Hormone replacement therapy method and hormone dispenser

• US 5,922,349 A
• Filed: 09/27/1996
• Issued: 07/13/1999
• Est. Priority Date: 09/28/1995
• Status: Expired due to Fees

• Current Assignee: Bayer Schering Pharma AG (Bayer AG)
• Original Assignee: Schering Ag (Merck & Co., Inc.)
• Inventors: Riedl, Jutta, Elliesen, Jorg
• Primary Examiner(s): BROUILLETTE, D GABRIELLE
• Application Number:
  US08/721,968
• Time in Patent Office: 1,019 Days
• Field of Search: 424/449, 424/434, 424/439
• US Class Current: 424/449
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/12 for climacteric disorders
• CPC Class Codes: A61P 5/24 of the sex hormones
• CPC Class Codes: B65D 35/22 with two or more compartments
• CPC Class Codes: B65D 81/325 Containers having parallel or coaxial compartments, provided with a piston or a movable bottom for discharging contents
• CPC Class Codes: B65D 83/0005 Containers or packages provided with a piston or with a movable bottom or partition having approximately the same section as the container B65D83/0072 takes precedence
• CPC Class Codes: B65D 83/0011 moved by a screw-shaft

Abstract

Varying the daily dose of either or both of the estrogen and the progestogen administered for hormone replacement therapy (HRT) is readily and inexpensively accomplished, without the necessity of the physician prescribing a new product each time the daily dose of the estrogen or progestogen is changed, by administering preferably transdermally the estrogen and the progestogen contained in separate extrudable pharmaceutical compositions from a dispenser which contains means, preferably adjustable only by the attending physician or dispensing pharmacist, for varying the volume of either or both of the respective compositions which is dispensed as a single dose from the dispenser in response to a defined digital dispensing manipulation of the dispenser thereby facilitating optimal compliance to a combination of HRT with individually adjusted dosages of the estrogen and progestogen.

Claims

1. A hormone replacement therapy method of self-administration by a human female of successive doses of an estrogen and a plurality of successive doses of a progestogen, wherein the female dispenses and self-administers successive individual doses of the estrogen and of the progestogen from containerized sources over a protracted period of time, during which period of time the amount of at least one of which doses is changed, which method comprises the steps of:

a) dispensing onto a delivery surface from a first containerized source of a first extrudable pharmaceutically acceptable composition containing a plurality of non-discrete doses of the estrogen, a metered volume of the first composition as a single dose of the estrogen;

b) concurrently dispensing onto the delivery surface, from a second containerized source of a second extrudable pharmaceutically acceptable composition containing a plurality of non-discrete doses of the progestogen, a metered volume of the second composition as a single dose of the progestogen;

c) transferring the dispensed doses of the first and second compositions from the delivery surface simultaneously to the site of administration of the estrogen and progestogen;

d) repeating steps a)-c) on a predetermined schedule; and

e) periodically, in response to the physiological symptoms associated with menopause or the hormone replacement therapy currently exhibited by the female, changing the metered volume of at least one of the first and second compositions which is dispensed onto the delivery surface as a single dose thereof.

2. A method according to claim 1, wherein the predetermined schedule of Step d) is daily.

3. A method according to claim 1, wherein the site of administration is an area of the skin of the female and the first and second pharmaceutically acceptable compositions are adapted to transdermal administration.

4. A method according to claim 3, wherein the delivery surface is the female'"'"'s hand and the compositions thereon are administered at the selected site of transdermal administration on the skin of the female by rubbing the hand against the the skin.

5. A method according to claim 1, wherein the pharmaceutical compositions are semi-solids which are dispensed as extrudates.

6. A method according to claim 1, wherein the first and second pharmaceutically acceptable compositions are dispensed simultaneously from the respective sources thereof.

7. A method according to claim 1, wherein the dispensed doses of the first and second pharmaceutically acceptable compositions are mixed before being dispensed onto the delivery surface.

8. A method according to claim 1, wherein the predetermined schedule of Step d) is daily;

wherein the site of administration is the skin of the female and the first and second pharmaceutically acceptable compositions are adapted to transdermal administration;

wherein the compositions thereon are delivered to the selected site of transdermal administration on the skin of the female by rubbing;

wherein the pharmaceutical compositions are semi-solids and are dispensed as extrudates simultaneously from the respective sources thereof; and

wherein the metered doses of the first and second pharmaceutically acceptable compositions are mixed before being extruded onto the delivery surface.

9. A method according to claim 1, wherein the source of the first pharmaceutical composition is a first compartment of a unitary dispensing means and the source of the second pharmaceutical composition is a second compartment of the dispensing means;

wherein the first and second pharmaceutical compositions are first extruded from their respective compartments into first and second metering chambers, respectively; and

wherein the contents of the metering chambers are then formed into a single extrudate which is then dispensed from the dispensing means.

10. A method according to claim 1, wherein the first and second pharmaceutical compositions are in the form of extrudates and wherein either the length of the extrudates which are extruded from the respective sources thereof is constant and the dosage of the hormones therein is changed in Step (e) by changing the diameter of one or both of the extrudates, or wherein the diameter of the extrudates of the first and second pharmaceutical compositions which are extruded from the respective sources thereof is constant and the dosage of the hormones therein is changed in Step (e) by changing the length of one or both of the extrudates.

11. A method according to claim 1, wherein the estrogen is ethinyl estradiol or estradiol or an ester thereof, estrone, estrone sulfate or conjugated estrogens and the progestogen is micronized progesterone, norethindrone or ester thereof, norgestrel, chlormadione acetate, cyproterone acetate, desogestrel, 3-ketodesogestrel, drospirenone, norethindrone, norgestimate, levonorgestrel or gestodene.

12. A method according to claim 1, wherein the estrogen is ethinyl estradiol or 17β

-estradiol and the progestogen is gestodene, levonorgestrel or 3-ketodesogestrel.

13. A method according to claim 12, wherein the predetermined schedule of Step d) is daily;

wherein the pharmaceutical compositions are semi-solids;

wherein the pharmaceutical compositions are metered from a dispenser in which the first and second containers both are housed, which the dispenser comprises mechanical means for changing the volumes of the pharmaceutical compositions which are dispensed from the containers in response to a defined constant digital manipulation employed to extrude from the container.