Pharmaceutical composition containing botulinum neurotoxin

Abstract

Method for treating a disease, condition, or syndrome in a subject comprising administering, to a subject in need thereof, a solid or liquid pharmaceutical composition comprising: (a) a high purity botulinum neurotoxin or a complex comprising botulinum neurotoxin, wherein the botulinum neurotoxin is of type A, B, C, D, E, F or G; and (b) a surfactant;
wherein the composition does not comprise albumin or a polysaccharide.

Claims

1. A method for treating wrinkles comprising administering to a subject in need thereof a composition comprising: (a) a high purity botulinum neurotoxin or a complex comprising botulinum neurotoxin, wherein the botulinum neurotoxin is of type A, B, C, D, E, F or G; and (b) a surfactant; wherein the composition does not comprise albumin or a polysaccharide.

2. The method of claim 1, wherein the composition further comprises sodium chloride.

3. The method of claim 1, wherein the composition further comprises a buffer capable of maintaining an aqueous solution at a pH between 5.5 and 7.5.

4. The method of claim 1, wherein the composition further comprises a disaccharide.

5. The method of claim 1, wherein the botulinum neurotoxin is a botulinum neurotoxin type A.

6. The method of claim 1, wherein the botulinum neurotoxin complex or high purity botulinum neurotoxin is administered in a therapeutically efficient quantity.

7. The method of claim 1, for treating glabellar frown lines.

8. The method of claim 1, for treating facial wrinkles.

Description

EXAMPLES

Example 1: A Liquid Pharmaceutical Composition Containing the Following Components is Prepared

(1) TABLE-US-00001 Clostridium botulinum type A1 neurotoxin complex 2,000 LD.sub.50 units/ml Sucrose 11.7 mM Histidine 10 mM Sodium chloride 0.3M Polysorbate 80 0.01% v/v pH 6.5

(2) The mixture containing nominally 2,000 LD.sub.50 units of botulinum toxin per ml is lyophilised in a sterilised vial, which is then sealed. The solid composition obtained is stable for at least 18 months when stored at a temperature between 2 and 8° C. and at least 6 months at 23 to 27° C.

Example 2: A Liquid Pharmaceutical Composition Containing the Following Components is Prepared

(3) TABLE-US-00002 Clostridium botulinum type A1 neurotoxin complex 500 LD.sub.50 units/ml Sucrose 11.7 mM Histidine 10 mM Sodium chloride 0.3M Polysorbate 80 0.01% v/v PH 6.5

(4) The liquid composition thus prepared is sealed in a syringe type device with no liquid/gaseous interface. Stored in these conditions, it is stable for at least six months at 23 to 27° C. and at least twelve months at 2-8° C.

Example 3: A Liquid Pharmaceutical Composition Containing the Following Components is Prepared

(5) TABLE-US-00003 Clostridium botulinum type A1 neurotoxin complex 500 LD.sub.50 units/ml Sucrose 11.7 mM Histidine 10 mM Sodium chloride 0.15M Polysorbate 80 0.01% v/v PH 6.5

(6) The liquid composition thus prepared is sealed in a syringe type device with no liquid/gaseous interface. Stored in these conditions, it is stable for at least six months at 23 to 27° C. and at least twelve months at 2-8° C.

(7) Analytical Methods

(8) House Toxicity Assay

(9) A mouse toxicity assay can be used to measure the toxicity of botulinum neurotoxin complex (type A, B, C, D, E, F or G) or high purity botulinum neurotoxin (type A, B, C, D, E, F or G). In the assay, a standard diluent will be used to prepare a range of dilutions at or about the estimated LD.sub.50 value. The range and scale of dilutions is arranged so as to establish an accurate LD.sub.50 value.

(10) Mice are injected intraperitoneally with a known and standardised volume of diluted toxin. After 96 hours, the number of deaths and survivors in each dilution group will be recorded. The LD.sub.50 value is the median dose which kills half of the injected animals within 96 hours.

(11) A composition according to the invention is considered stable over a certain period of time if at least 70% of the initial toxicity is maintained over said period of time relative to a reference preparation.