Skin treatment system

A skin treatment system comprises preparations for the topical application to the skin of histidine acting as a divalent cation chelator and exfoliant, pyridoxine and pantothenic acid and N-acetyl-D-glucosamine for increasing production of hyaluronic acid, superoxide dismutase and cysteine and vitamin E for decreasing the oxidative degradation of the hyaluronic acid, and pyroll carboxylic acid, or chemical salts thereof, and hyaluronic acid, or chemical salts thereof for providing increased hydration of the skin.

RELATED APPLICATIONS 
Benefit under Title 35, United States Code, Section 119(e) is claimed for 
the following U.S. Provisional Application which describes the invention 
which is the subject of this application: 
Provisional Application Number: 60/001,263 
Filed: Jul. 20, 1995 
Titled: Skin Treatment System 
BACKGROUND OF THE INVENTION 
A. Field of Invention 
This invention relates to the preparations for topical application to human 
skin and, more particularly, to new and improved skin cream or lotion 
compositions, which are especially useful in affecting the aging process 
of human skin. 
B. Description of Related Art 
The aging process of skin has been characterized by two main factors, the 
loss of elasticity and the loss of moisture, both of which are 
continuously lost over the course of the average human lifetime. 
Commercially available topical preparations have been designed to increase 
the moisture content of the skin. Most of the available topical 
moisturizing products provide only a short-term replenishment of 
moisture-providing ingredients. Some of such products contain glycolic 
acid alone and with other acids such as citric acid. Collectively, these 
acids may be referred to as "fruit acids," or "alpha-hydroxy" acids. The 
fruit acids are known to be capable, when applied to the skin, of aiding 
in the removal of older, dead, or keratinized skin cells, a process 
referred to as exfoliation. Exfoliation results in the exposure of the 
softer, younger skin cells, which otherwise lay below the older cells, and 
in this manner, exfoliation results in softer, younger appearing skin. 
Another positive consequence of the removal of the dead skin cells is that 
the still living, younger skin cells which are now exposed, produce, as a 
protective mechanism, increased amounts of at least one type of 
glycosaminoglycan molecule. Glycosaminoglycan molecules produced by the 
skin include hyaluronic acid, chondroitin sulfate, and dermatan sulfate. 
Hyaluronic acid is known to be produced in higher quantities by the skin 
cells in response to exfoliation. Hyaluronic acid has a large capacity for 
hydration. One gram of hyaluronic acid is able to hydrate to a volume of 3 
liters. The exposed, younger skin cells produce more hyaluronic acid than 
the older cells provided there are present sufficient substrates and 
co-factors required for hyaluronic acid synthesis by the skin cells. As a 
result, after exfoliation with fruit acids, a higher concentration of 
hyaluronic acid is produced in the skin. The hyaluronic acid, being a 
hydrating molecule, and being located deeper in the skin than topically 
applied hyaluronic acid or other topically applied moisturizers results in 
the ability of fruit acid application to the skin to act as, in effect, a 
long term moisturizer. The length of time of increased hydration of the 
skin can vary depending on the concentration and number of applications of 
fruit acids, as well as the endogenous stores of substrates and co-factors 
that are required and available to the skin for hyaluronic acid 
production. The combination of the two effects of topically applied fruit 
acids, exfoliation and increased skin production of hyaluronic acid, is 
believed to result in a lessening of the appearance of skin wrinkles. 
A negative consequence of the reliance upon exfoliation to appreciatively 
increase the amount of hyaluronic acid in the skin is that the skin, 
having been stripped of its protective layer of keratinized cells, is 
relatively unprotected but nevertheless is exposed to the elements. The 
younger, unprotected skin is susceptible to damage by environmental 
factors such as chemicals, and sunlight. It is also noted that after 
long-term use of fruit acids for exfoliation, endogenous stores of 
substrates and co-factors required for the production of hyaluronic acid 
can become depleted. As a result, the hyaluronic acid content, and 
subsequently the moisture content of the skin can actually be reduced by 
long-term, or chronic topical use of fruit acids in concentrations capable 
of exfoliation. Another disadvantage of the use of fruit acids is the fact 
that their use has been associated with a significant amount of 
irritation. 
Many skin cream compositions which are commercially available also address 
the other major component of skin aging, the loss of elasticity, through 
the use of moisturizers. One of the mechanisms of the loss of elasticity 
in aging skin is through the loss of elastin, a human protein which is a 
major component in elastic fibers and provides the skin with much of its 
elastic qualities. The break down of elastin is characterized by the 
deposition of lipids in the protein fold, followed by the attraction, by 
the lipids, of mineral salts. The accumulation of mineral salts, in 
particular calcium, decreases the elasticity of the elastin, and when the 
elastin molecule loses enough of its elasticity and becomes rigid, the 
molecule will break rather than elongate if enough tension is applied. 
When the elastin molecules break down, they are removed by endogenous 
immune surveillance mechanisms and may not be replaced at the same rate, 
resulting in a net loss of elastin in the skin tissue. At the area at the 
lateral folds of the eyes, the forehead, and on the neck, the chronic net 
loss of elastin, allows for the formation of wrinkles. Some commercial 
products include the molecule elastin in their formulations, However, as 
is the case with skin care moisturizers, there is no evidence that this 
exogenous elastin penetrates to a level that would be helpful, or that it 
remains in the skin long enough to provide any level of protection from, 
or reversal of, wrinkles. The known, available skin care products have not 
been demonstrated to interfere with the break down of elastin and the 
age-associated decrease in skin elasticity which in part characterizes the 
aging process of skin. 
SUMMARY OF THE INVENTION 
The present invention comprises formulations for skin cream or lotion 
compositions which are topically applied to the skin and contain chemical 
agents which in combination have the following properties: 
1. being a divalent cation chelator; 
2. being capable of the exfoliation of dead and keratinized skin cells 
without irritating the skin; 
3. being capable of increasing production of hyaluronic acid; 
4. providing rate limiting substrates for the production of hyaluronic acid 
by skin cells; 
5. being capable of reducing the oxidative degradation of hyaluronic acid; 
6. being capable of short term hydration of the skin; and 
7. being a water or lipid based delivery vehicle. 
The present invention comprises preferably the use of the amino acid, 
histidine, or a chemical derivative of histidine as the divalent cation 
chelating agent. When applied topically, and in adequate concentrations to 
the skin, histidine is an effective agent for simultaneously achieving 
exfoliation of dead and keratinized skin cells without irritating the skin 
as well as for chelating the calcium ions from the elastin molecules in 
the skin. 
The present invention further comprises concentrations of pyridoxine and 
pantothenic acid that are effective for inducing increased production of 
the hydrating glycosaminoglycan, hyaluronic acid, including in skin cells 
that have not been treated extensively, or at all, with an exfoliating 
agent. Inducing increased production of hyaluronic acid independently of 
exfoliation causes the hydration of the skin without increasing the risk 
of environmental damage to young skin cells. 
Hyaluronic acid, which is produced by all living skin of human beings, is a 
hydrating molecule, one gram being known to hydrate to a volume of 3 
liters. When young skin cells are exposed after exfoliation, they produce 
larger quantities of hyaluronic acid which is a glycosaminoglycan which is 
composed of a chain of alternating, repeating, D-glucuronic acid and 
N-acetyl-D-glucosamine molecules. N-acetyl-D-glucosamine is known to be a 
rate-limiting factor in the hyaluronic acid production by living cells. 
The topical application of glucosamine, or a readily metabolizable form of 
the glucosamine molecule, in particular N-acetyl-D-glucosamine, assists in 
the continued production of hyaluronic acid by increasing the available 
supply of a rate limiting substrate in the production of hyaluronic acid 
by skin cells. The molecules superoxide dismutase, cysteine, and vitamin 
E, are added to the preferred embodiment of the present invention to stop 
the oxidative degradation of the hyaluronic acid present in the skin, 
thereby slowing the depletion of that hydrating substance. The present 
invention includes the direct topical application of short term hydrating 
molecules such as pyroll carboxylic acid, or chemical salts thereof, and 
hyaluronic acid, or chemical salts thereof to the skin to provide 
hydration results that are more immediate than the results of the 
induction of increased production of hydrating substances by the skin. 
A principal objective of the present invention is to provide a new and 
improved skin care system for topical application which meets the 
foregoing requirements and which is capable of, and is safe to use for, 
the exfoliation of the skin without irritation. 
Another and further object and aim of the present invention is to provide a 
new and improved skin care system for topical application which meets the 
foregoing requirements and which is capable of, and is safe to use for, 
providing to the hyaluronic acid-producing skin cells, substances which 
are required by the skin for the production of hyaluronic acid. 
Yet another and further object and aim of the present invention is to 
provide a new and improved skin care system for topical application which 
meets the foregoing requirements and which is capable of inducing skin 
cells to produce hyaluronic acid, with a minimum of exfoliation. 
Yet another and further object and aim of the present invention is to 
provide a new and improved skin care system for topical application which 
meets the foregoing requirements and which is capable of providing 
increased moisturization of the skin afforded by fruit acid exfoliation 
with a minimum of exposure of young skin cells to damaging environmental 
factors. 
Yet another and further object and aim of the present invention is to 
provide a new and improved skin care system for topical application which 
meets the foregoing requirements and which is capable of providing to the 
hyaluronic acid-producing skin cells, substances required for the 
production of hyaluronic acid. 
Yet another and further object and aim of the present invention is to 
provide a new and improved skin care system for topical application which 
meets the foregoing requirements and which is capable of the inhibition or 
reversal of the break down of the molecule elastin in the skin. 
Yet another and further object and aim of the present invention is to 
provide a new and improved skin care system for topical application which 
meets the foregoing requirements and which is capable of the inhibition of 
the oxidative degradation of hyaluronic acid in the skin. 
Other objects and advantages of the invention will become apparent from the 
Description of the Preferred Embodiments and will be in part pointed out 
in more detail hereinafter. 
Further features of the present invention are set forth in the following 
detailed description. 
The invention consists in the elements, combination of elements and use 
thereof as hereinafter described and the scope of the invention will be 
indicated in the appended claims. 
DETAILED DESCRIPTION OF THE INVENTION 
The present invention comprises a combination of chemical agents for 
topical application to the skin. The topical formulations described in the 
detailed description will be referred to as, for the sake of simplicity, 
creams; the preferred embodiment of the present skin care system consists 
of a first preparation with a water soluble base and a second preparation 
having an emulsified solvent base containing both water and lipids. There 
are few limitations to the types of solvents which can be utilized in the 
skin care system. The most preferable solvents being those in which the 
ingredients are soluble and are pleasing to the consumer. 
The preferred embodiment of the water based preparation includes a divalent 
cation chelator for the purpose of reducing the concentration of mineral 
salts, particularly calcium salts. As described above, the aging human 
skin is characterized in part by a loss in elasticity which is attributed 
to the attraction of mineral salts, particularly calcium salts, by lipids 
deposited in the protein folds of elastin molecules, increasing the 
rigidity of, and solidifying the aging elastin molecules. The molecule 
histidine, and other divalent cation chelators, are able to remove when 
applied topically to the skin of human beings, mineral salts, in 
particular, the mineral salt calcium. It is believed that the topical 
application of cation chelator, in sufficient quantities, will create a 
concentration gradient of calcium, from deep to superficial, to occur, 
resulting in a reduction in the amount of calcium available to bind to 
elastin proteins, and, if the removal of calcium salts is aggressive 
enough, the concentration gradient created is significant enough that 
mineral salts already in the elastin protein folds are dislodged, thereby 
reversing a major step in the break down of elastin. 
Taurine and histidine are both amino acids and divalent cation chelators 
that were found to have the ability to remove calcium from the skin of 
humans. More particularly, histidine was found to chelate significant 
amounts of calcium from human skin at concentrations that were 
non-irritating. Histidine was found to cause an immediate softening of the 
skin after it is washed off and the mechanism for this softening, appears 
to include exfoliation of older skin cells. A variety of preparations 
including Histidine in concentrations from 0.1 to 20% by weight were 
tested and found to exhibit exfoliant activity. The exfoliant activity of 
Histidine is believed to be caused by the breakage of calcium dependent 
bonds and cross bridges contained in the intercellular proteins of the 
skin rather than the direct caustic effect of conventional exfoliants.

As illustrated in FIG. 1, in an experiment utilizing skin treated with 
various concentrations of histidine, it was found that, in a dose 
dependent manner, histidine was able to remove dead and keratinized skin 
cells. For the experiment, one milliliter of solutions containing either 
normal saline, or normal saline with 12.5, 6.25, 3.13, 1.56, 0.78, and 
0.39 percent histidine monohydrochloride:monohydrate, respectively were 
placed onto the skin of volunteers. After 10 minutes of the experimental 
solutions being in contact with the skin, the skin at each site was 
scraped with a glass slide to collect skin cells. 9 samples at each 
concentration were collected. The epithelial cells from each sample were 
counted using a model ZM, Coulter particle counter. The Coulter counter 
was calibrated using a Neubauer hemacytometer. The counting of cells by 
the particle counter was confirmed by microscopy. The y-axis of FIG. 1 
represents the total number of cells collected, while the x-axis 
represents the concentration of histidine used. At no concentration did 
any of the volunteers have demonstrable irritation or dermatitis or any 
other adverse side effect related to the application of the histidine. 
The preferred embodiment of the water soluble preparation of the present 
invention, therefore, contains the molecule histidine, or any one of its 
salts in a solution, or suspension, in a concentration by weight from 0.1 
to 20%. More preferably, the concentration of histidine is from 0.3 to 
12.5% by weight, and most preferably in a concentration between 0.6 and 
0.8% by weight. 
Alternatively, the molecules taurine, Ethylenediaminetetraacetic acid 
("EDTA"), or EGTA, or other divalent cation chelating agents could be 
substituted for histidine. A preparation of a concentrated solution of 
EDTA was experimentally applied to the skin, applying it to a forearm, 
while applying a control mixture to the other forearm. After 10 minutes, 
both solutions were rinsed from the forearms, and the arms dried and the 
result was that the treated arm was observably softer than the control 
arm. The subjective observation was confirmed by several other observers. 
A solution containing 1% by weight of EDTA was applied to the one forearm 
for several applications. Topical application of EDTA in higher 
concentrations was found to cause skin irritation. A 0.5% solution of EDTA 
has been found to have similar softening effects without irritation while 
a 1% solution by weight of EDTA caused skin irritation. 
The hypothesis that the topical application of a cation chelator such as 
EDTA was capable of removing calcium from human skin was tested 
experimentally. 2 Milliliters of 0.5% EDTA solution were placed onto one 
side of the previously washed (with cation-free soap) foreheads of three 
volunteers. A control solution of 0.5% sodium chloride was placed on the 
other side of each volunteer's forehead. After 10 minutes, the remaining 
solution was collected by scraping the skin. An equal weight of this 
solution from treated and control scrapings was then pooled for each group 
respectively and rehydrated to a volume of 5 Ml. Each of the samples was 
then analyzed for calcium concentration in a trace elements laboratory 
using an ICP analyzer. The treated samples contained 16.58 parts per 
million (PPM) of calcium, while the control sample contained 4.877 PPM of 
calcium, thus demonstrating that a cation chelator was capable of removing 
a significant quantity of calcium from the skin of humans. 
The preferred embodiment of the water based preparation, also contains a 
form of the molecule glucosamine, preferably N-acetyl-glucosamine. When 
added to the composition, N-acetyl-D-glucosamine ensures that the lack of 
a usable form of glucosamine does not rate-limit the hyaluronic acid 
production, that is induced either by the above-mentioned exfoliation or 
the alternative method described below. The preferred concentration of 
N-acetyl=D-glucosamine is between 0.005 and 12% by weight, more preferably 
0.01 and 5% by weight, and most preferably 0.1% by weight. The best 
results from the use of the water soluble preparation are obtained when it 
is applied and allowed to remain on the skin for approximately 10 minutes, 
when it is gently removed by rinsing it off with cool water. 
The preferred embodiment of the invention further comprises a second 
preparation having an emulsified water and lipid base that is most 
beneficially used by topical application and being left on the skin after 
application. Since the second preparation is to be left on the skin, it 
contains the molecule N-acetyl-D-glucosamine, which is useful for the same 
reasons stated above, but which will be available for a longer period of 
time to the skin cells. 
The preferred embodiment of the second preparation also contains the 
molecules pantothenic acid and pyridoxine, two vitamins which appear to 
work synergistically to increase cellular production of hyaluronic acid. 
The inclusion of pantothenic acid and pyridoxine is an alternative method 
of inducing hyaluronic acid production without relying on the exfoliation 
of the skin as described above to increase cellular production of 
hyaluronic acid. Topically applied pantothenic acid and pyridoxine were 
experimentally shown to be capable of inducing the production of 
hyaluronic acid in human skin. Approximately 0.5 mL of a solution 
containing 0.08% pantothenic acid and 0.2% pyridoxine in an aqueous base 
was applied to the skin of one hand of an individual, and the opposite 
hand served as a control, having only water applied to it at the same 
time. Within one week, the skin on the active ingredient treated hand was 
observed to be noticeably softer than the control treated hand. Then the 
active and control solutions were applied nearly daily for six weeks. Two 
weeks after discontinuation of the use of both of the solutions, a small 
piece of skin was removed from each of the treated hands (superficial 
biopsy), to obtain 100 micrograms of tissue. The tissue was digested and 
tested for hyaluronic acid using a very sensitive radio-immuno-assay. The 
skin sample from the active ingredient treated hand contained a much 
higher concentration of hyaluronic acid (522.51 nanogram/mg) than the skin 
sample from the control treated hand 115.58 nanogram/mg). This represents 
a greater than 450% increase in the amount of hyaluronic acid in the 
treated skin versus the control. Because the sample was taken 2 weeks 
after discontinuation of product use, a long term effect on the hyaluronic 
acid content of the skin by the topical application of a combination of 
pantothenic acid and pyridoxine is suggested. The preferred embodiment of 
the second preparation of the invention contains pantothenic acid in a 
concentration from at least 0.001 to a maximum of 2% by weight, with a 
more effective range of concentration being from 0.1% to 1.5% by weight. 
The most preferable concentration of pantothenic acid was found to be 
0.8%. The preferred embodiment of the second preparation of the invention 
also contains pyridoxine in a concentration from at least 0.0025% to a 
maximum of 5% by weight, with a more effective range of concentration 
being from 0.25% to 3.75% by weight. The most preferable concentration of 
pyridoxine was found to be 2%. 
The preferred embodiment of the second preparation also contains the enzyme 
super oxide dismutase (SOD), and the molecules cysteine, and tocopherol 
(vitamin E) which are known to inhibit the oxidative degradation of the 
molecule hyaluronic acid. Each of these three molecules are added in a 
concentration ranging from 0.001% to 1.5% by weight, most preferably in a 
concentration of between 0.1 and 0.5% by weight. By protecting the 
hyaluronic acid molecule from degradation, these additional agents provide 
for longer lasting hyaluronic acid molecules and subsequently, longer 
lasting hydration of the skin. 
In addition, the preferred embodiment of the second preparation includes 
the sodium salt of pyroll carboxylic acid (NaPCA) and the sodium salt of 
hyaluronic acid. Those molecules are included in the preferred embodiment 
of the present invention in the concentrations of 0.5% and 0.2% 
respectively to produce short-term hydration. 
According to the foregoing, the preferred embodiment of the skin care 
system of the present invention includes the following: 
A. The first, water soluble, preparation comprising the following active 
ingredients: 
1. histidine in a concentration by weight from 0.1 to 20%, and 
2. N-acetyl=D-glucosamine in a concentration by weight from 0.005 and 12% 
by weight; and 
B. The second, emulsified water and lipid based preparation comprising the 
following active ingredients: 
1. N-acetyl-D-glucosamine, and 
2. pantothenic acid in a concentration from at least 0.001 to a maximum of 
2% by weight, and 
3. pyridoxine in a concentration from at least 0.0025% to a maximum of 5% 
by weight, and 
4. super oxide dismutase (SOD) in a concentration ranging from 0.001% to 
1.5% by weight, and 
5. cysteine in a concentration ranging from 0.001% to 1.5% by weight, and 
6. tocopherol (vitamin E) in a concentration ranging from 0.001% to 1.5% by 
weight, and 
7. the sodium salt of pyroll carboxylic acid (NaPCA) in a concentration of 
0.5% by weight, and 
8. the sodium salt of hyaluronic acid in a concentration of 0.2% by weight. 
It will be appreciated that the foregoing may be altered in a number of 
ways with differing but still beneficial results. Specifically, the 
concentrations of active agents as given herein are believed to be 
optimal; however, it is anticipated that significant alterations in exact 
concentrations may be made without rendering the preparation harmful or 
ineffective. It will further be appreciated that the treatment of the 
present invention may be formulated entirely in a single water based 
preparation or in dual preparations as described without a water and lipid 
emulsion base for the second preparation. In the event only water based 
preparations are used, the hydrophobic tocopherol would preferably be 
emulsified, either chemically or physically for the better results. In 
addition, it is expected that the addition of other known skin treatment 
agents to the treatment preparation of the present invention may have 
beneficial results. 
While the preferred constituents and method of the foregoing invention have 
been set forth for purposes of illustration, the foregoing description 
should not be deemed a limitation of the invention herein. Accordingly, 
various modifications, adaptations and alternatives may occur to one 
skilled in the art without departing from the spirit and the scope of the 
present invention.