JP2687078B2 - Contact lens composed of polysaccharide matrix copolymer - Google Patents

Description

Description: BACKGROUND OF THE INVENTION The present invention relates to a cationic derivative of a polysaccharide (excluding dextran) which is matrix-polymerized with an unsaturated acid to produce a polymer useful as a biocompatible material. A polyion complex as a product is obtained, and a biocompatible material such as a contact lens is produced from a copolymer of the polyion complex and an olefin compound. BACKGROUND OF THE INVENTION Dextran, which is a type of polysaccharide, is a linear polysaccharide mainly produced by α (1 → 6) glucoside bonds with glucose as a repeating unit, which is produced by a bacterium of the genus Lactobacilluae. It is very soluble in water and is used as a plasma substitute. It is very stable in vivo and has very good biocompatibility because it is gradually degraded by enzymes in tissues . The cationic derivative of dextran is matrix-polymerized with an unsaturated acid to obtain a polyion complex, which is a polymerization product useful as a biocompatible material. Further, a copolymer of the polyion complex and an olefin compound is used to form a biomaterial such as a contact lens. Although the invention for producing an affinity material was made , similarly, an unsaturated acid is matrix-polymerized with a cationic derivative of a polysaccharide other than dextran to obtain a polyion complex which is a polymerization product useful as a biocompatible material, Further, they have found that a biocompatible material such as a contact lens is produced from a copolymer of this polyion complex and an olefin compound. [0003] Matrix polymerization is a polymerization method proposed by Cargin et al., And specifically, it is a hydrogen bond with a monomer or a growing chain, Coulomb force, charge transfer interaction, fan. Polymerization is carried out in the presence of a polymer, that is, a matrix, which interacts with the Delwars force, and the polymerization product exists as a complex of the polymerized monomer and the polymer to be the matrix. The polymer having such an intermolecular complex is a useful substance having a wide variety of uses. In particular, the interpolymer ion complex that forms a complex between polymers due to Coulomb force is drawing attention as a membrane or biomaterial. Especially, paying attention to its hydrophilicity, it can be applied to artificial kidney membranes, components, blood vessels substitutes, and contact lenses. DETAILED DESCRIPTION OF THE INVENTION The polysaccharide (excluding dextran) matrix copolymer of the present invention will be described in detail below. The polysaccharide (except dextran) matrix copolymer is obtained through the following two steps. I. The formula of the units of the cationic derivative of the modified polysaccharide (excluding dextran) of the matrix polymer is shown below. In addition to those in which the hydroxyl groups of the polysaccharides (excluding dextran) are partially substituted with an acid group such as a carboxymethyl group or a sulfate group by an ether bond, or partially substituted with an alkyl group in the above (formula 2) It may have a cationic functional group represented by X. As the unsaturated acid to be subjected to matrix polymerization, those represented by the following general formula can be considered. Embedded image Specifically, α, β unsaturated acids such as acrylic acid, methacrylic acid, crotonic acid, isocrotonic acid, α, β′-dimethylacrylic acid, angelic acid, tiglic acid, and maleic acid, fumaric acid. Unsaturated acids such as acids, citraconic acid, mesaconic acid, itaconic acid, aconitic acid, oleic acid are considered. The reaction is usually performed in an aqueous solution. That is, polysaccharides (excluding dextran
The above unsaturated acid is added to an aqueous solution of the cationic derivative of (i) and an initiator is added to react. As the initiator, a radical initiator such as potassium persulfate (KPS), azobisisobutylnitrile (AIBN), and benzoyl peroxide (BPO) is used. The reaction temperature can be widely selected from room temperature to 70 ° C. Polymer poly ions <br/> down complex produced in this reaction, water, alcohol, or acetone,
Since it is insoluble in organic solvents such as tetrahydrofuran, it is very inconvenient for forming a film or making a molded product. Therefore, as a result of various studies, it was discovered that the basic type of the cationic derivative of the polysaccharide (excluding dextran) was completely or partially dissolved in the unsaturated acid. For this reason, the basic type of the cationic derivatives of polysaccharides (excluding dextran) are dissolved in unsaturated acids, and
Matrix mass polymerization was possible using ordinary radical initiators such as N and BPO. The reaction temperature is 20 ° C
Various selections up to 70 ° C are possible. In addition, a cationic derivative of this polysaccharide (excluding dextran) dissolved in an unsaturated acid is mixed with another olefin compound to prepare a normal A
About 0.1% of the total amount of radical initiators such as IBN and BPO
-1.5% is used to start the polymerization, and the reaction temperature is 20-8.
It was discovered that it is possible to obtain a copolymer of this matrix polymer with another olefin compound, which is usually carried out in the range of 0 ° C., and the reaction is continued by substituting nitrogen if necessary. This copolymer has a more practical quality since the mechanical strength and the like are improved compared to the matrix polymer in the previous stage and various shapes such as rods or plates can be easily obtained. If necessary, after annealing at 80 to 100 ° C., it can be processed into various objects by cutting and polishing. Examples of this include artificial blood vessels, artificial bones, artificial kidneys, artificial corneas, dentures or denture bases, and in particular, this rod-shaped or plate-shaped matrix polymer having a distinctive characteristic of being transparent. Therefore, it is useful for contact lenses, intraocular lenses, and artificial lenses. II. Adjustment of the matrix copolymer For the above purpose, in the matrix polymer, the ratio of the matrix to the unsaturated acid or, when the matrix polymer is copolymerized with another olefin polymer, the ratio of the matrix polymer to the olefin polymer Can be selected variously according to the purpose. The olefin compound used here is, specifically, an alkyl ester of α, β-unsaturated acid such as acrylic acid or methacrylic acid, a lower alkyl-substituted cyclohexyl ester such as cyclohexyl ester, or 2 -Hydroxyethyl ester, 2-hydroxypropyl ester, 2-hydroxybutyl ester; acrylamide, methacrylamide, acrylamide, acryl- or methacryl-dimethylamide,
The alpha, beta-amino alkyl esters of C ₁ -C ₃ unsaturated acids, dialkylaminoalkyl esters of C ₁ -C _3, glycidyl ester, tetrahydrofurfuryl ester, benzyl ester, polyethylene glycol monoesters, acrylonitrile, methacryl Nitrile groups of α, β-unsaturated acids such as ronitrile; vinyl alcohol, methyl vinyl alcohol, dimethyl vinyl alcohol; vinyl alcohol such as vinyl acetate, vinyl propionate and vinyl butyrate, and C ₁ -of methyl substituted vinyl alcohol thereof. C ₃ alkyl ester; styrene;
Possible examples are vinyltoluene; vinylpyrrolidone; vinylmethylpyrrolidone. EXAMPLE 1 A 50% caustic soda solution was added to an aqueous solution of DEAE (diethylaminoethyl) pullulan hydrochloride having a nitrogen content of 5% and a pullulan having an average molecular weight Mw of 600,000 as a matrix, and a pH of 11.
10 g of base type DEAE pullulan that has precipitated above 0
Is dissolved in 20 ml of methacrylic acid, and this DEAE pullulan-methacrylic acid solution is further added with methyl methacrylate 45
Mix well with 0 ml, add 2.5 g of azobisisobutylnitrile (AIBN) as a polymerization initiator, diameter 15 mm
After being placed in a glass tube and thoroughly degassed, a polymerization reaction is carried out in a sealed tube at a reaction temperature of 50 ° C. and a polymerization time of 72 hours. Then, the mixture was heated in an air bath at 80 ° C. for 3 hours, cooled, the rod-shaped polymer was removed from the glass tube, and annealed in the air bath at 80 ° C. for 24 hours to obtain 469 g of a lump polymer. It was insoluble in water, methanol, and organic solvents such as acetone, n-hexane, and tetrahydrofuran. Vicat softening point 9
3 ° C (ASTM D1525), Rockwell hardness (M
Scale) 85 (ASTM D785), bending strength (k
g / mm ² ) 1200 (Autograph IM500, temperature 23 ° C, speed 2 mm / min, distance between fulcrums 70 mm)
DEAE pullulan is an ether-like diethylaminoethyl group introduced into glucose, which is a constituent unit of pullulan, and pullulan and 2-chloroethyl-
dietyl-aminohydrochlorid
DEA because it can be obtained by reacting e with an alkaline solution.
In addition to the E group, there is a tandem type of DEAE-DEAE group as a side reaction. In the titration of the basic type DEAE pullulan used in this example with hydrochloric acid, the equivalence points were PH 8.9 and 5.7, respectively, and the ratio of the single type to the tandem type was 1: 0.8. Looking at the infrared absorption spectrum of this copolymer, the absorption of CH ₂ -C due to DEAE pullulan was observed around 2650 cm ^-1 , and the absorption of C = O due to poly (methacrylic acid)
Observed around 1720 cm ^-1 , and almost no absorption around 1635 cm ^-1 due to -C = C-. In addition, since the copolymer formed in acetone, which is a good solvent for each of poly (methacrylic acid), poly (methyl methacrylate), and DEAE pullulan of the base type, is insoluble, the polycomplex copolymer consisting of these three components The existence can be confirmed. Example 2 The rod-shaped lump polymer obtained in Example 1 was cut with a lathe at 2000 rpm after hot-water treatment and dried, and roughened surface was processed at the same rotation speed to determine a constant curvature. The contact lens was fitted into a plate and polished at a lower part rotation of 200 times per minute and at an upper part rotation of 15 times per minute and beveled using a rear bevel machine to manufacture a contact lens. The contact lens had a good hydrophilic surface and the contact angle was 57 ° . Under the same measurement conditions, the conventional lens, poly (methyl methacrylate), was 72 °. This power is applied to the next person who cannot wear the conventional lens as 0.02 (1.0 × S −3.50) for the left eye and 0.02 (1.0 × S −3.50) for the right eye. When worn as 3.50 D (dioptre) , it was able to be worn for 8 hours, and the visual acuity produced 1.0 in both eyes. After wearing this contact lens for one year, the base curve and the power were measured, and no change occurred.
The following contact lenses were used. Example 3 Commercially available cornstarch (National Starch and
Chemical-produced DEAE (diethylaminoethyl) starch having a nitrogen content of 6% as a nitrogen content was added with 50% caustic soda solution to an aqueous solution of DEAE (diethylaminoethyl) starch hydrochloride. 10 g of starch was dissolved in 20 ml of methacrylic acid, this DEAE starch-methacrylic acid solution was further mixed well with 450 ml of methyl methacrylate, and azobisisobutylnitrile (AIBN) was used as a polymerization initiator.
After adding 2.5 g and putting it in a glass tube having a diameter of 15 mm and thoroughly degassing, the reaction temperature was 50 ° C. and the polymerization time was 72 in a sealed tube.
The polymerization reaction is carried out in time. Then, the mixture was heated in an air bath at 50 ° C. for 3 hours, cooled, the rod-shaped polymer was removed from the glass tube, and annealed in the air bath at 80 ° C. for 24 hours to obtain 470 g of a lump polymer. This is water, methanol, and acetone,
It was insoluble in organic solvents such as n-hexane and tetrahydrofuran. Vicat softening point 92 ° C (ASTM D152
5, Rockwell hardness (M scale) 83 (ASTM
D785). Bending strength (kg / mm ² ) 1200 (Autograph IM500, temperature 23 ° C, speed 2 mm / m
in, distance between fulcrums 70 mm). Example 4 The rod-shaped lump polymer obtained in Example 3 was cut with a lathe rotating at 2000 rpm after hot-water treatment and drying, and the uneven surface was processed at the same rotation speed to determine a constant curvature, and the pit of the lens polisher was determined. The contact lens was fitted into a plate and polished at a lower part rotation of 200 times per minute and at an upper part rotation of 15 times per minute and beveled using a rear bevel machine to manufacture a contact lens. This contact lens had a good hydrophilic surface and the contact angle was 56 °. Under the same measurement conditions, the conventional lens, poly (methyl methacrylate), was 72 °. This power is applied to the next person who cannot wear the conventional lens as 0.02 (1.0 × S −3.50) for the left eye and 0.02 (1.0 × S −3.50) for the right eye. When worn as 3.50 D , it was able to be worn for 8 hours, and the visual acuity produced 1.0 in both eyes. After wearing this contact lens for one year, the base curve and the power were measured, and no change occurred. The following contact lenses were used. Example 5 10 g of TEAE (triethylaminoethyl) cellulose obtained by introducing 6% TEAE (triethylaminoethyl) group as a nitrogen content into cellulose (Whatman Filter Paper, Whatman 4) was replaced with 60 g of acrylic acid.
Azobisisobutylnitrile (A) as a polymerization initiator.
IBN) (1.0 g) was added, and the mixture was placed in a glass tube having a diameter of 15 mm and sufficiently deaerated, and then the polymerization reaction was carried out in a sealed tube at a reaction temperature of 60 ° C. and a polymerization time of 100 hours. After heating for an hour, 125 g of a bulk polymer was obtained. It was insoluble in water, methanol, and organic solvents such as acetone, n-hexane, and tetrahydrofuran. Example 6 The rod-shaped lump polymer obtained in Example 5 was cut with a lathe at 2000 rpm after hot-water treatment and dried, and roughened surface was processed at the same rotation speed to determine a constant curvature, and the pit of the lens polisher was determined. The contact lens was fitted into a plate and polished at a lower part rotation of 20 O / min and an upper part rotation of 15 / min and beveled using a rear bevel machine to manufacture a contact lens. The contact lens had a good hydrophilic surface and the contact angle was 55 °. Under the same measurement conditions, the conventional lens and poly (methyl methacrylate) were at 72 °. This power is applied to the next person who cannot wear the conventional lens as 0.02 (1.0 × S −3.50) for the left eye and 0.02 (1.0 × S −3.50) for the right eye. When worn as 3.50 D , it was able to be worn for 8 hours, and the visual acuity produced 1.0 in both eyes. After wearing this contact lens for one year, the base curve and the power were measured, and no change occurred. The following contact lenses were used.

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Claims (1)

(57) [Claims] General formula In the formula, the unit formula of the cationic derivative of the polysaccharide (excluding dextran) is In the formula, the unit of the polymer of the unsaturated acid has the general formula: In the formula, the unit formula of the polymer of the olefin compound is And a matrix polymer obtained by polymerizing an unsaturated acid with a cationic derivative of a polysaccharide (excluding dextran) represented by (Chemical Formula 2) and (Chemical Formula 3), and (Chemical Formula 4). A radical mass copolymer of a matrix polymer formed by polymerizing an unsaturated acid with a cationic derivative of a polysaccharide (excluding dextran) represented by the general formula (Formula 1) and an olefin monomer. A contact lens consisting of. 2. The formula of the unit of the cationic derivative of the polysaccharide (excluding dextran) is represented by the formula: wherein the formula of the unit of the unsaturated acid polymer is Is represented by [Chemical Formula 3], in which the formula of the unit of the polymer of the olefin compound is represented by [Chemical Formula 4], and the cation of the polysaccharide (excluding dextran) consisting of (Chemical Formula 2) and (Chemical Formula 3) A cationic derivative of a polysaccharide (excluding dextran) represented by the general formula (Chemical formula 1), which is composed of a matrix polymer obtained by polymerizing an ionic derivative with an unsaturated acid and (Chemical formula 4), is used. A rod characterized by being obtained by radical block-copolymerization of a matrix polymer obtained by polymerizing a saturated acid and an olefin monomer.
The blocky polymer was dried with warm water and cut with a lathe at a constant rotation every minute.
A uniform curvature is created by shaving and processing the uneven surface at the same rotation speed.
The lens polisher, and fit it into the pit plate of the lens polisher
Rotation at a constant rotation speed per minute, upper rotation at a constant rotation speed per minute
Polished and then beveled using a bevel machine
How to make contact lenses.