JPH07179811A - Biocompatible smooth graft - Google Patents

Abstract

PURPOSE: To provide an article capable of yielding lubricity under both dry and wet conditions and having bio-adaptability by coating the surface of an article with a polymerizable composition composed of specific types of hydrophobic monomer and hydrophilic monomer and polymerizing the composition.

CONSTITUTION: A polymerizable coating composition is obtained by formulating a hydrophobic monomer consisting of perfluoro (meth)acrylate, a hydrophilic monomer consisting of acrylamide, hydroxyethyl (meth)acrylate, hdyroxypropyl (meth)acrylate or vinyl pyrrolidone, a UV initiator, and a solvent in such a way that the molar ratio of the hydrophilic and hydrophobic monomers is 1:1 to 1:5. The composition is coated onto the surface of an article made of partially vulcanized natural rubber or polymethyl methacrylate such as by dipping, and polymerized through irradiation with UV light to obtain an article having a coated surface.

COPYRIGHT: (C)1995,JPO

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION This invention relates to polymeric materials and articles formed therefrom. More particularly, this invention relates to polymer coatings and their use in the manufacture of articles intended for contact with wet body surfaces. Articles include lenses such as gloves and contact lenses for surgical and medical examinations, and intraocular lenses.

[0002]

Instead of using a lubricant such as powdered starch to improve the hand wearability of surgical gloves, a permanent thin layer of polymer is applied to the surface of the gloves. Can be chemically bound. This layer is required to improve dry and wet wear for comfort and be able to absorb sweat. Also, this layer should be harmless to human biological systems.

US Pat. No. 3,813,695 discloses a surgical glove in which an outer layer of a flexible material such as rubber and an inner layer of a hydrophilic material such as a hydrogel polymer are adhered. A hydrophilic coating on a flexible rubber article such as surgical gloves provides some slippage with the skin in contact with the glove surface, but this lubricity is effective only on dry skin and not when the skin is damp. Has been found. To solve this problem, the present invention seeks to provide a coating that provides good lubricity to both dry and moist skin.

Contact lenses and intraocular lenses are often made of relatively hydrophobic materials such as polymethylmethacrylate (PMMA), which can be uncomfortable for the wearer or patient. It has been found that coating such lenses with both hydrophobic and hydrophilic materials allows the lenses to be worn more comfortably. Intraocular lenses cause inflammation of the ocular tissues in the eye and can cause complications such as uveitis over a long period of time. Coatings for intraocular lenses have been developed that reduce cell adhesion and tissue damage on repeated contact. For example, US Pat. No. 4,655,770 discloses fluorocarbon coated medical implant chambers intended to reduce surface energy and prevent cell adhesions.

[0005]

According to the present invention, there is provided a polymerizable grafting composition comprising a monomer or a combination of monomers. In the present invention, the term hydrophilic monomer means a monomer that forms a polymer that absorbs at least 5% by weight of water after being polymerized and then immersed in water at 25 ° C. for 24 hours. On the other hand, the term hydrophobic monomer is a polymer that resists the diffusion of water on the surface after polymerization, and the water contact angle (measured by the latest meniscus method) is 45.
Means that is greater than or equal to °.

Hydrophilic or hydrophobic coatings have been developed for intraocular lenses and contact lenses. Hydrophilic coatings provide lubricity in the wet state and have low adhesion to cells, while hydrophobic coatings are characterized by low surface energy and low adhesion to proteins. While both types of coating have their respective advantages, a combination of hydrophilicity and hydrophobicity within the eye or on the surface of the contact lens is required for true biocompatibility. The inventors of this invention have developed a number of biocompatible grafting compositions that have both hydrophilic and hydrophobic properties that impart lubricity in both dry and wet states.

The coating composition consists of one or more hydrophilic monomers. Further, the coating composition comprises an oligomer having one or more polymerizable end groups, that is, a low molecular weight polymer. This invention provides a polymer composition consisting of residues derived from hydrophilic monomers and residues derived from perfluoroacrylate or perfluoromethacrylate, when contacted with either wet or dry skin.
Provide a surface coated article in a sufficient rate to provide lubricity.

According to an embodiment of the invention, the surface of the article is coated with a polymerizable composition comprising a hydrophilic monomer and a hydrophobic monomer of perfluoroacrylate or perfluoromethacrylate, and then for copolymerizing the monomer. A method of making a coated article comprising irradiating a coated composition is provided. The coated polymerizable composition is preferably irradiated with ultraviolet rays for polymerization. The surface coated with the polymerizable composition is more suitably a substrate on which the polymerizable composition can be graft polymerized. Suitable substrates for grafting are natural rubber, preferably slightly vulcanized natural rubber, acrylic resins such as polymethylmethacrylate.

Hydrophilic monomers suitable for use in this invention include acrylamide, hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, 2-hydroxypropyl acrylate, hydroxyethyl acrylate and vinylpyrrolidone. The coating composition consists of one or more hydrophilic monomers with perfluoroacrylates or methacrylates, and optionally other hydrophobic monomers such as methylmethacrylate. The molar ratio of hydrophilic monomer to total hydrophobic monomer (including perfluoroacrylate or methacrylate) is preferably at least 1: 1.

Generally, the molar ratio of hydrophilic component to hydrophobic component does not exceed 1:10. A suitable molar ratio is from about 1: 1 to about 1: 5. Perfluoro components suitable for use in the present invention include those represented by the following formulas and symbols and available from 3M Company.

[0011]

[Chemical 1] Hydrophilic components such as polyacrylamide, polyhydroxyethyl methacrylate, polyvinylpyrrolidone and polyhydroxyethyl acrylate in the graft layer provide excellent lubricity to dry skin. Hydrophobic components such as the perfluoroacrylates and perfluoromethacrylates illustrated above substantially improve lubricity on wet skin.

The coating composition also comprises a low or medium molecular weight polyethylene oxide (PE) terminated with one or two acrylate or methacrylate groups.
O) and a molecular weight of 300 to 2000. Such P
EO oligomers are a combination of hydrophilic and hydrophobic. We have found that some combinations of hydrogel monomers and perfluoroacrylates or perfluoromethacrylates grafted on the surface of rubber products such as surgical gloves give good lubricity to dry and wet skin. . According to the invention, the preferred combinations are hydroxyethyl methacrylate and perfluoroacrylate or perfluoromethacrylate and polyvinylpyrrolidone monomers.

This combination of monomers may be combined with a suitable radiation source,
Grafting is preferably carried out by a UV irradiation grafting method, more preferably a high-intensity UV lamp. One group of articles according to the present invention includes those made of rubber, preferably natural rubber. Articles are formed by dipping in a suitable latex (prior to being grafted with a hydrophilic, hydrophobic layer). After curing or vulcanization, hydrophilic / hydrophobic properties are grafted onto the rubber surface. The monomer solution preferably contains a UV initiator and is applied by dipping a rubber article in this solution.

Rubber products such as surgical gloves can be made as follows. (1) The rubber sample is washed with isopropanol (IPA), (2) the sample is dipped in a liquid composed of a hydrophilic monomer, a hydrophobic monomer, a UV initiator and a solvent, and (3) UV irradiation is performed to change the hydrophilic monomer Graft with a hydrophobic monomer, (4) wash the resulting rubber sample with IPA, and (5) air dry the sample.

Other articles that can be used in the present invention include condoms, examination gloves, catheters, ureters, sheets,
Includes other skin or tissue, including soft rubber items such as pod products. Generally, the overall performance of a material applied to biomedical treatment simultaneously satisfies the physical mechanical properties and the compatibility with the biological system involved. Physical-mechanical properties are generally governed by internal properties, and biocompatibility is regulated by surface chemistry and morphology. As such, the present invention improves the surface properties of prosthetic devices, particularly other groups of body-contacting articles such as intraocular lenses, contact lenses.

[0016]

EXAMPLES In order to fully understand the present invention, examples will be described below.

Example 1 A sample of natural rubber latex was prepared from isopropanol (IPA).
Washed with. The washed sample is then treated with 0.5% UV initiator (Irgacure 184); hydroxyethyl methacrylate for 30-60 minutes at a molar ratio of FX13 monomer of 1: 1.
Of 20% IPA and hexane. The immersed rubber samples were treated for 5-30 minutes with high intensity UV irradiation generated by a high or medium mercury arc lamp.

The treated rubber was washed with IPA and dried in air. The grafted rubber latex samples were characterized by contact angle measurement, FTIR-ATR, SEM and ESCA. The performance of the grafted rubber samples on dry and wet skin was evaluated by dry and wet rub measurements.
FTIR-ATR analysis showed that the graft material was chemically bonded to the surface of the rubber sample.

A study at ESCA confirmed the above analysis and showed that there were 20-30% fluorine atoms on the surface. Examples 2-22 Example 1 was repeated except that the monomers and solvents were replaced with those shown in Table 1.

[0020]

[Table 1] The dry and wet rubs of the grafted rubber samples were significantly improved. Table 2 shows one example.

[0021]

[Table 2]

The method shown below shows that grafting polymethylmethacrylate (PMMA) with UV radiation with a hydrophilic monomer (eg N-vinylpyrrolidone) improves the surface properties.

When the hydrophilic monomer is grafted onto the hydrophobic PMMA substrate, the contact angle of the substrate is significantly reduced.
Contact angle measurements are therefore used to characterize grafted PMMA.

Method A-Gas Phase Method 2 moles of NVP and 0.2 moles of initiator were mixed in a solvent. The initiator was Irgacure 184 or benzophenone. The solvent is acetone or ethanol. About 100 ml of the monomer solution was transferred to a crystallization dish and placed at the bottom of the reaction chamber. The PMMA sample to be grafted was placed in the reaction chamber on a sample holder with a polished surface. The chamber was tightly closed and replaced with nitrogen gas for 10 to 30 minutes so that the reaction system did not contain air. During this period, the temperature of the reaction chamber was raised to about 60 ° C. When the temperature in the chamber reaches the desired temperature (~ 60 ° C), turn the UV lamp on for a certain time (eg 5,1
The sample was directly irradiated for 0, 20 or 30 minutes. The UV irradiation time was intermittent in some cases and intermittent in others.

Remove PMMA sample (if any)
Soak in IPA for about 1 hour to remove residual monomer. It was dried in a vacuum oven preheated (~ 70 ° C) overnight and the contact angle was measured the next day. Comparative sample is also NVP in solution
Prepared in the same manner except that no monomer was included.

The following results were observed: Same as continuous exposure of sample to UV light
Only the contact angle with UV light exposed discontinuously at intervals
There was no difference to be made. For example, set A has 5 minutes UV
Similar contact angle between exposure and UV exposure for 20 minutes (5 minute intervals)
Met. 2. PMMA group after 30 minutes UV exposure in a 15-minute cycle
It appeared to make notable differences in body contact angles. Shi
However, the results are not reproducible and are large at 16.2 ° to 66 °.
Fluctuated. The surface of PMMA with low contact angle is
It looked dull and had significant cracking, but this
It may have been due to the drying process. ESCA is
The surface has a nitrogen content of about 6% and the ATR spectrum is 1
700 cm ^-1Showed a peak at. Monomer vaporization in reactor
The correct amount of air is adjusted and concentrated on the PMMA substrate surface.
Care should be taken to ensure that there is sufficient Nomer vapor.

Method B1-Immersion Method Using Irgacure 184 as an initiator, NV
Solutions of different concentrations of P in isopropanol were made. The solution used is as follows.

22% NVP + 18.6% Irgacure / Ethanol 10% NVP + 0.1% Irgacure / Isopropanol 5% NVP + 0.1% Irgacure / Isopropanol The percentage of Irgacure is based on the weight of the NVP monomer alone. The PMMA sample was immersed in the above solution for about 30 minutes and exposed to UV light for 15 minutes. Sample 1
It was immersed in isopropanol for a period of time to remove residual monomers and dried in a vacuum oven at 70 ° C. overnight. The next day,
The contact angle was measured for each sample. The comparative sample was treated in the same manner except that a solution containing no NVP monomer was used.

Method B1 gave contact angle measurements consistent with NVP monomer concentration. The contact angle of the treated surface is N in the solution.
It decreased as the VP concentration increased. 10 for grafting
When using% NVP (lot number 99-41), ES
CA showed an atomic concentration of nitrogen of 5% on the surface of the grafted PMMA and showed a clear peak in the 1700 cm ^-1 region in the ATR spectrum. A thick coating was found on the surface of the PMMA substrate, which was sometimes non-uniform, but this method is faster and gives more consistent results than method A.

Tables 3 and 4 show the contact angles of the samples prepared by the vapor phase method, and Table 5 shows the contact angles measured by the immersion method B1.

[0031]

[Table 3]

[0032]

[Table 4]

[Table 5]

Method B2-Dip Method Solutions of different concentrations of monomer or polymer were made in isopropynol with Irgacure 184 as an initiator. For HEMA, acetone and IPA
A mixed solvent of (4: 6) was used. Therefore, the HEMA monomer is easily deposited on the PMMA substrate.

Soak the PMMA or PMUV button in the above monomer or polymer solution for 30 minutes. Place this on a glass slide with a polished surface and let it sit in the hood for 15 minutes.
V-irradiated. The irradiated sample was washed with IPA for 30 minutes to remove residual monomer or polymer. Then dried in a vacuum oven at 70 ° C. overnight. The next day, samples were removed and cooled to room temperature and analyzed by contact angle goniometer, FTIR and optical microscopy.

The following results were observed. 1. NVP usually gave a thick coating on the surface. A bumpy surface was observed. NVP concentration is 5% to 20
%, And the contact angle changed from 66 ° to 40 °. FTIR analysis showed a clear peak at 1700 cm ^-1 . 2. HEMA grafting appeared to give a smooth surface. At high concentration (80% HEMA) some pits were observed on the substrate surface. When grafted at 80% HEMA concentration, the contact angle of the sample was about 54 °. Since the water contact angle of poly-HEMA is about 59-60 °, the maximum change in the contact angle of the graft PMUV is about 1
It is 5 °. FTIR showed a small OH peak at 3400 cm ^-1 .

3. Glyceryl monomethacrylate (GM
PMMA or PMUV grafted with (MA) gave a smooth surface. Under the microscope, some pits were visible on the surface. When the GMMA concentration is in the range of 10% to 80%, the water contact angle is in the range of 64 ° to 40 °. However, in the IR spectrum, there was no particular difference compared to RMUV or PMMA.

4. A polyethylene oxide polymer having both acrylate end groups and methacrylate end groups,
A series of photografts were performed. It has a molecular weight of 210,
252, 259 and 1000 polyethylene oxide chains were used. Methanol and isopropanol were used as the solvent. The concentration of the monomer is 10% to 80% V / V. Table 6 shows the results obtained.

[0038]

[Table 6]

5. Methacrylonitrile, methacrylic acid, acrylic acid, acrylamide did not give good coatings on PMUV. The contact angle for methacrylonitrile changed from 69 ° to 62 °. The methacrylic acid coating had a contact angle of 66 ° at 40% concentration. Acrylamide showed powder residue on the surface of the sample after grafting, and showed no significant change in contact angle.

In general, glyceryl monomethacrylate,
PEO (polyethylene glycol mono and dimethacrylate) and HEMA gave the best appearance and water contact angle results. NVP grafting is easily characterized by contact angle measurements and FTIR, but does not show consistent results. Known for its low protein absorption and low cell adhesion properties, polyethylene glycol 200 dimethacrylate is a photografted PM.
It is one of the preferred polymers for UV materials. Tables 7 and 8 show the contact angles measured for different monomers at various concentrations. Tables 9 and 10 show the properties of PEO oligomers grafted to PMUV.

[0041]

[Table 7]

[0042]

[Table 8]

[0043]

[Table 9]

[0044]

[Table 10]

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Reference number within the agency FI Technical indication location // C08F 20/22 MMT 7242-4J (72) Inventor Amitaba Gupta United States, California 91108, San Marino, Virginia Road 1606 (72) Inventor Michael Corbin United States, California 90365, Malibu, Pacific Coast Highway 25001

Claims (18)

[Claims] 1. A polymerizable coating composition comprising a hydrophobic monomer comprising perfluoroacrylate or perfluoromethacrylate and a hydrophilic monomer. 2. The composition according to claim 1, wherein the hydrophilic monomer comprises acrylamide, hydroxyethyl methacrylate, hydroxyethyl acrylate, hydroxypropyl methacrylate, hydroxypropyl acrylate or vinylpyrrolidone. 3. The composition according to claim 1, wherein the molar ratio of hydrophilic monomer to hydrophobic monomer is from about 1: 1 to about 1: 5. 4. An article having a surface coated with a polymerizable composition comprising residues derived from a hydrophilic monomer and residues derived from perfluoroacrylate or perfluoromethacrylate. 5. Article according to claim 4, wherein the polymerizable composition is grafted onto the surface of the article. 6. The article is a flexible article made of rubber.
Or the article according to 5. 7. Article according to claim 6, wherein the rubber is natural rubber. 8. The rubber according to claim 4, which is partially vulcanized.
Goods by. 9. The article is a surgical or laboratory glove, catheter, condom or ureter.
An article according to any one of. 10. The article is made of acrylic resin.
Or the article according to 5. 11. An article according to claim 10, wherein the acrylic resin is polymethylmethacrylate. 12. Article according to claim 4, 10 or 11 in the form of a contact lens or an intraocular lens. 13. A method comprising coating the surface of an article with a polymerizable composition comprising a hydrophilic monomer and a hydrophobic monomer comprising perfluoroacrylate or perfluoromethacrylate, and then subjecting the composition to irradiation for polymerization. A method of making an article having a coated surface. 14. The method according to claim 13, wherein the irradiation is ultraviolet irradiation. 15. A solution suitable for photografting, which comprises a low molecular weight polymer of ethylene oxide having one or more polymerizable groups at the end and an ultraviolet ray absorbing photocuring inhibitor. 16. The solution according to claim 15, wherein the ethylene oxide polymer has a molecular weight of 200 or more and 5000 or less. 17. Immersing the article in a solution suitable for photografting consisting of a low molecular weight polymer of ethylene oxide terminated with one or more polymerizable groups and a UV-absorbing photocuring inhibitor prior to UV irradiation. A method for forming an article, the surface of which is coated with a polymerizable composition comprising a residue derived from a hydrophilic monomer and a residue derived from perfluoroacrylate or perfluoromethacrylate. 18. An intraocular lens made of an acrylic copolymer having a band coating of the photografting solution of claim 15.