Abstract: A porous composite suitable for filling a recess or a through-passing hole in an implant. The composite includes particles A prepared from a bioactive material and particles B prepared from a non-bioactive material or weakly bioactive material, which is sintratable with the bioactive material, such that particles A and particles B have been sintered together to a porous composite. Particles A and particles B are essentially homogeneous in size. Also disclosed is an implant which contains a core and the composite.

Abstract: The invention is directed to a filamentous porous film that can act as a support for cellular attachment, growth and organization. The film is formed from filaments which define a matrix structure with pores.

Abstract: Biodegradable polymer compositions that degrade in vivo into non-toxic residues are described. In part, the present invention is directed to such polymers containing phosphorus and desaminotyrosyl L-tyrosine linkages in the polymer backbone. Processes for preparing such polymers, compositions containing such polymers and biologically active substances, articles useful for implantation or injection into the body fabricated from the compositions, and methods for controllably releasing biologically active substances using the polymers, are also described.

Abstract: A water insoluble, biocompatible composition that includes the reaction product of a polyanionic polysaccharide and an activating agent.

Abstract: A cell culture medium and hydrogel matrix for long term storage and proliferation of cells is provided. The cell culture medium and hydrogel matrix include an effective amount of polar amino acids, the polar amino acids selected from the group consisting of arginine, lysine, histidine, glutamic acid, and aspartic acid. The cell culture medium comprises about 5 to about 150 mM of polar amino acids. The hydrogel matrix comprises about 3 to about 150 mM of polar amino acids. Arginine and glutamic acid are preferably supplemented in the cell culture medium. Arginine, lysine, and glutamic acid are preferably supplemented in the hydrogel matrix. A method of maintaining viability and functioning of a transplant is also provided. The method of maintaining viability of a transplant includes encapsulating the cells in a hydrogel matrix and injecting the encapsulated cells into the host organism.

Abstract: A novel neurotrophic factor referred to as glial cell line-derived neurotrophic factor (GDNF) has been identified. Genes encoding GDNF have been cloned and sequenced. Methods and devices are disclosed for the delivery of GDNF using either an implantable cell which expresses human GDNF or a biocompatible semipermeable membrane containing genetically engineered cells which express and secrete the neurotrophic factor.

Abstract: A device and method is disclosed for continuously administering an analgesic to the neuraxis of an organism. The device comprises a polymeric matrix body loaded with the analgesic. The body is implanted in the neuraxis where the analgesic diffuses into the neuraxis.

Abstract: A stable injectable composition includes a non-aqueous parasitic agent in a therapeutically effect amount, chosen from the group of avermectin, ivermectin, doramectin, abamectin, milbemycin and moxidecting, and an antigen in combination with a liquid carrier that also acts as an adjuvant for use with warm-blooded animals and a method for treating parasitic diseases and preventing bacterial and viral diseases in warm-blooded animals.

Abstract: An implantable biological device including a semipermeable membrane formed into a geometric shape capable of encapsulating biological cells and capable of immunoisolating the biological cells upon introduction into the body, the semipermeable membrane including an amphiphilic copolymer network having hydrophobic segments and hydrophilic segments, wherein the hydrophobic segments include polyolefins terminated with radicals selected from the group consisting of acryloyl groups, methacryloyl groups and mixtures thereof and wherein the hydrophilic segments include polyacrylates. Also provided is a method of encapsulating and immunoisolating cells using the semipermeable membrane and method of treating ailments using the implantable biological device.

Abstract: An anti-oxidizing composition for scavenging free radicals, comprising at least one essential oil component containing a number of fat-soluble, low-molecular-weight compounds, a pharmaceutical composition comprising the above composition, and a process for preparing the same are described. Percutaneous absorption of the pharmaceutical composition is effective in treating immune diseases, particularly AIDS.

Abstract: The present invention involves filler for treating injured tissue sites made from compositions having variable permeability to bodily fluid to reduce the flow to these fluids (bleeding) from the site of injury into the surrounding tissue. The fillers are prepared by dispersing a pore-forming agent in a polymer with agitation. Density developing a variable concentration of pore-forming agent throughout the polymer through application of an external force acting on the mixture so that a portion of the filler has a variable impermeability to bodily fluids. After agitation and/or density development, the pore-forming agent is leached from the mixture to form a polymer matrix having variable permeability. Alternatively, the compositions can be made by fixedly combining a permeable material with an impermeable material to form a filler with reduced permeability to bodily fluid flow.

Abstract: A delivery system is disclosed for delivering a beneficial agent to an animal. The delivery system comprises a wall that surrounds a lumen, said wall comprising a composition that limits the passage of fluid into the system and a composition that permits the passage of fluid into the system. The lumen comprises a beneficial agent and an expandable member. The delivery system comprises an exit means for delivering the beneficial agent.

Abstract: A permselective graft polymer is disclosed that is formed by converting into intermediate reactive sites a portion of the cyano groups of a backbone polymer containing —CH2—CH(—C≡N)— units, and grafting polyalkylene oxide polymer chains to the backbone polymer through the reactive sites. Either the backbone polymer of a polymer resin or a permselective polymer membrane can be grafted. When a resin is used, it is formed into a permselective polymer membrane using known methods. The resulting permselective membrane can be formed into hollow fibers or flat sheets for the encapsulation of living cells. The encapsulated cells are then implanted into a patient in need of the biologically active factors produced by the cells. The permselective graft polymer membrane exhibits good molecular diffusion with minimal protein adsorption.

Abstract: Osteogenic compositions, and methods for preparing same, which compositions comprise a porous or semi-porous matrix, an osteogenic factor and an agent such as growth factors, nutrient factors, drugs, calcium-containing compounds, blood products, large molecular weight proteins, or combinations thereof. These materials can be used in a wide range of clinical procedures to replace and restore osseous or periodontal defects.

Abstract: The present invention provides improved osteogenic compositions having enhanced by the sorption of growth factors, of nutrient factors, or drugs onto or into the compositions. Compositions may consist of collagen and demineralized bone materials onto and into which growth factors, antimicrobial agent,s nutrient factors, or other soluble factors may be sorbed to enhance the osteogenic factor. These materials can be used in a wide range of clinical procedures to replace and restore osseous or periodontal defects.

Abstract: The present invention provides a method for treating Hemophilia A or B which comprises implanting in fluid communication with the bloodstream of a mammal in need of such treatment a permeable membrane having one or more walls, a hollow chamber therewithin, a plurality of holes extending through the walls of the membrane and permitting fluid to enter and exit the chamber of the membrane, each of the holes being sized so that it is large enough to permit inactive Factor VII to enter the chamber of the membrane and activated Factor VIIa to exit the chamber of the membrane but small enough to prevent fibrinogen from entering the chamber of the membrane, a plurality of supports being disposed within the chamber, and an effective amount of a Factor VII activator or a source of the activator being bound to the supports, wherein inactive Factor VII in blood passing through the membrane becomes activated into Factor VIIa upon contact with the activator within the chamber.

Abstract: Biologically active materials are provided in a cylindrical carrier medium with better control over the rate of delivery and length of time of delivery by providing a carrier having dissolved or dispersed therein at least two compounds having a common biologically active nucleus, but with different solubility parameters. The combination of the two different variants of the same drug with different solubility parameters provides the material with control over the rate of release of the compounds (by varying the proportions of the variants) and most importantly, extending the useful life of the device by enabling release of effective levels of the compounds over a longer period of time. The cylindrical carrier medium, comprised of silicone, further includes a tail, a skirt, or a rate-limiting membrane.

Abstract: Blends of biodegradable polymers, preferably poly(caprolactone) and poly(D,L-lactic-co-glycolic) acid are discussed as well as their applications in the medical field, particularly with regard to bone tissue engineering. Preferably, hydroxyapatite ("HA") granules are incorporated into the blends and the resulting blends have desirable mechanical, physical, and biological characteristics. Even more preferably the compositions of the present invention are utilized to form osteoconductive composites that supported bone cell growth on the surface as well as throughout the scaffold.

Abstract: The invention provides an intracoronary stent coated with a quinazolinone derivative of formula (I), wherein n is 1 or 2, R.sub.1 is a member of the group consisting of hydrogen, halogen, nitro, benzo, lower alkyl, phenyl and lower alkoxy; R.sub.2 is a member of the group consisting of hydroxy, acetoxy and lower alkoxy, and R3 is a member of the group consisting of hydrogen and lower alkenoxy-carbonyl, and physiologically acceptable salts thereof, for preventing restenosis after angioplasty.

Abstract: The invention is directed to a device for delivering an active agent formulation for a predetermined administration period. An impermeable reservoir is divided into a water-swellable agent chamber and an active agent formulation chamber. Fluid from the environment is imbibed through a semipermeable plug into the water-swellable agent chamber and the active agent formulation is released through a back-diffusion regulating outlet. Delivery periods of up to 2 years are achieved.

Abstract: Periodontal disease can be treated by the administration of metal ions, preferably silver ions, to the site where the microorganisms that cause this disease reside. Administration can be to periodontal pockets or adjacent to exposed tooth roots or alveolar bone during periodontal surgical procedures. The metal ions can be administered in polymeric microparticles, deformable films or microparticles embedded within deformable films. The metal ions are particularly microbiocidal to the bacterial pathogens that are the causative agents of periodontal disease.

Abstract: A process for modifying a surface of an article that includes treating a surface with a solution that includes an organic solvent, and the reaction product of a substantially water insoluble polymer and a polyalkylene imine to form a modified surface.

Abstract: The present invention relates to personal care compositions. These compositions comprise an adhesive copolymer and a solvent for the copolymer selected from the group consisting of water, ethanol, n-propanol, isopropanol, acetone, propylene glycol, and mixtures thereof. The compositions, when dried, exhibit a cohesive strength of greater than about 0.5 kgf/mm.sup.2, a total energy absorption per unit volume of greater than about 0.55 kgfmm/mm.sup.3, and an impact strength of greater than about 7000 ergs. Preferred are hairspray embodiments of the present invention having improved removeability from hair as defined by a hair stiffness value of from 0 to about 3.5 (0 to 4 scale) and a hair flaking value of from 0 to about 3.5 (0 to 4 scale), which values are determined by the removeability methodology defined herein.

Abstract: The present invention relates to the discovery that biocompatible anionic polymers can effectively inhibit fibrosis, scar formation, and surgical adhesions. The invention is predicated on the discovery that anionic polymers effectively inhibit invasion of cells associated with detrimental healing processes, and in particular, that the effectiveness of an anionic polymer at inhibiting cell invasion correlates with the anionic charge density of the polymer. Thus the present invention provides a large number of materials for use in methods of inhibiting fibrosis and fibroblast invasion. Anionic polymers for use in the invention include but are not limited to natural proteoglycans, and the glycosaminoglycan moieties of proteoglycans. Additionally, anionic carbohydrates and other anionic polymers may be used. The anionic polymers dextran sulfate and pentosan polysulfate are preferred. In a more preferred embodiment, dextran sulfate, in which the sulfur content is greater than about 10% by weight, may be used.

Abstract: A sealed, implantable, encapsulation device (20) for diffusing a biologically active product or function to an individual which includes a substantially non-porous fitting (32) including an inner surface (33) defining an access port (34). A permselective, porous, membrane (21), having an interior surface (22), cooperates with the fitting inner surface (33) to form a storage cavity (23) therebetween. The membrane interior surface (22) is in substantially cell-tight dry sealing engagement with fitting (32) to seal cavity (23). Living cells (24) are disposed in the cavity (23) which are capable of secreting the biologically active product to an individual. The membrane (21) is of a material capable of permitting the passage of substances between the individual and cells required to provide the biological product or function. A plug member (35) is positioned in the access port (34) and seated in cell-tight sealing engagement with the fitting inner surface (33).

Abstract: Psychogenic impotence can be ameliorated without substantial undesirable side effects by administration of apomorphine and an antiemetic agent in an amount sufficient to substantially reduce nausea symptoms associated with the use of apomorphine.

Abstract: A coating and method for implantable open lattice metallic stent prostheses are disclosed. The coating includes a relatively thin layer of biostable elastomeric material containing an amount of biologically active material, particularly heparin, dispersed in the coating in combination with a non-thrombogenic surface. In one embodiment, the surface is provided with sites of high electronegativity species by coating with fluorosilicone which aid in controlling elution, particularly the initial release rate, and reduced thrombogenic activity. Other non-thrombogenic outer layers for heparin such as covalently bound polyethylene glycol (PEG) are also disclosed.

Abstract: The invention relates to a bone replacement material which comprises one or more polypeptides having the biological action of fibroblast growth factors in a porous matrix. The healing-in properties correspond to those of autologous bone transplantation.

Abstract: A novel controlled release device employing microporous membranes with or without a nonporous coating and aqueous-organic partitioning of the bioreactive substances to be delivered is provided. Devices and methods for delivering pharmaceuticals, pest-control substances, hormones, nutrients and fragrances to humans, animals or any environment are also provided.

Abstract: A coating and method for a coating an implantable device or prostheses are disclosed. The coating includes an undercoat of polymeric material containing an amount of biologically active material, particularly heparin, dispersed therein. The coating further includes a topcoat which covers less than the entire surface of the undercoat and wherein the topcoat comprises a polymeric material substantially free of pores and porosigens. The polymeric material of the topcoat can be a biostable, biocompatible material which provides long term non-thrombogenicity to the device portion during and after release of the biologically active material.

Abstract: The invention relates to implants with phasewise release of pharmaceutical substance, which consist of a core and layers arranged concentrically around it. The core and at least one of the layers contain different pharmaceutical substances or the same pharmaceutical substance in different doses. The pharmaceutical substance-containing areas consist of surface-eroding biodegradable polymer materials.

Abstract: An immunoisolatory vehicle for the implantation into an individual of cells which produce a needed product or provide a needed metabolic function. The vehicle is comprised of a core region containing isolated cells and materials sufficient to maintain the cells, and a permselective, biocompatible, peripheral region free of the isolated cells, which immunoisolates the core yet provides for the delivery of the secreted product or metabolic function to the individual.

Abstract: The present invention relates to the discovery that biocompatible anionic polymers can effectively inhibit fibrosis, scar formation, and surgical adhesions. The invention is predicated on the discovery that anionic polymers effectively inhibit invasion of cells associated with detrimental healing processes, and in particular, that the effectiveness of an anionic polymer at inhibiting cell invasion correlates with the anionic charge density of the polymer. Thus the present invention provides a large number of materials for use in methods of inhibiting fibrosis and fibroblast invasion. Anionic polymers for use in the invention include but are not limited to natural proteoglycans, and the glycosaminoglycan moieties of proteoglycans. Additionally, anionic carbohydrates and other anionic polymers may be used. The anionic polymers dextran sulfate and pentosan polysulfate are preferred. In a more preferred embodiment, dextran sulfate, in which the sulfur content is greater than about 10% by weight, may be used.

Abstract: The self-supporting sheet-like material of cross linked fibrin has a regular pore size. It is used as a bio-mechanical barrier for the treatment of internal traumatic lesions, in particular for the prevention of adhesion formation as a post-operative complication. In the course of this it can be used either alone or in combination with a fibrin glue acting as a haemostatic agent. Since the material in terms of its composition and general structure is similar to endogenous products, it has, inter alia, an excellent bio-compatibility, bio-degradability and bio-resorbability.

Abstract: Methods are provided for inhibiting stenosis following vascular trauma or disease in a mammalian host, comprising administering to the host a therapeutically effective dosage of a therapeutic conjugate containing a vascular smooth muscle binding protein that associates in a specific manner with a cell surface of the vascular smooth muscle cell, coupled to a therapeutic agent dosage form that inhibits a cellular activity of the muscle cell. Methods are also provided for the direct and/or targeted delivery of therapeutic agents to vascular smooth muscle cells that cause a dilation and fixation of the vascular lumen by inhibiting smooth muscle cell contraction, thereby constituting a biological stent. Also discussed are mechanisms for in vivo vascular smooth muscle cell proliferation modulation, agents that impact those mechanisms and protocols for the use of those agents.

Abstract: The invention is directed to a biodegradable implant precursor having a two-part structure made of an outer sac and a liquid content. The implant precursor is composed of a biodegradable, water-coagulable thermoplastic polymer and a water-miscible organic solvent. When administered to an implant site in an animal, the implant precursor will solidify in situ to a solid, microporous matrix by dissipation of the organic solvent to surrounding tissue fluids and coagulation of the polymer. The invention also includes methods of making the implant precursor, an apparatus for forming the precursor, and a kit containing the apparatus. Also provided are methods of using the implant precursor for treating a tissue defect in an animal, for example, for enhancing cell growth and tissue regeneration, wound and organ repair, nerve regeneration, soft and hard tissue regeneration, and the like, for delivery of biologically-active substances to tissue or organs, and other like therapies.

Abstract: This invention relates to formulations comprising film-forming components capable of forming per se a physical barrier to pathogens. Thermoreversible gels such as poloxamers are particularly preferred for that use. The film-forming formulations may further comprise microbicides, spermicides or any other drug, which choice is guided by the pathogen, organism or the disease to be inactivated or treated. The formulations are therefore efficient as a physical, and optionally, as a chemical or pharmacological barrier as well as usable as a sustained drug-release system at the locus of administration. A part of the drug may also be entrapped in liposomes or other drug carriers. These formulations are intended for use in the prevention of sexually transmitted diseases, as well as in the treatment of infections, cancer, inflammation or any disease or state which requires a pharmacological treatment. Formulations are applicable to mucosae, skin and eye, for example.

Abstract: Intraocular devices which are capable of sustained release of a cell proliferation modulating agent, together with methods for their preparation and use, are provided. The proliferation modulating agent is associated either covalently or non-covalently with the material from which the intraocular device is prepared, generally a biologically inert polymer which is physiologically compatible with ocular tissue. The intraocular devices are implanted in the tissue, and the drug is released from the intraocular device such that the drug is substantially retained within the implant region. The device may be used to inhibit cellular proliferation around the implant. The device can be provided as a sterile kit, preferably in a form suitable for immediate use.

Abstract: Microfabricated filters utilizing a bulk substrate structure and a thin film structure and a method for constructing such filters. The pores of the filters are defined by spaces between the bulk substrate structure and the thin film structure and are of substantially uniform width, length and distribution. The width of the pores is defined by the thickness of a sacrificial layer and therefore may be smaller than the limit of resolution obtainable with photolithography. The filters provide enhanced mechanical strength, chemical inertness, biological compatibility, and throughput. The filters are constructed using relatively simple fabrication techniques. Also, microfabricated containment wells and capsules constructed with such filters for the immunological isolation of cell transplants and a method for constructing such containment wells and capsules.

Abstract: The invention features an empty device for receiving a bioactive agent. The device includes a biocompatible and semi-permeable membrane that defines an enclosed space; the membrane also has at least one end that defines an opening for introducing the bioactive agent into the enclosed space. The device is configured to be placed in an animal.In one embodiment of the invention, the membrane has an inner surface and an outer surface, where the inner surface defines the inner surface, and includes a biocompatible adhesive in the general region of the opening to allow sealing of the opening after the introduction of the bioactive agent into the enclosed space.Another embodiment of the invention includes a biocompatible frame mounted in supporting relationship to the membrane and defining an opening for introducing the bioactive agent into the enclosed space. The frame has greater porosity than the membrane.

Abstract: Skin equivalents and processes for preparing them are described. The living skin equivalent comprises a layer of cultured keratinocyte cells, a layer of high purity, non-porous collagen and a dermal layer of cultured fibroblast cells in a porous, cross-linked collagen sponge. Processes are described for producing the skin equivalent with descriptions on how to obtain and treat skin precursor materials to yield suitable fibroblasts and keratinocytes.The collagen layers, the physical forms thereof, and treatments thereof are also described. Preferably, the non-porous, highly-purified collagen is selected from Type 1, Type 3, or mixtures of Type 1 and Type 3 collagen. The collagen is purified ideally by treatment with pepsin, to remove antigenic substances.The collagen sponge used can be any suitable form of collagen sponge which will support fibroblast growth.The keratinocytes used in the invention are preferably prepared by the "drop" method spotted evenly on culture media and incubated to coalescence.

Abstract: The present invention provides novel compositions and methods for using the S(+) enantiomer of desmethylselegiline (N-methyl-N-(prop-2-ynyl)-2-aminophenylpropane), for the treatment of selegiline-responsive diseases and conditions. Diseases and conditions responsive to selegiline include those produced by neuronal degeneration or neuronal trauma and those due to immune system dysfunction. Effective dosages are a daily dose of at least about 0.015 mg/kg of body weight.

Abstract: This invention relates to coating formulations for coating sustained-release drug implants. The coating formulations are capable of formulations are capable of forming a porous film coat over a biologically active agent to provide a release of the active agent at a constant rate over a prolonged period of time. The pore forming agent is used in the formulation of the invention in the amount effective to regulate the release of a biologically active compound at a desired rate. Preferably, the effective amount of the pore forming agent provides long term delivery of the active agent. The invention also provides an improved implant for the sustained administration of a biologically active compound suitable for subcutaneous implantation. The invention also relates to methods for making and using the formulation and the implant of the invention.

Abstract: An artificial pancreas is described herein which comprises one or more viable and physiologically active pancreatic islet cells capable of producing insulin, encapsulated within a semipermeable spheroidal membrane comprising agar gel. Further disclosed are a method for producing agar microbeads, a tissue implantation method and a reseeding method for the artificial pancreas.

Abstract: The present invention relates to the discovery that biocompatible anionic polymers can effectively inhibit fibrosis, scar formation, and surgical adhesions. The invention is predicated on the discovery that anionic polymers effectively inhibit invasion of cells associated with detrimental healing processes, and in particular, that the effectiveness of an anionic polymer at inhibiting cell invasion correlates with the anionic charge density of the polymer. Thus the present invention provides a large number of materials for use in methods of inhibiting fibrosis and fibroblast invasion. Anionic polymers for use in the invention include but are not limited to natural proteoglycans, and the glycosaminoglycan moieties of proteoglycans. Additionally, anionic carbohydrates and other anionic polymers may be used. The anionic polymers dextran sulfate and pentosan polysulfate are preferred. In a more preferred embodiment, dextran sulfate, in which the sulfur content is greater than about 10% by weight, may be used.

Abstract: A novel neurotrophic factor referred to as glial cell line-derived neurotrophic factor (GDNF) has been identified and isolated from serum free growth medium of B49 glioblastoma cells. Rat and human genes encoding GDNF have been cloned and sequenced. A gene encoding GDNF has been subcloned into a vector, and the vector has been used to transform a host cell in order to produce biologically active GDNF in a recombinant DNA process. An implantable device containing recombinant GDNF secreting cells encapsulated in a semipermeable membrane may be used to treat nerve damage in patients suffering from disorders such as Parkinson's disease.

Abstract: Crosslinked compositions formed from a water-insoluble copolymer are disclosed. These compositions are copolymers having a bioresorbable region, a hydrophilic region and at least two crosslinkable functional groups per polymer chain. These compositions are able to form hydrogels in aqueous environments when crosslinked. These hydrogels are good sealants for implantable prostheses when in contact with an aqueous environment. In addition, such hydrogels can be used as delivery vehicles for therapeutic agents.

Abstract: An encapsulating apparatus comprising a spinning cup adjustably rotatable about its central axis for forming droplets and projecting them radially outward, and one or more collection basins surrounding the bead forming spinning cup independently rotatable and positioned to collect the beads projected from the cup. The method for forming tissue microcapsules using the spin disk encapsulation apparatus wherein a supply mixture is introduced into a mixing chamber of the cup from a single, multiple or concentric needles. As the cup spins, the coated particles are propelled upward by the centrifugal force from the mixing chamber along the inner surface of the cup, projected radially outward, as beads, into the gelling solution in one of the selected basins.

Abstract: A delivery device having a first chamber containing an osmotic agent, a membrane forming a wall of the first chamber through which fluid is imbibed by osmosis, a second chamber containing a beneficial agent to be delivered, and a moveable piston separating the two chambers. In fluid communication with the second chamber is an orifice which comprises a slit valve. In the presence of pressure, the beneficial agent pushes through the slit, opening up a channel for delivery of the beneficial agent and creating flow. Because the slit remains closed in the absence of flow (or when the pressure is below the pressure required to open the slit), back diffusion of external fluids is eliminated when the slit is closed, which prevents contamination of the beneficial agent in the second chamber by external fluids. In addition, forward diffusion of the beneficial agent out of the capsule is prevented when the slit is closed.

Abstract: The present invention relates to the discovery that biocompatible anionic polymers can effectively inhibit fibrosis, scar formation, and surgical adhesions. The invention is predicated on the discovery that anionic polymers effectively inhibit invasion of cells associated with detrimental healing processes, and in particular, that the effectiveness of an anionic polymer at inhibiting cell invasion correlates with the anionic charge density of the polymer. Thus the present invention provides a large number of materials for use in methods of inhibiting fibrosis and fibroblast invasion. Anionic polymers for use in the invention include but are not limited to natural proteoglycans, and the glycosaminoglycan moieties of proteoglycans. Additionally, anionic carbohydrates and other anionic polymers may be used. The anionic polymers dextran sulfate and pentosan polysulfate are preferred. In a more preferred embodiment, dextran sulfate, in which the sulfur content is greater than about 10% by weight, may be used.