Topical micronutrient delivery system and uses thereof

Details Topical micronutrient delivery system and uses thereof Topical micronutrient delivery system and uses thereof

2001-04-11

2002-10-15

Azpuru, Carlos (Department: 1615)

Drug, bio-affecting and body treating compositions

Preparations characterized by special physical form

Cosmetic, antiperspirant, dentifrice

C424S078030, C424S423000, C424S433000, C424S436000, C424S447000, C424S449000

Reexamination Certificate

active

06464992

ABSTRACT:

FIELD OF THE INVENTION
This invention relates to a topical micronutrient delivery system. The system is useful in, e.g., delivery of desirable and/or necessary materials, such as micronutrients, to a subject in need of same. Therapeutic uses of the system are also described.
BACKGROUND AND PRIOR ART
The skin plays multiple roles in protection from environmental insults. Environmental exposure results in the progressive deterioration of skin that is initially cosmetic but can lead to end stage diseases such as actinic keratosis and skin cancer.
Skin deterioration results from damage to DNA and protein, and compelling evidence indicates that reactive oxygen species (“ROS” hereafter) are involved in the generation of DNA damage that results in the loss of genomic integrity of skin cells. Skin cells contain inherent mechanisms for the maintenance of genomic integrity. A growing body of evidence demonstrates that micronutrients including vitamins B6, B12, C, E, folate, and niacin are involved in the maintenance of genomic integrity via mechanisms ranging from scavenging ROS, to the repair of DNA damage. Sub-clinical micronutrient deficiencies are prevalent even in advanced societies and micronutrient status decreases with age.
Skin is a complex organ system, consisting of multiple layers. The uppermost, or “stratum corneum” layer consists of non-living material derived primarily from the terminal differentiation of epidermal keratinocytes, and provides a protective barrier for the underlying components of skin. The epidermis contains a number of cell types, although keratinocytes are the major cell type. Dermal fibroblasts are embedded within a matrix comprised of collagen, elastin, proteoglycans, and other extracellular matrix molecules. Blood capillaries are found in the dermis, but the epidermis is non-vascular.
As people age, progressively deleterious changes in skin appearance occur. The initial changes are the loss of smooth skin texture and the appearance of age spots, followed by changes in elasticity that lead to the appearance of skin wrinkles. The age at which these changes appear and the rate at which one stage progresses to the next varies greatly from individual to individual. During the normal aging process, both the epidermis and dermis become thinner, with a loss of cell number and connective tissue, leading to the appearance of fine wrinkles. Ultraviolet (UV) irradiation from the sun causes photodamage that accelerates skin deterioration. In contrast to the thinning observed in sun-protected skin, photodamaged skin has a thickened and rough appearance with an increase in deeper skin wrinkling. Photodamage also causes end-stage skin deterioration, including pre-malignant lesions termed actinic keratosis, and skin cancer.
Compelling evidence now indicates that oxidative stress, defined as an abnormal accumulation of ROS, is involved in the pathophysiology of skin deterioration. ROS include superoxides, the hydroxyl radical, hydrogen peroxide, singlet oxygen, nitric oxide, peroxynitrite, and hypochlorite. See, e.g., Simonian, et al., Ann. Rev. Pharmacol. Toxicol. 36:83-106 (1996), incorporated by reference. All cells are exposed to ROS during the normal course of energy metabolism, via environmental exposure and/or immune surveillance. While ROS are involved in normal cell signaling pathways, elevation of ROS during oxidative stress disrupts signaling pathways, often resulting in cell death by apoptosis or necrosis. Thus, it is likely that ROS are involved in the loss of cell numbers observed even in sun-protected skin over time. Exposure to the ultraviolet rays of sunlight is a major source of skin oxidative stress. Two major targets for damage by ROS in skin are DNA and protein. DNA damage is of particular interest in that unrepaired damage can lead to the loss of skin cells and to an altered function of cells that survive genotoxic stress.
While some changes in skin during aging can not be avoided, much of the skin deterioration that occurs at an early age is avoidable. Skin cells contain a number of protective mechanisms for the prevention and repair of damage to DNA and proteins caused by ROS. First, a number of intracellular molecules, including glutathione and the antioxidant vitamins C and E, play key roles in scavenging ROS before they can react with cellular macromolecules. Indeed, the antioxidant vitamins have already found application in the prevention of skin deterioration, as they are components of many skin creams. Second, cells contain complex mechanisms for the maintenance of genomic integrity. Of particular interest herein is the accumulating evidence for the involvement of micronutrients in maintenance of DNA structure and in DNA repair mechanisms. There are approximately 40 micronutrients that are required, in small amounts, to maintain normal human metabolism (Ames, Ann. N.Y. Acad. Sci 889: 87-106 (1999), incorporated by reference). For many of these micronutrients, a sizeable portion of the population consumes significantly less of the micronutrient than what has been established as the recommended daily intake see Wilson, et al. Data Tables: Combined Results from USDA's 1994 and 1995 continuing survey of food intakes by individuals and 1994 and 1995 diet and health knowledge survey (USDA/ARS Food Surveys Research Group, Beltsville Human Nutrition Research Center, Riverdale, Md. (1997), incorporated by reference. The percentage of the U.S. population that is deficient in a particular micronutrient ranges from 2 to 20%. Ames, supra. To complicate matters, micronutrient status deteriorates further with increasing age. Bates, et al., Br. J. Nutr 82(1):7-15 (1999). Much of our knowledge about the relationship between micronutrients and various diseases such as cancer derives from measurements of micronutrient levels in plasma. While there is much to learn regarding plasma micronutrient levels and target tissue levels, there is evidence that deficiencies observed in plasma are also observed in skin. See Peng, et al., Canc. Epidermiol Biomarkers Prev 2(2): 145-50 (1993). This is not surprising, since the epidermal layer of skin does not contain blood vessels, making delivery of dietary micronutrients to skin inefficient. Of particular concern for skin deterioration are observations that micronutrient deficiencies can mimic radiation- and chemical-induced DNA damage, by effecting single-and double-strand breaks and/or oxidative lesions. Ames, supra. Specifically, deficiencies in folic acid, B12, B6, niacin, vitamin C, vitamin E, iron, and zinc can result in DNA damage. Ames, supra. For each of these micronutrients, there are known metabolic pathways that describe the rationale by which a deficiency results in DNA damage in the absence of genotoxic stress. Additionally, the micronutrient deficiencies would be expected to exacerbate the deleterious effects of genotoxic stress. The above information indicates that improving the micronutrient status of skin cells is desirable, as this will improve the health of skin and likely retard skin deterioration.
It is an object of the invention to provide a tropical delivery system which is useful in making micronutrients available, or making these micronutrients available in greater quantities than possible in the past.
It is a further object of the invention to arrest or to prevent deterioration of organs such as skin, by making micronutrients available in amounts sufficient to arrest or to prevent the deterioration.
How this is accomplished will be seen from the disclosure which follows.


REFERENCES:
patent: 5185325 (1993-02-01), Brawn et al.

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