Title:  Transdermal rate-controlled delivery of Huperzine A for treatment of alzheimer's disease

United States Patent:  6,352,715

Assignee:  Sagittarius Life Science Corp (Taipei Shien, TW)

Filed:  June 12, 2000

This invention relates to a novel transdermal drug delivery system whereby Huperzine A ("Hup A"), a naturally occurred Acetylcholine esterase inhibitor traditionally used to alleviate memory problem, is formulated for transdermal administration suitable for the treatment of Alzheimer's Disease ("AD") to increase the efficacy and convenience for outpatient care of AD patients. A controlled-release skin patch designed for once-a-week application of Hup A is provided for easy AD medication according to the invention.

SUMMARY OF INVENTION

This invention relates to a novel transdermal delivery device for a pharmaceutical composition comprising Hup A which has been proven to reduce and temper the effects of Alzheimer's Disease.

One aspect of the invention is to provide for a transdermal drug delivery device suitable for transdermal administration of Hup A to provide therapeutical benefits to patients with Alzheimer disease. The transdermal drug delivery device comprises (i) a concentration of Hup A in an amount sufficient to enable said Hup A to exhibit anti-Alzheimer activity through said transdermal administration; (ii) at least an aprotic solvent in a concentration sufficient to dissolve said Hup A to from a Hup A reservoir; (iii) a gelling agent in an amount sufficient to gelled said Hup A reservoir; and (iv) at least a polymeric membrane added to encapsulate said gelled Hup A reservoir to form a controlled-release formulation. The Hup A reservoir is adjusted to a pH range in which said Hup A is predominantly in a neutral form to achieve maximum transdermal delivery of said Hup A to provide the therapeutical benefits to the patients. The transdermal drug delivery device according to the invention may be in a form of skin patch with the aid of a drug-impermeable metallic-plastic laminate to said polymeric membrane. Preferably, the pH range of the Hup A reservoir is between 7 to 9.

Another aspect of the invention is to provide for an adhesive-type transdermal drug delivery device suitable for transdermal administration of Hup A to provide therapeutical benefits to patients with Alzheimer disease. Briefly, the adhesive-type transdermal drug delivery device comprises (i) a concentration of Hup A in an amount sufficient to enable said Hup A to exhibit anti-Alzheimer activity through said transdermal administration; (ii) at least a pressure-sensitive adhesive polymer in a concentration sufficient to dissolve said Hup A to from a Hup A adhesive solution in presence of an organic solvent; and (iii) a sheet of drug-impermeable backing laminate added to coat said Hup A adhesive solution to form a pressure-sensitive adhesive formulation. Preferably, the Hup A adhesive solution has a pH value in the range of 7 to 9.

One more aspect of the invention is to provide for a method for preparing the aforementioned transdermal drug delivery device which comprises weighing a concentration of Hup A in an amount sufficient to enable said Hup A to exhibit anti-Alzheimer activity through transdermal administration; dissolving said Hup A in at least an aprotic solvent in a pH range enabling said Hup A existing predominantly in a neutral form to form a Hup A reservoir; adding a gelling agent to gell said Hup A reservoir; and adding at least a polymeric membrane to encapsulate said gelled Hup A reservoir to form a controlled-release formulation.

One further aspect of the invention is to provide for a method for preparing the aforementioned adhesive-type transdermal drug delivery device which comprises weighing a concentration of Hup A in an amount sufficient to enable said Hup A to exhibit anti-Alzheimer activity through transdermal administration; dissolving said Hup A in at least a pressure-sensitive adhesive polymer in presence of a suitable solvent to from a Hup A adhesive solution in a pH range in which said Hup A is predominantly in a neutral form to form a Hup A adhesive solution; and adding a sheet of drug-impermeable backing laminate to coat said Hup A adhesive solution to form a pressure-sensitive adhesive formulation.

Still one further aspect of the invention is to provide for a method for providing therapeutical benefits of Hup A to a human patient diagnosed with Alzheimer disease. The method comprises preparing the aforementioned transdermal drug delivery device and administrating the same to a human patient through dermal administration for a period of time sufficient to exhibit the Alzheimer activities in the human patient.

Claim 1 of 15 Claims

What is claimed is:

1. A rate-controlled transdermal drug delivery device for transdermal delivery of Huperzine A at a therapeutically effective rate in a linear square root of time manner for up to at least 7 days to provide therapeutical benefits to patients with Alzheimer's disease, comprising;

(a) a concentration of Huperzine A in an amount sufficient to enable transdermal delivery of said Huperzine A at said therapeutically effective rate of no less than 0.833-1.46 ug/cm².h to exhibit said therapeutical benefits;

(b) a solution of adhesive polymer in a concentration sufficient to form a Huperzine A dispersing pressure-sensitive adhesive with said concentration of Huperzine A wherein said solution of adhesive polymer is adjusted to a pH range in which said concentration of Huperzine A is predominantly in a neutral form to achieve transdermal delivery of said Huperzine A at said therapeutically effective rate in said linear square root of time manner for up to at least 7 days per one administration; and

(c) a sheet of drug-impermeable backing laminate added to support said Huperzine A dispersing pressure-sensitive.

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