Intrauterine delivery system for contraception

Abstract

The invention relates to a method for contraception and for reducing menstrual problems and inducing amenorrhea, wherein an intrauterine delivery device is used for the controlled release of a combination of progestogen or a drug having a progestogenic activity and at least one therapeutically active substance capable of preventing or suppressing abnormal and/or irregular endometrial bleeding over a prolonged period of time.

1 - 27 . (canceled) 
     
     
         28 . An improved method for contraception and for reducing menstrual problems and for inducing amenorrhea, wherein an intrauterine delivery system is used for the controlled release of progestogen or a drug having a progestogenic activity over a prolonged period of time and at a level required for contraception and wherein the intrauterine delivery system comprises a body construction and at least one reservoir comprising a core and optionally a membrane encasing the core, the core and membrane essentially consisting of a same or different polymer composition, characterized in that said intrauterine delivery system additionally comprises at least one therapeutically active substance capable of preventing or suppressing abnormal and/or irregular endometrial bleeding wherein said substance is selected from the group consisting of tranexamic acid, mefenamic acid, danazol and an angiogenesis inhibitor. 
     
     
         29 . A method according to  claim 28 , characterised in that a progestogen, or a drug having a progestogenic activity, and a therapeutically active substance capable of preventing or suppressing abnormal and/or irregular endometrial bleeding are in the same reservoir. 
     
     
         30 . A method according to  claim 28 , characterised in that a progestogen, or a drug having a progestogenic activity, and a therapeutically active substance capable of preventing or suppressing abnormal and/or irregular endometrial bleeding are in separate reservoirs. 
     
     
         31 . A method according to any of the  claims 28 - 30 , characterised in that the progestogen, or a drug having a progestogenic activity, is selected from the group of progesterone and its derivatives, cyproterone acetate, desogestrel, etonogestrel, levonorgestrel, lynestrenol, medroxyprogesterone acetate, norethisterone, norethisterone acetate, norgestimate, drospirenone, gestodene, 19-nor-17-hydroxy progesterone esters, 17α-ethinyltestosterone and derivatives thereof, 17α-ethinyl-19-nor-testosterone and derivatives thereof, ethynodiol diacetate, dydrogesterone, norethynodrel, allylestrenol, medrogestone, norgestrienone, ethisterone and dl-norgestrel. 
     
     
         32 . A method according to  claim 31 , characterised in that the progestogen, or a drug having a progestogenic activity, is levonorgestrel. 
     
     
         33 . A method according to  claim 28 , characterized in that the core of the reservoir comprises two or more segments, each segment consisting of a same or different polymer composition and comprising a progestogen, or a drug having a progestogenic activity, or at least one therapeutically active substance capable of preventing or suppressing abnormal and/or irregular endometrial bleeding. 
     
     
         34 . A method according to  claim 33 , characterized in that at least two of the segments are separated by an inert membrane or segment consisting essentially of a same or different polymer composition. 
     
     
         35 . A method according to  claim 28 , characterized in that the polymer compositions of the core, membrane and inert separating membrane or segment in the delivery system are selected from the group consisting of
 a polymer composition comprising poly(dimethylsiloxane),   a polymer composition comprising a siloxane-based polymer comprising 3,3,3-trifluoropropyl groups attached to the Si-atoms of the siloxane units,   a polymer composition comprising poly(alkylene oxide) groups, said poly(alkylene oxide) groups being present as alkoxy-terminated grafts or blocks linked to the polysiloxane units by silicon-carbon bonds,   
       or a mixture of these forms, and
 a combination of at least two thereof. 
 
     
     
         36 . A method according to  claim 35 , characterized in that in the siloxane-based polymer from 1 to approximately 50% of the substituents attached to the Si-atoms of the siloxane units are 3,3,3-trifluoropropyl groups. 
     
     
         37 . A method according to  claim 35 , characterized in that the poly(alkylene oxide) groups are poly(ethylene oxide) groups. 
     
     
         38 . An intrauterine delivery system for the controlled release of progestogen or a drug having a progestogenic activity over a prolonged period of time and at a level required for contraception, wherein the intrauterine delivery system comprises a body construction and at least one reservoir comprising a core and optionally a membrane encasing the core, the core and membrane essentially consisting of a same or different polymer composition, characterized in that said intrauterine delivery system additionally comprises at least one therapeutically active substance capable of preventing or suppressing abnormal and/or irregular endometrial bleeding wherein said substance is selected from the group consisting of tranexamic acid, mefenamic acid, danazol and an angiogenesis inhibitor. 
     
     
         39 . The intrauterine delivery system according to  claim 38 , characterised in that a progestogen, or a drug having a progestogenic activity, and a therapeutically active substance capable of preventing or suppressing abnormal and/or irregular endometrial bleeding are in the same reservoir. 
     
     
         40 . The intrauterine delivery system according to  claim 38 , characterised in that a progestogen, or a drug having a progestogenic activity, and a therapeutically active substance capable of preventing or suppressing abnormal and/or irregular endometrial bleeding are in separate reservoirs. 
     
     
         41 . The intrauterine delivery system according to  claim 38 , characterised in that the progestogen, or a drug having a progestogenic activity, is selected from the group of progesterone and its derivatives, cyproterone acetate, desogestrel, etonogestrel, levonorgestrel, lynestrenol, medroxyprogesterone acetate, norethisterone, norethisterone acetate, norgestimate, drospirenone, gestodene, 19-nor-17-hydroxy progesterone esters, 17α-ethinyltestosterone and derivatives thereof, 17α-ethinyl-19-nor-testosterone and derivatives thereof, ethynodiol diacetate, dydrogesterone, norethynodrel, allylestrenol, medrogestone, norgestrienone, ethisterone and dl-norgestrel. 
     
     
         42 . The intrauterine delivery system according to  claim 41 , characterised in that the progestogen, or a drug having a progestogenic activity, is levonorgestrel. 
     
     
         43 . The intrauterine delivery system according to  claim 38 , characterized in that the core of the reservoir comprises two or more segments, each segment consisting of a same or different polymer composition and comprising a progestogen, or a drug having a progestogenic activity, or at least one therapeutically active substance capable of preventing or suppressing abnormal and/or irregular endometrial bleeding. 
     
     
         44 . The intrauterine delivery system according to  claim 43 , characterized in that at least two of the segments are separated by an inert membrane or segment consisting essentially of a same or different polymer composition. 
     
     
         45 . The intrauterine delivery system according to  claim 38 , characterized in that the polymer compositions of the core, membrane and inert separating membrane or segment in the delivery system are selected from the group consisting of
 a polymer composition comprising poly(dimethylsiloxane),   a polymer composition comprising a siloxane-based polymer comprising 3,3,3-trifluoropropyl groups attached to the Si-atoms of the siloxane units,   a polymer composition comprising poly(alkylene oxide) groups, said poly(alkylene oxide) groups being present as alkoxy-terminated grafts or blocks linked to the polysiloxane units by silicon-carbon bonds,   
       or a mixture of these forms, and
 a combination of at least two thereof. 
 
     
     
         46 . The intrauterine delivery system according to  claim 45 , characterized in that in the siloxane-based polymer from 1 to approximately 50% of the substituents attached to the Si-atoms of the siloxane units are 3,3,3-trifluoropropyl groups. 
     
     
         47 . The intrauterine delivery system according to  claim 45 , characterized in that the poly(alkylene oxide) groups are poly(ethylene oxide) groups. 
     
     
         48 . Use of progestogen or a drug having progestogenic activity and at least one therapeutically active substance capable of preventing or suppressing abnormal and/or irregular bleeding wherein said substance is selected from the group consisting of tranexamic acid, mefenamic acid, danazol and an angiogenesis inhibitor, for the preparation of an intrauterine delivery system for contraception and for reducing menstrual bleeding problems and for inducing amenorrhea. 
     
     
         49 . Progestogen or a drug having progestogenic activity and at least one therapeutically active substance capable of preventing or suppressing abnormal and/or irregular bleeding wherein said substance is selected from the group consisting of tranexamic acid, mefenamic acid, danazol and an angiogenesis inhibitor, for use in a method for contraception and for reducing menstrual bleeding problems and for inducing amenorrhea, wherein said progestogen or a drug having a progestogenic activity and at least one therapeutically active substance capable of preventing or suppressing abnormal and/or irregular bleeding are released from an intrauterine delivery system over a prolonged period of time. 
     
     
         50 . The use according to  claim 48  or  49  wherein the intrauterine delivery system comprises a body construction and at least one reservoir comprising a core and optionally a membrane encasing the core.