Contact Lenses E-Book

Johannes Karl Fink

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 555

Veröffentlichungsjahr: 2022

Beschreibung

CONTACT LENSES The book focuses on the chemistry and properties of contact lenses and their fabrication methods. With research & development continuing in the field, this comprehensive book takes a look at the last 10 years in terms of new materials, chemistry methods, applications, and fabrication techniques. New applications include drug delivery, lenses for augmented reality, electronic contact lenses, and wearable smart contact lenses. In addition, the book discusses simulation methods for contact lenses, such as ocular topography parameters, gas permeable lenses, and computerized videokeratography. On the fabrication front, several common fabrication methods for contact lenses are detailed, including the computer-aided contact lens design, methods for the fabrication of colored contact lenses, and the fabrication of decentered contact lenses. Special processes are reviewed, including, mold processes, reactive ion etching, electrospinning, and others. Also discussed are the properties of contact lenses and methods for the measurement. Many of the standard methods are discussed, but other issues are taken up too including a discussion on the assessment of cytotoxic effects, the Schirmer tear test, and others. The book concludes with a chapter detailing the possible medical problems related to contact lenses and how to avoid them. These include eye diseases, allergic and toxic reactions, as well as methods for medical treatment such as disinfection agents. Audience The book will be used by chemists, polymer scientists, ophthalmologists, engineers in the contact lens industry as well as polymer industries.

Leseprobe

Table of Contents

Cover

Title Page

Copyright

Preface

Acknowledgements

1 Types of Lenses

1.1 History of Contact Lenses

1.2 Materials

1.3 Monomers

1.4 Soft Lenses

1.5 Water Absorbable Formulations

1.6 Bandage Contact Lenses

1.7 Functional Contact Lenses

1.8 Scleral Contact Lenses

1.9 Multifocal Contact Lenses

1.10 Augmented Reality Contact Lens Systems

1.11 Siloxane Macromers

1.12 Oxygen-Permeable Lenses

1.13 Natural Protein Polymer Contact Lenses

1.14 Ultrathin Coating

1.15 Anti-Biofouling Contact Lenses

1.16 Drug Delivery via Hydrogel Contact Lenses

1.17 Simulation Methods

References

2 Fabrication Methods

2.1 Computer-Aided Contact Lens Design and Fabrication

2.2 Contact Lenses with Selective Spectral Blocking

2.3 Colored Contact Lenses

2.4 Decentered Contact Lenses

2.5 Stabilized Contact Lenses

2.6 Additive Manufacturing

2.7 Mold Process

2.8 Reactive Ion Etching

2.9 Electrospinning

2.10 Rigid Plastic Lenses

2.11 Soft Plastic Lenses

2.12 Coating Methods

2.13 Disinfection of Contact Lenses

2.14 Integrated Microtubes

2.15 Injection Molding

2.16 Handling Tools

References

3 Properties

3.1 Ophthalmic Compatibility Requirements

3.2 Standards

3.3 Eye Model with Blink Mechanism

3.4 Assessment of Cytotoxic Effects

3.5 Special Functions

3.6 Cleaning of Contact Lenses

3.7 Biofouling

3.8 Wettability

3.9 Material Properties and Antimicrobial Efficacy

3.10 Microscopic Examination

3.11 Schirmer Tear Test

3.12 Ocular Surface Disease Index Test

3.13 Corneal Fluorescein Staining Test

3.14 Ion Permeability

3.15 Hydrodell Water Permeability Technique

3.16 Oxygen Permeability and Transmissibility

3.17 Optical Biometer

References

4 Drug Delivery

4.1 Basic Issues

4.2 Methodologies for the Design of Therapeutic Contact Lenses

4.3 Hydrogels

4.4 Contact Lens Gels

4.5 Molecularly Imprinted Contact Lenses

4.6 Special Drugs

References

5 Medical Problems

5.1 Eye Diseases

5.2 Corneal Edema

5.3 Presbyopia and Myopia Control

5.4 Toxic Soft Lenses

5.5 Disinfection Agents

5.6 Silicone Hydrogels

5.7 Limbal Stem Cell Deficiency

5.8 Computer Vision Syndrome

5.9 Dry Eye Problems

5.10 Orthokeratology

References

Index

Acronyms

Chemicals

General Index

End User License Agreement

List of Illustrations

Chapter 1

Figure 1.1 Monomers for side-chain-linked amino acids.

Figure 1.2 Compounds for a block copolymer.

Figure 1.3 Hydrophilic methacrylamide-based monomers.

Figure 1.4 Monomers for hydrophilic polymers.

Figure 1.5 Bisacrylamide monomers.

Figure 1.6 Polyfunctional methacrylate compounds.

Figure 1.7 Hydrophobic monomers.

Figure 1.8 Hydrophilic monomers.

Figure 1.9 Hydrophobic strengthening monomers.

Figure 1.10 Crosslinking monomers.

Figure 1.11 Monomers and comonomers.

Figure 1.12 Azo initiators.

Figure 1.12 (cont) Peroxy initiators.

Figure 1.12 (cont) Photoinitiators.

Figure 1.12 (cont) Photoinitiators.

Figure 1.13 Tinting agents.

Figure 1.13 (cont) Tinting agents.

Figure 1.14 2-Alkenyl azlactones.

Figure 1.14 (cont) Cycloalkyl azlactones.

Figure 1.15 2-Isopropenyl-4,4-dimethyl-2-oxazolin-5-one.

Figure 1.16

n

-Nonanol.

Figure 1.17 Diethylene glycol monoethyl ether.

Figure 1.18 Methyl enanthate or Methyl heptanoate.

Figure 1.19 3-[Tris(trimethylsiloxy)silyl]propyl methacryloyloxyethyl succinate.

Figure 1.20 Monomers for telechelic macromonomers (20).

Figure 1.21 Nucleating agents (31).

Figure 1.22 Cross-sectional view of a contact lens mold assembly (31).

Figure 1.23 Synthesis of

N

-carbomethoxymethyl-

N

-methacryloylamidopropyl-

N

,

N

-dime...

Figure 1.24 Sugars in hyaluronic acid.

Figure 1.25 Crosslinking agents.

Figure 1.26 Monomers.

Figure 1.27 Poly(siloxane) monomers.

Figure 1.28 Trifluoromethanesulfonic acid.

Figure 1.29 Drugs.

Figure 1.30 Target biomarkers.

Figure 1.30 (cont) Target biomarkers.

Figure 1.31 Prodan (1-(6-(Dimethylamino)naphthalen-2-yl)propan-1-one).

Figure 1.32 Synthesis of Quin-C18.

Figure 1.33 Block diagram of sensor (60).

Figure 1.34 Hormones.

Figure 1.35 Chipless functional contact lens (61).

Figure 1.36 Electronic contact lens system (65).

Figure 1.37 Accessory device (65).

Figure 1.38 Beam pattern generated by an accessory device (65).

Figure 1.39 Lens manufacturing system (103).

Figure 1.40 4-(Phenyldiazenyl) phenyl methacrylate.

Figure 1.41 UV-blocking agents.

Figure 1.42 Silicone monomers.

Figure 1.43 Monomers for non-silicone hydrogels.

Figure 1.44 Crosslinking agents.

Figure 1.45 Catalysts.

Figure 1.46 Hydrophilic monomers.

Figure 1.47 Initiators.

Figure 1.48 Catalysts.

Figure 1.49 Peroxides.

Figure 1.49 (cont) Peroxides.

Figure 1.50 Monomers.

Figure 1.51 Isocyanates.

Figure 1.51 (cont) 1,3,5-Tris(6-isocyanatohexyl) biuret.

Figure 1.52 2-Isocyanatoethyl methacrylate.

Figure 1.53 Contact lens structure (128).

Figure 1.54 Contact angle of water of a silicone rubber sheet coated by a methan...

Figure 1.55 Synthesis of 2-methacryloyloxyethyl phosphorylcholine and (2-methacr...

Figure 1.56 Bis(trimethylsilyloxy)methylsilylpropyl glycerol methacrylate.

Figure 1.57 Bicinchoninic acid.

Figure 1.58 4’,6-Diamidin-2-phenylindol.

Figure 1.59 Chitosan structure.

Figure 1.60 Naphazoline.

Figure 1.61 2-Methacryloxyethyl phosphate.

Figure 1.62 Ligand concentrations versus naphazoline content.

Figure 1.63 Monomers for an ophthalmic drug delivery system.

Chapter 2

Figure 2.1 Special contact lens (8).

Figure 2.2 Decentered contact lens structure (16).

Figure 2.3 Front of a stabilized contact lens (17).

Figure 2.4 Mold insert (19).

Figure 2.5 Side elevation of a contact lens (21).

Figure 2.6 Contact lens mold assembly (22).

Figure 2.7 1-Vinyl-2-pyrrolidinone.

Figure 2.8 Monomeric acids for mat-forming polymers.

Figure 2.9 Comonomers for mat production.

Figure 2.9 (cont) Comonomers for mat production.

Figure 2.9 (cont) Comonomers for mat production.

Figure 2.10 Hydrophilic monomers.

Figure 2.11 Crosslinking agents.

Figure 2.12 Genipin.

Figure 2.13 Di-

sec

-butyl peroxy dicarbonate.

Figure 2.14 Hydrazine salts.

Figure 2.15 Etidronic acid.

Figure 2.16 Compounds in isotonic buffered saline solution.

Figure 2.17 Method of inserting a contact lens (51).

Chapter 3

Figure 3.1 Benzalkonium Chlorides.

Figure 3.2 Lens materials.

Figure 3.3 Diethylenetriamine penta(methylenephosphonic acid).

Figure 3.4 Equilibrium water content vs. monomer content (84).

Figure 3.5 Transparency vs. monomer content (84).

Figure 3.6 Oxygen permeability vs. monomer content (84).

Figure 3.7 Amount of

Staphylococcus aureus

on the surface vs. monomer content (8...

Figure 3.8 Optical measurement system (112).

Figure 3.9 Swept source optical coherence tomography system (107).

Chapter 4

Figure 4.1

α

-Cyclodextrin.

Figure 4.2 Vitamin E.

Figure 4.3 Oleic acid.

Figure 4.4 Cationic drugs.

Figure 4.5 Unsaturated fatty acids.

Figure 4.6 Betaxolol hydrochloride.

Figure 4.7 Chemicals for the synthesis of a HEMA-chitosan polymer.

Figure 4.8

N

,

N

’-Carbonyldiimidazole and its methacrylic acid derivative.

Figure 4.9 Cyclosporine A.

Figure 4.10 Disodium cromoglycate.

Figure 4.11 Disuccinimidyl carbonate.

Figure 4.12 Biotin.

Figure 4.13 Tobramycin.

Figure 4.14 Vancomycin.

Figure 4.15 Amount of drug release vs. time (64).

Figure 4.16 Diazeniumdiolate.

Figure 4.17 Acetazolamide.

Figure 4.18 Flurbiprofen.

Figure 4.19 Timolol.

Figure 4.20 Change of drug release rate vs. Vitamin E concentration (107).

Figure 4.21 Dexamethasone.

Figure 4.22 Trisodium citrate.

Figure 4.23 Ketotifen fumarate.

Figure 4.24 Ketotifen fumarate in the tear fluid as a function of time (133).

Figure 4.25 Cumulative release of ketotifen fumarate (95).

Figure 4.26 Ciprofloxacin.

Figure 4.27 3-Methacryloxypropyltris(trimethylsiloxy) silane.

Figure 4.28 Antibacterial ocular drugs.

Figure 4.29 4-Methyl-4-pentenoic acid.

Figure 4.30

In-vitro

release as a function of time (141).

Figure 4.31 Polymyxin B.

Figure 4.32 Vancomycin.

Figure 4.33 Epinastine.

Figure 4.34 Bimatoprost.

Figure 4.35 Dipicolylamine.

Figure 4.36 Gatifloxacin.

Figure 4.37 Dorzolamide.

Figure 4.38 Ethoxzolamide.

Figure 4.39 Monomers for hydrogels.

Figure 4.40

L

-Histidine.

Figure 4.41 Hyaluronic acid.

Figure 4.42 Compounds used in Preparation 4–4.

Figure 4.43 Cumulative release of hyaluronic acid (90).

Figure 4.44 Preparation of the ring-implanted contact lenses, reprinted from Mac...

Figure 4.45 Lifitegrast (

N

-[[2-(6-Benzofuranylcarbonyl)-5,7-dichloro-1,2,3,4-tet...

Figure 4.46 Diclofenac sodium.

Figure 4.47 Release of diclofenac sodium vs. (M/T) ratio (161).

Figure 4.48 Cetalkonium chloride.

Figure 4.49 Moxifloxacin.

Figure 4.50

N

-[Tris(trimethylsiloxy)silylpropyl]acrylamide.

Figure 4.51 Norfloxacin.

Figure 4.52 Sparfloxacin.

Figure 4.53 Latanoprost.

Figure 4.54 Loteprednol etabonate.

Figure 4.55 Template molecules.

Chapter 5

Figure 5.1 Oxamic acid.

Figure 5.2 Average corneal swelling vs. time (19).

Figure 5.3 Thimerosal.

Figure 5.4 Poly(hexamethylene) biguanide.

Figure 5.5 Compounds for eye drops.

Figure 5.6 Denatonium benzoate.

Figure 5.7

N

-Vinyl-2-pyrrolidone and Vinylimidazolium methochloride.

Figure 5.8 Saccharides (46).

Figure 5.8 (cont) Saccharides (46).

Figure 5.9 Chelating agents.

Figure 5.10 Preservatives.

Figure 5.11 Hexamethylene biguanide.

Figure 5.12 5-Bromo-2’-deoxyuridine.

Figure 5.13 Hematoxylin.

Figure 5.14 Compounds for derivatizing.

Figure 5.15 Diquafosol.

Figure 5.16 Refractive error change with time (90, 97).

List of Tables

Chapter 1

Table 1.1 History of contact lenses (2).

Table 1.2 Monomers for contact lenses.

Table 1.3 Monomers (18).

Table 1.4 Side-chain-linked amino acids (18).

Table 1.5 Hydrophilic methacrylamide-based monomers (23).

Table 1.6 Hydrophilic polymers (23).

Table 1.7 Multifunctional monomers (23).

Table 1.8 Monomers (19).

Table 1.9 Mechanical properties (19).

Table 1.10 Monomers (26).

Table 1.11 Initiators (26).

Table 1.12 Azlactone monomers (28).

Table 1.13 Monomers for controlling water content (30).

Table 1.14 Nucleating agents (31).

Table 1.15 Crosslinking agents (39).

Table 1.16 Monomers (43).

Table 1.17 Poly(siloxane) monomers (43).

Table 1.18 Target biomarkers (52).

Table 1.19 Examples of target analytes (61).

Table 1.20 Common species in tears and blood (61).

Table 1.21 Glucose biosensors developed for contact lenses (66).

Table 1.22 UV-blocking agents (21).

Table 1.23 Silicone monomers (21).

Table 1.24 Composition for a multifocal contact lens (21).

Table 1.25 Monomers for non-silicone hydrogels (31).

Table 1.26 Crosslinking agents for non-silicone hydrogels (31).

Table 1.27 Free radical catalysts and initiators (31).

Table 1.28 Initiators.

Table 1.29 Contents of the contact lenses (125).

Table 1.30 Free radical generating initiators (126).

Table 1.31 Synthesis and properties of polymers.

Table 1.32 Monomers (127).

Table 1.33 Isocyanates (127).

Table 1.34 Protein absorption of artificial tear fluid on the surface of sample ...

Table 1.35 Number of colony-forming units (141).

Chapter 2

Table 2.1 Optical design software.

Table 2.2 Inks and pigment levels (13).

Table 2.3 Formulation of contact lens (25).

Table 2.4 Polymers for mat production (27).

Table 2.5 Comonomers for mat production (27).

Table 2.6 Hydrophilic monomers (31).

Table 2.7 Formulation for preparing contact lenses (40).

Chapter 3

Table 3.1 Standards for testing contact lenses.

Table 3.2 Potential uses of contact lenses (44).

Table 3.3 Pluronic® surfactants (55).

Table 3.4 Cleaning composition for contact lenses (55).

Table 3.5 Daily disposable lenses (73).

Table 3.6 Roughness values (91).

Chapter 4

Table 4.1 Setschenow constants.

Table 4.2 Drugs for molecularly imprinted contact lenses (68).

Table 4.3 monomer mixture for silicone contact lenses (130, 132).

Table 4.4 Formulations of the contact lenses (95).

Table 4.5 Loss of drugs (132).

Chapter 5

Table 5.1 Eye diseases.

Table 5.2 Properties of the lenses (19).

Table 5.3 Saccharides (45).

Table 5.4 Chelating agents (45).

Table 5.5 Results of dry-eye study (89).

Guide

Cover

Table of Contents

Copyright

Preface

Begin Reading

Index

General Index

Also of Interest

End User License Agreement

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Scrivener Publishing100 Cummings Center, Suite 541JBeverly, MA 01915-6106

Publishers at Scrivener

Martin Scrivener ([email protected])Phillip Carmical ([email protected])

Contact Lenses

Materials, Chemicals, Methods and Applications

Johannes Karl Fink

Montanuniversität Leoben, Austria

This edition first published 2022 by John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA and Scrivener Publishing LLC, 100 Cummings Center, Suite 541J, Beverly, MA 01915, USA

© 2022 Scrivener Publishing LLC

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Library of Congress Cataloging-in-Publication Data

ISBN 978-1-119-85735-8

Cover image: Pixabay.com

Cover design by Russell Richardson

Set in size of 11pt and Minion Pro by Manila Typesetting Company, Makati, Philippines

Printed in the USA

10 9 8 7 6 5 4 3 2 1

Preface

This book focuses on the chemistry and properties of contact lenses and their fabrication methods.

The text starts with a chapter in which a detailed history of contact lenses spanning over almost 500 years is presented

Next, common materials that are used for the fabrication of contact lenses are listed and explained, including both the monomers and polymers that are used in their production. Special issues regarding soft lenses, clear contact lenses, and functional contact lenses are also discussed.

Functional contact lenses can be used for remote health monitoring and ocular drug delivery systems. Besides the materials used here, these issues are detailed in further separate chapters. Also, special fabrication methods are discussed, e.g., the fabrication of multifocal contact lenses and the fabrication of ultrathin coatings.

There is also an important discussion on additives that can be used, e.g., for oxygen-permeable materials or anti-biofouling materials.

The chapter ends with a discussion of simulation methods for contact lenes, such asocular topography parameters, gas-permeable lenses, and computerized videokeratography.

In the second chapter, several common fabrication methods for contact lenses are discussed. Here, computer-aided contact lens design, methods for the fabrication of colored contact lenses, and the fabrication of decentered contact lenses are detailed.

Also, special processes are reviewed, including mold processes, reactive ion etching, electrospinning and others.

Another chapter discusses the properties of contact lenses and methods of measurement. Here, a lot of standard methods are discussed. Besides standard methods, other issues are discussed such as the assessment of cytotoxic effects, the Schirmer tear test and others.

A chapter is devoted to drug delivery of contact lenses, a comparatively new issue.

Finally, a chapter details the possible medical problems related to contact lenses and how to avoid them. These are eye diseases, allergic and toxic reactions. Also, disinfection agents that can be used and methods for the medical treatment of such problems are detailed.

The text focuses on the literature of the past decade. Beyond education, this book will serve the needs of industry engineers and specialists who have only a passing knowledge of the plastics and composites industries but need to know more.

How to Use This Book

Utmost care has been taken to present reliable data. Because of the vast variety of material presented here, however, the text cannot be complete in all aspects, and it is recommended that the reader study the original literature for more complete information.

The reader should be aware that mostly US patents have been cited where available, but not the corresponding equivalent patents in other countries. For this reason, the author cannot assume responsibility for the completeness, validity or consequences of the use of the material presented herein. Every attempt has been made to identify trademarks; however, there were some that the author was unable to locate.

Index

There are three indices: an index of acronyms, an index ofchemicals, and a general index.

In the index of chemicals, compounds that occur extensively, e.g., “acetone,” are not included at every occurrence, but rather when they appear in an important context.

Acknowledgements

I am indebted to our university librarians, Dr. Christian Hasenhüttl, Margit Keshmiri, Friedrich Scheer, Christian Slamenik, Renate Tschabuschnig, and Elisabeth Groß for their support in literature acquisition. I also want to express my gratitude to all the scientists who have carefully published their results concerning the topics dealt with herein. This book could not have been otherwise compiled.

In addition, I am very grateful to the ophthalmologists Dr. Anna Schlanitz-Bolldorf and Dr. Ferdinand Schlanitz, who inspired me to write this text. Last, but not least, I want to thank the publisher, Martin Scrivener, for his abiding interest and help in the preparation of the text. In addition, my thanks go to Jean Markovic, who made the final copyedit with utmost care.

Johannes Fink

Leoben, December 2, 2021

1Types of Lenses

1.1 History of Contact Lenses

A history of contact lenses spanning over almost 500 years has been detailed (1, 2). It is based on historical works, scientific papers and journal articles and looks at both the modern disposable lens as well as the hard and soft lenses that came before. Some important events are collected in Table 1.1.

Table 1.1 History of contact lenses (2).

Year

Inventor

Issue

1508

Leonardo da Vinci

Corneal neutralization

1637

René Descartes

Fluid-filled tube

1685

Philippe de La Hire

Neutralization of cornea

1801

Thomas Young

Three color theory of perception

1827

George Biddell

Theory of astigmatism

1845

Sir John F. W. Herschel

Convex lenses

1846

Carl Zeiss

Optical instruments

1851

Johann Nepomuk Czermak

Water-filled goggle

1887

Adolf Eugen Fick

First successful contact lens

1961

Otto Wichterle

Soft contact lenses

1979

Kyoichi Tanaka

Silicone hydrogel materials

In 1508, Leonardo da Vinci first had the idea of placing a corrective lens directly onto the surface of the eye (3–5). In 1637, René Descartes proposed another idea in which a glass tube filled with liquid is placed in direct contact with the cornea.

In 1887, Adolf Eugen Fick, a German physiologist, created the first successful contact lens (6). Glass-blown scleral lenses remained the only form of contact lens until 1938, when poly(methyl methacrylate) (PMMA) was developed, and Mullen and Obring used the plastic to manufacture scleral lenses. Obring developed the Plexiglass series in New York in 1940 (4).

In 1961, the Czech chemist Otto Wichterle invented soft contact lenses (7, 8). In 1970, rigid gas-permeable contact lenses were developed, and widely accepted for the advantages of small diameter (about 9 mm) and gas permeability. Silicone hydrogel materials were developed in 1979 (9). In 1999, an important development was the launch of the first silicone hydrogels onto the market. These new materials showed an extremely high oxygen permeability with comfort performance (4).

The factors that influenced the development of special materials have been reported (10). Accounts of early attempts to improve vision by use of a lens contacting the eye are limited to a few isolated observations (11). Practical success was not realized until techniques for fabrication of lenses from glass were sufficiently developed (12). PMMA replaced glass in the late 1930s. This material is more durable, more readily fabricated and was claimed by some authors to show a better ocular compatibility (13). During the same broad period of time, there was also a change in emphasis from scleral to corneal contact lenses, which placed different demands on material design and development.

More is demanded from ophthalmic treatments using contact lenses, which are currently used by over 125 million people around the world (14). Improving the material of contact lenses is currently a rapidly evolving discipline (10).

A search has been performed of the titles of papers in the Scopus database to identify contact lens-related articles published this century (15). The ten most highly cited papers were determined from the total list of 4,164 papers found. Rank-order lists by count were assembled for the top 25 in each of four categories: authors, institutions, countries and journals. A 20-year subject-specific contact lens h-index was derived for each author, institution, country and journal to serve as a measure of impact in the field. The top 10 constituents (of the top 25) of each category were ranked and tabulated (15).

1.2 Materials

Contact lens materials (10) are typically based on polymer- or silicone-hydrogel, with additional manufacturing technologies employed to produce the final lens. These processes are simply not enough to meet the increasing demands for contact lenses and the ever-increasing number of contact lens users (14).

An advanced perspective on contact lens materials has been presented, with an emphasis on materials science employed in developing new contact lenses (14, 16). The future trends for contact lens materials are to graft, incapsulate, or modify the classic contact lens material structure to provide new or improved functionality. Also, some of the fundamental material properties are discussed, and the outlook for related emerging biomaterials is presented.

Contact lens materials and lens types, treatment for contact lens and tear film complications, and myopia correction and contact lenses for abnormal ocular conditions have been detailed (17). Current topics in this field are miniscleral lenses, keratoconus, corneal crosslinking, and pediatric, cosmetic and prosthetic contact lenses. Furthermore, simulation programs for scleral lens fitting, sagittal values, soft toric mislocation, front vertex power, orthokeratology and rigid lens design are discussed.

1.3 Monomers

The monomers that can be used for contact lenses, which are described in the following sections and in both tables and references, are collected in Table 1.2.

These issues will be detailed in the following sections of this chapter.

1.3.1 Monomers for Block Copolymers

A block copolymer that contains both hydrophobic and hydrophilic blocks with amino acid groups has been described (18).

The principal monomers for such block copolymers are a combination of two monomers capable of forming a hydrogel; such monomers are collected in Table 1.3.

Table 1.2 Monomers for contact lenses.

Monomers and monomer types

Usage

References

2-Hydroxyethyl methyacrylate

N

-Vinyl-2-pyrrolidone Methyl methacrylate Isobornyl methacrylate

tert

-Butylcyclohexyl methacrylate

Soft lenses

(19)

Hydrophobic monomers

Strengthening agents

Table 1.8

Hydrophilic monomers

Table 1.8

Hydrophilic monomers

Hydrogels

Table 1.10

Azlactones

Surface treatment

Table 1.12

Acrylamide

N

-Hydroxyethyl acrylamide

N

-Isopropyl acrylamide 2-Acrylamido-2-methylpropane-sulfonic acid 2-Hydroxyethyl methacrylate 2-Hydroxyethyl acrylate

Macromers

(20)

Acryl monomers

Water absorbable

Table 1.16

Poly(siloxane)

Water absorbable

Table 1.17

4-(Phenyldiazenyl) phenyl methacrylate

Blue-light blocking

(21)

Acrylates

UV-blocking

Table 1.22

Silicone hydrogel

Multifocal lenses

Table 1.23

Acrylates

Non-silicone hydrogel

Table 1.25

Crosslinking agents

Non-silicone hydrogel

Table

Table 1.26

Oxyperm

Oxygen permeable

Table 1.32

Ionoperm

Oxygen permeable

Table 1.32

Table 1.3 Monomers (18).

Monomer

Monomer

2-Ethylphenoxy acrylate

2-Ethylphenoxy methacrylate

2-Ethylthiophenyl acrylate

2-Ethylthiophenyl methacrylate

2-Ethylaminophenyl acrylate

2-Ethylaminophenyl methacrylate

Phenyl acrylate

Phenyl methacrylate

Benzyl acrylate

Benzyl methacrylate

2-Phenylethyl acrylate

2-Phenylethyl methacrylate

3-Phenylpropyl acrylate

3-Phenylpropyl methacrylate

3-Propylphenoxy acrylate

3-Propylphenoxy methacrylate

4-Butylphenoxy acrylate

4-Butylphenoxy methacrylate

4-Phenylbutyl acrylate

4-Phenylbutyl methacrylate

Side-chain-linked amino acids are collected in Table 1.4. Some of these compounds are shown in Figure 1.1.

Table 1.4 Side-chain-linked amino acids (18).

Monomer

Monomer

Acryloyl-

L

-lysine

Acryloyl-

L

-serine

Acryloyl-

L

-threonine

Acryloyl-

L

-tyrosine

Acryloyl-

L

-amino-phenylalanine

Acryloyl-

L

-cysteine

Acryloyl-

L

-oxy-proline

N

ϵ

-acryloyl-N

α

-Oelityl-L-Lysine

The synthesis of a variety of such monomers has been detailed (18). For example, the synthesis of (S)-6-acrylamido-2-aminohexanoic acid monomers is performed via a copper complex (18):

Preparation 1–1: L-lysine (14.62 g; 100 mmol) was dissolved in 150 ml deionized water and heated to about 80°C. Copper carbonate (16.6 g; 75 mmol) was added in portions over a period of 30 min. The reaction was stirred for an additional 30 min. The hot, deep-blue suspension was filtered through silica gel. The filter was washed with a small amount of water. On the following day, the lysine copper complex containing the combined filtrate was cooled in an ice bath, and 100 ml tetrahydrofuran was added. A solution of acryloyl chloride in methyl-tert-butylether (8.9 ml, 110 mmol) was added dropwise during a period of 1 h. The pH was initially maintained between 8 and 10 by parallel, dropwise addition of 10% sodium hydroxide solution. After half of the acryloyl chloride solution had been added, the product began to precipitate. When most of the acryloyl chloride had been added, addition of sodium hydroxide was slowed down to allow the pH to drop to about 6 and the temperature of the reaction mixture was allowed to reach room temperature. The blue suspension was stirred for an additional 2 h and was then filtered. The solid material retained on the filter was washed with water and acetone and then dried. A yield of 6.5 g of acryloyl-L-lysine copper complex was obtained. Acryloyl-L-lysine copper complex (29.5 g) was suspended in 300 ml deionized water and cooled in an ice bath. H2S gas was bubbled into the suspension until copper sulfide precipitation was complete; then 3 g of active charcoal was added to the suspension. The suspension was heated briefly to 100°C. After cooling to room temperature, 500 ml acetone was added to the suspension which was then filtered on silica gel. The clear filtrate was put in a rotary evaporator. After evaporation of the solvent, the solid product was recrystallized from 200 ml of 50% aqueous acetone. A yield of 17.76 g (69.76%) of white powder was obtained. The structure of the compound was verified by nuclear magnetic resonance spectroscopy and LC-MS spectroscopy.

Figure 1.1 Monomers for side-chain-linked amino acids.

The preparation of a block copolymer containing a hydrophilic cellophil polymer and a lipid-like copolymer was done by raft polymerization as follows (18):

Preparation 1–2: Step A

In a 50 ml round-bottom flask, a solution of 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (6.13 mg, 0.017 mmol), N,N-Dimethyl acrylamide (0.624 ml, 6.05 mmol), and iso-decyl acrylate (0.163 ml, 0.673 mmol) in 10 ml N,N-dimethylformamide was degassed using ultrasonic treatment. Subsequently, 2-benzyl-2-(dimethylamino)-4’-morpholinobutyrophenone (6.40 mg, 0.017 mmol) was added, and polymerization was induced by UV light. After 4 h of polymerization under stirring, the reaction mixture was purified by extensive dialysis against deionized water using a membrane with a 3.5 kDa MWCO. The mixture was subsequently lyophilized. The average molecular weight (12 kDa) and PDI (1.19) of the block copolymer was verified by GPC measurement.

Step B

The lyophilized macro-CTA prepared in step A (300 mg, 6.82 µmol) was mixed with acryloyl-L-lysine (100 mg, 0.499 mmol) in 10 ml deionized water. The mixture was degassed using ultrasonic treatment. 2,2’-Azobis(2-methylpropionamidine) dihydrochloride (4.62 mg, 0.017 mmol) was added to the mixture. The polymerization was induced by heating the mixture in a reaction vessel to 50°C. After 4 h of polymerization at 50°C, the resulting block copolymer was purified by extensive dialysis against deionized water using a membrane with a 3.5 kDa MWCO. The cellophil block copolymer was subsequently lyophilized. The average molecular weight (18 kDa) and PDI (1.25) of the block copolymer were verified by GPC measurement. Larger block copolymers (32 kDa, PDI 1.28; 58 kDa, PDI 1.24) were obtained by decreasing the ratio of CTA to monomers in step A from 1/100 to 1/200 (32 kDa) and 1/400 (58 kDa), respectively, whereas the molar ratios of i-decylacrylate (7.5 mol of 5), DMA (63.9 mol of 5) and AK (28.6 mol of 5) were kept constant.

Some of the compounds mentioned in Preparation 1–2 are shown in Figure 1.2.

1.3.2 Silicone Acrylamides

Examples of hydrophilic methacrylamide monomers are collected in Table 1.5. Some of these compounds are shown in Figure 1.3. Also, several other similar monomers have been detailed (22).

These alkyl and aryl groups can be straight or branched. Of these monomers, the N-(2-hydroxyethyl)methacrylamide monomer is preferable from a perspective of increasing the transparency of the so obtained polymer.

The monomer mixture for synthesizing the polymer additionally may contain between about 1% and about 30% of a hydrophilic polymer with a molecular weight of about 1000 Dalton or higher in the monomer and polymer component of the monomer mixture in order to enhance the wettability, resistance to adhesion of proteins, resistance to adhesion of lipids and combinations thereof.

Figure 1.2 Compounds for a block copolymer.

Figure 1.3 Hydrophilic methacrylamide-based monomers.

Table 1.5 Hydrophilic methacrylamide-based monomers (23).

Compound

N

-Hydroxymethyl methacrylamide

N

-(2-Hydroxyethyl) methacrylamide

N

-(2-Hydroxypropyl) methacrylamide

N

-(3-Hydroxypropyl) methacrylamide

N

-(2-Hydroxybutyl) methacrylamide

N

-(3-Hydroxybutyl) methacrylamide

N

-(4-Hydroxybutyl) methacrylamide

N

-(2-Hydroxymethylphenyl) methacrylamide

N

-(3-Hydroxymethylphenyl) methacrylamide

N

-(4-Hydroxymethylphenyl) methacrylamide

Examples of hydrophilic polymers that can be used in the polymer are shown in Table 1.6. Some of the monomers of these compounds are shown in Figure 1.4.

Hydrophilic polymers selected from poly(vinyl pyrrolidone), poly(N,N-dimethyl acrylamide), poly(acrylic acid), and poly(vinyl alcohol) may be particularly effective for enhancing the wettability of silicone hydrogels (23). Poly(vinyl pyrrolidone) and poly(N,N-dimethyl acrylamide) provide a balance between the wettability and the compatibility of the polymerization mix in certain formulations.

The polymer can also include a monomer with two or more reactive groups as a copolymerization component. In this case, the polymer becomes solvent resistent.

Preferable monomers with two or more vinyl groups include bifunctional and polyfunctional acrylates. Examples are shown in Table 1.7. Some bisacrylamide monomers are shown in Figure 1.5. Polyfunctional methacrylate compounds are shown in Figure 1.6.

A polymerization initiator may be added to enhance the polymerization traction. Suitable initiators include thermal polymerization initiators, such as a peroxide compound or an azo compound, or photopolymerization initiators. Also, photoinitiators can be added in order to enhance the polymerization.

Table 1.6 Hydrophilic polymers (23).

Polymer compound

Poly(

N

-vinyl pyrrolidone)

Poly(

N

-vinyl-2-piperidone)

Poly(

N

-vinyl-2-caprolactam)

Poly(

N

-vinyl-3-methyl-2-caprolactam)

Poly(

N

-vinyl-3-methyl-2-piperidone)

Poly(

N

-vinyl-4-methyl-2-piperidone)

Poly(

N

-vinyl-4-methyl-2-caprolactam)

Poly(

N

-vinyl-3-ethyl-2-pyrrolidone)

Poly(

N

-vinyl-4,5-dimethyl-2-pyrrolidone)

Poly(2-vinylimidazole)

Poly(

N

-vinyl formamide)

Poly(

N

-vinyl acetamide)

Poly(

N

-methyl-

N

-vinyl acetamide)

Poly(

N

,

N

-dimethyl acrylamide)

Poly(

N

,

N

-diethyl acrylamide)

Poly(

N

-isopropyl acrylamide)

Poly(vinyl alcohol)

Poly(acrylate)

Poly(ethylene oxide)

Poly(2-ethyl oxazoline)

Heparine Polysaccharide

Poly(acryloyl morpholine)

Table 1.7 Multifunctional monomers (23).

Compound

Compound

Ethylene glycol acrylate

Ethylene glycol dimethacrylate

Diethylene glycol diacrylate

Diethylene glycol dimethacrylate

Triethylene glycol diacrylate

Triethylene glycol dimethacrylate

Neopentyl glycol diacrylate

Neopentyl glycol dimethacrylate

Tetraethylene glycol diacrylate

Tetraethylene glycol dimethacrylate

Glyceryl triacrylate

Glyceryl trimethacrylate

Pentaerythritol tetraacrylate

Pentaerythritol tetramethacrylate

Trimethylol propane triacrylate

Trimethylol propane trimethacrylate

N

,

N’

-Methylene bisacrylamide

N

,

N’

-Ethylene bisacrylamide

N

,

N’

-Propylene bisacrylamide

Figure 1.4 Monomers for hydrophilic polymers.

Figure 1.5 Bisacrylamide monomers.

Several examples of the polymerization procedure have been detailed (23).

1.4 Soft Lenses

1.4.1 Hydrogels

Soft contact lens materials are made by polymerizing and crosslinking hydrophilic monomers such as 2-hydroxyethyl methyacrylate, N-vinyl-2-pyrrolidone, and combinations thereof (19).

The polymers produced by polymerizing these hydrophilic monomers exhibit significant hydrophilic character themselves, and are capable of absorbing a significant amount of water in their polymeric matrices. Due to their ability to absorb water, these polymers are often referred to as hydrogels.

These hydrogels are optically clear and, due to their high levels of water of hydration, are particularly useful materials for making soft contact lenses. However, the high levels of water of hydration of hydrogels contributes to their relative lack of physical strength, which results in hydrogel contact lenses being relatively easy to tear (19).

Figure 1.6 Polyfunctional methacrylate compounds.

Various hydrophobic monomers have been copolymerized with these hydrophilic monomers in order to obtain polymers with an improved physical strength. Such hydrophobic monomers include styrene, and various acrylates and methacrylates such as methyl methacrylate, isobornyl methacrylate, and tert-butylcyclohexyl methacrylate. The last two compounds are shown in Figure 1.7.

Figure 1.7 Hydrophobic monomers.

While these hydrophobic monomers do increase the physical strength of hydrogel polymers, they also produce polymers with lower levels of water of hydration than the unmodified hydrogels.

So, an attempt was made to provide polymeric materials with an increased physical strength and high levels of water of hydration (19).

It has been found that certain hydrophobic monomers act as strengthening agents when copolymerized with hydrophilic monomers and crosslinkers. Examples of these monomers are shown in Table 1.8 and in Figures 1.8, 1.9, and 1.10.

Most preferred contact lenses have an oxygen transport rate of at least about 2 × 10−6cm3sec−1cm−2atm−1, which makes them hydrolytically stable, biologically inert, transparent, and resilient. Furthermore, they should preferably have a softness of about 60 or below on the Shore hardness A scale when hydrated. The more preferred materials have a Shore hardness between 25 to 35 on the A scale.

The tensile modulus of elasticity of these hydrated polymers is at least about 50 gmm−2, preferably from about 75 gmm−2 to about 100 gmm−2, and the tear strength is at least about 2.0 gmm−1 thickness, preferably from about 2.0 gmm−1 to about 250 gmm−1 thickness. High tensile modulus of elasticity is desirable for strength and durability. High tear strength is desirable in order to prevent damage to the contact lens due to tearing during patient use, i.e., the removing and placing of the lens on the eye, and to prevent damage to the lens during cleansing and disinfecting.

Table 1.8 Monomers (19).

Hydrophilic monomers

2-Hydroxyethyl methacrylate

N

-(2-Hydroxy ethyl)-methacrylamide

N

-Vinyl-2-pyrrolidone

Glyceryl methacrylate

N

-Methacryloyl glycine

2-Hydroxyl-3-methacryl(propyl)-4-methoxy phenyl ether

2-Hydroxy cyclohexyl methacrylate

Hydrophobic strengthening agent monomers

4-

tert

-Butyl-2-hydroxycyclohexyl methacrylate

4-

tert

-Butyl-2-hydroxycyclopentyl methacrylate

Methacryloylamino-4-

tert

-butyl-2-hydroxycyclohexane

6-Isopentyl-3-hydroxycyclohexyl methacrylate

Methacryloylamino-2-isohexyl-5-hydroxy cyclopentane

Crosslinking monomers

Allyl methacrylate

Ethylene glycol dimethacrylate

Divinyl ethylene urea

1,3-Bis(4-methacryloxybutyl) tetramethyl disiloxane

Figure 1.8 Hydrophilic monomers.

Figure 1.9 Hydrophobic strengthening monomers.

Figure 1.10 Crosslinking monomers.

A soft contact lens formulation is illustrated in the following example (19):

Preparation 1–3: A mixture was made containing 77.0 g of glyceryl methacylate, 22.5 g of 4-tert-butyl-2-hydroxycyclohexyl methacrylate, and 0.5 g of ethylene glycol dimethacrylate. To this mixture was added 0.5 g of benzoin methyl ether, an ultraviolet-induced polymerization initiator. The solution was cast between glass plates separated by a Teflon perfluoro polymer gasket, 0.3 mm thick and cured. After curing, the film was released from the glass plates and hydrated and extracted in hot distilled water for 4 h.

Then, the film was placed in a borate buffered saline solution for testing. The resultant material was optically clear and had a water content of 53% and an oxygen permeability of 18 × 10−11cm3cmseccm2mmHg−1.

The mechanical properties were measured according to the following test methods and gave the results shown in Table 1.9.

Table 1.9 Mechanical properties (19).

Standard

Ref.

Name

Value

ASTM-D 1708

(24)

Young’s modulus of elasticity

60

g mm

‒

2

ASTM-D 1708

(24)

Tensile strength

84

g mm

‒

2

ASTM-D 1708

(24)

% Elongation

164 %

ASTM-D 1938

(25)

Tear Initiation

3.8

g mm

‒

1

1.4.1.1 Polymerizable Contact Lens Formulations

Hydrogel contact lenses, polymerizable compositions useful for making such lenses, packaging systems for use with such lenses and methods of producing such lenses have been discovered (26). These contact lenses have a relatively low surface friction and are able to release hydrophilic polymers present in the contact lenses for prolonged periods of time.

The contact lenses have a lens body. The lens body is the reaction product of a polymerizable composition containing one or more monomers, and a crosslinker that crosslinks the monomers during a polymerization reaction to form a first polymer component. The polymerizable composition also contains a hydrophilic polymer component, which is substantially unreactive during the polymerization.

Thus, the resulting lens body includes a first polymer component formed from the one or more monomers present in the polymerizable composition, and the second polymer component, the hydrophilic polymer component that is physically entangled with the first polymer component in the lens body.

The hydrophilic polymer component is unreactive or substantially unreactive during the polymerization process. Thus, the resulting hydrogel lens body can be understood to be a network of a first polymeric component, formed from the monomers present in the polymerizable composition, and a second polymeric component, the hydrophilic polymer component, in which the hydrophilic polymer component is substantially physically entrapped by the first polymer component. Although there may be some small amounts of reactivity of the hydrophilic polymer component, the reactivity is not sufficient to prevent leaching or release of the hydrophilic polymer from the lens body. The present contact lenses can be understood to consist of an interpenetrating polymer network where the formation of the first polymer component occurs in the presence of the hydrophilic polymer component. However, as discussed herein, in the present contact lenses, it is possible for the hydrophilic polymer component to be released from the lens body even though it is entrapped by the first polymer component.

Examples of these monomers are shown in Table 1.10 and in Figure 1.11.

Polymerization initiators can be used in the polymerizable composition. Thermal initiators that may be used are azo or peroxide compounds, such as those having a half-life at the polymerization temperature of at least 20 min. Examples of initiators are shown in Table 1.11 and in Figure 1.12.

A tinting agent can be any agent that imparts a visibility to the otherwise clear hydrogel lens body. The tinting agent may be a water-soluble dye, or particles of pigment, or combinations thereof. Some examples of tinting agents include copper phthalocyanine blue, Vat Blue 6, Reactive Blue 4, and Reactive Blue 19. These compounds are shown in Figure 1.13.

Figure 1.11 Monomers and comonomers.

Table 1.10 Monomers (26).

Monomers for the first polymer

2-Hydroxyethyl methacrylate

2-(3-Phenyl-3-methylcyclobutyl)-2-hydroxyethyl methacrylate

2-Hydroxyethyl acrylate

2-Hydroxypropyl methacrylate

2-Hydroxypropyl acrylate

3-Hydroxypropyl methacrylate

Glycerol mono acrylate

Glycerol mono methacrylate

n

-Vinyl pyrrolidone

Acrylamide

Hydrophilic monomers for the second polymer

2-Methacryloyloxyethyl phosphorylcholine

Hydrophilic comonomers for the second polymer

n

-Butyl methacrylate

Methacryloyloxyethyl ethylene oxide

Methacryloyloxyethyl propylene oxide

Figure 1.12 Azo initiators.

Table 1.11 Initiators (26).

Azo initiators

2,2’-Azo-bis-isobutyronitrile

2,2’-Azo-bis(2,4-dimethylvaleronitrile)

1,1’-Azo-bis(cyclohexane carbonitrile)

2,2’-Azo-bis(2,4-dimethyl-4-methoxyvaleronitrile)

Peroxy initiators

Isopropyl percarbonate

tert

-Butyl peroctoate

Benzoyl peroxide

Lauroyl peroxide

Decanoyl peroxide

Acetyl peroxide

Succinic acid peroxide

Methyl ethyl ketone peroxide

tert

-Butyl peroxyacetate

Propionyl peroxide

2,4-Dichlorobenzoyl peroxide

tert

-Butyl peroxypivalate

Pelargonyl peroxide

2,5-Dimethyl-2,5-bis(2-ethylhexanoylperoxy)hexane

p

-Chlorobenzoyl peroxide

tert

-Butyl peroxybutyrate

tert

-Butyl peroxymaleic acid

tert

-Butyl-peroxyisopropyl carbonate

Bis(1-hydroxycyclohexyl)peroxide

Photoinitiators (23, 26)

Diethoxyacetophenone

1-Hydroxycyclohexyl phenyl ketone

2,2-Dimethoxy-2-phenylacetophenone

Phenothiazine

Diisopropylxanthogen disulfide

Benzoin

Benzoin methyl ether

2-Hydroxy-2-methyl-1-phenyl-propan-1-one

Bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentyl phosphine oxide

Bis(2,4,6-trimethylbenzoyl)-phenyl phosphine oxide

2,4,6-Trimethylbenzoyl diphenylphosphine oxide

Figure 1.12 (cont) Peroxy initiators.

Figure 1.12 (cont) Photoinitiators.

Figure 1.12 (cont) Photoinitiators.

Figure 1.13 Tinting agents.

An effective amount of the tinting agent used can vary depending on factors such as the type of tinting agent, the reactive monomer composition, or the non-reactive polymers present in the composition. In general, the amount of tinting agent used may be up to about 15% of the polymerizable composition (26).

1.4.1.2 Surface Treatment for Silicone Hydrogel Contact Lenses

The usage of transparent silicone rubber for corneal contact lenses was first described in 1966 (27).

Figure 1.13 (cont) Tinting agents.

Silicone lenses have been subjected to plasma surface treatment to improve their surface properties; for example, to make the surface more hydrophilic, deposit-resistant, or scratch-resistant (28).

A method of surface treatment has been described that consists of coating the device with a carbon layer, followed by the attachment of hydrophilic polymer chains to the surface of the carbon layer. Then, the carbon layer is plasma treated to form reactive functionalities containing oxygen, nitrogen, and/or sulfur. Complementary reactive functionalities in monomeric units along a hydrophilic reactive polymer are then reacted with the reactive functionalities on the carbon layer. Also, a contact lens surface can be pretreated with an oxidizing plasma prior to deposition of the carbon layer in order to improve adhesion of the carbon layer.

Silicone hydrogels generally have a water content of 10% to 80%. Such materials are usually prepared by polymerizing a mixture containing at least one silicone-containing monomer and at least one hydrophilic monomer. Either the silicone-containing monomer or the hydrophilic monomer may function as a crosslinking agent. Examples of silicon-containing monomeric units are bulky polysiloxanylalkyl(meth)acrylic monomers.

Plasma surface treatments involve passing an electrical discharge through a gas at low pressure (28). The electrical discharge may be at radio frequency (typically 13.56 MHz), although microwave and other frequencies can be used. Electrical discharges produce ultraviolet radiation, in addition to being absorbed by atoms and molecules in their gas state, resulting in energetic electrons and ions, atoms, molecules, and radicals. So, a plasma is a complex mixture of atoms and molecules in both ground and excited states, which reach a steady state after the discharge is begun. The circulating electrical field causes these excited atoms and molecules to collide with one another as well as the walls of the chamber and the surface of the material being treated.

The deposition of a coating from a plasma onto the surface of a material has been shown to be possible from high-energy plasmas without the assistance of sputtering. Monomers can be deposited from the gas phase and polymerized in a low pressure atmosphere, at preferably 0.001 torr to 1.0 torr, onto a substrate utilizing continuous or pulsed plasmas, suitably as high as about 1000 W. A modulated plasma may be applied 100 ms on then off. In addition, liquid nitrogen cooling has been utilized to condense vapors out of the gas phase onto a substrate and subsequently use the plasma to chemically react these materials with the substrate. However, plasmas do not require the use of external cooling or heating to cause the deposition. Low or high wattage (20 W to 500 W) plasmas can coat even the most chemical-resistant substrates, including silicones.

The method of fabrication can be done as follows (28):

Subjecting the surface of a lens substrate to a plasma polymerization deposition with a C

1

to C

10

saturated or unsaturated hydrocarbon to form a polymeric carbonaceous layer (or

carbon layer

) on the lens surface,

Forming reactive functionalities on the surface of the carbon layer, and

Attaching hydrophilic polymer chains to the carbon layer by reacting the reactive functionalities on the carbon layer with complementary isocyanate or ring-opening reactive functionalities along a reactive hydrophilic polymer.

It has been found that in the case of silicone hydrogels, the use of diolefins, such as 1,3-butadiene or isoprene, are particularly preferred, resulting in coatings that are more flexible and expandable in water (28). More flexible coatings are especially preferred for high-water lenses that expand considerably upon hydration.

There are various ways to attach a polymer chain to a carbon layer, including plasma oxidation or other means to provide surface reactive functional groups that can react with the polymer. Preferably, a nitrogen-containing gas is used to form amine groups on the carbon layer. However, oxygen- or sulfur-containing gases may alternatively be used to form oxygen- or sulfur-containing groups, such as hydroxy or sulfide groups or radicals, on the carbon layer. Thus, the carbon layer is rendered reactive (functionalized) to promote the covalent attachment of the hydrophilic polymer to the surface.

To create a reactive functional group on the carbon layer, such an oxidation preferably utilizes a gas composition consisting of an oxidizing media such as ammonia, ethylene diamine, C1 to C8 alkyl amine, hydrazine, or other oxidizing compounds. Preferably, the oxidation of the hydrocarbon layer is performed for a period of about 1 min to 10 min, a discharge frequency of 13.56 MHz at about 20 W to 500 W and about 0.1 torr to 1.0 torr. The lens substrate may be treated on both sides at once or each side sequentially.

The hydrophilic reactive polymer may contain monomeric units derived from azlactone-functional, epoxy-functional and acid-anhydride-functional monomers. Azlactone monomers are listed in Table 1.12 and in Figure 1.14.

Table 1.12 Azlactone monomers (28).

2-Alkenyl azlactones

2-Ethenyl-1,3-oxazolin-5-one

2-Ethenyl-4-methyl-1,3-oxazolin-5-one

2-Isopropenyl-1,3-oxazolin-5-one

2-Isopropenyl-4-methyl-1,3-oxazolin-5-one

2-Ethenyl-4,4-dimethyl-1,3-oxazolin-5-one

2-Isopropenyl-4-dimethyl-1,3-oxazolin-5-one

2-Ethenyl-4-methyl-ethyl-1,3-oxazolin-5-one

2-Isopropenyl-4-methyl-4-butyl-1,3-oxazolin-5-one

2-Ethenyl-4,4-dibutyl-1,3-oxazolin-5-one

2-Isopropenyl-4-methyl-4-dodecyl-1,3-oxazolin-5-one

2-Isopropenyl-4,4-diphenyl-1,3-oxazolin-5-one

2-Isopropenyl-4,4-pentamethylene-1,3-oxazolin-5-one

2-Isopropenyl-4,4-tetramethylene-1,3-oxazolin-5-one

2-Ethenyl-4,4-diethyl-1,3-oxazolin-5-one

2-Ethenyl-4-methyl-4-nonyl-1,3-oxazolin-5-one

2-Isopropenyl-methyl-4-phenyl-1,3-oxazolin-5-one

2-Isopropenyl-4-methyl-4-benzyl-1,3-oxazolin-5-one

2-Ethenyl-4,4-pentamethylene-1,3-oxazolin-5-one

Cycloalkyl azlactones

2-Isopropenyl-4,4-dimethyl-2-oxazolin-5-one

2-Vinyl-4,4-dimethyl-2-oxazolin-5-one

Spiro

-4’-(2’-isopropenyl-2’-oxazolin-5-one) cyclohexane

Cyclohexane-

spiro

-4’-(2’-vinyl-2’-oxazol-5’-one)

2-(1-Propenyl)-4,4-dimethyl-oxazol-5-one

The synthesis of such monomers has been described in detail (29). The synthesis of 2-isopropenyl-4,4-dimethyl-2-oxazolin-5-one can be done as follows (29):

Preparation 1–4: 1. Methacryloylation:

In a 500 ml 3-neck round-bottom flask equipped with a mechanical stirrer, thermometer and an addition funnel, 51.5 g (0.5 mol) of α-aminoisobutyric acid and 40 g (1 mol) of NaOH were dissolved in 150 ml of H2O. The reaction flask was cooled to 0°C to 5°C in a CH3OH ice bath and 0.5 mol of methacrylate chloride was added dropwise while the temperature of the reaction mixture was kept below 0°C. After stirring for an additional hour, the reaction mixture was acidified with concentrated HCl with a pH of 3 to precipitate out the intermediate, which was then filtered, washed with cold H2O and air dried. Further drying was accomplished in a vacuum oven at 80°C overnight to obtain 44.9 g (0.26 mol 53%) N-methacryloyl-α-aminoisobutyric acid, which was suitable for the synthesis of 2-isopropenyl-4,4-dimethyl-2-oxazolin-5-one.

Figure 1.14 2-Alkenyl azlactones.

Figure 1.14 (cont) Cycloalkyl azlactones.

Cyclization, synthesis of 2-isopropenyl-4,4-dimethyl-2-oxazolin-5-one:

In a 500 ml dry 3-neck round-bottom flask, 0.26 mol of n-methacryloyl-α-aminoisobutyric acid was dispersed in 300 ml of dry hexane and allowed to react with mechanical stirring by dropwise addition of triethylamine (0.52 mol) while the temperature of the reaction mixture was maintained at 45°C to 0°C. During the addition, the copious evolution of carbon dioxide and the formation of white precipitate of TEA-HCl were observed. The reaction mixture was stirred for an additional 2 h. After cooling to room temperature, a white precipitate was filtered off and hexane evaporated off yielding an oil. Pure 2-isopropenyl-4,4-dimethyl-2-oxazolin-5-one was obtained after being recrystallized twice in hexane at dry ice/acetone temperature. The yield was 29 g (73%).

2-Isopropenyl-4,4-dimethyl-2-oxazolin-5-one is shown in Figure 1.15.

Figure 1.15 2-Isopropenyl-4,4-dimethyl-2-oxazolin-5-one.

Azlactone-functional monomers can be copolymerized with other monomers in various combinations of amounts (28). Using a monomer of similar reactivity ratio to that of an azlactone monomer will result in a random copolymer. Alternatively, use of a comonomer having a higher reactivity to that of an azlactone will tend to result in a block copolymer chain with a higher concentration of azlactone functionality near the terminus of the chain.

After producing a lens with the desired final shape, it is desirable to remove residual solvent from the lens before edge-finishing operations. This is because, typically, an organic diluent is included in the initial monomeric mixture in order to minimize phase separation of the polymerized products produced by polymerization of the monomeric mixture and to lower the glass transition temperature of the reacting polymeric mixture, which allows for a more efficient curing process and ultimately results in a more uniformly polymerized product. Sufficient uniformity of the initial monomeric mixture and the polymerized product are of particular concern for silicone hydrogels, primarily due to the inclusion of silicone-containing monomers which may tend to separate from the hydrophilic comonomer.

Suitable organic diluents include, for example, monohydric alcohols, such as n-hexanol and n-nonanol (cf. Figure 1.16), diols such as ethylene glycol, polyols such as glycerin, ethers such as diethylene glycol monoethyl ether (cf. Figure 1.17), ketones such as methyl ethyl ketone, esters such as methyl enanthate (cf. Figure 1.18), and hydrocarbons such as toluene.

Figure 1.16n-Nonanol.

Figure 1.17 Diethylene glycol monoethyl ether.

Figure 1.18 Methyl enanthate or Methyl heptanoate.

Preferably, the organic diluent is sufficiently volatile to facilitate its removal from a cured article by evaporation at or near ambient pressure. Generally, the diluent is included at 5% to 60% of the monomeric mixture, with 10% to 50% being especially preferred.

The cured lens is then subjected to solvent removal, which can be accomplished by evaporation at or near ambient pressure or under vacuum. An elevated temperature can be employed to shorten the time necessary to evaporate the diluent. The time, temperature and pressure conditions for the solvent removal step will vary depending on such factors as the volatility of the diluent and the specific monomeric components, as can be readily determined by one skilled in the art. According to a preferred embodiment, the temperature employed in the removal step is preferably at least 50°C. A series of heating cycles in a linear oven under inert gas or vacuum may be used to optimize the efficiency of the solvent removal. The cured article after the diluent removal step should preferably contain not more than 5%.

After solvent removal, the lens is next subjected to mold release and optional machining operations. The machining step includes, for example, buffing or polishing a lens edge and/or surface. Finally, the lens is subjected to a surface treatment (28).

1.4.1.3 Hydrophilicity Improvement

The hydrophilicity of the surface of a silicone hydrogel lens can be improved with a poly(oxy ethylene) derivative with a plurality of hydroxyl groups (30). The surface treatment can be done as follows (30):

Preparation 1–5: First, 60 parts by mass of 3-[tris(trimethylsiloxy)silyl] propyl methacryloyloxyethyl succinate, shown in Figure 1.19, 39 parts by mass of 2-hydroxyethyl methacrylate, 0.5 part by mass of ethylene glycol dimethacrylate, and 0.5 part by mass of azobisisobutyronitrile were mixed and dissolved. Then the solution was flowed into a cell sandwiched between a glass plate and a polypropylene plate through the use of a poly(ethylene terephthalate) sheet having a thickness of 0.1 mm as a spacer. After an oven had been purged with nitrogen, the solution was heated at 100°C for 2 h to be polymerized, followed by molding into a film shape. After polymerization, the cured film was removed from the cell, and was immersed in a mixed liquid containing ethyl alcohol and ion-exchanged water at a ratio of 3/1 for 12 h, and in ion-exchanged water for 12 h to produce a water-containing film. The produced water-containing film was placed in a discharging apparatus, and the pressure in a chamber was reduced to about 2.66 Pa. After that, a plasma discharge treatment was performed under an oxygen gas atmosphere at about 13.3 Pa for 10 min (frequency: 13.56 MHz, high-frequency output: 50 W). After that, a peroxide (peroxide group) was produced on the surface of the water-containing film by storing it under an oxygen gas atmosphere for a minimum of 10 min.

Figure 1.19 3-[Tris(trimethylsiloxy)silyl]propyl methacryloyloxyethyl succinate.

Examples of preferred monomers for use in the base material of a silicone hydrogel contact lens to control the water content include water-soluble monomers. These materials are collected in Table 1.13.

Table 1.13 Monomers for controlling water content (30).

Compound

Compound

(Meth)acrylic acid

Itaconic acid

Crotonic acid

Cinnamic acid

Vinylbenzoic acid

Glycerol (meth)acrylate

N

-Vinylformamide

N

-Vinylacetamide

2-Hydroxyethyl (meth)acrylate

2,3-Dihydroxypropyl (meth)acrylate

N

-Methyl-

N

-vinylacetamide

N

-Vinyl-2-pyrrolidone

2-(Meth)acryloyloxyethyl phosphorylcholine

Polyalkylene glycol mono(meth)acrylate

Polyalkylene glycol monoalkyl ether (meth)acrylate

The usage amount of any monomer in Table 1.13 is typically from 10 parts by mass to 50 parts by mass, preferably from 20 parts by mass to 40 parts by mass with respect to 100 parts by mass of the monomer composition of the silicone hydrogel contact lens base material (30).

1.4.1.4 Interpenetrating Polymer Network Hydrogel Contact Lenses

Interpenetrating polymer network hydrogels have been described that have high oxygen permeability, strength, water content, and resistance to protein adsorption (20).

The hydrogels include two interpenetrating polymer networks. The first polymer network is based on a hydrophilic telechelic macromonomer. The second polymer network is based on a hydrophilic monomer. The hydrophilic monomer is polymerized and crosslinked to form the second polymer network in the presence of the first polymer network.

The telechelic macromonomer is preferably poly(ethylene) glycol diacrylate or poly(ethylene) glycol dimethacrylate. The hydrophilic monomer can be acrylic acid, acrylamide, N-hydroxyethyl acrylamide, N-isopropyl acrylamide, methacrylic acid (MA), 2-acrylamido-2-methylpropanesulfonic acid, 2-hydroxyethyl methacrylate, or 2-hydroxyethyl acrylate, cf. Figure 1.20.

Figure 1.20 Monomers for telechelic macromonomers (20).

One surface of the interpenetrating polymer network hydrogel should be surface modified. Preferably, at least one surface is modified with a layer of poly(ethylene) glycol macromonomers, polymerized poly(ethylene) glycol diacrylate, or polymerized poly(ethylene) glycol dimethacrylate.

The steps required for synthesis of an interpenetrating polymer network hydrogel are as follows (20):

The starting material for the hydrogel is a solution of telechelic macromonomers with functional end groups. The telechelic macromonomers are polymerized to form a first polymer network. Next, hydrophilic monomers are added to the first polymer network. Hydrophilic monomers are then polymerized and crosslinked in the presence of the first polymer network to form a second polymer network.

1.4.1.5 Poly(olefin) Contact Lenses

New lens molds and methods useful in producing soft contact lenses have been discovered. Poly(propylene) (PP) contact lens molds and methods of making such soft contact lenses, such as hydrogel contact lenses, by using such molds have been described (31).

The present molds and methods provide contact lenses with consistent high optical quality; for example, producing lenses with fewer surface defects and with less severe surface defects or a reduced optical distortion caused by surface defects. Furthermore, the present molds and methods use reduced amounts of energy, shorten contact lens production cycle time and achieve reduced machinery wear and tear. Such advantageous results are relative to producing identical soft contact lenses from molds made of thermoplastic poly(olefin), in particular PP, resin having a melt flow rate of less than 10 g (10min)−1, for example, 1.9 g (10min)−1.

The term melt flow rate denotes the industry known standard ASTM D1238-13 (32). This parameter is usually available from suppliers of commercial resins. Such mold member or members may be conventionally produced, for example, by injection molding processing. Preferably, both mold members are injection molded from one or more of such resins.

These benefits of producing soft contact lenses can be obtained without requiring molds made from thermoplastic poly(olefin) resins having a melt flow rate of at least about g (10min)−1, as described in a previous publication (33) for rigid gas-permeable contact lenses. Also, molds made out of Ziegler-Natta catalyst-based poly(olefin) resin are not required, as noted in a publication of Ansell and Yin (34).

Here, methods of producing soft contact lens products, e.g., soft hydrophilic or hydrogel contact lens products, are provided. These methods consist of placing a soft lens-forming composition in a cavity formed between a first mold member and a second mold member, subjecting the soft lens-forming composition in the cavity to conditions effective to form a contact lens product from the lens-forming composition, and repeating the placing and subjecting steps a plurality of times, for example, at least about 100 times or at least about 1000 times or at least about 10,000 times, thereby producing a plurality of soft contact lens products.

At least the first mold members, and advantageously all of the first and second mold members, consist of a nucleated thermoplastic poly(olefin) resin having a melt flow rate in a range of 10 g (10min)−1 to about 40 g (10min)−1 (31).

A nucleating agent is specifically utilized to increase the rate of crystallization of the poly(olefin) component as it cools from the melt as compared to the same or identical poly(olefin) component without the nucleating agent. Many nucleating agents are suitable for inclusion with the thermoplastic poly(olefin) resin formulations useful in the present invention.

Nucleating agents for PP have been described (35, 36). Examples of suitable nucleating agents are collected in Table 1.14 and shown in Figure 1.21.