Formulation for stabilizing proteins, which is free of mammalian excipient

• US 9,198,856 B2
• Filed: 04/16/2010
• Issued: 12/01/2015
• Est. Priority Date: 04/17/2009
• Status: Active Grant

• Current Assignee: Merz Pharma GmbH & Company Kgaa
• Original Assignee: Merz Pharma GmbH & Company Kgaa
• Inventors: Burger, Markus, Mander, Gerd J., Taylor, Harold Victor
• Primary Examiner(s): ZISKA, SUZANNE E
• Application Number:
  US13/138,884
• Publication Number:
  US 20120093866A1
• Time in Patent Office: 2,055 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2800/91 Injection
• CPC Class Codes: A61K 38/4893 Botulinum neurotoxin (3.4.24.69)
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 8/345 containing more than one hydroxy group
• CPC Class Codes: A61K 8/60 Sugars; Derivatives thereof
• CPC Class Codes: A61K 8/64 Proteins; Peptides; Derivatives or degradation products thereof
• CPC Class Codes: A61K 8/735 Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
• CPC Class Codes: A61K 8/86 Polyethers
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin
• CPC Class Codes: C12N 9/52 derived from bacteria or Archaea
• CPC Class Codes: C12N 9/96 Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
• CPC Class Codes: C12Y 304/24069 : Bontoxilysin (3.4.24.69), i.e. botulinum neurotoxin
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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, and wherein the formulation is free of stabilizing proteins.

Claims

1. A formulation consisting essentially of:

(a) hyaluronic acid,

(b) a mixture of a polyalcohol and a sugar, and wherein the weight ratio of polyalcohol to sugar is from 2;

1 to 5;

1 (wt-%),

(c) a surfactant, and

(d) a Clostridium botulinum toxin,

wherein the formulation is free of human serum albumin (HSA), gelatin, histidine, lysine, methionine immunoglobulins.

2. The formulation of claim 1, wherein the polyalcohol is selected from mannitol, inositol, lactilol, isomalt, xylitol, erythritol, sorbitol, and mixtures thereof.

3. The formulation of claim 1, wherein the sugar is selected from monosaccharides, disaccharides, polysaccharides, and mixtures thereof.

4. The formulation of claim 1, which is lyophilized.

5. The formulation of claim 1, which comprises Clostridium botulinum toxin, hyaluronic acid, mannitol, sucrose, polysorbate 80 and, optionally, water for injection.

6. An injectable solution comprising the formulation of claim 1.

7. The formulation of claim 1, in the form of a cosmetic product, a cosmeceutical product or a diagnostic product.

8. The formulation of claim 1, comprising a therapeutically effective amount of the Clostridium botulinum 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.

9. A kit comprising

(a) one or more containers comprising the formulation of claim 1, and

(b) instructions for use of the formulation of claim 1, and optionally,

(c) a pharmaceutically acceptable sterile solvent.