synthesis and properties - Wiley Online Library

22 downloads 4437 Views 213KB Size Report
state the developed material has high mechanical properties, transparency, hydrophilicity, oxygen and water permeability. The developed new technology ...
POLYMERS FOR ADVANCED TECHNOLOGIES Polym. Adv. Technol. 2006; 17: 872–877 Published online in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/pat.820

A new polymeric silicone hydrogel for medical applications: synthesis and propertiesy N. A. Chekina1, V. N. Pavlyuchenko1*, V. F. Danilichev2, N. A. Ushakov2, S. A. Novikov2 and S. S. Ivanchev1 1

St Petersburg Department of the Boreskov Institute of Catalysis of the Siberian Branch of the Russian Academy of Sciences, St Petersburg, Russia 2 Military Medical Academy, St Petersburg, Russia Received 28 November 2005; Revised 30 January 2006; Accepted 14 February 2006

A novel silicone hydrogel polymeric material is developed. The preparation method is based on sequential interpenetrating network synthesis. A silicone network is obtained by the interaction between two siloxane oligomers comprising hydride and vinyl functional groups. A hydrophilic network is prepared by radical copolymerization of hydrophilic monomers (N-vinyl pyrrolidone, N,N-dimethylacrylamide) and crosslinking agent (ethylene glycol dimethacrylate). In the hydrated state the developed material has high mechanical properties, transparency, hydrophilicity, oxygen and water permeability. The developed new technology affords obtaining a silicone hydrogel material with a good wettability without additional chemical or plasma surface treatment. Copyright # 2006 John Wiley & Sons, Ltd. KEYWORDS: silicones; hydrogels; interpenetrating polymer networks (IPNs); N-vinyl pyrrolidone; N,N-dimethylacrylamide

INTRODUCTION The use of soft contact lenses (SCLs) for cosmetics and vision correction purposes is well known. The safety of SCL application is mainly determined by physical and chemical properties of the polymeric materials used for their production. For this reason biocompatible polymers have become an object of numerous studies. In addition, the lens should allow oxygen to reach the cornea in an amount which is sufficient for long-term corneal health.1,2 High oxygen permeability is needed because the eye has no blood circulation and extracts the oxygen required for its cells directly from the atmosphere. Thus, SCLs must allow oxygen to diffuse through the lens to reach the cornea. Another requirement for SCLs is that the lens must not strongly adhere to the eye.2 Clearly, a consumer should be able to easily remove the lens from the eye for disinfecting, cleaning, or disposal. However, the lens must also be able to move on the eye in order to encourage tear flow between the lens and the eye. Thus, wettability is essential for wearer comfort. Resistance to protein and mucus deposits from fluids that bathe the outer surface of the eye is essential since without this feature the lens pores become clogged and both visual acuity and the oxygen permeability of the lens suffer.3

*Correspondence to: V. N. Pavlyuchenko, St Petersburg Department of the Boreskov Institute of Catalysis of the Siberian Branch of the Russian Academy of Sciences, prospect Dobrolyubova, 14, St Petersburg, 197198, Russia. E-mail: [email protected] y 8th International Symposium on Polymers for Advanced Technologies 2005 (PAT 2005), Budapest, 13–16 September, 2005, Part 2.

In order to balance the biocompatibility and consumer comfort requirements in designing a SCL, hydrogels were used. Conventional hydrogel lenses are prepared from monomeric mixtures predominantly containing hydrophilic monomers such as 2-hydroxyethyl methacrylate (HEMA) or N-vinylpyrrolidone (NVP).4,5 These lenses move well on the eye and provide sufficient oxygen permeability for daily wear, but not for extended periods. Silicon and fluorine containing polymers have significantly higher oxygen permeability, however they also cannot be applied for extended wear SCLs due to their poor wettability. A surface modification of polysiloxanes or fluoro-containing polymers6 allows the preparation of lenses combining high oxygen permeability and wettability but their performances are hampered by poor water permeability. Random copolymers of silicon- and fluorine-containing compounds with hydrophilic comonomers7–9 also provide materials with moderate oxygen permeability and hydrophilicity without fitting the whole complex requirements for prolonged wearing of SCLs. One known way to increase the oxygen permeability of the hydrogels is to add silicon-containing monomers to the hydrogel formulations. The most promising approach to obtaining extended wear SCLs is based on the synthesis of biphase materials comprising both silicone and hydrogel phases. Such materials are essentially represented by block-copolymers including polysiloxane and a hydrophilic polymer [poly (N,N-dimethylacrylamide), poly(N-vinylpyrrolidinone) or poly(hydroxyethyl methacrylate)] block; possessing excellent

Copyright # 2006 John Wiley & Sons, Ltd.

A silicone hydrogel polymeric material

combination of high hydrophilicity and oxygen permeability.10–13 However, the existing process for producing these biphase materials is quite expensive and complicated in view of the necessity in performing a surface plasma treatment at the last stage. In the studies in this article a new method for a biphase material preparation based on sequential interpenetrating polymer network (IPN) formation has been developed.

where Cw2 is the polymer network 2 content, WIPN is the IPN weight and W1 is the polymer network 1 weight before IPN synthesis. Physicochemical and mechanical properties were measured for polymeric films of 100–200 mm in thickness. Water content of the hydrogels was determined using a gravimetric method: Cwð%Þ ¼

EXPERIMENTAL Materials N,N-Dimethylacrylamide (DMAA), ethylene glycol dimethacrylate (EGDM), 2,2-dimethoxy-2-phenylacetophenone (DMPA) and dibutyl tin dilaurate (DTD) were purchased from Sigma, Aldrich Co. NVP was provided by Fluka Chemical Co. Toluene, chloroform, isopropanol and sodium chloride were obtained from Vekton Co. (Russia). NVP copolymer was supplied from Concor Co. (Russia) under the trade name SCL LM-70 VP. Functional oligosiloxanes and catalyst for hydrosilylation (H2PtCl6) were kindly submitted by Dr G. Grigorian (Institute of Synthetic Rubber, St Petersburg, Russia). The oligosiloxane performances are listed in Table 1. All the reagents were used as received.

Methods IPN chemical composition was determined by a gravimetric method: Cw2 ð%Þ ¼

WIPN  W1  100 WIPN

873

Wwet  Wdry  100 Wwet

where Wwet and Wdry are wet and dry weights of hydrogel correspondingly. The contact angle was measured according to the bubble technique.14 Moisture permeability (P) was examined at 208C by estimation of the rate of water elimination through hydrogel film:

the air the the

Dm  a Dt  p  S



where Dm is the water weight decrease for the period Dt (in g), a is the film thickness (in cm), p the pressure of water saturated vapour (in mm Hg) and S is the area of the film (in cm2). Oxygen permeability of the hydrogels was measured by the polarography method.15 The short-term tensile properties were measured using a universal tensile testing machine RTM-1 (Japan) at 238C and deformation rate 20 mm/min. Morphological investigations of the rabbit cornea after 30 days of wearing different SCLs were performed with

Table 1. The properties of oligosiloxanes Performances

Chemical structure of oligosiloxane

CH3 CH3

CH3

HO

C2H5

CH3

Si O

Si

CH3

H

CH3

CH3

C2H5

CH3

CH3

Si O

Si O

Si O

Si

CH3

H

CH3

CH3

Si

O

x

CH3

CH3

CH3 H2C CH Si

O

CH3

n

Si CH3

9

CH2 CH2 CF3

Functional group content (wt%)

98

1.4338

0.3

[H] 0.55

y

FSO-1

98

1.4122

0.7

[H] 0.68

FSO-2

98

1.3998

1.0

FSO-3

98

1.4010

CH3 O

Si CH3

z

CH3

CH3

CH3 Si

SO-1

n20 D

Viscosity (Pa sec)

CH3

CH2 CH2 CF3

Si O

Si O

CH3

Lettering

Light transmission of layer (10 mm) (%)

CH3 O Si OH n

CH3

CH3

CH3

Si O

Si

CH2

CH3

CH3 O

9 n

Si

CH CH2

[CH2 ¼ CH–] 0.32

CH3

CH2 CF3 Copyright # 2006 John Wiley & Sons, Ltd.

Polym. Adv. Technol. 2006; 17: 872–877 DOI: 10.1002/pat

874

N. A. Chekina et al.

Table 2. Preparation conditions and some properties of silicone hydrogels obtained by silicone network incorporation into hydrogel one

Type of reaction

Oligosiloxane mixture composition

B

FSO-1/FSO-2 ¼ 1:5

A

FSO-1/FSO-3 ¼ 1:10

Catalyst concentration (wt%) related to olygosiloxane mixture

Oligosiloxane mixture concentration (g/ml)

Silicone/hydrogel weight ratio in the final product

Contact angle (deg)

Water content (wt%)

2.0 4.0 2.0 4.0 4.0 4.0 4.0 4.0 0.04 0.04

0.14 0.14 0.20 0.20 0.40 0.50 0.53 0.60 0.40 0.50

17.4:82.6 25.3:74.7 16.9:83.1 37.6:62.4 42.8:57.2 43.3:56.7 36.9:63.1 26.6:73.4 13.0:87.0 15.0:85.0

60 62 58 68 70 72 68 63 56 58

70 68 75 65 60 59 63 68 76 72

solvent evaporation under vacuum. Then the silicone network was soaked for 20 hr in the reaction mixture containing hydrophilic monomers, EGDM and DMPA dissolved in toluene. Photoinduced polymerization was carried out under UV irradiation (0.4 W/cm2) at 208C for 30 min. IPNs prepared according to both methods were washed several times with the solvent and distilled water to eliminate the residual non-reacted components. Both IPN synthesis reactions were carried out in a closed polymeric mold made of a transparent fluoropolymer (tetrafluoroethylene-hexafluoropropylene copolymer).

optical photomicroscope ‘Polyvar’ (Germany). Cornea mounts of 3–5 mm in thickness were prepared with microtome. Before investigations the mounts were dyed with hematoxylin eosin.

IPN preparation by silicone network incorporation into the hydrophilic one NVP copolymer (SCL LM-70 VP) was used as a hydrophilic polymer. This hydrophilic network was saturated with a mixture comprising two functional oligosiloxanes (FSO-1 þ FSO-2 or FSO-1 þ FSO-3), catalyst (DTD or H2PtCl6) and solvent (chloroform) for the compatibilization of the components. The silicone network was synthesized at 808C for 4 hr.

RESULTS AND DISCUSSION Silicone hydrogel IPNs prepared according to the earlier methods are free of covalent binding between hydrophilic and silicone fragments. The linkage is achieved due to interlacing of two networks formed by different mechanisms. IPNs were synthesized via sequential processes. The first method comprises the following sequential stages:

IPN preparation by hydrophilic network incorporation into the silicone one First a silicone network was obtained by the reaction between FSO-3 and SO-1 (weight ratio 10:1) in toluene (oligosiloxane/ solvent volume ratio 1:1) in the presence of H2PtCl6. The reaction was carried out at 208C for 24 hr followed by the

Table 3. The propertiesa of polymeric materials for SCLs St Petersburg Department of the Institute of Catalysis (Russia)

Ciba Vision (Switzerlland)

Bausch&Lomb (USA)

Polymer hydrogel No 9.5 38 7.7

Silicone þ hydrogel (NVP þ DMAA) IPN No 130–150 20–25 5.3

Lotrafilcon A Silicone þ hydrogel DMAA Block-copolymer Plasma oxidation 140 24 —

Balafilcon A Silicone þ hydrogel HEMA Block-copolymer Plasma coating 110 35 —

30 98 1.430 0.4

40–45 90 1.415 0.7

50b — — 1.2

55b 92b — 1.2

Material producer

Concor Co. (Russia)

Trade name Chemical composition

Hypolan-2 HEMA

Material type Surface treatment Oxygen permeability (BU) Equilibrated water content (wt%) h i cmÞ Moisture permeability  109 ðminÞ ðg cm2 mm Hg Contact wetting angle (deg) Light transparency (%) Refractive index Elasticity modulus (MPa) a b

All properties were determined for the materials in the hydrated state. The data was obtained at the Institute of Catalysis.

Copyright # 2006 John Wiley & Sons, Ltd.

Polym. Adv. Technol. 2006; 17: 872–877 DOI: 10.1002/pat

A silicone hydrogel polymeric material

Table 4. Chemicals for silicone hydrogel IPN preparation Stage

Chemical

1

SO-1 FSO-3 H2PtCl6 Toluene Silicone prepared at stage 1 NVP DMAA EGDM DMPA Toluene

2

Weight in parts 1.0 10.0 0.0043 11.0 50.0 12.5 4.0 0.2 0.083 33.3

(1) Radical copolymerization of vinyl monomers using a crosslinking agent. (2) Incorporation of oligosiloxanes and catalysts into the network prepared at the first stage and curing through the mechanisms:

A.

Si CH=CH2 + H Si C2H5

FSO-3

CH2

CH3

O Si

C2H5

O

CH3

O

Si OH +

FSO-2

CH2

FSO-1

CH3 CH3

Si

O

CH3

B.

CH3

O

CH3

H Si C2H5 O

O Si O Si CH3

C2H5 + H2

O

FSO-1

The results are shown in Table 2. The data show that method A does not provide a sufficient level of silicone incorporation into the hydrophilic network probably determined by too low a compatibilization of oligosiloxane FSO-3 with the hydrophilic network. Method B affords higher silicone content. The silicon content in composite hydrogels

875

depends on the catalyst and oligosiloxane concentrations. The highest silicone content is achieved at oligosiloxane concentration in the reaction mixture 0.5 g/ml. A further concentration increase deteriorates the results due to poor hydrogel swelling in the reaction mixture containing high oligosiloxane amounts. The contact angle values for these materials were quite high (60–708). Therefore, these kind of materials cannot be used for contact lens preparation because of their too low wettability. The optimum value of contact angle is likely to be in the range from 308 to 558. The data on contact angle for well known lenses on the basis of usual hydrogels and silicone hydrogels (Table 3) confirm this statement. The opposite sequence of network formation provided much better results with the process comprising the following two stages: (1) Silicone network preparation according to the earlier scheme A. (2) Incorporation of a toluene solution of vinyl monomers, crosslinker and photoinitiator into the silicone network and copolymerization under UV light. Toluene was applied simultaneously as a solvent for oligosiloxanes and compatibilizer of the components. The processes were carried out according to the recipes presented in Table 4. After the synthesis the IPN material was washed several times with isopropanol and distilled water. The obtained IPN is featured with a biphase nature. This is confirmed by its opacity in the dry state due to different refractive indices of polysiloxane (1.4) and hydrophilic polymer (1.5). However, after hydration of the hydrophilic component the indices level off and the material turns transparent. The properties of the materials prepared according to the earlier recipes are shown in Table 3. For comparative analysis Table 3 also includes performances of the well-known



Siloxane SCL synthesis by interacting of oligosiloxanes in toluene in a closed polymeric form

Silicone hydrogel SCL washing in isopropyl alcohol or hexane

Siloxane SCL separation and drying

Siloxane SCL saturation with hydrophilic monomers in a toluene solution containing a crosslinking agent and photoinitiator

Silicone-hydrogel SCL washing in distilled water followed by sterilization in water at 100 °C

UV-irradiation of the saturated siloxane SCL in a closed polymeric form via the transparent upper window, polymerization of hydrophilic monomers and IPN formation

Silicone-hydrogel SCL storage in a container with a conservating solution

Figure 1. Flow-chart of SCL preparation. Copyright # 2006 John Wiley & Sons, Ltd.

Polym. Adv. Technol. 2006; 17: 872–877 DOI: 10.1002/pat

876

N. A. Chekina et al.

Swelling degree, %

materials used for the production of extended wear SCLs,10 and for a conventional polymeric hydrogel based on HEMA. The properties of the material are found to be similar to those of Lotrafilcon A and Balafilcon A. The most exciting feature of the novel material is its high oxygen permeability exceeding 125 BU acceptable for extended wear SCL production.16 Furthermore, the material is also featured with a good wettability and water permeability with the latter being only slightly lower in comparison with poly (hydroxyethyl methacrylate). Hence the developed material is promising for obtaining SCLs for extended wear. In addition, it is also worth to underline that the developed method is advantageous in being free of the material surface treatment. This procedure is usually employed for wettability improvement and is obligatory for silicone hydrogels prepared on the basis of block copolymers. The developed IPN silicone hydrogels can be obtained without this step. The flow-chart of SCL synthesis is presented in Fig. 1. The reaction mixture composition at stage 2 is worthy of a particular consideration. For both stages of the process the same mold was used, therefore the silicone precursor of the final lens should occupy a certain volume in the mold. This volume should be able to absorb all the amount of the reaction mixture charged into the mold of stage 2. In other words, the system must be uniform before copolymerization. Only these conditions eliminate macrophase separation during the copolymerization and formation of the lens with a regular shape. Figure 2 shows swelling degree depending on the monomer/solvent volume ratio. In accordance with the recipe the silicone precursor of the lens occupies half of the mold volume. Consequently, the smallest swelling degree should be at least 100%. Thus the monomer/toluene ratio is to be no more than 0.43. This factor determined the selection of this value for the earlier recipe at stage 2. Some experimental samples of SCLs were made for medical and biological investigations. Toxicological studies performed according to the Russian standard17 indicated no toxicity. In order to estimate possible hypoxic effects caused by hampered diffusion through the lens material they were

200

Figure 3. Morphological changes of the rabbit cornea after 30 days of wearing different SCLs. (A) initial cornea (no lens); (B) silicone hydrogel SCL developed in the Institute of Catalysis; (C) ‘‘Pure Vision’’ silicone hydrogel SCL; (D) ‘‘Proclear Compatibles’’ hydrogel SCL. tested on animals. This involved studying morphology changes in the rabbit eye corneal fibers after the developed contact lens was worn for 30 days; the results were compared with well-known silicone hydrogel counterparts ‘‘Pure Vision’’ (Bausch & Lomb Co.) and conventional hydrogel lenses ‘‘Proclear Compatibles’’ (Hydron Co.) designed for daily wear. Figure 3 shows that significant and irreversible corneal fiber changes are observed only for conventional hydrogel SCLs. For silicone hydrogel SCLs (both ‘‘Pure Vision’’ and novel material) only slight corneal changes are observed after 30 days of permanent wear followed by the complete recovery of the cornea in 15 days.

CONCLUSION The study of physicochemical properties for the developed silicone hydrogels showed that their main performances (oxygen permeability, hydrophilic and mechanical properties) are similar to those for the worldwide leading counterparts produced by Ciba Vision and Bausch & Lomb for extended wear silicone hydrogel SCLs. According to medico-biological tests indicating appropriately low level of hypoxic complications, morphology changes and toxicoallergic effects the developed SCL can be considered as a promising and competitive product relating to commercially available lenses manufactured by market leading companies. The advantages of novel SCLs are also determined by more simple process for their preparation free of the expensive plasma treatment of the synthesized lens surface necessary for the above counterparts.

100

Acknowledgments 0 0,2

The authors would like to thank Prof. G. Sofronov, Prof. S. Chepur and Dr N. Andreeva for their assistance with medical and biological investigations.

0,3

0,4

0,5

monomer / toluene ratio Figure 2. The polysiloxane swelling degree depending on monomer/toluene volume ratio. Copyright # 2006 John Wiley & Sons, Ltd.

REFERENCES 1. Ladage PM, Jester JV, et al. Role of oxygen in corneal epithelial homeostasis during extended contact lens wear. Eye & Contact Lens. 2003; 29: 2–5. Polym. Adv. Technol. 2006; 17: 872–877 DOI: 10.1002/pat

A silicone hydrogel polymeric material 2. Nicolson PC, et al. Extended wear ophtalmic lens. US patent no. 5,965,631, 1999. 3. Moradi O, Modarress H, Noroozi M. Experimental study of albumin and lysozyme adsorption onto acrylic acid and 2-hydroxyethyl methacrylate surfaces. J. Col. Inter. Sci. 2004; 271: 16–19. 4. Nicolson PC. Continuous wear contact lens surface chemistry and wearability. Eye & Contact Lens. 2003; 29: 30–32. 5. Vanderaan DG, et al. Soft contact lenses. US patent no. N 2002/0107324 A1, 2002. 6. Valint PL Jr, et al. Surface modification of polymer objects. US patent no. N 5219965, 1993. 7. Ivani EJ. Silicone-vinyl acetate composition for contact lenses. US patent no. N 4500695, 1985. 8. Tanaka K, et al. Copolymer for soft contact lens, its preparation and soft contact lens made thereof. US patent no. N 4139513, 1979. 9. Novicky N. Comfortable, oxygen permeable contact lenses and the manufacture thereof. US patent no. N 4948855, 1990.

Copyright # 2006 John Wiley & Sons, Ltd.

877

10. Tighe B. Silicone hydrogels: The rebirth of continuous wear contact lenses. Sweeney D (ed.). Butterworth-Heinemann, Oxford, 2000; 1–21. 11. Kunzler J, Ozark R. Fluorosilicone hydrogels. US patent no. N 5321108, 1994. 12. Maiden AC, Vanderllaan DG, Turner DC, et al. Hydrogel with internal wetting agent. US patent no. N 6367929, 2002. 13. Makendra N, Rajan B, Chin LY. Process for making silicone containing hydrogel lenses. US patent no. N 5260000, 1993. 14. Ajvazov BV. Training for chemistry of surface effects and adsorption. Vysshaya shkola: Moscow, 1973; 24–25 (in Russian). 15. Hitchman ML, Huglin MB, Zakaria MB. Observations relating to oxygen permeability measurements on membranes. Polymer 1984; 25: 1441–1445. 16. Harvitt DV, Bonnano JA. Minimum contact lens transmissibility values for daily and extended wear lenses. Optometry and Vision Sci. 1998; 12: 189–203. 17. Gacyra VV. Primary pharmacological test methods of biological-active substances. Medicina: Moscow, 1974; 120–138 (in Russian).

Polym. Adv. Technol. 2006; 17: 872–877 DOI: 10.1002/pat