High viscosity liquid controlled delivery system and medical or surgical device

Abstract

The present invention relates to novel nonpolymeric compounds and compositions that form liquid, high viscosity materials suitable for the delivery of biologically active substances in a controlled fashion, and for use as medical or surgical devices. The materials can optionally be diluted with a solvent to form a material of lower viscosity, rendering the material easy to administer. This solvent may be water insoluble or water soluble, where the water soluble solvent rapidly diffuses or migrates away from the material in vivo, leaving a higher viscosity liquid material.

1 - 88 . (canceled)  
     
     
         89 . A pharmaceutical composition comprising: 
 a non-water soluble, high viscosity, liquid carrier material comprising a nonpolymeric ester or mixed ester of one or more carboxylic acids, having a viscosity of at least 5,000 cP at 37 C, that does not crystallize neat under ambient or physiological conditions, wherein said liquid carrier material has the general formula of     R 1 —O—(CH 2 ) n —O—R 2    III:   wherein n is an integer between 4 and 8, and R 1  and R 2  are independently selected from the group consisting of hydrogen, alkanoyl, hydroxy-substituted alkanoyl, and acyloxy-substituted alkanoyl.    
     
     
         90 . The composition of  claim 89 , wherein the liquid carrier material is present in an amount of from about 0.20 to 99.5 percent by weight relative to the total weight of the pharmaceutical composition.  
     
     
         91 . The composition of  claim 89 , further comprising a solvent for the liquid carrier material.  
     
     
         92 . The composition of  claim 91 , wherein the solvent is selected from the group of acetone, benzyl alcohol, benzyl benzoate, N-(betahydromethyl)lactamide, butylene glycol, caprolactam, caprolactone, corn oil, decylmethylsulfoxide, dimethyl ether, dimethyl sulfoxide, 1-dodecylazacycloheptan-2-one, ethanol, ethyl acetate, ethyl lactate, ethyl oleate, glycerol, glycofurol (tetraglycol), isopropyl myristate, methyl acetate, methyl ethyl ketone, N-methyl-2-pyrrolidone, esters of caprylic and/or capric acids with glycerol or alkylene glycols, oleic acid, peanut oil, polyethylene glycol, propylene carbonate, 2-pyrrolidone, sesame oil, [±]-2,2-dimethyl-1,3-dioxolane-4-methanol, tetrahydrofuran, diethylene glycol monoethyl ether, carbitol, triacetin, triethyl citrate, and combinations thereof.  
     
     
         93 . The composition of  claim 91 , wherein the solvent is present in an amount from about 1 to 95 percent by weight relative to the total weight of the pharmaceutical composition.  
     
     
         94 . The composition of  claim 89  further comprising an additive.  
     
     
         95 . The composition of  claim 94 , wherein the additive is selected from the group of biodegradable polymers, non-biodegradable polymers, natural oils, synthetic oils, carbohydrates, carbohydrate derivatives, inorganic salts, bovine serum albumin (BSA), surfactants, organic compounds, sugars, organic salts, and water.  
     
     
         96 . The composition of  claim 94 , wherein the additive is present in an amount from about 0.01 to 20 percent by weight relative to the total weight of the pharmaceutical composition.  
     
     
         97 . The composition of  claim 89  further comprising a substance to be delivered from the pharmaceutical composition.  
     
     
         98 . The composition of  claim 97 , wherein the substance is a biologically active substance, drug, agent, compound, vaccine, antigen, or pharmacological material.  
     
     
         99 . The composition of  claim 98 , wherein the substance is a biologically active substance selected from the group of proteins, peptides, nucleoproteins, mucoproteins, lipoproteins, synthetic polypeptides, nucleic acids, nucleotides, nucleosides, oligonucleotides, and genes.  
     
     
         100 . The composition of  claim 99 , wherein the substance is a peptide or protein selected from the group of human growth hormone, fibroblast growth factor (FGF), erythropoietin (EPO), platelet derived growth factor (PDGF), granulocyte colony stimulating factor (g-CSF), bovine somatotropin (BST), tumor necrosis factor (TNF), transforming growth factor-beta (TGF-Beta), interleukins, insulin, and interferon.  
     
     
         101 . The composition of  claim 99 , wherein the substance is selected from the group of immunosuppressants, antioxidants, anesthetics, analgesics, chemotherapeutic agents, steroids, retinoids, hormones, antibiotics, antivirals, antifungals, antiproliferatives, antihistamines, anticoagulants, antiphotoaging agents, nonsteroidal and steroidal anti-inflammatory compounds, antipsychotics, and radiation absorbers.  
     
     
         102 . The composition of  claim 97 , wherein the substance is present in an amount from about 0.1 to 20 percent by weight relative to the total weight of the pharmaceutical composition.  
     
     
         103 . The composition of  claim 89  in the form of a liquid, an emulsion, a suspension, or a paste.  
     
     
         104 . The composition of  claim 89  wherein said composition is in a form suitable for administration by injection or by spraying.  
     
     
         105 . A pharmaceutical composition for the controlled release of a substance, said composition comprising: 
 a non-water soluble, high viscosity, liquid carrier material comprising a nonpolymeric ester or mixed ester of one or more carboxylic acids, having a viscosity of at least 5,000 cP at 37 C, that does not crystallize neat under ambient or physiological conditions, wherein said liquid carrier material has the general formula of     R 1 —O—(CH 2 ) n —O—R 2    III:   wherein n is an integer between 4 and 8, and R 1  and R 2  are independently selected from the group consisting of hydrogen, alkanoyl, hydroxy-substituted alkanoyl, and acyloxy-substituted alkanoyl.    
     
     
         106 . The composition of  claim 105 , wherein the substance is a biologically active substance, drug, agent, compound, vaccine, antigen, or pharmacological material.  
     
     
         107 . The composition of  claim 106 , wherein the substance is a biologically active substance selected from the group of proteins, peptides, nucleoproteins, mucoproteins, lipoproteins, synthetic polypeptides, nucleic acids, nucleotides, nucleosides, oligonucleotides, and genes.  
     
     
         108 . The composition of  claim 107 , wherein the substance is a peptide or protein selected from the group of human growth hormone, fibroblast growth factor (FGF), erythropoietin (EPO), platelet derived growth factor (PDGF), granulocyte colony stimulating factor (g-CSF), bovine somatotropin (BST), tumor necrosis factor (TNF), transforming growth factor-beta (TGF-Beta), interleukins, insulin, and interferon.  
     
     
         109 . The composition of  claim 107 , wherein the substance is selected from the group of immunosuppressants, antioxidants, anesthetics, analgesics, chemotherapeutic agents, steroids, retinoids, hormones, antibiotics, antivirals, antifungals, antiproliferatives, antihistamines, anticoagulants, antiphotoaging agents, nonsteroidal and steroidal anti-inflammatory compounds, antipsychotics, and radiation absorbers.  
     
     
         110 . The composition of  claim 105 , wherein the substance is present in an amount from about 0.1 to 20 percent by weight relative to the total weight of the pharmaceutical composition.  
     
     
         111 . The composition of  claim 105 , wherein the liquid carrier material is present in an amount of from about 0.20 to 99.5 percent by weight relative to the total weight of the pharmaceutical composition.  
     
     
         112 . The composition of  claim 105 , further comprising a solvent for the liquid carrier material.  
     
     
         113 . The composition of  claim 112 , wherein the solvent is selected from the group of acetone, benzyl alcohol, benzyl benzoate, N-(betahydromethyl) lactamide, butylene glycol, caprolactam, caprolactone, corn oil, decylmethylsulfoxide, dimethyl ether, dimethyl sulfoxide, 1-dodecylazacycloheptan-2-one, ethanol, ethyl acetate, ethyl lactate, ethyl oleate, glycerol, glycofurol (tetraglycol), isopropyl myristate, methyl acetate, methyl ethyl ketone, N-methyl-2-pyrrolidone, esters of caprylic and/or capric acids with glycerol or alkylene glycols, oleic acid, peanut oil, polyethylene glycol, propylene carbonate, 2-pyrrolidone, sesame oil, [±]-2,2-dimethyl-1,3-dioxolane-4-methanol, tetrahydrofuran, diethylene glycol monoethyl ether, carbitol, triacetin, triethyl citrate, and combinations thereof.  
     
     
         114 . The composition of  claim 112 , wherein the solvent is present in an amount from about 1 to 95 percent by weight relative to the total weight of the pharmaceutical composition.  
     
     
         115 . The composition of  claim 105  further comprising an additive.  
     
     
         116 . The composition of  claim 115 , wherein the additive is selected from the group of biodegradable polymers, non-biodegradable polymers, natural oils, synthetic oils, carbohydrates, carbohydrate derivatives, inorganic salts, bovine serum albumin (BSA), surfactants, organic compounds, sugars, organic salts, and water.  
     
     
         117 . The composition of  claim 115 , wherein the additive is present in an amount from about 0.01 to 20 percent by weight relative to the total weight of the pharmaceutical composition.  
     
     
         118 . The composition of  claim 105  in the form of a liquid, an emulsion, a suspension, or a paste.  
     
     
         119 . The composition of  claim 105  wherein said composition is in a form suitable for administration by injection or by spraying.