Abstract: A composition for the induction of bone growth is disclosed. The composition includes a substrate, bone growth protein, and sources of calcium and phosphate. The composition is acidic which promotes high activity of the bone growth protein. The calcium and phosphate sources can be provided as an acidic calcium phosphate salt. Also disclosed are methods of the making the composition and methods of using it.

Abstract: A method and apparatus for preparing a bone product are disclosed. The method includes contacting an interior section of a cylindrical bone portion with a high pressure fluid medium to remove at least a portion of cancellous bone matrix from the bone portion. The apparatus includes multiple stations of opposing high pressure nozzles holding the cylindrical bone portion from each end and for contacting the interior surfaces of a bone portion with a fluid medium. The apparatus also includes a third nozzle for contacting the exterior surface of the bone portion with a fluid medium.

Abstract: An angiogenic factor comprising a mixture of proteins derived from bone. The angiogenic protein mixture is produced by a series of steps that allow the proteins to be kept in solution. The angiogenic mixture of bone proteins is produced by a multi-step process that includes at least one ultrafiltration step, an anion exchange chromatography step, a cation exchange chromatography step and a high performance liquid chromatography (HPLC) purification step.

Abstract: An angiogenic factor comprising a mixture of proteins derived from bone. The angiogenic protein mixture is produced by a series of steps that allow the proteins to be kept in solution. The angiogenic mixture of bone proteins is produced by a multi-step process that includes at least one ultrafiltration step, an anion exchange chromatography step, a cation exchange chromatography step and a high performance liquid chromatography (HPLC) purification step.

Abstract: Pharmaceutical compositions, useful for treating abnormal calcium and phosphate metabolism, which contain geminal-diphosphonic acid compounds; and a method of treating diseases characterized by abnormal calcium and phosphate metabolism utilizing these pharmaceutical compositions.

Abstract: Disclosed is a product which includes calcium carbonate and bone growth factor useful for the promotion of bone formation when implanted in the body. The calcium carbonate is preferably in the form of aragonite which can be recovered from naturally occurring coral. A preferred bone growth factor of the present invention is a protein mixture purified from bone. Also disclosed is a process for the induction of bone formation which includes implanting the product in a body. The product and process of the present invention are particularly useful in hip replacement operations, knee replacement operations, spinal fusion operations, repair of periodontal defects, treatment of osteoporosis, repair of bone tumor defects and repair of bone fractures.

Abstract: The present invention relates to novel heterocycle-substituted diphosphonic acids, and the pharmaceutically-acceptable salts and esters thereof, in which the diphosphonate-substituted carbon atom moiety is attached to a carbon atom in a nitrogen-containing six membered ring heterocycle, preferably a piperidine ring. The heterocycle-substituted diphosphonic acid compounds have the general structure: ##STR1## wherein Z is a nitrogen-containing six membered ring heterocycle moiety selected from piperidinyl, diazinyl and triazinyl; m, n and m+n are from 0 to 10; Q is a covalent bond or a moiety selected from oxygen, sulfur or nitrogen; and R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are substituent groups.The present invention further relates to pharmaceutical compositions containing these novel compounds. Finally this invention relates to methods for treating or preventing diseases characterized by abnormal calcium and phosphate metabolism by utilizing a compound or pharmaceutical composition of the present invention.

Abstract: A method for purifying bone-derived osteoinductive factors including an ultrafiltration process, an anion exchange process, a cation exchange process, and a reverse phase HPLC process. The ultrafiltration process preferably includes a first ultrafiltration step using a membrane having a nominal molecular weight cutoff of approximately 100 kilodaltons (kD) and a second ultrafiltration step employing a membrane having a nominal molecular weight cutoff of approximately 10 kD. For the anion exchange process, a strongly cationic resin is used, preferably having quaternary amine functional groups. Typically, the eluant for the anion exchange process has a conductivity from about 10,260 micromhos (.mu.mhos) (1.026.times.10.sup.-2 siemens (S)) to about 11,200 .mu.mhos (1.120.times.10.sup.31 2 S). For the cation exchange process, a strongly anionic resin is used, preferably having sulfonic acid functional groups. The eluant for the cation exchange process typically has a conductivity from about 39,100 .mu.mhos (3.91.

Abstract: The present invention relates to novel heterocycle-substituted diphosphonic acids, and the pharmaceutically-acceptable salts and esters thereof, in which the diphosphonate-substituted carbon atom moiety is attached to a carbon atom in a nitrogen-containing six membered ring heterocycle, preferably a piperidine ring. The heterocycle-substituted diphosphonic acid compounds have the general structure: ##STR1## wherein Z is a nitrogen-containing six membered ring heterocycle moiety selected from piperidinyl, diazinyl and triazinyl; m, n and m+n are from 0 to 10; Q is a covalent bond or a moiety selected from oxygen, sulfur or nitrogen; and R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are substituent groups.The present invention further relates to pharmaceutical compositions containing these novel compounds. Finally this invention relates to methods for treating or preventing diseases characterized by abnormal calcium and phosphate metabolism by utilizing a compound or pharmaceutical composition of the present invention.

Abstract: A method for purifying bone-derived osteoinductive factors including an ultrafiltration process, an anion exchange process, a cation exchange process, and a reverse phase HPLC process. The ultrafiltration process preferably includes a first ultrafiltration step using a membrane having a nominal molecular weight cutoff of approximately 100 kilodaltons (kD) and a second ultrafiltration step employing a membrane having a nominal molecular weight cutoff of approximately 10 kD. For the anion exchange process, a strongly cationic resin is used, preferably having quaternary amine functional groups. Typically, the eluant for the anion exchange process has a conductivity from about 10,260 micromhos (.mu.mhos) (1.026.times.10.sup.-2 siemens (S)) to about 11,200 .mu.mhos (1.120.times.10.sup.-2 S). For the cation exchange process, a strongly anionic resin is used, preferably having sulfonic acid functional groups. The eluant for the cation exchange process typically has a conductivity from about 39,100 .mu.mhos (3.91.

Abstract: This invention relates to pyrindine-diphosphonic acid derivatives which are useful in treating or preventing diseases characterized by abnormal calcium and phosphate matabolism, in particular those which are characterized by abnormal bone metabolism. This invention further relates to pharmaceutical compositions which contain the novel compounds of the present invention, and to a method of treating or preventing diseases characterized by abnormal calcium and phosphate metabolism utilizing a compound of the present invention.

Abstract: The present invention relates to novel heterocycle-substituted diphosphonic acids, and the pharmaceutically-acceptable salts and esters thereof, in which the diphosphonate-substituted carbon atom moiety is attached to a carbon atom in a nitrogen-containing six membered ring heterocycle, preferably a piperidine ring. The heterocycle-substituted diphosphonic acid compounds have the general structure: ##STR1## wherein Z is a nitrogen-containing six membered ring heterocycle moiety selected from piperidinyl, diazinyl and triazinyl; m, n and m+n are from 0 to 10; Q is a covalent bond or a moiety selected from oxygen, sulfur or nitrogen; and R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are substituent groups.The present invention further relates to pharmaceutical compositions containing these novel compounds. Finally this invention relates to methods for treating or preventing diseases characterized by abnormal calcium and phosphate metabolism by utilizing a compound or pharmaceutical composition of the present invention.

Abstract: The present invention relates to oral compositions, such as dentifrices, toothpastes and mouthwashes, which provide an anticalculus benefit. These compositions comprise a safe and effective amount of an anticalculus agent which is a polyepoxysuccinic acid, or its pharmaceutically-acceptable salts, along with a pharmaceutically-acceptable carrier. The present invention also relates to a method for inhibiting or reducing the development of dental calculus by contacting the oral cavity with a safe and effective amount of an anticalculus agent which is a polyepoxysuccinic acid, or its pharmaceutically-acceptable salt.

Abstract: Diphosphonate-derivatized macromolecules, such as proteins, suitable for use as technetium-99m-based scanning agents and as anticalcification agents are disclosed. The scanning agents are prepared by combining Tc-99m in a +3, +4 and/or +5 oxidation state with the diphosphonate-derivatized macromoleules. Also disclosed are pharmaceutical compositions containing these diphosphonate-derivatized macromolecules and methods for scintigraphic imaging using these diphosphonate-derivatized macromolecules labeled with Tc-99m.

Abstract: Novel cyclic geminal-diphosphonic acid compounds, and pharmaceutical compositions containing these compounds, which are useful for treating diseases characterized by abnormal calcium and phosphate metabolism; and a method of treating diseases characterized by abnormal calcium and phosphate metabolism utilizing these novel cyclic diphosphonic acid compounds.

Abstract: Methods of treating non-inflammatory diseases characterized by abnormal calcium and phosphate metabolism comprising administering a pharmaceutical composition comprising a geminal diphosphonic acid compound in which the diphosphonic acid-containing carbon is linker via a sulfur atom or a sulfur-containing chain to a 6-membered aromatic ring containing one or more nitrogen atoms.

Abstract: The present invention relates to oral compositions, such as dentrifices, toothpastes and mounthwashes, which provide an anticalculus benefit. These compositions comprise a safe and effective amount of an anticalculus agent which is a polyepoxysuccinic acid, or its pharmaceutically-acceptable salts, along with a pharmaceutically-acceptable carrier. The present invention also relates to a method for inhibiting or reducing the development of dental calculus by contacting the oral cavity with a safe and effective amount of an anticalculus agent which is a polyepoxysuccinic acid, or its pharmaceutically-acceptable salt.

Abstract: Diphosphonate-derivatized macromolecules, such as proteins, suitable for use as technetium-99m-based scanning agents and as anticalcification agents are disclosed. The scanning agents are prepared by combining Tc-99m in a +3, +4 and/or +5 oxidation state with the diphosphonate-derivatized macromolecules. Also disclosed are pharmaceutical compositions containing these diphosphonate-derivatized macromolecules and methods for scintigraphic imaging using these diphosphonate-derivatized macromolecules labeled with Tc-99m.

Abstract: Novel cyclic geminal-diphosphonic acid compounds, and pharmaceutical compositions containing these compounds, which are useful for treating diseases characterized by abnormal calcium and phosphate metabolism; and a method of treating diseases characterized by abnormal calcium and phosphate metabolism utilizing these noval cyclic diphosphonic acid compounds.

Abstract: Oral compositions containing as an anticalculus agent an acrylic acid polymer or copolymer having a mass average molecular weight of from about 3500 to about 7500 are described herein.