The invention further features a kit including a composition formulated for topical administration including (i) a small molecule EGFR inhibitor selected from leflunomide, gefitinib, erlotinib, lapatinib, canertinib, vandetanib, CL-387785, PKI166, pelitinib, HKI-272, and HKI-357; and (ii) an additional biologically active agent selected from an antihistamine, an anti-inflammatory, a retinoid, an anti-androgen, an immunosuppressant, a channel opener, an antibiotic, and an antimicrobial. In one embodiment, the small molecule EGFR inhibitor is gefitinib or erlotinib and the additional biologically active agent is a channel opener selected from minoxidil, diazoxide, and phenytoin.
Time related stuff from the patent:
for applying the composition to the skin of a subject once or twice daily, for applying the composition to the skin of a subject for at least 2, 3, 4, 5, 6, 7, 8, 9, or even 10 consecutive days, for administering the composition during the night, or administering the composition during the day. The invention features a method for generating a hair follicle or stimulating a hair growth on the skin of a subject by (i) disrupting the skin of the subject (for example, resulting in the induction of reepithelialization of the skin of the subject) and (ii) contacting the cells of the skin with a small molecule EGFR inhibitor, or a metabolite thereof, in an amount sufficient to generate hair follicles or stimulate hair growth on the skin. In certain embodiments, step (a) is performed less than two weeks, 10 days, 8 days, 5 days, or even 3 days prior to step (b). In other embodiments, step (a) is performed simultaneous with, or more than one day, two days, 3 days or one week after step (b).
The very simpleist embodiment of the patent:
In a particular embodiment of the methods, kits, and compositions of the invention, the EGFR inhibitor is administered, formulated, or is part of a kit with an anti-androgen (e.g., finasteride ) and a channel opener (e.g., minoxidil).
In still another embodiment of the methods, kits, and compositions of the invention, the topical formulation is a cream, lotion, stick, ointment, gel, spray, foam, patch, aerosol, wound dressing, or drop.
The disruption of the epidermis can be induced between 3-12 days (e.g., 4-12, 5-12, 4-11, 6-11, 6-10, 6-9, 7-8, 5-11, 5-10, or 7-10 days) prior to the addition of the compositions of the invention.
Any of the above-described methods may be used to remove a precise amount of epidermal tissue. For example, the methods of abrasion described herein may be used to achieve:
• Removal of the stratum comeum through removal of the first 10-30 μm of dead skin cells.
I’d like to add an editorial note here…3 days after wouding, or better yet 4, is likely when the skin will have re-epilithialized unless you took off more than the stratum cornelium in a human being. Hair germs were detected in human skin on the SCID mice at day 7. We heal quicker than mice do. So, on about day 4 or 5, one can probably feel reasonably safe to use the egf blocker and minox. One can be on finas for the entire time…
Most important example in the patent:
Example 7: EDIHN induces new hair follicles in human skin. Grafting. Discarded human adult scalp from the preauricular area obtained from plastic surgery was grafted onto immunodeficient (scid) mice. The graft was bandaged and allowed to heal, then was used in the wound healing study 3 months after grafting.
Results: To determine whether human skin responded to EDIHN as did mouse skin, human skin was grafted onto SCID (immuno-defϊcient) mice and subjected to depilation by plucking and wound induction three days later. Seven days following wound induction, formation of new HF was observed in the human skin (Figure 2 IA; arrows indicate new HF) by hematoxylin and eosin staining of paraffin embedded tissue sections.
In additional experiments, adult human skin was grafted onto mice, abraded, and examined at 7 days post-abrasion. New HF were generated in the human skin, which mimicked normal hair follicle formation during fetal development, as evidenced by staining for S100A6 or S100A4 (Figure 21B).
The results of this Example show that EDIHN can be used to generate hair growth in human skin as for mouse skin