NZ332905A - Transdermal pharmaceutical composition comprising liposomal bee venom - Google Patents

Abstract

The transdermal composition comprises 0.01% to 20%w/w liposomal bee venom in a carrier comprising a phosphatidylcholine fraction, a lecithin fraction, ethanol and water. The liposomal bee venom is associated with its carrier by a microfluidisation procedure, forming a bilayer vesicle of from 150 to 500nm. This composition may be used for the treatment of rheumatoid, oesteoarthritis and tendinitis.

Description

PATENTS ACT, 1953 No: 332905 Date: 19 November 1998 COMPLETE SPECIFICATION "Bee Venom Liposomes" m We, IMMUNO LABORATORIES LIMITED, a company duly incorporated under the laws of New Zealand of Unit G, 40 Stanley Street, Parnell, Auckland, New Zealand,, do hereby declare the invention for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: The present invention relates to a delivery system for bee venom and related procedures and products.

Bee venom is a desirable active ingredient for the purpose of medicinal application for example acute and chronic trauma such as rheumatoid and osteoarthritis and tendinitis.

The present invention is directed to procedures whereby the venom may be delivered transdermally into a mammalian host (preferably a human being).

In a first aspect therefore the present invention consists in a transdermal composition comprising or including liposomal bee venom.

In still a further aspect the present invention consists in a method of transdermal delivery of bee venom which comprises topically applying liposomal bee venom to the skin.

In some preferred forms of the present invention the liposomal bee venom is or has been prepared by microfluidisation which preferably forms multilamellar vesicles.

Preferably said microfluidisation has involved phosphatidylcholine (purified from soybean lecithin) and Lecithin fraction and a water stream (preferably including ethanol as a preservative).

Preferably said procedure results in a bilayer vesicle 150-500nm in size.

In other procedures preloading concentrate procedures, for example, substantially hereinafter may be utilized or thin film evaporative procedures substantially hereinafter described may be utilized.

This invention may also be said broadly to consist in the parts, elements and features referred to or indicated in the specification of the application, individually or collectively, and any or all combinations of any two or more of said parts, elements or features, and where specific integers are mentioned herein which have known equivalents in the art to which this invention relates, such known equivalents are deemed to be incorporated herein as if individually set forth.

The invention consists in the foregoing and also envisages constructions of which the following gives examples.

Preferred forms of the present invention will now be described. "1/ Microfluidisation.

This process is believed to form multilamellar vesicles providing excellent retention of water soluble molecules.

- Uses phosphatidylcholine (purified from soybean lecithin) and lecithin as the lipid preparation.

- Uses water and ethanol (preservative) as the aqueous phase.

- The lipid preparation and aqueous phase (containing bee venom) are pumped at high pressure (~ 200Mpa) through microchannels to collide with each other at high velocity.

- This forms a bilayer vesicle-150-500nm.

Other encapsulating methodologies, are: 2/ Preloading Concentrate - Preparation of a purified hydrated bilayers concentrated suspension consisting of unsaturated soya bean phosphatidylcholine & hydrophillic medium.

- Liposome formation resulting during mixing and active loading stage with addition of water and NaCl solution.

- This will form bilayer vesicles or oligo-lamellar vesicles. 3/ Thin Film Evaporation.

- Using ethanol as a solvent with the phospholipid.

- Evaporating, the resultant film is mixed with water and Bee Venom.

- Slowly agitated with glass beads.

- This is likely to form unilamellar vesicles "150-500nm".

Preferably a preferred composition in accordance with the present invention is s follows: Phosphatidylcholine can be used in the following forms and components; with glycerol 0.1% up to % w/w with butylene glycol 0.1% up to % w/w with propylene glycol 0.1% up to % w/w hydrogenated 0.1% up to 80% w/w as soya bean lecthin 0.1% up to 80% w/w purified phosphatydyl choline 0.1% up to 80% w/w negatively charged 0.1% up to 80% w/w overall from 0.1% to 80% • ethanol • tocopherol acetate Office of NZ 2 0 NOV 2000 0.1% up to 80% w/w received 0.05% up to 5% w/w 332905 Entrapment Profile • water soluble (hydrophilic) and • oil soluble (Lipophilic) with maximum retention of trapped material (Bee Venom) Bee Venom at 0.01% to 20% w/w The procedures of the present invention giving rise to liposomal bee venom ensures increased availability of the bee venom. ,nte2®fual Property Office of NZ NOV 2000 received 332905

Claims (12)

WHAT WE CLAIM IS:

1. A transdermal composition comprising or including liposomal bee venom and an acceptable carrier therefor.

2. A composition as claimed in claim 1 wherein said carrier is a liquid carrier.

3. A composition as claimed in claim 1 or claim 2 wherein the liposomal bee venom has an association with its carrier through having been associated therewith by a microfluidisation procedure.

4. A composition of claim 3 wherein said microfluidisation procedure forms multilamellar vesicles.

5. A composition as claimed in any one of the preceding claims wherein said carrier includes phosphatidylcholine.

6. A composition as claimed in any one of the preceding claims wherein said carrier includes a lecithin fraction

7. A composition as claimed in any one of the preceding claims wherein said carrier includes water.

8. A composition as claimed in any one of the preceding claims wherein said liposomal bee venom is carried in a liquid carrier with which it has been associated by a microfluidisation procedure which provides a bilayer vesicle of from 150-500nm in size.

9. A composition of any one of claims 1 to 8 wherein the liposomal bee venom comprises from 0.01% to 20% w/w.

10. A composition as claimed in claim 1 substantially as hereinbefore described with or without reference to any example thereof.

11. Use of liposomal bee venom and an acceptable carrier thereof in the manufacture of a transdermal composition for the treatment of rheumatoid, osteoarthritis and tendinitis.

12. A method of formulating a composition of any one of claims 1 to 10 when performed substantially as hereinbefore described. AJ Par DATED THIS Dowfyfa/ PER AOBHTS FOl Intellectual Property Office of NZ 20 NOV 2000 received