MXPA00009098A - Use of selegiline or desmethylselegiline for treating wounds, burns and dermatological damage - Google Patents

Abstract

The present invention is directed to methods that can be used in the treatment of wounds, burns, and photodamaged skin. Methods can be used for both humans and animals and involve the administration of compositions containing selegiline and/or desmethylselegiline.

Description

USE OF SELECTED OR NON-DEMONSTRATION TO TREAT HERI DAS, QUEMADUAS AND DERMATOLOGICAL DAMAGE Field of the invention The present invention relates to methods for treating wounds, burns or dermatological damage by administering topical compositions containing selegiline and / or desmethylselegiline.

BACKGROUND OF THE INVENTION A. Free radicals Free radicals are molecules with one or more unpaired electrons in their outer orbitals. The presence of these electrons together with the tendency of the molecules to look for the state of less stable energy causes that the free radicals are highly reactive and usually have a short life. Among the free radicals commonly found in vivo are oxygen, superoxide anion and hydroxyl radical. Normally these are referred to as "oxidants" and are often the result of cascades in which electrons are passed from molecule to molecule. . { B. Injuries and free radical damage Injuries, such as injuries and burns, generate free radicals that have both local and systemic effects. Locally, free radicals have been implicated in both tissue ischemia (Granger, et al., Gastroenterology 81: 22-29 (1981), Parks, et al., Gastroenterology 82: 9- 1 5 (1 982)). in reperfusion injuries (Schiller, et al., Critical Care Med. 21: S92-S100 (1993)). Systemically, burns often cause dysfunction of the heart, lungs and liver. Researchers have found that healing of burns is improved when lipid peroxidation (usually caused by the action of free radicals) is reduced (LaLonde, et al., J. Burns Care &Rehabilitation 1 7: 379-383 (1 996)).

C. Photodamage Exposure of skin to electromagnetic radiation in the ultraviolet and visible portions of the spectrum and ionizing radiation can result in damage to both proteins and DNA in skin cells. Such "photodamage" has been correlated with the induction of non-melanoma skin cancer, suppression of immune function and photoaging. Exposure of the skin to ultraviolet and ionizing radiation and the concomitant pathobiologies have been linked to the generation of oxidants, as well as to a reduction in anti-oxidant and activity levels (Stewart, et al., J. Inv. Dermatol. 1 06: 1 086-1 089 (1996), Darr, et al., Brit. J. Dermatol 127: 247-253 (1992)). Specifically, research has shown that there is a reduction in the activity of epidermal superoxide dismutase and vitamin C and vitamin E levels after exposure to UVB radiation. The removal of oxidants (for example, by application of exogenous anti-oxidants) or prevention of oxidant production (for example, by reduction of exposure to ionizing radiation) can alleviate or prevent dermatological damage. Adverse effects of ionizing radiation include edema, vasodilatation, lymphocytic and neutrophilic infiltration in the dermis, dyskeratotic keratinocytes and epidermal spongiosis.

D. Use of anti-oxidants to detoxify free radicals A variety of different strategies have been used to try to prevent or reduce free radical damage. Endogenous anti-oxidants, for example, superoxide dismutase, catalase or glutathione peroxidase, can be used to protect cell membranes and agents, such as ascorbic acid and glutathione, can be used to protect cytosols. Other anti-oxidants, such as alpha-tocopherol and tretinoin, have also been used to improve the effect of free radicals. The administration of superoxide dismutase, post-ischemia, prevents increased capillary permeability which accompanies reperfusion injury (Granger, et al., Gastroenterology 81: 22-29 (1988)) and ablation of the generation of free radicals before, and at the time of, reperfusion can prevent or diminish the severity of multiple system failure syndrome of system organs (Schiller, et al., Critica! Care Med. 21: S92-S 1 00 (1 993)). Stewart, et al. have shown that damage to UVB-induced DNA in human keratinocytes is attenuated by supplementing the culture medium surrounding the cells with anti-oxidants, such as vitamin C, selenite or water-soluble vitamin E analog (J. Dermatol 1 06: 1 086-1 089 (1 996)).

E. Selegiline and desmethylselegiline Monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) are enzymes found in both the central nervous system and peripheral tissues. MAO-A and MAO-B catalyze the oxidative deamination of primary amines, including neuroactive and vasoactive amines, resulting in the formation of toxic free radical species and cascades generating free radicals. Selegiline is a potent and selective inhibitor of monoamine oxidase B and has been reported to have an action to protect or rescue neurons of the central nervous system (Knoll, Mount Sinai J. Med. 55: 67-74 (1988)). Although the exact mechanism by which selegiline causes its effects is not known, there is evidence to suggest that it may provide neuroprotection or neuronal salvage by reducing oxidative damage caused by monoamine oxidase and / or other oxidants (Jenner, et al., Neurology 47: S 162-S 1 70 (1 996)). In this regard, it has been shown that selegiline increases the activity of the endogenous anti-oxidants superoxide dismutase, catalase and glutathione peroxidase (Id.). Desmetilselegilina, one of the metabolites of selegiline, exhibits reduced MAO-B inhibitory activity compared to selegiline and its activity with respect to the inhibition of MAO-A is decreased to an even greater degree. Thus, it is expected that desmethylselegiline should produce neuroprotective effects on selegiline with a reduced risk of side effects associated with inhibition of MAO-A. Although selegiline has been used to treat Parkinson's disease, its use as a treatment for injuries, such as burns and wounds, and to alleviate dermatological damage, such as photodamage, has not been known until now. The present invention is directed to methods that rely on the administration of selegiline or desmethylselegiline to accelerate healing and reduce the complications associated with these conditions.

BRIEF DESCRIPTION OF THE INVENTION The present invention is based on the discovery that compositions comprising selegiline and / or desmethylselegiline can be used in the treatment of wounds, burns and photodamaged skin. In the case of burns and wounds, the compositions should be administered for a sufficient time to promote epithelization. In the case of photodamaged skin, the composition should be administered for a sufficient duration to promote healing, as evidenced by a reduction in one or more of the symptoms associated with photodamaged skin. These symptoms include edema, vasodilation, lymphocytic and neutrophilic infiltration in the dermis, dyskeratotic keratinocytes and epidermal spongiosis. Although the invention encompasses administration by any route, delivery by means of a topical composition containing between 1 x 10 0 1 1 moles / liter and 1 x 10 0"3 moles / liter selegiline and / or desmethylselegiline is preferred. The topical compositions can be delivered by means of an atomizer, patch, ointment, cream, lotion or gel. As used herein, the term "desmethylselegiline" refers to either the enantiomeric form R (-) of the medicament, the enantiomeric form S (+) of the medicament or a racemic mixture of the two. To perform the present methods, the R (-) enantiomer can be used in the substantial absence of the S (+) enantiomer or vice versa. An enantiomer is substantially absent if it constitutes less than 10% of the combined desmethylselegiline enantiomers. The compositions may contain water, suspending agents, thickeners, humectants, preservatives, emollients, emulsifiers and film formers. They can be applied either directly to the skin of a patient, or they can be applied as part of a patch. Although not preferred, non-topical routes of administration are compatible with the present invention and can be used. The dosage of selegiline or desmethylselegiline when used non-orally, it should be at least 0.01 5 mg per kg of body weight, calculated on the basis of free secondary amine, using progressively higher doses depending on the route of administration and the subsequent response to therapy. Normally, the daily non-oral dose will be approximately 0.10 mg / kg and may be extended to approximately 1.0 mg / kg (recalculating all those doses based on the free secondary amine).

DETAILED DESCRIPTION OF THE INVENTION In the following description, reference will be made to several methodologies well known to those skilled in the art of medicine and pharmacology. Such methodologies are described in standard reference works that expose the general principles of these disciplines. Unless indicated otherwise, the descriptions apply to selegiline and all enantiomeric forms of desmethylselegiline.

Dosage The optimum daily dose of selegiline and / or desmethylselegiline useful for the purposes of the present invention can be determined by methods known in the art, based on clinical conditions, such as, the severity of the injury, the condition of the subject to whom It is giving you a treatment, the desired therapeutic response and the concomitant therapies being administered to the patient or animal. However, ordinarily, it is expected that the attending physician or veterinarian will apply a topical composition containing a concentration of selegiline and / or desmethylselegiline between 1 x 10"1 1 mole / liter and 1 x 10" 3 mole / liter, preferably between 1 x 1 0"9 moles / liter and 1 x 1 0" 3 moles / liter. Sufficient composition should be administered to completely cover the damaged area on the individual's skin. If the doctor chooses non-oral routes of administration, at least 0.01 mg / kg of selegiline and / or desmethylselegiline should be admitted daily, with the most normal dose being around 0.10 mg / kg. The daily dosage can be increased to approximately 1.0 mg / kg. In all cases, the doses are calculated based on the secondary amine form of the agent being administered. These guide lines also require that the actual dosage be carefully titrated by the attending physician or veterinarian depending on the age, weight, clinical conditions and observed response of the individual being treated.

Topical compositions can be applied several times during the day to wounded, burned or photodamaged skin. Similarly, daily dosages of non-oral preparations can be admired in a single or multiple dosing regimen. In addition, dosage forms that permit the continuous release of active agent, e.g., a transdermal patch, can be used for delivery of medicament.

Route of administration for dosage forms As noted above, topical administration and topical dosage forms are generally preferred for the present methods. However, any of the numerous dosage forms described in the literature for the administration of selegiline may be used and desmethylselegiline may be included as desired. For example, U.S. Patent 4, 81 2,481 describes the use of selegiline, in combination with amantadine, in oral, pectoral, internal, pulmonary, rectal, nasal, vaginal, lingual, intravenous, intraarterial, intracardial, intramuscular, intraperitoneal, intracutaneous formulations. and subcutaneous. US Pat. No. 4,117,550 describes a dosage form for selegiline having an outer wall with one or more pores in the impermeable wall for selegiline but permeable for external fluids. This dosage form may have applicability for oral, sublingual or buccal administration. Similarly, U.S. Patent 4,387,61 describes a variety of selegiline compositions, including tablets, pills, capsules, powders, aerosols, suppositories, skin patches, parenterals and oral fluids, including suspensions, solutions and oily emulsions. . Furthermore, devices and formulations of sustained release (long acting) containing selegiline are described in the same. Topical dosage forms can be prepared according to conventional techniques, with creams generally preferred. The topical cream can be a cream / lotion / emulsion oil in water, cosmetically elegant, containing the desired specified concentration of selegiline and / or desmethylselegiline. Such moisturizer formulations may contain a carrier, a buffer system to maintain the vehicle at an appropriate pH, and an acceptable antimicrobial preservative system. The cream may also contain thickeners, humectants, emollients, emulsifiers and film formers. Methods for preparing the appropriate formulations are well known in the art (see, for example, Remington's Pharmaceutical Sciences, 16th ed., A. Oslo, Ed., Easton PA (1980)). Transdermal dosage forms can be prepared using a variety of techniques that have been described in the art. Examples can be found in U.S. Patent Nos. 4,861, 800; 4, 868, 218; 5, 1 28, 145; 5, 1 90, 763; and 5,242, 950; and in the foreign patent documents EP-A-404807; EP-A-509761; and EP-A 593807. A monolithic patch structure can be used, in which the medicament is directly incorporated into the adhesive and this mixture can be emptied onto a backed sheet. EP-A 593807 discloses a composition in which selegiline is administered as an acid addition salt by incorporating it into a multilayer patch, which promotes a conversion of the salt into the free base form of selegiline. One can also employ a device using a crystalline, lyotropic, liquid composition in which, for example, 5-1 5% selegiline is combined with a mixture of liquid and solid polyethylene glycols, a polymer and a nonionic surfactant, optionally with the addition of propylene glycol and an emulsifying agent. For further details on the preparation of such transdermal formulations, reference can be made to EP-A 5509761. The buccal and sublingual dosage forms of selegiline and / or desmethyselegine can be prepared using techniques described in, for example, U. S. 5, 1 92, 550; 5,221, 536; 5,266, 332; 5, 057, 321; 5,446,070; 4, 826, 379; or 5, 354, 885.

Chemical form of selegiline or desmethylselegiline The present invention is not limited to any particular form of selegiline and / or desmethylselegiline, and drugs may be used either as free bases or as pharmaceutically acceptable acid addition salts. In the latter case, the hydrochloride salt is generally preferred. However, other salts derived from organic and inorganic acids can also be used.

Way of treatment The methods described herein can be used for both human and non-human subjects. With respect to the latter, the methods are in particular, but not exclusively, directed to domesticated mammals, such as canine and feline species. In the case of wounds and burns, the treatment by administration of selegiline and / or desmethylselegiline should be continued until the epithelialization is complete. For dermatological damage, treatment should be continued until the related symptoms subside, such as edema, vasodilatation, lymphocytic and neutrophilic infiltration or spongiosis of the epidermis. The medicaments can be either administered at regular intervals (eg, twice a day) or in an essentially continuous manner (eg, via a transdermal patch).

EXAMPLES Example 1: Protective effects of selegiline and desmethylselegiline against photodamage The ability of selegiline and / or desmethylselegiline to prevent photodamage can be correlated with the reduction of cellular apoptosis following exposure to UVB radiation. Previous research has shown that primary human keratinocytes grown in a serum-free medium are susceptible to UVB-induced apopotsis when exposed to 600-800 J / m2. In addition, the deprivation of growth factors, specifically insulin, increases the sensitivity of keratinocytes to UVB radiation, with apoptosis occurring at UVB levels of 200 J / m2.

Two sets of human keratinocytes are grown in complete and deprived growth factor (GFD) media for a total of four sets of cultures. The keratinocytes are then placed in GFD or complete media containing 0.1 x 1 0"9, 1 x 1 0" 8, 1 x 10"7, 1 x 1 0 ~ 5, 1 x 1 0" 6, 1 x 1 0 ~ 4 and 1 x 10"3 M of selegiline or desmethylselegiline Twenty-four hours after the addition of the drugs, the keratinocytes that grew in the GFD medium are irradiated with zero or 200 J / m2 UVB and the keratinocytes that grew in medium The whole are irradiated with zero or 800 J / m2 UVB.Using morphological examination, DAPI staining, Annexin V-FITC FACS analysis and PARP cut-off analysis, keratinocytes are tested for apoptosis 15 hours after irradiation. , keratinocytes are examined by morphological signs of apoptosis.After morphological examination, cells are harvested by trypsinization and pelleted by low speed centrifugation.Each pellet is divided into three parts for the remaining evaluation.DAPI spotting is used to examine the cells by nuclear condensation characteristic of cellular apoptosis. An aliquot of each cell pellet is washed with PBS, fixed in H istochoice, and resuspended in DAPI spotting solution for one hour. Cells are subsequently washed in PBS and attached to microscope slides by cytoblotters. The cells are then visualized by epifluorescent microscopy and the percentage of apoptotic cells is determined.

The analysis of Annexin V-FIT FACS is used to determine the exposure to extracellular phosphatidylserine. In the early stages of cellular apoptosis, portions of the plasma membrane are transubjected causing the normally intracellular phosphatidylserine to move the extracellular surface of the plasma membrane. Annexin V binds to extracellular phosphatidylserine and the amount of such binding is measured by flow cytometry. An aliquot of each cell pellet is washed in PBS and resuspended in a binding buffer. The cells are then incubated in the dark for 15 minutes in the presence of Annexin V-FIT and propidium iodide. Following the incubation, the percentage of apoptotic cells is determined using FACS analysis. The apoptotic cells are Annexin V-FACS positive and propidium iodide negative. The PARP cutoff analysis is used to measure the proteolytic cascade, which occurs during apoptosis. One of the substrates for proteases related to apoptosis is poly (ADP-ribose) polymerase, or PARP. After cutting, PARP is reduced to a characteristic 85 kD fragment. One aliquot of each cell pellet is resuspended in RI PA buffer containing 7% urea and protein. The resulting cellular proteins are then transferred to I mmobilin P membranes by semi-dry electrophoresis and incubated in TSB buffer (150 mM sodium chloride).; 1 00 mM Tris-base, pH 7.5; 2% blocking reagent B: Boehringer Mannheim) for 2 hours at room temperature. Anti-PARP monoclonal antibodies (clone C-2-10) are diluted in TSB and 2% B-blocking reagent. Following one hour of incubation, the membrane is washed three times with TSB buffer containing 0. 1% Tween20 . After the incubation was complete, biotinylated goat anti-mouse Ig (Fab 'fragments) diluted in TSB was added to the membrane and the membrane was then washed three times with TSB buffer containing 0. 1% Tween20. Streptavidin-horseradish peroxidase conjugate was added to the membrane and protein bands visualized using Enhanced Chem illuminescent Plus (Amersham). The percentage of PARP cut is determined using densitometry to compare the total PARP protein with the cut PARP fragment (85 kD).

Example 2: Curing effects of selegiline and desmethylselegiline on burns The ability of seleglycine and desmethylselegiline to assist in the healing of burns was tested using a second degree burn wound model. In second-degree burns, the entire surface of the epidermis is destroyed. An epidermal coating is regenerated from the remaining epithelial and epidermal cells adjacent to the burns. This phase of the healing process is called epithelization.

A. Materials and methods Experimental animals Pigs were used for experimental research in animals because their skin has many morphological similarities to human skin. Seven young pigs, females, free of specific pathogens (SPF: Ken-O-Kaw Farms, Windsor, I L), weighing 25-30 kg, were kept at home for two weeks before starting the experiment. These animals were fed a basal diet ad libitum and were housed individually in facilities with light (1 2h / 1 2h LD) and temperature controlled (1 9-21 ° C).

Wound Technique The experimental animals were peeled with standard animal shearers on the day of the experiment. The skin on the back and both sides of the animal was prepared to injure it by washing with a soap without antibiotic and sterile water. Each animal was anesthetized i. m. with ketamine-HCI (20 mg / kg), xylazine (2 mg / kg) and atropine (0.05 mg / kg), followed by mask inhalation of a combination of isoflurane and oxygen. Five cylindrical bronze bars, specially designed, weighing 358 g each, were heated in a boiling water bath at 100 ° C. A bar was removed from the bathroom and wiped with a cloth before being applied to the surface of the skin to prevent the water droplets from creating a burn of steam on the skin. The bronze bar was held in a vertical position on the skin for six seconds, applying all the pressure by gravity, in order to make a burn of 8.5 mm in diameter x 0.8 mm in depth. Immediately after the burn, the cover of the blister of the burn was removed with a sterile spatula. The burn wounds were made approximately every 2 cm of each other.

Approximately 90 wounds were made in the previous two thirds of the animal. The posterior third of the animal can not be used due to the anatomical differences in the healing of the burn wound (a faster healing of burns has been observed in that position). Burn wounds were randomly assigned to seven treatment groups and applied in the pattern shown in Table 1.

Table 1: Treatment groups Number of Animal groups treatment 1 Agent A (dose X) Agent A (dose Y) Agent A (dose Z) 1 Agent A (dose Y) Agent A (dose Z) Agent B (dose X) 1 Agent A (dose Z) Agent B (dose X) Agent B (dose Y) 1 Agent B (dose X) Agent B (dose Y) Agent B (dose Z) 1 Agent B (dose Y) Agent B (dose Z) Exposed to air, control 1 Agent A (dose X) Agent B (dose Z) Exposed to air, control 1 Agent A (dose X) Agent A (dose Y) Exposed air, control Agent A = selegiline dose X = 1 0"4 M Agent B = desmethylselegiline HCl dose Y = 1 0" 6 M dose Z = 1 0 8 M A total of seven animals was used and a total of fifteen was analyzed Wounds per treatment group on each of the days 7-12 after the wound. The treatments were coded to maintain the blind study submission. Burn wounds were treated with 25 ug of the test article (enough to cover each wound). The treatments were allowed to penetrate the sites for at least a period of 20 minutes. Each treatment was applied within 20 minutes of the removal of the blister and the treatment occurred once a day for the first five days.

Evaluation of the epidermal migration Beginning on day seven after the wound (day 0) and every day thereafter for four to six daysFive burn wounds and the surrounding normal skin of each treatment were cut using an electrokeratome. Any specimen that was not cut intact was discarded. Wounds and surrounding normal cut skin were incubated in 0.5 M NaBr for 24 hours at 37 ° C. After incubation, the specimens were separated into epidermal and dermal layers. The epidermis was examined macroscopically for defects in the area of the burn wounds. The epithelization was considered complete if no defect was present (cured). Any defect in the burned area indicated that the healing was incomplete. The epidermal sheet was placed on a cardboard for a permanent record.

B. Outcome After the study was completed, the codes were revealed and the data tabulated. The number of healed wounds (fully epithelialised) was divided by the total number of wounds sampled per day and multiplied by 100. The results are shown in Table 2.

Table 2: Results of epithelialization (combined data) 4 * Wounds are presented as the number of healed wounds (fully epithelialized) on the number of wounds assessed. () Percentage of completely epithelialized wounds Code: A = selegiline HCl; 2 = 1 0"6 M B = desmethylselegiline HCl 3 = 1 0" 8 M 1 = 10"4 M All wounds absorbed the administered compounds within 10 minutes to 15 minutes of application. During the first three days of treatment, the wound crust in all treatment groups turned white during absorption of an applied agent. This was more pronounced with treatments A and B. After 15 minutes, the color of the crust became normal again. No residual, erythema or infection was observed in any treatment group. The results shown in Table 2 can be summarized as follows: Day 7-9: None of the burn wounds were completely epithelialized. Day 1 0: Twenty percent (20%) of the wounds that were treated with selegiline HCl at concentrations of 1 x 1 0"4 M and 1 x 1 0" 6 M completely epithelized. None (0%) of the wounds of any other group completely epithelialized. Day 1 1: Thirty-three percent (33%) of wounds treated with either selegiline HCl (1 0 4 M and 1 0"6 M), desmethylselegiline HCl (1 0" 6 M and 1 0"8 M) or saline solution completely epithelized, Seven percent (7%) of the wounds treated with desmethyl selegiline HCl (10"4 M) completely epithelized. None of the wounds treated with selegiline HCl (1 0 8 M) completely epithelized.

Day 12: Thirty-three percent (33%) and forty percent (40%) of wounds treated with selegiline HCl (1 0 4 M and 1 0"6 M respectively), completely epithelialized, only seven percent (7%) of wounds treated with the concentration 1 0"8 M of selegiline HCl completely epithelized. Thirty-three percent (33%), forty-seven percent (47%) and sixty-seven percent (67%) of wounds treated with desmethylselegiline HCl (1 0 4 M, 1 0"6 M and 10" 8 M, respectively ) were completely epithelialized. Forty percent (40%) of wounds treated with saline, ie, control cells, were completely epithelialized. Day 1 3: Thirty-three (33%) and forty (40%) percent of wounds treated with selegillin HCl (10 ~ 4 M and 10 ~ 6 M, respectively) completely epithelialized. Thirty-eight percent of wounds treated with the 1 0"8 M selegiline HCl epithelialized completely, Sixty-nine (69%), one hundred (100%) and sixty-seven (67%) percent of wounds treated with desmethylselegiline HCl ( 1 0"4 M, 1 0" 6 M and 1 0"8 M, respectively) epithelialized completely. Sixty-seven (67%) percent of the wounds treated with saline, that is, controls, epithelialized completely.

C. Discussion The data from these studies suggest that wounds treated with selegiline HCl (1 0"4 M and 10 ~ 6 M) were able to initiate epithelialization earlier than all other treatment groups. Wounds treated with desmethylselegiline HCl (all concentrations) had a higher percentage of fully epithelialized wounds by day 13. Wounds treated with desmethylselegiline HCl (1 0 6 M) epithelialized completely earlier than all other treatment groups.

Example 3: Use of selegiline and desmethylselegiline to improve the appearance of photodamaged skin Test subjects, women exhibiting moderate to severe photoaging on the dorsal portions of their forearms and hands, are randomly assigned to receive their vehicle plus selegiline or vehicle alone. During a period of 16 weeks, the test subjects apply enough cream to cover the designated test area BI D. Clinical assessments of the appearance of the test area are made prior to the administration of the cream and in the weeks number two, eight, sixteen and twenty-four.

Example 4: Use of selegiline to preserve the positive effects of tretinoin on photoaged skin Test subjects, women exhibiting moderate to severe photoaging on the face and dorsal portions of their forearms, are randomly assigned to apply either the vehicle combination plus selegiline or vehicle alone. For an initial period of sixteen weeks, all test subjects treat bilateral aspects of their face, forearms and hands with a tretinoin cream once a day. During a subsequent week period, all test subjects did not use treatment in the test areas. During the following sixteen-week period, the test subjects apply cream, either containing vehicle alone or vehicle plus selegiline to cover one-half of the designated BI area. Clinical assessments of the test areas are made prior to administration of the test. cream and throughout the study. All references cited herein are incorporated herein by reference. Having now fully described the invention, those skilled in the art will understand that the invention can be realized within a broad and equivalent range of conditions, parameters and the like, without affecting the spirit or scope of the invention or any modality thereof.

Claims (30)

1. REIVI NDI CATIONS 1 . A method for treating a wound in a subject, comprising administering a composition comprising selegiline and / or desmethylselegiline to said subject for a time sufficient to promote epithelialization of said wound.
2. 2. The method of claim 1, wherein said composition is a topical composition comprising selegiline at a concentration between 1 x 1 0 1 1 mole / liter and 1 x 1 0"3 mole / liter
3. 3. The method of the claim 1, wherein said composition is a topical composition comprising desmethylselegiline at a concentration of between 1 x 1 0 1 1 mol / liter and 1 x 10"3 mol / l
4. 4. The method of claim 1, wherein said composition comprises desmethylselegiline in the form of its R (-) enantiomer and the S (+) enantiomer is substantially absent
5. 5. The method of claim 1, wherein said composition comprises desmethylselegiline in the form of its S (+) enantiomer and the R-enantiomer. (-) is substantially absent
6. 6. The method of either claim 2 or 3, wherein said composition is in the form of a cream
7. 7. The method of either claim 2 or 3, wherein said topical composition. is in the form d and a gel
8. 8. The method of claim 1, wherein said composition comprises selegiline delivered by means of a patch.
9. 9. The method of claim 1, wherein said composition comprises desmetilselegili na delivered by means of a patch.
10. The method of claim 1, wherein said composition further comprises one or more compounds selected from the group consisting of water, suspending agents, thickeners, humectants, preservatives, emollients, emulsifiers and film formers. eleven .
11. A method for treating a burn in a subject comprising administering a composition comprising selegiline and / or desmethylselegiline to said subject for a time sufficient to promote epithelialization of said burn.
12. The method of claim 1, wherein said composition is a topical composition comprising selegiline at a concentration of between 1 x 1 0"1 1 mol / liter and 1 x 1 0" 3 mol / liter.
13. The method of claim 1, wherein said composition is a topical composition comprising desmethylselegiline at a concentration of between 1 x 1 0"1 1 mol / liter and 1 x 1 0" 3 mol / liter.
14. The method of claim 1, wherein said composition comprises desmethylselegiline in the form of its R (-) enantiomer and the S (+) enantiomer is substantially absent.
15. The method of claim 1, wherein said composition comprises desmethylselegiline in the form of its S (+) enantiomer and the R (-) enantiomer is substantially absent.
16. The method of either claim 12 or 13, wherein said topical composition is in the form of a cream.
17. 17. The method of either claim 12 or 13, wherein said topical composition is in the form of a gel.
18. The method of claim 1, wherein said composition comprises selegiline delivered by means of a patch.
19. The method of claim 1, wherein said composition comprises desmethylselegiline delivered by means of a patch.
20. 20. The 1 1 re-excitation method, wherein said composition further comprises one or more compounds selected from the group consisting of water, suspending agents, thickeners, humectants, preservatives, emollients, emulsifiers and film formers. twenty-one .
21. A method for treating a subject by photodamaged skin, comprising administering a composition comprising selegiline and / or desmethylselegiline to said subject for a sufficient time to promote healing of said photodamaged skin.
22. 22. The method of claim 21, wherein said composition is a topical composition comprising selegiline at a concentration of between 1 x 1 0 1 1 mol / liter and 1 x 1 0"3 mol / liter.
23. 23. The method of claim 21, wherein said composition is a topical composition comprising desmethylselegiline at a concentration of between 1 x 10"1 1 mole / liter and 1 x 10" 3 mole / liter.
24. The method of claim 21, wherein said composition comprises desmethylselegiline in the form of its R (-) enantiomer and the S (+) enantiomer is substantially absent.
25. 25. The method of claim 21, wherein said composition comprises desmethylselegiline in the form of its S (+) enantiomer and the R (-) enantiomer is substantially absent.
26. 26. The method of either claim 22 or 23, wherein said topical composition is in the form of a cream.
27. 27. The method of either claim 22 or 23, wherein said topical composition is in the form of a gel.
28. The method of claim 21, wherein said composition comprises selegiline delivered by means of a patch.
29. 29. The method of claim 21, wherein said composition comprises desmethylselegiline delivered by means of a patch. The method of claim 21, wherein said composition further comprises a diluent or carrier, comprising one or more compounds selected from the group consisting of water, suspending agents, thickeners, humectants, preservatives, emollients, emulsifiers and film formers. icle SUMMARY The present invention is directed to methods that can be used in the treatment of wounds, burns and photodamaged skin. The methods can be used for both humans and animals, and involve the administration of compositions containing selegiline and / or desmethylseleglycine.