Methods and Compositions for the Treatment of Alopecia and Other Disorders of the Pilosebaceous Apparatus
a technology of pilosebaceous apparatus and composition, which is applied in the field of methods and compositions for the treatment of alopecia and other disorders of the pilosebaceous apparatus, can solve the problems of not overwhelmingly successful in treating balding males, hyperandrogenism in some pcos patients, and inability to restore hair growth, so as to enhance the activity of either the isis or the androgen receptor activity of a mammal, and inhibit or induce the activity of a
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example 1
[0044] The Effect of a Biguanide ISIS on Hair Loss in Mice
[0045] The objective of the experiments in this Example is to examine the effects of the biguanide ISIS metformin on hair loss in aged female obese (C57BL / 6J—ob / ob) mice. The hypothesis tested is that metformin, when administered in these mice at a relatively young age, will increase insulin sensitivity, thereby preventing or slowing the progression of hair loss.
[0046] Metformin (Glucophage®, Bristol-Myers Squibb Co., Princeton, N.J.) is a biguanide ISIS used clinically for the treatment of type II (non-insulin dependent) diabetes (refer to packaging insert for metformin). The antihyperglycemic effect of metformin has been ascribed to increased peripheral glucose disposal, suppression of glucose production by the liver and a decreased rate of intestinal glucose absorption (Hermann, L. S., Diabetes Metab. 5:233-245 (1979)). The plasma insulin level is not increased. In animal studies with the obese (ob / ob—Thieller background...
example 2
[0053] Formulation of Metformin HCl, a Biguanide ISIS
[0054] Metformin hydrochloride (HCl) is a white crystalline powder which is highly soluble in water. For production of the test materials described herein, it is dissolved in water to twice the desired final concentration, then mixed with an equal volume of a solution of 4% butylene glycol in special denatured alcohol (SDA) for a final concentration of 50% SDA and 2% butylene glycol. Metformin HCl is soluble in water up to 20% or more, allowing for concentrations of at least 10% by weight. Depending on patient sensitivity to this compound, concentrations of metformin HCl can be reduced as necessary. Preferred concentrations are about 0.8% to about 2.0%.
[0055] The pH of this metformin HCl solution is normally 6.5-7.0, but may be adjusted using sodium hydroxide (NaOH) to pH 13 to improve penetration to the dermis. Penetration of metformin HCl improves as pH increases. Any pH between 6.5 and 13.5 is acceptable, but pH values above ...
example 3
[0061] Topical Activity and Formulation of a Biguanide ISIS and its Synthetic or Natural Derivatives
[0062] Biguanide (NH2C(═NH)NHC(═NH)NH2) and its synthetic derivatives, such as monomethyl, dimethyl, trimethyl, tetramethyl and phenyl compounds are all water soluble, highly alkaline bases with limited long-term chemical stability in water. When neutralized with an appropriate concentration of a strong acid (e.g., HCl, H2SO4) or a weak organic acid (e.g., glycolic, lactic, citric, pamoic) to about a neutral pH value of approximately 4 to 8, the topical activity of biguanide and its derivatives is maintained, and its chemical stability in water is improved.
[0063] When pharmaceutically acceptable salts of biguanide were applied in reasonable concentrations (e.g., about 0.5% to about 10%) in a suitable topical vehicle (e.g., solution, tincture, gel, lotion, cream or ointment) containing a suitable penetration enhancing agent (e.g., surfactant, DMSO, N-methylpyrrolidone), the growth of...
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