| Method of promoting natural bypass -> Monitor Keywords |
|
|
 
Method of promoting natural bypassRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Peptide Containing (e.g., Protein, Peptones, Fibrinogen, Etc.) Doai, Cyclopeptides, 25 Or More Peptide Repeating Units In Known Peptide Chain StructureMethod of promoting natural bypass description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20060194729, Method of promoting natural bypass. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation-in-part of U.S. Ser. No. 09/173,989, filed Oct. 16, 1998 and entitled "Protein Mixtures to Induce Therapeutic Angiogenesis," which is incorporated herein by reference. STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT [0002] Not applicable. FIELD OF THE INVENTION [0003] The present invention relates to a method for inducing the growth of blood vessels in instances where it is desirable to increase the supply of blood to a portion of a living body. More particularly, the present invention comprises a novel angiogenic factor. Still more particularly, the present invention relates to the use of mixtures of protein extracted from bone to cause a natural vascular bypass effect. BACKGROUND OF THE INVENTION [0004] There are many medical circumstances in which an increase in the supply of blood to living tissue is indicated. These include: bums and wound healing, in which the incorporation of angiogenic factors into artificial skin may facilitate the formation of blood vessels in the healing wound and reduce the risk of infection; cardiovascular disease, in which repair of anginal or ischemic cardiac tissue can be effected by causing the ingrowth of new blood vessels; stroke, where increased blood supply to the brain can reduce the risk of transient ischemic attack and/or cerebral arterial deficiency; and peripheral vascular disease, in which blood flow in the extremities is diminished. In each case, it is believed that the growth of new blood vessels will increase the volume of blood circulating through the tissue in question, and correspondingly increase the amount of oxygen and nutrients available to that tissue. [0005] One common cause of decreased blood flow is atherosclerosis. Atherosclerosis affects the blood vessels, including those of the heart, and is a major cause of cardiovascular disease, stroke and peripheral vascular disease. This disease may have its beginnings early in life and is first noted as a thickening of the arterial walls. This thickening is an accumulation of fat, fibrin, cellular debris and calcium. The resultant narrowing of the lumen of the afflicted vessel is called stenosis. Stenosis impedes and reduces blood flow. Hypertension and dysfunction of the organ or area of the body that suffers the impaired blood flow can result. As the buildup on the inner wall of a vessel thickens, the vessel wall loses the ability to expand and contract. Also, the vessel loses its viability and becomes weakened and susceptible to bulging, also known as aneurysm. In the presence of hypertension or elevated blood pressure, aneurysms will frequently dissect and ultimately rupture. [0006] Small vessels, such as the arteries that supply blood to the heart, legs, intestines and other areas of the body, are particularly susceptible to atherosclerotic narrowing. When an artery in the leg or intestine is affected, the resultant loss of blood supply to the leg or segment of the intestine may result in gangrene. Atherosclerotic narrowing of one or more of the coronary arteries limits and in some instances prevents blood flow to portions of the heart muscle. Depending upon the severity of the occlusion and its location within the coronary circulation system, pain, cardiac dysfunction or death may result. Because the consequences of blocked arteries are so serious, reliable treatments are highly desirable. [0007] In many instances, it is possible to correct aneurysms and stenosis of major arteries using plastic reconstruction that does not require any synthetic graft or patch materials. In other instances, such as where the disease is extensive and the vessel is no longer reliable, the blocked or weakened portion of the vessel is usually replaced with a graft. In such case, the affected vessel section is transected and removed and a synthetic patch, conduit or graft is sewn into its place. These types of procedures, including coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA), are routinely performed for the purpose of alleviating ischemia. [0008] Nevertheless, coronary artery disease alone is responsible for approximately 550,000 deaths each year in the United States. Peripheral vascular disease results in lower limb amputation in about 150,000 patients each year, with a subsequent mortality rate of 40% within two years of amputation. Some of the difficulty in treating arterial occlusion may lie in the fact that each of these surgical procedures is associated with a certain incidence of restenosis and may not be appropriate in certain instances. This is particularly true when the patient is elderly or has undergone a previous CABG or PTCA procedure. Furthermore, in such cases, a less invasive technique would be preferred. In particular, it would be advantageous to be able to stimulate the surrounding tissue to produce for itself new vessels that would compensate for the occluded vessels. [0009] While angiogenic, or "vessel-growing," factors in general have been the subject of much research, no angiogenic factor has yet been found to be effective for promoting the desired natural bypass effect. Examples of such growth factors are transforming growth factor beta (TGF-.beta.), osteonectin or SPARC, platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). All of these growth factors are either synthetic, meaning they are manufactured chemically from non-living sources, or are produced by recombinant manufacturing processes. Each of these angiogenic factors comprises only a single protein and possesses only a single functionality. In addition, many of the known angiogenic compounds are exceedingly difficult and/or expensive to manufacture. [0010] Hence, it is desired to provide an effective angiogenic factor that is easy to manufacture from readily available materials, easily administered by the surgeon and effective at stimulating the growth of new blood vessels into the treated tissue. BRIEF SUMMARY OF THE INVENTION [0011] The present invention comprises an angiogenic factor that is easily manufactured from readily available materials, easily administered by the surgeon and effective at stimulating the growth of new blood vessels into the treated tissue. The angiogenic factor of the present invention comprises a group of proteins extracted from bone. It has been found that the mixtures of proteins produced by certain processes are particularly effective angiogenic agents. These angiogenic agents can be administered as part of the treatment of an existing vascular disorder, or can play a role in early intervention and prevention if administered in certain cases. In particular, the present angiogenic agents can be introduced into tissue in the vicinity of an occluded vessel so as to cause the formation of new vessels that bypass the occluded vessel. In this manner, a natural bypass mechanism is provided. [0012] The angiogenic mixtures of bone proteins used according to the present invention are 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. [0013] In particularly preferred embodiments, the invention provides a method for promoting natural bypass in a mammal so provide increased blood flow to tissue served by an occluded or partly occluded vessel, a method for promoting vessel growth to heal a heart artery that has been blocked, or a method for promoting angiogenesis to assist in recovery from tissue damage. [0014] In each instance, the method preferably comprises administering to the mammal a mixture of proteins derived from ground bone. The mixture of proteins preferably comprises at least two growth factors selected from the group consisting of bone morphogenic protein-2 (BMP-2), bone morphogenic protein-3 (BMP-3), bone morphogenic protein-4 (BMP-4), bone morphogenic protein-5 (BMP-5), bone morphogenic protein-6 (BMP-6), bone morphogenic protein-7 (BMP-7), transforming growth factor .beta.1 (TGF-.beta.1), transforming growth factor .beta.2 (TGF-.beta.2), transforming growth factor .beta.3 (TGF-p3), and fibroblast growth factor 1 (FGF-1). [0015] The mammal to which the present method is applied can be a human, and the mixture can be administered subcutaneously, intramuscularly, or intravenously. The bone-derived protein mixture may be derived from bovine bone. The mixture can be administered discretely or continuously. [0016] In a preferred embodiment, the mixture further comprises a growth factor selected from insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), hepatocyte growth factor (HGF), transforming growth factor .alpha. (TGF-.alpha.), or platelet-derived growth factor (PDGF), and optionally includes a preservative or an adjuvant. Particularly preferred mixtures comprises BMP-2, BMP-3, BMP-7, TGF-.beta., and FGF, or the mixture derived by (i) grinding mammalian bone, to produce ground bone; (ii) cleaning the ground bone, to produce cleaned ground bone; (iii) demineralizing the cleaned ground bone, to produce demineralized cleaned ground bone; (iv) extracting protein from the demineralized cleaned ground bone using a protein denaturant; to yield extracted protein; (v) ultrafiltering the extracted protein to separate out high molecular weight proteins; (vi) ultrafiltering the extracted protein to separate out low molecular weight proteins; (vii) transferring the extracted protein to a non-ionic denaturant; (viii) subjecting the extracted protein to an anion exchange process; (ix) subjecting the extracted protein to a cation exchange process; and (x) subjecting the extracted protein to a reverse phase HPLC process. BRIEF DESCRIPTION OF THE DRAWINGS [0017] For a more detailed description of the present invention, reference will now be made to the accompanying Figures, wherein: [0018] FIG. 1 illustrates an SDS-PAGE of one embodiment of the present angiogenic protein mixture, both in reduced and non-reduced forms; Continue reading about Method of promoting natural bypass... Full patent description for Method of promoting natural bypass Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Method of promoting natural bypass patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. Start now! - Receive info on patent apps like Method of promoting natural bypass or other areas of interest. ### Previous Patent Application: Glp-1 derivatives and transmicosal absorption preparations thereof Next Patent Application: Methods and systems for nerve regeneration Industry Class: Drug, bio-affecting and body treating compositions ### FreshPatents.com Support Thank you for viewing the Method of promoting natural bypass patent info. IP-related news and info Results in 0.1128 seconds Other interesting Feshpatents.com categories: Qualcomm , Schering-Plough , Schlumberger , Seagate , Siemens , Texas Instruments , 174 |
 * Protect your Inventions * US Patent Office filing 
PATENT INFO |
|
