Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1999-08-09
2001-05-29
Cook, Rebecca (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S227800, C514S336000, C514S342000, C514S343000, C514S880000
Reexamination Certificate
active
06239164
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to methods of treating hair loss and stimulating the revitalization and germination of hair. More particularly, it relates to methods of administering pyrrolidine carboxylate compounds as novel agents for treatment of hair loss and for the germination and revitalization of hair.
2. Description of the Related Art
Hair loss occurs in a variety of situations. These situations include male pattern alopecia, alopecia senilis, alopecia areata, diseases accompanied by basic skin lesions or tumors, or systematic disorders such as nutritional disorders and internal secretion disorders. The mechanisms causing hair loss are very complicated but in some instances can be attributed to aging, genetic disposition, the activation of male hormones, the loss of blood supply to hair follicles, and scalp abnormalities.
The immunosuppressant drugs FK506, rapamycin and cyclosporin are well-known as potent T-cell specific immunosuppressants, and are effective against graft rejection after organ transplantation. It has been reported that topical, but not oral, application of FK506 (Yamamoto et al, J. Invest. Dermatol, 1994, 102, 160-164; Jiang et al., J. Invest. Dermatol. 1995, 104, 523-525) and cyclosporin (Iwabuchi et al, J. Dermatol. Sci. 1995, 9, 64-69) stimulated hair growth in a dose-dependent manner. One form of hair loss, alopecia areata, is known to be associated with autoimmune activities, hence, immunomodulatory compounds were expected to demonstrate efficacy for treating that type of hair loss. The hair growth stimulating effects of FK506 have been the subject of an international patent filing covering FK506 and structures related thereto for hair growth stimulation (Honbo et al., EP 0 423 714 A2). Honbo et al. discloses the use of relatively large tricyclic compounds, known for their immunosuppressive effects, as hair revitalizing agents.
The hair growth and revitalization effects of FK506 and related agents are disclosed in many U.S. patents. (Goulet et al., U.S. Pat. No. 5,258,389; Luly et al., U.S. Pat. No. 5,457,111; Goulet et al., U.S. Pat. No. 5,532,248; Goulet et al., U.S. Pat. No. 5,189,042; and Ok et al., U.S. Pat. No. 5,208,241; Rupprecht et al., U.S. Pat. No. 5,284,840; Organ et al., U.S. Pat. No. 5,284,877). These patents claim FK506 related compounds. Although they do not claim methods of hair revitalization, they disclose the known use of FK506 for effecting hair growth. Similar to FK506 (and the claimed variations in the Honbo et al. patent) the compounds claimed in these patents are relatively large. Further, the cited patents relate to immunomodulatory compounds for use in autoimmune related diseases, for which FK506's efficacy is well known.
Other U.S. Patents disclose the use of cyclosporin and related compounds for hair revitalization. (Hauer et al., U.S. Pat. No. 5,342,625; Eberle, U.S. Pat. No. 5,284,826; Hewitt et al., U.S. Pat. No. 4,996,193). These patents also relate to compounds useful for treating autoimmune diseases and cite the known use of cyclosporin and related immunosuppressive compounds for hair growth.
However, immunosuppressive compounds by definition suppress the immune system and also exhibit other toxic side effects. Accordingly, there is a need for non-immunosuppressant, small molecule compounds which are useful as hair revitalizing compounds.
Hamilton and Steiner disclose novel pyrrolidine carboxylate compounds which bind to the immunophilin FKBP12 and stimulate nerve growth but which lack immunosuppressive effects, in U.S. Pat. No. 5,614,547. Unexpectedly, it has been discovered that these non-immunosuppressant compounds promote hair growth with an efficacy similar to FK506. Yet their novel small molecule structure and non-immunosuppressive properties differentiate them from FK506 and related immunosuppressive compounds found in the is prior art.
SUMMARY OF THE INVENTION
The present invention relates to methods of treating hair loss by administering pyrrolidine carboxylate and pyrrolidine amide compounds, and particularly N-glyoxyl prolyl esters, as novel hair revitalizing, germination, and regrowth compounds. Although these compounds are known as having an affinity for FKBP-type immunophilins, they are unexpectedly potent as hair growth agents. A key feature of the compounds of the present invention is that they do not exert any significant immunosuppressive activity in addition to their hair growth activity.
A preferred embodiment of this invention is a method of revitalizing hair growth which comprises: administering to an animal an effective amount of a non-immunosuppressive pyrrolidine carboxylate and pyrrolidine amide compound.
Another preferred embodiment of this invention is a method of hair germination which comprises: administering to an animal an effective amount of a non-immunosuppressive pyrrolidine carboxylate pyrrolidine amide compound.
Another preferred embodiment of this invention is a method of preventing hair loss which comprises: administering to an animal an effective amount of a pyrrolidine carboxylate and pyrrolidine amide compound.
Another preferred embodiment of this invention is the treatment of male pattern alopecia, alopecia senilis, alopecia areata, hair loss from skin lesions or tumors, and hair loss from systematic disorders such as nutritional disorders and internal secretion disorders which comprises: administering to an animal an effective amount of a pyrrolidine carboxylate and pyrrolidine amide compound.
Another preferred embodiment of this invention is the treatment of hair loss resulting from chemotherapy which comprises: administering to an animal an effective amount of a pyrrolidine carboxylate and pyrrolidine amide compound.
Another preferred embodiment of this invention is the treatment of hair loss resulting from radiation which comprises: administering to an animal an effective amount of a pyrrolidine carboxylate and pyrrolidine amide compound.
Another preferred embodiment of this invention is the treatment of hair loss which comprises: administering to an animal an effective amount of a pyrrolidine carboxylate and pyrrolidine amide compound.
Yet another embodiment of this invention is treating hair loss and stimulating revitalization and germination which comprises: administering to an animal an effective amount of a N-(glyoxyl)prolyl ester.
REFERENCES:
patent: 4945093 (1990-07-01), Maignan et al.
patent: 4996193 (1991-02-01), Hewitt et al.
patent: 5189042 (1993-02-01), Goulet et al.
patent: 5192773 (1993-03-01), Armistead et al.
patent: 5208241 (1993-05-01), Ok et al.
patent: 5236950 (1993-08-01), Aoyama et al.
patent: 5258389 (1993-11-01), Goulet et al.
patent: 5284826 (1994-02-01), Eberle
patent: 5284840 (1994-02-01), Rupprecht et al.
patent: 5284877 (1994-02-01), Organ et al.
patent: 5292747 (1994-03-01), Davis et al.
patent: 5342625 (1994-08-01), Hauer et al.
patent: 5385918 (1995-01-01), Connell et al.
patent: 5457111 (1995-10-01), Luly et al.
patent: 5470878 (1995-11-01), Michnick et al.
patent: 5506228 (1996-04-01), Norton et al.
patent: 5532248 (1996-07-01), Goulet et al.
patent: 5614547 (1997-03-01), Hamilton et al.
patent: 0 423 714 A2 (1991-04-01), None
patent: 0 564 924 A2 (1993-10-01), None
patent: WO 96/41609 (1996-12-01), None
patent: WO 97/36869 (1997-10-01), None
CA 113:103206, Aoyama et al, Aug. 25, 1989.*
CA118:233885, Koga et al, Sep. 3, 1992.*
CA111:134182, Maignan et al, Feb. 9, 1989.*
CA 125 : 293042, Ahlowaha et al, Sep. 6, 1996.*
Birkenshaw, T.N. et al., “Synthetic FKBP12 Ligands. Design and Synthesis of Pyranose Replacements,”Bioorganic&Medicinal Chemistry Letters, (1994) 4:21, 2501-2506.
Caffrey, M.V. et al., “Synthesis and Evaluation of Dual Domain Macrocyclic FKBP12 Ligands,”Bioorganic&Medicinal Chemistry Letters, (1994) 4:21, 2507-2510.
Hauske, J.R. et al., “Design and Sythesis of Novel FKBP Inhibitors,”J. of Medicinal Chemistry, (1992) 35, 4284-4296.
Holt, D.A. et al., “Design, Synthesis, and Kinetic Evaluation of High-Affinity FKBP Ligands and the X-Ray Crystal Structures of Their Comp
Hamilton Gregory S.
Steiner Joseph P.
Cook Rebecca
GPI Nil Holdings Inc.
Heiman Lee C.
Juneau Todd L.
Nath Gary M.
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