Scalp treatment

A scalp treatment for reducing average daily hair loss periodically applies to the scalp a composition containing an active chelating agent sufficient to chelate at least 0.3 milligrams of divalent calcium ion per milliliter of the composition and leaving the chelating agent in contact with the scalp for at least eight hours. Particularly preferred chelating agents comprise ethylene diamine tetraacetic acid, citric acid, and soluble salts thereof.

BACKGROUND OF THE INVENTION 
This invention concerns a scalp treatment shown to decrease average daily 
hair loss in a number of people in statistically significant tests. An 
overall decrease of 21 percent of average daily hair loss has been shown 
after two months of treatment of a test panel. Average daily hair loss 
decreased for over 75 percent of the panelists. Statistically, there is a 
more than 90 percent confidence level that a decrease in average daily 
hair loss occurred in the test group as a whole. 
There is no present evidence that the technique stimulates hair growth, and 
no tests for this effect have been made. No claims are made that this 
treatment affects "male pattern" baldness, and no tests have been made for 
such an effect. No tests have been conducted for abnormal hair conditions. 
The whole topic of hair growth connotes elements of folklore, superstition, 
and even "quackery." Still a large number of valid scientific studies on 
hair growth or hair loss exist. 
Falling hair has been approached in many different ways throughout history. 
Records from Egyptian tombs relate cures for baldness dating from the 
Bronze Age. Fats of the snake, hippopotamus, and other animals were 
regarded as topical treatments for hair loss. Since that remote period, 
little has changed until recently. 
Modern approaches to the problem of hair loss have stressed several 
possible avenues of treatment. 
The nutrient/microcirculation approach centers on supplying alleged 
nutritional factors or oxygen that the hair follicles may be lacking. No 
research to date has given evidence to support the concept that hair 
follicles senesce and fall in response to a vital nutrient or oxygen which 
becomes limiting. Similarly, treatment of falling hair by supplying 
nutrients has not been shown to have any effect. 
A second approach has stressed "unplugging" of the hair follicle. This view 
suggests that the hair follicle is "strangled" by buildup of sebaceous 
secretions in the pilary canal. Treatment of this imaginary microscopic 
strangulation with products containing polyoxyethylene sorbitan fatty acid 
esters, such as polysorbate-60 or polysorbate-80, has gained some 
underground popularity, but again there is no scientific evidence of 
benefit. 
Interest in hair loss and in hair growth has recently been rekindled by the 
promise of topically applied drugs (minoxidil, diazoxide, or viprostal, 
for example) which in some cases support hair regrowth in balding persons. 
The mechanism of actions of these drugs is not known and their safety and 
effectiveness are under study. 
Human hair grows in cyclic fashion with each of the individual hair 
follicles responding independently to the physiological condition of the 
person. At any given time some 85 to 90 percent of the human scalp hair 
follicles are in the active stage of growth known as "anagen." This anagen 
state is characterized by active production of cells which keratinize to 
form the growing hair shaft. The growth of any individual hair follicle 
may proceed continuously for a variable period of up to six years. For 
reasons which are not fully understood, the anagen follicle passes into a 
state of metabolic quiescence (catagen) and then into a state of senesence 
(telogen) characterized by deterioration of the bulb and eventual loss of 
the structure, including the hair shaft. Under normal conditions the 
"germ" of the new anagen bulb is left behind by the extruded follicle so 
that a new bulb will differentiate and grow at virtually the same location 
as its predecessor. 
When the cyclic nature of this process becomes unbalanced, that is, when 
generation of new anagen bulbs is retarded with respect to the entry of 
bulbs into catagen and telogen states, hair loss occurs. Balding, 
therefore, is the result of many cycles of hair growth out of balance, 
which is characterized by gradual diminution of the number of anagen bulbs 
over successive cycles. It is reasonable to assume that if hair follicles 
can be maintained in the active anagen state for a longer period, there 
will be less hair loss as follicles pass to the catagen and telogen 
states. The fewer bulbs lost in the normal progression of hair follicles 
or senescence, the fewer new bulbs need to take their place. 
It is therefore desirable to provide a treatment which modulates the normal 
rate of conversion of active anagen bulbs to quiescent or senescent ones. 
It is desirable that such a treatment decrease the rate of shedding of 
hair. It is desirable that such a treatment maintain the anagen phase of 
bulb activity. It is desirable that such a treatment employ inexpensive, 
harmless materials and be performed by individuals without professional 
assistance.

SUMMARY OF THE INVENTION 
There is, therefore, provided in practice of this invention according to a 
presently preferred embodiment, a topical scalp treatment which decreases 
the average daily hair loss in many individuals susceptible to such loss. 
Such a treatment comprises distributing onto the scalp a composition 
containing a sufficient amount of active chelating agent to chelate at 
least 0.3 mg of divalent calcium per milliliter of the composition and 
leaving the composition in contact with the scalp for at least eight 
hours. Preferably initial treatments distribute the composition onto the 
scalp at least daily. After a period of initial treatment, the frequency 
of application may be reduced to alternate days. 
DESCRIPTION 
Histochemical studies of hair follicles strongly indicate that anagen 
follicles differ from catagen and telogen follicles with respect to 
presence of calcium ions. Anagen follicles stain very sparingly for 
calcium, while catagen and telogen bulbs stain strongly for the ion. 
Vellus follicles react still more strongly to the stain. Vellus refers to 
the diminutive, nongrowing, nonpigmented, incompletely keratinized hair 
characteristic of the bald scalp. This is the common "peach fuzz" 
appearance of the scalp on bald persons. 
Somewhat more quantitatively, it appears that the average calcium content 
of anagen bulbs is in the order of one nanogram per bulb. The average 
calcium content of catagen bulbs appears to be about twice as high. The 
calcium content of telogen bulbs appears to average about 4 nanograms per 
bulb, although some bulbs have shown calcium contents as high as 20 
nanograms per bulb. 
We believe that there is a progressive interaction of calcium ions with 
hair bulbs which produces gradual declining cell activity. When some 
threshold calcium concentration is present, the follicle activity shifts 
toward dormancy, and eventual loss of the follicle and attached hair 
shaft. In other words, we believe that calcium ion is a causative factor 
in progression of hair follicles from anagen to catagen to telogen states, 
rather than simply being an indicator or consequence of such progression. 
Although not being bound by theory, we believe that during the active phase 
of growth, the hair follicle is "protected" from divalent calcium ion by 
virtue of a high content of strongly anionic sulfated mucopolysaccharides 
(SMPS) in the vicinity of the bulbs. Thus, an anionic gradient of calcium 
is created in which the divalent calcium ion is largely held away from the 
bulb by the anionic SMPS. 
Accompanying the shift of follicles to dormancy is a precipitous decline in 
SMPS in the vicinity of the bulbs, which we believe allows the calcium ion 
gradient to approach the bulb, and may precipitate its senescence. 
It is known that the roll of calcium ions in molecular biology is central. 
Calcium ion is involved in virtually every regulatory process. At low 
concentrations divalent calcium ion is essential for the growth of cells, 
but at high concentrations it becomes inhibitory. Calcium ions are central 
to the mechanisms of hormone-cell interactions, neurotransmission, muscle 
contraction, cell-cell adhesions, cell membrane fluidity, gene activation, 
and many other biological processes. Indeed calcium ion is a central 
regulating factor in terms of minute ionic fluxes which are "sensed" by 
cells and direct the triggering of various responses. It is reasonable to 
assume that calcium ion also plays a regulatory role in the health and 
activity of hair follicles. 
We therefore theorize that inhibiting the interaction of calcium with hair 
follicles may reduce the rate of senescence and reduce hair loss. We 
therefore provide a topically applied product which contains material that 
can bind, chelate, sequester, or otherwise interact with and prevent the 
progressive ionic attack of calcium on hair follicles. Delaying the 
progressive influence of calcium on the hair bulbs may spare some of them 
from early passage to the telogen state, and prolong the period of active 
hair growth. 
A composition employed in practice of this invention comprises at least one 
active ingredient consisting essentially of active chelating agent. An 
ability to chelate at least 0.3 milligrams of divalent calcium per 
milliliter of composition is preferred. Such a composition is distributed 
on the scalp and left in place at least eight hours. Preferably such an 
application of the composition is made daily for at least the first month 
of treatment. 
A preferred active ingredient is ethylene-diaminetetraacetic acid (EDTA) or 
soluble salts thereof, such as the sodium salt. Another desirable 
chelating agent is citric acid or soluble salts thereof. Other suitable 
chelating agents include glutamic acid, aspartic acid, lactic acid, 
glycine, and soluble salts and derivatives thereof such as, for example, 
dimethylglycine. Other difunctional carboxylic acids may also be used. It 
is preferred to use such materials as compared with possibly toxic, strong 
chelating agents such as oxalic acid. EDTA is probably the most powerful 
nontoxic chelating agent for calcium, and is therefore particularly 
preferred. 
In such a composition, the concentration of active EDTA or equivalent 
calcium chelating agent is in the range of from 0.1 to 1 percent by 
weight. Preferably the concentration of EDTA is in the range of from 0.2 
to 0.3 percent by weight. In addition to disodium EDTA or as a substitute 
therefor, the composition may comprise up to about 5 percent by weight of 
citric acid or glutamic acid. An exemplary composition comprises 0.1 
percent by weight sodium glutamate in addition to 0.2 percent by weight 
disodium EDTA. 
These proportions appear sufficient to provide the desired result without 
surplus concentration of the moderately expensive ingredients. It appears 
that these concentrations are appropriate for obtaining the desired result 
in a reasonably short period although a somewhat lower concentration may 
be satisfactory for a "maintenance" treatment. 
It is particularly preferred that the active chelating agent for divalent 
calcium ion be present in the composition in a concentration sufficient to 
chelate at least 0.3 milligrams of calcium per milliliter of solution. 
This assures that there is adequate active chelating concentration on the 
scalp after carriers such as water and/or alcohol have evaporated. 
Preferably the concentration of EDTA or equivalent is no more than one 
sufficient to chelate about 1.5 milligrams of calcium per milliliter of 
solution. Higher concentrations result in insufficient spreading of the 
composition over the scalp on application and may result in nonuniform 
concentrations in areas that are inadequately wetted. 
The chelating agent in the composition is active, that is, it has not 
already reacted with polyvalent ions such as iron or calcium in the water 
or other vehicle used with the active ingredient. EDTA and the like are 
sometimes used in hair treatment compositions made with tap water to avoid 
discoloration due to iron in hard water and similar effects. The amount of 
EDTA in the composition is typically slightly more than needed to 
sequester the iron, calcium and the like in the tap water, and little 
active chelating agent remains. 
It is preferred that the composition for application to the scalp comprise 
as a vehicle a somewhat viscous liquid for ease of application to the 
scalp and avoidance of waste. Surfactants, preservatives, hair 
conditioners and the like may be included in such a composition. The 
vehicle should be safe enough for application to the scalp for 
non-volatile components to remain in place on the scalp for at least eight 
hours, and preferably substantially continuously. 
The treatment comprises applying a composition containing the active 
chelating agent to the scalp at least daily during an initial month of 
treatment. Thereafter, treatment may be maintained by application of the 
composition on alternate days. An exemplary regimen is to apply the 
composition to the scalp before retiring to leave the active chelating 
agent in contact with the skin for about eight hours. It is also 
appropriate to apply the composition after shampooing to permit it to 
remain in contact with the scalp throughout the day. Strict adherence to 
such a schedule of application is not mandatory and occasional days of 
application of the composition to the scalp may be missed without 
detrimental results. For example, application of the composition to the 
scalp five or six days a week appears equivalent to application on a daily 
basis during the first month of treatment. 
A suitable mode of application of the composition to the scalp is by way of 
droplets applied directly to the scalp in seprrated locations sufficient 
to cover the entire scalp. Preferably from five to seven milliliters of 
solution are applied. When applied as a liquid composition, flow can be 
expected to spread such droplets along the scalp so that the entire 
desired area is wetted. Such flow can be promoted by gentle massaging or 
rubbing with the finger tips. 
In an exemplary embodiment, a viscous liquid composition containing the 
active calcium chelating agent may be packaged in small, relatively hard 
plastic bottles. A bottle holding about 60 ml. is conveniently manipulated 
and contains sufficient solution for about one week of treatment. Such a 
bottle is fitted with a tubular applicator cap having a small orifice at 
the end of the tube to contact the scalp. Simply touching the tip of the 
applicator to the scalp may result in sufficient liquid being placed on 
the scalp. The amount of liquid can be augmented by simply squeezing the 
bottle to extrude a droplet of liquid. Such droplets are applied directly 
to the scalp in scattered areas over the entire head and preferably gently 
rubbed to assure complete coverage. Some wetting of the hair inevitably 
occurs during such application. 
The carrier for the active calcium chelating agent comprises deionized 
water, alcohol such as SD-40, or mixtures thereof. Water is preferred 
since it is inexpensive, and it is preferred to employ a slightly viscous 
liquid rather than the fluid "tonics" more commonly associated with 
alcohol-containing compositions. Alcohol may be included in the 
composition to expedite drying if desired. 
Since the composition is applied to the scalp and left in place, it is 
desirable to include conditioners and the like which are separately 
beneficial to the hair and/or scalp. It is desirable to include 
surfactants in the composition for stabilizing the solution, for 
viscosity, and for promoting thorough wetting of the scalp. It is 
desirable to include preservatives for inhibiting growth of 
microorganisms. 
It is preferred that the pH of the composition be in the range of from 4 to 
7, and preferably in the range of from 5 to 5.5. This is a suitable pH for 
a composition to be left in contact with the skin and hair as provided in 
practice of this invention. Generally speaking, the materials employed in 
the composition are acidic in nature, and the pH may be adjusted to the 
desired range by additions of sodium hydroxide. 
Thus an exemplary composition comprises the active calcium chelating agent, 
up to about 3 percent by weight surfactant, up to about 3 percent by 
weight conditiners for the hair and scalp, sufficient preservatives to 
inhibit growth of microorganisms, fragrance, and materials for increasing 
viscosity such as glycerin and sodium chloride. 
An exemplary composition is largely water containing 0.2 percent by weight 
EDTA and 0.1 percent by weight glutamic acid, both in the form of the 
sodium salt. Such a composition may include conditioners such as 
Polyquaternium-11 or equivalent, up to about 2.5 percent by weight. An 
exemplary composition comprises 2 percent by weight Polyquaternium-11. 
This and similar quaternary ammonium salts also act as preservatives. 
Such a composition may include up to about 2 percent by weight 
diethanolamine-oleth-3-phosphate. An exemplary composition comprises 1 
percent by weight DEA-oleth-3-phosphate. 
Such a composition may include up to about 1 percent by weight of 
polysorbate 80 or Tween 80. An exemplary composition comprises 0.5 percent 
by weight of such a surfactant. 
Such a composition may include up to about 1 percent by weight octoxynol-9 
or Triton X-100, a surfactant particularly suitable for stabilizing 
fragrance additives in the composition. Typically such a material is 
present at about 4 to 6 times the proportion of fragrance to provide such 
stabilization. For example, such a composition having 0.05 percent by 
weight fragrance oils has 0.2 percent by weight of octoxynol-9. 
A mixture of such surfactants is employed in practice of this invention for 
stabilization of a mixture of conditioners, fragrances, and the like. 
A desirable conditioner employed in practice of this invention comprises up 
to about 0.3 percent by weight of allantoin acetyl methionine. An 
exemplary composition comprises 0.2 percent by weight of this conditioner 
for the scalp. This material has a particularly soothing and healing 
characteristic. 
The composition may comprise up to about 0.5 percent by weight of 
panthenol. An exemplary composition comprises 0.1 percent by weight 
panthenol as a conditioner. 
The composition may comprise up to about 0.1 percent by weight of live 
yeast cell derivative. It is believed that such live yeast cell derivative 
evolves oxygen and may oxygenate tissue as well as condition the hair. 
Another conditioner employed in practice of this invention may be up to 
about 0.5 percent by weight of zinc protein complex. An exemplary 
composition comprises 0.15 percent by weight of zinc protein complex. The 
presence of the zinc may inhibit dandruff. Such live yeast cell derivative 
and zinc protein complex are available from Brooks Industries, South 
Plainfield, N.J. 
Another suitable ingredient in the composition comprises up to about 0.2 
percent by weight of tocopheryl-nicotinate. An exemplary composition 
comprises 0.1 percent tocopheryl-nicotinate. Such material is a vitamin E 
derivative and a mild irritant which may stimulate hair growth. The 
material is available from BASF Incorporated, New York, N.Y. Other hair 
growth. stimulants may be included. 
A complex of preservatives is desirable in the composition since the 
surfactants and conditioners provide considerable nutrition for 
microorganism contamination. Thus, for example, the composition may 
comprise up to about 0.5 percent by weight methylparaben and up to about 
0.5 percent by weight diazolidinyl urea. An exemplary composition 
comprises 0.25 percent methylparaben and 0.3 percent by weight 
diazolidinyl urea. It is also desirable to include up to about 0.4 percent 
by weight of sorbic acid for inhibition of molds. An exemplary composition 
comprises 0.001 percent sorbic acid. 
It may also be desirable to include sodium chloride or glycerin for 
increasing viscosity for the composition. For example, up to about 1 
percent by weight of glycerin may be added. 
Over the last few years we have conducted various studies of calcium in 
hair bulbs and efficacy of treatment involving applying an active 
chelating agent for divalent calcium to the scalp. In an exemplary study 
conducted with a panel of 14 volunteers who completed the test regimen, 
there was an overall decrease of 21 percent in average daily hair loss 
after two months of treatment, and 78 percent of the panelists showed a 
decrease. 
In this test an exemplary composition had as its active chelating agent 0.2 
percent by weight disodium EDTA and 0.1 percent by weight sodium 
glutamate. The composition also comprised 2 percent by weight 
polyquaternium-11 one percent by weight DEA-oleth-3-phosphate, 0.5 percent 
by weight polysorbate 80, 0.2 percent by weight octoxynol-9, 0.2 percent 
by weight allantoin acetyl methionine, 0.1 percent by weight panthenol, 
0.015 percent by weight live yeast cell derivative, 0.15 percent by weight 
zinc protein complex, and 0.1 percent by weight tocopheryl-nicotonate. As 
preservatives the composition comprised 0.25 percent by weight 
methylparaben, 0.3 percent by weight diazolidinyl urea, and 0.001 percent 
by weight sorbic acid. The composition also comprised 0.001 percent by 
weight glycerin and 0.05 by weight fragrance oils. The balance of the 
composition was deionized water. 
The test panel, comprising seven men and seven women who completed the 
three-month test regimen, ranged in age from about 20 to 55 years old. 
There was one black, two hispanic, two orientals, and the balance 
caucasians. 
Each panelist was issued the same type of hairbrush and received a 
hairbrushing demonstration. Each panelist was requested to brush his or 
her hair the first thing upon arising in the morning before other 
grooming. The hairbrushing comprised approximately ten vigorous strokes 
over the entire head from front to back, ten strokes from back to front, 
and ten strokes from each side to the opposite side. Brushing was over a 
towel or other light cloth to collect any hairs that fell. In addition, 
all of the hairs in the brush were removed with tweezers. The total number 
of hairs collected each day were counted and saved in identified dated 
envelopes. The panelists were requested to continue their routine hair 
shampooing and grooming techniques and compositions with the only change 
being superimposing of the brushing and treatment according to practice of 
this invention. 
During the first month the panel did only the standard brushing, and 
collecting and counting the hairs lost to provide a base for comparison. 
For the second and third months, the scalp was treared by adding the test 
composition. 
The test composition was provided in a two-ounce (60 milliliter) bottle 
having a tubular applicator tip with a small orifice. Drops of liquic were 
applied to the scalp and gently rubbed around to wet the entire scalp. On 
average, about 5 to 7 ml of test solution was used per application. The 
test solurion was added in the evening before retiring for the night. 
There were a very small number of days when either the treatment or 
brushing was missed by a panelist, but the number of missed days is small 
enough that there should be no effect on the results. 
The number of hairs collected by each panelist was averaged for each month 
of the test. The following table sets forth the number of hairs collected 
from each panelist for each of the three months. In this table "Month 0" 
refers to the base period prior to treatment. Months 1 and 2 refer to the 
first and second months of treatment. 
______________________________________ 
AVERAGE DAILY HAIR LOSS PER SUBJECT 
Month A B C D EF G H I* JK L M N 
______________________________________ 
0 42 16 34 36 23 9 47 36 86 35 40 
75 123 71 
1 44 16 28 21 23 4 40 24 70 30 35 
82 70 59 
2 45 11 22 23 20 3 33 26 100 30 29 
86 65 56 
______________________________________ 
*Test panelist "I" was a man who appeared emaciated and developed anemia 
in the second month of the test. This condition may have contributed to 
the increase in hair loss as compared with the first month, which showed 
decrease from the base. The actual influence of this condition was not 
determined, and the results were retained in the survey. 
*Test panelist "I" was a man who appeared emaciated and developed anemia in 
the second month of the test. This condition may have contributed to the 
increase in hair loss as compared with the first month, which showed a 
decrease from the base. The actual influence of this condition was not 
determined, and the results were retained in the survey. 
The results were analyzed by the standard student T-test. During the course 
of each month's collections, the numbers of hairs collected daily deviated 
from the mean by about plus or minus 20 percent. The data show that after 
one month of product use, the average daily hair loss decreased in 10 of 
the 14 panelists, as compared with the base month without treatment. 
Similarly, after two months of treatment, the average daily hair loss 
decreased in 11 of the 14 panelists, as compared with the base, that is, 
in 78 percent of the panelists. 
Statistically, there is a 90 percent confidence level that there was a 
decrease in average daily hair loss for the group as a whole. There is not 
a 90 percent confidence level that there was a decrease in average daily 
hair loss for men in the group. However, if test panelist "I" is excluded, 
there is a 90 percent confidence level that there was a decrease in 
average daily hair loss due to the treatment. For women, there is a 90 
percent confidence level that the treatment resulted in a decrease in 
average daily hair loss. When considering only the third month of the 
test, that is, the second month of treatment, there is a 99 percent 
confidence level that the treatment resulted in a decrease in average 
daily hair loss by women in the group. 
When the data are divided into groups of those under 40 years of age and 
those over 40 there is a confidence level of more than 95 percent and less 
than 99 percent that there was a decrease in average daily hair loss in 
the second month of treatment for those panelists over 40. There was a 
99.9 percent confidence level that there was a decrease in average daily 
hair loss for individuals under 40. 
For the men as a group, there was an 11 percent decrease in average daily 
hair loss in the second month of treatment as compared with the base. 
Similarly, there was a 30 percent decrease in average daily hair loss for 
women as a group. For persons over 40 there was a 12 percent decrease in 
average daily hair loss. For person's under 40 there was a 25 percent 
decrease in average daily hair loss. 
Analysis of hair bulbs retrieved from hairs collected during the test show 
an average calcium content in bulbs collected during the second month of 
treatment about one-half of the calcium content of bulbs collected during 
the month before treatment commenced. Thus, not only was there a decrease 
in average daily hair oss due to treatment, but also tne calcium content 
of hair follicles on the hair lost decreased about 50 percent, thereby 
suggesting that the active calcium chelating agent was actually reducing 
calcium content of the bulbs or inhibiting increase of calcium 
concentration in hair bulbs which would otherwise occur. 
It might be noted that the chelating capacity of the active chelating agent 
in the composition increases with pH. Thus, although it is desirable to 
increase pH to enhance the chelating capacity, it is also desirable to 
maintain an acidic pH for best compatibility with the skin and hair for a 
"leave in" product which remains in contact with the scalp for several 
hours. 
A concentration of EDTA or equivalent, sufficient to chelate at least 0.3 
milligrams of calcium per milliliter of solution may be desirable since a 
higher concentration of chelating agent on the scalp should not inactivate 
as quickly as a lower concentration. A concentration sufficient to chelate 
0.3 milligrams of calcium per milliliter of solution is known to be safe 
and not cause itching, dandruff, or other untoward problems. Higher 
concentrations are also acceptable for some applications. 
Although the preferred composition provided in practice of this invention 
comprises a variety of surfactants, conditioners, preservatives, and the 
like, it will be apparent that the principal active ingredient is the 
active chelating agent for calcium ion, and such materials added to the 
solution to make it suitable for application to the scalp may be deleted 
to provide a compositon having properties somewhat different from those 
described. The use of conditioners and the like in the formula is 
considered desirable since the material is left in the hair and body, 
luster, et cetera, may be enhanced. In addition, it appears that the EDTA 
enhances these effects as compared with a "placebo" composition that is 
the same except for the presence of the active chelating agent. 
It will also be apparent that a variety of different conditioners, 
surfactants, preservatives, fragrances, coloring agents and the like, may 
be provided in such a product. It is, therefore, to be understood that 
within the scope of the appended claims the invention may be practiced 
otherwise than as specifically described.