Rheologically modified and osmotically balanced fill material for implant

A rheologically modified, osmotically balanced dispersion for an implant for the body. The dispersion includes an osmotic control agent of preferably polyvinylpyrrolidinone, a rheological agent of preferably guar gum, and an antimicrobial. Methods for filling an implant are also disclosed. The osmotic control agent or first polymeric osmotic control agent is present in the dispersion in an amount effective to substantially balance the osmotic pressure of the implant with the osmotic pressure of the portion of the body into which it is implanted. The rheological agent or second polymeric agent forms a three-dimensional network and is present in the dispersion in an amount effective such that the fill material is pseudoplastic. Both the first and second polymeric agents are biocompatible.

BACKGROUND OF THE INVENTION 
The present invention relates generally to implants introduced into the 
body, particularly to fill material for such implants, and specifically to 
rheologically modified fill material for implants. 
For implants such as breast and testes prosthesis as well as other implants 
and prosthesis, silicone has been the fill material of choice. However, 
silicone as a fill material has fallen into disfavor. This has prompted 
efforts to find replacements for silicone. These replacements are often if 
not always undesirable because such replacements have been unable to match 
the feel provided by silicone. The inventors of the present invention have 
investigated the rheological parameters of certain fluid formulations in 
an effort to provide a fill material having the heretofore unmatched feel 
of silicone. Thus, it is important to understand some basics of rheology 
to have an understanding of the present invention. 
Rheology is the science of the deformation and flow of matter. It is 
concerned with the response of materials to mechanical force. Polymer 
rheology deals with polymeric materials and biorheology deals with 
biological fluids. 
Deformation is the relative displacement of points of a body and can be 
divided into two general types: flow and elasticity. Flow is irreversible 
deformation; when the stress is removed, the material does not revert to 
its original configuration. Elasticity is reversible deformation; the 
deformed body recovers its original shape. 
The usual way of defining the rheological properties of a material is to 
determine the resistance to deformation. Resistance to deformation is 
measured by two indexes or yardsticks: 1) viscosity (the index or 
yardstick for flow; viscosity is the resistance to flow of a liquid); and 
2) the degree of elasticity (elastic deformation). 
A liquid is a material that continues to deform as long as it is subjected 
to a tensile or shear stress. For a liquid under shear, the rate of 
deformation (shear rate) is proportional to the shearing stress. 
Thixotropy is the decrease in viscosity with time when sheared at a 
constant shear rate. Rheopexy, a relatively rare occurrence, is the 
increase in viscosity of a fluid in response to shear. For example, as to 
thixotropy, when a shearing action begins, such as when one applies a 
latex house paint with a brush, the viscosity decreases quickly to permit 
the paint to be easily brushed to a thin film and provide a short period 
of time for the brushmarks to level. When the shearing action stops, such 
as when the paint leaves the brush and clings to the wall, the viscosity 
of the latex house paint increases to prevent running and sagging. 
Thixotropy may be a time dependent effect. 
A single fluid may be subject to a number of shear rates. For example, a 
paint may be pumped during manufacture or immediately prior to application 
(intermediate shear rate), sprayed onto a wall (high shear rate), coalesce 
and flow to form a uniform film (intermediate to low shear rate), and sag 
or run under gravity (low shear rate). A given liquid or material may work 
well at one or two of the shear rates, but fail at other shear rates. 
SUMMARY OF THE INVENTION 
General objects of the present invention include a unique rheologically 
modified dispersion for an implant for a body and unique methods for 
filling the implant. 
Another object of the present invention is to provide such a rheologically 
modified dispersion which uniquely includes an osmotic control agent. 
Another object of the present invention is to provide such a rheologically 
modified dispersion wherein the osmotic control agent uniquely includes a 
poly-N-vinylamide. 
Another object of the present invention is to provide such a rheologically 
modified dispersion wherein the poly-N-vinylamide uniquely includes 
polyvinylpyrrolidinone. 
Another object of the present invention is to provide such an osmotically 
controlled and rheologically modified dispersion wherein the rheological 
agent uniquely includes a three-dimensional network. 
Another object of the present invention is to provide such an osmotically 
controlled and rheologically modified dispersion wherein the 
three-dimensional rheological agent uniquely includes gum. 
Another object of the present invention is to provide such an osmotically 
controlled and rheologically modified dispersion wherein the gum uniquely 
includes a natural gum. 
Another object of the present invention is to provide such an osmotically 
controlled and rheologically modified dispersion wherein the natural gum 
uniquely includes guar gum or locust bean gum and their derivatives. 
Another object of the present invention is to provide such an osmotically 
controlled and rheologically modified dispersion wherein the gum uniquely 
includes xanthan and its derivatives. 
Another object of the present invention is to provide such an osmotically 
controlled and rheologically modified dispersion wherein the gum uniquely 
includes a synthetic gum. 
Another object of the present invention is to provide such an osmotically 
controlled and rheologically modified dispersion wherein the synthetic gum 
uniquely includes poly(vinyl alcohol), polyethylene oxide, polypropylene 
oxide, polyacrylamide, or copolymers of polyvinylpyrrolidinone. 
Another object of the present invention is to provide such an osmotically 
controlled and rheologically modified dispersion which uniquely is a 
pseudoplastic. Such a pseudoplastic dispersion mimics the rheology of body 
fluid and tissue. 
Another object of the present invention is to provide such an osmotically 
controlled and rheologically modified dispersion in which uniquely all of 
the components of the dispersion are biocompatible. Accordingly, even in 
the worst case scenario in which the implant bursts, little or minimal 
danger is presented. 
An advantage of the present invention is that the fill material of an 
implant is osmotically balanced with its environment. With an osmotic 
balance, the implant retains its desired volume. Such is in contrast to an 
implant which includes a low osmotic pressure; here, water or another 
solvent flows out of the implant, perhaps causing fold flaw fracture. A 
high osmotic pressure in the implant may lead to a bursting of the 
implant. 
Another advantage of the present invention is that the fill material is 
rheologically modified to be pseudoplastic. This provides a feel or 
responsive fill material which mimics body tissue.

All Figures are drawn for ease of explanation of the basic teachings of the 
present invention only; the extensions of the Figures with respect to 
number, position, relationship, and dimensions of the parts to form the 
preferred embodiment will be explained or will be within the skill of the 
art after the following description has been read and understood. Further, 
the exact dimensions and dimensional proportions to conform to specific 
force, weight, strength, and similar requirements will likewise be within 
the skill of the art after the following description has been read and 
understood. 
Where used in the various figures of the drawings, the same numerals 
designate the same or similar parts. Furthermore, when the terms "inner", 
"outer", and "upper" and similar terms are used herein, it should be 
understood that these terms have reference only to the structure shown in 
the drawings as it would appear to a person viewing the drawings and are 
utilized only to facilitate describing the preferred embodiments. 
DESCRIPTION 
In general, the present invention relates to a safe fill material for an 
implant. The fill material preferably includes water, an osmotic control 
agent such as a poly-N-vinylamide or polyvinylimide, a rheological agent 
such as a gum. Optionally, the fill material may include cross-linkers for 
the rheological agent (i.e. the thixotrope or gellant) and/or other 
additives such as antioxidants, preservatives such as antimicrobials, 
wetting agents, and lubricants. The fill material is biocompatible. 
Osmotic control agent, for the purposes of the present invention, means 
that which is added to the fill material to prevent or minimize osmosis, 
i.e. flow of solvent (water) through the membrane of the implant. Osmosis 
is minimized by providing interior of the implant with an osmotic pressure 
which is equal to the osmotic pressure of the environment outside of the 
implant. Accordingly, osmotic control agent further means that which 
provides an osmotic pressure similar to the body or body tissue or fluid 
or to the portion of the body into which the implant is to be located. The 
most preferred osmotic pressure provided by the osmotic control agent, 
when combined with the rheological agent of the present invention, is 
between about 250 and about 350 milliosmoles. 
Still further, the osmotic control agent is a polymer or polymers or 
copolymer or copolymers that contributes substantially to the desired 
osmotic pressure of between about 250 and 350 milliosmoles. Such a 
substantial contribution is made when the polymeric osmotic control agent 
is added to the fill material in an amount preferably between about 90% to 
99.9% w/w, more preferably between about 95% to 99.9% w/w, and most 
preferably between about 98% to 99% w/w of the osmotic control agents. If 
required, salts may be added to fine tune the osmotic pressure of the 
implant. These salts preferably include biocompatible salts such as sodium 
chloride, sodium lactate and sodium acetate in an amount of between about 
1% and 10% w/w of the osmotic control agents. For radiolucency, sodium 
lactate and sodium acetate are preferred. It should be noted that osmotic 
pressure is a colligative property that depends on the number of solute 
particles. 
Still further, it should be noted that osmotic control agents which are 
preferred provide lubricity to the interior wall of the implant. In sum, 
it is preferred that the osmotic control agent: 1) is a polymer or 
copolymer or blend thereof; 2) is present in an amount effective to 
provide an osmotic pressure to the implant of between about 250 and 350 
milliosmoles without the use of salts; and 3) is present in an amount 
effective to provide lubricity to the fill material (i.e. to the interior 
wall of the implant). 
The osmotic control agent is preferably a protective colloid which is 
water-soluble or water-dispersable. Examples of preferred colloids include 
poly-N-vinylamides, poly-N-vinylamide copolymers, polyvinylimides. 
Poly-N-vinylamide hydrogels are most preferred. 
The poly-N-vinylamides may be either linear or cyclic. Examples of 
poly-N-vinylamides prepared from linear derivatives include 
poly(acetamide), poly(methylacetamide), poly(ethylacetamide), 
poly(phenylacetamide), poly(methylpropionamide), poly(ethylpropionamide), 
poly(methylisobutyramide), and poly(methylbenzylamide). Poly-N-vinylamides 
derived from cyclic structures are more preferred. Examples of these 
polymers include polyvinylpyrrolidinone, polyvinylcaprolactam, 
poly-2-piperidinone, poly 5-methyl-2-pyrrolidinone, 
poly-2,2,5-trimethyl-2-pyrrolidinone, and poly 5-methyl-2-pyrrolidinone. 
Polyvinylpyrrolidinone and polyvinylcaprolactam are even more preferred 
with polyvinylpyrrolidinone being most preferred. 
Polyvinylpyrrolidinone (PVP or povidone or poly(N-vinyl-2-pyrrolidinone)) 
is one of the few poly-N-vinylamides prepared from cyclic structures, if 
not the only one, available in a commercial quantity. Polyvinylcaprolactam 
has been commercialized to some extent. 
Poly-N-vinylamide copolymers include poly(vinylpyrrolidinone-co-vinyl 
acetate), poly(vinylpyrrolidinone-co-maleic anhydride), 
poly(vinylpyrrolidinone-co-methyl methacrylate), 
poly(vinylpyrrolidinone-co-dimethylaminoethyl methacrylate), 
poly(vinylpyrrolidinone-co-butyl methacrylate), 
poly(vinylpyrrolidinone-co-hydroxyethyl methacrylate), 
poly(vinylpyrrolidinone-co-ethyl acrylate), 
poly(vinylpyrrolidinone-co-ethylhexyl acrylate), 
poly(vinylpyrrolidinone-co-acrylic acid), 
poly(vinylpyrrolidinone-co-acrylamide), 
poly(vinylpyrrolidinone-co-acrylonitrile, 
polyvinylpyrrolidinone-co-styrene), poly(vinylpyrrolidinone-co-ethylene), 
and poly(vinylpyrrolidinone-co-crotonic acid) and their derivatives. 
For the purposes of the present invention, the molecular weight of the 
osmotic control agent is in the range of preferably about 1,000 to about 
100,000, more preferably about 1,000 to about 40,000, and even more 
preferably about 3,000 to about 20,000, and most preferably about 10,000. 
Poly-N-vinylamides, such as PVP, at molecular weights higher than about 
100,000 may not be excretible from the human body. Poly-N-vinylamides, 
such as PVP, at weights below about 100,000 may be bioexcretable, with 
those having molecular weights below 30,000 being more likely to be 
quickly excretable, such as through the human kidney. The molecular 
weights noted herein are in daltons. 
A higher molecular weight of the poly-N-vinylamide, such as PVP, generally 
relates to a higher degree of polymerization and a greater intrinsic 
viscosity. Further, the viscosity of the poly-N-vinylamide (such as PVP) 
in water generally increases with the solid concentration. 
In the fill material according to the present invention, the osmotic 
control agent is present in the range of preferably from about 0.5% to 
about 60%, more preferably from about 2.5% to about 40%, and most 
preferably from about 3.5% to about 20% (w/w). 
Such a range of concentration, when combined with one or more of the 
rheological agents of the present invention, provides an osmolarity of 
preferably between about 100 milliosmoles and about 500 milliosmoles, more 
preferably between about 200 milliosmoles and about 400 milliosmoles, and 
most preferably between about 250 and about 350 milliosmoles. It should be 
noted that such an osmolarity is preferably obtained without the use of 
salts. It should further be noted that PVP, when alone in solution without 
a three dimensional network, does not provide the desired pseudoplasticity 
to the solution. 
Rheological agent means a material which modifies the normal solution 
properties to increase or decrease its resistance to flow and to increase 
or decrease its elasticity. Rheological agent further means that which 
provides a pseudoplasticity to the fill material to the implant. The fill 
material of the present invention as a whole is pseudoplastic. In other 
words, when shear stress is applied to the fill material, the viscosity of 
the fill material is reduced in proportion to the amount of shear. Upon 
release of the shear, total viscosity recovery of the fill material occurs 
almost instantaneously. 
That the fill material of the present invention is pseudoplastic is 
advantageous. This feature of decreased apparent viscosity at high shear 
rates facilitates mixing, pumping, and pouring. Further, when in the body, 
such pseudoplasticity mimics body tissue and fluid, such as the breast 
body tissue and fluid. For example, the undesired bounce of conventional 
saline implants is minimized. 
The rheological agent includes pseudoplastic agents or thixotropic agents. 
Pseudoplastic agents are preferred. 
The rheological agent is preferably a polymer which provides a 
three-dimensional network within the implant. This three-dimensional 
network provides a backbone for the polymeric osmotic control agent, which 
may contribute in part to the three-dimensional network. 
The rheological agent is preferably one which contributes little to the 
osmotic pressure of the implant. As noted above, osmotic pressure is a 
colligative property that depends on the number of solute particles. With 
the present invention, even though it is a massive "particle", the 
polymeric rheological agent and its three-dimensional network behaves like 
a single particle. Accordingly, it contributes little to the osmotic 
balance. Conversely, a portion of the polymeric osmotic control agent 
contributes to the three-dimensional network, while the remaining portion 
of the polymeric osmotic control agent dictates the osmotic pressure of 
the fill material in the implant. It is believed that the combinations of 
the present invention are synergistic; that is, the osmotic pressure of 
the present invention relates little, if at all, to a corresponding amount 
of an osmotic control agent dispersed only in water. 
Advantageously, it should be noted that the polymeric osmotic control 
agents of the present invention move through the three-dimensional network 
relatively slowly. In contrast, salts are distributed rather quickly even 
in the presence of a three-dimensional network of the present invention. 
The rheological agent is preferably a gum which is water-dispersible. 
Examples include gums which are natural polymers and gums which are 
synthetic polymers. Examples of natural polymer gums include 
polysaccharides, proteins, and natural rubbers and chemically modified 
natural polymers such as hydroxyethylcellulose. Examples of synthetic 
polymer gums include poly(vinyl alcohol) and polyethylene oxide. 
Generally, the rheological agent is added to the fill material in a 
concentration of preferably from about 0.05% to about 36%, more preferably 
from about 0.1% to about 24%, even more preferably from about 0.1% to 
about 12%, and most preferably from about 0.1% to about 2.0% (w/w). 
A gum is a polymeric substance which, in an appropriate solvent or swelling 
agent, form highly viscous dispersions or gels at low, dry substance 
content. Gums may or may not be water-soluble. 
The gum preferably is a water soluble polysaccharide (glycan). Examples 
include seed gums such as corn starch, guar gum, and locust bean gum; 
tuber and root gums such as potato starch and tapioca starch; seaweed 
extracts such as algin, carageenan, agar, and furcellaran; plant extracts 
such as pectin; exudate gums such as gum arabic; fermentation (microbial) 
gums such as xanthan (qv), dextran (qv) and welan (polysaccharide S-130); 
and derived gums such as carboxymethylcellulose, 
hydroxyalkylmethylcellulose, methylcellulose, starch acetate, starch 
phosphate, hydroxyethylstarch, hydroxypropylstarch, oxidized starches, and 
dextrinized starches. Seed gums are most preferred. Of the seed gums, guar 
gum is most preferred. The glycan is added to the fill material in a 
concentration of preferably from about 0.1% to about 25%, more preferably 
from about 0.1% to about 15%, and most preferably from about 0.01% to 
about 10% (w/w). 
Examples of gums which are galactommannans (a polymer of D-galactose and 
D-mannose) include guaran (the purified polysaccharide from guar gum), 
locust bean gum, and tara gum. Of these guaran is preferred. Guar gum, 
locust bean, and tara gum also means, for the purposes of the present 
invention, their blends, and the endosperms, high purity splits, 
derivatives, granules, and powders of such gums. Examples of guar 
derivatives include hydroxypropyl-, hydroxyethyl-, sodium carboxymethyl-, 
sodium carboxymethylhydroxypropyl-, and 2-hydroxypropyl(trimethyl)ammonium 
guar gums. 
The galactommannan is added to the fill material in a concentration of 
preferably from about 0.05% to about 6%, more preferably from about 0.1% 
to about 4.0%, and most preferably from about 0.1% to about 2% (w/w). 
Chemically modified natural polymers or derived gums preferably include 
cellulose derivatives such as an hydroxyalkylcellulose. Examples of 
hydroxyalkylcellulose include carboxymethylcellulose, 
hydroxyethylcellulose, hydroxypropylcellulose, ethylhydroxyethylcellulose. 
The derived gum is added to the fill material in a concentration of 
preferably from about 0.5% to about 30%, more preferably from about 5% to 
about 25%, and most preferably from about 8% to about 15% (w/w). 
Xanthan (or xanthan gum) may be used as the sole rheological agent of the 
present invention or in combination with locust bean and/or guar gum. When 
used alone, xanthan is added to the fill material in a concentration of 
preferably from about 0.05% to about 6%, more preferably from about 0.1% 
to about 4.0%, and most preferably from about 0.1% to about 2.0% (w/w). 
The amount of xanthan in locust bean gum or in a locust bean/guar gum blend 
may be between about 1% and about 99% w/w. The amount of locust bean or 
guar gum in such a blend may be between about 1% and about 99% w/w. The 
xanthan and/or locust bean and/or guar blend is added to the fill material 
in a concentration preferably from about 0.05% to about 6%, more 
preferably from about 0.1% to about 4.0%, and most preferably from about 
0.1% to about 2% (w/w). 
Examples of synthetic polymer gums, where such form biocompatible 
water-dispersable and water-soluble gums, include poly(vinyl alcohol), 
polyethers such as the poloxamers polyethylene oxide and polypropylene 
oxide, polyacrylamide, their copolymers and blends, and copolymers of 
poly-N-vinylamides, including copolymers of polyvinylpyrrolidinone such as 
poly(N-1-vinylpyrrolidone)-co-2-methylaminoethylmethacrylate, 
poly(1-vinylpyrrolidone)-co-acrylic acid, and 
poly(1-vinylpyrrolidone)-co-vinylacetate. As to polyethylene oxide and 
polypropylene oxide and their copolymers and blends, the totality of the 
Tautvydas et al. U.S. Pat. No. 5,407,445 is hereby incorporated by 
reference. 
The synthetic polymer gum is added to the fill material in a concentration 
of preferably from about 0.5% to about 60%, more preferably from about 
0.5% to about 40%, and still more preferably from about 0.5% to about 20% 
(w/w). Still further, in the case of polyethylene oxide or polypropylene 
oxide, the most preferred range is about 0.6% to about 5.0% of the fill 
material. Of the biodegradable synthetic polymers, poly(vinyl alcohol) and 
polyethylene oxide are preferred. 
The gum of the present invention preferably includes those gums which have 
been identified as the safest gums for an implant in the body. Such gums 
include guar, a cellulose derivative (selected from the group of 
carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, 
ethylhydroxyethylcellulose), xanthan, a xanthan/locust bean mixture, 
polyethylene oxide, and poly(vinyl alcohol). Guar, polyethylene oxide, and 
poly(vinyl alcohol) are most preferred. 
It should be noted that it is preferred that the rheological agent of the 
present invention is one which contributes little, if any, to the osmotic 
pressure of the implant fill material. As osmolarity is a function of the 
number of particles, it is preferred that the rheological agent have a 
sufficiently high molecular weight. Guar, for example, typically includes 
a molecular weight between about 200,000 and about 240,000. Locust bean 
gum typically includes a molecular weight between about 300,000 and 
360,000. The compound (or compounds) forming the three-dimensional network 
includes a molecular weight preferably between about 4,000 and 4,000,000, 
and more preferably between about 100,000 and 600,000. 
An example of a biocompatible compound which forms a three-dimensional 
network but which is neither a gum nor a polymer is gelatin. Gelatin is a 
heterogeneous mixture of water-soluble proteins of high average molecular 
weight. Gelatin is not found in nature but is derived from collagen. 
Gelatin may be obtained by boiling skin, tendons, ligaments, bones, etc. 
with water. 
Examples of means for preventing microbial growth include irradiation 
(gamma radiation) of the fill material and antimicrobial preservatives 
such as benzoates and parabens, and non food grade preservatives. The 
preservatives are added to the fill material in concentrations at or less 
than about 1% w/w, or more preferably at or less than about 0.5% w/w, and 
still more preferably at or less than 2.5 w/w. 
It should be noted that the rheological agents of the present invention 
include those rheological agents which have been irradiated prior to 
introduction into the dispersion or formation of gum. These pre-irradiated 
rheological agents include pre-irradiated guar or xanthan gums. As to 
pre-irradiated rheological agents, the totality of the Burgum U.S. Pat. 
No. 5,273,767 is hereby incorporated by reference. 
Optionally, the fill material includes a reactant such as a cross-linking 
agent for the rheological agent. These cross-linking agents include 
Al.sub.2 (SO.sub.4).sub.3 and its analogs, borates such as borax, boric 
acid and its analogs, titonates, chrome complexes, zirconium, and calcium 
compounds. Generally, these cross-linking agents are added to the fill 
material in a concentration of preferably at or less than 1% w/w and more 
preferably at or less than 1% of the concentration of the rheological 
agent. Cross-linking or hydrogen bonding in the three-dimensional network 
of the present fill material may provide a viscoelastic fill material. 
It should be noted that one object of the present invention is to provide a 
safer fill material for an implant. A safer fill material is one which 
includes the least possible amount of nontoxic foreign components. 
It should be noted that the lubricity of the fill material is preferably 
provided by the polymeric osmotic control agent, such as the colloid, the 
poly-N-vinylamide, or polyvinylpyrrolidinone. The amount of the polymeric 
osmotic control agent effective to provide an osmotic pressure to the 
implant of between about 250 and 350 milliosmoles is more than required to 
provide lubricity to the fill material. 
The viscosity, or apparent viscosity, of the fill material is in the range 
of preferably between about 100 and 20,000 centipoise, more preferably 
between about 200 and about 10,000 centipoise, and most preferably between 
about 400 and about 500 centipoise. 
The implant according to the present invention may be a breast or testes 
prosthesis, a penile implant, or an implant containing a drug to be 
dispersed over time. The shell of the implant may be permeable or 
impermeable. For example, the shell may be permeable to water vapor or may 
be impermeable to water vapor, or may be permeable to other fluids or 
compounds such as drugs or pharmaceutical agents. Examples of shells which 
are permeable to water vapor include the shell set forth in U.S. patent 
application Ser. No. 08/473,284, filed Jun. 7, 1995, the totality of which 
is hereby incorporated by reference. Examples of shells which are 
permeable to water vapor include the conventional silicone or polyurethane 
shell. 
A breast implant is shown in FIG. 1. It includes a shell 11, a fill 
material 12 of the present invention, and a closure or joint 13 for 
closing the shell 11 and Sealing the fill material therein. The closure 13 
is a room temperature vulcanized silicone button seal. The closure 13 is 
formed of the same material as the shell 11 and includes an inner disk 
shaped silicone layer 20 having a greater diameter than the outer disk 
shaped layer 22 such that an annular portion 24 of the inner layer 20 
extends beyond the outer layer 22. The outer surface of the annular 
portion 24 is bonded via a vulcanized weld to the inner surface of the 
shell 11. The outer disk shaped layer 22 has a diameter substantially 
equal to the diameter of the opening 26 formed by the mandrel in the 
manufacture of the shell 11. A leaf valve assembly or primary closure 28 
is fixed to the inner surface of the disk shaped portion 20. The leaf 
valve assembly 28 includes an outlet 30 and an inlet disposed adjacent to 
the center of the disk shaped portion 20. The opposing flap sides of the 
leaf valve assembly 28 cling together to minimize passage of fluid through 
the assembly 28. After the closure 13 has been vulcanized to the shell 11 
to close the shell 11, a needle filled with the filling material 12 
penetrates the closure 13 and extends into the inlet of the leaf assembly 
28. The needle is then operated to push the fill material 12 into the 
shell 11. After the shell has been filled, a pocket of air typically 
exists in the upper portion of the shell 11. This air may be withdrawn by 
operation of the needle. The hole formed in the center of the closure 13 
by the penetration of the needle is then sealed with a biocompatible 
silicone to form the domed button seal or secondary closure 32. It should 
be noted that the closure 13 may alternatively include a valve such as 
compression valve or septa. As noted above, the shell 11 may be of a 
material which is permeable or impermeable to water vapor. The shell 11 
may be silicone, polyurethane, or another elastomeric material. 
FIG. 2 shows an implant 40 containing the fill material 12 and a drug or 
pharmaceutical or therapeutic agent 42 to be dispersed over time. The 
implant 40 includes a spherical ovoid or coin-like shell 44 which is 
permeable or semipermeable relative to the agent 42. When the shell is 
silicone, examples of the agent include silicone permeable hormones such 
as progesterone, Estradiol including 17-B-Estradiol, Melatonin, and 
Levonorgestrel, silicone permeable narcotic analgesics such as Fentanyl 
and morphine sulfate, and silicone permeable antianginal agents or 
vasodilators such as nitroglycerin. 
Procedures for filling the implants include the following method. The 
temperature of double distilled water is adjusted to 35.degree. F. 
(1.67.degree. C.). The components are then preferably added to the double 
distilled water in the following order: the preservative if desired, the 
cross-linking agent if desired, the osmotic control agent, and then the 
rheological agent. Then the dispersion is agitated and the temperature of 
the dispersion is permitted to rise in an environment at room temperature 
until the desired swelling has occurred. The dispersion is then injected 
into the implant. The implant is then rotated such that the dispersion 
remains uniformly dispersed, thereby allowing the rheological agent to 
fully hydrate (and cross-link if a cross-linking agent has been added to 
provide a three dimensional network if the rheological agent alone does 
not provide such). 
It should be noted that "biocompatible" means that which remains in 
unchanged form in the body without causing adverse reaction, that which 
may be metabolized, and/or that which may be excreted without being 
metabolized. 
It should further be noted that the fill material of the present invention 
is radiolucent. The fill material is not radiographically dense, nor does 
the fill material result in under-exposure of x-ray film. The fill 
material includes an optical density from about 1.2 to about 1.3 and an 
x-ray penetrance of from about 9.2 to about 30 milliroentgens. The osmotic 
control agents and rheological agents of the present invention include 
elements with relatively low atomic numbers which do not interfere with 
radiolucency. 
EXAMPLE 1 
(PVP and guar) 
Eight hundred (800) grams of high purity water were mixed with 200 g of PVP 
[poly(2-vinylpyrrolidone), Povidone K-17, (ISP Povidone C-15)] at room 
temperature to form a yellow liquid. Two and one half grams of 
methyl-4-hydroxybenzoate and two and one half grams of 
propyl-4-hydroxybenzoate were added to the PVP solution with vigorous 
stirring. Fifteen grams of Jaguar 8600 guar gum (Rhone-Poulenc, Specialty 
Chemical Division, Prospect Plains Road, Cranberry N.J.) were added by 
carefully dispersing the gum into the vortex of a rapidly (ca 2,000 rpm) 
stirring laboratory mixer to form a responsive gel. 
EXAMPLE 2 
(PVP and guar) 
Eight hundred (800) grams of high purity water were mixed with 200 g of PVP 
(poly(2-vinylpyrrolidone)), at room temperature to form a yellow liquid. 
Two and one half grams of methyl-4-hydroxybenzoate and two and one half 
grams of propyl-4-hydroxybenzoate were added to the PVP solution with 
vigorous stirring. Thirty grams of Jaguar 8600 guar gum were added by 
carefully dispersing the gum into the vortex of a rapidly (ca 2,000 rpm) 
stirring laboratory mixer to form a responsive gel. 
EXAMPLE 3 
(PVP and guar) 
Eight hundred (800) grams of high purity water were mixed with 200 g of PVP 
(poly(2-vinylpyrrolidone)) at room temperature to form a yellow liquid. 
Two and one half grams of methyl-4-hydroxybenzoate and two and one half 
grams of propyl-4-hydroxybenzoate were added to the PVP solution with 
vigorous stirring. Forty-five grams of Jaguar 8600 guar gum were added by 
carefully dispersing the gum into the vortex of a rapidly (ca 2,000 rpm) 
stirring laboratory mixer to form a responsive gel. 
EXAMPLE 4 
(PVP and guar) 
Eight hundred (800) grams of high purity water were mixed with 200 g of PVP 
(poly(2-vinylpyrrolidone)) at room temperature to form a yellow liquid. 
Two and one half grams of methyl-4-hydroxybenzoate and two and one half 
grams of propyl-4-hydroxybenzoate were added to the PVP solution with 
vigorous stirring. Fifty-five grams of Jaguar 8600 guar gum were added by 
carefully dispersing the gum into the vortex of a rapidly (ca 2,000 rpm) 
stirring laboratory mixer to form a responsive gel. 
EXAMPLE 5 
(PVP and pectin) 
Two hundred grams of a 20% w/w solution of PVP (poly(2-vinylpyrrolidone)) 
(with a base of high purity water) were mixed with Carex F/G Arabinose 
Galactan (a pectin from the larch tree) by adding the Galactan to the 
vortex of rapidly stirred water. The temperature was raised slowly, over 
the course of one hour, to 97.degree. C. with moderate stirring to form a 
responsive gel. 
EXAMPLE 6 
(PVP and gelatin) 
Gelatin (Knox household gelatin) was added to a 20% (w/w) PVP 
(poly(2-vinylpyrrolidone)) solution as described in Example 1. The 
dispersion was heated until all the gelatin dissolved forming a clear 
solution. Upon cooling a responsive gel formed. Several concentrations 
were prepared using this same technique to provide gels of varying 
consistency. 
EXAMPLE 7 
(PVP and polyethylene oxide) 
Four hundred grams of deionized water and one hundred grams of PVP 
(poly(2-vinylpyrrolidone)) were mixed with vigorous stirring. To this 
solution three grams of Polyox 303 (polyethylene oxide, Union Carbide) 
were added. The rapid formation of a responsive gel was noted. 
EXAMPLE 8 
(PVP and polyethylene oxide) 
Four hundred grams of deionized water and one hundred grams of PVP 
(poly(2-vinylpyrrolidone)) were mixed with vigorous stirring. To this 
solution three grams of Polyox 303 (polyethylene oxide, Union Carbide) 
were added. The rapid formation of a responsive gel was noted. 
EXAMPLE 9 
(PVP and polyethylene oxide) 
Four hundred grams of deionized water and one hundred grams of PVP 
(poly(2-vinylpyrrolidone)) were mixed with vigorous stirring. To this 
solution six grams of Polyox 303 (polyethylene oxide, Union Carbide) were 
added. The rapid formation of a responsive gel was noted. 
EXAMPLE 10 
(PVP and polyethylene oxide) 
Eight hundred grams of deionized water and one hundred grams of PVP 
(poly(2-vinylpyrrolidone)) were mixed with vigorous stirring. To this 
solution twenty-five grams of Polyox 303 (polyethylene oxide, Union 
Carbide) were added. The rapid formation of a responsive gel was noted. 
EXAMPLE 11 
(PVP and PVP copolymer) 
Two hundred grams of a 20% solution of 
poly(N-1-vinylpyrrolidone)-co-2-methylaminoethylmethacrylate were mixed 
with two hundred and fifty-eight grams of high purity water to form a 
responsive gel. Thirty six grams of PVP (poly(2-vinylpyrrolidone)) were 
added to the mixture. Upon standing a responsive viscous gel was formed. 
EXAMPLE 12 
(PVP and PVP copolymer) 
Nine hundred forty-nine grams of 20% (w/w) PVP (Poly(2-vinylpyrrolidone)) 
solution were mixed with fifty-one grams of 
poly(1-vinylpyrrolidone)-co-acrylic acid were mixed together and heated at 
70.degree. C. for one hour to form a responsive gel. 
EXAMPLE 13 
(PVP and PVP copolymer) 
One hundred grams of Poly(1-vinylpyrrolidone)-co-vinylacetate were mixed 
with eight hundred and thirty grams of deionized water and mixed with 
vigorous stirring. Seventy grams of PVP (poly(2-vinylpyrrolidone)) were 
added to the mixture with vigorous stirring to form a responsive gel. 
Thus since the invention disclosed herein may be embodied in other specific 
forms without departing from the spirit or general characteristics 
thereof, some of which forms have been indicated, the embodiments 
described herein are to be considered in all respects illustrative and not 
restrictive. The scope of the invention is to be indicated by the appended 
claims, rather than by the foregoing description, and all changes which 
come within the meaning and range of equivalents of the claims are 
intended to be embraced therein.