- Reaction score
- 320
https://patents.google.com/patent/US9962360B2/en
-> Preferably trimebutine is trimebutine maleate or N-desmethyl trimebutine. Compositions are preferably in a form for topical administration, such as a gel.
-> We previously have shown that SKPs when transplanted in the dermis can induce formation of new hair follicles and induce hair to grow. In addition, we have also shown that SKPs can generate new cells to replenish and maintain the dermis and participate in skin wound healing
-> SKPs can express at least one, two, three, or more of the following molecular markers: nestin, WNT-1, vimentin, versican, fibronectin, S100β, slug, snail, twist, Pax3, Sox9, Dermo-1, and Sox2. SKPs may also express increased levels of slug, snail, twist, and Pax3 relative to central nervous system neural stem cells
-> In one non-limiting embodiment, the composition comprises between 2% to 10% (v/v) of at least one active compound described herein (e.g., trimebutine maleate (TM) or N desmethyl trimebutine). In another embodiment, the total daily dose of the composition (e.g., trimebutine maleate (TM) or N-desmethyl trimebutine) described herein is from about 50 mg/daily to about 200 mg/daily
-> Thus, alprostadil and TM increase SKP proliferation and self-renewal
These results demonstrate that Alp and TM promote proliferation and increase blood vessels in the wound bed.
In one week of topical treatment with TM or Alp, the number of Ki67 positive proliferating cells were increased in the dermis and within three weeks of TM or Alp treatment, an increase in dermal thickness was seen
In contrast, neither Alp nor TM increased the phosphorylated, activated forms of STAT3, GSK3beta, Akt1, or CREB compared to control (
-> Combination Therapy
The compositions described herein may also be used in combination with compounds known to promote hair growth that are available as drugs, such as finasteride,dutasteride, as well as flutamide, bicalutamide, pregnane derivatives, progesterone derivatives, experimental agents (FCE 28260), Spironolactone and other diuretics may also be utilized as it is indicated for women in some cases (also known as Aldactone: an aldosterone receptor antagonist). Minoxidil (Rogaine), Herbal remedies that may have 5-alpha reductase inhibitory action may include: Saw Palmetto and Pygeum africanum. Other agents that may have such activity are Beta-sisterol, Sepicontrol and Licorice, gamma-linolenic acid, zinc and zinc salts, EGCG, and other unsaturated fatty acids. Grape seed, apple seed, apple juice and barley extracts may also be potential agents that may induce hair growth.
Additional combinations may include other known stimulators of hair growth, such as zinc, calcineurin inhibitors, such as FK506 (Tacrolimus, Fujimycin), a macrolide antibiotic produced by Streptomyces tsukubaensis, and its derivatives, or Cyclosporin A,alprostadil, latanoprost, and a T cell-specific immunosuppressant, and the like.
-> Preferably trimebutine is trimebutine maleate or N-desmethyl trimebutine. Compositions are preferably in a form for topical administration, such as a gel.
-> We previously have shown that SKPs when transplanted in the dermis can induce formation of new hair follicles and induce hair to grow. In addition, we have also shown that SKPs can generate new cells to replenish and maintain the dermis and participate in skin wound healing
-> SKPs can express at least one, two, three, or more of the following molecular markers: nestin, WNT-1, vimentin, versican, fibronectin, S100β, slug, snail, twist, Pax3, Sox9, Dermo-1, and Sox2. SKPs may also express increased levels of slug, snail, twist, and Pax3 relative to central nervous system neural stem cells
-> In one non-limiting embodiment, the composition comprises between 2% to 10% (v/v) of at least one active compound described herein (e.g., trimebutine maleate (TM) or N desmethyl trimebutine). In another embodiment, the total daily dose of the composition (e.g., trimebutine maleate (TM) or N-desmethyl trimebutine) described herein is from about 50 mg/daily to about 200 mg/daily
-> Thus, alprostadil and TM increase SKP proliferation and self-renewal
These results demonstrate that Alp and TM promote proliferation and increase blood vessels in the wound bed.
In one week of topical treatment with TM or Alp, the number of Ki67 positive proliferating cells were increased in the dermis and within three weeks of TM or Alp treatment, an increase in dermal thickness was seen
In contrast, neither Alp nor TM increased the phosphorylated, activated forms of STAT3, GSK3beta, Akt1, or CREB compared to control (
-> Combination Therapy
The compositions described herein may also be used in combination with compounds known to promote hair growth that are available as drugs, such as finasteride,dutasteride, as well as flutamide, bicalutamide, pregnane derivatives, progesterone derivatives, experimental agents (FCE 28260), Spironolactone and other diuretics may also be utilized as it is indicated for women in some cases (also known as Aldactone: an aldosterone receptor antagonist). Minoxidil (Rogaine), Herbal remedies that may have 5-alpha reductase inhibitory action may include: Saw Palmetto and Pygeum africanum. Other agents that may have such activity are Beta-sisterol, Sepicontrol and Licorice, gamma-linolenic acid, zinc and zinc salts, EGCG, and other unsaturated fatty acids. Grape seed, apple seed, apple juice and barley extracts may also be potential agents that may induce hair growth.
Additional combinations may include other known stimulators of hair growth, such as zinc, calcineurin inhibitors, such as FK506 (Tacrolimus, Fujimycin), a macrolide antibiotic produced by Streptomyces tsukubaensis, and its derivatives, or Cyclosporin A,alprostadil, latanoprost, and a T cell-specific immunosuppressant, and the like.