Hormone replacement therapy method

• US 6,551,611 B2
• Filed: 05/01/2000
• Issued: 04/22/2003
• 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, Jörg
• Primary Examiner(s): Clardy, S. Mark
• Assistant Examiner(s): Williamson, Michael A.
• Application Number:
  US09/562,316
• Publication Number:
  US 20020142028A1
• Time in Patent Office: 1,086 Days
• Field of Search: 424/449, 424/434, 424/439, 221/206, 221/207, 222/14, 222/15, 222/71, 222/94, 222/97, 222/544
• 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: 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 method for self-administration by a human female of a plurality of successive doses of an estrogen and a plurality of successive doses of a progestogen according to a protocall of self administration, wherein the female dispenses and self-administers successive individual doses of a selected volume of the estrogen and a selected volume of the progestogen over a protracted period of time, during which period of time the amount of at least one of which doses is changed, the method comprising:

providing a first containerized source of a first extrudable pharmaceutically acceptable composition containing a plurality of non-discrete doses of the estrogen,

providing a first meter for measuring and determining the volume of the dispensed doses of estrogen and varying the volume according to the protocall of self-administration;

providing a second containerized source of a second extrudable pharmaceutically acceptable composition containing a plurality of non-discrete doses of the progestogen;

providing a second meter for measuring and determining the volume of the dispensed doses of progestogen and varying the volume according to the protocall of self-administration;

placing the first and second meters in proximity with one another wherein measured doses of estrogen and progestogen are immediately available for topical application by the patient so as to facilitate a the protocol for self-administration of the estrogen and progestogen on a repeated schedule, periodically in response to the physiological symptoms associated with menopause or the hormone replacement therapy currently exhibited by the female, so that the metered volume of at least one of the first and second compositions may be dispensed.

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

3. A method according to claim 1, wherein the first and second containerized sources are positioned adjacent to one another so that the pharmaceutically acceptable compositions are dispensed simultaneously from the respective sources thereof.

4. A method according to claim 1, wherein the meters have merged outputs into a mixing chamber so that dispensed doses of the first and second pharmaceutically acceptable compositions are mixed before being dispensed for application.

5. A method according to claim 1, wherein the containerized source of the first pharmaceutical composition is a first compartment of a unitary dispenser and the containerized source of the second pharmaceutical composition is a second compartment of the unitary dispenser;

wherein the first and second pharmaceutical compositions are first extruded from their respective compartments into the first and second meters, which meters are configured as 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 through a dispenser nozzle.

6. A method according to claim 1, wherein the extrudates of the first and second pharmaceutical compositions have lengths which are extruded from the respective containerized sources which are constant and the dosage of the hormones therein is changed 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 by changing the length of one or both of the extrudates.

7. 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, chlornadione acetate, cyproterone acetate, desogestrel, 3-ketodesogestrel, drospirenone, norethindrone, norgestimate, levonorgestrel or gestodene.

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

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

9. A method according to claim 8, wherein the pharmaceutical compositions are semi-solids;

wherein the pharmaceutical compositions are metered from a dispenser in which the first and second containerized sources are both housed, and

wherein the dispenser includes adjusters 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 the pharmaceutical compositions from the container.

10. A method for using an HRT kit for self-administration by a human female of a plurality 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 over a protracted period of time, during which period of time the amount of at least one of which doses is changed, which kit comprises:

a first containerized source of a first extrudable pharmaceutically acceptable composition containing a plurality of non-discrete doses of the estrogen,

a second containerized source of a second extrudable pharmaceutically acceptable composition containing a plurality of non-discrete doses of the progestogen,

first and second meters in proximity with one another for receiving and indicating measured volumes of the first and second compositions thereon, wherein first and second measured doses of estrogen and progestogen are immediately available from the meters for topical application by the patient so as to facilitate a protocol for self-administration of the estrogen and progestogen on a repeated schedule, periodically in response to the physiological symptoms associated with menopause or the hormone replacement therapy currently exhibited by the female, so that a metered volume of at least one of the first and second compositions may be dispensed and applied.

11. The method of claim 10, wherein the first and second containerized sources are squeezable tubes containing the plurality of doses of estrogen and progestogen, respectively, and

wherein the first and second meters are first and second arrays of linear markings on panel means, the first array receiving an estrogen extrudate in juxtaposition therewith and the second array for receiving a progestogen extrudate in juxtaposition therewith, whereby the ratio of estrogen to progestogen is visually apparent by the length of the extrudates on the panel means.

12. The method of claim 11 wherein the panel means is a single panel with the arrays of markings located adjacent one another thereon.

13. The method of claim 12, 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.

14. The method of claim 12, wherein the estrogen is ethinyl estradiol or 17β

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

15. The method of claim 10, 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.

16. The method of claim 10, wherein the estrogen is ethinyl estradiol or 17β

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