Compositions and Methods For Modulation of Vascular Structure and/or Function

Abstract

The present invention relates to compositions comprising semi-crystalline β-1-4-N-acetylglucosamine polymers (p-GlcNac) and methods utilizing such polymers modulation of vascular structure and/or function. The compositions and methods disclosed are useful for stimulating, in a p-GlcNac concentration-dependent manner, endothelin-1 release, vasoconstriction, and/or reduction in blood flow out of a breached vessel, as well as for contributing to or effecting cessation of bleeding. The methods of the present invention comprise topical administration of materials comprising semi-crystalline p-GlcNac polymers that are free of proteins, and substantially free of single amino acids as well as other organic and inorganic contaminants, and whose constituent monosaccharide sugars are attached in a β-1-4 conformation.

1 - 25 . (canceled) 
     
     
         26 . A method for reducing blood flow in a tissue or an organ associated with a surgical procedure, a diagnostic procedure, an embolization procedure or a condition in a patient in need thereof, comprising:
 topically applying directly to the bleeding tissue or organ or to the site adjacent to or contiguous with the bleeding tissue or organ in the patient a composition comprising poly-β-1→4-N-acetylglucosamine polymer;   wherein the poly-β-1→4-N-acetylglucosamine polymer comprises up to about 150,000 N-acetylgucosamine monosaccharides covalently attached in a β-1→4 conformation, and wherein at least 70% of the monosaccharides of the poly-b-1-4-N-acetylglucosamine polymer are N-acetylated;   wherein the patient is afflicted with coagulopathy; and   wherein the condition is a wound in the spleen, a wound in the liver, a deep wound to the body, a bleeding ulcer, bleeding varices, menorrhagia, an abdominal aneurism, a cerebral aneurysm, a uterine fibroid lesion or a burn.   
     
     
         27 . The method of  claim 26 , which is for reducing blood flow associated with a surgical procedure, wherein the surgical procedure is a standard surgical procedure or a minimally invasive surgical procedure. 
     
     
         28 . The method of  claim 26 , which is for reducing blood flow associated with a surgical procedure, wherein the surgical procedure is a surgical repair of an aneurysm, an excision of a tumor, an excision of a polyp, endometriosis surgery, or an operation on the gallbladder. 
     
     
         29 . The method of  claim 26 , which is for reducing blood flow associated with a diagnostic procedure, and wherein the diagnostic procedure is a biopsy. 
     
     
         30 . The method of  claim 29 , wherein the diagnostic procedure is a procedure resulting in a biopsy wound in the liver or kidney. 
     
     
         31 . The method of  claim 26 , which is for reducing blood flow associated with an embolization procedure. 
     
     
         32 . The method of  claim 31 , wherein the embolization procedure is an embolization treatment of a tumor, an uterine fibroid lesion or a cerebral aneurism. 
     
     
         33 . The method of  claim 26 , which is for treating the condition, wherein the condition is a wound in the spleen or a wound in the liver. 
     
     
         34 . The method of  claim 26 , which is for treating the condition, wherein the condition is a deep wound to the body. 
     
     
         35 . The method of  claim 26 , wherein the poly-β-1→4-N-acetylglucosamine polymer comprises about 50 to 150,000 N-acetylglucsamine monosaccharides covalently attached in β-1→4 conformation having a molecular weight of about 10,000 daltons to about 30 million daltons 
     
     
         36 . The method of  claim 26 , wherein the poly-β-1→4-N-acetylglucosamine polymer comprises about 50 to about 50,000 N-acetylglucosamine monosaccharides covalently attached in a β-1→4 conformation, and said polymer has a molecular weight of about 10,000 daltons to about 10 million daltons. 
     
     
         37 . The method of  claim 26 , wherein the poly-β-1→4-N-acetylglucosamine polymer comprises about 50 to about 10,000 N-acetylglucosamine monosaccharides covalently attached in a β-1→4 conformation, and said polymer has a molecular weight of about 10,000 daltons to about 2 million daltons. 
     
     
         38 . The method of  claim 26 , wherein the poly-β-1→4-N-acetylglucosamine polymer comprises about 50 to about 4,000 N-acetylglucosamine monosaccharides covalently attached in a β-1→4 conformation, and said polymer has a molecular weight of about 10.000 daltons to about 800.000 daltons. 
     
     
         39 . The method of  claim 26 , wherein at least 90% of the monosaccharides of the poly-β-1→4-N-acetylglucosamine polymer are acetylated. 
     
     
         40 . The method of  claim 26 , wherein the poly-β-1→4-N-acetylglucosamine polymer is fully acetylated. 
     
     
         41 . The method of  claim 26 , wherein the patient is a human. 
     
     
         42 . The method of  claim 26 , wherein the composition is applied in conjunction with compression. 
     
     
         43 . The method of  claim 26 , wherein the poly-β-1→4-N-acetylglucosamine polymer is used in a concentration from 2 mg/cm 2  to 100 mg/cm 2 . 
     
     
         44 . The method of  claim 26 , wherein the poly-β-1→4-N-acetylglucosamine polymer is used in a concentration from 14 μg/ml to 140 μg/ml. 
     
     
         45 . The method of  claim 26 , wherein the composition is in the form of a film, a membrane, a mat, or a bandage. 
     
     
         46 . The method of  claim 26 , wherein the composition is in the form of an ultra thin uniform membrane less than 1 micron thick. 
     
     
         47 . The method of  claim 26 , wherein the composition is in the form of a gel or a sponge. 
     
     
         48 . The method of  claim 26 , wherein the composition is in the form of a solution, a suspension, an emulsion, a spray, or a foam. 
     
     
         49 . The method of  claim 26 , wherein the patient has been administered an anticoagulant. 
     
     
         50 . The method of  claim 49 , wherein the anticoagulant is a coumadin or heparin. 
     
     
         51 . The method of  claim 26 , wherein the poly-β-1→4-N-acetylglucosamine polymer has an ordered and regular structure as demonstrated by sharp, well-resolved peaks when the poly-β-1→4-N-acetylglucosamine polymer is analyzed by infra-red absorption spectroscopy. 
     
     
         52 . The method of  claim 26 , wherein the poly-β-1→4-N-acetylglucosamine polymer is free of detectable protein contaminants. 
     
     
         53 . The method of  claim 26 , wherein the poly-β-1→4-N-acetylglucosamine polymer is derived from microalgae. 
     
     
         54 . The method of  claim 26 , wherein the composition further comprises a barrier-forming material, or the composition is applied in conjunction with a barrier-forming material. 
     
     
         55 . The method of  claim 26 , wherein the composition further comprises a component of a clotting cascade, or wherein the composition is applied in conjunction with a component of a clotting cascade. 
     
     
         56 . The method of  claim 26 , further comprising repeating said application. 
     
     
         57 . A method for reducing blood flow out of a breached vessel in a tissue, wherein the blood flow is associated with a surgical procedure, a diagnostic procedure resulting in a biopsy wound, a wound in the spleen, a wound in the liver, an embolization procedure, a bleeding ulcer, bleeding varices, or menorrhagia, in a human patient in need thereof, comprising:
 topically applying directly to the bleeding tissue or to the site adjacent to or contiguous with the bleeding tissue in the patient a composition comprising poly-β-1→4-N-acetylglucosamine polymer;   wherein the poly-β-1→4-N-acetylglucosamine polymer comprises about 50 to 150,000 N-acetylglucsamine monosaccharides covalently attached in β-1→4 conformation having a molecular weight of about 10,000 daltons to about 30 million daltons, and wherein at least 70% of the monosaccharides of the poly-b-1-4-N-acetylglucosamine polymer are N-acetylated;   wherein the patient is afflicted with coagulopathy.   
     
     
         58 . The method of  claim 57 , wherein at least 90% of the monosaccharides of the poly-β-1→4-N-acetylglucosamine polymer are acetylated. 
     
     
         59 . The method of  claim 57 , wherein the poly-β-1→4-N-acetylglucosamine polymer is used in a concentration from 2 mg/cm 2  to 100 mg/cm 2  or in a concentration from 14 μg/ml to 140 μg/ml. 
     
     
         60 . The method of  claim 57 , wherein the patient has been administered an anticoagulant. 
     
     
         61 . The method of  claim 57 , wherein the poly-β-1→4-N-acetylglucosamine polymer has an ordered and regular structure as demonstrated by sharp, well-resolved peaks when the poly-β-1→4-N-acetylglucosamine polymer is analyzed by infra-red absorption spectroscopy.