Hair loss abstract
A method for ameliorating a cellular dysfunction of a tissue such
as the cosmetic treatment of hair loss and stimulation of hair growth
is disclosed. The method comprises administering substituted or
unsubstituted 2,2,6,6-tetramethyl-1-piperdinyloxyl (TEMPO) to the
affected tissue.
Hair loss claims
I claim:
1. A method for inhibiting the activity of hydroxyl and oxygen
free radicals in tissue of an organism, comprising the step of:
administering substituted or unsubstituted 2,2,6,6-tetramethyl-1-piperidinyloxyl
to the tissue in an effective amount to inhibit the free radicals.
2. The method of claim 1, whereto the administration step is topical.
3. The method of claim 2, wherein the 2,2,6,6-tetramethyl-1-piperdinyloxyl
is in the form of a dispersion, suspension or emulsion selected
from creams, lotions, shampoos and cream rinses.
4. The method of claim 3, wherein the dispersion, suspension or
emulsion comprises from about 0.01 to about 20 percent by weight
of said piperidinyloxyl.
5. The method of claim 1, wherein the 2,2,6,6-tetramethyl-1-piperidinyloxyl
includes a substituent selected from 4-amino; 4-(2-bromoacetamido);
4-(ethoxyfluorophosphonyloxy); 4-hydroxy; 4-(2-iodoacetamido); 4-maleimido;
4-(4-nitrobenzoyloxyl); 4-oxo; and 4-phosphonooxy.
6. The method of claim 1, wherein the administration step is internal.
7. A method for stimulating hair growth, comprising the step of:
administering an effective amount of substituted or unsubstituted
2,2,6,6-tetramethyl-1-piperdinyloxyl to the affected area.
8. The method of claim 7, wherein the administration step is topical.
9. The method of claim 8, wherein the 2,2,6,6-tetramethyl-1-piperidinyloxyl
is in the form of a dispersion, suspension or emulsion selected
from creams, lotions, shampoos and cream rinses.
10. The method of claim 7, wherein the 2,2,6,6-tetramethyl-1-piperidinyloxyl
includes a substituent selected from 4-amino; 4-(2-bromoacetamido);
4-(ethoxyfluorophosphonyloxy); 4-hydroxy; 4-(2-iodoacetamido); 4-maleimido;
4-(4-nitrobenzoyloxyl); 4-oxo; and 4-phosphonooxy.
11. The method of claim 9, wherein the dispersion, suspension or
emulsion comprises from about 0.01 to about 20 percent by weight
of said piperidinyloxyl.
12. A method for inhibiting the activity of hydroxyl and oxygen
free radicals in tissue of an organism, comprising the step of:
administering a dispersion, suspension or emulsion of from about
0.01 to about 20 percent by weight of substituted or unsubstituted
2,2,6,6-tetramethyl-1-piperidinyloxyl to the tissue.
Hair loss description
FIELD OF THE INVENTION
This invention relates to a method for treating hair loss using
2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO).
BACKGROUND OF THE INVENTION
Several compounds have recently gained recognition for ameliorating
cellular dysfunction. One type of dysfunction which has been well
studied is alopecia for which anti-alopecia agents such as minoxidil
and cyoctol have gained attention. However, most of these anti-alopecia
agents are only minimally effective in some cases and/or can cause
adverse dermatological or systemic reactions. Thus, the search continues
for new, safer and more effective anti-alopecia agents as well as
agents useful for treating other dysfunctionalities.
SUMMARY OF THE INVENTION
Applicant has discovered that 2,2,6,6-tetramethyl-1-piperidinyloxyl
(TEMPO) can inhibit free radicals in the tissue to which it is administered.
TEMPO has properties in the body for ameliorating certain cellular
dysfunctions in tissue attributed, in part, to high energy oxygen
and hydroxyl free radicals, and enhancing recuperation of the tissue.
2,2,6,6-Tetramethyl-1-piperidinyloxyl can be administered, for example,
as an anti-alopecia agent to stimulate cosmetic hair growth, or
as a protectant to minimize hair loss during cancer treatments known
to induce hair loss.
DETAILED DESCRIPTION OF THE INVENTION
In the present invention, 2,2,6,6-tetramethyl-1-piperidinyloxyl
(TEMPO) is compounded in a pharmaceutical formulation or carrier
for topical or internal administration. The topical pharmaceutical
carrier in which the TEMPO is generally substantially homogeneously
dispersed can be an aqueous dispersion or suspension, or a water-in-oil
or oil-in-water emulsion depending on the administration route.
Topical pharmaceutical carriers which can be mentioned include water,
urea, alcohols and glycols such as methanol, ethanol, propanol,
butanol, ethylene glycol, propylene glycol, and the like. Internally
administered pharmaceutical carriers typically include a sterile
vehicle such as water or ethanol in which the TEMPO is suspended,
dispersed or dissolved.
Suitable water-in-oil emulsions are commercially available under
the designations Aquaphor, cold cream, Eucerin, hydrous lanolin,
Hydrosorb hydrophilic petrolatum, Nivea, Polysorb, Qualatum and
Velvachol. Suitable oil-in-water emulsions are available commercially
under the designations acid mantle cream, Almay emulsion cream,
Cetaphil, Dermabase, Dermavan, hydrophilic ointment, Keri cream,
Lubriderm cream, Multibase cream, Neobase cream, Unibase cream,
Vanibase cream and Wibi. The carrier may further contain various
other emollients, emulsifiers, water, perfumes, colorants, preservatives,
and the like. The topical formulation is in the form of a cream,
lotion, shampoo, cream rinse, or the like.
TEMPO is a stable nitroxide radical which is a commercially available
spin label. TEMPO can be unsubstituted or substituted, typically
in the 4 position, for example, 4-amino, 4-(2-bromoacetamido), 4-(ethoxyfluorophosphonyloxy),
4-hydroxy, 4-(2-iodoacetamido), 4-isothiocyanato, 4-maleimido, 4-(4-nitrobenzoyloxyl),
4-oxo, 4-phosphonooxy, and the like.
Effective amounts of the TEMPO generally range from about 0.01
to about 20% by weight of the administered composition, more preferably
from about 0.1 to about 10% by weight, most preferably from about
0.5 to about 3% by weight, but more or less can be present in the
composition depending on the particular TEMPO formulation and the
treatment conditions.
The TEMPO can be used alone or in combination with other additaments
which are available to enhance the function of hair growth stimulation
such as, for example, the hydroxyl radical scavengers, antiandrogens
and others described in International Publication No. WO 87/00427
(International Application No. PCT/US86/01393) published on Jan.
29, 1987; and European Patent Application No. 89300785.6, Publication
No. 0327263/A1, published Aug. 9, 1989; both of which are hereby
incorporated in their entirety herein as though fully set forth
verbatim, including reference therein to the publication of Ross
& Ross, "Selected Specific Rates of Reactions of Transients
From Water In Aqueous Solution. III. Hydroxyl Radical and Pure Hydroxyl
Radicals and Their Radical Ions," National Standard Reference
Data Series, National Bureau of Standards, 59 (1977), which is also
incorporated herein by reference.
According to the present invention, the TEMPO can be administered
to the skin to be treated, such as the scalp. Depending on the type
of hair loss or alopecia being treated and the conditions thereof,
the stimulation of hair growth can usually be obtained by topical
application, preferably repeated daily application for a period
of 3-6 months. The utility of topically applied TEMPO is not limited
thereto, however, and the stimulation of hair growth can include
an increased rate of growth, increased hair diameter, follicular
neogenesis, and the like; inhibiting hair loss or alopecia from
progressing, for example, in male pattern baldness, or during the
course of treatment with other therapeutic agents known to induce
hair loss, such as chemotherapy or radiation therapy in cancer treatment;
as well as, ameliorating the rate of protein oxidation, DNA scission,
cell viability loss, and the like in the tissue of internal organs
such as the heart and brain; and ameliorating capillary loss, tissue
atrophy characterized by a decrease in collagen and/or elastin and
a decreased number, size and reproduction potential of fibroblasts,
and strengthening the dermal-epidermal junction in skin; ischemic
reperfusion injury secondary to myocardial infarction, stroke and
surgical procedures; wound healing, for example, in burns and diabetic
ulcerations; inflammatory and degenerative diseases such as rheumatoid
arthritis, lupus and the like; fibrotic diseases such as Peyronie's
disease, scarring, pulmonary fibrosis, and vitreous fibrosis; prevention
of free-radical-induced vascular damage such as in atherosclerosis;
other free radical diseases as outlined in Proctor et al., "Free
Radicals and Disease in Man," Physiological Chemistry and Physics
and Medical NMR, volume 16, pp. 175-195 (1984) which is hereby incorporated
herein by reference; and the like.
The invention is illustrated by way of the following examples:
EXAMPLE 1
A TEMPO shampoo is prepared by mixing 0.5 g of 4-hydroxy-TEMPO
in 500 ml of a commercially available shampoo. The shampoo is used
daily on the scalp for normal shampooing of the hair for a period
of from 3 to 6 months to obtain cosmetic hair growth.
EXAMPLE 2
A solution of TEMPO is prepared and used in the course of radiation
treatment. 4-Hydroxy-TEMPO, obtained commercially from Aldrich Chemical
Company, is dissolved in 70 percent ethanol/30 percent water at
a concentration of 70 mg/ml. Topical application of the solution
is made prior to irradiation exposure at 20Gy to 50Gy. Hair loss
in the treated TEMPO subjects is less severe and returns to normal
more rapidly than in the control group similarly treated with the
same ethanol/water solution without TEMPO. Skin samples obtained
from the treated group test positive for the presence of 4-hydroxy-TEMPO,
while other tissue and blood specimens generally test negative.
The application of the solution can also continue daily after the
irradiation exposure. See Goffman, et al., "Topical Application
of Nitroxide Protects Radiation-Induced Alopecia in Guinea Pigs,"
International Journal of Radiation Oncology, Biology and Physics,
Volume 22, pp. 803-806, 1992, which is hereby incorporated herein
by reference.
EXAMPLE 3
A 0.4 or 1 mM solution of TEMPO is used to significantly reduce
cardiac injury caused by reperfusion arrhythmia-ventricular fibrillation
and ventricular tachycardia, as well as, post ischemic release of
lactate dehydrogenase and OH- formation in isolated rat heads subjected
to regional ischemia. The rat heads are obtained and perfused using
a modified Krebs-Henseleit (KH) buffer, as detailed in Gelvan et
al., "Cardiac Reperfusion Damage Prevented by a Nitroxide Free
Radical," Proceedings of the National Academy of Sciences,
USA, Medical Sciences, Vol. 88, pp. 4680-4684, June 1991, which
is hereby incorporated herein by reference, in which the TEMPO solution
was added to the perfusate. After reperfusion, head function and
resulting damage is analyzed. TEMPO is found to strongly protect
against reperfusion injury by preventing OH-formation rather than
by decreasing heart rate or by direct suppression of arrhythmia.
The invention is described above and illustrated herein with reference
to specific chemical formulas, preparations and therapeutic and
cosmetic applications. Many variations and modifications will become
apparent to those skilled in the art in view of the foregoing disclosure.
It is intended that the following claims are not to be limited thereby,
and are to be construed in accordance with the spirit and scope
thereof. |