WO2007125731A1 - Soft contact lens solution, drug-sustained release soft contact lens prepared by using the solution - Google Patents
Soft contact lens solution, drug-sustained release soft contact lens prepared by using the solution Download PDFInfo
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- WO2007125731A1 WO2007125731A1 PCT/JP2007/057431 JP2007057431W WO2007125731A1 WO 2007125731 A1 WO2007125731 A1 WO 2007125731A1 JP 2007057431 W JP2007057431 W JP 2007057431W WO 2007125731 A1 WO2007125731 A1 WO 2007125731A1
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- soft contact
- contact lens
- solution
- polyphenol
- allergen
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- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
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- 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
-
- 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
- A61P27/14—Decongestants or antiallergics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
Definitions
- Soft contact lens solution drug sustained release soft contact lens obtained using the same, and method for producing the same
- the present invention relates to a soft contact lens solution, a drug sustained-release soft contact lens obtained using the same, and a method for producing the same, and in particular, polyphenol as an allergen-reducing component or an allergen-inactivating component.
- the present invention relates to a solution for soft contact lenses containing.
- Patent Document 1 specifies tannic acid, which is a kind of polyphenol, in order to remove allergens such as environmental power mites. It has been clarified that compositions containing these solvents are used for walls, floors, clothing, etc. in the form of liquids, sprays, aerosols and the like.
- Patent Document 2 discloses an allergen remover containing as an active ingredient at least one component selected from the group consisting of organic solvents, polyphenols such as tannic acid, hydroxyapatite, and cationic surfactants, and The allergen remover is sprayed into the space in the form of fine particles, directly sprayed and applied to allergen deposits, held alone in the container, and collected by passing air containing the allergen. A method for removing allergens has been clarified. Further, Patent Document 3 discloses a wiping sheet for tatami mats using an aromatic hydride compound such as tannic acid or catechin as an allergen deactivating component. ing.
- Patent Document 4 discloses that tranilast is applicable to eyes wearing contact lenses. Anti-allergic drug power has been clarified.
- anti-allergic drugs such as force and karanilast are generally highly irritating (scratching to the eyes), and most of them require instillation about 4 to 6 times a day. Yes, it was very troublesome with many eye drops.
- antiallergic drugs are those in which powerful drugs are absorbed into the body and exert their actions, so their effects differ depending on the person, and there are also problems such as side effects Met.
- Patent Document 1 Japanese Patent Application Laid-Open No. 61-44821
- Patent Document 2 Japanese Patent Laid-Open No. 2000-264837
- Patent Document 3 Japanese Patent Laid-Open No. 2003-79554
- Patent Document 4 Japanese Unexamined Patent Publication No. 2003-81840
- the present invention has been made against the background of harsh circumstances, and the problem to be solved is to provide a solution for soft contact lenses with less eye irritation. There is. Another solution is to provide a method for producing soft contact lenses that can reduce allergic symptoms without frequent instillation of drugs.
- the present invention has been completed on the basis of strong knowledge, and in order to solve the problems described above or the problems grasped from the entire description of the specification, various kinds of problems as listed below can be obtained.
- the embodiments can be preferably implemented, but the embodiments described below can be adopted in any combination. Note that aspects or technical features of the present invention are not limited to those described below, and the description of the entire specification can be recognized based on the inventive idea disclosed therein. Should be understood.
- a solution for soft contact lenses comprising polyphenol as an allergen deactivating component in an aqueous medium.
- a manufacturing method comprising:
- the use of polyphenol as an allergen deactivating component makes it possible to stimulate the eye such as the drug sees the eye when instilled. Therefore, it is possible to advantageously obtain a soft contact lens solution with a low content.
- the allergen deactivating component is gradually added to the eye. Since it can be continuously released, allergic symptoms can be advantageously reduced with a small number of instillations without frequent instillation of drugs.
- the soft contact lens solution according to the present invention contains polyphenol as an allergen-reducing component or allergen-inactivating component in an aqueous medium.
- polyphenol used there Any of those conventionally known can be used.
- flavonoid polyphenols include flavones, flavonols, isoflavones, flavans, flavanols, flavanones, flavonols, chalcones. , Anthocyanidins, phenylcarboxylic acid polyphenols, etc. It can be illustrated.
- tannic acid power S which is a kind of catechins and phenylcarboxylic acid-type polyphenols, among flavanols, which is a kind of flavonoid-type polyphenols, is particularly preferably used.
- catechins pointed out above more specifically, catechin, epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate and methylated derivatives thereof, tea extract (including tea tea) )
- tea extract including tea tea
- a plant extract component other than tea it is possible to list grapes (fruits, leaves, trees), bamboo, bear buds, perilla, roses, gardenia fruits, yew, aloe, rosemary, etc. Needless to say, it is not limited in any way. These compounds can be used alone or in combination of two or more.
- allergen deactivating component when allergen deactivating component is instilled, the allergens such as pollen on the lens are advantageously reduced. It can be inactivated, or can be made into a contact lens solution that can advantageously suppress irritation to the eye, such as when the medicine is instilled into the eye.
- Powerful polyphenols have the advantage that they are relatively easy to obtain and are excellent in safety and stability.
- the strong polyphenol is a force that can be appropriately used in an amount effective for deactivating allergens.
- the content is 0.001 to 10% on a weight basis. Is used at a content of 0.1-5%. This is because if the content is too low, the allergen deactivation effect due to the inclusion of polyphenols may not be sufficiently exerted, and if the content exceeds the above range, polyphenols may be used. This is because when catechin is used, there is a possibility that problems such as coloring may occur in the lens that is brought into contact with the solution for the soft contact lens.
- the contact lens solution according to the present invention is prepared by adding and incorporating the above-described components into an appropriate aqueous medium in the same manner as in the prior art.
- an appropriate aqueous medium in addition to water itself such as tap water, purified water, and distilled water, the aqueous medium used at that time is highly water-safe and ophthalmic as long as the solution is mainly water. Can be used as long as it is sufficiently acceptable to is there.
- a solution that is contained in a polyphenol-based aqueous medium is used as a soft contact lens solution.
- the soft contact lenses to which such a solution is applied are various known soft contact lenses.
- examples of non-ionic soft contact lenses include soft contact lenses such as butyl acetate and DMAA.
- examples of the ionic soft contact lens include HEMA type, N-VP type, MAA type and the like into which an ionic group such as a carboxyl group is introduced.
- ionic soft contact lens it is advantageous to be an ionic soft contact lens.
- ionic soft contact lenses include those described above, for example, HEMA (hydroxylethyl methacrylate), N_VP (N-vinyl-1-pyrrolidone), and MAA (methacrylic acid).
- HEMA hydroxylethyl methacrylate
- N_VP N-vinyl-1-pyrrolidone
- MAA methacrylic acid
- an ionic soft contact lens is applied as a powerful soft contact lens, whereby an allergen-inactivating component-containing solution force S ionic soft contact lens when in contact with the ionic soft contact lens
- S ionic soft contact lens when in contact with the ionic soft contact lens
- catechin polyphenol
- catechin is slightly soluble in water, but it is basically a highly hydrophobic substance, so in the case of non-ionic soft contact lenses.
- Non-ionic lens and catechin (polyphenol) interact hydrophobicly This is considered to be because catechin (polyphenol) aggregates on the lens, and coloring of the lens and a change in size are caused.
- the soft contact lens solution according to the present invention in addition to the above-described components, if necessary, various additive components conventionally used in contact lens solutions, For example, one or more of a thickening agent, a pH buffering agent, a cleansing agent, a refreshing agent, a surfactant, an osmotic pressure adjusting agent, a vasoconstrictor, vitamins, an anti-inflammatory agent and a flavoring agent. Even if two or more kinds are appropriately selected and contained in a normal content ratio, there is no problem. However, as such additive components (additives), those that are highly safe to the living body and that are ophthalmically acceptable and that do not affect the shape and physical properties of the contact lens are advantageously selected. The Rukoto.
- the soft contact lens solution in the present invention is a force that can be applied to the soft contact lens in various conventionally known embodiments.
- ophthalmic solutions for eyes wearing a soft contour lens In addition, it is also used as a mounting solution, an eyewash solution, a multi-purpose solution, a preservative solution or a distribution preservative solution, and the soft contact lens is soaked in these liquid agents.
- the multi-purpose solution means a solution that can perform at least two or more of cleaning, rinsing, disinfection, and storage of contact lenses in one solution.
- a disposable soft contact lens capable of sustained release of a clean drug can be easily obtained.
- the effects of the present invention can be advantageously achieved.
- an aqueous liquid preparation containing polyphenol as an allergen deactivating component is prepared in order to produce a soft contact lens capable of sustained drug release using the soft contact lens solution described above.
- a manufacturing method including a step and a step of bringing a soft contact lens into contact with a force and a liquid aqueous solution and incorporating an allergen deactivating component into the forceful soft contact lens is adopted.
- the soft contact lens force is immersed in the aqueous liquid agent or the aqueous liquid agent is adhered.
- the time is too short, there is a risk that the allergen-inactive component uptake amount of the soft contoured external lens capable of sustained drug release produced in this way may not be sufficient. There is a possibility that the effect cannot be enjoyed advantageously. If the time is longer than the above-mentioned time, the amount of allergen deactivating components taken into the lens reaches saturation, and there is a risk that the effect of soaking for longer than this time cannot be obtained.
- force techkins or tannic acid is advantageously used as the force or karyopolyphenol, and the content of force or kraft polyphenol is generally 0. 001-10%, and in addition, as a soft contact lens that works, an ion soft contact lens is advantageously targeted.
- the drug can be gradually released by bringing the soft contact lens into contact with an aqueous solution containing polyphenol as an allergen deactivating component so that the allergen deactivating component is incorporated into the strong soft contact lens. This makes it possible to advantageously obtain a soft contact lens.
- a soft contact lens produced by the above-described method and impregnated with polyphenol as an allergen deactivating component functions advantageously as a drug sustained-release soft contact lens. To do.
- a soft contact lens that can advantageously suppress irritation to the eye, such as when it is instilled, since polyphenol is used as an allergen deactivating component.
- the solution for use can be advantageously obtained.
- a drug sustained-release soft contact lens in which an allergen deactivating component is impregnated in the soft contact lens, when a powerful lens is attached to the eye, it is taken into the lens on the eye.
- the allergen deactivating component can be released gradually, in other words, the force, the allergen deactivating component can be released little by little continuously.
- the allergen deactivating component is released from the strong soft contact lens continuously on the eye for a long time, so that the allergen reducing effect or the deactivating effect is advantageously enjoyed for a long time. This makes it possible to reduce the need for frequent instillation of drugs. It is possible to reduce or alleviate allergic symptoms advantageously with no instillation.
- the antibody for solid phase against the cedar pollen antigen Cryj l is immobilized on a 96-well plate, and there are epicatechin (EC): about 7%, epicatechin gallate (ECG): about 12%, and epigallocatechin (EGC): about 25%, Epigalocatechin gallate (EGCG): Phosphate-Buffered Salts solution containing 0.1% Lw / v% urine serum albumin (hereinafter 0.1% BSA-containing PBS solution) of the remaining catechin mixture (hereinafter the same) And a mixture of 0.1% BSA-containing PBS solution of cedar pollen antigen Cryj l, followed by addition of peroxidase-labeled anti-Cryj l antibody as a fluorescently labeled antibody, and absorbance at 490 nm Was measured, and the fluorescence emission rate was determined.
- Table 1 shows the concentrations of reagents used in the catechin mixture and the ELISA test, and the fluorescence emission efficiency obtained.
- Example 1 1 10 2 500 0 ⁇ Example 2 0.5 10 2 500 0 ⁇ Example 3 0.1 10 2 500 45 ⁇ Comparative Example 1 0 10 0 500 0 X Comparative Example 2 0 10 2 500 100 X
- Example 4 0.1 10 0.5 500 27 ⁇ Example 5 0.01 10 0.5 500 40 O Comparative example 3 0 10 0.5 500 100 X
- Example 7, 8-An ELI SA test was performed in the same manner as in Example 6 except that the tannoic acid concentration was changed to the concentration shown in Table 2 below, and the fluorescence emission rate was determined. The results are also shown in Table 2 below.
- Example 10 An ELISA test was carried out in the same manner as in Example 2 except that epicarocatechin 3 "-O-methyl (hereinafter abbreviated as EGCG-Me) was used instead of the catechin mixture to determine the fluorescence emission rate.
- EGCG-Me epicarocatechin 3 "-O-methyl
- Table 3 shows the concentrations of the reagents used in the EGCG-Me and ELISA tests, and the fluorescence efficiency obtained.
- CG force techin gallate
- ECG epicatechin gallate
- FITC-labeled antibody fluorescently labeled antibody
- a flow cytometry test was carried out in the same manner as in Example 31 except that the concentration of catechin mixture and the amount of cedar pollen were changed to the concentrations shown in Table 10 below, and the fluorescence emission rate was determined. The results are also shown in Table 10 below.
- Comparative Example 10 11-A flow cytometry test was conducted in the same manner as Comparative Examples 6 and 7 except that the amount of cedar pollen was changed to the concentration shown in Table 10 below. Asked. The results are also shown in Table 10 below.
- the polyphenol used as an allergen deactivating component effectively inhibits the cedar pollen antigen cryj l and the cedar pollen allergen. Inactivated, such pollen etc. Even if the allergen adheres to the lens, it can be advantageously deactivated, so that allergic symptoms caused by such allergen can be effectively reduced or mitigated. It becomes.
- Example 36 except that a DMAA (N, N dimethylacrylamide) non-ionic high water content soft contact lens (water content: 72%) was used instead of the HEMA type ionic high water content soft contact lens.
- DMAA N, N dimethylacrylamide
- HEMA HEMA type ionic high water content soft contact lens
- the amount of EGCG released was measured over time in the same manner as in Example 36, except that an epigallocatechin gallate (EGCG) aqueous solution was used instead of the aqueous solution of the catechin mixture.
- EGCG epigallocatechin gallate
- the obtained release EGCG concentration and release rate after 4 hours are also shown in Table 11 below.
- the colorability of the lens by EGCG at various concentrations and the change in lens size were also confirmed.
- DMAA N, N—dimethyl Chill acrylamide
- water content 7. 7, except that there use 2%
- the EGCG amount emitted was measured over time.
- the obtained release EGCG concentration and release rate after 4 hours are also shown in Table 11 below.
- the colorability of the lens by EGCG at various concentrations and the change in lens size were also confirmed.
- Example 38 EGCG released in the same manner as in Example 38, except that a silicone nano-mouth gel soft contact lens having a silicon component (water content: 24%) was used instead of the HEMA ionic high water content soft contact lens. The amount was measured over time. The obtained release EGCG concentration and release rate after 4 hours are also shown in Table 11 below. We also confirmed the coloration of the lens by EGCG and the size change of the lens at various concentrations.
- any of the soft contact lenses apparent from the results in Table 11 above, it was found that the polyphenol was effectively retained and gradually released over time. Compared with non-ionic soft contact lenses, ionic soft contact lenses have a higher polyphenol concentration (release rate) after 4 hours. It has been found that a sustained release of 1 liter takes place over a longer period of time. Further, it was found that when epicarocatechin gallate (EGCG) is used as polyphenol, sustained release over a long period of time is advantageously performed.
- EGCG epicarocatechin gallate
- the lens size change due to polyphenol in the HEMA ionic high water content soft contact lens, no lens size change was observed even at a high polyphenol concentration.
- the lens size decreases when the polyphenol concentration is 0.1% or more, and the lens size decreases by about 20% when the polyphenol concentration is 0.5% or more. Admitted.
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Abstract
Disclosed is a soft contact lens solution which can alleviate an allergic condition without the need of administering a medicinal agent frequently in the form of an eye drop. Also disclosed is a method for production of the solution. A soft contact lens is contacted with a soft contact lens solution comprising an aqueous medium and polyphenol as an allergen-deactivating component contained in the aqueous medium, so that the allergen-deactivating component can be incorporated into the soft contact lens.
Description
明 細 書 Specification
ソフトコンタクトレンズ用溶液及びそれを用いて得られる薬剤徐放性ソフト コンタクトレンズ並びにその製造方法 Soft contact lens solution, drug sustained release soft contact lens obtained using the same, and method for producing the same
技術分野 Technical field
[0001] 本発明は、ソフトコンタクトレンズ用溶液及びそれを用いて得られる薬剤徐放性ソフ トコンタクトレンズ並びにその製造方法に係り、特に、アレルゲン低減化成分乃至は アレルゲン失活成分として、ポリフエノールを含有するソフトコンタクトレンズ用溶液に 関するものである。 The present invention relates to a soft contact lens solution, a drug sustained-release soft contact lens obtained using the same, and a method for producing the same, and in particular, polyphenol as an allergen-reducing component or an allergen-inactivating component. The present invention relates to a solution for soft contact lenses containing.
背景技術 Background art
[0002] 従来から、コンタクトレンズを日常的に装用している人においては、アレルギー性結 膜炎等のアレルギー性の眼疾患の発症率力 S、花粉等のアレルゲンがコンタクトレンズ に付着し、レンズ上に留まることにより、コンタクトレンズを日常的に装用していない人 と比べて、高くなると考えられてきている。 [0002] Conventionally, in people who wear contact lenses on a daily basis, allergic eye diseases such as allergic conjunctivitis have an incidence S, pollen and other allergens adhere to the contact lens, By staying on top, it is believed that it will be higher than those who do not wear contact lenses on a daily basis.
[0003] ところで、近年、ポリフエノールは、花粉、ハウスダスト、ダニ、真菌、ペットの毛等の 環境中のアレルゲンに対して、アレルゲン低減化効果乃至はアレルゲン失活効果を 有することが知られてきてレ、る。 [0003] By the way, in recent years, polyphenols have been known to have an allergen reducing effect or an allergen deactivating effect on allergens in the environment such as pollen, house dust, mites, fungi, and pet hair. I'm going.
[0004] このような、ポリフヱノールのアレルゲン失活効果を利用した技術としては、例えば、 特許文献 1には、環境力 ダニ等のアレルゲンを除去するために、ポリフエノールの 一種であるタンニン酸と特定の溶剤を含有した組成物を、液体、スプレー、エアゾル 等の形態で壁、床、衣類等に対して使用することが明らかにされている。また、特許 文献 2には、有機溶剤、タンニン酸などのポリフエノール類、ハイドロキシアパタイト、 カチオン性界面活性剤からなる群より選ばれる少なくとも 1種以上の成分を有効成分 とするアレルゲン除去剤、及び、このアレルゲン除去剤を、空間に微粒子状に噴霧す る力、アレルゲン付着物に直接噴霧 ·塗布する力、容器内で単体に保持させ、アレル ゲンを含有する空気を通過させて捕集することにより、アレルゲンを除去する方法が 、明らかにされている。さらに、特許文献 3には、タンニン酸、カテキン等の芳香族ヒド 口キシィ匕合物をアレルゲン失活成分として使用する畳用清拭シートが、明らかにされ
ている。 [0004] As a technique using the allergen deactivation effect of polyphenol, for example, Patent Document 1 specifies tannic acid, which is a kind of polyphenol, in order to remove allergens such as environmental power mites. It has been clarified that compositions containing these solvents are used for walls, floors, clothing, etc. in the form of liquids, sprays, aerosols and the like. Patent Document 2 discloses an allergen remover containing as an active ingredient at least one component selected from the group consisting of organic solvents, polyphenols such as tannic acid, hydroxyapatite, and cationic surfactants, and The allergen remover is sprayed into the space in the form of fine particles, directly sprayed and applied to allergen deposits, held alone in the container, and collected by passing air containing the allergen. A method for removing allergens has been clarified. Further, Patent Document 3 discloses a wiping sheet for tatami mats using an aromatic hydride compound such as tannic acid or catechin as an allergen deactivating component. ing.
[0005] し力 ながら、上述の特許文献 1〜3等のように、従来からのポリフエノールのアレル ゲン失活効果を利用した薬剤は、力かる薬剤を布や紙に浸透させたものを用いてァ レルゲンを拭き取る形態のものや、力、かる薬剤をスプレーにて衣服等に噴霧して使 用する形態のものであるところから、それをそのまま眼用には適用出来なレ、ものであ つた。 [0005] However, as in the above-mentioned Patent Documents 1 to 3, etc., a conventional drug using the allergen deactivation effect of polyphenol is obtained by impregnating a powerful drug into cloth or paper. It can be used to wipe off allergens, or it can be used by spraying power or chemicals on clothes etc. with a spray. I got it.
[0006] 一方、そのようなアレルギー症状を低減化乃至は緩和させるための、抗アレルギー 薬としては、例えば、特許文献 4に、コンタクトレンズ装用中の眼に対しても適用可能 なものとして、トラニラスト等の抗アレルギー薬力 明らかにされている。 [0006] On the other hand, as an antiallergic drug for reducing or alleviating such allergic symptoms, for example, Patent Document 4 discloses that tranilast is applicable to eyes wearing contact lenses. Anti-allergic drug power has been clarified.
[0007] し力 ながら、力、かるトラニラスト等の抗アレルギー薬は、一般に、刺激が強く(眼に しみる)、また、その殆どが、 1日に 4〜6回程度もの点眼を要するものであり、点眼回 数が多ぐ非常に面倒なものであつたのである。更に、そのような抗アレルギー薬は、 力かる薬剤が体内に吸収されて、その作用を発揮するものであるため、人によってそ の効果が異なるものであり、更に、副作用等の問題もあるものであった。 [0007] However, anti-allergic drugs such as force and karanilast are generally highly irritating (scratching to the eyes), and most of them require instillation about 4 to 6 times a day. Yes, it was very troublesome with many eye drops. In addition, such antiallergic drugs are those in which powerful drugs are absorbed into the body and exert their actions, so their effects differ depending on the person, and there are also problems such as side effects Met.
[0008] 特許文献 1 :特開昭 61— 44821号公報 Patent Document 1: Japanese Patent Application Laid-Open No. 61-44821
特許文献 2:特開 2000— 264837号公報 Patent Document 2: Japanese Patent Laid-Open No. 2000-264837
特許文献 3 :特開 2003— 79554号公報 Patent Document 3: Japanese Patent Laid-Open No. 2003-79554
特許文献 4:特開 2003— 81840号公報 Patent Document 4: Japanese Unexamined Patent Publication No. 2003-81840
発明の開示 Disclosure of the invention
発明が解決しょうとする課題 Problems to be solved by the invention
[0009] ここにおいて、本発明は、力くの如き事情を背景にして為されたものであって、その 解決課題とするところは、眼に対する刺激の少なレ、ソフトコンタクトレンズ用溶液を提 供することにある。また、薬剤を頻繁に点眼することなくアレルギー症状を低減化させ ることが出来るソフトコンタクトレンズの製造方法を提供することをも、その解決課題と している。 [0009] Here, the present invention has been made against the background of harsh circumstances, and the problem to be solved is to provide a solution for soft contact lenses with less eye irritation. There is. Another solution is to provide a method for producing soft contact lenses that can reduce allergic symptoms without frequent instillation of drugs.
課題を解決するための手段 Means for solving the problem
[0010] そして、本発明者等は、そのような課題を解決すベぐ鋭意検討を重ねた結果、ァ レルゲン失活成分として、ポリフエノールを使用することにより、眼に刺激を与えず、
眼にしみることのなレ、、アレルゲン失活成分を含有するソフトコンタクトレンズ用溶液 を得ることが出来ることを見いだしたのである。また、ソフトコンタクトレンズを適当に選 択して、力かるコンタクトレンズ中に前記アレルゲン失活成分を取り込ませることにより 、力、かるアレルゲン失活成分を徐放するソフトコンタクトレンズを有利に得ることが出 来ることを見いだしたのである。 [0010] And, as a result of repeated intensive studies to solve such a problem, the present inventors, as a result of using polyphenol as an allergen deactivating component, does not irritate the eyes, It was found that a solution for soft contact lenses containing an allergen-inactivating component can be obtained that does not penetrate into the eyes. In addition, by appropriately selecting a soft contact lens and incorporating the allergen deactivating component into the powerful contact lens, it is possible to advantageously obtain a soft contact lens that gradually releases the powerful, allergen deactivating component. I found out that it came out.
[0011] 従って、本発明は、力かる知見に基づいて完成されたものであって、上記した課題 又は明細書全体の記載から把握される課題を解決するために、以下に列挙せる如き 各種の態様において、好適に実施され得るものであるが、また、以下に記載の各態 様は、任意の組み合わせにおいても、採用可能である。なお、本発明の態様乃至は 技術的特徴は、以下に記載のものに何等限定されることなぐ明細書全体の記載乃 至はそこに開示の発明思想に基づいて、認識され得るものであることが、理解される べきである。 [0011] Accordingly, the present invention has been completed on the basis of strong knowledge, and in order to solve the problems described above or the problems grasped from the entire description of the specification, various kinds of problems as listed below can be obtained. In the embodiments, the embodiments can be preferably implemented, but the embodiments described below can be adopted in any combination. Note that aspects or technical features of the present invention are not limited to those described below, and the description of the entire specification can be recognized based on the inventive idea disclosed therein. Should be understood.
[0012] (1) アレルゲン失活成分として、ポリフエノールを、水性媒体中に含有せしめてなる ことを特徴とするソフトコンタクトレンズ用溶液。 [0012] (1) A solution for soft contact lenses, comprising polyphenol as an allergen deactivating component in an aqueous medium.
[0013] (2) 前記ポリフエノールカ S、カテキン類又はタンニン酸であることを特徴とする上記 態様(1)に記載のソフトコンタクトレンズ用溶液。 [0013] (2) The solution for soft contact lenses according to the aspect (1), which is the polyphenol S, catechins, or tannic acid.
[0014] (3) 前記ポリフエノールの含有量力 0. 001〜: 10%であることを特徴とする上記態 様(1)又は(2)に記載のソフトコンタクトレンズ用溶液。 [0014] (3) The soft contact lens solution according to the above aspect (1) or (2), wherein the polyphenol content power is 0.001 to 10%.
[0015] (4) 前記ソフトコンタクトレンズ力 イオン性ソフトコンタクトレンズであることを特徴と する上記態様(1)乃至(3)の何れか一つに記載のソフトコンタクトレンズ用溶液。 [0015] (4) The soft contact lens force The soft contact lens solution according to any one of the above aspects (1) to (3), which is an ionic soft contact lens.
[0016] (5) マルチパーパスソリューション、保存液又は流通保存液として、用いられることを 特徴とする上記態様(1)乃至 (4)の何れか一つに記載のソフトコンタクトレンズ用溶 液。 [0016] (5) The soft contact lens solution according to any one of the above aspects (1) to (4), which is used as a multipurpose solution, a preservation solution, or a distribution preservation solution.
[0017] (6) 薬剤徐放可能なソフトコンタクトレンズを製造する方法にして、 (6) A method for producing a soft contact lens capable of sustained drug release,
a)アレルゲン失活成分としてポリフエノールを含有する水性液剤を準備する工程と b)該水性液剤にソフトコンタクトレンズを接触せしめ、該ソフトコンタクトレンズ中 に、前記アレルゲン失活成分を取り込ませる工程とを、
含むことを特徴とする製造方法。 a) preparing an aqueous solution containing polyphenol as an allergen deactivating component; and b) bringing a soft contact lens into contact with the aqueous solution and incorporating the allergen deactivating component into the soft contact lens. , A manufacturing method comprising:
[0018] (7) 前記ポリフエノールカ S、カテキン類又はタンニン酸であることを特徴とする上記 態様(6)に記載の薬剤徐放可能なソフトコンタクトレンズの製造方法。 [0018] (7) The method for producing a soft contact lens capable of sustained drug release according to the above aspect (6), wherein the polyphenola S, catechins or tannic acid is used.
[0019] (8) 前記ポリフエノールの含有量力 0. 001〜10%であることを特徴とする上記態 様(6)又は(7)に記載の薬剤徐放可能なソフトコンタクトレンズの製造方法。 [0019] (8) The method for producing a soft contact lens capable of sustained drug release as described in the above aspect (6) or (7), wherein the polyphenol content is 0.001 to 10%.
[0020] (9) 前記ソフトコンタクトレンズ力 イオン性ソフトコンタクトレンズであることを特徴と する上記態様(6)乃至(8)の何れか一つに記載の薬剤徐放可能なソフトコンタクトレ ンズの製造方法。 [0020] (9) The soft contact lens force of the soft contact lens capable of sustained drug release according to any one of the above aspects (6) to (8), wherein the soft contact lens force is an ionic soft contact lens. Production method.
[0021] (10) 上記態様(6)乃至(9)の何れか一つに記載の製造方法によって製造された、 ソフトコンタクトレンズ内にアレルゲン失活成分としてのポリフエノールが含侵せしめら れていることを特徴とする薬剤徐放性ソフトコンタクトレンズ。 (10) Polyphenol as an allergen deactivating component is impregnated in the soft contact lens produced by the production method according to any one of the above aspects (6) to (9). A drug sustained-release soft contact lens characterized by
発明の効果 The invention's effect
[0022] 従って、このような本発明に従うソフトコンタクトレンズ用溶液によれば、アレルゲン 失活成分として、ポリフエノールを用いていることにより、点眼時に薬剤が眼にしみる 等、眼に対しての刺激の少ないソフトコンタクトレンズ用溶液を、有利に得ることが出 来るのである。 Therefore, according to the soft contact lens solution according to the present invention as described above, the use of polyphenol as an allergen deactivating component makes it possible to stimulate the eye such as the drug sees the eye when instilled. Therefore, it is possible to advantageously obtain a soft contact lens solution with a low content.
[0023] また、適用するコンタクトレンズとしてソフトコンタクトレンズを選択し、力かるソフトコ ンタクトレンズ中にアレルゲン失活成分を取り込ませるようにすることにより、かかるァ レルゲン失活成分を眼の中で少しずつ連続的に放出せしめることが出来、以て、薬 剤を頻繁に点眼することなぐ少ない点眼回数で有利にアレルギー症状を低減化し 得ることとなる。 [0023] In addition, by selecting a soft contact lens as the contact lens to be applied and incorporating the allergen deactivating component into the powerful soft contact lens, the allergen deactivating component is gradually added to the eye. Since it can be continuously released, allergic symptoms can be advantageously reduced with a small number of instillations without frequent instillation of drugs.
発明を実施するための最良の形態 BEST MODE FOR CARRYING OUT THE INVENTION
[0024] ところで、本発明に従うソフトコンタクトレンズ用溶液は、アレルゲン低減化成分乃至 はアレルゲン失活成分として、ポリフエノールを、水性媒体中に含有せしめてなるもの であるが、そこで用いられるポリフエノールとしては、従来より公知のものが何れも採 用可能であって、例えば、フラボノイド系のポリフエノールとして、フラボン類、フラボノ ール類、イソフラボン類、フラバン類、フラバノール類、フラバノン類、フラバノノール 類、カルコン類、アントシァニジン類等、フエ二ルカルボン酸系のポリフエノール等を、
例示することが出来る。そして、それらの中でも、特に、フラボノイド系ポリフエノール の一種である、フラバノール類のうち、カテキン類及びフエ二ルカルボン酸系ポリフエ ノールの一種であるタンニン酸力 S、好ましく用いられることとなる。 By the way, the soft contact lens solution according to the present invention contains polyphenol as an allergen-reducing component or allergen-inactivating component in an aqueous medium. As a polyphenol used there, Any of those conventionally known can be used. For example, flavonoid polyphenols include flavones, flavonols, isoflavones, flavans, flavanols, flavanones, flavonols, chalcones. , Anthocyanidins, phenylcarboxylic acid polyphenols, etc. It can be illustrated. Of these, tannic acid power S, which is a kind of catechins and phenylcarboxylic acid-type polyphenols, among flavanols, which is a kind of flavonoid-type polyphenols, is particularly preferably used.
[0025] また、上で指摘のカテキン類として、更に具体的には、カテキン、ェピカテキン、ェ ピガロカテキン、ェピカテキンガレート、ェピガロカテキンガレート及びこれらのメチル 化誘導体、茶抽出物 (甜茶も含む)、また茶以外の植物抽出成分として、柿 (実、葉、 木)、竹、くま笹、シソ、バラ、クチナシ実、イチヨウ、アロエ、ローズマリー等を挙げるこ とが出来る力 これら例示のものに、何等限定されるものでないことは言うまでもない ところである。なお、それら化合物は、それぞれ単独で、或いは二種以上を組み合わ せて、用いることが可能である。 [0025] Further, as the catechins pointed out above, more specifically, catechin, epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate and methylated derivatives thereof, tea extract (including tea tea) ) In addition, as a plant extract component other than tea, it is possible to list grapes (fruits, leaves, trees), bamboo, bear buds, perilla, roses, gardenia fruits, yew, aloe, rosemary, etc. Needless to say, it is not limited in any way. These compounds can be used alone or in combination of two or more.
[0026] そして、上述したようなポリフエノールを、アレルゲン失活成分として使用することに よって、力、かるアレルゲン失活成分を点眼したときに、レンズ上の花粉等のアレルゲ ンを有利に低減化乃至は失活せしめることが出来、また点眼時に、薬剤が眼にしみ る等、眼に対しての刺激を有利に抑えることの出来るコンタクトレンズ用溶液とするこ とが出来るのである。なお、力かるポリフエノールは、比較的入手が容易であり、また 安全性及び安定性にも優れているといった利点をも有している。 [0026] By using polyphenol as described above as an allergen deactivating component, when allergen deactivating component is instilled, the allergens such as pollen on the lens are advantageously reduced. It can be inactivated, or can be made into a contact lens solution that can advantageously suppress irritation to the eye, such as when the medicine is instilled into the eye. Powerful polyphenols have the advantage that they are relatively easy to obtain and are excellent in safety and stability.
[0027] ここで、力かるポリフエノールは、アレルゲンの失活に有効な量において適宜に用い られ得るものである力 一般には、重量基準にて、 0. 001〜10%の含有量において 、好ましくは 0. 1〜5%の含有量にて用いられることとなる。力かる含有量よりも少なく なると、ポリフエノールを含有せしめることによるアレルゲンの失活化効果が充分に発 揮され得なくなる恐れがあるからであり、また上記した範囲よりも多くなると、特にポリ フエノールとしてカテキンを用いた場合に、力、かるソフトコンタクトレンズ用溶液に接触 せしめられるレンズに着色等の問題が惹起される恐れがあるからである。 [0027] Here, the strong polyphenol is a force that can be appropriately used in an amount effective for deactivating allergens. Generally, it is preferable that the content is 0.001 to 10% on a weight basis. Is used at a content of 0.1-5%. This is because if the content is too low, the allergen deactivation effect due to the inclusion of polyphenols may not be sufficiently exerted, and if the content exceeds the above range, polyphenols may be used. This is because when catechin is used, there is a possibility that problems such as coloring may occur in the lens that is brought into contact with the solution for the soft contact lens.
[0028] そして、本発明に従うコンタクトレンズ用溶液は、上述の如き成分を、従来と同様に して、適当な水性媒体中に、添加、含有せしめることにより、調製されることとなるので あるが、それに際して用いられる水性媒体としては、水道水や精製水、蒸留水等の水 そのものの他にも、水を主体とする溶液であれば、生体への安全性が高ぐ尚且つ眼 科的に充分に許容され得るものである限りにおいて、何れも、利用することが可能で
ある。 [0028] The contact lens solution according to the present invention is prepared by adding and incorporating the above-described components into an appropriate aqueous medium in the same manner as in the prior art. In addition to water itself such as tap water, purified water, and distilled water, the aqueous medium used at that time is highly water-safe and ophthalmic as long as the solution is mainly water. Can be used as long as it is sufficiently acceptable to is there.
[0029] また、本発明においては、上述のようなアレルゲン失活成分として、ポリフエノール 力 水性媒体中に含有せしめられてなる溶液を、ソフトコンタクトレンズ用溶液として 用レ、るものである力 そのような溶液の適用対象となるソフトコンタクトレンズは、公知 の各種のソフトコンタクトレンズであって、例えば、非イオン性ソフトコンタクトレンズとし ては、酢酸ビュル系、 DMAA系等のソフトコンタクトレンズを挙げることが出来、また イオン性ソフトコンタクトレンズとしては、カルボキシル基の如きイオン性基が導入され た、 HEMA系、 N—VP系、 MAA系等のものを挙げることが出来る。 [0029] Further, in the present invention, as an allergen deactivating component as described above, a solution that is contained in a polyphenol-based aqueous medium is used as a soft contact lens solution. The soft contact lenses to which such a solution is applied are various known soft contact lenses. For example, examples of non-ionic soft contact lenses include soft contact lenses such as butyl acetate and DMAA. Examples of the ionic soft contact lens include HEMA type, N-VP type, MAA type and the like into which an ionic group such as a carboxyl group is introduced.
[0030] 特に、それらソフトコンタクトレンズの中でも、有利には、イオン性ソフトコンタクトレン ズカ 対象とされることとなる。そのようなイオン性ソフトコンタクトレンズとしては、上述 したような、例えば、 HEMA (ヒドロキシルェチルメタタリレート)系や N_VP (N—ビ ニル一 2_ピロリドン)系、 MAA (メタクリル酸)系のものを挙げることが出来る。更に、 それらの中でも、含水率が 50%以上のイオン性高含水ソフトコンタクトレンズ力 有利 に対象とされるのである。 [0030] In particular, among these soft contact lenses, it is advantageous to be an ionic soft contact lens. Examples of such ionic soft contact lenses include those described above, for example, HEMA (hydroxylethyl methacrylate), N_VP (N-vinyl-1-pyrrolidone), and MAA (methacrylic acid). Can be mentioned. Furthermore, among them, the ionic high water content soft contact lens force having a water content of 50% or more is advantageously targeted.
[0031] このように、アレルゲン失活成分を含有してなる溶液を、ソフトコンタクトレンズ用の 溶液とすることによって、そのようなアレルゲン失活成分が、レンズに接触した際に、 力かるレンズ内に有利に取り込まれることとなり、従って、その取り込まれたアレルゲン 失活成分が、眼上で少しずつ連続的に長時間に亘つて放出されるようになり、以て、 新たにアレルゲンがレンズ上に付着したりした場合にあっても、新たにアレルゲン失 活成分を点眼する必要がないところから、少ない点眼回数で、有利にアレルギー症 状を低減化乃至は緩和し得ることとなるのである。 [0031] Thus, by using a solution containing an allergen deactivating component as a solution for a soft contact lens, when such allergen deactivating component comes into contact with the lens, Therefore, the incorporated allergen-inactivating component is released little by little on the eye continuously over a long period of time, so that allergen is newly added to the lens. Even if it adheres, since it is not necessary to instill a new allergen-inactivating component, allergic symptoms can be advantageously reduced or alleviated with a small number of instillations.
[0032] さらに、本発明においては、力かるソフトコンタクトレンズとして、イオン性ソフトコンタ クトレンズを適用することにより、アレルゲン失活成分含有溶液力 Sイオン性ソフトコンタ クトレンズに接触したときに、力かるレンズのポリフエノール (特に、カテキン類)による 着色、及びサイズの変化等の影響を、有利に回避することが出来るのである。この理 由は未だ充分に明らかではなレ、が、カテキン(ポリフエノール)はわずかに水に溶ける が、基本的には疎水性の高い物質であるために、非イオン性のソフトコンタクトレンズ の場合、力かる非イオン性のレンズとカテキン (ポリフエノール)が疎水性相互作用す
ることにより、レンズにカテキン(ポリフエノール)が凝集し、かかるレンズの着色及びサ ィズの変化等が惹起されるためであると考えられている。 [0032] Further, in the present invention, an ionic soft contact lens is applied as a powerful soft contact lens, whereby an allergen-inactivating component-containing solution force S ionic soft contact lens when in contact with the ionic soft contact lens The effects of color change and size change due to polyphenols (especially catechins) can be advantageously avoided. The reason for this is still not clear enough, but catechin (polyphenol) is slightly soluble in water, but it is basically a highly hydrophobic substance, so in the case of non-ionic soft contact lenses. , Non-ionic lens and catechin (polyphenol) interact hydrophobicly This is considered to be because catechin (polyphenol) aggregates on the lens, and coloring of the lens and a change in size are caused.
[0033] 力 0えて、本発明に従うソフトコンタクトレンズ用溶液においては、上述の如き成分の 他にも、更に必要に応じて、従来より、コンタクトレンズ用溶液に用いられている各種 の添加成分、例えば、粘稠化剤、 pH緩衝剤、キレー Hヒ剤、清涼化剤、界面活性剤 、浸透圧調整剤、血管収縮剤、ビタミン類、消炎剤及び嬌味剤等のうちの 1種乃至は 2種以上が適宜に選択されて、通常の含有割合において含有せしめられていても、 何等、差支えない。尤も、そのような添加成分(添加剤)としては、生体への安全性が 高ぐ尚且つ眼科的に許容され、しかもコンタクトレンズの形状や物性に対して影響 のないものが、有利に選択されることとなる。 [0033] In addition to the above-described components, the soft contact lens solution according to the present invention, in addition to the above-described components, if necessary, various additive components conventionally used in contact lens solutions, For example, one or more of a thickening agent, a pH buffering agent, a cleansing agent, a refreshing agent, a surfactant, an osmotic pressure adjusting agent, a vasoconstrictor, vitamins, an anti-inflammatory agent and a flavoring agent. Even if two or more kinds are appropriately selected and contained in a normal content ratio, there is no problem. However, as such additive components (additives), those that are highly safe to the living body and that are ophthalmically acceptable and that do not affect the shape and physical properties of the contact lens are advantageously selected. The Rukoto.
[0034] なお、本発明におけるソフトコンタクトレンズ用溶液は、従来から公知の各種の態様 においてソフトコンタクトレンズに対して適用され得るものである力 一般に、ソフトコン タ外レンズを装用した眼に対する点眼液として用いられる他、装着液、洗眼液、マル チパーパスソリューション、保存液又は流通保存液としても、用いられ、それら液剤中 に、ソフトコンタクトレンズが浸漬せしめられることによって、より一層有利に、本発明 の効果が奏され得ることとなる。なお、ここで、マルチパーパスソリューションとは、コン タクトレンズの洗浄、すすぎ、消毒、保存のうち少なくとも 2つ以上を 1液で行なうこと が出来る液剤を意味している。また、本発明のソフトコンタクトレンズ用溶液を流通保 存液として、使い捨てコンタクトレンズに対して用いることによって、清潔な状態の薬 剤徐放可能な使い捨てソフトコンタクトレンズが容易に得られることとなり、以て、有利 に、本発明の効果が奏され得ることとなる。 [0034] It should be noted that the soft contact lens solution in the present invention is a force that can be applied to the soft contact lens in various conventionally known embodiments. Generally, ophthalmic solutions for eyes wearing a soft contour lens. In addition, it is also used as a mounting solution, an eyewash solution, a multi-purpose solution, a preservative solution or a distribution preservative solution, and the soft contact lens is soaked in these liquid agents. The effect of can be produced. Here, the multi-purpose solution means a solution that can perform at least two or more of cleaning, rinsing, disinfection, and storage of contact lenses in one solution. Further, by using the soft contact lens solution of the present invention as a distribution preservation solution for a disposable contact lens, a disposable soft contact lens capable of sustained release of a clean drug can be easily obtained. Thus, the effects of the present invention can be advantageously achieved.
[0035] そして、本発明においては、上記したソフトコンタクトレンズ用溶液を用いて、薬剤 徐放可能なソフトコンタクトレンズを製造するために、アレルゲン失活成分としてポリフ ヱノールを含有する水性液剤を準備する工程と、力、かる水性液剤にソフトコンタクトレ ンズを接触せしめ、力かるソフトコンタクトレンズ中にアレルゲン失活成分を取り込ま せる工程とを含む製造方法が、採用されるのである。 In the present invention, an aqueous liquid preparation containing polyphenol as an allergen deactivating component is prepared in order to produce a soft contact lens capable of sustained drug release using the soft contact lens solution described above. A manufacturing method including a step and a step of bringing a soft contact lens into contact with a force and a liquid aqueous solution and incorporating an allergen deactivating component into the forceful soft contact lens is adopted.
[0036] ここで、上記のソフトコンタクトレンズ中にアレルゲン失活成分を取り込ませる工程に おいては、ソフトコンタクトレンズ力 水性液剤中に浸漬されたり、水性液剤を付着せ
しめたりすることによって、水性液剤に接触させられることとなる力 そのような工程は[0036] Here, in the step of incorporating the allergen-inactivating component into the soft contact lens, the soft contact lens force is immersed in the aqueous liquid agent or the aqueous liquid agent is adhered. The force that can be brought into contact with an aqueous solution by tightening
、有利には、 30分〜 16時間程度を要して実施されることとなる。力かる時間よりも短く なると、そのようにして製造された薬剤徐放可能なソフトコンタ外レンズのアレルゲン 失活成分の取り込み量が充分でなくなる恐れがあり、従って、ソフトコンタクトレンズの 徐放性の効果が有利に享受出来ない恐れがある。また、上記した時間よりも長い場 合には、アレルゲン失活成分のレンズへの取り込み量が飽和に達し、かかる時間以 上浸漬することによる効果が得られなレ、恐れがある。 Advantageously, it takes about 30 minutes to 16 hours. If the time is too short, there is a risk that the allergen-inactive component uptake amount of the soft contoured external lens capable of sustained drug release produced in this way may not be sufficient. There is a possibility that the effect cannot be enjoyed advantageously. If the time is longer than the above-mentioned time, the amount of allergen deactivating components taken into the lens reaches saturation, and there is a risk that the effect of soaking for longer than this time cannot be obtained.
[0037] また、上述した理由と同様な理由により、有利には、力、かるポリフエノールとして、力 テキン類又はタンニン酸が用いられ、更に、力、かるポリフエノールの含有量は、一般 に 0. 001〜10%であり、加えて、力かるソフトコンタクトレンズとしては、有利には、ィ オン性ソフトコンタクトレンズが対象とされるのである。 [0037] Further, for the same reason as described above, force techkins or tannic acid is advantageously used as the force or karyopolyphenol, and the content of force or kraft polyphenol is generally 0. 001-10%, and in addition, as a soft contact lens that works, an ion soft contact lens is advantageously targeted.
[0038] このように、アレルゲン失活成分としてポリフヱノールを含有する水性液剤にソフトコ ンタクトレンズを接触せしめ、力かるソフトコンタクトレンズ中にアレルゲン失活成分を 取り込ませるようにすることによって、薬剤徐放可能なソフトコンタクトレンズを有利に 得ることが可能となるのである。 [0038] As described above, the drug can be gradually released by bringing the soft contact lens into contact with an aqueous solution containing polyphenol as an allergen deactivating component so that the allergen deactivating component is incorporated into the strong soft contact lens. This makes it possible to advantageously obtain a soft contact lens.
[0039] そして、上述のような方法に従って製造された、ソフトコンタクトレンズ内にアレルゲ ン失活成分としてのポリフエノールが含浸せしめられてなるものは、薬剤徐放性ソフト コンタクトレンズとして、有利に機能するのである。 [0039] A soft contact lens produced by the above-described method and impregnated with polyphenol as an allergen deactivating component functions advantageously as a drug sustained-release soft contact lens. To do.
[0040] すなわち、そこでは、アレルゲン失活成分として、ポリフエノールが用いられていると ころから、点眼時に眼にしみる等、眼に対しての刺激を有利に抑えることが可能なソ フトコンタクトレンズ用溶液を有利に得ることが出来ることとなる。また、ソフトコンタクト レンズ内にアレルゲン失活成分が含浸せしめられている薬剤徐放性ソフトコンタクトレ ンズとすることによって、力かるレンズを眼に装着したときに、眼上において、レンズ中 に取り込まれたアレルゲン失活成分を徐放することが出来、換言すれば力、かるアレル ゲン失活成分を少しずつ連続的に放出せしめることが出来るのである。 [0040] That is, there is a soft contact lens that can advantageously suppress irritation to the eye, such as when it is instilled, since polyphenol is used as an allergen deactivating component. The solution for use can be advantageously obtained. In addition, by using a drug sustained-release soft contact lens in which an allergen deactivating component is impregnated in the soft contact lens, when a powerful lens is attached to the eye, it is taken into the lens on the eye. In addition, the allergen deactivating component can be released gradually, in other words, the force, the allergen deactivating component can be released little by little continuously.
[0041] 従って、アレルゲン失活成分が、力かるソフトコンタクトレンズから、連続的に、長時 間、眼上で放出されるところから、アレルゲン低減化効果乃至は失活化効果を有利 に長く享受することが可能となるのであり、以て、薬剤を頻繁に点眼することなぐ少
ない点眼回数で、有利にアレルギー症状を低減化乃至は緩和せしめることが可能と なるのである。 [0041] Therefore, the allergen deactivating component is released from the strong soft contact lens continuously on the eye for a long time, so that the allergen reducing effect or the deactivating effect is advantageously enjoyed for a long time. This makes it possible to reduce the need for frequent instillation of drugs. It is possible to reduce or alleviate allergic symptoms advantageously with no instillation.
実施例 Example
[0042] 以下に、本発明の幾つかの実施例を示し、本発明を更に具体的に明らかにするこ ととする力 本発明が、そのような実施例の記載によって、何等の制約をも受けるもの でないことは、言うまでもないところである。また、本発明には、以下の実施例の他に も、本発明の趣旨を逸脱しない限りにおいて、当業者の知識に基づいて、種々なる 変更、修正、改良等を加え得るものであることが、理解されるべきである。 [0042] The following are some examples of the present invention, and the power to further clarify the present invention. The present invention is not limited by the description of such examples. It goes without saying that it is not something to receive. In addition to the following examples, various changes, modifications, improvements, and the like can be added to the present invention based on the knowledge of those skilled in the art without departing from the spirit of the present invention. Should be understood.
[0043] 先ず、本発明で用いられるアレルゲン失活成分の、スギ花粉抗原に対する有効性 及びスギ花粉に対する有効性を、 ELISA法(実施例 1〜30、比較例:!〜 5)によって 評価し、その結果を、下記表 1〜9に示した。さらに、フローサイトメトリー(FCM)法( 実施例 31〜35、比較例 6〜11)によって評価した結果を、下記表 10に示した。なお 、評価は、蛍光発光率 (活性率)が 0%以上 45%以下の場合を〇、 45%超のものを Xとして、行った。 [0043] First, the efficacy against the cedar pollen antigen and the efficacy against the cedar pollen of the allergen-inactivating component used in the present invention were evaluated by ELISA (Examples 1 to 30, Comparative Examples:! To 5), The results are shown in Tables 1 to 9 below. Furthermore, the results evaluated by the flow cytometry (FCM) method (Examples 31 to 35, Comparative Examples 6 to 11) are shown in Table 10 below. Note that the evaluation was performed when the fluorescence emission rate (activity rate) was 0% or more and 45% or less, and X was given when X was over 45%.
[0044] 実施例 1 [0044] Example 1
96穴プレートに、スギ花粉抗原 Cryj lに対する固相用抗体を固定化し、そこに、ェ ピカテキン (EC):約 7%、ェピカテキンガレート(ECG):約 12%、ェピガロカテキン( EGC):約 25%、ェピガロカテキンガレート(EGCG):残部からなるカテキン混合物( 以下、同じ)の 0. lw/v%ゥシ血清アルブミン含有 Phosphate-Buffered Salts溶液( 以下、 0. 1%BSA含有 PBS溶液と略称する)とスギ花粉抗原 Cryj lの 0. 1 %BSA 含有 PBS溶液との混合溶液を添加した後、蛍光標識抗体としてペルォキシダーゼラ ベル化抗 Cryj l抗体を添加して、 490nmにおける吸光度を測定し、蛍光発光率を 求めた。カテキン混合物及び ELISA試験に用いた試薬の濃度並びに求めた蛍光発 光効率を、下記表 1に示す。 The antibody for solid phase against the cedar pollen antigen Cryj l is immobilized on a 96-well plate, and there are epicatechin (EC): about 7%, epicatechin gallate (ECG): about 12%, and epigallocatechin (EGC): about 25%, Epigalocatechin gallate (EGCG): Phosphate-Buffered Salts solution containing 0.1% Lw / v% urine serum albumin (hereinafter 0.1% BSA-containing PBS solution) of the remaining catechin mixture (hereinafter the same) And a mixture of 0.1% BSA-containing PBS solution of cedar pollen antigen Cryj l, followed by addition of peroxidase-labeled anti-Cryj l antibody as a fluorescently labeled antibody, and absorbance at 490 nm Was measured, and the fluorescence emission rate was determined. Table 1 below shows the concentrations of reagents used in the catechin mixture and the ELISA test, and the fluorescence emission efficiency obtained.
[0045] 実施例 2, 3— [0045] Example 2, 3—
カテキン混合物の濃度を、下記表 1に示す濃度とした以外は、実施例 1と同様にし て、 ELISA試験を行レ、、蛍光発光率を求めた。その結果を、下記表 1に併せて示す
[0046] 比較例 1 Except that the concentration of the catechin mixture was changed to the concentration shown in Table 1 below, the ELISA test was conducted in the same manner as in Example 1 to obtain the fluorescence emission rate. The results are also shown in Table 1 below. [0046] Comparative Example 1
96穴プレートに、スギ花粉抗原 Cryj lに対する固相用抗体を固定化し、そこに、 0. 1 %BSA含有 PBS溶液を添加した後、蛍光標識抗体としてペルォキシダーゼラベル 化抗 Cryj l抗体を添加して、 490nmにおける吸光度を測定し、蛍光発光率を求めた 。カテキン混合物及び ELISA試験に用いた試薬の濃度並びに求めた蛍光発光効 率を、下記表 1に示す。 Immobilize antibody for solid phase against cedar pollen antigen Cryj l in 96-well plate, add 0.1% BSA-containing PBS solution, then add peroxidase-labeled anti-Cryj l antibody as fluorescently labeled antibody Then, the absorbance at 490 nm was measured to determine the fluorescence emission rate. Table 1 below shows the concentrations of the catechin mixture and the reagents used in the ELISA test and the fluorescence emission efficiency obtained.
[0047] 一比較例 2— [0047] Comparative Example 2—
96穴プレートに、スギ花粉抗原 Cryj lに対する固相用抗体を固定化し、そこに、ス ギ花粉抗原 Cryj lの 0. 1 %BSA含有 PBS溶液を添加した後、蛍光標識抗体として ペルォキシダーゼラベル化抗 Cryj l抗体を添加して、 490nmにおける吸光度を測 定し、蛍光発光率を求めた。カテキン混合物及び ELISA試験に用いた試薬の濃度 並びに求めた蛍光発光効率を、下記表 1に示す。 Immobilize antibody for solid phase against cedar pollen antigen Cryj l in 96-well plate, add 0.1% BSA-containing PBS solution of cedar pollen antigen Cryj l to it, and then peroxidase label as fluorescently labeled antibody Anti-Cryjl antibody was added, and the absorbance at 490 nm was measured to determine the fluorescence emission rate. Table 1 below shows the concentrations of the reagents used in the catechin mixture and the ELISA test, and the fluorescence emission efficiency obtained.
[0048] 実施例 4, 5— [0048] Example 4, 5—
カテキン混合物の濃度及びスギ花粉抗原 Cryj l濃度を、下記表 1に示す濃度とし た以外は、実施例 1と同様にして、 ELISA試験を行い、蛍光発光率を求めた。その 結果を、下記表 1に併せて示す。 An ELISA test was carried out in the same manner as in Example 1 except that the catechin mixture concentration and the cedar pollen antigen Cryjl concentration were those shown in Table 1, and the fluorescence emission rate was determined. The results are also shown in Table 1 below.
[0049] 比較例 3— [0049] Comparative Example 3—
スギ花粉抗原 Cryj l濃度を、下記表 1に示す濃度とした以外は、比較例 2と同様に して、 ELISA試験を行い、蛍光発光率を求めた。その結果を、下記表 1に併せて示 す。 An ELISA test was carried out in the same manner as in Comparative Example 2 except that the cedar pollen antigen Cryjl concentration was changed to the concentration shown in Table 1, and the fluorescence emission rate was determined. The results are also shown in Table 1 below.
[0050] [表 1]
[0050] [Table 1]
カ于キン混合物 固相用抗体 抗原(Cryj l ) H RP—抗 Cryj l 蛍光発光率 Liquid mixture Antibody for solid phase Antigen (Cryj l) H RP—Anti-Cryj l Fluorescence emission rate
抑制 濃度 (taCryj lパ 度 ίΛίί·濃度 (活性率) Inhibition Concentration (taCryj l Degree ίΛίί · Concentration (Activity)
(w/v%) ( χ/ g/mL) ngz mし) (ng/mし 効果 (w / v%) (χ / g / mL) ngz m) (ng / m effect)
( %) (%)
実施例 1 1 10 2 500 0 〇 実施例 2 0.5 10 2 500 0 〇 実施例 3 0.1 10 2 500 45 〇 比較例 1 0 10 0 500 0 X 比較例 2 0 10 2 500 100 X 実施例 4 0.1 10 0.5 500 27 〇 実施例 5 0.01 10 0.5 500 40 O 比較例 3 0 10 0.5 500 100 X Example 1 1 10 2 500 0 ○ Example 2 0.5 10 2 500 0 ○ Example 3 0.1 10 2 500 45 ○ Comparative Example 1 0 10 0 500 0 X Comparative Example 2 0 10 2 500 100 X Example 4 0.1 10 0.5 500 27 〇 Example 5 0.01 10 0.5 500 40 O Comparative example 3 0 10 0.5 500 100 X
[0051] 一実施例 6— [0051] Example 6—
カテキン混合物に代えて、タンニン酸を用いた以外は、実施例 1と同様にして、 ELI SA試験を行い、蛍光発光率を求めた。タンニン酸及び ELISA試験に用いた試薬の 濃度並びに求めた蛍光発光効率を、下記表 2に示す。 An ELI SA test was conducted in the same manner as in Example 1 except that tannic acid was used in place of the catechin mixture, and the fluorescence emission rate was determined. Table 2 below shows the concentrations of the reagents used in the tannic acid and ELISA tests, and the fluorescence emission efficiency obtained.
[0052] 一実施例 7, 8 - タンユン酸濃度を、下記表 2に示す濃度とした以外は、実施例 6と同様にして、 ELI SA試験を行い、蛍光発光率を求めた。その結果を、下記表 2に併せて示す。 [0052] One Example 7, 8-An ELI SA test was performed in the same manner as in Example 6 except that the tannoic acid concentration was changed to the concentration shown in Table 2 below, and the fluorescence emission rate was determined. The results are also shown in Table 2 below.
[0053] [表 2] [0053] [Table 2]
実施例 9 Example 9
カテキン混合物に代えて、ェピガロカテキン 3"—〇一メチル(以下、 EGCG— M eと略称する)を用いた以外は、実施例 2と同様にして、 ELISA試験を行い、蛍光発 光率を求めた。 EGCG— Me及び ELISA試験に用いた試薬の濃度並びに求めた蛍 光発光効率を、下記表 3に示す。
[0055] 実施例 10— An ELISA test was carried out in the same manner as in Example 2 except that epicarocatechin 3 "-O-methyl (hereinafter abbreviated as EGCG-Me) was used instead of the catechin mixture to determine the fluorescence emission rate. Table 3 below shows the concentrations of the reagents used in the EGCG-Me and ELISA tests, and the fluorescence efficiency obtained. [0055] Example 10—
EGCG— Me濃度を、下記表 3に示す濃度とした以外は、実施例 9と同様にして、 E LISA試験を行い、蛍光発光率を求めた。その結果を、下記表 3に併せて示す。 Except that the concentration of EGCG-Me was changed to the concentration shown in Table 3 below, the ELISA test was conducted in the same manner as in Example 9 to obtain the fluorescence emission rate. The results are also shown in Table 3 below.
[0056] [表 3] [0056] [Table 3]
[0057] 一実施例 11一 [0057] One Example 11
カテキン混合物に代えて、ェピガロカテキンガレート(以下、 EGCGと略称する)を 用いた以外は、実施例 1と同様にして、 ELISA試験を行い、蛍光発光率を求めた。 E GCG及び ELISA試験に用いた試薬の濃度並びに求めた蛍光発光効率を、下記表 4に示す。 An ELISA test was performed to determine the fluorescence emission rate in the same manner as in Example 1, except that epicarocatechin gallate (hereinafter abbreviated as EGCG) was used instead of the catechin mixture. Table 4 below shows the concentrations of the reagents used in the EGCG and ELISA tests and the determined fluorescence emission efficiency.
[0058] 一実施例 12, 13— [0058] Examples 12, 13—
EGCG濃度を、下記表 4に示す濃度とした以外は、実施例 11と同様にして、 ELIS A試験を行い、蛍光発光率を求めた。その結果を、下記表 4に併せて示す。 An ELISA test was performed in the same manner as in Example 11 except that the EGCG concentration was changed to the concentration shown in Table 4 below, and the fluorescence emission rate was obtained. The results are also shown in Table 4 below.
[0059] [表 4] [0059] [Table 4]
一実施例 14一 Example 14
カテキン混合物に代えて、力テキンガレート(以下、 CGと略称する)を用いた以外は 実施例 1と同様にして、 ELISA試験を行レ、、蛍光発光率を求めた。 CG及び ELIS
A試験に用いた試薬の濃度並びに求めた蛍光発光効率を、下記表 5に示す。 Instead of the catechin mixture, force techin gallate (hereinafter abbreviated as CG) was used in the same manner as in Example 1, and an ELISA test was performed to determine the fluorescence emission rate. CG and ELIS Table 5 below shows the concentration of the reagent used in the A test and the obtained fluorescence emission efficiency.
[0061] 実施例 15, 16— [0061] Examples 15, 16—
CG濃度を、下記表 5に示す濃度とした以外は、実施例 14と同様にして、 ELISA試 験を行い、蛍光発光率を求めた。その結果を、下記表 5に併せて示す。 An ELISA test was carried out in the same manner as in Example 14 except that the CG concentration was changed to the concentration shown in Table 5 below, and the fluorescence emission rate was determined. The results are also shown in Table 5 below.
[0062] [表 5] [0062] [Table 5]
[0063] 実施例 17— [0063] Example 17-
カテキン混合物に代えて、ェピカテキンガレート(以下、 ECGと略称する)を用いた 以外は、実施例 1と同様にして、 ELISA試験を行レ、、蛍光発光率を求めた。 ECG及 び ELISA試験に用いた試薬の濃度並びに求めた蛍光発光効率を、下記表 6に示す An ELISA test was carried out in the same manner as in Example 1 except that epicatechin gallate (hereinafter abbreviated as ECG) was used in place of the catechin mixture, and the fluorescence emission rate was determined. Table 6 below shows the concentrations of the reagents used in the ECG and ELISA tests, as well as the calculated fluorescence emission efficiency.
[0064] 実施例 18— [0064] Example 18-
ECG濃度を、下記表 6に示す濃度とした以外は、実施例 17と同様にして、 ELISA 試験を行い、蛍光発光率を求めた。その結果を、下記表 6に併せて示す。 An ELISA test was carried out in the same manner as in Example 17 except that the ECG concentration was changed to the concentration shown in Table 6 below, and the fluorescence emission rate was determined. The results are also shown in Table 6 below.
[0065] [表 6] [0065] [Table 6]
実施例 19 Example 19
96穴プレートに、スギ花粉抗原 Cryj2に対する固相用抗体を固定化し、そこに、力
テキン混合物の 0. 1 %BSA含有 PBS溶液とスギ花粉抗原 Cryj2の 0. 1 %BSA含有 PBS溶液との混合溶液を添加した後、蛍光標識抗体としてペルォキシダーゼラベル 化抗 Cryj2抗体を添加して、 490nmにおける吸光度を測定し、蛍光発光率を求めた 。カテキン混合物及び ELISA試験に用いた試薬の濃度並びに求めた蛍光発光効 率を、下記表 7に示す。 An antibody for solid phase against cedar pollen antigen Cryj2 was immobilized on a 96-well plate, After adding a mixed solution of 0.1% BSA-containing PBS solution of the Tekin mixture and 0.1% BSA-containing PBS solution of cedar pollen antigen Cryj2, add peroxidase-labeled anti-Cryj2 antibody as a fluorescently labeled antibody. The absorbance at 490 nm was measured to determine the fluorescence emission rate. Table 7 below shows the concentrations of the catechin mixture and the reagents used in the ELISA test and the fluorescence emission efficiency obtained.
[0067] 一実施例 20〜22— [0067] One Example 20-22—
カテキン混合物の濃度を、下記表 7に示す濃度とした以外は、実施例 19と同様にし て、 ELISA試験を行い、蛍光発光率を求めた。その結果を、下記表 7に併せて示す An ELISA test was carried out in the same manner as in Example 19 except that the concentration of the catechin mixture was changed to the concentration shown in Table 7 below, and the fluorescence emission rate was determined. The results are also shown in Table 7 below.
[0068] 一比較例 4一 [0068] One Comparative Example 4
96穴プレートに、スギ花粉抗原 Cryj2に対する固相用抗体を固定化し、そこに、 0. 1 %BSA含有 PBS溶液を添加した後、蛍光標識抗体としてペルォキシダーゼラベル 化抗 Cryj2抗体を添加して、 490nmにおける吸光度を測定し、蛍光発光率を求めた 。カテキン混合物及び ELISA試験に用いた試薬の濃度並びに求めた蛍光発光効 率を、下記表 7に示す。 Immobilize a solid phase antibody against the cedar pollen antigen Cryj2 in a 96-well plate, add 0.1% BSA-containing PBS solution, and then add peroxidase-labeled anti-Cryj2 antibody as a fluorescently labeled antibody. The absorbance at 490 nm was measured to determine the fluorescence emission rate. Table 7 below shows the concentrations of the catechin mixture and the reagents used in the ELISA test and the fluorescence emission efficiency obtained.
[0069] 比較例 5— [0069] Comparative Example 5—
96穴プレートに、スギ花粉抗原 Cryj2に対する固相用抗体を固定化し、そこに、ス ギ花粉抗原 Cryj2の 0. 1 %BSA含有 PBS溶液を添加した後、蛍光標識抗体として ペルォキシダーゼラベル化抗 Cryj 2抗体を添加して、 490nmにおける吸光度を測 定し、蛍光発光率を求めた。カテキン混合物及び ELISA試験に用いた試薬の濃度 並びに求めた蛍光発光効率を、下記表 7に示す。 Immobilize a solid phase antibody against cedar pollen antigen Cryj2 in a 96-well plate, add 0.1% BSA-containing PBS solution of cedar pollen antigen Cryj2 to it, and then add peroxidase-labeled anti-fluorescent antibody as a fluorescent-labeled antibody. Cryj 2 antibody was added, and the absorbance at 490 nm was measured to determine the fluorescence emission rate. Table 7 below shows the concentration of the catechin mixture and the reagents used in the ELISA test and the fluorescence emission efficiency obtained.
[0070] [表 7] カテキン混合物 固相用抗体 抗原(Cryj2) HRP—抗 Cryj2 蛍光発光率 [0070] [Table 7] Catechin mixture Solid phase antibody Antigen (Cryj2) HRP-anti-Cryj2 Fluorescence emission rate
(抗 Cryj2)濃度 抑制 (Anti-Cryj2) concentration suppression
;辰 ナ几体 ί辰度 (活性率) ; 辰 辰 体 ί 辰 度 (Activity)
(w/v°/o) (; U gZmL) kng/ mL) 効果 (w / v ° / o) (; U gZmL) kng / mL) Effect
(ng/mL) (%) 実施例 1 9 1 10 5 250 0 O 実施例 2 0 0.5 10 5 250 0 0 実施例 2 1 0.1 10 5 250 0 o 実施例 2 2 0.01 10 5 250 3 o 比較例 4 0 10 0 250 0 X 比較例 5 0 10 5 250 100 X
[0071] 実施例 23— (ng / mL) (%) Example 1 9 1 10 5 250 0 O Example 2 0 0.5 10 5 250 0 0 Example 2 1 0.1 10 5 250 0 o Example 2 2 0.01 10 5 250 3 o Comparative Example 4 0 10 0 250 0 X Comparative Example 5 0 10 5 250 100 X [0071] Example 23-
カテキン混合物に代えて、ェピガロカテキンガレート(EGCG)を用いた以外は、実 施例 19と同様にして、 ELISA試験を行い、蛍光発光率を求めた。 EGCG及び ELIS A試験に用いた試薬の濃度並びに求めた蛍光発光効率を、下記表 8に示す。 An ELISA test was conducted to determine the fluorescence emission rate in the same manner as in Example 19 except that epicarocatechin gallate (EGCG) was used instead of the catechin mixture. Table 8 below shows the concentrations of the reagents used in the EGCG and ELISA tests and the obtained fluorescence emission efficiency.
[0072] 一実施例 24〜26— [Example] 24-26-
EGCG濃度を、下記表 8に示す濃度とした以外は、実施例 23と同様にして、 ELIS A試験を行い、蛍光発光率を求めた。その結果を、下記表 8に併せて示す。 An ELISA test was performed in the same manner as in Example 23 except that the EGCG concentration was changed to the concentration shown in Table 8 below, and the fluorescence emission rate was determined. The results are also shown in Table 8 below.
[0073] [表 8] [0073] [Table 8]
[0074] 実施例 27— [0074] Example 27-
カテキン混合物に代えて、タンニン酸を用いた以外は、実施例 19と同様にして、 E LISA試験を行い、蛍光発光率を求めた。タンニン酸及び ELISA試験に用いた試薬 の濃度並びに求めた蛍光発光効率を、下記表 9に示す。 An ELISA test was conducted in the same manner as in Example 19 except that tannic acid was used in place of the catechin mixture, and the fluorescence emission rate was determined. Table 9 below shows the concentrations of the tannic acid and the reagents used in the ELISA test and the obtained fluorescence emission efficiency.
[0075] 実施例 28〜30— [0075] Examples 28-30-
EGCG濃度を、下記表 9に示す濃度とした以外は、実施例 27と同様にして、 ELIS A試験を行い、蛍光発光率を求めた。その結果を、下記表 9に併せて示す。 An ELISA test was performed in the same manner as in Example 27 except that the EGCG concentration was changed to the concentration shown in Table 9 below, and the fluorescence emission rate was obtained. The results are also shown in Table 9 below.
[0076] [表 9]
タンニン酸 固相用抗体 抗原(Cryj2) H P-¾Cryj2 蛍光発光率 [0076] [Table 9] Tannic acid Solid phase antibody Antigen (Cryj2) H P-¾Cryj2 Fluorescence emission rate
抑制 Suppression
'展度 (抗 Cryj2)濃度 ミ辰度 1·几体 i展度 (活性率) 'Degree of spread (anti-Cryj2) concentration level 1 · Body i level of spread (activity)
(w/v%) ( // g/mL) tng/mし) (ng/ mL) 効果 (w / v%) (// g / mL) tng / m) (ng / mL) Effect
(%) 実施例 2 7 1 10 5 250 0 〇 実施例 2 8 0.5 10 5 250 0 〇 実施例 2 9 0.1 10 5 250 0 0 実施例 3 0 0.01 10 5 250 31 〇 比較例 4 0 10 0 250 0 X 比較例 5 0 10 5 250 100 X (%) Example 2 7 1 10 5 250 0 ○ Example 2 8 0.5 10 5 250 0 ○ Example 2 9 0.1 10 5 250 0 0 Example 3 0 0.01 10 5 250 31 ○ Comparative example 4 0 10 0 250 0 X Comparative Example 5 0 10 5 250 100 X
[0077] 実施例 31 - スギ花粉に、カテキン混合物の 0. 1 %BSA含有 Pollen-Sorting Bufferと抗 Cryj l 抗体との混合物を添加した後、抗体を認識する蛍光標識抗体 (FITCラベル抗体)と して、 FITCラベル抗マウス IgG抗体を添加して、 488nmのアルゴンレーザーを照射 し、蛍光波長: 525nm (励起波長: 495nm)における蛍光強度を測定し、蛍光発光 率を求めた。カテキン混合物及びフローサイトメトリー試験に用いた試薬の濃度並び に求めた蛍光発光効率を、下記表 10に示す。 Example 31-After adding a mixture of 0.1% BSA-containing Pollen-Sorting Buffer of catechin mixture and anti-Cryj l antibody to cedar pollen, a fluorescently labeled antibody (FITC-labeled antibody) that recognizes the antibody and Then, a FITC-labeled anti-mouse IgG antibody was added, irradiated with a 488 nm argon laser, the fluorescence intensity at a fluorescence wavelength: 525 nm (excitation wavelength: 495 nm) was measured, and the fluorescence emission rate was determined. Table 10 below shows the concentration of the reagents used in the catechin mixture and the flow cytometry test, and the fluorescence emission efficiency obtained.
[0078] 一実施例 32— [0078] One Example 32—
カテキン混合物の濃度を、下記表 10に示す濃度とした以外は、実施例 31と同様に して、フローサイトメトリー試験を行レ、、蛍光発光率を求めた。その結果を、下記表 10 に併せて示す。 Except that the concentration of the catechin mixture was changed to the concentration shown in Table 10 below, a flow cytometry test was conducted in the same manner as in Example 31 to obtain the fluorescence emission rate. The results are also shown in Table 10 below.
[0079] 比較例 6— [0079] Comparative Example 6—
スギ花粉に、バッファ溶液を添加した後、抗体を認識する蛍光標識抗体 (FITCラベ ル抗体)として、 FITCラベル抗マウス IgG抗体を添加して、 488nmのアルゴンレーザ 一を照射し、蛍光波長: 525nm (励起波長: 495nm)における蛍光強度を測定し、蛍 光発光率を求めた。フローサイトメトリー試験に用いた試薬の濃度並びに求めた蛍光 発光効率を、下記表 10に示す。 After adding a buffer solution to the cedar pollen, add a FITC-labeled anti-mouse IgG antibody as a fluorescent-labeled antibody that recognizes the antibody (FITC-labeled antibody), irradiate it with an argon laser of 488 nm, and emit a fluorescence wavelength of 525 nm The fluorescence intensity at (excitation wavelength: 495 nm) was measured, and the fluorescence emission rate was determined. Table 10 below shows the concentration of the reagents used in the flow cytometry test and the fluorescence emission efficiency obtained.
[0080] 比較例 7- スギ花粉に、抗 Cryj l抗体を添加した後、抗体を認識する蛍光標識抗体 (FITCラ ベル抗体)として、 FITCラベル抗マウス IgG抗体を添加して、 525nmにおける蛍光 強度を測定し、蛍光発光率を求めた。フローサイトメトリー試験に用いた試薬の濃度
並びに求めた蛍光発光効率を、下記表 10に示す。 Comparative Example 7- After adding anti-Cryj l antibody to cedar pollen, FITC-labeled anti-mouse IgG antibody is added as a fluorescent-labeled antibody that recognizes the antibody (FITC-labeled antibody), and the fluorescence intensity at 525 nm Was measured, and the fluorescence emission rate was determined. Concentration of reagents used for flow cytometry test The obtained fluorescence efficiency is shown in Table 10 below.
[0081] 実施例 33, 34、比較例 8, 9— [0081] Examples 33, 34, Comparative Examples 8, 9—
抗 Cryj l抗体に代えて、抗 Cryj 2抗体を使用した以外は、実施例 31 , 32、比較例 6, 7と同様にして、フローサイトメトリー試験を行い、蛍光発光率を求めた。その結果 を、下記表 10に併せて示す。 A flow cytometry test was carried out in the same manner as in Examples 31 and 32 and Comparative Examples 6 and 7 except that an anti-Cryj 2 antibody was used in place of the anti-Cryj 1 antibody, and the fluorescence emission rate was determined. The results are also shown in Table 10 below.
[0082] 一実施例 35— [0082] Example 35—
カテキン混合物の濃度及びスギ花粉量を、下記表 10に示す濃度とした以外は、実 施例 31と同様にして、フローサイトメトリー試験を行レ、、蛍光発光率を求めた。その結 果を、下記表 10に併せて示す。 A flow cytometry test was carried out in the same manner as in Example 31 except that the concentration of catechin mixture and the amount of cedar pollen were changed to the concentrations shown in Table 10 below, and the fluorescence emission rate was determined. The results are also shown in Table 10 below.
[0083] 一比較例 10, 11 - スギ花粉量を、下記表 10に示す濃度とした以外は、比較例 6, 7と同様にして、フロ 一サイトメトリー試験を行レ、、蛍光発光率を求めた。その結果を、下記表 10に併せて 示す。 [0083] Comparative Example 10, 11-A flow cytometry test was conducted in the same manner as Comparative Examples 6 and 7 except that the amount of cedar pollen was changed to the concentration shown in Table 10 below. Asked. The results are also shown in Table 10 below.
[表 10] [Table 10]
上記表 1〜表 10の結果から明らかな如く、本発明に従うソフトコンタクトレンズ用溶 液において、アレルゲン失活成分として用いられるポリフエノールは、スギ花粉抗原 c ryj l及びスギ花粉のアレルゲンを効果的に失活せしめ、以て、そのような花粉等のァ
レルゲンが、レンズに付着した場合であっても、有利にそれを失活せしめ、以て、そ のようなアレルゲンによって惹起されるアレルギー症状を、効果的に低減化乃至は緩 和せしめることが可能となるのである。 As is clear from the results in Tables 1 to 10, in the soft contact lens solution according to the present invention, the polyphenol used as an allergen deactivating component effectively inhibits the cedar pollen antigen cryj l and the cedar pollen allergen. Inactivated, such pollen etc. Even if the allergen adheres to the lens, it can be advantageously deactivated, so that allergic symptoms caused by such allergen can be effectively reduced or mitigated. It becomes.
[0085] また、本発明で用いられるアレルゲン失活成分の放出試験を行レ、(実施例 36〜40 )、その結果を、下記表 11に示した。更に、アレルゲン失活成分としてのポリフエノー ノレによるレンズの着色性及びサイズ変化についての検討も併せて行った。 [0085] Further, a release test of allergen-inactivating components used in the present invention was conducted (Examples 36 to 40), and the results are shown in Table 11 below. Furthermore, the coloring property and size change of the lens by polyphenol as an allergen deactivating component were also examined.
[0086] 一実施例 36— [0086] One Example 36—
ヒドロキシル基を有する HEMA系イオン性高含水ソフトコンタクトレンズ (含水率: 5 5%)を、下記表 11に示す各種濃度のカテキン混合物の水溶液中に 16時間浸漬し た後、 0. 9重量%の生理食塩水に浸漬して、放出されるカテキン混合物の量を、経 時的に測定した。そして、得られた 4時間後の放出されたカテキン混合物の濃度及び 放出率を、下記表 11に併せて示す。また、各種濃度におけるカテキン混合物による レンズの着色性及びレンズのサイズ変化にっレ、ても、確認した。 After immersing a HEMA ionic high water content soft contact lens having a hydroxyl group (water content: 55%) in an aqueous solution of a catechin mixture having various concentrations shown in Table 11 below for 16 hours, 0.9% by weight The amount of the catechin mixture released by immersion in physiological saline was measured over time. Table 11 below shows the concentration and release rate of the catechin mixture released after 4 hours. In addition, the coloration of the lens and the size change of the lens by the catechin mixture at various concentrations were also confirmed.
[0087] 実施例 37— [0087] Example 37-
HEMA系イオン性高含水ソフトコンタクトレンズに代えて、 DMAA(N, N ジメチ ルアクリルアミド)系の非イオン性高含水ソフトコンタクトレンズ (含水率: 72%)を用い る以外は、実施例 36と同様にして、放出されるカテキン混合物の量を、経時的に測 定した。そして、得られた 4時間後の放出カテキン混合物の濃度及び放出率を、下記 表 11に併せて示す。また、各種濃度におけるカテキン混合物によるレンズの着色性 及びレンズのサイズ変化にっレ、ても、確認した。 Example 36 except that a DMAA (N, N dimethylacrylamide) non-ionic high water content soft contact lens (water content: 72%) was used instead of the HEMA type ionic high water content soft contact lens. Thus, the amount of catechin mixture released was measured over time. The concentration and release rate of the obtained catechin mixture after 4 hours are also shown in Table 11 below. In addition, the coloration of the lens by the catechin mixture at various concentrations and the size change of the lens were also confirmed.
[0088] 実施例 38— [0088] Example 38-
カテキン混合物の水溶液に代えて、ェピガロカテキンガレート(EGCG)水溶液を 用いる以外は、実施例 36と同様にして、放出される EGCG量を、経時的に測定した 。得られた 4時間後の放出 EGCG濃度及び放出率を、下記表 11に併せて示す。ま た、各種濃度における EGCGによるレンズの着色性及びレンズのサイズ変化につい ても、確認した。 The amount of EGCG released was measured over time in the same manner as in Example 36, except that an epigallocatechin gallate (EGCG) aqueous solution was used instead of the aqueous solution of the catechin mixture. The obtained release EGCG concentration and release rate after 4 hours are also shown in Table 11 below. In addition, the colorability of the lens by EGCG at various concentrations and the change in lens size were also confirmed.
[0089] 一実施例 39— [0089] One Example 39—
HEMA系イオン性高含水ソフトコンタクトレンズに代えて、 DMAA (N, N—ジメ
チルアクリルアミド)系の非イオン性高含水ソフトコンタクトレンズ (含水率:72%)を用 いる以外は、実施例 38と同様にして、放出される EGCG量を、経時的に測定した。そ して、得られた 4時間後の放出 EGCG濃度及び放出率を、下記表 11に併せて示す。 また、各種濃度における EGCGによるレンズの着色性及びレンズのサイズ変化につ いても、確認した。 Instead of HEMA ionic high water content soft contact lenses, DMAA (N, N—dimethyl Chill acrylamide) based nonionic high water content soft contact lenses (water content: 7, except that there use 2%), in the same manner as in Example 38, the EGCG amount emitted was measured over time. The obtained release EGCG concentration and release rate after 4 hours are also shown in Table 11 below. In addition, the colorability of the lens by EGCG at various concentrations and the change in lens size were also confirmed.
[0090] 一実施例 40— [0090] One Example 40—
HEMA系イオン性高含水ソフトコンタクトレンズに代えて、シリコン成分を有するシリ コンノヽイド口ゲルソフトコンタクトレンズ (含水率:24%)を用いる以外は、実施例 38と 同様にして、放出される EGCG量を、経時的に測定した。そして、得られた 4時間後 の放出 EGCG濃度及び放出率を、下記表 11に併せて示す。また、各種濃度におけ る EGCGによるレンズの着色性及びレンズのサイズ変化にっレ、ても、確認した。 EGCG released in the same manner as in Example 38, except that a silicone nano-mouth gel soft contact lens having a silicon component (water content: 24%) was used instead of the HEMA ionic high water content soft contact lens. The amount was measured over time. The obtained release EGCG concentration and release rate after 4 hours are also shown in Table 11 below. We also confirmed the coloration of the lens by EGCG and the size change of the lens at various concentrations.
[0091] [表 11] [0091] [Table 11]
上記表 11の結果から明らかな如 何れのソフトコンタクトレンズにあっても、ポリフ ェノールが有効に保持され、そして経時的に漸次放出されるものであることが認めら れたが、その中でも、特に、イオン性ソフトコンタクトレンズは、非イオン性ソフトコンタ クトレンズに比べて、 4時間後の放出ポリフエノール濃度(放出率)が高ぐポリフエノ
一ルの徐放が、より長い時間に亘つて行われることが分かった。また、ポリフエノール としては、ェピガロカテキンガレート(EGCG)を用いた場合に、有利に、長時間に亘 る徐放が行われることが分かった。 In any of the soft contact lenses apparent from the results in Table 11 above, it was found that the polyphenol was effectively retained and gradually released over time. Compared with non-ionic soft contact lenses, ionic soft contact lenses have a higher polyphenol concentration (release rate) after 4 hours. It has been found that a sustained release of 1 liter takes place over a longer period of time. Further, it was found that when epicarocatechin gallate (EGCG) is used as polyphenol, sustained release over a long period of time is advantageously performed.
[0093] また、ポリフエノールによるレンズの着色性については、 HEMA系イオン性高含水 ソフトコンタクトレンズにおいては、ポリフエノール濃度が 0. 5%以上で黄緑色に呈色 する力 透明性は高いことが認められた。一方、 DMAA系非イオン性高含水ソフトコ ンタクトレンズにおいては、ポリフエノール濃度が 0. 5%以上で茶褐色(喑色)に呈色 することが認められた。 [0093] Regarding the colorability of the lens with polyphenol, in the HEMA-based ionic high water content soft contact lens, the power to develop a yellow-green color when the polyphenol concentration is 0.5% or more is highly transparent. Admitted. On the other hand, in the DMAA non-ionic high water content soft contact lens, it was observed that the polyphenol concentration was 0.5% or more and the color turned brown (dark blue).
[0094] さらに、ポリフエノールによるレンズのサイズ変化については、 HEMA系イオン性高 含水ソフトコンタクトレンズにおいては、高いポリフエノール濃度においても、レンズの サイズ変化は認められなかった。一方、 DMAA系非イオン性高含水ソフトコンタクト レンズにおいては、ポリフヱノール濃度が 0. 1 %以上でレンズサイズが小さくなり、ポ リフエノール濃度が 0. 5%以上では約 2割程度のレンズサイズの縮小が認められた。
[0094] Further, regarding the lens size change due to polyphenol, in the HEMA ionic high water content soft contact lens, no lens size change was observed even at a high polyphenol concentration. On the other hand, in the case of DMAA non-ionic high water content soft contact lenses, the lens size decreases when the polyphenol concentration is 0.1% or more, and the lens size decreases by about 20% when the polyphenol concentration is 0.5% or more. Admitted.
Claims
[1] アレルゲン失活成分として、ポリフヱノールを、水性媒体中に含有せしめてなること を特徴とするソフトコンタクトレンズ用溶液。 [1] A solution for soft contact lenses, comprising polyphenol as an allergen deactivating component in an aqueous medium.
[2] 前記ポリフヱノールが、カテキン類又はタンニン酸であることを特徴とする請求項 1 に記載のソフトコンタクトレンズ用溶液。 2. The soft contact lens solution according to claim 1, wherein the polyphenol is catechins or tannic acid.
[3] 前記ポリフヱノールの含有量力 0. 001〜10%であることを特徴とする請求項 1又 は請求項 2に記載のソフトコンタクトレンズ用溶液。 [3] The soft contact lens solution according to [1] or [2], wherein the polyphenol content power is 0.001 to 10%.
[4] 前記ソフトコンタクトレンズ力 イオン性ソフトコンタクトレンズであることを特徴とする 請求項 1乃至請求項 3の何れか一つに記載のソフトコンタクトレンズ用溶液。 [4] The soft contact lens solution according to any one of claims 1 to 3, wherein the soft contact lens force is an ionic soft contact lens.
[5] マルチパーパスソリューション、保存液又は流通保存液として、用いられることを特 徴とする請求項 1乃至請求項 4の何れか一つに記載のソフトコンタクトレンズ用溶液。 [5] The soft contact lens solution according to any one of claims 1 to 4, wherein the soft contact lens solution is used as a multipurpose solution, a preservation solution, or a distribution preservation solution.
[6] 薬剤徐放可能なソフトコンタクトレンズを製造する方法にして、 [6] A method for producing a soft contact lens capable of sustained drug release,
a)アレルゲン失活成分としてポリフエノールを含有する水性液剤を準備する工程と b)該水性液剤にソフトコンタクトレンズを接触せしめ、該ソフトコンタクトレンズ中 に、前記アレルゲン失活成分を取り込ませる工程とを、 a) preparing an aqueous solution containing polyphenol as an allergen deactivating component; and b) bringing a soft contact lens into contact with the aqueous solution and incorporating the allergen deactivating component into the soft contact lens. ,
含むことを特徴とする製造方法。 A manufacturing method comprising:
[7] 前記ポリフエノールカ カテキン類又はタンニン酸であることを特徴とする請求項 6 に記載の薬剤徐放可能なソフトコンタクトレンズの製造方法。 [7] The method for producing a soft contact lens capable of sustained drug release according to [6], which is the polyphenolcatechin or tannic acid.
[8] 前記ポリフエノールの含有量力 0. 001〜10%であることを特徴とする請求項 6又 は請求項 7に記載の薬剤徐放可能なソフトコンタクトレンズの製造方法。 [8] The method for producing a soft contact lens capable of sustained drug release as described in [6] or [7], wherein the polyphenol content power is 0.001 to 10%.
[9] 前記ソフトコンタクトレンズ力 イオン性ソフトコンタクトレンズであることを特徴とする 請求項 6乃至請求項 8の何れか一つに記載の薬剤徐放可能なソフトコンタクトレンズ の製造方法。 [9] The method for producing a soft contact lens capable of sustained drug release according to any one of [6] to [8], wherein the soft contact lens force is an ionic soft contact lens.
[10] 請求項 6乃至請求項 9の何れか一つに記載の製造方法によって製造された、ソフト コンタクトレンズ内にアレルゲン失活成分としてのポリフエノールが含侵せしめられて レ、ることを特徴とする薬剤徐放性ソフトコンタクトレンズ。
[10] The soft contact lens produced by the production method according to any one of claims 6 to 9 is impregnated with polyphenol as an allergen deactivating component. The drug sustained release soft contact lens.
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JP2008513120A JPWO2007125731A1 (en) | 2006-04-28 | 2007-04-03 | Soft contact lens solution, drug sustained release soft contact lens obtained using the same, and method for producing the same |
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Cited By (6)
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WO2012029160A1 (en) * | 2010-09-02 | 2012-03-08 | 株式会社メニコン | Stabilized polyphenol solution and method for stabilizing polyphenol solution |
WO2012172274A1 (en) * | 2011-06-13 | 2012-12-20 | Altacor Limited | Ophthalmic compositions |
JP5140757B2 (en) * | 2009-02-20 | 2013-02-13 | 株式会社シード | Drug sustained release hydrogel contact lens and drug release method using drug sustained release hydrogel contact lens |
JP2014032405A (en) * | 2012-07-31 | 2014-02-20 | Johnson & Johnson Vision Care Inc | Inversion marking for contact lenses |
JP2021532079A (en) * | 2018-07-12 | 2021-11-25 | オキュソフト インコーポレイテッドOCuSOFT, Inc. | Eye anti-allergic composition and eyelid cleansing wipe |
JP2022071097A (en) * | 2014-07-24 | 2022-05-13 | 株式会社プロテクティア | Allergen activity inhibitor and applications thereof |
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WO2002060495A1 (en) * | 2001-01-09 | 2002-08-08 | Louis Johan Wagenaar | Procedure and composition of treatment and/or care of the eye |
JP2003081840A (en) * | 2001-07-04 | 2003-03-19 | Rohto Pharmaceut Co Ltd | Refreshing method, refreshing preparation and composition for external use |
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IL154144A0 (en) * | 2000-07-28 | 2003-07-31 | Immupharm Aps | Method of treating symptoms of common cold, allergic rhinitis and infections relating to the respiratory tract |
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2007
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Patent Citations (2)
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WO2002060495A1 (en) * | 2001-01-09 | 2002-08-08 | Louis Johan Wagenaar | Procedure and composition of treatment and/or care of the eye |
JP2003081840A (en) * | 2001-07-04 | 2003-03-19 | Rohto Pharmaceut Co Ltd | Refreshing method, refreshing preparation and composition for external use |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP5140757B2 (en) * | 2009-02-20 | 2013-02-13 | 株式会社シード | Drug sustained release hydrogel contact lens and drug release method using drug sustained release hydrogel contact lens |
WO2012029160A1 (en) * | 2010-09-02 | 2012-03-08 | 株式会社メニコン | Stabilized polyphenol solution and method for stabilizing polyphenol solution |
JPWO2012029160A1 (en) * | 2010-09-02 | 2013-10-28 | 株式会社メニコン | Stabilized polyphenol solution and method for stabilizing polyphenol solution |
WO2012172274A1 (en) * | 2011-06-13 | 2012-12-20 | Altacor Limited | Ophthalmic compositions |
US9931428B2 (en) | 2011-06-13 | 2018-04-03 | Oraldent Limited | Ophthalmic compositions |
JP2014032405A (en) * | 2012-07-31 | 2014-02-20 | Johnson & Johnson Vision Care Inc | Inversion marking for contact lenses |
JP2022071097A (en) * | 2014-07-24 | 2022-05-13 | 株式会社プロテクティア | Allergen activity inhibitor and applications thereof |
JP7419416B2 (en) | 2014-07-24 | 2024-01-22 | 株式会社プロテクティア | Allergen activity inhibitors and their uses |
JP2021532079A (en) * | 2018-07-12 | 2021-11-25 | オキュソフト インコーポレイテッドOCuSOFT, Inc. | Eye anti-allergic composition and eyelid cleansing wipe |
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