JP2008139895A - Transport and storage liquid for contact lens and transport and storage method for contact lens using same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a transport and storage liquid for a contact lens capable of significantly reducing changes in the base curve of a lens during wet transport and storage of a contact lens, and to provide a transport and storage method using the liquid. <P>SOLUTION: The transport and storage liquid for a contact lens contains polyvinylpyrrolidone having a weight average molecular weight of 500 to 200,000 and containing no surfactant. The transport and storage method for a contact lens features immersing a contact lens in the above transport and storage liquid for a contact lens. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a distribution storage solution for contact lenses and a distribution storage method for contact lenses using the same.

  In general, contact lenses, especially oxygen-permeable hard contact lenses, mostly contain a silicone component, so that the lens surface becomes hydrophobic and the wettability during initial wearing is disturbed. Problems such as reduction or insufficient visual acuity are likely to occur.

  Therefore, the oxygen-permeable hard contact lens is subjected to surface treatment or pre-saved storage solution such as physiological saline in order to maintain the surface water wettability from the time of manufacture until the patient wears it. It is wet-stored and distributed for example by being immersed in

  However, when such wet storage and circulation using physiological saline is performed, there is a problem that the base curve, which is one of the important standards of contact lenses, may change during the distribution process. is there.

  In addition, since many of the conventional circulation preservation solutions usually contain a surfactant, there is a problem that the size change such as the base curve change of the contact lens is likely to occur.

  The present invention has been made in view of the above prior art, and a distribution storage solution capable of remarkably reducing the change in the base curve during wet storage distribution of contact lenses, particularly oxygen-permeable hard contact lenses, and a An object of the present invention is to provide a method for distributing and storing used contact lenses.

  The present invention comprises (1) a distribution storage solution for contact lenses that contains polyvinylpyrrolidone having a weight average molecular weight of 500 to 200,000 and does not contain a surfactant, and (2) a weight average molecular weight of 500 to 200,000. Polyvinylpyrrolidone having a K value of 20 to 100, 0.2 to 3 w / v%, polyhexamethylene biguanide 0.000005 to 0.0002 w / v%, and ethylenediaminetetraacetic acid or ethylenediaminetetraacetic acid sodium salt or ethylenediaminetetraacetic acid sodium salt A contact lens circulation storage solution containing 0.02 to 0.3 w / v% hydrate and not containing a surfactant, and (3) a contact lens immersed in each of the contact lens circulation storage solutions The present invention relates to a distribution and storage method for contact lenses.

  The storage solution for contact lenses of the present invention is excellent in solubility and appearance, and has almost no odor. Using such a storage solution for contact lenses, wet storage and distribution of contact lenses, particularly oxygen-permeable hard contact lenses. As a result, the change in the base curve, which is one of the important standards for contact lenses, is greatly reduced.

  As described above, the distribution preservation solution for contact lenses of the present invention contains polyvinylpyrrolidone having a weight average molecular weight of 500 to 200,000 and does not contain a surfactant.

  In the circulation storage solution for contact lenses of the present invention, polyvinylpyrrolidone is used as an active ingredient for reducing the change in the base curve of the contact lens during the circulation during wet storage.

  The weight average molecular weight of polyvinyl pyrrolidone is 500 or more, preferably 1000 or more, considering that a certain degree of molecular weight is necessary to sufficiently obtain the effect of stabilizing the base curve of the contact lens. Considering the possibility that the solubility in the medium will be lowered and it may be difficult to obtain a uniform contact lens stock solution, and the problem of handling properties due to an increase in viscosity, etc., it is 200000 or less, preferably 150,000 or less.

  The K value of polyvinylpyrrolidone (described in the Japanese Pharmacopoeia) is desirably 20 or more, preferably 25 or more in order to sufficiently obtain the effect of stabilizing the base curve of the contact lens. Considering that the solubility with respect to water may be reduced, and it may be difficult to obtain a uniform storage solution for contact lenses, and handling problems due to an increase in viscosity may be taken into account. desirable. Examples of the polyvinyl pyrrolidone having a K value in such a range include polyvinyl pyrrolidone K25, polyvinyl pyrrolidone K30, and polyvinyl pyrrolidone K90.

  The content of the polyvinyl pyrrolidone in the distribution storage solution for contact lenses is set to be 0.1% in order to sufficiently exhibit the effect of reducing the change in the base curve of the contact lens during wet storage distribution by using such polyvinyl pyrrolidone. 1w / v% or more, preferably 0.2w / v% or more, and there is a problem in handling such that the contact lens circulation stock solution is too high in viscosity and the contact lens is likely to become dirty during drying. In order to eliminate the possibility of occurrence, it is desirable that the amount be 10 w / v% or less, preferably 3 w / v% or less.

  In addition to the polyvinyl pyrrolidone, it is preferable that the circulation preservation solution for contact lenses of the present invention contains, for example, a preservative and a chelating agent.

  The preservative has the property of preventing contact circulation solution for contact lenses from being contaminated by bacteria and preventing contact lenses from being contaminated by various bacteria during distribution storage.

  The preservative is not particularly limited as long as it is ophthalmologically acceptable, and examples thereof include compounds containing at least one of a quaternary ammonium group, a biguanide group and a quaternary phosphonium group. As typical examples of such compounds and other examples, for example, the general formula (I):

（式中、Ｚはたとえば炭素数２〜１８のポリオキシアルキレン基などの２価の有機基、ｆは３以上の整数を示す（ただし、Ｚはポリマー全体で同一であってもよく、異なっていてもよい））で表わされる繰り返し単位を有するポリマー（Ｉ）、式（II）：

(In the formula, Z represents a divalent organic group such as a polyoxyalkylene group having 2 to 18 carbon atoms, and f represents an integer of 3 or more (provided that Z may be the same or different in the whole polymer). The polymer (I) having a repeating unit represented by formula (II):

で表わされる繰り返し単位を有するポリマー（II）、一般式（III）：

Polymer (II) having a repeating unit represented by formula (III):

（式中、Ｒ¹は水素原子またはメチル基、Ｒ²は炭素数１〜８のアルキレン基、Ｒ³は炭素数１〜１８のアルキル基、Ｘ¹はたとえば塩素原子、臭素原子、ヨウ素原子などのハロゲン原子を示す）で表わされる繰り返し単位を有するポリマー（III）、一般式（IV）：

(Wherein R ¹ is a hydrogen atom or a methyl group, R ² is an alkylene group having 1 to 8 carbon atoms, R ³ is an alkyl group having 1 to 18 carbon atoms, X ¹ is, for example, a chlorine atom, a bromine atom, an iodine atom, etc. A polymer (III) having a repeating unit represented by the general formula (IV):

（式中、Ｒ⁴は水素原子またはメチル基、Ｒ⁵は炭素数１〜８のアルキレン基、Ｒ⁶は炭素数１〜１８のアルキル基、Ｘ²はたとえば塩素原子、臭素原子、ヨウ素原子などのハロゲン原子を示す）で表わされる繰り返し単位を有するポリマー（IV）などの化合物；硝酸フェニル水銀、酢酸フェニル水銀、チメロサールなどの水銀系防腐剤；塩化ベンザルコニウム、臭化ピリジニウムなどの界面活性剤系防腐剤；クロロヘキシジン、ポリヘキサメチレンビグアニド、クロロブタノールなどのアルコール系防腐剤；メチルパラベン、プロピルパラベン、ジメチロールジメチルヒダントイン、イミダゾリウムウレアなどのほか、たとえば一般式（Ｖ）：

(Wherein R ⁴ is a hydrogen atom or a methyl group, R ⁵ is an alkylene group having 1 to 8 carbon atoms, R ⁶ is an alkyl group having 1 to 18 carbon atoms, X ² is, for example, a chlorine atom, a bromine atom, an iodine atom, etc. A compound having a repeating unit represented by (IV), a mercury-based preservative such as phenylmercuric nitrate, phenylmercuric acetate, and thimerosal; a surfactant such as benzalkonium chloride and pyridinium bromide Preservatives: alcohol preservatives such as chlorohexidine, polyhexamethylene biguanide, chlorobutanol; methylparaben, propylparaben, dimethyloldimethylhydantoin, imidazolium urea, etc., for example, general formula (V):

（式中、Ｒ¹は水素原子またはメチル基、Ｒ²は炭素数１〜８のアルキレン基、Ｒ³は炭素数１〜１８のアルキル基、Ｘ¹はたとえば塩素原子、臭素原子、ヨウ素原子などのハロゲン原子を示す）で表わされるモノマー（Ｖ）、一般式（VI）：

(Wherein R ¹ is a hydrogen atom or a methyl group, R ² is an alkylene group having 1 to 8 carbon atoms, R ³ is an alkyl group having 1 to 18 carbon atoms, X ¹ is, for example, a chlorine atom, a bromine atom, an iodine atom, etc. Monomer (V) represented by the general formula (VI):

（式中、Ｒ⁴は水素原子またはメチル基、Ｒ⁵は炭素数１〜８のアルキレン基、Ｒ⁶は炭素数１〜１８のアルキル基、Ｘ²はたとえば塩素原子、臭素原子、ヨウ素原子などのハロゲン原子を示す）で表わされるモノマー（VI）などと、たとえばヒドロキシメチル（メタ）アクリレート、ヒドロキシエチル（メタ）アクリレート、ヒドロキシプロピル（メタ）アクリレート、ヒドロキシブチル（メタ）アクリレートなどのヒドロキシアルキル（メタ）アクリレートなどの水溶性モノマーとの共重合体などがあげられる。

(Wherein R ⁴ is a hydrogen atom or a methyl group, R ⁵ is an alkylene group having 1 to 8 carbon atoms, R ⁶ is an alkyl group having 1 to 18 carbon atoms, X ² is, for example, a chlorine atom, a bromine atom, an iodine atom, etc. And a monomer (VI) represented by a hydroxyalkyl (meta) such as hydroxymethyl (meth) acrylate, hydroxyethyl (meth) acrylate, hydroxypropyl (meth) acrylate, hydroxybutyl (meth) acrylate, etc. ) Copolymers with water-soluble monomers such as acrylates.

  Furthermore, since various known forms of biguanide derivatives are commercially available, in the present invention, they can be appropriately selected from such commercially available products and used as preservatives.

  Among the preservatives, at least one selected from the polymer (I), the polymer (II), the polymer (III) and the polymer (IV) from the viewpoint that the effect of preventing contamination by bacteria and various bacteria is more effective. Particularly preferred are seed compounds, polyhexamethylene biguanide, and monomers (V) or copolymers of monomer (VI) and water-soluble monomers.

  The content of the preservative in the distribution preservation solution for contact lenses is 0.000005 w / v% (0.05 ppm) or more, preferably 0.00005 w / v% (0) in order to develop a sufficient antiseptic effect. 0.5 ppm) or more, and if the content of such a preservative is too high, it may cause eye damage if such preservative enters directly into the eyes. Depending on the type of preservative, there is a tendency to adversely affect the specifications and properties of the contact lens, so that 0.5 w / v% (5000 ppm) or less, preferably 0.0005 w / v% (5 ppm) In the following, it is more preferable that it is 0.0002 w / v% (2 ppm) or less.

  The chelating agent has a property of preventing calcium contained in a contact lens circulation preservation solution or adhering tears from being deposited on the contact lens.

  The chelating agent is not particularly limited as long as it is ophthalmologically acceptable, and representative examples thereof include ethylenediamine tetraacetate such as ethylenediaminetetraacetic acid and its sodium salt, and the ethylenediaminetetraacetate. Hydrate of: phytic acid, citric acid and the like. Among these, ethylenediaminetetraacetic acid, ethylenediaminetetraacetate, and ethylenediaminetetraacetate hydrate are particularly preferred because the effect of preventing calcium deposition is greater and more effective.

  The content of the chelating agent in the contact lens circulation preservation solution is 0.01 w / v% or more, preferably 0. 0%, in order to sufficiently exhibit the effect of preventing calcium and the like from being deposited on the contact lens. It is desirable that the content is not less than 02 w / v%, and when the content of such a chelating agent is too large, the improvement in the effect due to the addition of more than this is small, which is uneconomical. It is desirable that it is v% or less, preferably 0.3 w / v% or less.

  Furthermore, in addition to the preservatives and chelating agents, the contact lens circulation preservation solution of the present invention may contain compounding agents such as buffering agents and tonicity agents.

  The buffering agent makes the pH of the obtained contact lens circulation preservation solution constant within a range of about 5 to 9 close to tears, suppresses changes in pH due to external factors, and the shape of the contact lens during circulation storage It has the property of protecting optical properties.

  The buffer is not particularly limited as long as it is ophthalmologically acceptable, and typical examples thereof include boric acid and its sodium salt, phosphoric acid and its sodium salt, citric acid and its sodium salt, and the like. And amino acids such as lactic acid and its sodium salt, glycine and glutamic acid and its sodium salt, and malic acid and its sodium salt.

  The content of the buffering agent in the flow preservation solution for contact lenses is 0.005 mol / liter or more, preferably 0.01 mol / liter or more in order to give a sufficient buffering effect, Further, when the content of such a buffering agent is too large, the buffering effect is not so high, and tends to affect the shape of the contact lens, such as increasing the osmotic pressure. It is desirable that it is not more than liter, preferably not more than 0.15 mol / liter.

  The isotonic agent brings the osmotic pressure of the obtained circulation preservation solution for contact lenses close to the osmotic pressure of tears (280 to 300 mOs / kg) so that the shape of the contact lens can be more easily maintained during circulation preservation. It has the property of making.

  The isotonic agent is not particularly limited as long as it is ophthalmologically physiologically acceptable, and typical examples thereof include inorganic salts such as sodium chloride, potassium chloride, calcium chloride, and the aforementioned buffering agents. It is done.

  The content of the isotonic agent in the preserving fluid for contact lenses is 0.01 mol / liter or more, preferably 0.05 mol / liter or more, in order to give a sufficient osmotic pressure. Desirably, if the content of such an isotonic agent is too large, the osmotic pressure tends to increase and the shape of the contact lens tends to be affected. Is preferably 0.15 mol / liter or less.

  The preservatives, chelating agents, buffering agents and tonicity agents can be used alone or in admixture of two or more.

  As described above, the distribution preservation solution for contact lenses of the present invention contains polyvinylpyrrolidone having a specific weight average molecular weight as an active ingredient, and further, if necessary, preservatives, chelating agents, other compounding agents, etc. However, as these media, for example, water such as distilled water or purified water may be blended. In addition, what is necessary is just to use such aqueous media, such as water, so that the whole quantity of the distribution | circulation preservation | save liquid for contact lenses may be 100%.

  For example, polyvinyl pyrrolidone is put in a predetermined amount of an aqueous medium, and a preservative, a chelating agent, a buffering agent, an isotonic agent and the like are added as necessary. It can be prepared by mixing and stirring well to dissolve and filtering.

  The viscosity of the contact lens circulation preservation solution of the present invention is not particularly limited, but it is preferably about 200 cP or less at 25 ° C. in consideration of handling properties when the contact lens is distributed and preserved.

  Further, the pH of the circulation preservation solution for contact lenses is preferably 5 to 9, which is about the same as that of tears, and there is almost no possibility that such circulation preservation solution is directly applied to the eyes. In view of the case where it is worn on the surface, it is more preferably 6.6 to 7.6.

  Among the distribution preservation solutions for contact lenses of the present invention, 0.2 to 3 w / v% of polyvinylpyrrolidone having a weight average molecular weight of 500 to 200,000 and a K value of 20 to 100, polyhexamethylene biguanide 0. Containing 0.0005 to 0.0002 w / v% (0.05 to 2 ppm) and 0.02 to 0.3 w / v% hydrate of ethylenediaminetetraacetic acid or ethylenediaminetetraacetic acid sodium salt or ethylenediaminetetraacetic acid sodium salt A distribution storage solution that does not contain a surfactant is particularly preferred because it has a greater effect of reducing changes in the base curve during wet storage distribution of contact lenses.

  By immersing the contact lens in the contact lens circulation storage solution of the present invention thus obtained, various contact lenses can be distributed and stored with almost no change in the base curve thereof.

  In the method for storing and storing contact lenses according to the present invention, for example, a contact container and an amount of the contact lens storing solution that can be immersed in the contact lens are placed in a predetermined container and sealed. Save it.

  In addition, the contact lens used in the distribution storage method of the present invention is not particularly limited, and any type of water can be applied regardless of whether it is hydrous, non-hydrous, soft, or hard. For example, oxygen-permeable hard contact lenses obtained by polymerizing polymerization components containing silicone compounds such as siloxanyl (meth) acrylate monomers, siloxanyl styrene monomers, siloxanyl fumarate, siloxanyl itaconate, etc. Even in this case, the change in the base curve is greatly reduced during wet storage distribution.

  Next, the distribution storage solution for contact lenses of the present invention and the distribution storage method of contact lenses using the same will be described in more detail based on examples. However, the present invention is not limited only to such examples. .

Example 1
Polyvinylpyrrolidone K30 (weight average molecular weight: 45000, K value: 30), polyhexamethylene biguanide and ethylenediaminetetraacetic acid trisodium salt dihydrate were added to distilled water and stirred at room temperature for about 60 minutes. Was dissolved and further filtered to prepare 300 ml of a circulation preservation solution for contact lenses. The content of each component is as follows.

Polyvinylpyrrolidone K30: 1.0 w / v%
Polyhexamethylene biguanide: 1.0 ppm
Ethylenediaminetetraacetic acid trisodium salt dihydrate: 0.10 w / v%

Example 2
In Example 1, polyvinylpyrrolidone K90 (weight average molecular weight: 110000, K value: 90) was used instead of polyvinylpyrrolidone K30, the content of polyvinylpyrrolidone K90 was 0.5 w / v%, and the content of polyhexamethylene biguanide 300 ml of a contact lens circulation stock solution was prepared in the same manner as in Example 1 except that the amount was 0.5 ppm.

  The solubility, appearance, odor, pH and viscosity of the contact lens circulation preservation solutions obtained in Examples 1 and 2 were examined according to the following methods. The results are shown in Table 1.

(A) Solubility The presence or absence of insoluble matter in the circulation preservation solution for contact lenses was visually examined and evaluated based on the following evaluation criteria.

(Evaluation criteria)
A: There is no insoluble matter at all.
B: Slight insoluble matter is observed.
C: Insoluble matter is amazing.

(B) Appearance The appearance of the distribution preservation solution for contact lenses was visually observed and evaluated based on the following evaluation criteria.

(Evaluation criteria)
A: Uniform and transparent.
B: Slightly cloudy.
C: Cloudiness is remarkable.

(C) Odor From the distance of 5 cm, the odor of the circulation preservation solution for contact lenses was examined and evaluated based on the following evaluation criteria.

(Evaluation criteria)
A: There is no odor at all.
B: Slight odor is observed.
C: The odor is great.

(D) pH
The pH of the circulating storage solution for contact lenses at 25 ° C. was measured with a glass electrode type pH meter (HORIBA pH METER F-13, manufactured by Horiba, Ltd.).

(E) Viscosity Viscosity (cP) of a circulating storage solution for contact lenses at 25 ° C. was measured with a B-type viscometer.

  Next, a polymerization component consisting of 50 parts by weight of siloxanyl methacrylate, 40 parts by weight of trifluoroethyl methacrylate, 10 parts by weight of methyl methacrylate and 5 parts by weight of ethylene glycol dimethacrylate is copolymerized and molded to a thickness of 0.12 mm. An oxygen permeable hard contact lens was manufactured.

  Five pieces of this oxygen-permeable hard contact lens were prepared for each of the contact lens circulation storage solutions obtained in Examples 1 and 2, and the respective base curves were measured in advance.

  Next, the oxygen permeable hard contact lens and the contact lens distribution storage solution are placed in a contact lens distribution case, and the oxygen permeable hard contact lens is immersed in the contact lens distribution storage solution, sealed, and sealed at 40 ° C. Each base curve was measured after 2 weeks and 4 weeks.

  Calculate the amount of change in the base curve from the difference between the base curve after storage and the base curve measured in advance, calculate the average amount of change for the five contact lenses, and calculate the average value of the base curves for the five contact lenses before storage From this, the change rate (%) of the base curve was determined based on the following equation. The results are shown in Table 1.

Base curve change rate (%)
= {(Average change in base curve) / (average value of base curve before storage)} × 100

Comparative Example 1
The change rate of the base curve was determined in the same manner as in Examples 1 and 2 using physiological saline instead of the contact lens circulation preservation solution of Examples 1 and 2. The results are shown in Table 1.

  From the results shown in Table 1, each of the contact lens circulation preservation solutions obtained in Examples 1 and 2 has an appropriate pH and viscosity, excellent solubility and appearance, and has no odor. I know that there is.

  In addition, when the contact lens was stored using the contact lens circulation storage solution obtained in Examples 1 and 2, compared with the case of using the physiological saline of Comparative Example 1, when stored for 2 weeks Of course, it can be seen that the change rate of the base curve of the contact lens is extremely small even when stored for 4 weeks.

Claims (9)

Polyvinylpyrrolidone having a weight average molecular weight of 500 to 200,000 and a K value of 20 to 100, 0.05 to 5 ppm of polyhexamethylene biguanide or the general formula (V)

Wherein R ¹ is a hydrogen atom or a methyl group, R ² is an alkylene group having 1 to 8 carbon atoms, R ³ is an alkyl group having 1 to 18 carbon atoms, and X ¹ is a halogen atom. V) or general formula (VI):

Wherein R ⁴ is a hydrogen atom or a methyl group, R ⁵ is an alkylene group having 1 to 8 carbon atoms, R ⁶ is an alkyl group having 1 to 18 carbon atoms, and X ² is a halogen atom. A contact lens comprising a preservative that is a copolymer of VI) and a water-soluble monomer, and a chelating agent, and the contact lens is immersed in a distribution solution for contact lenses that does not contain an oxidizing agent and a surfactant. Distribution storage method. The method for distributing and storing contact lenses according to claim 1, wherein the contact lenses are oxygen-permeable hard contact lenses. The method for circulating and storing contact lenses according to claim 1 or 2, wherein the amount of the preservative is 0.05 to 2 ppm. The method for circulating and storing contact lenses according to claim 1 or 2, wherein the amount of polyvinylpyrrolidone is 0.2 to 3 w / v%. The osmotic pressure is 280 to 300 mOs / kg, and the contact lens circulation storage method according to any one of claims 1 to 4. The viscosity of the contact lens according to any one of claims 1 to 5, wherein the viscosity at 25 ° C is 200 cP or less. The method for circulating and storing a contact lens according to claim 1, wherein the chelating agent is ethylenediaminetetraacetic acid, ethylenediaminetetraacetate or ethylenediaminetetraacetate hydrate. The method for circulating and storing a contact lens according to any one of claims 1 to 7, wherein the amount of the chelating agent is 0.02 to 0.3 w / v%. The method for circulating and storing a contact lens according to any one of claims 1 to 8, wherein the pH is 6.6 to 7.6.