Note: Descriptions are shown in the official language in which they were submitted.
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Tiale oltlle lllvelllion
I~iocompatible Optically Transparent rolymeric Material I~ased Upon
Collagen and Method of ~zlkin~
10 .RP1~te(1 A~)plication
This appli~ on is a con~inl-~fioll-in-part application of U.S. patent applic~ion Serial No.
08/279,303, filed July 22, 1994, which application is incorporated by reference in its entirety.
15 P'ield of lhe Invention
This invention relates to a biocompatible polymer cont~ining the copoly.~ ion
product of a mi~cture of hydrophobic and hydrophilic acrylic and/or allelic monomers, and
telo-coll~en pre1imin~rily purified from glucoproteins and proteogluc~nps. The rn~ri~l is
20 useful for lhe pro-iuction of soft intraocular lenses, refractive intraocular contact lenses, and
standard contact lenses useful for example, in correc~ing aphekia, myopia and hy~GI---tl-ol~ia.
I~ackground of t~le Invention
25Ol.linal~ polymers, based upon pure non-polyenic acryla~es or allelic monomers, do not
have on their surfaces water-solvent ionic layers on their surfaces whicll are buffered against the
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sorption of proteins. Providing waLer-solvent iollic layers on lhe surface of the polymer is
desirable because SuCIl layers will grea~ly improve the bio-compalibility of the lens with cell
membranes of the recipient's eye.
Polyenic water-solvent ionic monomers may be used in or(Jer to produce a water-solvent
layer. However, this decreases tl)e rÇ~i~t~nCe of such copolyrners against swelling. For
example, the system of polyenic copolymers, I)ased upon acrylarnid or acrylic acid wilh HEMA
has a t~ondency towards excessive swelling beyond all bounds. This happens because pure
homopolymers, polyacrylamide or polyacrylic acid, contained in Ihis system, dissolve in water.
Therefore, it is an advantage to produce a polymer which would be able to form such a vital
water-solvent layer, and would not affect the polymer resislance against swelling.
References concerning graft-copolymers of collagen include U.S. Patent No. 4,388,428
aune 14, 1983) and U.S. Palent No. 4,452,925 aune 5, 19g4). In these p~t~.n~.~, a system of
water-soluble monomers and A telo-collagen is used. However, this system is not hydrolytically
stable and is not sufficiently optically transparent. In U.S. Patent No. 4,452,925, nothing is
mentioned of special optical conditions needed for transparent polymer production. The water-
solvent A telo-collagen di~closed in this patent does not have the capacity to form a gel in the
organic monomer solution, and lherefore the collagen precipitales or coagulates.
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51~rnn~ y of ~e Invention
An object of the present invenlion is to provide a biocompatible optically transparent
polymeric material based on telo-collagen.
A further object of the present invenLion is to provide a biocompatible polymer cont~ining
the copolymerization product of a mixture of llydropllol)ic and hydrophilic acrylic and/or allelic
type-monomers and telo-collagen.
~n obiect of the present invention is to provide a metllod of making a biocompatible,
optically transparent, polymeric material based on collagen
A further object of tlle present invention is to provide a method of making a
biocompatible polymer containing t1le copolymerization product of a mixture of hydrophobic and
15 llydrophilic acrylic and/or allelic type-monomers and telo-collagen.
The present invention is directed to metllods of making a biocompatible polymeric
material based on collagen for use in the production of derormable lenses.
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The present invention is also directe(l lo an derormable lens comprised of the present
optically transparent, biocompatible, polymeric material.
The present invention is further directed to methods for making deformable lenses.
s
The present invenlion is also directed to methorls for correcting aphekia (absence of the
lens of the eye), myopia or hypermetropia in a patient by surgically implanling in the eye of the
patient, tlle present deformable lens.
The biocompatible polymeric material according to the present invention is made as a
copolymerization product of a mixture of hydrophol)ic and hydrophilic acrylic and/or allelic
monomers graft polymerized with telo-collagen. For example, one or more hydrophobic acrylic
and/or allelic monomers are mixed wilh one or more hydrophilic acrylic and/or allelic
monomers, and the resul~nt solution is then mixed with telo-collagen dissolved in one or more
15 hydrophilic acrylic and/or allelic monomers. Tlle resul~ing malerial is then irradiated to form
the present biocompatible optically transparent polymeric m~eri~l
The telo-collagen used in the present invention is ~centi~lly type IV collagen obtained
from pig's eye sclera or cornea. The collagen is a naturally stable polyenic, which comprises
20 hydrophobic, hydroxylic and polarized amino-acids (l~tcum--ra, T., }~ ion~hip Between
Amino-Acid Composition and Differentiation of Collagen, Lut. J. Biochem. 3(15):265-274
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_ 5 _
(1972), and Traub W., and Piez K.A., The l'hPn-icfry and Slructure of Collagen, Advances in
Pro~ein Cffern 25:243-352, (1971). It is nol a~ visable lo use a modified collagen in the system
according to the present invention since this collagen biodegrades wilh time (U.S. Palent No.
4,978,352, December 18, 1990).
The resulling biocompalible polymeric malerial is an elaslic biopolymer, basf~ upon the
mixture of llle hydrophobic and hydrophilic monomers and telo-collagen. The product of the
hydropllobic and hydrophilic monomer copolymerizalion exhibils an elevated hydrolytic stability
and a mucll higher index of refraction, if compared wilh a polymer which is based upon
10 hydrophilic monomers alone.
The high molecular mass of lelo-collagen molecules (320,000D), their size (up to
lOOOA), the disorientalion of molecules in space, the refraclion index 1.47 (Hogan J. J. et. al.,
~Iistology of Huma~l Eyes, A~ Atla~ an~l Text~ook, rhiladelphia, London, Toronto, (1971)), and
15 other characleristics of collagen make it impossible to produce oplically Iransparent hydrogel
impl~nfc made of collagen alone. The refraclion index of the hydrogel base substance, the
aqueous number is equal to 1.336, whicll is subsf~n~iz.lly ~fifferent from the refractive index of
collagen 1.47, resulting in opacificalion of Ihe gel, if a suspension of collagen in aqueous
monomer is made.
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In order to produce an optically homogeneous gel in the mixlure of organic monomers
it is nPcecs~y to utilize telo-collagen containing lelo-peplide. Telo-peptide is tlle basic element
of inl~ tion among collagen molecules. Tllis produces a stable gel in the mixture of
hydrophobic and hydrophilic monomerS, and this gel neilher precipitates nor coagulates.
For the purpose of increasing the oplical transparency and homogeneity in this system,
the refraction index of polymer and of lelo-collagen should be appro~im~ly equal, so that the
intensity of light diffusion is close lo zero, in accordance wilh Reley's equation (U.G. I;rolof,
Course of Colidle C~lemistry, Moskva Chemia, 1989):
~ fN,2 - N 2 \ c.v2
WHEREAS, I = Io 24~r3 ~ (1 + COS2 w)
N,2 + 2No2 ~ Pl /
15 L-- is intensity of inrident light;
-- is the intensity of diffused ligl-t as a Ul1it of radiation
volume;
20 P, = flict~nce to detector;
w = light diffusion angle;
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C = concentration of particles per volume unit;
= lengtll of incident lighl wave;
5 N = refraction index of particles;
N. = refraction index of basal substance; and
V = volume of particles.
If N = No~ then Ir = O. Thus Ille inlensily of light diffusion is zero.
A preferred llydropllilic acrylic monomer for use in the present invention is 2-
hydroxyelllyl me~h~crylate (HEMA) and a preferred hydrophobic monomer for use in the
15 present invenlion is 4-metharyloxy-2-hydroxybenzophenone. Tlle lelo-colla~en is preferably
produced from pig s eye sclera or cornea.
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-- 8
Detailed ~es~ liorl of ~e Preferre~ Emboditnents
I. Defnitions:
Tl1e below definitions serve to provide a clear and concictent understanding of the
specification and claims, including the scope to be given such terms.
Telo-collagen. By tlleterm "telo-collagen" is intended for the purposes of this invenlion
a naturally stable polyenic, that contains hydropllobic, llydroxylic and polarized amino-acids
(M~ mllra, T., 12e~ nnch ip Between Amino-Acicl Composition and Differçn~i~tion of Collagen
Lut. J. Bioc~lem 3(15J:265-274 (1972).
The present telo-collagen is essenlially type IV telo-collagen preferably made from pig's
eye sclera or cornea, and has a viscosily of greater tllan or equal to lOOOcPs. The present telo-
collagen retains the telo-peptides and has a refractive index of about 1.44 to 1.48.
I~ioeo~ tible polymeric matenal. By the terminology "biocompalible polymeric
materialH is in~er~ l a material whicll is made by coml)illing or mixing one or more hydrophobic
monomers (acrylic and/or allelic monomers), and one or more hyclrophilic monomers (acrylic
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and/or allelic monomers), and graft-copolymerizin~ tlle resultant mixture with a
telo-collagen/hydropllilic monomer/acid SO~ iOII.
Monomer. By the term "monomer" denotes llle molecular unit that by repetition,
S con~ti~ s a large struclure or polymer. I~or example etllylene CH2=CH2 is the monomer of
polyelhylene, H(CH2)NH.
Allyl. By lhe lerm "allyl" is i~llellded 2-propenyl, lhe monovalent radical,
CH2 =CHCH2-.
Organic Acid. By the lenn "organic acid" is inlended an acid made up of molecules
con~qinin~ organic radicals. Such acids include for example, formic acid I~H-COOH), acetic acid
(CH3COOH) and citric acid (C6H,~O7), all of which contain the ionizable -COOH group.
Acrylic. By the term "acrylic" is intended synlhelic plaslic resins derived from acrylic
acids.
Optically 'rtansparent. By the terminology "optically transparent" is inten(le~l the
plUpel ly of a polymeric malerial lo allow the passage of light at or above the threshold of visual
20 senQq~ion (i.e., the minimum amount of ligllt intensity invoking a visual sensation). Preferably,
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lhe present biocompalible polymeric malerial including COLLAMER has a refractive inde~c in
the range of 1.44 to 1.48, more preferably 1.45 lo 1.47, and most preferably 1.45 to 1.46. The
best mode of the present invention is tlle biocompatible polymeric material COLLAMER.
Polyrnerizatfon. By the term "polymerization" is in~Pnded a process in which monomers
combine to form polymers. Such polymerizalion can include "addition pol~ne.i~tionH where
monomers combine and no olher producLs are produced, and "cnnden~tion polymerization"
where a by-product (e.g. water) is also formed. Known suitable polymerization processes can
be readily selected and employed for Ihe production of the present biocompatible polymeric
mateAal by those of ordinary skill in the art to which the present invention pertains.
Polyene. By the term "polyene" is inLended a chemic~l compound having a series of
conjugated (alternating) double bonds, e.g., Ihe carotenoids.
Refractive Index. By the terminology "refractive index" is intended a measurement of
the degree of refraction in translucentllransparent subslances, e~peci~lly the ocular media. The
"refractive index" is measured as the relative velocity of light in anotller medium (such as the
,
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present polymeric malerial) as compared lo Llle velocity of light in air. For example in the case
~ of air to crown glass Ihe refractive index(n) is 1.52 in Ille case of air to water n= 1.33.
Tensile Strengt~l. By the terminology "lensile strenglh" is intçncied the m~xim~l stress
5 or load that a malerial is capable of s~ inillg expressed in kPa. The present biocompatible
polymeric material including COLLAMER has a lensile strength in the range of about 391-1778
kPa preferably 591-1578 kl'a more preferably 791-1378 kPa and most preferably in the range
of from 991 kPa to 1178 kPa. The presenl material "COLLAMER" has a tensile strength of
preferably 1085 i 493 kPa. The tensile strenglll of a polymeric m~çri~l can be readily
10 determined using known melhods by those of ordinary skill in the art.
Hypennetropia. By the term "hypermetropia" (h.) is intended
farsiglltef~nP-s~/longsigllt~lnç~s i.e. long or far sight which is an oplical condilion in which only
convergent rays can be brought to focus on the retina. Such conditions include: (1) absolute h.--
15 that cannot be overcome by an effort of accommodalion; (2) axial h.--h. that is due to shortening
of tlle anteroposterior f1i~mçtçr of the globe of the eye; (3) curvature h.--h. which is due to the
dec~ased refraction of the anterior di~me~r of Lhe globe of Ille eye; (4) manifest.--h. that can
be comp.on~ by accommodation; (5) facultative h.-- manifest h.; (6) latent h.-- the difference
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between total and manifest h.; and (7) total In-- Ihat wllicll can be determined after complete
paralysis of accommodation by means of a cycloplegic; (8) index h.--ll. arising from decreased
refractivity of tlle lens.
Myopia. By ll~e term myopia (m) is intended sllortsighl~ ineSs; near~ighlPlness; near
or short sight; that optical condition in wllicll only rays a finite ~ nce from lhe eye focus on
tlle retina. Such conditions include: (1) axial m.--m. due to elongation of the globe of the eye;
(2) curvalure.-- m. due to refractive errors rçs llting irom excessive corneal curvature; (3)
degenerative.--patllologic m.; (4) index m.--m. arising from increased refractivity of the lens
as in nuclear sclerosis; (5) malignant.--palllologic m.; (6) night.--m. occurring in a normally
emmetropic eye because long light rays focus in front of tlle retina; (7) pathologic.--degenerative
or m~ n~nt progressive. marked by fundus changes posterior staphyloma and subnormal
corrected acuity; (8) prematurity m. .--m. observed in infants of low birtll weight or in
association with retrolental fibroplasia; (9) senile lenticular.--second sight; (10) simple m.--m.
arising from failure of correla~ion of the refraclive power of the anterior segment and the length
of the eyeball; (11) space.--a type of m. arising when no contour is imaged on the retina; and
(12) tr~nci~n~--m. observed in accommodative spasm seconr~ry to iridocyclitis or ocular
co~ t-- ~ior
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~ IydropJIilic allelic motlo-ner. By lhe lerm "hydropllilic allelic monomer" is int~.ndelJ
for the purposes of lhe present inventioll any monomer conlaining an allyl group wllich monomer
is soluble in water.
~ ydrop~lilic acrylic rnonomer. By Ihe terminology "hydrophilic acrylic monomer" is
in~n(lecl any monomer cQnt~ining an acrylic group whicll monomer is solul)le in water. ~or
PY~mrle, HEMA is a hydropllilic acrylic monomer because il is soluble in water even though
it contains bolh hydrophilic groups and l-ydropllobic groups.
~Iydrop~lobic allelic monorner. By ll-e lenn "hydropllobic allelic monomer" is inlended
for tlle purposes of llle present invenlion, any monomer contai~iing an allyl group, whicl
monomer is not soluble in water.
~Iydrop~obic ac~ylic monorner. By Ille term "hydropllobic acrylic monomer" is intendef~
for the purposes of the present invention, any monomer containing an acrylic group, which
monomer is not soluble in water.
Defonnable lens. By the term "deformable lens" is intended any type of deformable
lens, for eY~mplt-, for correcting hypermetropia or myopia, where tlle lens comprises the present
material. Such lenses include those disclosed in U.S. Patent Applicalion Serial Nos. 08/318,991
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and 08/225,060. All of the foregoing are hereby incorporaled by reference llerein. Such lenses
include: intraocular lenses for implantation inlo a palienl's eye, for example, into Ille anterior
cllamber, in the bag or in the sulcas; refraclive inlraocular lenses for impl~n~ti- n into a patient's
eye, for example, into the anterior chamber or in tlle sulcas; and standard sort contact lenses.
s
~ mplan~. By the term "implant" is intended tlle surgical melllod of introducing the
present lens into the eye of a palient, for example, into the anterior chamber, in the bag or in
the sulcas, by Ihe melhods described in U.S. Palent Applicalion Serial Nos. 08/195,717,
08/318,991, and 08/220,999 using for example, surgical devices disclosed in U.S. Palent
Application Serial Nos. 08/197,604, 08/196,855, 08/345,360, and 08/221,013. All of the
foregoing are hereby incorporaled by reference.
The present hydropllilic monomers and hydrophobic monomers must be selec~d such that
the hydrophobic monomer(s) is soluble in tlle llydrophilic monomer(s). The hydrophilic
15 monomer acts as a solvent for the hydropllol)ic monomer. Suitable monomers can be readily
sele~t-oJl by those of ordinary skill in the art lo which the presenl invention pertains.
Examples of suilable ~Iydrop~lobic monomers, include:
1) 4-methacryloxy-2-hydroxybenzophenone (acrylic);
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2) ethyl-3 benzoil acrylate (acrylic);
3) 3-allyl-4-hydroxyacetophenone (allelic);
4) 2-(2'-hydroxy-3'-allyl-5'-1llelllylpllenyl)-2H-benzotriazole (allelic);
5) N-propyl me.lf-~rrylale (acrylic);
6) allyl benzene (allelic);
7) allyl butyrate (allelic);
8) allylanisole (allelic);
9) N-propyl melhacrylale (acrylic);
10) ethyl-melh~crylate (acrylic);
11) metllyl metll~crylate (acrylic);
12) n-heptyl melhacrylate (acrylic).
Various examples of suitable ~yclt-op~lillc monomers, include:
1) 2-hydroxyethyl melhacrylale (HEMA) (acrylic);
2) hydroxypropyl methacrylate (acrylic);
3) 2-hydroxyetllyl me.lh:lr.rylate (acrylic);
4) hydroxypropyl methacrylate (acrylic);
5) allyl alcohol (allelic);
6) poly(ethylene glycol)n monomelhacrylate (acrylic);
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7) 4-hydroxybutyl me~ crylate {acrylic);
8) allyl glucol carbonate (allelic).
II. A~etJIod of Making t~e r'resent Polymeric ~ate~ial l~ased on Collagen
s
The following is a descriplion of a pre~erred metllod of making lhe biocQmp~ible
polymeric material according lo lhe present invenlion.
Step 1:
The hydrophilic monomer is mixed wilh an acid, in particular formic acid. The
weigllt ratio of hydrophilic monomer to acid is preferably in the range of about 5:1 to about
50:1, preferably 14:1 to 20:1, and most preferably, 14:1. This solulion is preferably filtered
through a 0.2 microfiller.
Step 2:
In an independent step, an acidic telo-collagen solulion is prepared by mixing
telo-collagen wilh organic acid (preferably formic acid). The solution is preferably 2 % by
20 weight telo-collagen in 1 M formic acid.
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Step 3:
The solutions resul~ g from steps l and 2 are lhen mixed togelller. The res~ nt
solution is preferably mixed from about 10 minutes to 60 minules, ntost preferably 20 min~ s
S at a lemperalure of 15-30~C. Tlle ratio of lelo-collagell to hydropllilic monomer is about 1:2 to
about 1:7, preferably 1:3 to 1:6, and most preferably 1:4.
Step 4:
In an independent slep, lhe hydropllobic monomer and hydropllilic monomer are
mixed logelher in a weigllt ratio of aboul lO: l lo l: l, preferably 8: l to 3:1, and most preferably
5:1. The monomers are mixed wilh stirring for about 30 lo 90 minutes, preÇerably 60 minu~es
at 70 to 95~C, preferably 80-95~C, and most preferably 80-92~C. The res~ in~ solution is
preferably filtered through a 0.2 micron filller.
Step 5:
The solulions from sleps 3 and 4 are mixed logelher in a weighe ralio in the range
of about 1:1 to 50: 1, preferably 2: I to 5: l, and most preferably 3: 1. The solution is prererably
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mixed 20 minutes with no heating at a temperalure of 25-40~C. Mixing is preferably performed
with a homogenizer.
Step 6:
The resulting material from Step 5 is thell preferably degassed (i.e., using
centrifugalion or other means well-known to tllose of ordinary skill in the art to whicll the
present invention applies).
0 Slep 7:
The resulting material from Step 6 is irradiated to form a final product that can be dried,
and stored, (i.e., stored in a desiccator due to its hydroscopic nature). The material from Step 6
can also be stored in a refrigerator, for example at 5~C to 10~C, prior to irradiation.
A polymeric material according to the present invention is obtained from an interaction
l~etw~ll a solution of telo-collagen complex, and the hydropllilic and the hydrophobic monomers
under radiation of lMrad/hr for a to~al dose of from 0.20 to 0.80Mrad, preferably 0.30 to
0.60Mrad, and most prererably rrom 0.35 to 0.50Mrad (lMrad = 10 Kgray).
r
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A turbo-type mixer such as a homogellizer, is preferably employed for mixing lhe
solulions of at least Steps 3 and 5, auld llle IlliXillg limes set forlll above are based on using a
turbo-type mixer. Tllose of ordinary skill in the arl can readily select and employ other known
mixers and melhods, as well as time ranges.
In a preferred embodimellt lhe present polymeric material is made by mixing lhe
hydrophobic monomer in two slages to increase the solution viscosity, where in stage one the
lelo-collagen complex and a mixture of rormic acid willl 2-hydroxyethyl-me~ rylale are used
as a stabilizer of ultra-colloidal state solution and in stage Iwo a hydrophobic blend of at least
10 one monomer is introduced into the gel produced.
Staltdardized MetJlod for tJle Co~npounditlg of tJIe present COLL~MER
f~. Preparation of ~lcidic Collagerl Solution
A lM acid solution, pre~erably lM formic acid is prepared. The quantity of acid
solution l~uir~d for dissolution of llle swollen lissue is calculaled using a ratio of swollen
collagen tissue: (sclera or cornea) acid solution of about 40:0.5 to 55:2, preferably about 45:1
lo about 52:1.5, most preferably about 50:1.
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Tlle swollen tissue is Ihen dispellse(l in a llomogenizer for about 10 to 20 minutes,
preferably about 15 minu~es at 2 to 10 RPM, preferal~ly 4-5 RPM, at room tem~e~lu~t:. The
produced solution is Illen fillered througll a funnel glass filter willl a pore size of 100-150
microns, the filtrate is Ihen fil~ered Ihrougll a second funnel glass filter wilh a pore size of
5 75-100 microns. The produced llomogenic solulioll is then Iransferred inlo a container.
. Ilydrop~lobic an~ ~Iydrop~lilic SolulioJI Prepal~tion
1. The hydrophilic monomer, prererably HEMA is mixed wilh the hydropllobic
10 monomer, preferably MHr~PH in a weight ralio of about 5:1 a~id healed for one hour at 80~C
to 92~C wilh s~irrin~ (e.g., using a stirrer hot plate). The heated solu~ion is Illen filtered through
5.0 micron filter.
2. HEM~ is mixed wilh an org ulic acid (preferably formic acid), preferably in
15 a weight ratio of about 14:1. This mixture is added to the collagen solution produced (A) in a
weight ratio of HEMA solu~ion:collagen solution of about 1:3, and mixed for about 20 minutes
at room le.,.pe.~ture. The mixing is preferably perrormed using a homogelli e- at a rale of 6000
RPM.
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3. The HEM~ M~IBPH solulioll of 13.(1) is Illen mixed in Slllall portions willl
~ the HEMA telo-collagen solution of B.(2). Tlle mixing is preferably ~elrol.ned in a
homogenizer for 10 minules at room lemperalure.
S C Production of COLLAMEI~
Glass vials are then coaled willl approximalely 7mm of paraffm wax. The
solulion of 1~(3) }s then poured into the glass vials and degassed (e.g., centriruged for 15 minules
to remove air). The vials are subsequenlly irradialed al 5 Kgray. (Nole: prior to irr~ ior
10 the vials can be slored in a refrigeralor, for example al 5~C to 10~C.)
IY. Guid~nce for Selecting t~le Presen~ Monorners
Tlle following equalion can be used lo aid in the seleclion of the ap~loplialc
15 conc~qntralion of monomer necessary lo result in Ihe presenl polymeric malerial having an index
of refraction in the present desired range (1.44 to 1.48, preferably 1.45 lo 1.47, and most
~l~rer~bly 1.45 lo 1.46).
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The monomer of copolymerizalion with telo-collagen comple~c is sP.I~ such that:
N = (K, ~ N~) ~ (1 - K,)Np = Nc + 0.02
K, = coefflcient of swelling
N~ = refractive index of water (1.336)
Np = refractive index of dry polymer
N~ = refractive index of telo-collagen (about 1.45 to 1.46)
~i =n
where Np = A ~ N; ~ Ci
~i=n /
N; = refractive index of i-monomer
C; = concentration of i-monomer
A = coeffi-~ient of increase in refractive index due to polyllleriz~tion
n = number of monomers
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i = monomer number
The hydrophobic and l-ydrophilic monomers must be selecled such tllat the llydlopllilic
monomer is a solvent for lhe hydrophobic monomer, i.e., lhe hydropllobic monomer is soluble
5 in the hydropllilic monomer.
Tlle manner and melhod of carrying out lhe present invention may be more fully
understood by lllose of skill in lhe art lo whicll tlle presenl invention pertains by reference lo lhe
following examples, which examples are nol inlellded in any manner lo limit lhe scope of lhe
10 present invention or of lhe claims direcled therelo.
Examples
Example ~: Compounding COLLAAIER
~. ~'reparatioll of acidic collagen solution
Under an eYh~ust hood, 1 liter of dislilled waler was measured inlo a 3 liter glass beaker.
52 grams of formic acid was then added to the beaker and mixed unlil dissolved. Swollen
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collagen conl~inil-g lissue (frolll yig's eyes) was tllell a~l~le~l lo llle aci~ solulion in the below
ralios of swollen tissue:acid solulion.
S1l~0lle~ 'ssr e ~cia' Solrllion
1. 517.00 grams 10.21 grams
2. 50.64 grams 1.00 graltls
The mixlure was lhel1 slored in a rerrigeralor al a lempera~ure or5~C, and was thereafler
dispersed in a homogenizer for 15 millules at 4-5 RPM at room lemperalure.
The produced solulion was lllen fillered lllrougll a funllel glass filler wilh a pore size of
100-150 microns. Tl1erearler, the fil~rale was fillere(l ll1rougll a funnel glass filter wilh a pore
size of 75-100 microns. The final holnogellic solulion was thell lransrerred inLo a 250ml
conlainer.
1~'. A~ PlI and ~IEll~ solrltion prepaJ~tion
1. 527.4g of I~EMA was mixecl wilh 106.2g of MHI~PI~ and healed for one hour
at 80~C using a slirrer ho~ plale. The healed solulion was fillered Illrougll an Acro 50-5.0
micron filler.
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2. 1415.6g ofI~E M A waslllen n~ixe~ willl99.4g offomlic aci~ in a hermelic
glass con~iner wilh a Tenon licl. 100g porlions or ll~eIIE M ~/aci~l solulion were added inlo
333g of lelo-collagen solulion and mixe~l for 20 millules at roon~ lemperalure. The mixing was
perfonned in a holt1ogenizer at a rale of6000 I~I'M.
3. TheI-IE M A/M H~PI~solulion waslllen ad~ed in small porlions lo lhe H EM A
lelo-collagen soluLiol1. The mixil1g was performed in a llomogenizer for 10 minutes at room
lempcralure.
C. Prodllction of COLLMI~ER
Glass vials were coaled wilh approximalely 7mlll of paramn wax. The resultant solulion
of Slep B(3) was lllen poured inlo ll~e glass vials and cenlrifuged for 15 minules to remove air.
Tlle vials were ll1en irradialed al SKgray lo polymerize and cross-link lhe present malerial.
Example 2: Pt-epar-ation of a Uiocor rpalible Polyrneric Oplically Transparent Mate/ial
In ll~is example, pig's eye sclera was used. 300g of 2-llydroxyelhyl melhacrylale was
mixed willl 16g of rormic acid. 50g of lelo-collagen was fillered purified from sclera using
~lk~ hydrolysis willl 200g NaOI~ an(J 200g of Na2SO~in 2.5 Iilers of waler, and fillered
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througll a 100 micron filller. Tlle lelo-coll~gen was mixe(l with 2-llydroxyelllyl melhacrylale and
lhe formic acid solulion conlaillill~ 2-l~ydroxyelllyl metllacrylale. 20~ of 4-~ne~ ~ryloxy-2-
hydroxybellzopllenone (MHBrH) dissolved in ~EM~ was then added. This mixture was
radialed wilh gamllla radialion in IllC range of 3.5-5.0 Kgray lo polymerize and cross-link ail
5 tlle components.
Hydrophol)ic monomers werc used in IhiS syslem lo reduce tlle absorplion of waler and
swelling of lhe polymerized ma~erial when inlroduced inlo lhe aqueous media of tlle eye. In
addilion, lhe hydropllobic monolller was chosen so lllat lhe refraclive index of the resullant
10 polymer increase~l lo be approximalely equal lo lile rerraclive index of lelo-collagen.
Example 3:
The same procedure in ~xample 2 c~ul be ulilized, excepl lllc following monomers can
15 be subsliluled:
1) elllyl-3-benzoilacrylale (ilydropllol)ic acrylic mollomer), plus
2) 2-hydlu~cyelllyl melhacrylale (1~I3M~), (llydroplli1ic acrylic .nollome,).
2(~
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Example 4:
The same proccdure in Example 2 can be ulilized, excepl lhe ~ollowing monomers can
be subsliluled
s
1) 3-allyl-4-hydroxyacelo~ ellolle (l~ydropllobic allelic monomer), plus
2) 2-llydroxyelllyl melllacrylale (III~MA), (llydropl~ilic acrylic monomer).
Example 5:
Tlle same procedure in Examl)le 2 call l~e utilize(l, except Ille following monomers can
be subsliluled:
1) 2-(2'-hydroxy-3'-allyl-5'-me~llylphcnyl)-2H-benzotriazole (hydropl~obic allelic
monomer), plus
2) hydroxypropyl metllacrylale, (llydropl~ilic acrylic monomer~.
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E~ample 6:
Tlle same proce~lure in Exanlple 2 can bc ulilized, eXcept Ihe rollowing monollters can
be subsliluled:
s
1) melllyl melllacrylate (hydropllobic acrylic monomer), plus
2) llydroxypropyl melhacrylate (lly~lropllilic acrylic mollolller).
~ artlple 7:
The same procedure in Example 2 can be ulilized, except Ille rollowing monomers can
be subsliluled:
1) 2-(2'-hydroxy-3'-allyl-5'-melllyll)llellyl)-21~-bellzolriazole (hydropllobic allelic
monomer), plus
2) hydro~y~lo~yl melhacrylale (hy(lropllilic acrylic monomer).
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Example 8:
f~. Tensile Slrengl~l ï'esling of COLl~A~EI~ Malerial
S The purpose of l11is ~est was lo delen11i11e llle lensi1e properlies of llle presen~ co11amer
malerial. This includes ~ensi1e s~ren~,l1), Young's modulus, and percent elongalio11 at failure.
T1le da~a collecled was used lo conslruct slandards Çor inspcclio1l. The lensi1e lesl is similar lo
lhe silicone lensile lesl. The saml)1e geon1clry is difrcre11l bu~ llle slress fundamenta1s remai
tlle same.
1~. Malenals
COLLAMEI~ samples
Inslron tensile lesler (Model 1122)
lS forceys
log book
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C. Proced~re
1. S~mple l'repal~tion
S a. The dry malerial samples were cut inlo rings. Tlle ~ c~olls
are: Oulside diameler = 10 ~ .I mm, inside diameler = B + .1
mm, llliclclless = 1.0 -~ .01 mlll. Tlle malerial was ~Jl~ed
following Ille procctJures used tu manufaclure lenses. Lcnses were
hydraled following MSOI' ~f 1 13
2. Tesling
a. The inslron lestcr was sel up for ~ensile spe~-im~nc~ following
ESOI' 202, RMX-3 Slab Pull Test, Rev I3. The fixlures were
placed inlo lhe jaws an(l lhe filxlures were brought together so lhat
llle lop and bollolll porlion touclled, by moving the c,v~ (l up
or down. Wllen Ille fixlures were louchin~, there was
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apyroximalely 8 mlll belween llle lwo pms. This was llIe starlillg
posilion of jaw scparalioll, so ll~e Inslroll posilion coorclinales wcre
sel to zero.
b. Tlle load dial was seL lo 2 kg full scale outpul, llle c,ussllead speed
lo 500 mm/mill an~l llle chart recorder to 500 mm/lllin. Tlle cllart
speed ~;oll~spoll(led lo auld recorded jaw separation. The cllart
bullons marked "I'I~N" and "TIME" wcre dclJI~s;~d.
c. The wel lesl sample was removed rrom ils vial and ylaced so it
was almosl sLrelclled belween llle ~wo pillS. When lhe sample was
in place, llle "UP" bulloll on the crosshea~ conlrol panel was
imllledialely pressed. Tllis sample was Illen loaded lo failure.
~- Wllen llle sallll)lc ~ailc~, llle "sroP" l~ullon on lhe c;,o~ eA~I
conlrol panel was presse~. Tllc charl bullolls marked "PEN~ and
"TIME" were lllen depressed so lllal tlley were in llle up posilion.
lhe relurn on llle crossllead conlrol panel was lhen pressed to
relurn llle crosshea~l Lo slarling posilion.
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e. Tl~e failure point in tl1e cllan was tllell marked by noting tlle load
at failure (in kg) ancl jaw separalion.
f. Sleps 2a lllrougll 2e were repealed unlil all samples were all lesle~.
G Da~a
C'nlel~rntiortfor Ullimate Tetlsile Slretlg~J
(1) a = ~/A
Where:
~ = Ullimale Tensile Slrellglll, I'ascals, (Pa).
F = Force required to brcak tlle lesl specimen, Newtons, (N)
A = Hydrale(l cross seclional area of specimen, square melers, (m2).
ô = Swell Faclor, 1.17
w= Wi(Jlll~ mm
~ = lllic~less, mlll
.
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civell:
= .29 kg x 9.81 m/s2 = 2.84 N
A = 2[~(w) x ~(t)]=2[(1.17 x 1.0) x (1.17 x 1.0)] = 2.74 mm2
S Conversion from mm2 lo m2: 2.74 mm2 = 2.74 x 10~ m2
A = 2.74 x l0-6 m2
I;il~(l:
Ullimale Tensile Slrengtll,
Solulioll:
~ = ~/A = 2.84N12.74 x 10-6 m2 = 1038.3 kl'a
lS To converl kPa lo psi, mlllliply ~y 145.04 x 103
1038.3 kPa x 145.04 x 10-3 = 150.6 psi
= 1038.3 krn or a = 150.6 psi
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~n~CI~/ntioJt for l'ercent Elongation
(2) ~ = 200tL/M C~S)]
Wllere:
~ = elongatioll (specirled), percent,
L = increase in jaw separalioll at specified elongalion, (mm), and
MC~rS~ = meall circumrerel-ce of test specimen, mm,
circum~erellce =
Givell:
L = 41.5 mm
MC~TS~ rdl + 7r(1~)/2 = (~r x 10 mm ~ ~r x 8 mm)/2 = 28.27 mm
Filld:
Elongation,
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Sollltio~
= 200[L~M C~s)] = 200~41.5 Itllll/28.27 mln] = 293.6%
= 293.C%
C~ r~1nt;onfor Yor~llg's A~o~ lus
(3) E = Pl/Ae
1 0 Wllere:
E = Young's Modulus, I'ascals, (Pa)
P = ~orce, Newlons, (N)
l = lenglll of sample, melers (m)
A = Cross Seclional Arca, square melers, (m2)
e = Gross Longiludinal Deformalion, melers, (m).
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Cive~l:
r = .29 kg x 9.81 m/s2 = 2.84 N
I = .008 m
A - A = 2[~(w) x ~(1)] = 2 t(l.l7 x 1.0) x (1.17 x 1.0)~ = 2.74 mm2
Conversion from mm2 lo m2 2.74 mm2 = 2.74 x lo-6 m2
A = 2.74 x 1o6 nl2
e = .0415 m
Filld:
Young's Modulus, E
SoluLion:
~ = rl/~e = (2.84 N x .OU8 m)/(.0415 m x 2.74 x 10-6 m2) = 200.2 kPa
To convert kPa to psi, mulliply by 145.04 x 10-3
199.8 kPa x 145.04 x 10-3 = 29.0 psi
~ = 199.8 I~r~ or 29.0 psi
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E, Discl~ssio~l
Tlle Ins~ron was set up and calibraled accordillg lo ESOP IY202. The lesling rlxlures were
brought togelher so the cenlerlines were aligned and Ihere was approximalely 8 mm belween lhe
5 posts. This was designaled ~ero and the fixlllres relurned lo this poSilioll every time afler the
test. Crosshe~(l speed and lhe chart recorder speed were sel lo 500 mm/min.
The chart recorder was set al zero loa(l ancl defleclioll berore every lest. Tlle chart
recorder recorded kilograms-force load and jaw separalioll. Load is used lo delermine tlle
10 ~ m~P tensile strenglll (see formula 1, Tesl Dala Seclion), lhe slress at wllicll the sample fails.
The sample was not set up to tesl elongalion using a slan~iard gage length but a formula in the
ASTM D412 standard is used to calculale llle elon~ation (see formula 2, Data Section).
The performance of the specimen proved the malerial to be elaslic and willl the stress
15 increasing at a linear rale unlil failure. The linear increase can be one of two things: (1) it is
possible the speci-nçns have slress risers Oll the inside di~meler. Slress risers would be caused
by lhe milling process, becausefil doesn'l l~ave llle surface finish of tlle lallle-lurned ouler
melçr; tllis may not allow llle malerial lo neck down during lhe plaslic deformation stage of
tlle test. The majorily of the slress is concelllraled Oll tlle inlernal circulnference, which loads
20 the stress risers more than if they were on the oulside circumference; (2) Ihe material may not
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neck down (p1astic derormalioll) as do olher plaslic malerials such as Kaplon film. lt reacts lilce
RMX-3 wilh lhe cross secliollal area gellil)g smaller as elongalion increases wllich is indicalive
of Hooke's law.
Tlle present malerial showed COLLAMER good resi~l~ncP~ lo tear propagation whichwould happen at auly slress risers. Tlle cross seclional area of Ihe failed part was llat wllich
was indicalive of elaslic failure.
E. COJI cl~lsioll
The coml)ined data frotn lhe present COLLAMEI~ samples gave an average tensile
slrength of 1084.6 kilopascals (kra) an(l an average elonga~ion of 324.9 percent (%). The
tolerance ~or average lensiie slrenglll was calculaled as -~ 3 limes Ihe standard devialion giving
an upper tolpr~nce of 1578 kPa (229 psi) and a lower lolerance of 591 kPa (86 psi). The
tolerance for llle elongalion is calculaled in lhe san~e manner. The upper lolerance is 395 %
elongation ancl the lower tolerance is calculale~l as 255 % elongalion. See Appendix 3 for lhe
calculalions. The tensile slreng~h standard is 1085 ~- 493 kPa (157 + 71 psi) and the elongation
is 325% i 70. Young's modulus standard is 189 + 25 kl'a (27 + 11 psi).
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eferellces
ASTM D412 Properlies of Rubber in Tensio
ESOP 202 - RMX-3 Slab Pull Tesl, Rev I3.
Mark's S~andard Mand~ookfor Mec~anical E~lgirleers, Ninlh Edilion
All references ciled are hereby incorporaled by reference. Now having fully dese~ ed
lhis invention, it will be underslood by lhose of skill in lhe arl lllal lhe scope may be performed
wilhin a wide and equivalenl range of con~lilions, paramelers, and lhe like, wilhout affecling lhe
10 spirit or scope of lhe invenlion or of any eml)odilnenl thereof.
