KR100392241B1 - Optically transparent biocompatible polymeric material mainly containing collagen and its manufacturing method - Google Patents

Abstract

The present invention relates to a biocompatible polymer comprising a copolymerization product of a telo-collagen and a graft-polymerized hydrophobic and hydrophilic acrylic and / or allel monomer mixture. The materials of the present invention are useful in the production of deformable lenses such as apecia, intraocular lenses, refractive intraocular contact lenses and standard contact lenses useful for correcting hyperopia and myopia.

Description

Optically clear biocompatible polymer materials based on collagen and methods for their preparation

Conventional polymers based on pure non-polyene acrylate or allel monomers do not have a water-solvent ion layer that mitigates the sorption of proteins on their surface. Providing a water-solvent ion layer on the surface of this polymer is preferred because this layer greatly enhances the biocompatibility of the lens with respect to the eye cell membrane of the wearer.

Polyene water-solvent ionic monomers may be used to form the water-solvent layer. However, this reduces the resistance of the copolymer to swelling. For example, a polyene copolymerization system based on acrylic acid or acrylamide having HEMA tends to swell excessively beyond the range. This is a phenomenon that occurs because the pure homopolymer, polyacrylamide or polyacrylic acid included in the system is dissolved in water. Thus, it is useful to prepare polymers that can form important water-solvent layers and do not affect polymer resistance to swelling.

References for graft-copolymers of collagen include US Pat. No. 4,388,428 (filed June 14, 1983) and US Pat. No. 4,452,925 (filed June 5, 1994). These patents use a system of water soluble monomers and A telogen-collagen. However, this system is not stable to hydrolysis and does not have sufficient optical transparency. U. S. Patent No. 4,452, 925 does not mention specific optical conditions required for the production of transparent polymers. The water-solvent A telogen-collagen described in this patent cannot form a gel in an organic monomer solution, so that the collagen precipitates or aggregates.

This application is part of US Patent Application Serial No. 08 / 279,303, filed Jul. 22, 1994, which is hereby incorporated by reference in its entirety.

The present invention relates to a biocompatible polymer comprising a copolymerization product of a mixture of hydrophobic and hydrophilic acrylic monomers and / or allelic monomers with pre-purified telo-collagen from glycoproteins and proteoglucans. . This material is useful for the manufacture of intraocular soft lenses, intraocular refractive contact lenses, and standard contact lenses useful for correcting aphakia, myopia and hyperopia.

It is a first object of the present invention to provide an optically clear biocompatible polymer based on telogen-collagen.

It is a second object of the present invention to provide a biocompatible polymer comprising copolymerization products of hydrophobic and hydrophilic acrylic monomers and / or mixtures of alleloid-monomers with telogen-collagen.

It is a third object of the present invention to provide a method for producing an optically transparent biocompatible polymer material based on collagen.

It is a fourth object of the present invention to provide a process for preparing biocompatible polymers comprising copolymerization products of hydrophobic and hydrophilic acrylic monomers and / or mixtures of alleloid-monomers with telogen-collagen.

The present invention relates to a method for producing a biocompatible polymer material based on collagen useful for the production of deformable lenses.

The invention also relates to a deformable lens composed of an optically clear biocompatible polymeric material.

The invention also relates to a method of manufacturing a deformable lens.

The present invention also relates to a method for correcting ataxia (without wearing a lens on the eye), myopia or hyperopia by surgically implanting the deformable lens of the present invention in the eye of a patient.

The biocompatible polymer material according to the invention is prepared as a copolymerization product of a mixture of telo-collagen and graft polymerized hydrophobic and hydrophilic acrylic monomers and / or allel monomers. For example, one or more hydrophobic acrylic monomers and / or allel monomers may be mixed with one or more hydrophilic acrylic monomers and / or allel monomers, and the resulting solution may be telo dissolved in one or more hydrophilic acrylic monomers and / or allel monomers. Mix with collagen. The resulting material is then irradiated with radiation to form the optically clear biocompatible polymeric material of the present invention.

The telogen collagen used in the present invention is mainly composed of type IV collagen obtained from the sclera or cornea of the pig's eye. The collagen is a naturally stable polyene, which includes hydrophobic amino acids, amino acids with hydroxyl groups, and polar amino acids. (Matsumura, T., Relationship Between Amino-Acid Composition and Differentiation of Collagen, Lut. J. Biochem. 3 (15) : 265-274 (1972), and Traub W., and Piez KA, The Chemistry and Structure of Collagen) Advances In Protein Chem 25 : 243-352 (1971). The use of modified collagen in the system of the present invention is not recommended as the collagen is biodegraded over time (US Pat. No. 4,978,352, filed Dec. 18, 1990).

The resulting biocompatible polymeric material is an elastic biopolymer based primarily on a mixture of hydrophobic and hydrophilic monomers and telogen-collagen. Copolymer products of hydrophobic and hydrophilic monomers exhibit improved hydrolytic stability and high refractive index compared to polymers based solely on hydrophilic monomers.

High molecular weight telo-collagen molecules (320,000 D), their size (1000 A or less), loss of spatial orientation of the molecules, refractive index 1.47 (Hogan JJ et al., Histology of Human Eyes An Atlas and Textbook , Philadelphia, London, Toronto, (1971) ), And other properties of collagen make it impossible to prepare optically clear hydrogel implants made from collagen alone. When preparing a suspension of collagen in an aqueous monomer, the refractive index, or aqueous number, of the hydrogel based material is 1.336, which is almost different from the refractive index of 1.47 of collagen, resulting in turbidity of the gel.

It is essential to use telo-collagen containing telo-peptide to prepare an optically homogeneous gel in a mixture of organic monomers. Telo-peptides are the basic elements of the interaction between collagen molecules. This produces a stable gel in a mixture of hydrophobic and hydrophilic monomers. This gel does not precipitate or aggregate.

In order to increase optical transparency and homogeneity in this system, the refractive index of telogen-collagen and polymer should be about the same, and as a result, the light diffusing intensity is almost in accordance with Reley's equation (UG Frolof, Course of Colidle Chemistry , Moskva Chemia, 1989). Close to zero.

[Equation 1]

Wherein I ₀ is the intensity of incident light;

I is the intensity of diffused light as a unit of irradiation volume;

P _r is the distance to the detector;

w is the diffusion angle of light;

C is the concentration of particles per unit volume;

λ is the length of the incident light wavelength;

N ₁ is the refractive index of the particles;

N ₀ is the refractive index of the base material;

V is the volume of the particle.

When N ₁ is equal to N ₀ , I _p is 0. Therefore, the intensity of light diffusion is zero.

Preferred hydrophilic acrylic monomers for use in the present invention are 2-hydroxyethyl methacrylate (HEMA), and preferred hydrophobic monomers for use in the present invention are 4-methacryloxy-2-hydroxybenzophenone. Telo-collagen is preferably produced from the pig's eye sclera or cornea.

I. Term Definition

The following definitions of terms help to clearly and consistently understand the specification and claims, including the scope of such terms.

Telo-collagen: Telo-collagen is a term that refers to naturally stable polyenes comprising hydrophobic amino acids, amino acids with hydroxyl groups, and polar amino acids (Matsumura, T., Relationship Between Amino-Acid Composition and Differentiation of Collagen, Lut) J. Biochem. 3 (15) : 265-274 (1972)).

The telo-collagen of the present invention is preferably composed mainly of type IV telo-collagen obtained from porcine eye sclera or cornea, which has a viscosity of 1000 cPs or more. The telo-collagen of the present invention has a telo-peptide and the refractive index is about 1.44 to 1.48.

Biocompatible Polymer Materials: Blend or mix one or more hydrophobic monomers (acrylic monomers and / or allel monomers) with one or more hydrophilic monomers (acrylic monomers and / or allel monomers) and combine the resulting mixture with telogen-collagen / hydrophilic monomers. Refers to a material prepared by graft-copolymerization with an acid solution.

Monomer: means a molecular unit constituting a macrostructure or polymer by repetition. For example, ethylene CH ₂ = CH ₂ is a monomer of polyethylene, H (CH ₂ ) NH.

Allyl: ₂ ^- propenyl which is a monovalent radical CH ₂ = CHCH 2-.

Organic acid: Refers to an acid consisting of molecules containing organic radicals. Examples of such acids include formic acid (H-COOH), acetic acid (CH ₃ COOH) and citric acid (C ₆ H ₈ O ₇ ), all of which contain ionizable -COOH groups.

Acrylic: Means a synthetic plastic resin derived from acrylic acid.

Optical transparency: The nature of the polymeric material through which light passes at or above the threshold of visual perception (ie, the minimum amount of light intensity that stimulates visual perception). Preferably the biocompatible polymer materials of the present invention, including the collager, have a refractive index of 1.44 to 1.48; More preferably 1.45 to 1.47; Most preferably, it is 1.45-1.46. The best aspect of the present invention is a biocompatible polymer material COLLAMER.

Polymerization: A process in which monomers combine to form a polymer. The polymerization includes "addition polymerization" in which monomers are bonded and no other product is produced, and "condensation polymerization" in which water is formed as a by-product. Those skilled in the art to which the present invention pertains can readily select and use known suitable polymerization reactions to prepare the biocompatible polymer materials of the present invention.

Polyene: refers to a compound, such as a carotenoid, having a series of conjugated (alternative) double bonds.

Refractive Index: A measure of refractive index in translucent / transparent materials, especially eye media. Refractive index is a measure of the relative velocity in other media (eg, the polymeric material of the present invention) relative to the velocity of light in air. For example, the refractive index n of air with respect to the crown glass is 1.52 and the refractive index n of air with respect to water is n = 1.33.

Tensile Strength: means the maximum stress or load the material can bear, expressed in kPa. Biocompatible polymer materials of the present invention, including collagers, have a tensile strength in the range 391-1778 kPa, preferably 591-1578 kPa, more preferably 791-1378 kPa, and most preferably 991 to 1178 kPa. The material "collamer" of the present invention preferably has a tensile strength of 1085 +493 kPa. Tensile strength of the polymer material can be easily measured using a known method if one of ordinary skill in the art.

Hypermetropia: Hyperopia (h.) Refers to vision that is easily seen in the distance, that is, an optical condition in which only the convergent light focuses on the retina. Such conditions include the following: (1) Absolute h .-- primitives that cannot be overcome by perspective control of the lens; (2) axial h .-- a circle due to the shortening of the eyeballs; (3) curvature h .-- primitive due to a decrease in the forward refraction of the eye; (4) manifest manifestation--a primitive that can be corrected by perspective control of the lens; (5) conditional primitive--present manifestation; (6) latent h .-- difference between idyllic and overt primitive primitives; (7) total h .-- primitive measurable after complete paralysis of perspective control by a paralytic drug; And (8) index h.—primitives caused by reduced refractive power of the lens.

Myopia: Myopia (m) is an optical condition that appears near or in a short distance, where only a limited distance of light from the eye focuses on the retina. Such optical conditions include the following: (1) axial myopia--caused by the long front and rearview of the eye; (2) curved myopia--causes refractive errors resulting from excessive curvature of the cornea; (3) degenerative approximation--pathological myopia; (4) refractive index myopia--induced by increased refractive properties of the lens, such as nucleus sclerosis; (5) malignant myopia--pathological myopia; (6) Night myopia--usually occurs in the eye of the seeker because long rays focus in front of the retina; (7) pathological myopia--degenerative or malignant, progressive myopia characterized by basal changes, posterior grapeoma and subnormal corrected vision; (8) Immature myopia--myopia observed in infants with low birth weight or associated with posterior capsular fibrosis; (9) senile lens myopia--appearing cranial; (10) simple myopia--myopia caused by failure in correcting the length of the eye and the refractive power of the anterior part; (11) spatial myopia--myopia that occurs when there is no imaged image on the retina; (12) Temporary myopia--myopia observed in iris-moditis or perspective-controlled convulsions incidental to the bruise of the eye.

Hydrophilic Allen Monomer: refers to any monomer of the present invention that is soluble in water and includes an allyl group.

Hydrophilic Acrylic Monomer: refers to any monomer that contains an acrylic group and is soluble in water. For example, HEMA is a hydrophilic acrylic monomer because it is soluble in water even though it contains both hydrophilic and hydrophobic groups.

Hydrophobic Allen Monomer: refers to any monomer that includes an allyl group and is not soluble in water.

Hydrophobic Acrylic Monomer: refers to any monomer that contains an acrylic group and is not soluble in water.

Deformable Lens: Any type of deformable lens, such as a lens for correcting hyperopia or myopia, refers to a lens comprising the material of the present invention. Such lenses include those disclosed in US Patent Application Serial Nos. 08 / 318,991 and 08 / 225,060. The above patent applications are incorporated herein by reference. Examples of such lenses include: intraocular lenses for implantation into the patient's eye, such as the anterior chamber, bag or sphere; Refractive intraocular lenses for implantation into a patient's eye, such as an anterior chamber or a sphere; And standard soft contact lenses.

Implantation: The term “transplantation” refers to a surgical method for placing the lens of the present invention in a patient's eye, such as an anterior chamber, bag or sphere, which method is US patent application Ser. No. 08 / 195,717. Illustrated in 08 / 318,991 and 08 / 220,999, surgical devices used in the method are described in US Patent Application Serial Nos. 08 / 197,604, 08 / 196,855, 08 / 345,360 and 08/08. 221,013. All these patents are incorporated herein by reference.

Hydrophilic monomers and hydrophobic monomers of the present invention should be selected such that the hydrophobic monomer (s) are soluble in the hydrophilic monomer (s). Hydrophilic monomers act as solvents for hydrophobic monomers. Suitable monomers can be readily selected by those of ordinary skill in the art to which this invention pertains.

Examples of suitable hydrophobic monomers include the following:

1) 4-methacryloxy-2-hydroxybenzophenone (acrylic);

2) ethyl-3-benzoyl acrylate (acrylic);

3) 3-allyl-4-hydroxyacetophenone (allel);

4) 2- (2'-hydroxy-3'-allyl-5'-methylphenyl) -2H-benzotriazole (allel);

5) N-propyl methacrylate (acrylic);

6) allyl benzene (allel);

7) allyl butyrate (allel);

8) allylanisole (allel);

9) N-propyl methacrylate (acrylic);

10) ethyl-methacrylate (acrylic);

11) methyl methacrylate (acrylic);

12) n-heptyl methacrylate (acrylic).

Examples of suitable hydrophilic monomers include:

1) 2-hydroxyethyl methacrylate (HEMA) (acrylic);

2) hydroxypropyl methacrylate (acrylic);

3) 2-hydroxyethyl methacrylate (acrylic);

4) hydroxypropyl methacrylate (acrylic);

5) allyl alcohol (allel);

6) poly (ethylene glycol) monomethacrylate (acrylic);

7) 4-hydroxybutyl methacrylate (acrylic);

8) Allyl Glucol carbonate (Allel).

II. Method for producing a polymer material of the present invention based on collagen

Preferred methods for preparing the biocompatible polymer material according to the present invention are as follows.

Stage 1:

The hydrophilic monomer is mixed with an acid, in particular formic acid. The weight ratio of hydrophilic monomer: acid is about 5: 1 to about 50: 1, preferably 14: 1 to 20: 1, most preferably 14: 1. This solution is preferably filtered through a 0.2 microfilter.

Step 2:

As an independent step, an acidic telo-collagen solution was prepared by mixing telo-collagen with an organic acid (preferably formic acid). This solution is preferably a solution of 2% by weight of telogen-collagen in 1M formic acid.

STEP 3:

The solutions calculated in steps 1 and 2 were then mixed with each other. The resulting solution is preferably mixed at 15 to 30 ° C. for about 10 to 60 minutes, more preferably for 20 minutes. The ratio of telo-collagen: hydrophilic monomer is about 1: 2 to about 1: 7, preferably 1: 3 to 1: 6, most preferably 1: 4.

STEP 4:

As an independent step, the hydrophobic and hydrophilic monomers are mixed with each other in a weight ratio of about 10: 1 to 1: 1, preferably 8: 1 to 3: 1, most preferably 5: 1. These monomers were mixed with stirring at 70-95 ° C., preferably 80-95 ° C., most preferably 80-92 ° C. for about 30-90 minutes, preferably 60 minutes. The resulting solution is preferably filtered through a 0.2 micron filter.

Step 5:

The solutions obtained in steps 3 and 4 were mixed with each other in a weight ratio of about 1: 1 to 50: 1, preferably 2: 1 to 5: 1, most preferably 3: 1. This solution is preferably mixed for 20 minutes at a temperature of 25-40 ° C. without heating. Mixing is preferably carried out in a homogenizer.

Step 6:

The material produced in step 5 is preferably degassed using centrifugation or other means well known to those skilled in the art.

Step 7:

The material obtained in step 6 was irradiated to produce a final product that could be dried and stored (ie, due to their hygroscopic nature, they should be stored in a dryer). The material obtained in step 6 may be stored in a refrigerator, such as 5-10 ° C., before irradiation.

The polymer material according to the invention has a telolo- under conditions such that the total dosage is 0.20 to 0.80 Mrad, preferably 0.30 to 0.60 Mrad, most preferably 0.35 to 0.50 Mrad (1 Mrad = 10 Kgray) at an irradiation rate of 1 Mrad per hour. Obtained from the interaction of hydrophilic and hydrophobic monomers with solutions of collagen complexes.

A turbo-type mixer, such as a homogenizer, mixes the solution in at least three and five stages, and the mixing time set above is based on using a turbo type mixer. One of ordinary skill in the art can readily select and utilize a range of times as well as other known mixers and methods.

In a preferred embodiment, the polymeric material of the present invention is prepared by mixing the hydrophobic monomer in two steps to increase the viscosity of the solution, in the first step, the telo-collagen complex, formic acid and 2-hydroxyethyl-methacrylate The mixture of was used as a stabilizer of the solution in the ultra-colloidal state and in the second step a hydrophobic blend of one or more monomers was added to form a gel.

III. Standard Formulation Method of the Collamer of the Invention

A. Preparation of Acidic Collagen Solution

A 1 M acid solution, preferably 1 M formic acid, was prepared. The amount of acid solution required for dissolution of the swollen tissue is about 40: 0.5 to 55: 2, preferably about 45: 1 to about 52: 1.5, and most preferably about 50: 1 of the swollen collagen tissue: (sclera or Corneal) was calculated using the proportion of acid solution.

The swollen tissue was then treated in a homogenizer at 2-10 RPM, preferably 4-5 RPM, at room temperature for about 10-20 minutes, preferably about 15 minutes. The resulting solution was then filtered through a funnel glass filter having a pore size of 100 to 150 microns, and the filtrate was filtered through a second funnel glass filter having a pore size of 75 to 100 microns. The resulting homogeneous solution was transferred to a container.

B. Preparation of Hydrophobic and Hydrophilic Solutions

1. A hydrophilic monomer, preferably HEMA, was mixed with a hydrophobic monomer, preferably MHBPH in a weight ratio of about 5: 1 and heated at 80-92 ° C. for 1 hour with stirring (using a stirrer hot plate). The heated solution was filtered through a 5.0 micron filter.

2. HEMA is preferably mixed with an organic acid (preferably formic acid) in a weight ratio of about 14: 1. This mixture was added to the collagen solution produced in (A) in a weight ratio of HEMA solution: collagen solution of about 1: 3 and mixed at room temperature for about 20 minutes. Mixing is preferably carried out using a homogenizer at a speed of 6000 RPM.

3. The HEMA MHBPH solution of B (1) was mixed in small portions with the HEMA telo-collagen solution of B (2). Mixing is preferably carried out in a homogenizer at room temperature for 10 minutes.

C. Preparation of Collamers

The vial was covered with about 7 mm paraffin wax. The solution of B (3) was then poured into a glass bottle and degassed (by centrifugation for 15 minutes to remove air). The vials were then irradiated with 5 Kgray of radiation. (Note: it can be stored in a refrigerator, eg 5 to 10 ° C., before irradiation to the vial.)

IV. Guidelines for Selecting Monomers of the Invention

It is helpful to use the following formula to select the appropriate concentration of monomer needed to yield the polymer material of the present invention having a refractive index in the predetermined range (1.44 to 1.48, preferably 1.45 to 1.47, most preferably 1.45 to 1.46). Becomes

Monomers copolymerized with the telogen-collagen complex are selected as follows:

[Equation 2]

Where Ks is the swelling coefficient,

N _a is the refractive index of water (1.336),

N _p is the refractive index of the anhydrous polymer,

N _c is the refractive index (about 1.45-1.46) of telogen collagen.

N _i = refractive index of the _i -monomer;

C _j = concentration of i-monomer;

A = coefficient of increase of the refractive index by the polymerization reaction;

n = number of monomers;

i = monomer number.

Hydrophobic and hydrophilic monomers are chosen such that the hydrophilic monomer is the solvent for the hydrophobic monomer, ie the hydrophobic monomer must be chosen to be soluble in the hydrophilic monomer.

Although the present invention has been described with reference to the following examples so that those skilled in the art can fully understand the manner and method of carrying out the present invention, the scope of the present invention is not limited thereto.

Example 1 Combination of Collagers

A. Preparation of Acidic Collagen Solution

Under the exhaust hood, one liter of distilled water was measured into a three liter glass beaker. 52 g of formic acid was then added to the beaker and mixed until dissolved. Swelled collagen containing tissue (tissue from pig's eye) was then added to the acid solution in the ratio of swelled tissue: acid solution as follows.

Swelled tissue acid solution

1.517.00 g 10.21 g

2. 50.64g 1.00g

The mixture was then stored in a refrigerator at a temperature of 5 ° C. and then dispersed at 4-5 RPM in a homogenizer at room temperature for 15 minutes.

The resulting solution was then filtered through a funnel glass filter with a pore size of 100-150 microns. The filtrate was then filtered through a funnel glass filter having a pore size of 75-100 microns. The final homogeneous solution was transferred into a 250 ml container.

B. MHBPH and HEMA Solution Preparation

1. 527.4 g HEMA was mixed with 106.2 g MHBPH and heated at 80 ° C. using a stirrer hotplate for 1 hour. The heated solution was filtered through an Acro 50-5.0 micron filter.

2. 1415.6 g HEMA was then mixed with 99.4 g formic acid in a sealed glass container with a Teflon lid. 100 g portions of HEMA / acid solution were added into 333 g of telo-collagen solution and mixed for 20 minutes at room temperature. The mixing step was carried out at a speed of 6000 RPM in a homogenizer.

3. HEMA / MHBPH solution was then added in small portions to the HEMA telo-collagen solution. The mixing step was carried out for 10 minutes at room temperature in a homogenizer.

C. Preparation of Collamers

The vial was covered with about 7 mm paraffin wax. The solution obtained in step B (3) was then placed in a glass jar and centrifuged for 15 minutes to remove air. The bottle was then irradiated with 5 Kgray of radiation to polymerize and crosslink the material.

Example 2: Preparation of Optically Clear Biocompatible Materials

In this example, an ocular sclera of pigs was used. 300 g of 2-hydroxyethyl methacrylate were mixed with 16 g of formic acid. 50 g of telogen-collagen were filtered and purified from sclera using alkaline hydrolysis using 200 g of NaOH and 200 g of Na ₂ SO ₄ dissolved in 2.5 liters of water, followed by filtration through a 100 micron filter. Telo-collagen was mixed with formic acid solution containing 2-hydroxyethyl methacrylate and 2-hydroxyethyl methacrylate. Then 20 g of 4-methacryloxy-2-hydroxybenzophenone (MHBPH) dissolved in HEMA were added. The mixture was irradiated with gamma radiation in the range of 3.5-5.0 Kgray to polymerize and crosslink all components.

In this system hydrophobic monomers were used to reduce water uptake and swelling of the polymerized material when injected into the aqueous medium of the eye. In addition, the hydrophobic monomer was chosen such that the refractive index of the resulting polymer was increased approximately equal to the refractive index of telogen-collagen.

Example 3:

The same procedure as in Example 2 was used except for the following monomer replacements:

1) ethyl-3-benzoylacrylate (hydrophobic acrylic monomer), and

2) 2-hydroxyethyl methacrylate (HEMA) (hydrophilic acrylic monomer).

Example 4:

The same procedure as in Example 2 was used except for the following monomer replacements:

1) 3-allyl-4-hydroxyacetophenone (hydrophobic allel monomer), and

2) 2-hydroxyethyl methacrylate (HEMA) (hydrophilic acrylic monomer).

Example 5:

The same procedure as in Example 2 was used except for the following monomer replacements:

1) 2- (2'-hydroxy-3'-allyl-5'-methylphenyl) -2H-benzotriazole (hydrophobic allel monomer), and

2) 2-hydroxypropyl methacrylate (hydrophilic acrylic monomer).

Example 6:

The same procedure as in Example 2 was used except for the following monomer replacements:

1) methyl methacrylate (hydrophobic acrylic monomer), and

2) hydroxypropyl methacrylate (hydrophilic acrylic monomer).

Example 7:

The same procedure as in Example 2 was used except for the following monomer replacements:

1) 2- (2'-hydroxy-3'-allyl-5'-methylphenyl) -2H-benzotriazole (hydrophobic allel monomer), and

2) hydroxypropyl methacrylate (hydrophilic acrylic monomer).

Example 8

A. Tensile Strength Test of Collamer Material

The purpose of this test is to specify the tensile properties of the collager material of the present invention. The test includes tensile strength, Young's Modulus, and percent elongation at break. Collected data were used to prepare criteria for the test. Tensile tests are similar to silicone tensile tests. The conformation of the samples is different, but the stress principle remains the same.

B. Material

Collamer Sample

Instron Tensile Tester (Model 1122)

pincette

journal

C. Procedure

1. Sample Manufacturing

a. Samples of dried material were cut into rings. The dimensions are as follows: outer diameter = 10 ± 0.1 mm, inner diameter = 8 ± 0.1 mm, thickness = 1.0 ± 0.01 mm. The material was prepared according to the procedure used to make the lens. The lens was hydrated according to MSOP # 113AG.

2. Testing

a. Instron testers were installed for use in tensile specimens in accordance with ESOP 202, RMX-3 Slab Traction Test, Rev B. The fixtures were mounted in jaws and the fixtures were moved together so that the top and bottom could be reached by moving the crosshead up or down. When the fixtures contacted, it was about 8 mm between the two pins. This was set as the starting position of the jaw separation, and the instron position coordinate was set to zero.

b. The load dial was set to 2 kg full scale output, the crosshead speed was set to 500 mm / min, and the chart recorder to 500 mm / min. The chart speed recorded its separation value corresponding to the jaw separation. The chart buttons displaying "PEN" and "TIME" were pressed.

c. The wet test sample was removed from the bottle and placed so that the sample was nearly stretched between the two pins. When the sample was placed in place, the "UP" button on the crosshead control panel was immediately pressed. The sample was then loaded to the point of failure.

d. When the sample broke, the "STOP" button on the crosshead control panel was pressed. The chart buttons labeled "PEN" and "TIME" were then pressed so that they were in the up position. The crosshead was then returned to the starting position by pressing the return button on the crosshead control panel.

e. The break point in the chart was then indicated by observing the load at break (kg) and jaw separation.

f. Steps 2a to 2e were repeated until all samples were tested.

C. Data

Calculation of final tensile strength

[Equation 3]

σ = F / A

Where

σ = final tensile strength, Pascals (Pa)

F = force required to break test specimen, Newtons (N)

A = hydrated cross section of the sample, square meters (m ² )

δ = swelling coefficient, 1.17

w = width in mm

t = thickness in mm

Theory:

F = 0.29 kg x 9.81 m / s ² = 2.84 N

F = 2 [δ (w) x δ (t)] = 2 [(1.17 x 1.0) x (1.17 x 1.0)] = 2.74 mm ²

Conversion from mm ² to m ² : 2.74 mm ² = 2.74x10 ^-6 m ²

A = 2.74x10 ^-6 m ²

Found:

Final tensile strength, σ

solution:

σ = F / A = 2.84 N / 2.74 x 10 ^-6 m ² = 1038.3 kPa

kPa to psi, multiplied by 145.04x10 ^-3

1038.3 kPax145.04x10 ^-3 = 150.6 psi

σ = 1038.3 kpa or σ = 150.6 psi

Calculation for% elongation

[Equation 4]

δ = 200 [L / MC _(TS) ]

Where

δ = elongation (specified), percent

L = increase in jaw separation under the specified elongation (mm), and

MC _(TS) = mean circumference of the test specimen, mm

Circumference = πd

Theoretical:

L = 41.5 mm

MC _(TS) = (πd ₁ + πd ₂ ) / 2 = (πx10mm + πx8mm) / 2 = 28.27 mm

Found:

Elongation, δ

solution:

δ = 200 [L / MC _(TS) ] = 200 (41.5 mm / 28.27 mm) = 293.6%

δ = 293.6%

Calculation for Young's Modulus

[Equation 5]

E = Pl / Ae

Where

E = Young's Modulus, Pascals (Pa)

P = force, Newtons (N)

l = length of sample in meters

A = cross sectional area, square meters (m ² )

e = total longitudinal deformation in meters (m).

Theory:

P = 0.29 kgx9.81 m / s ² = 2.84 N

l = 0.008 m

A = A = 2 [δ (w) x δ (t)] = 2 [(1.17 x 1.0) x (1.17 x 1.0)] = 2.74 mm ²

Conversion from mm ² to m ² : 2.74 mm ² = 2.74x10 ^-6 m ²

A = 2.74x10 ^-6 m ²

e = 0.0415 m

Found:

Young's Modulus, E

solution:

E = Pl / Ae = (2.84Nx0.008 m) / (0.0415 mx 2.74x10 ^-6 m ² ) = 200.2 kPa

kPa to psi, multiplied by 145.04x10 ^-3

199.8 kPax145.04x10 ^-3 = 29.0 psi

E = 199.8 kPa or 29.0 psi

E. Discussion

Instron was installed and tested according to ESOP # 202. The test fixtures were moved together so that the centerline was aligned and there was about 8 mm gap between the columns. It was returned to this position after zeroing and after testing the fixture. Crosshead speed and chart recorder speed were set to 500 mm / minute.

The chart recorder was set to zero load and deflection before each test. The chart recorder recorded force loads and jaw separation in kilograms. The load is used to measure the final tensile strength (Equation 3, part of the test data), i.e. the stress at the time the sample breaks. Samples were not installed according to test elongation using standard gauge lengths and elongation was calculated using the criteria of ASTM D412 (Equation 4, data portion).

The performance of the specimens proved that the material is elastic and the stress increases at a linear rate until it breaks. The linear increase may be one of two things: (1) The specimen may have a stress rising factor on the inner diameter. The stress riser is caused by the grinding process because it does not have a surface finish of the shelf-rotated outer diameter; This allows the material to not be necked down during the plastic deformation phase of the test. Most of the stress is concentrated on the inner circumference, which loads more stress rising elements than if the stress is on the outer circumference. (2) The material cannot be necked (plastically deformed) like other plastic materials such as Kapton film. The material reacts like RMX-3, and as the elongation increases, the cross sectional area becomes smaller, suggesting Hook's law.

The material of the present invention exhibited excellent resistance of the collager to tear propagation that could occur in any stressor. The cross section of the fractured material was flat, suggesting elastic fracture.

E. Conclusion

The combined data from the collager samples of the present invention showed a tensile strength of 1084.6 kPa and an average elongation of 324.9%. Tolerance for average tensile strength was calculated as three times the ± standard deviation, with an upper limit of 1578 kPa (229 psi) and a lower limit of 591 kPa (86 psi). Tolerance to elongation was also calculated in the same manner. The upper limit is 395% elongation and the lower limit is calculated as 255% elongation. See Appendix 3 for the calculation process. Tensile strength is based on 1085 ± 493kPa (157 ± 7l psi) and elongation is 325% ± 70. The standard Young's modulus is 189 ± 25 kPa (27 ± 11 psi).

F. References

ASTM D412 Properties of Rubber Under Tension

ESOP 202-RMX-3 Slab Traction Test, Rev B.

Mark's Standard handbook for Mechanical Engineers , 9th Edition

All documents cited are incorporated herein by reference. The present invention has been described above sufficiently, and it will be apparent to those skilled in the art that the present invention can be carried out using a wide range of equivalent conditions, parameters and the like without departing from the spirit or scope of protection or any embodiment thereof. There will be.

Claims (18)

At least one hydrophilic acrylic monomer or allel monomer and at least one hydrophobic acrylic monomer or allene monomer; And Telo-collagen containing telo-peptide, The at least one hydrophilic acrylic monomer or allel monomer and the at least one hydrophobic acrylic monomer or allel monomer are graft-polymerized with the telogen-collagen to form an optically clear biocompatible polymer material composed mainly of collagen. Optically clear biocompatible polymer material. The optically clear biocompatible polymer material of claim 1, wherein the telogen collagen has a viscosity of at least 1000 cPs. The method of claim 1, wherein the at least one hydrophilic acrylic monomer or allel monomer is selected from the group consisting of HEMA (acrylic); 2-hydroxyethyl methacrylate (HEMA) (acrylic); Hydroxypropyl methacrylate (acrylic); 2-hydroxyethyl methacrylate (acrylic); Hydroxypropyl methacrylate (acrylic); Allyl alcohol (allel); Poly (ethylene glycol) monomethacrylate (acrylic); 4-hydroxybutyl methacrylate (acrylic); Allyl glucol carbonate (allel); The at least one hydrophobic acrylic monomer or allel monomer may be selected from the group consisting of 4-methacryloxy-2-hydroxybenzophenone (MHBPH) (acrylic); Allyl benzene (allel); Allyl butyrate (allel); 4-allyl anisole (allel); 3-allyl-4-hydroxyacetophenone (allel); 2- (2'-hydroxy-3'-allyl-5'-methylphenone) -2H-benzotriazole (allel); N-propyl methacrylate (acrylic); Ethyl-methacrylate (acrylic); Methyl methacrylate (acrylic); Ethyl-3-benzoyl acrylate (acrylic); And n-heptyl methacrylate (acrylic), And wherein said at least one hydrophobic monomer is soluble in said at least one hydrophilic monomer. 4. The optically clear biocompatible polymer material of claim 3, wherein the hydrophilic monomer is HEMA and the hydrophobic monomer is MHBPH. 2. The optically clear biocompatible polymer material of claim 1, wherein the refractive index of the optically clear biocompatible polymer material is from 1.44 to 1.48. 6. The optically clear biocompatible polymer material according to claim 5, wherein the refractive index is from 1.45 to 1.47. 5. The optically clear biocompatible polymer material of claim 1, wherein the refractive index of the optically clear biocompatible polymer material is between 1.45 and 1.46. 6. The optically clear biocompatible polymeric material prepared by the process of claim 1 comprising the following steps: Dissolving the acid-telo-collagen solution in at least one hydrophilic monomer to form a collagen / hydrophilic solution; Dissolving at least one hydrophobic monomer in at least one hydrophilic monomer to form a hydrophobic / hydrophilic solution; Combining the collagen / hydrophilic solution and the hydrophobic / hydrophilic solution to form a residual solution; And Graft-polymerizing the resulting solution to form an optically clear biocompatible polymer material based on collagen. Dissolving the acid-telo-collagen solution in at least one hydrophilic monomer to form a collagen / hydrophilic solution; Dissolving at least one hydrophobic monomer in at least one hydrophilic monomer to form a hydrophobic / hydrophilic solution; Combining the collagen / hydrophilic solution with the hydrophobic / hydrophilic solution to form a product solution; And Graft-polymerizing the resulting solution to form an optically clear biocompatible polymer material based on collagen. 10. The method of claim 9, wherein the graft-polymerization step comprises irradiating the product solution with radiation. A deformable lens comprising an optically clear biocompatible polymer material mainly comprising the collagen of claim 1. 12. The deformable lens of claim 11, wherein said deformable lens is a contact lens. 12. The deformable lens according to claim 11, wherein said deformable lens is a soft intraocular lens. 12. The deformable lens of claim 11, wherein the deformable lens is a refractive guide lens. 15. A method for correcting aphakia, hyperopia or myopia comprising implanting the intraocular lens of claim 13 or 14 into an eye. The optically clear biocompatible polymeric material of claim 1, wherein the tensile strength of the polymeric material is between about 591 and 1578 kPa. The deformable lens of claim 11, wherein the deformable lens has a tensile strength of about 591 to 1578 kPa. A deformable lens comprising the optically clear biocompatible polymeric material of claim 4.