Use of sex steroid function modulators to treat wounds and fibrotic disorders

Abstract

The present application relates to the use of compounds that influence the sex hormone system for the treatment of wounds and/or fibrotic disorders. Preferred compounds for use in such treatments are steroid hormones and especially the oestrogens.

1 . The use of a compound that promotes oestrogenic activity in the manufacture of a medicament for accelerating the healing of wounds of tissues other than the genito-urinary tract.  
     
     
         2 . The use of a compound that promotes oestrogenic activity in the manufacture of a medicament for accelerating the healing of skin wounds.  
     
     
         3 . The use as claimed in claims  1  or  2  wherein said compound is an oestrogen or an oestrogen receptor agonist selected from ethinyloestradiol, dienoestrol, mestranol, oestradiol; oestriol, conjugated oestrogens, piperazine oestrone sulphate, stilboestrol, fosfesterol tetrasodium, polyestradial phosphate, tibolone or a phytoestrogen.  
     
     
         4 . The use as claimed in  claim 1  or  2  wherein said compound is one of: an inhibitor of oestrogen breakdown, an inhibitor of oestrogen receptor agonist breakdown; or a modulator of the activity of luteinising hormone, follicle stimulating hormone or chorionic gonadotrophin.  
     
     
         5 . The use as claimed in  claim 3  wherein said compound is an oestrogen hormone.  
     
     
         6 . The use as claimed in  claim 5  wherein said compound is 17 β-Oestradiol.  
     
     
         7 . The use as claimed in  claim 6  wherein the medicament contains between 0.01% and 4% 17 β-Oestradiol.  
     
     
         8 . The use according to any preceding claim wherein the wound is an acute wound.  
     
     
         9 . The use according to  claim 8  wherein the wound is a penetrative injury, a burn or resulting from elective surgery.  
     
     
         10 . The use according to any one of claims  1 - 7  wherein the wound is a chronic wound.  
     
     
         11 . The use according to  claim 8  wherein the wound is a diabetic, venous or decubitus ulceration.  
     
     
         12 . The use of a compound other than tamoxifen that inhibits oestrogenic activity for the manufacture of a medicament for inhibiting fibrosis.  
     
     
         13 . The use as claimed in  claim 12  wherein said inhibitor of oestrogenic activity is an oestrogen receptor antagonist.  
     
     
         14 . The use as claimed in  claim 13  wherein said oestrogen receptor antagonist is clomiphene citrate or cyclofenil.  
     
     
         15 . The use as claimed in  claim 12  wherein said inhibitor of oestrogenic activity is an inhibitor of oestrogen production selected from the group consisting of anastrozole. 4-hydroxy androstenedione, exemestane, oestrone-3-O-sulphate, fadrazole hydrochloride or formestane) or a phytoestrogen.  
     
     
         16 . The use according to any one of claims  12 - 15  for reducing or preventing scarring.  
     
     
         17 . The use of a compound that promotes androgenic activity in the manufacture of a medicament for accelerating the healing of wounds.  
     
     
         18 . The use as claimed in  claim 17  wherein the wound is a skin wound.  
     
     
         19 . The use as claimed in claims  17  or  18  wherein said compound is an androgen hormone or androgen receptor agonist selected from testosterone, dihydrotestosterone, 5α-androstanediol, testosterone undecanoate, testosterone enanthate, testosterone esters, testosterone proprionate, mesterolone, danazol and gesttrinone.  
     
     
         20 . The use as claimed in claims  17  or  18  wherein said compound is one of: an inhibitor of androgen breakdown or an inhibitor of androgen receptor agonist breakdown; or a modulator of the activity of luteinising hormone, follicle stimulating hormone or chorionic gonadotrophin.  
     
     
         21 . The use as claimed in  claim 20  wherein the compound is an inhibitor of androgen breakdown or an inhibitor of androgen receptor agonist breakdown and is aminoglutethamide.  
     
     
         22 . The use of a compound that inhibits androgenic activity in the manufacture of a medicament for inhibiting fibrosis.  
     
     
         23 . The use as claimed in  claim 22  wherein said compound is an androgen receptor antagonist.  
     
     
         24 . The use as claimed in  claim 23  wherein said compound is cyproterone acetate or flutamide.  
     
     
         25 . The use as claimed in  claim 22  wherein said compound is an inhibitor of androgen production.  
     
     
         26 . The use as claimed in any one of claims  22 - 25  for reducing or preventing scarring.  
     
     
         27 . The use of a compound that promotes progesterone activity in the manufacture of a medicament for inhibiting fibrosis.  
     
     
         28 . The use as claimed in  claim 27  wherein said compound is progesterone or a progesterone receptor agonist selected from the group of compounds consisting of allyoestrenol, desogestrel, dydrogesterone, ethynodiol diacetate, gestodene, gestranol hexanoate, hydroxyprogesterone hexanoate, levonorgestrel, megestrol acetate, medroxyprogesterone acetate, norethisterone, norethisterone acetate, norethisterone enanthate, norgestimate or norgesterel.  
     
     
         29 . The use as claimed in  claim 27  wherein the compound is one of: an inhibitor of progesterone breakdown or an inhibitor of progesterone receptor agonist breakdown; or a modulator of the activity of luteinising hormone, follicle stimulating hormone or chorionic gonadotrophin.  
     
     
         30 . The use as claimed in any one of claims  27 - 29  for reducing or preventing scarring.  
     
     
         31 . The use of a sex steroid hormone precursor in the manufacture of a medicament for accelerating the healing of wounds.  
     
     
         32 . The use as claimed in  claim 31  wherein said compound is a precursor of an oestrogen or androgenic sex steroid hormone.  
     
     
         33 . The use as claimed in  claim 32  wherein said compound is Dehydroepiandrosterone (DHEA) or DHEA sulphate (DHEAS).  
     
     
         34 . The use as claimed in any preceding claim for non-systemic application.  
     
     
         35 . The use as claimed in any preceding claim for the manufacture of a medicament in the form of a liquid, ointment, cream, gel, hydrogel, powder, aerosol or implant.  
     
     
         36 . The use as claimed in any one of  claims 1  to  34  for the manufacture of a medicament in the form of eye drops.  
     
     
         37 . The use as claimed in any preceding claim wherein the medicament contains 0.001% to 4% by weight of said compound.  
     
     
         38 . A method of accelerating wound healing comprising providing at the site of a wound or fibrotic disorder a therapeutically effective amount of a compound as defined in any one of claims  1 - 11 ,  17 - 21  and  31 - 33 .  
     
     
         39 . A method of inhibiting fibrosis comprising providing at the site of a wound or fibrotic disorder a therapeutically effective amount of a compound as defined in any one of claims  12 - 16  and  22 - 30 .  
     
     
         40 . (New) A method of accelerating the healing of wounds comprising administering to a person in need thereof a compound that promote androgenic activity.  
     
     
         41 . (New) The method as claimed in  claim 40  wherein the wound is a skin wound.  
     
     
         42 . (New) The method as claimed in  claim 40  wherein said compound is an androgen hormone or androgen receptor agonist selected from the group consisting of: 
 testosterone, dihydrotestosterone,  5 α-androstanediol, testosterone undecanoate, testosterone proprionate, mesterolone, danazol and gesttrinone.  
 
     
     
         43 . (New) The method as claimed in  claim 40  wherein said compound is selected from the group consisting of: 
 an inhibitor of androgen breakdown or an inhibitor of androgen receptor agonist breakdown; a modulator of the activity of luteinising hormone, follicle stimulating hormone or chorionic gonadotrophin.  
 
     
     
         44 . (New) The method as claimed in  claim 43  wherein said compound is an inhibitor of androgen breakdown or an inhibitor of androgen receptor agonist breakdown and is aminoglutethamide.  
     
     
         45 . (New) The method as claimed in  claim 40  wherein said compound is applied non-systemically.  
     
     
         46 . (New) The method as claimed in  claim 40  wherein said compound is formulated as a liquid, ointment, cream, gel, hydrogel, powder, aerosol or implant.  
     
     
         47 . (New) The method as claimed in  claim 40  wherein said compound is formulated as eye drops.  
     
     
         48 . (New) The method as claimed in  claim 40  wherein a medicament comprising  0 . 001 % to  4 % by weight of said compound is administered to the persom.  
     
     
         49 . (New) A method of inhibiting fibrosis comprising administering to a person in need thereof a compound that inhibits androgenic activity.  
     
     
         50 . (New) The method as claimed in  claim 49  wherein said compound is an androgen receptor antagonist.  
     
     
         51 . (New) The method as claimed in  claim 50  wherein said compound is cyproterone acetate or flutamide.  
     
     
         52 . (New) The method as claimed in  claim 49  wherein said compound is an inhibitor of androgen production.  
     
     
         53 . (New) The method as claimed in  claim 49  wherein said compound is applied non-systemically.  
     
     
         54 . (New) The method as claimed in  claim 49  wherein said compound is formulated as a liquid, ointment, cream, gel, hydrogel, powder, aerosol or implant.  
     
     
         55 . (New) The method as claimed in  claim 49  wherein said compound is formulated as eye drops.  
     
     
         56 . (New) The method as claimed in  claim 49  wherein a medicament comprising 0.001% to 4% by weight of said compound is administered to the person.  
     
     
         57 . (New) The method as claimed in  claim 49  for reducing or preventing scarring.  
     
     
         58 . (New) A method of inhibiting fibrosis comprising administering to a person in need thereof a compound that promotes progesterone activity.  
     
     
         59 . (New) The method as claimed in  claim 58  wherein said compound is progesterone or a progesterone receptor agonist selected from the group of compounds consisting of: allyoestrenol, desogestrel, dydrogesterone, ethynodiol diacetate, gestodene, gestranol hexanoate, hydroxyprogesterone hexanoate, levonorgestrel, megestrol acetate, medroxyprogesterone acetate, norethisterone, norethisterone acetate, norethisterone enanthate, norgestimate or norgesterel.  
     
     
         60 . (New) The method as claimed in  claim 58  wherein the compound is selected from the group of compounds consisting of: an inhibitor of progesterone breakdown or an inhibitor of progesterone receptor agonist breakdown; or a modulator of the activity of luteinising hormone, follicle stimulating hormone or chorionic gonadotrophin.  
     
     
         61 . (New) The method as claimed in  claim 58  wherein said compound is applied non-systemically.  
     
     
         62 . (New) The method as claimed in  claim 58  wherein said compound is formulated as a liquid, ointment, cream, gel, hydrogel, powder, aerosol or implant.  
     
     
         63 . (New) The method as claimed in  claim 58  wherein said compound is formulated as eye drops.  
     
     
         64 . (New) The method as claimed in  claim 58  wherein a medicament comprising 0.001% to 4% by weight of said compound is administered to the person.  
     
     
         65 . (New) The method as claimed in  claim 58  for reducing or preventing scarring.  
     
     
         66 . (New) A method of accelerating the healing of wounds comprising administering to a person in need thereof a sex steroid hormone precursor.  
     
     
         67 . (New) The method as claimed in  claim 66  wherein said compound is a precursor of an oestrogen or androgenic sex steroid hormone.  
     
     
         68 . (New) The method as claimed in  claim 66  wherein said compound is Dehydroepiandrosterone (DHEA) or DHEA sulphate (DHEAS).  
     
     
         69 . (New) The method as claimed in  claim 66  wherein said compound is applied non-systemically.  
     
     
         70 . (New) The method as claimed in  claim 66  wherein said compound is formulated as a liquid, ointment, cream, gel, hydrogel, powder, aerosol or implant.  
     
     
         71 . (New) The method as claimed in  claim 66  wherein said compound is formulated as eye drops.  
     
     
         72 . (New) The method as claimed in  claim 66  wherein a medicament comprising 0.001% to 4% by weight of said compound is administered to the person.