Stable Non-Aqueous Pharmaceutical Compositions

• US 20100144592A1
• Filed: 05/30/2008
• Published: 06/10/2010
• Est. Priority Date: 06/01/2007
• Status: Abandoned Application

• Current Assignee: Novo Nordisk A/S
• Original Assignee: Novo Nordisk A/S
• Inventors: Havelund, Svend, Föger, Florian Anders, Bjerregaard Jensen, Simon
• Application Number:
  US12/601,884
• Publication Number:
  US 20100144592A1
• Time in Patent Office: Days
• US Class Current: 514/5.900
• CPC Class Codes: A61K 38/22 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61K 9/1688 resulting in pure drug agglomerate optionally containing up to 5% of excipient
• 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 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

The present invention relates to shelf stable non-aqueous pharmaceutical compositions, and to the use thereof in methods of treating diabetes and hyperglycaemia, comprising dehydrated active polypeptide comprising 10-100 amino acids and at least one semi-polar protic organic solvent.

Claims

1. Pharmaceutical non-aqueous composition comprising a mixture of

a) a dehydrated therapeutically active polypeptide comprising 10-100 amino acids, and

b) at least one semi-polar protic organic solvent

which polypeptide has been dehydrated at a target pH which is at least 1 pH unit from the pI of the polypeptide in aqueous solution.

2. The pharmaceutical composition according to claim 1, wherein the organic solvent is selected from the group consisting of propylene glycol and glycerol.

3. The pharmaceutical composition according to any one of claims 1-2, wherein the solubility of dehydrated polypeptide in the organic solvent is at least 20 mg/ml.

4. The pharmaceutical composition according to any one of claims 1-3, wherein the target pH is in the range from about 6.0 to about 9.0.

5. The pharmaceutical composition according to any one of claims 1-4, wherein the organic solvent is present in an amount of at least 20% w/w.

6. The pharmaceutical composition according to any one of claims 1-5, which comprises less than 10% w/w water.

7. The pharmaceutical composition according to any one of claims 1-6, wherein the composition is adapted for pulmonary treatment, oral treatment, nasal treatment or buccal treatment.

8. The pharmaceutical composition according to any one of claims 1-7, wherein the polypeptide is selected from the group consisting of insulin peptides, amylin, amylin analogues, amylin derivatives, α

-MSH, α

-MSH analogues, α

-MSH derivatives and/or any combination thereof.

9. The pharmaceutical composition according to any one of claims 1-8, wherein the insulin peptide is an insulin analogue.

10. Pharmaceutical composition according to any one of claims 1-9 for use as a medicament for treatment or prevention of hyperglycemia, type 2 diabetes, impaired glucose tolerance and type 1 diabetes.