CA2075592A1

CA2075592A1 - Composition for treating baldness

Info

Publication number: CA2075592A1
Application number: CA002075592A
Authority: CA
Inventors: Douglas Slamko
Original assignee: Individual
Current assignee: Individual
Priority date: 1992-08-07
Filing date: 1992-08-07
Publication date: 1994-02-08

Abstract

ABSTRACT OF THE DISCLOSURE
A composition for treating male pattern baldness using readily available ingredients includes 70.65 to 78.09%
by weight water, from 8 to 12% by weight of an emulsifying agent, from 7.5 to 8.5% by weight tissular fluid extract, from 0.95 to 1.05% by weight urea, from 0.71 to 0.79% by weight menthol, from 0.95 to 1.05% by weight yeast extract, from 1.5 to 1.7% by weight soluble serum protein, from 0.66 to 0.74% by weight hydrolysed mucopolysaccharide, from 0.47 to 0.52% by weight of each of methyl para-aminobenzoic acid, butchersbroom extract and horsechestnut extract, from .28 to.32% by weight soluble collagen extract, from 0.095 to 0.105% by weight of each of 3-pyridinecarboxylic acid, inositol, para-aminobenzoic acid, d-pantothenyl alcohol and 1-cysteine, from 0.023 to 0.027 biotin, and from 0.24 to 0.26% by weight salicylic acid.

Description

2~7~7~2 This lnvention relates to a composition for treating baldness, and in particular male pattern baldness.
There are many commercially available products for treating male pattern baldness. Many of the products in question have no proven efficacy. The object of the present invention is to provide a composition for treating male pattern baldness which is an aqueous solution containing readily available ingredients.
Accordingly, the present invention relates to a composition for treating baldness comprising from 70.65 to 78.09% by weight water, from 8 to 12~ by weight of an emulsifying agent, from 7.5 to 8.5~ by weight tissular fluid extract, from 0.95 to 1.05% by weight urea, from 0.71 to 0.79%
by weight menthol, from 0.95 to 1.05% by weight yeast extract, from 1.5 to 1.7~ by weight soluble serum protein, from 0.66 to 0.74~ by weight hydrolysed mucopolysaccharide, from 0.47 to 0.52% by weight of each of methyl para-aminobenzoic acid, butchersbroom extract and horsechestnut extract, from .28 to.32% by weight soluble collagen extract, from 0.095 to 0.105% by weight of each of 3-pyridinecarboxylic acid, inositol, para-aminobenzoic acid, d-pantothenyl alcohol and 1-cysteine, from 0.023 to 0.027 biotin, and from 0.24 to 0.26%
by weight salicylic acid.
The ingredients used in the composition of the present invention are listed in Table 1.

: 2~7~7~2 INGREDIENT ~WEIGEIT/VOLUME
. _ . _ .
Water 70.65 - 78.09 Polysorb 80 (TM) 8 - 12 Tissular Fluid Extract 7.5 - 8.5 Urea 0.95 - 1.05 Menthol 0.71 - 0.79 Yeast Extract 0.95 - 1.05 Soluble Serum Protein 1.5 - 1.7 Hydrolysed Mucopolysaccharide 0.66 - 0.74 Methyl Paraben 0.47 - 0.52 Butchersbroom Extract 0.47 - 0.52 Horsechestnut 0.47 - 0.52 Soluble Collagen Extract 0.28 - 0.32 Niacin (TM) 0.095 - 0.105 Inositol 0.095 - 0.105 Biotin 0.023 - 0.~27 Para-aminobenzoic acid 0.095 - 0.105 D-Pantothenyl Alcohol 0.095 - 0.105 L-Cysteine 0.095 - 0.105 Salicylic Acic 0.24 - 0.26 A fragrance can be added to the composition, as required.
Polysorb 80 is a polyoxylene sorbitan monooleate available under the trademark "Tween 80". The tissular fluid extract is available under the trademark "Biopol II", and the soluble serum protein is available under the trademark "Serum ~7~2 Pro EN-10". Paraben is a preservative also known as methyl para-hydroxybenzoate. Butchersbroom and horsechestnut extracts are glycolic herbal extracts. Soluble collagen extract is sold under the trademark "Solu-Cell", and "Niacin"
is a trademark for 3-pyridinecarboxylic acid. Biotin is also known as cis-hexahydro-2-oxo-lH-thieno-[3,4]-imidazoline-4-valeric acid.
The preferred composition in accordance with the invention is set out in Table 2, which follows:

_ INGREDIENT %WEIGHT/VO_UME

Water 74.375 Polysorb (TM) 10.0 Tissular Fluid Extract 8.0 Urea 1.0 Menthol 0.75 Yeast Extract 1.0 Soluble Serum Protein 1.6 Hydrolysed Mucopolysaccharide 0.7 Methyl Paraben 0.5 Butchersbroom Extract 0.5 Horsechestnut Extract 0.5 Soluble Collagen Extract 0.3 Niacin (TM) 0.1 Inositol 0.1 Biotin 0.025 2~7~92 :
Para-Aminobenzoic ~cid 0.1 D-Pantothenyl Alcohol 0.1 - L-Cysteine 0.1 Salicylic Acid 0.25 The above described preferred composition was subjected to clinical testing as set out in the following:
EXPERIMENTS
A twenty four week clinical trial was conducted including fifty normotensive men with discernable male pattern baldness of the crown (alopecia androgenetica) using the preferred composition oE Table 2. Evaluations were performed at baseline, after twelve weeks and after twenty-four weeks measuring the diameter of the bald area, and counting vellus and non-vellus hair in a designated one-inch target area o~
the scalp. Particular attention was paid to safety, and medical examinations and laboratory tests were performed at baseline and after twenty-four weeks. Forty-three subjects completed the study. The drug was well tolerated and no adverse reactions were noted during the study. Statistically significant reduction in mean bald area diameter, and increase in mean vellus hair count were observed.
The forty-three subjects who completed the study all attended the dermatology clinic seeking treatment for hair loss. They ranged in age from 23 to 49 years (mean 37.3~ and had experienced hair loss from 2 to 26 years (mean 11.6). The .

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age at onset of hair loss ranged from 15 to 41 years (mean 25.7).
A complete medical histoxy was taken from each patient, and a physical examination performed as part of the screening process. Twelve channel electrocardiogram, chest x-ray, complete blood cell count, urine analysis and comprehensive serum chemistry were also done before acceptance into the program and repeated at the end of the study. Those with indications of hypertensive, cardiac, renal, hepatic or endocrine conditions were excluded. So were those having scalp disease, or taking drugs that might interfere with the composition being tested.
The baldness pattern of each participant was classified according to the modified Hamilton scale (Hamilton, J.B., "Patterned Loss of Hair in Men: Types and Incidence", Ann N.Y. Academic Science, 1951, 53:708-11). The predominant patterns were number V (21 patients) and number III Vertex (15 patients~. The bald area was measured across its greatest diameter, the perimeter being determined visually. A one inch circular area within the bald part of the posterior scalp was chosen for study, and outlined with a scalp marker. A plastic template was also made up to permit the same area to be identified during subsequent visits, should the scalp markings come off. (The distance from the right ear was also measured and recorded.) Any existing hair in the study area was trimmed to facilitate counting. Vellus :
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(thin, non-pigmented, baby hair) and non-vellus hair (thicker, pigmented hair, similar to that elsewhere on the scalp) within the study area were counted with the aid of a magnifying glass.
Background observations with respect to baseline age, length of hairline symptoms, and age at onset of baldness are summarized in Table 3.

PARAMETERS OF BASELINE VARIABLES

AVERAGE STANDARD
MIN MAX AGE DEVIATION
.
AGE 23 4937.3 7.0 AGE AT ONSET OF HAIR LOSS 15 41 25.7 5.9 DURATION OF HAIR LOSS 2 2611.6 6.3 BALD AREA DIAMETER (cm) 2.5 13.5 7.2 2.7 The participants were given a 50 ml bottle with a plastic dropper (titrated to 1.5 ml per drop) and asked to apply one drop per day, and briefly massage the solution on the bald (or balding) area. All used the same strength solution. All were given the same size bottle independent of the size of the bald area with the implication that some patients would have a relatively thicker application over a smaller area than others. A new bottle was provided every four weeks. The patients were asked to leave the solution on .
,'- . ~ ' ~: 2075~ 2 for a minimum of six hours before shampooing. (Other topical products were prohibited for the duration of the study.) Diameter measurements and hair counts were repeated after twelve and twenty-four weeks; physical examination and laboratory tests after twenty-four weeks; and vital signs at each visit. Photographs of the bald area were taken at baseline, twelve, and twenty-four weeks. Visual assessments were also made of the amount of hair growth - from minimal to dense new growth.
Statistical methods were applied to categorical as well as continuous variables. Diameter measurements and hair counts were regarded as continuous. Analysis of variance (repeated measures) were applied to the baseline, twelve week and twenty-four week diameter and hair count measurements of all participants to investigate changes in mean levels during the first twelve weeks, the second twelve weeks, and over the course of the study period. Differences in means response levels between the two patterns (V and III Vertex) with the largest number of participants were investigated by means of t-tests. This was done primarily for the sake of completeness, and there was no reason to believe that drug response would differ across pat~erns. (There is, however, some indication of possible differences in response between front and back, anterior scalp regrowth generally being poor.
See Savin, 1987, p.704.) Categorical observations on the visual classification of amount of regrowth were analyzed with '. ' , ', ' ' . '' - ' ' ~' ',' . ' " ~ . '.
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the chi-square test for homogeneity. To allow for the (remote) possibility that the ANOVA assumptions of normality and homogeneity of variance might not be satisfied, the hair ~; count and diameter measurements were also analyzed using the Wilcoxon matched-pairs ranks test.
Results were viewed as statistically significant if the p-value obtained was less than .05. One-tail tests were used as the direction of influence was regarded as known a . priori.
RESULTS
Laboratory parameters and medical indicators were normal for all participants at baseline, and remained within normal ranges throughout the study. Because no adverse reactions were observed, there was no indication that the composition of the present invention would not be safe. Nor is there reason, a priori, to believe that it would not be safe. Because drug safety is such an important aspect, however, separate analyses were performed for possible minor changes within the normal range of medical indicators.
Pulse, blood pressure, white blood cells, and SGOT readings were singled out. Repeated measures analysis of variance, and matched parts t-tests were performed, but no significant differences were observed.
Observations with respect to bald area diameter, and changes in diameter, are given in Table 4.

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2~7~2 BALD AREA DIAMETER (cm) AT BASELINE, TWEI,VE WEEKS, AND TWENTY-FOUR WEEKS
AND CHANGE OBSERVED
AVERAGE MIN MAX

BASELINE 7.2 2.5 13.5 TWELVE WEEKS 6.2 2.0 11.5 TWENTY-FOUR WEEKS 5.5 2.0 11.0 - 10 FIRST TWELVE WEEKS -.9 0 -3.0 SECOND TWELVE WEEKS -.7 .5 -2.2 TOTAL -1.7 -.5 -3.7 : The mean reductions observed (in cm) were .9 and .7, for a ; total of 1.7 (rounded to one decimal). All were highly significant (p < .000).
Two hundred additional strands over a one-inch diameter of the scalp is sufficient to have some cosmetic effect, even if they were vellus hairs, and some participants had more than twice this growth. The observations with respect to vellus hairs are summarized in Table 5.

NUMBER OF VELLUS HAIR AT BASELINE, AFTER SIX WEEKS, AND AFTER TWELVE WÆEKS AND CHANGE OBSERVED
AVERAGE MIN MAX .

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2075~92 As set out in Table 6 below, the mean number of strands of non-vellus hair at baseline, twelve and twenty-four weeks were 110, 133, 117, respectively, indicating a mean increase of 23 ( p <~020) during the first and a mean decrease of 16 ~p < .044) during the second twelve weeks, for a net gain of 7 (p ~ .26) on average. With respect to non-vellus hair it appears that the changes observed in mean levels are typical also for the majority of participants - a gain during the first twelve-week period, and a loss during the second.
About two-thirds of the participants experienced net growth of non-vellus hair and one-third a net loss.

NUMBER OF VELLUS HAIR AT BASELINE, AFTER SIX WEEKS, AND AFTER TWELVE WEEKS AND CHANGE OBSERVED
AVERAGE MIN MAX
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2~7~ 92 In comparison to other studies, the results for non-vellus hair compares most closely to that of Savin for vellus hair - an increase over the first three months and a decrease over the following eight (Ibid., p. 700). Katz found with another hair growth product, that the rate of growth declined from the first, to the second, to the third four-month period (see e.g. Katz et al, :L987, p. 713). Others found that the level of terminal ha:ir remained unchanged during the first three months, and steadily increasing to its twelve month level ~see e.g. Savin, 1987, p. 700). These differences between studies and the products tested may be due to different active ingredients in the drugs having different effects on the pattern of hair growth.
A comparison between patients with pattern V and III
Vertex, the only two groups large enough to permit a statistical comparison, found no significant differences, with the exception of the variance in the number of non-vellus hair at twelve weeks ~ p ~ .064) and twenty-four weeks ( p ~ .010).
The meaning of this finding is unclear, but it suggests greater heterogeneity in baldness symptoms among pattern V
males than among pattern III vertex males. secause the two groups were very similar with respect to age, onset and duration of hair loss, and other characteristics, no other explanation is apparent.
A test for differences in hair growth (vellus, non-vellus, and diameter) between age groups (23-31; 32-40; 41-49) '' ' ' :

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found no significant efEects. From the data gathered within the time frame of the study, it appears -that the composition was well tolerated and no adverse reactions were noted.
A statistically significant reduction in the mean bald area diameter and an increase in the mean vellus hair count were observed. There was no statistically significant improvement in non-vellus hair growth. Vellus hair is thin, non-pigmented, baby hair, whereas non-vellus hair is thicker, pigmented hair, similar to that found elsewhere on the scalp.
With the reduction in mean bald area diameter and an increase in the means vellus hair count the patients received some cosmetic relief from their baldness.

Claims

THE EMBODIMENTS OF THE INVENTION IN WHICH AN
EXCLUSIVE PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS
FOLLOWS:

1. A composition for treating baldness comprising from 70.65 to 78.09% by weight water, from 8 to 12% by weight of an emulsifying agent, from 7.5 to 8.5% by weight tissular fluid extract, from 0.95 to 1.05% by weight urea, from 0.71 to 0.79% by weight menthol, from 0.95 to 1.05% by weight yeast extract, from 1.5 to 1.7% by weight soluble serum protein, from 0.66 to 0.74% by weight hydrolysed mucopolysaccharide, from 0.47 to 0.52% by weight of each of methyl para-aminobenzoic acid, butchersbroom extract and horsechestnut extract, from .28 to.32% by weight soluble collagen extract, from 0.095 to 0.105% by weight of each of 3-pyridinecarboxylic acid, inositol, para-aminobenzoic acid, d-pantothenyl alcohol and l-cysteine, from 0.023 to 0.027 biotin, and from 0.24 to 0.26% by weight salicylic acid.

2. A composition for treating baldness comprising 74.375% by weight water, 10.0% by weight of an emulsifying agent, 8.0% by weight tissular fluid extract, 1.0% by weight urea, 0.75% by weight menthol, 1.0% by weight yeast extract, 1.6% by weight soluble serum protein, 0.7% by weight hydrolysed mucopolysaccharide, 0.5% by weight of each of methyl para-aminobenzoic acid, butchersbroom extract and horsechestnut extract, 0.3% by weight soluble collagen extract, 0.1 by weight of each of 3-pyridinecarboxylic acid, inositol, para-aminobenzoic acid, d-pantothenyl alcohol and l-cysteine, 0.025% by weight biotin, and 0.25 % by weight salicylic acid.

3. A composition according to claim 1 or 2, wherein the emulsifying agent is a polyoxylene sorbitan monooleate.