Pharmaceutical composition comprising betahistine

• US 10,456,386 B2
• Filed: 02/02/2018
• Issued: 10/29/2019
• Est. Priority Date: 02/02/2017
• Status: Active Grant

• Current Assignee: Otolanum Ag
• Original Assignee: Otolanum Ag
• Inventors: Wraight, Christopher John, Meyer, Thomas
• Primary Examiner(s): Heyer, Dennis
• Application Number:
  US15/887,388
• Publication Number:
  US 20180214432A1
• Time in Patent Office: 634 Days
• Field of Search: None
• CPC Class Codes: A61K 31/4402 only substituted in position 2, e.g. pheniramine, bisacodyl
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 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 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 27/16 Otologicals

Abstract

The present disclosure relates to a pharmaceutical composition comprising as active substance betahistine or a pharmaceutically acceptable salt thereof, for use in the treatment of otological or neurological disorders in a human subject by intranasal application.

Claims

1. A pharmaceutical composition for intranasal delivery to a human patient, comprising a solution or suspension of a therapeutically effective amount of betahistine dihydrochloride, a viscosity enhancing agent, a moisturizing agent, and a buffer, wherein the pH of the pharmaceutical composition is about 4.4 to about 6.4.

2. The pharmaceutical composition of claim 1, wherein the viscosity enhancing agent is selected from the group consisting of polyvinyl pyrrolidone, polyvinyl alcohol, methylcellulose, carboxymethyl cellulose-Na, hydroxyethylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyethylene-oxide, Carbopol, polyethylene glycol, propylene glycol, glycerin, alginates, carrageenan, pectins, maltodextrin, sodium starch glycolate tragacanth gum, gum arabic, microcrystalline cellulose and combinations thereof.

3. The pharmaceutical composition of claim 2, wherein the viscosity enhancing agent is polyvinyl pyrrolidone.

4. The pharmaceutical composition of claim 1, wherein the moisturizing agent is selected from the group consisting of glycerin, ethylene glycol, propylene glycol, propylene glycol 400, hexalene glycol, butylene glycol, dextrose, glyceryl triacetate, polydextrose, glycerol, glyceryl triacetate, sorbitol, mannitol, and combinations thereof.

5. The pharmaceutical composition of claim 4, wherein the moisturizing agent is selected from the group consisting of glycerin, polyethylene glycol 400 and propylene glycol.

6. The pharmaceutical composition of claim 1, wherein the composition comprises betahistine dihydrochloride at a concentration of about 1 mg/mL to about 1000 mg/mL.

7. The pharmaceutical composition of claim 6, wherein the composition comprises betahistine dihydrochloride at a concentration of about 10 mg/mL to about 400 mg/mL.

8. The pharmaceutical composition of claim 1, wherein the composition is in the form of a unit dose comprising the betahistine in an amount of about 5 mg to about 100 mg.

9. The pharmaceutical composition of claim 1, wherein the composition is in the form of a unit dose comprising the betahistine in an amount of about 5 mg, about 10 mg, about 20 mg, about 40 mg, or about 80 mg.

10. The pharmaceutical composition of claim 1, wherein the composition is in the form of a unit dose, comprising about 1 μ

L to about 1000 μ

L of the composition per unit dose.

11. The pharmaceutical composition of claim 1, wherein the composition is capable of being administered as a spray or aerosol.

12. The pharmaceutical composition of claim 1, wherein the composition is an aqueous solution.

13. The pharmaceutical composition of claim 1, wherein a single dose of the composition comprises 20 mg or 40 mg of betahistine.

14. The pharmaceutical composition of claim 1, further comprising at least one enzyme inhibitor or absorption promoter.

15. The pharmaceutical composition of claim 1, comprising a preservative.

16. The pharmaceutical composition of claim 15, wherein the preservative is selected from the group consisting of benzethonium chloride, benzoxonium chloride, benzododecinium bromide, alkyltrimethilammonium bromide, cetrimonium bromide, benzalkonium chloride, phenylethyl alcohol, benzoic acid and esters and salts thereof, parabens, potassium sorbate, sorbic acid, calcium sorbate, sodium sorbate, chlorhexidine, boric acids and phenols.

17. A method of treating an inner ear disorder, a vestibular disorder, ADHD, dementia, obesity or weight gain, comprising intranasally administering the pharmaceutical composition of claim 1 to a subject in need thereof.

18. The method of claim 17, wherein the method is for treating a vestibular disorder.

19. The method of claim 18, wherein the vestibular disorder is vestibular vertigo or Meniere'"'"'s disease.

20. The method of claim 17, wherein the method is for treating an inner ear disorder selected from tinnitus or hearing loss.