초록 ▼

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 vitr

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.

대표청구항 ▼

1. A bioresorbable implant composition comprising:a calcium phosphate; a first agent that directly or indirectly stimulates osteoclast activity, wherein said first agent modulates the resorption of the calcium phosphate at an implant site; and a second agent that is biologically active, wherein said

1. A bioresorbable implant composition comprising:a calcium phosphate; a first agent that directly or indirectly stimulates osteoclast activity, wherein said first agent modulates the resorption of the calcium phosphate at an implant site; and a second agent that is biologically active, wherein said first and second agents are different. 2. The implant composition of claim 1 wherein said first agent is selected from the group consisting of interleukin-1, colony stimulating factors, macrophage-colony stimulating factors, transforming growth factor α, tumor necrosis factor, interleukin-6, interleukin-11, interleukin-3, para-thyroid hormone, vitamin D metabolites, prostaglandins, and oxygen free radicals.3. The implant composition of claim 1 further comprising at least one bone-resorbing cell.4. The implant composition of claim 3 wherein the at least one bone-resorbing cell is selected from the group consisting of a progenitor cell, a stem cell, an osteocyte, an osteoclast, an osteoblast, a chondrocyte, a macrophage, a myoblast, a fibroblast, a bone- or cartilage-producing cell, a muscle cell, an hepatocyte, a parenchymal cell, a cell of intestinal origin, a nerve cell, and a skin cell.5. The implant composition of claim 1, wherein said second agent is selected from the group consisting of anti-AIDS substances, anti-cancer substances, antibiotics, antiseptics, ACE inhibitors, adrenergic antagonists, antacids, immunosuppressants or immunomodulatory factors, anti-viral substances, enzyme inhibitors, neurotoxins, neurotransmitters, opiods, hypnotics, antihistamines, lubricants, tranquilizers, anti-convulsants, muscle relaxants, anti-Parkinson substances, anti-spasmodics, muscle contractants, anti-diarrheals, anti-emetics, laxatives, diuretics, miotics, anti-cholinergics, anti-glaucoma compounds, anti-parasite compounds, anti-protozoal compounds, anti-hypertensives, analgesics, anti-pyretics, anti-inflammatory agents, anti-tussive agents, anti-vertigo medications, antinertigic medications, anti-motion sickness medications, local anesthetics, ophthalmics, prostaglandins, anti-depressants, anti-psychotic substances, imaging agents, specific targeting agents, trophic factors, growth factors, neurotransmitters, cell response modifiers, vaccines, compounds that enhance or allow ingrowth of the lymphatic network or nerve fiber, an endothelial growth factor (EGF), vitamins, hormones, and nucleic acids.6. The implant composition of claim 1 wherein the calcium phosphate comprises a powder mixture of:an amorphous calcium phosphate having a calcium to phosphate ratio (Ca:P) of 1.1:1.0 to 1.9:1.0; and a calcium phosphate promoter selected to promote conversion of the amorphous calcium phosphate into a bioresorbable poorly crystalline apatitic (PCA) calcium phosphate. 7. The implant composition of claim 6 further comprising:a physiologically acceptable aqueous solution in an amount sufficient to hydrate the calcium phosphate and to form a calcium phosphate paste or putty. 8. The implant composition of claim 7 wherein the physiologically acceptable aqueous solution is selected from the group of water, buffered pH solution, saline solution, serum and tissue culture medium.9. The implant composition of claim 6 wherein the calcium phosphate promoter comprises an acidic calcium phosphate.10. The implant composition of claim 9 wherein the acidic calcium phosphate is selected from the group of calcium metaphosphate, dicalcium phosphate dihydrate, heptacalcium decaphosphate, tricalcium phosphate, calcium pyrophosphate dihydrate, crystalline hydroxyapatite, calcium pyrophosphate, monetite, octacalcium phosphate, and poorly crystalline apatitic (PCA) calcium phosphate.11. The implant composition of claim 1 wherein the overall calcium to phosphate ratio (Ca:P) of the calcium phosphate is less than 1.5:1.0.12. The implant composition of claim 6 wherein the amorphous calcium phosphate and the calcium phosphate promoter are present in about equal amounts by weight.13. The implant composition of claim 6 wherein the calcium phosphate promoter comprises dicalcium phosphate dihydrate (DCPD).14. The implant composition of claim 1, wherein at least about 80% of said implant composition is resorbed within twelve months.15. The implant composition of claim 1, wherein at least about 80% of said implant composition is resorbed within nine months.16. The implant composition of claim 1, wherein at least about 80% of said implant composition is resorbed within six months.17. The implant composition of claim 1, wherein at least about 80% of said implant composition is resorbed within three months.18. The implant composition of claim 1, wherein at least about 80% of said implant composition is resorbed within one month.