Methods For Treating Baldness And Promoting Hair Growth

Abstract

The invention relates to methods of treating baldness, treating alopecia, promoting hair growth, and/or promoting hair follicle development and/or activation or stimulation on an area of the skin of a subject (for example, a human) by subjecting said area of the skin to integumental perturbation. Integumental perturbation can be used in combination with other treatments for promoting hair growth. The invention provides devices for integumental perturbation for promoting hair growth, and provides pharmaceutical compositions for use in combination with integumental perturbation for promoting hair growth.

1 . A method for promoting vellus hair growth in a human subject suffering from baldness, wherein the method comprises:
 a) integumental perturbation of an area of the bald scalp of the human subject; and   b) administering a hair growth promoting agent.   
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the hair growth promoting agent is selected from the group consisting of: a potassium channel opener, an ATP-sensitive potassium channel (KATP opener), minoxidil, diazoxide, or phenyloin, a 5α-reductase inhibitor, finasteride, dutasteride (e.g., Avodart), turosteride, bexlosteride, izonsteride, epristeride, epigallocatechin, MK-386, azelaic acid, FCE 28260, and SKF 105,111, ketoconazole, fluconazole, spironolactone, flutamide, diazoxide, 17-alpha-hydroxyprogesterone, 11-alpha-hydroxyprogesterone, ketoconazole, RU58841, dutasteride (marketed as Avodart), fluridil, or QLT-7704, an antiandrogen oligonucleotide, a prostaglandin F2α analogs, prostaglandin analogs, a prostaglandin, bimatoprost (e.g., Latisse, Lumigan), latanoprost (trade name Xalatan), travoprost (trade name Travatan), tafluprost, unoprostone, dinoprost (trade name Prostin F2 Alpha), AS604872, BOL303259X, PF3187207, carboprost (trade name Hemabate), kopexil (for example, the product Keranique™), CaCl2, botilinum toxin A, adenosine, ketoconazole, DoxoRx, Docetaxel, FK506, GP11046, GP11511, LGD 1331, ICX-TRC, MTS-01, NEOSH101, HYG-102440, HYG-410, HYG-420, HYG-430, HYG-440, spironolactone, CB-03-01, RK-023, Abatacept, Viviscal®, MorrF, ASC-J9, NP-619, AS101, Metron-F-1, PSK 3841, Targretin (e.g. 1% gel), MedinGel, PF3187207, BOL303259X, AS604872. THG11331, PF-277343, PF-3004459, Raptiva, caffeine, coffee, a herb (such as, e.g., saw palmetto,  glycine soja, Panax ginseng, Castanea Sativa, Arnica Montana, Hedera Helix Geranium Maculatum ), triamcinolone acetonide, a topical irritant (e.g., anthralin) or sensitizer (e.g., squaric acid dibutyl ester [SADBE] or diphenyl cyclopropenone [DPCP]), clomipramine, unsaturated fatty acids (e.g. gamma linolenic acid), a fatty acid derivative, a thickener (such as, e.g. carbomer, glycol distearate, cetearyl alcohol), a hair loss concealer, niacin, nicotinate esters and salts, adenosine, methionine, an androgen receptor inhibitor, a copper peptide, a compound with superoxide dismutation activity, an agent that increases nitric oxide production (e.g. arginine, citrulline, nitroglycerin, amyl nitrite, or sildenafil (Viagra)), a compound that mobilizes bone marrow-derived stem cells (e.g., growth factors such as G-CSF and/or chemical agents such as plerixafor (Mozobil®)), a compound that regulates the differentiation of stem cells into gender-specific specialized human hair follicles (e.g., finasteride, fluconazole, spironolactone, flutamide, diazoxide, 11-alpha-hydroxyprogesterone, ketoconazole, RU58841, dutasteride, fluridil, or QLT-7704, an antiandrogen oligonucleotide, cyoctol, topical progesterone, topical estrogen, cyproterone acetate, ru58841, combination 5α-reductase inhibitors, oral contraceptive pills), an antiestrogen, an estrogen, or estrogen-like drug, an anti-oxidants (e.g., glutathione, ascorbic acid, tocopherol, uric acid, or polyphenol antioxidants), inhibitors of reactive oxygen species (ROS) generation (e.g., superoxide dismutase inhibitors; stimulators of ROS breakdown, such as selenium; mTOR inhibitors, such as rapamycin: or sirtuins or activators thereof, such as resveratrol, or other SIRT1. SIRT3 activators, or nicotinamide inhibitors), an agent that induces an immune response or causes inflammation (e.g., tetanus toxoid, topical non-specific irritants (anthralin), or sensitizers (squaric acid dibutyl ester [SADBE] and diphenyl cyclopropenone [DPCP]), and an antiapoptotic compound. 
     
     
         4 . The method of  claim 1 , wherein, at 3 months after the integumental perturbation, the area of the scalp of the subject has at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or at least 100% more vellus hair compared to immediately before the integumental perturbation. 
     
     
         5 . The method of  claim 1  further comprising: applying a wound healing dressing. 
     
     
         6 . The method of  claim 5 , wherein the wound healing dressing is non-occlusive. 
     
     
         7 . The method of  claim 6 , wherein the wound healing dressing is a cream, gel, lotion, emulsion, suspension, oil, non-aqueous solution, aqueous solution, or drop. 
     
     
         8 . The method of  claim 5 , wherein the wound healing dressing is applied for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or 31 days after the integumental perturbation. 
     
     
         9 . The method of  claim 1 , wherein the hair growth promoting agent is administered topically. 
     
     
         10 . The method of  claim 1 , wherein the hair growth promoting agent is administered once reepithelialization is completed, or 1, 2, 3, 4, 5, 6, 7, 8, 9. 10, 11, 12, 13, 14, 15, or 16 weeks after integumental perturbation. 
     
     
         11 . The method of  claim 1 , wherein the hair growth promoting agent is administered before and after integumental perturbation. 
     
     
         12 . The method of  claim 1 , wherein the hair growth promoting agent is administered for a period of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 weeks. 
     
     
         13 . The method of  claim 1 , wherein the integumental perturbation is performed by dermabrasion. 
     
     
         14 . The method of  claim 13 , wherein the dermabrasion is performed until pinpoint bleeding occurs. 
     
     
         15 . The method of  claim 13 , wherein the dermabrasion is performed to a depth of between 30 μm to 200 μm. 
     
     
         16 . The method of  claim 13 , wherein the maximum depth of the dermabrasion is 30, 40, 50, 60, 70, 80, 85, 90, 95, 100, 105, 110, 120, 130, 140, 150, 160, 170, 180, 190 or 200 μm. 
     
     
         17 . The method of  claim 13 , wherein the dermabrasion step is performed using a dermabrader that comprises:
 (i) a dermabrasion tip on a dermabrasion hand piece,
 (a) wherein the dermabrasion tip comprises:
 a housing having a first opening substantially aligned with a longitudinal axis of the housing and a second opening disposed at an angle to the longitudinal axis; 
 a transmission unit disposed in the housing, the transmission unit comprising:
 a first set of gears; 
 a linkage assembly adjacent to the first set of gears; and 
 a second set of gears adjacent to the linkage assembly; and 
 
 a platform to receive an abrasive disk, 
 wherein the transmission unit converts a rotational motion of the dermabrasion hand piece to a reciprocating motion causing the platform to reciprocate; or 
 
 (b) wherein the dermabrasion tip comprises:
 a housing having a first opening substantially aligned with a longitudinal axis of the housing and a second opening disposed at an angle to the longitudinal axis; 
 a transmission unit disposed in the housing, the transmission unit comprising:
 a first set of gears; 
 a second set of gears; and 
 a linkage assembly disposed between the first set of gears and the second set of gears; and 
 
 an abrasive disk, 
 wherein the transmission unit converts a rotational motion of the dermabrasion hand piece to a reciprocating motion causing the abrasive disk to reciprocate, and wherein the abrasive disk is disposed at an angle with the longitudinal axis of the housing; or 
 
 (c) wherein the dermabrasion tip comprises:
 a housing having a first opening substantially aligned with a longitudinal axis of the housing and a second opening disposed at an angle to the longitudinal axis; 
 a transmission unit disposed in the housing, the transmission unit comprising:
 a first set of bevel gears; 
 a linkage assembly adjacent to the first set of gears, the linkage assembly including an input drive wheel, an output drive wheel and at least one coupling rod; and 
 a second set of bevel gears adjacent to the linkage assembly; and 
 
 an abrasive disk, 
 wherein the transmission unit converts a rotational motion of the dermabrasion hand piece to a reciprocating motion causing the abrasive disk to reciprocate, and 
 wherein the abrasive disk is disposed at an angle with the longitudinal axis of the housing; or 
 
 (d) wherein the dermabrasion tip comprises:
 a housing having a first opening substantially aligned with a longitudinal axis of the housing and a second opening disposed at an angle to the longitudinal axis; 
 a means for converting a rotational motion of the dermabrasion hand piece to a reciprocating motion; and 
 an abrasive disk, 
 wherein the abrasive disk is disposed at an angle with the longitudinal axis of the housing; or 
 
   (ii) (a) a control unit;
 (b) a hand piece having a longitudinal axis and comprising:
 a housing; 
 a transmission unit disposed in the housing, the transmission unit comprising:
 a first set of gears; 
 a linkage assembly adjacent to the first set of gears; and 
 a second set of gears adjacent to the linkage assembly; and 
 
 an abrasive disk, and 
 
 (c) a cord that connects the hand piece to the control unit; 
 wherein the transmission unit converts a rotational motion of the dermabrasion hand piece to a reciprocating motion causing the abrasive disk to reciprocate, and 
 wherein the abrasive disk is disposed at an angle with the longitudinal axis of the hand piece. 
   
     
     
         18 . (canceled) 
     
     
         19 . The method of  claim 17 , wherein:
 (i) the angle is approximately 45 degrees;   (ii) the linkage assembly comprises an input drive wheel, and output drive wheel, and a coupling rod;   (iii) wherein the first set and second set of gears are bevel gears; and/or   (iv) the reciprocating motion ranges between +/−45 degrees.   
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . The method of  claim 1 , wherein the subject has androgenetic alopecia (AGA), scarring alopecia, male pattern baldness, female pattern baldness, discoid lupus erythematosis, or lichen planopilaris. 
     
     
         24 . A dermabrader having a dermabrasion hand piece with dermabrasion tip comprising:
 a housing having a first opening substantially aligned with a longitudinal axis of the housing and a second opening disposed at an angle to the longitudinal axis;   a transmission unit disposed in the housing, the transmission unit comprising:
 a first set of gears; 
 a second set of gears; and 
 a linkage assembly disposed between the first set of gears and the second set of gears; and 
   an abrasive disk; and   wherein the transmission unit converts a rotational motion of the dermabrasion hand piece to a reciprocating motion causing the abrasive disk to reciprocate, and   wherein the abrasive disk is disposed at an angle with the longitudinal axis of the housing.   
     
     
         25 . (canceled) 
     
     
         26 . A method for promoting vellus hair growth in a human subject suffering from baldness, wherein the method comprises:
 (i) integumental perturbation of an area of the bald scalp of the human subject, wherein the integumental perturbation is performed by dermabrasion using the dermabrader of  claim 24 ; and   (ii) administering a hair growth promoting agent.