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MEMPHIS, TN, United States

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 100.00K | Year: 2006

DESCRIPTION (provided by applicant): MDI 301 is a synthetic retinoid that is similar to all-trans retinoic acid (RA) in its ability to stimulate collagen synthesis and inhibit the major collagen-degrading enzymes in skin. A major feature that distinguishes MDI 301 from RA is its lack of irritation when applied topically to skin. Recent studies from our laboratory have shown that topical treatment of diabetic rats with RA improves the healing of subsequently-induced abrasion wounds. Based on this, we have proposed the prophylactic use of RA as a way to improve structure/function in diabetic skin at risk for ulcer formation. A potential drawback to this strategy is skin irritation. If retinoid use in diabetic skin provokes irritation, this could result in non-use (as is does in other groups of retinoid users). Additionally, if the degree of irritation is too great, the irritation could counter-act the beneficial effects of retinoid treatment in the at-risk skin. The overall goal of the proposed studies is to determine if topical pretreatment of skin with MDI 301 will, like RA itself, improve healing of subsequently-induced wounds but do so without provoking irritation. If it can be shown that MDI 301 is as effective as RA without the negative consequence seen with RA use, it will provide a better agent for development as a chronic wound preventative. To achieve our overall goal, we will compare the effects of topical MDI 301 treatment with topical RA on dermal structure/function in streptozotocin diabetic (STZ-D) rats and compare healing of abrasion wounds in control rats, STZ-D rats and STZ-D rats that have been pretreated with topical RA or topical MDI 301.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 1.02M | Year: 2005

DESCRIPTION (provided by applicant): This application represents the Phase II version of SBIR grant R43 AR049621 entitled "Non-Irritating Retinoids for the Treatment of Aging Skin". Studies carried out prior to Phase I and during the Phase I portion of this project have demonstrated that a synthetic retinoid (identified as MDI-301) is as effective as all-trans retinoic acid (RA) in stimulating collagen repair in the dermis of mice (topically treated) and human skin (in organ culture) but, unlike RA, is non-irritating. We expect, therefore, that MDI-301 will ultimately provide a non-irritating alternative to RA for topical use in the prevention and treatment of aged/photoaged skin. In this Phase II application, we have identified a number of critical issues that need to be addressed as part of the development process of MDI-301. The three specific aims of this Phase II application identify the issues and our approach for addressing each of them. In Specific Aim I we will compare MDI-301 and RA for ability to stimulate extracellular matrix production and inhibit extracellular matrix degradation in human skin transplanted to severe-combined immunodeficient (scid) mice. As part of these studies, we will determine if treatment results in a histologically-evident improvement in the structure of the transplanted skin and determine if function (i.e., wound-healing capacity) is concomitantly improved in the treated skin. In Specific Aim II, MDI-301 and RA will be compared for their ability to modulate events in human skin that contribute to irritation. The information from theses studies will be used to help understand, at the cellular and molecular levels, why MDI-301 is non-irritating under conditions in which RA is irritating. Finally, in Specific Aim III, we will begin the safety evaluation of MDI-301 necessary to file an Investigational New Drug (IND) application with the FDA. The major goal of the Phase II effort is to develop MDI-301 to the point where we can attract a drug-development partner having the resources to obtain regulatory approvals (IND, clinical trials, NDA) and to market the drug effectively.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 100.00K | Year: 2008

DESCRIPTION (provided by applicant): MDI-301 is a synthetic retinoid. MDI-301, like RA, induces collagen synthesis and reduces expression of collagen-degrading matrix metalloproteinases in the skin. This agent also induces epidermal thickening. However, un like RA, MDI-301 is non-irritating when applied topically. In a recent study we showed that MDI-301 was effective in promoting the healing of superficial abrasion wounds in hairless rats with skin made atrophic by corticosteroid treatment. Given these find ings, we propose in this Phase I SBIR grant application to topically treat aged hairless rats with MDI-301 for a two-week period. Control animals will be treated with vehicle alone or with RA as a positive control. During the treatment period, animals will be examined for skin irritation. Following treatment, skin will be obtained and analyzed for collagen production and for elaboration of collagen-degrading enzymes. In other animals, superficial abrasion wounds will be induced following treatment. Healing in control and MDI-301-treated animals will be compared. If we can demonstrate that MDI-301 promotes healing of superficial abrasion wounds in aged skin but does not induce significant irritation, this will provide a strong impetus for development of this agent as a non-irritating wound preventative . The medical benefit and commercial potential will be significant. PUBLIC HEALTH RELEVANCEThe goal of this work is to develop a non-irritating retinoid for topical use in aged skin. The non-irritating retinoid will, hopefully, improve the structure and function of aged skin so that it will resist formation on non-healing wounds. It should do so without irritation.

Molecular Design International, Inc. | Date: 2014-05-29

Anti-aging cream containing a retinoic ingredient not for medical purposes; Cosmetic creams for skin care; Cosmetic preparations for skin care; Cosmetic preparations for skin renewal; Cosmetic skin fresheners; Moisturizing preparations for the skin; Moisturizing solutions for the skin; Non-foaming cosmetic preparations for skin care; Non-medicated cleansers for personal use, namely, skin; Non-medicated preparations all for the care of skin, hair and scalp; Non-medicated serums for use on skin; Non-medicated skin care preparations, namely, creams, lotions, gels, toners, cleaners and peels; Non-medicated skin creams; Non-medicated skin toners; Skin care preparations, namely, skin peels; Skin care products, namely, non-medicated skin serum; Skin cleansing cream; Skin cleansing lotion; Skin conditioners; Skin conditioning creams for cosmetic purposes; Skin cream; Skin creams; Skin creams in liquid and in solid form; Skin creams in liquid and solid; Skin creams in liquid and solid form; Skin emollients; Skin fresheners; Skin lotion; Skin lotions; Skin masks; Skin moisturizer; Skin moisturizing gel; Skin soap; Skin toners; Skin whitening creams; Skin whitening preparations; Wrinkle removing skin care preparations.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 99.00K | Year: 2003

DESCRIPTION (provided by applicant): Molecular Design International, Inc. (MDI) has designed and synthesized three synthetic retinoids based on the removal of the free carboxylic acid proton and replacement with an ester moiety in 14-all trans retinoic acid (RA), 13-cis retinoic acid (13-cis RA) and 9-cis retinoic acid (9-cis RA), respectively. Based on our preliminary studies in the rhinomouse model, one of these agents (MDI-301; the 9-cis RA derivative) has activity in models that predict efficacy in treatment of acne and efficacy in dermal repair. At the same time, this molecule appears to be significantly less irritating than the natural retinoids. The primary goal of the Phase I studies is to extend these preliminary findings with MDI-301 from animal models to preclinical models with human organ-cultured skin. Another important but ancillary goal of the Phase I research is to begin elucidating the cellular and molecular basis for retinoid irritation in the skin. The use of a non-irritating synthetic agent in conjunction with the naturally-occurring analogues should provide significant insight into the mechanisms by which the naturally occurring agents produce irritation. To achieve the overall objectives of the Phase I studies, we will compare MDI-301 with RA for efficacy (i.e., increased epidermal and dermal proliferation, increased procollagen production and decreased elaboration of matrix metalloproteinases) and for induction of irritation in organ cultures of human skin. Finally, we will utilize the rhinomouse model to examine MDI-403 (13-cis RA derivative) and MDI-101 (RA derivative) for i) reduction of superficial cysts (utriculi) formation, ii) induction of dermal repair and iii) induction of skin irritation. If MDI-301 or either of the other two agents proves to have efficacy without producing irritation, they will provide strong candidates for replacement of currently used retinoids in topical applications.

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