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Treatment of skin disorders

a technology for skin disorders and compositions, applied in the direction of drug compositions, dermatological disorders, biocide, etc., can solve the problems of significant cosmetic problems, source of discomfort, keloids and hypertrophic scars that can become so large that they are crippling

Inactive Publication Date: 2006-05-16
HADASIT MEDICAL RES SERVICES & DEVMENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a composition for treating skin disorders caused by abnormal cell behavior. The composition includes a compound of formula (I) or (II) described above, which is a member of a group consisting of hydrogen, halogen, nitro, benzo, lower alkyl, phenyl, and lower alkoxy. The compound is combined with a pharmaceutically acceptable carrier. The invention also provides a method for manufacturing a medicament for treating skin disorders caused by abnormal cell behavior. The medicament includes the compound of formula (I) or (II) described above. The compound is particularly effective in treating keloid-like growths, which are skin disorders characterized by abnormal cell behavior.

Problems solved by technology

First, they represent a significant cosmetic problem, particularly on the face where they can be highly disfiguring and a source of considerable distress to the patient.
Second, they can also be a source of discomfort through pruritus and even pain.
Indeed, both keloids and hypertrophic scars can become so large that they are crippling [D. D. Datubo-Brown, Brit. J. Plas. Surg., Vol 43, p.
Furthermore, although keloids on the cornea are rare, they can potentially result in blindness [D. D. Datubo-Brown, Brit. J. Plas. Surg., Vol 43, p.
Finally, all three conditions are caused by a genetic defect in skin cells, which causes these cells to show abnormal behaviors.
Unfortunately, currently available treatments to inhibit the formation and growth of keloids and hypertrophic scars, and to treat psoriasis, are not completely successful.
However, neither treatment can prevent the lesion from recurring, and surgery especially carries a risk of increased morbidity.
However, the side effects of such medications are potentially dangerous and are not universally successful.
Other treatments, such as radiation, also showed variable effectiveness and are associated with other potential side effects [Rockwell, W. B. et al., Plastic and Recon. Surg., Vol. 84, p.
Unfortunately, only a few inhibitors of collagen synthesis are available, despite the importance of this protein in sustaining tissue integrity and its involvement in various disorders.
Unfortunately, none of these inhibitors are collagen-type specific.
Also, there are serious concerns about the toxic consequences of interfering with biosynthesis of other vital collagenous molecules, such as Clq in the classical complement pathway, acetylcholine esterase of the neuro-muscular junction endplate, conglutinin and pulmonary surfactant apoprotein.
Their prolonged use causes lathritic syndrome and interferes with elastogenesis, since elastin, another fibrous connective tissue protein, is also cross-linking.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Collagen Synthesis in Keloid-Derived Tissue

[0060]The presence of large amounts of collagen protein, as well as of the expression of the collagen α1(I) gene, were demonstrated in keloid-derived tissue. The results are shown in FIGS. 1A and 1B. The experiment was conducted as follows.

[0061]A keloid, which had arisen in response to the piercing of the ear for insertion of an earring, was removed from the ear lobe of a 21 year-old male. The keloid tissue was sectioned so that histological studies could be performed. Briefly, the tissue samples were collected into phosphate-buffered saline (PBS) and fixed overnight in 4% paraformaldehyde in PBS at 4° C. Serial 5 um sections were prepared after the samples had been dehydrated in graded ethanol solutions, cleared in chloroform and embedded in Paraplast. Differential staining of collagenous and non-collagenous proteins was performed with 0.1% Sirius red and 0.1% fast green as a counter-stain in picric acid. This procedure stains collagen re...

example 2

Inhibitory Effect of Halofuginone on Collagen Synthesis in Keloid-Derived Tissue

[0064]Halofuginone was shown to specifically inhibit collagen synthesis in keloid-derived tissue. The results are shown in FIG. 2. The experiment was conducted as follows.

[0065]The keloid was removed as described in Example 1 above. The keloid-derived cells were incubated with and without Halofuginone for 24 hours in 0.5 ml glutamine-free DMEM containing 5% FCS (Fetal Calf Serum), ascorbic acid (50 μg / ml), B-aminopropionitrile (50 μg / ml) and 2 μCi of [3H]proline. At the end of incubation, the medium was decanted and the cells were incubated with or without collagenase for 18 hours, followed by precipitation of proteins by the addition of TCA (trichloroacetic acid). The amount of radiolabelled collagen was estimated as the difference between total labelled-proline containing proteins and those left after collagenase digestion [Granot, I. et al., Mol. Cell Endocrinol., Vol. 80, p. 1-9, 1991].

[0066]The rati...

example 3

Halofuginone Inhibition of Sulfate Incorporation into ECM of Cultured Endothelial Cells

[0067]As noted above, skin cell hyperproliferation is enabled by the deposition of ECM components. The following examples illustrate the ability of Halofuginone to inhibit such deposition of ECM components, further supporting the use of Halofuginone as a treatment for psoriasis. These examples illustrate the unexpected finding that Halofuginone completely abolishes deposition of all ECM components, and not just collagen, thereby preventing cell proliferation which is enabled by the formation of ECM. Cultures of bovine corneal endothelial cells were established from steer eyes and maintained as previously described [D. Gospodarowicz, et al., Exp. Eye Res., No. 25, pp. 75-99 (1977)]. Cells were cultured at 37° C. in 10% CO2 humidified incubators and the experiments were performed with early (3-8) cell passages.

[0068]For preparation of sulfate-labelled ECM (extra-cellular matrix), corneal endothelial...

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Abstract

An effective treatment for skin disorders characterized by abnormal skin cell behavior, including a pharmaceutically effective amount of Halofuginone. Skin disorders which can be treated include keloids, hypertrophic scars, psoriasis, acne, seborrhea and alopecia. Halofuginone can reduce or eliminate clinical symptoms of these disorders, as well as substantially prevent the formation of keloids and hypertrophic scars.

Description

FIELD AND BACKGROUND OF THE INVENTION[0001]The present invention relates to a method and a composition for the treatment of skin disorders and, more particularly, to a method and a composition for the treatment and prevention of psoriasis, hypertrophic scars and keloids.[0002]Keloids are benign fibrotic tumors which are believed to arise from the reticular dermis. They are characterized by increased tissue fibrosis and collagen deposition [Friedman, D. W. et al., J. Surg. Res., Vol. 55, p. 214-222, 1993]. Keloids usually first appear when a patient is between the ages of 10 and 30 years, and are often associated with trauma. They occur most commonly on the upper back, anterior chest, shoulders and ear lobes. Keloids are especially frequently seen in patients of African or Asian descent.[0003]Hypertrophic scars are somewhat related to keloids, in that they are also characterized by increased tissue fibrosis and collagen deposition [Friedman, D. W. et al., J. Surg. Res., Vol. 55, p. 2...

Claims

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Application Information

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Patent Type & Authority Patents(United States)
IPC IPC(8): A61K31/519A61K31/517C07D401/06A61P17/02A61P17/06A61P17/08A61P17/10A61P17/14
CPCA61K31/517A61P17/00A61P17/02A61P17/06A61P17/08A61P17/10A61P17/14
Inventor PINES, MARKNAGLER, ARNON
Owner HADASIT MEDICAL RES SERVICES & DEVMENT
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