borneol, d-camphor or geraniol

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne une composition ophtalmique contenant du polysorbate (80) et un agent de refroidissement. La polydispersité du polysorbate (80) dans ladite composition ophtalmique est comprise entre 1,00 et 1,26.
PCT/JP2015/060989 2014-04-09 2015-04-08 Composition ophtalmique WO2015156321A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US15/302,636 US20170056335A1 (en) 2014-04-09 2015-04-08 Ophthalmic Composition
CN201580016532.7A CN106163565A (zh) 2014-04-09 2015-04-08 眼科组合物

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
JP2014080315 2014-04-09
JP2014-080315 2014-04-09
JP2014110926A JP5654704B1 (ja) 2014-05-29 2014-05-29 眼科組成物
JP2014-110926 2014-05-29
JP2014-181068 2014-09-05
JP2014181068 2014-09-05
JP2014204950A JP2016053014A (ja) 2014-04-09 2014-10-03 眼科組成物
JP2014-204950 2014-10-03

Publications (1)

Publication Number Publication Date
WO2015156321A1 true WO2015156321A1 (fr) 2015-10-15

Family

ID=54287894

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2015/060989 WO2015156321A1 (fr) 2014-04-09 2015-04-08 Composition ophtalmique

Country Status (1)

Country Link
WO (1) WO2015156321A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017183714A1 (fr) * 2016-04-22 2017-10-26 ロート製薬株式会社 Composition ophtalmique
EP3199162A4 (fr) * 2014-09-25 2018-04-25 Kowa Company Ltd. Produit pharmaceutique
CN109069421A (zh) * 2016-04-22 2018-12-21 乐敦制药株式会社 眼科组合物
CN116509732A (zh) * 2023-05-15 2023-08-01 广州市拓瑞科技有限公司 一种清洁杀菌除臭宠物卫生湿巾浓缩液及其制备方法

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11180858A (ja) * 1997-12-18 1999-07-06 Rohto Pharmaceut Co Ltd 清涼化剤を含有するコンタクトレンズ用点眼剤
JP2001354592A (ja) * 2000-06-16 2001-12-25 Lion Corp 点眼剤
JP2004346262A (ja) * 2003-05-26 2004-12-09 Du Pont Mitsui Fluorochem Co Ltd 含フッ素重合体水性分散液
WO2005002595A1 (fr) * 2003-07-03 2005-01-13 Menicon Co., Ltd. Composition ophtalmique
JP2006022087A (ja) * 2004-06-08 2006-01-26 Rohto Pharmaceut Co Ltd 眼科用清涼組成物
JP2006022055A (ja) * 2004-07-08 2006-01-26 Rohto Pharmaceut Co Ltd 洗眼セット
JP2006232946A (ja) * 2005-02-23 2006-09-07 Dai Ichi Kogyo Seiyaku Co Ltd 乳化重合用乳化剤

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11180858A (ja) * 1997-12-18 1999-07-06 Rohto Pharmaceut Co Ltd 清涼化剤を含有するコンタクトレンズ用点眼剤
JP2001354592A (ja) * 2000-06-16 2001-12-25 Lion Corp 点眼剤
JP2004346262A (ja) * 2003-05-26 2004-12-09 Du Pont Mitsui Fluorochem Co Ltd 含フッ素重合体水性分散液
WO2005002595A1 (fr) * 2003-07-03 2005-01-13 Menicon Co., Ltd. Composition ophtalmique
JP2006022087A (ja) * 2004-06-08 2006-01-26 Rohto Pharmaceut Co Ltd 眼科用清涼組成物
JP2006022055A (ja) * 2004-07-08 2006-01-26 Rohto Pharmaceut Co Ltd 洗眼セット
JP2006232946A (ja) * 2005-02-23 2006-09-07 Dai Ichi Kogyo Seiyaku Co Ltd 乳化重合用乳化剤

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
J. SOC. COSMET. CHEM., vol. 30, 1979, pages 415 - 427, XP055229882 *
TOXICOL. IN VITRO, vol. 25, 2011, pages 1425 - 1434 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3199162A4 (fr) * 2014-09-25 2018-04-25 Kowa Company Ltd. Produit pharmaceutique
WO2017183714A1 (fr) * 2016-04-22 2017-10-26 ロート製薬株式会社 Composition ophtalmique
CN109069421A (zh) * 2016-04-22 2018-12-21 乐敦制药株式会社 眼科组合物
US11331390B2 (en) 2016-04-22 2022-05-17 Rohto Pharmaceutical Co., Ltd. Ophthalmic composition
CN116509732A (zh) * 2023-05-15 2023-08-01 广州市拓瑞科技有限公司 一种清洁杀菌除臭宠物卫生湿巾浓缩液及其制备方法
CN116509732B (zh) * 2023-05-15 2023-10-20 广州市拓瑞科技有限公司 一种清洁杀菌除臭宠物卫生湿巾浓缩液及其制备方法

Similar Documents

Publication Publication Date Title
JP5797720B2 (ja) 眼科用組成物
JP6315755B2 (ja) 異物感緩和点眼剤
JP7455901B2 (ja) 点眼型洗眼薬用組成物
WO2015156321A1 (fr) Composition ophtalmique
JP2015071554A (ja) オロパタジン含有点眼剤
JP6148957B2 (ja) プラノプロフェン含有水性組成物
JP2021178845A (ja) 眼科組成物
JP2017197524A (ja) 眼科組成物
JP5654704B1 (ja) 眼科組成物
US20170056335A1 (en) Ophthalmic Composition
JP2023033557A (ja) 複合目症状改善用眼科組成物
JP2020109125A (ja) 眼科組成物
JP7320638B2 (ja) 眼科組成物による眼への刺激を緩和する方法、眼科組成物中のメントールの芳香性を持続させる方法、及び、眼科組成物によるソフトコンタクトレンズの変質を抑制する方法
JP6607976B2 (ja) 異物感緩和点眼剤
JP6345492B2 (ja) 点眼剤
JP2016053014A (ja) 眼科組成物
WO2019176947A1 (fr) Composition inhibant l'éclatement du pollen
JP2016088922A (ja) 眼科組成物
JP2017197525A (ja) 水性組成物
JP2022029416A (ja) ソフトコンタクトレンズ用組成物
JP2016088907A (ja) 眼科組成物
JP2017197527A (ja) 眼科組成物
WO2017183714A1 (fr) Composition ophtalmique
JP2019218369A (ja) 異物感緩和点眼剤
JP6537223B2 (ja) ソフトコンタクトレンズ用組成物

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 15776035

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 15302636

Country of ref document: US

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 15776035

Country of ref document: EP

Kind code of ref document: A1