Formulation for stabilizing proteins, which is free of mammalian excipient

Abstract

The present invention pertains to a formulation comprising a hydrophilic polymer, a mixture of a polyalcohol and a sugar, wherein the weight ratio of polyalcohol to sugar is between 2:1 to 5:1 (wt-%), a detergent, wherein the formulation is free of stabilising proteins.

1 . A formulation comprising
 (a) a hydrophilic polymer,   (b) a mixture of a polyalcohol and a sugar, wherein the weight ratio of polyalcohol to sugar is from 2:1 to 5:1 (wt-%),   (c) a detergent, and   
       wherein the formulation is free of stabilizing proteins. 
     
     
         2 . The formulation of  claim 1 , wherein the hydrophilic polymer is selected from hyaluronic acid, polyvinylpyrollidone (PVP), copolymers of N-vinylpyrollidone, a cellulose derivative, dextran, polyethyleneglycol (PEG), PEG/PPG block copolymers, homo- and copolymers of acrylic and methacrylic acid, polyurethanes, polyvinyl alcohol, polyvinylethers, maleic anhydride based copolymers, polyesters, vinylamines, polyethyleneimines, polyethyleneoxides, poly(carboxylic acids), polyamides, polyanhydrides, polyphosphazenes, and mixtures thereof. 
     
     
         3 . The formulation of  claim 2 , wherein the cellulose derivative is selected from hydroxypropyl methyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, methyl cellulose and carboxymethyl cellulose. 
     
     
         4 . The formulation of  claim 1 , wherein the polyalcohol is selected from mannitol, inositol, lactilol, isomalt, xylitol, erythritol, sorbitol, and mixtures thereof. 
     
     
         5 . The formulation of  claim 1 , wherein the sugar is selected from monosaccharides, disaccharides, polysaccharides, and mixtures thereof. 
     
     
         6 . The formulation of  claim 1 , wherein the detergent is selected from non-ionic surfactants, anionic surfactants and cationic surfactants. 
     
     
         7 . The formulation of  claim 1 , further comprising a peptide, a protein or a mixture thereof. 
     
     
         8 . The formulation of  claim 7 , which is lyophilized. 
     
     
         9 . The formulation of  claim 7 , wherein the protein is selected from toxins, chondroitin, elastin, actin, myosin, aprotinin, growth hormone, growth hormone releasing factor, parathyroid hormone, thyroid stimulating hormone, lipoproteins (LDL, IDL, VLDL, VHDL, HDL), apolipoproteins (ApoA-1, ApoA-II, ApoA-IV, ApoC-I, ApoC-II, ApoC-III, ApoD, ApoE), α-1 Antitrypsin, insulin, proinsullin, follicle stimulating hormone, calcitonin, oxytocin, vasopressin, leuprolide acetate, somatostatin, luteinizing hormone, glucagons, clotting factors, anti-clotting factors, plasminogen activator, human macrophage inflammatory protein, vascular endothelin growth factor (VEGF), rheumatoid factors, bone derived neurotrophic factor (BDNF), nerve growth factor-β (NGF-β), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), transforming growth factor (TGF-β1, TGF-β2, TGF-β3, TGF-β4, TGF-β5), erythropoietin, interleukins (IL-1 to IL-10), bone morphogenic protein (BMP) parathyroid hormone, DNAse, cationic ferritin, interferon (α, β, γ) and mixtures thereof. 
     
     
         10 . The formulation of  claim 9 , wherein the toxin is selected from a  botulinum  toxin, diphtheria toxin, tetanus toxin and mixtures thereof. 
     
     
         11 . The formulation of  claim 1 , which comprises  Clostridium botulinum  toxin, hyaluronic acid, mannitol, sucrose, polysorbate 80 and, optionally, water for injection. 
     
     
         12 . An injectable solution comprising the formulation of  claim 7 . 
     
     
         13 . The formulation of  claim 7 , in the form of a cosmetic product, a cosmeceutical product or a diagnostic product. 
     
     
         14 . The formulation of  claim 10 , comprising a therapeutically effective amount of the toxin for the treatment of a disease or condition caused by or associated with hyperactive cholinergic innervation of muscles or exocrine glands in a patient. 
     
     
         15 . A kit comprising
 (a) one or more containers comprising the formulation/composition of any of the preceding claims, and   (b) instructions for use of the formulation of  claim 1 , and optionally,   (c) a pharmaceutically acceptable sterile solvent.   
     
     
         16 . A method for stabilizing proteins, peptides, or mixtures thereof, comprising admixing the formulation of  claim 1  with a protein, peptide, or mixtures thereof.