PROCESS FOR STABILIZING LEVOGYRE ASCORBIC ACID (LAA), A...

Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form

Reexamination Certificate

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C424S491000, C424S493000, C549S315000

Reexamination Certificate

active

06685965

ABSTRACT:

FIELD OF THE INVENTION
The present invention refers to a process of stabilizing levogyre ascorbic acid, also known as LAA or, more popularly “Vitamin C”, and to cosmetic, pharmaceutical or nutritional stable aqueous—or water-containing—compositions containing LAA.
BACKGROUND OF THE INVENTION
The levogyre ascorbic acid, hereinafter called LAA, presents the following formula:
and is an element known since long ago in the pharmacopeia, in medicine and in the cosmetic industry. Its application aims at the most varied benefits, from the treatment of stomachal problems, regeneration of skin signs hygienization and attenuation of skin marks. The expression “skin signs” as used herein means the signs of skin aging, such as wrinkles resulting from the action of time and from external factors such as climatic actions (sunshine, wind and temperature).
Examples of the employ of LAA in medicine are described in U.S. Pat. No. 2,132,662, granted in November, 1938 to Abbott Laboratories, the inventors of which are Ernst H. Volwiler and others, in this case as an antiscorbutic agent, and in U.S. Pat. No. 2,721,161, granted in 1955 to the inventor Maise and others, who taught the use of LAA plus a non-ionic surfactant in preparing oral or intravascular compositions for restoring the level of LAA in the blood.
The same is true of the cosmetic industry, where the LAA in molecular form, either associated or not with its salts and esters, has been employed in fighting the cutaneous aging process. In large part, in the segment of cosmetics, the salts and esters of the LAA alone are employed more frequently than the LAA in its molecular form, since the former are chemically more stable, which has been resulting in less effective products than the case would have been if the LAA in its molecular form had been used.
As to the form of action intended by the cosmetics industry for fighting cutaneous aging, be it by using the LAA or its derivatives, studies carried out by the applicant and the literature show that skin aging comprises a regressive phase of the life cycle with anatomic and physiological alterations, with degradation of certain organs and tissues.
Some literature references which incorporate the studies made by the applicant include: 1- DARR, D.; COMBS, S.; PINNELL, S. Ascorbic acid and collagen synthesis: Rethinking a role for lipid peroxidation.
Archives of Biochemistrv and Biophysics.
307, 331-5, 1993; 2- PINNEL, S.; MURAD, S. Vitamin C and collagen metabolism. In: KLIGMAN, A. M.; TAKASE, Y., Cutaneous aging Du University Medical Cancer, 275-92, 1988; 3- PINNELL S. Vitamina C tópica (Topical Vitamin C).
Revista de Cosmiatria & Medicina Estética.
31-6, 4
0
. trim 1995; 4- DARR, D.; COMBS, S.; DUNSTON, S.; MANNING, T.; PINNEL, S. Topical Vitamin C protects porcine skin from ultraviolet radiation-induced damage.
British Journal of Dermatology.
127, 247-53, 1992; 5- PINNELL, S. Regulation of collagen biosynthesis by ascorbic acid: a review.
The Yale Journal of Biology and Medicine,
58, 553-9, 1985.
The aging manifests itself on the skin by the loss of elasticity, loss of turgency, formation of wrinkles and the appearance of stains. Among the physiological alterations which actively contribute to this process, we can mention decrease in immunological functions, decline of basal metabolism, alterations in the structure of the conjunctive tissue, decrease in the capability of renewing the cutaneous lipids and in the hygroscopic components, leading to a lesser power of hydric retention and, consequently, to dehydration of the skin.
All of these alterations are the reflex of a series of internal and external factors which jointly contribute to the aging process.
As internal factors, directly controlled by the genetic patterns of the individual, the following can be cited: the chronological factor, defined by the aging, influenced by the genetic information contained in the cells; the immunological factor, given by the decrease of the Langerhans cells, responsible for the immunity vigilance of the skin; the hormonal factor, given by the decrease of the hormonal activity, especially of androgenic hormones, impairing the capability of hydric retention of the epidermis.
Interacting with the internal factors, a series of external factors too modulate the cutaneous aging, such as the photoaging, caused by the UV-A and UV-B radiations. The ultraviolet radiation acts at intercellular levels, inducing alterations in the DNA capable of forming incorrect proteins and enzymes, accelerating and altering the activities of cells. At the extracellular level, it may cause structural alterations in the collagen and elastin fibers and in the proteoglycans, which are fundamental in maintaining the turgor and the structure of the dermic layer. These alterations form groups of amorphous mass, which cause a lowering in the outer surface of the skin, also known as wrinkles. In addition to these damages, the UV radiation also promotes reactions of the molecular oxygen with lipids and proteins of the cellular membranes (lipoperoxidation), forming free radicals, which are molecules extremely dangerous to the cells.
In addition, one can point out as external factors the so-called Environmental Factors, for example, excessively low or high temperatures, wind, low relative moisture of the air and pollution, which in turn attack the protecting hydrolipidic mantle, leading to the loss of transepidermal, water with the consequent dehydration of the skin. There are equally the Emotional Factors and the Living Habits, generally stressing in the big cities and characterized by poor alimentation, smoking and drinking, which cause either alterations or unbalances in the metabolism of the lipids and proteins of the dermic layer.
These factors affect the skin in some way and can be enhanced by the age of the individual or by the biological cycle.
The biological cycles of an individual are constituted by a set of alterations resulting from these external and internal factors already described. The way in which each cycle has been lived by the individual will result in the degree of alterations.
The cutaneous aging can be divided into 3 main cycles: the first one begins at the age of 30, the second one comprises the range from 45 to 60 years of age, and the third one from the age of 60 on.
In the age group of from 30 to 45 the skin, in general, does not present any visible marks. The action of the free radicals decreases the activity of cells involved in the immunological responses. Every 10 years the skin loses 10% of this defense mechanism. Collagen and elastin, damaged by the UV radiation, have their restoration decreased. Natural aging and the action of free radicals are also responsible for this reduction.
Between 45 and 60 years of age, there is a drop in the production of tallow by the sebaceous glands, due to the lesser concentration of androgenic hormones. The signs of weakening of the circulatory system become more evident. The damages caused by free radicals intensify and the deficiencies of the immune system become more accented, in addition to a decrease in efficiency of the fibroblasts, impairing the restoration of collagen. There is also a reduction in the production of elastic fibers and of glucosaminoglycans, leading to the loss of sustainment.
From 60 years of age on, the signs which began in the preceding cycle become more accented. The sebaceous glands are virtually destroyed, because they receive less androgenic stimulus and the deficient circulatory picture becomes accented, thus decreasing the nutritional contribution and the elimination of toxins. An increase in the immunologic deficiency is noted, especially in the areas which are exposed to UV radiation, and the wrinkles become accented with an increase in seriousness of the previously described picture, due to the drop in production of collagen, elastin and glucosaminoglycans.
The technologies for treatment of the skin have tried to treat not only the visible signs of aging, but also to actuate more and more deeply on the causes thereof, by preventing

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