Estradiol compositions and methods for topical application

• US 5,128,138 A
• Filed: 07/17/1991
• Issued: 07/07/1992
• Est. Priority Date: 07/21/1989
• Status: Expired due to Fees

• Current Assignee: Izhak Blank
• Original Assignee: Izhak Blank
• Inventors: Blank, Izhak
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): BROUILLETTE, D GABRIELLE
• Application Number:
  US07/732,348
• Time in Patent Office: 356 Days
• Field of Search: 424/447, 424/448, 424/449, 424/65, 401/213, 514/946, 514/947, 514/944
• US Class Current: 424/449
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• 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 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/7053 obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
• CPC Class Codes: A61K 9/7061 Polyacrylates

Abstract

A mixture of estradiol or other estrogen and an uncrosslinked, water-insoluble vinylpyrrolidone copolymer provides a matrix which gradually releases the medicament upon application to the skin of a patient in the form of an ointment, gel or film. The polymer provides for the slow and sustained release of the medicament upon topical application to the skin so that the concentration of drug in the blood plasma of the patient is maintained within the levels required for clinical efficacy.

Claims

1. A method for providing for the sustained transdermal administration of an estrogen selected from the group consisting of 17β

-estradiol, ethinylestradiol and 17β

-estradiol esters, which comprises applying to the skin of a patient, a gel, ointment or film containing the estrogen and an uncrosslinked, water-insoluble vinylpyrrolidone copolymer which contains at least 10% by weight of vinylpyrrolidone and a comonomer which is copolymerizable therewith by free radical polymerization, and wherein the estrogen concentration is in the range of 0.01% to about 1% of the total weight of the composition.

2. The method of claim 1, wherein the gel or ointment is applied on a carrier selected from the group consisting of a gauze, tape or bandage.

3. The method of claim 1, wherein the gel is applied to the skin of a patient from a roll-on dispenser.

8. The method of claim 1, wherein the comonomer is styrene.

4. A method for providing for the sustained transdermal administration of an estrogen selected from the group consisting of 17β

-estradiol, ethinylestradiol and 17β

-estradiol esters, which comprises applying to the skin of a person, a gel, ointment or film containing the estrogen and an uncrosslinked, water-insoluble vinylpyrrolidone copolymer which contains at least 10% by weight of vinylpyrrolidone and a comonomer which is an ester of an unsaturated acid selected from the group consisting of acrylic acid, methacrylic acid, crotonic acid, maleic acid and the corresponding anhydrides, wherein the estrogen concentration is within the range of 0.01% to about 1% of the total weight of the composition.

5. The method of claim 4, wherein the comonomer is an ester selected from the group consisting of the acrylic and methacrylic esters of C₁ to C₄₀ linear and branched alkanols.

6. The method of claim 4 wherein the ester is selected from the group consisting of lauryl methacrylate and 2-ethylhexyl acrylate.

9. The method of claim 4 wherein the uncrosslinked, water-insoluble vinylpyrrolidone copolymer contains units derived from an unsaturated acid selected from the group consisting of acrylic acid, methacrylic acid, crotonic acid, maleic acid and the corresponding anhydrides.

7. A method for providing for the sustained transdermal administration of an estrogen selected from the group consisting of 17β

-estradiol, ethinylestradiol and 17β

-estradiol esters, which comprises applying to the skin of a person, a gel, ointment or film containing the estrogen and an uncrosslinked, water-insoluble vinylpyrrolidone copolymer which contains at least 10% by weight of vinylpyrrolidone and a comonomer which is an ester of a saturated acid selected from the group consisting of the vinyl and allyl esters of C₁ to C₄₀ carboxylic acids, wherein the estrogen concentration is within the range of about 0.01% to about 1% of the total weight of the composition.