Collagen Corporation

The Ohio State University

Celtrix Pharmaceuticals, Inc.

Hanne Bentz

Woonza M Rhee

Frank A DeLustro

Donald G Wallace

Louis Fries

Alan S Michaels

Ramon A Burns, Jr

Rosa Armstrong

Larry Ellingsworth

Saeid Seyedin

Thomas Thomas

Karl A Piez

Ranga Nathan

Jeffrey Alan Hubbell

Jacqueline Anne Schroeder

Gaozhong Zhu

Steven Paul Schwendeman

Andrea Y Thompson

Jichao Kang

David M Rosen

Anna S Shenderova

Wenlei Jiang

Trudy D Estridge

Saied Seyedin

Methods for reducing or inhibiting the irreversible inactivation of water-soluble biologically active agents in biodegradable polymeric delivery systems which are designed to release such agents over a prolonged period of time, such as PLGA delivery systems are provided. The method comprises preparing a PLGA delivery systems whose microclimate, i.e. the pores where the active agent resides, uniformly or homogenously maintain a pH of between 3 and 9, preferably between 4 and 8, more preferably between 5 and 7.5 during biodegradation. Depending on the size of the delivery system, and the initial bulk permeability of the polymer, this result is achieved by (a) incorporating a water-soluble carrier into the delivery system, (b) incorporating a select basic additive (or antacid) into the delivery system, (c) incorporating both a water soluble carrier and a select basic additive into the delivery system, (d) adding a pore forming molecule for increasing the rate of release of low molecular weight monomers and oligomers into the delivery system, (e) using a PLGA polymer with reduced glycolide content, i.e. PLGA with from 100% to 75% lactide and 0 to 25% glycolide) (f) using a microencapsulation method that yields a more extensive pore-network, e.g. oil-in-oil emulsion-solvent extraction as opposed to water-in-oil-in water-solvent evaporation method, and (g) combinations thereof.

Methods for stabilizing biologically active agents encapsulated in biodegradable controlled-release polymers

Affinity bound collagen matrices for the delivery of biologically active agents, and methods for preparing such matrices, are disclosed. A preferred method for preparing the matrices of the invention comprises mixing a binding ligand and an active agent together, allowing the resulting binding ligand-active agent mixture to form an affinity bound complex, then combining the resulting affinity bound complex with collagen to form a matrix. Particular affinity bound matrices comprising collagen, heparin, and an active agent are also disclosed, as well as methods for using the matrices of the invention for delivery of biologically active agents.

Affinity bound collagen matrices for the delivery of biologically active

Pharmaceutically acceptable, non-immunogenic compositions are formed by covalently binding atelopeptide collagen to pharmaceutically pure, synthetic, hydrophilic polymers via specific types of chemical bonds to provide collagen/polymer conjugates. The atelopeptide collagen can be type I, type II or type III and may be fibrillar or non-fibrillar. The synthetic hydrophilic polymer may be polyethylene glycol and derivatives thereof having a weight average molecular weight over a range of from about 100 to about 20,000. The compositions may include other components such as liquid, pharmaceutically acceptable, carriers to form injectable formulations, and/or biologically active proteins such as growth factors. The collagen-polymer conjugates of the invention generally contain large amounts of water when formed. The conjugates can be dehydrated to form a relatively solid object. The dehydrated, solid object can be ground into particles which can be suspended in a non-aqueous fluid such as an oil and injected into a living being for the purpose of providing soft tissue augmentation. Once in place, the particles rehydrate and expand in size five fold or more.

Polymer conjugates ophthalmic devices comprising collagen-polymer

Collagen, particularly atelopeptide collagen, exhibits improved handling characteristics when chemically conjugated and/or crosslinked with a synthetic hydrophilic polymer.

Implants coated with collagen-polymer conjugates

Method of preparing collagen-polymer conjugates

Collagen-polymer conjugates containing an ether linkage

Collagen-polymer conjugates

Bone morphogenetic proteins -2 and -3 (BMPs -2 and -3) work in synergistic combination with TGF-.beta.z to provide compositions with increased osteogenic activity. Methods of treating bone defects, inducing bone growth and increasing bone marrow cell production using these compositions are also disclosed.

Use of bone morphogenetic protein in synergistic combination with

Method of augmenting tissue using collagen-polymer conjugates

Pharmaceutically acceptable, non-immunogenic compositions are formed by covalently binding biologically inactive, natural, biocompatible polymer to pharmaceutically pure, synthetic, hydrophilic polymers via specific types of chemical bonds to provide biocompatible conjugates. The synthetic hydrophilic polymer may be polyethylene glycol and derivatives thereof having a weight average molecular weight over a range of from about 100 to about 20,000. The compositions may include other components such as liquid, pharmaceutically acceptable, carriers to form injectable formulations, and/or biologically active proteins such as growth factors. The conjugates of the invention generally contain large amounts of water when formed. The conjugates can be dehydrated to form a relatively solid object. The dehydrated, solid object can be ground into particles which can be suspended in a non-aqueous fluid such as an oil and injected into a living (preferably human) being for the purpose of providing soft tissue augmentation. Once in place, the particles rehydrate and expand in size five fold or more.

Biologically inert, biocompatible-polymer conjugates

Method of augmenting tissue with collagen-polymer conjugates

Composition for bone repair

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Newark, CA, United States of America

Hanne Bentz