Etex Corporation

Dosuk D Lee

Maria Aiolova

Christian Rey

Aliassghar N Tofighi

Atul Nagras

Aron D Rosenberg

Pramod Chakravarthy

Laurent D Gilles De Pelichy

Daniel Egan

Anthony M Majahad

William T Conner

Manish Sutaria

Youngmi M Lee, Legal Representative

Michele Krause

Ali Tofighi

A method and composition are provided for treating cancer in a mammal. The method includes administering to a tumor site of the mammal an anticancer composition comprising a mixture of an anticancer agent and a nanocrystalline or poorly crystalline calcium phosphate paste, said paste comprised of one or more calcium phosphates and a physiologically acceptable fluid, the paste having an injectable or formable consistency at the time of administration and hardenable at the tumor.

Chemotherapeutic composition using nanocrystalline calcium phosphate paste

Osteogenic bone implant compositions that approximate the chemical composition of natural bone are provided. The organic component of these implant compositions is osteoinductive despite the presence of the inorganic component and, further, is present in an amount sufficient to maximize the regenerative capabilities of the implant without compromising its formability and mechanical strength. The composition may be an osteoinductive powder, including demineralized bone matrix (DBM) particles, a calcium phosphate powder, and, optionally, a biocompatible cohesiveness agent. The powder may be combined with a physiologically-acceptable fluid to produce a formable, osteoinductive paste that self-hardens to form a poorly crystalline apatitic (PCA) calcium phosphate having significant compressive strength. The bone implant materials retain their cohesiveness when introduced at an implant site and are remodeled into bone in vivo. Methods for using these implant materials to repair damaged bone and a method of assaying the content of DBM particles, by weight, in a bone implant material are also provided.

Osteoinductive bone material

The invention features delayed-setting calcium phosphate pastes which are useful for the preparation of delivery vehicles for biologically active agents, useful for the treatment of orthopedic conditions and can be stored for long periods without prematurely setting.

Delayed-setting calcium phosphate pastes

The present invention provides a novel process for producing a calcium phosphate cement or filler which hardens in a temperature dependent fashion in association with an endothermic reaction. In the reaction a limited amount of water is mixed with dry calcium phosphate precursors to produce a hydrated precursor paste. Hardening of the paste occurs rapidly at body temperature and is accompanied by the conversion of one or more of the reactants to poorly crystalline apatitic calcium phosphate. The hardened cements, fillers, growth matrices, orthopedic and delivery devices of the invention are rapidly resorbable and stimulate hard tissue growth and healing. A composite material is provided including a strongly bioresorbable, poorly crystalline apatitic calcium phosphate composite and a supplementary material. The supplementary material is in intimate contact with the hydroxyapatite material in an amount effective to impart a selected characteristic to the composite. The supplemental material may be biocompatible, bioresorbable or non-resorbable. A method for treating a bone defect also is provided by identifying a bone site suitable for receiving an implant, and introducing a strongly resorbable, poorly crystalline apatitic calcium phosphate at the implant site, whereby bone is formed at the implant site. The implant site may be a variety of sites, such as a tooth socket, non-union bone, bone prosthesis, an osteoporotic bone, an intervertebral space, an alveolar ridge or a bone fracture.

Method of preparing a poorly crystalline calcium phosphate and methods of its use

The present invention provides a novel process for producing a calcium phosphate cement or filler which hardens in a temperature dependent fashion in association with an endothermic reaction. In the reaction a limited amount of water is mixed with dry calcium phosphate precursors to produce a hydrated precursor paste. Hardening of the paste occurs rapidly at body temperature an is accompanied by the conversion of one or more of the reactants to poorly crystalline apatitic calcium phosphate. The hardened cements, fillers, growth matrices, orthopedic and delivery devices of the invention are rapidly resorbable and stimulate hard tissue growth and healing.

Neutral self-setting calcium phosphate paste

The present invention provides a synthetic, poorly crystalline apatite (PCA) calcium phosphate containing a biologically active agent and/or cells (preferably tissue-forming or tissue-degrading cells). The compositions provided by the present invention are useful for a variety of in vivo and in vitro applications, including drug delivery (for example, to bony sites, the central nervous system, intramuscular sites, subcutaneous sites, interperitoneal sites, and occular sites) tissue growth (preferably bone or cartilage) osseous augmentation, and methods of diagnosing disease states by assaying tissue forming potential of cells isolated from a host. The invention also provides methods of preparing delivery vehicles, of altering delivery vehicle characteristics, and of delivering biologically active agents to a site. The invention further provides in vitro cell culture systems and cell encapsulation materials. The invention is useful for both medical and veterinary applications.

Bioceramic compositions

The present invention provides machinable calcium phosphate bone substitute material implants having mechanical properties comparable to those of natural bone. The implants include intimately mixed solid precursor materials that react under physiological conditions to form poorly-crystalline hydroxyapatite and eventually are remodeled into bone in vivo. The implants can include a biocompatible polymer to increase density and strength and control resorbability.

Machinable preformed calcium phosphate bone substitute material implants

A method of obtaining a porous titanium surface suitable for medical implants is provided. The titanium surface is exposed to a plasma comprising a reactive plasma gas, the reactive plasma gas comprising an active etching species and a sputtering gas. The plasma conditions are effective to modify the titanium surface and provide surface porosity. The plasma conditions are effective to non-uniformly etch and sputter the titanium surface.

Surface modification of medical implants

The present invention provides a synthetic, poorly-crystalline apatitic (PCA) calcium phosphate material seeded with cells. Preferably, the cells are tissue-forming or tissue-degrading cells. The compositions provided by the present invention are useful for a variety of applications, including in vivo and in vitro tissue growth (preferably bone or cartilage), osseous augmentation, and methods of diagnosing disease states by assaying tissue-forming potential of cells isolated from a host. The invention also provides in vitro cell culture systems and cell encapsulation matrices.

Cell seeding of ceramic compositions

The present invention provides delivery vehicles comprising a synthetic, poorly crystalline apatite (PCA) calcium phosphate and a biologically active agent. The PCA calcium phosphate offers many advantages over known delivery materials and is particularly useful for delivery of agents to bone sites, the central nervous system, intramuscular sites, subcutaneous sites, interperitoneal sites, and occular sites. The invention also provides methods of preparing delivery vehicles, of altering delivery vehicle characteristics, and of delivering biologically active agents to a site. The invention is useful for both medical and veterinary applications.

Delivery vehicle

An irregularly etched metallic medical implant device is provided having random non-uniform relief patterns on the surface ranging from about 0.3 &mgr;m to less than about 20 &mgr;m in depth. The random, irregular surface as defined by the etch micromorphology and respective dimensional properties is sobtained by exposing a surface to a reactive plasma in a chamber wherein said reactive plasma produces a reaction product with the surface to thereby etch the surface, said reaction product or a complex thereof having a vapor pressure lower than a pressure in the chamber; providing a dynamic masking agent during the etching process; and removing the reaction products.

A composite material is provided including a strongly bioresorbable, poorly crystalline apatitic calcium phosphate composite and a supplementary material. The poorly crystalline apatitic calcium phosphate is characterized in that, when placed in an intramuscular or subcutaneous site, resorption of at least 1 g of the material is complete within one year. The supplementary material is in intimate contact with the hydroxyapatite material in an amount effective to impart a selected characteristic to the composite. The supplemental material may be biocompatible, bioresorbable or non-resorbable.

Bioresorbable ceramic composites

A method for treating a bone defect is provided by identifying a bone site suitable for receiving an implant; and introducing a strongly resorbable, poorly crystalline apatitic calcium phosphate at the implant site, whereby bone is formed at the implant site. A bone defect may be treated by identifying a bone site suitable for receiving an implant; and introducing a hydrated precursor to a strongly resorbable, poorly crystalline apatitic calcium phosphate at the implant site, whereby the hydrated precursor is converted in vivo to a poorly crystalline apatitic calcium phosphate and whereby bone is formed at the implant site. The implant site may be a variety of sites, such as a tooth socket, non-union bone, bone prosthesis, an osteoporatic bone, an intervertebral space, an alveolar ridge or a bone fracture.

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Brookline, MA, United States of America

Dosuk D Lee