or View PDF file

Innovation you can build on™
T
e
xt
Capig n™ P
English
CAPIGEN™ SP
Prevention of hair loss
and
stimulating hair-tonic
All use of this file for commercial or advertising purposes requires the prior written authorization
of the SEDERMA Company
Non- Warranty: The information in this publication is given in good faith by Sederma by way of general guidance and for
reference purposes only. The information should not be construed as granting a license to practice any methods or
compositions of matter covered by patents. Sederma assumes no liability in relation to the information and gives no
warranty regarding the suitability of the product and/or ingredients described for a particular use. The use made of the
product and/or ingredients described by the recipient and any claims or representations made by the recipient in respect
of such product and/or ingredients are the responsibility of the recipient. The recipient is solely responsible for ensuring
that products marketed to consumers comply with all relevant laws and regulations.
CAPIGEN™ SP
CONTENT
1.
INTRODUCTION ................................................................................................... 3
2.
DESCRIPTION OF CAPIGEN™ SP ...................................................................... 5
3.
EFFICACY TEST (tests performed with CAPIGEN™ paraben version) ................. 8
3.1. Clinical study...................................................................................................
3.2. Study of seborrhea..........................................................................................
3.3. Phototrichogram .............................................................................................
4.
COSMETIC INTEREST OF CAPIGEN™ SP ....................................................... 24
5.
PHYSICO-CHEMICAL PROPERTIES AND ANALYSIS ..................................... 25
5.1. Specifications..................................................................................................
5.2. Analysis ..........................................................................................................
REFERENCES ........................................................................................................... 28
12/2011/V2
-1-
CAPIGEN™ SP
-2-
CAPIGEN™ SP
1.
INTRODUCTION
Cosmetic hair treatments are mainly concerned with three types of problem:
∗
alopecia
∗
the presence of dry or greasy dandruff
∗
hyperseborrhea.
Alopecia is more common in men than women (it is referred to as androgenic alopecia).
Cosmetic research has devoted much work to this problem.
The physiology of hair growth is extremely complex. Thus, the causes of alopecia (whether
temporary or permanent) have been studied in detail, but there are few solutions.
For instance, some correlation has been observed between excessive seborrhea of the
scalp and hair loss, although this parallelism has not been confirmed in all cases.
In itself, hair loss is a natural phenomenon. Hair growth follows a cycle which involves the
birth and development of the follicle, a stationary phase and a final phase during which the
hair is expelled.
This alternation of phases of growth or the anagenic phase, of regression or the catagenic
phase and of rest or the telogenic phase is due to the specific secretion of the hair
follicle,which acts as a gland and progressively produces a mass of keratin which it
eliminates and then replaces after a resting period.
The cycle begins with the development of the hair follicle, which rises up from the dermis
which contains large number of mesenchymatous cells, resulting in the formation of a dermic
papilla.
During the final stage, the "anagenic" phase, the cellssurrounding the dermic papilla divide
actively every 12 hours in order to produce the tells which line up, grow longer and begin to
keratinize: this is hair growth.
During the "catagenic" phase, there is no longer any mitosis, the bulb detaches itself from the
papilla and rises towards the surface.
During the "telogenic" phase, the hair is fully keratinized and is ready to be expelled.
After three to four months, another mitotic cycle begins in the germinative zone of the hair
and another active follicle is formed (Figure 1).
-3-
CAPIGEN™ SP
Catagenic
phase
Anagenic phase
Telogenic
phase
Figure 1:
The various phases of the hair cycle after ACKERMAN [1]
The loss of between fifty and a hundred hairs a day is nothing to worry about but quite
normal. However, if the number of hairs lost increases and they are not renewed, the
problem of alopecia arises and appropriate treatment is required.
Some medical treatments involve steroid hormones, which are not appropriate for cosmetic
use, and others include novel substances such as Minoxidil, sulfur derivatives (10 mg of
sulfur per day and per kg bodyweight are required for healthy growth and maintenance of
the hair) and antibacterial and antimycosal substances (in the case of persistent dandruff).
CAPIGEN™ SP
a new hair care substance from SEDERMA, is based on an association of three active
ingredients intended to:
-
slow excessive hair loss
-
stimulate renewal of the hair by regeneration
-
intervene in seborrhea regulation, which is often involved in alopecia-type
phenomena (seborrheic alopecia).
-4-
CAPIGEN™ SP
2.
DESCRIPTION OF CAPIGEN™ SP
CAPIGEN™ SP consists of three active constituents, which have a complementary and
synergistic action.
These constituents, all of which contain sulfur, are of differing chemical nature and have
distinct biological activities.
•
CAPIGEN™ SP contains a novel active constituent, homotaurine (3-amino propane
sulfonic acid) [SEDERMA patent] with the following formula:
NH2-CH2-CH2-CH2-SO3H
Why homotaurine?
As its name indicates, homotaurine is a homologue of the natural amino acid taurine which
has an extra CH2 group in its chain. In order to make the value of homotaurine clearer, we
will give a brief description of the properties of taurine.
Taurine is the most common free amino acid in mammalian tissue. This amino acid (which is
not coded by the genetic code) is also found in nerve axons; its possible role as a
neurotransmitter is still under discussion.
Taurine is involved primarily in embryonic development and in young subjects, in many
processes particularly focused on cell proliferation, migration and differentiation. Taurine has
a protective and stabilizing effect on cell membranes, protecting their permeability and
playing an osmoregulatory role. The literature also refers to taurine as an essential
constituent of infant nutrition, as protecting against oxidants and free radicals. In addition, it is
effective against certain cardiac abnormalities.
Homotaurine, a synthetic molecule which is not found in animal tissues, has some properties
which differ from those of taurine.The biochemical literature compares the efficacy and
specificity of taurine, homotaurine and gamma-amino-butyric acid (GABA).This last molecule
is in fact an analog of homotaurine: the sulfonic group -SO3H is replaced by a carboxyl group
-COOH.
Without going into the biochemical details of the various studies carried out on the three
molecules, we will refer to those aspects which we consider to be most important with regard
to a "hair care action".
-5-
CAPIGEN™ SP
Homotaurine is described as a molecule which has a hypotensive effect by blocking
vasoconstriction and increasing blood flow [2]. This property will improve irrigation of the
scalp by the bloodstream.
Homotaurine is also used in the treatment of hyperlipidemia [3]and acts as an
anticholesterolemic [4] by inhibiting the accumulation of lipids within the liver [5].
It is therefore involved in the regulation of the lipid metabolism.
Homotaurine has an antifibrinolytic action [6] and inhibits platelet aggregation [7].
Homotaurine also acts as a cell transporter for various metal ions such as calcium,
magnesium and possibly other ions. The role of sodium, potassium, manganese, copper
and zinc ions in certain metabolic disorders of the scalp is currently much studied.
GABA is known to be a neurotransmitter and we will not describe all its activities here. We
should note simply that a GABA derivative has been described as an active ingredient in
hair care products.
The structural analogy between homotaurine and GABA is therefore of interest, it can
therefore be supposed that these two molecules have similar biological activity.
To summarize, homotaurine:
-
improves vascular circulation (vasodilator effect)
-
actively transports some metal ions which are known
to be of importance in hair physiology
-
has a regulatory effect on lipid metabolism
-
imitates some of the effects of GABA
-
in addition, is a sulfur-containing amino acid which is
beneficial for the hair in general.
The second constituent of CAPIGEN™ SP is a bacterial filtrate obtained from a strain of
microorganisms cultured in a specific medium which induces a secretion of metabolites
with stimulatory activity:
-
the basic medium consists of selected peptones, the ingredients of the culture
medium are chosen in order to direct the metabolic pathways (deficiencies, enzyme
induction by high concentrations of certain substrates, sulfur-containing ones for
example).
-6-
CAPIGEN™ SP
-
the bacterial filter obtained after decantation, filtration and purification contains
principally high levels of peptides.
•
The third constituent of CAPIGEN™ SP is a sulfomucopolysaccharide extract of
marine origin.
The sulfomucopolysaccharides play an essential role in the field of hair follicle hygiene,
particularly in the regulation of sebaceous secretions.
This is a complex of sulfated polysaccharides which are soluble in water, and which is found
in the connective tissue and synovial fluid.
It has been shown that organic sulfur is essential for the synthesis of follicular protein, where
it provides the stable disulfide bonds of the hair.
In man and in rodents, sulfur is obtained primarily from dietary protein, and any metabolic
disturbance associated with a deficiency in the synthesis or utilization of these proteins
results in disruption of the hair cycle.
Treatments with sulfur (by oral or cutaneous route) have a marked slowing effect on the
degradation processes.
-7-
CAPIGEN™ SP
3.
EFFICACY TEST
3.1.
Clinical study (tests performed with CAPIGEN™ parabens version)
A hair lotion containing 10% CAPIGEN™ was used for 11 weeks in a study monitored by Dr.
Gabbai, dermatologist, in which 10 male volunteers, aged from 26 to 50 years, with hair loss
problems took part.
ANALYSIS OF THE CLINICAL RESULTS
1.
Greasy, normal or dry appearance of the hair
-
On D0, 4 of the participants had dry hair.
Their hair was less dry at the end of the study.
-
On D0, 5 participants had greasy hair.
At the end of the study, their hair was :
-
•
less greasy in 3 cases,
•
unchanged in 2 cases.
On D0, 1 participant had normal hair.
The hair was unchanged at the end of the trial.
The subjective impressions of the participants are exactly the same.
-8-
CAPIGEN™ SP
2.
Hair thickness
-
On D0, 5 participants had fine hair.
At the end of the study, their hair was unchanged.
-
On D0, 4 participants had thick hair and another normal hair.
-
These 5 cases remained unchanged at the end of the test.
Subjective impressions:
One of the participants (4) who had fine hair considered that they were thicker at the end of
the trial.
3.
Dandruff
Initially dandruff was visible in 8 cases.
At the end of the trial, of these 8 cases:
4.
-
5 had improved
-
3 were unchanged.
Subjective assessment of hair loss
After daily application of the test substance for 2½ months, the participants thought that their
hair loss:
-
had decreased in 7 cases,
-
was the same in 1 case,
-
had stopped in 1 case,
-
had increased in 1 case (this impression is doubtless due to the fact that this
participant was not used to using hair lotion and found hair on his hands when
he massaged).
-9-
CAPIGEN™ SP
5.
Clinical safety
The subjective and objective tolerability were excellent in all cases.
CONCLUSION
Daily application of the SEDERMA product CAPIGEN™ for 2½ months in this trial involving
10 cases improved the appearance of the hair (making dry hair less dry and greasy hair less
greasy) and reduced the dandruff initially present in 8 subjects.
Seven participants thought that their hair loss had been slowed at the end of the trial and
another that it had stopped.
Clinical safety was excellent in all cases.
Paris, January 18, 1991
- 10 -
CAPIGEN™ SP
3.2.
Study of seborrhea
(This study involved 9 of the 10 subjects treated.)
The rate of sebum secretion was measured by the Sebutape™ method. Sebutape patches
were applied to the volunteer's forehead near the hairline. The evaluation was carried out by
image analysis (number and size of the transparent spots). The Parameter "activity", number
of active glands and distribution of the size of the glands were determined.
Figures 2 and 3 and Tables 1 and 2 show that the results agree
completely with the clinical observations.
Seborrheic activity is restored to normal: the subjects with greasy
hair found a marked reduction in the number and activity of
sebaceous glands and those with dry hair found a slight increase
towards the mean value.
Figure 4 describes the change in the distribution of the mean size of
the sebaceous glands, indicating a reduction in the percentage of
hypertrophic glands and an increase in the percentage of small
glands, i.e., a regulation toward the normal value.
Table 1:
Global sebaceous activity CAPIGEN™
Subjects
1
2
3
4
5
6
7
8
9
Before
42.00
7158.00
2.00
1241.00
150.00
8371.00
6866.00
612.00
5171.00
- 11 -
After
980.00
1505.00
75.00
332.00
463.00
3024.00
2890.00
46.00
1790.00
CAPIGEN™ SP
Before
After
9
9
Mean
3290.33
1233.89
Standard deviation
3530.12
1148.71
Number of values
Significant difference
T
=
2.42
p
≤ 0.042
Table 2:
Number of active sebaceous glands CAPIGEN™
Subjects
Before
After
1
2
3
4
5
6
7
8
9
3.00
159.00
0.00
62.00
11.00
144.00
197.00
39.00
136.00
62.00
70.00
8.00
20.00
29.00
125.00
87.00
3.00
37.00
Before
After
9
9
Mean
83.44
49.00
Standard deviation
75.95
40.33
Number of values
No significant difference
T
=
1.8
p
> 0.05
To conclude, the use of a lotion containing 10% CAPIGEN™ for 11 weeks regularized
and normalized sebum secretion which was reflected in particular by a 62% (p<0.05) of
the mean sebaceous activity.
- 12 -
CAPIGEN™
Sebaceaous activity
CAPIGEN™ SP
- 13 -
CAPIGEN™
Number of active sebaceaous glands
CAPIGEN™ SP
- 14 -
CAPIGEN™
Distribution of the size of sebaceous glands
CAPIGEN™ SP
- 15 -
CAPIGEN™ SP
3.3.
Phototrichogram
The study began by cutting the hair over an area of a few square centimeters. The hair was
cut very close to the skin. A macrophotograph of the zone was taken after cutting.
Three days later, another macrophotograph of the test zone was taken.
For eleven weeks, the participants used the hair lotion containing 10% CAPIGEN™ in daily
massages, avoiding the use of any other treatments, with the exception of shampoo during
the regular washing.
At the end of the treatment period, the same analysis protocol was implemented: a small
zone was clipped at the back of the skull and macrophotographs taken at an interval of 3
days.
The efficacy of CAPIGEN™ was then evaluated from these elements.
Computerized analysis of the images and the change seen after 3 days of treatment made it
possible to count the distribution of hairs in anagenic, catagenic and telogenic groups, since
there was some natural regrowth of hair within this period. The photographs are
superimposable and it was possible to distinguish clearly the places where hair growth had
occurred (anagenic), where the hair had not changed (catagenic) and the places where the
hair had disappeared (telogenic).
- 16 -
CAPIGEN™ SP
Day 0
Day + 3
Example of macrophotographs used for the
phototrichograms
- 17 -
CAPIGEN™ SP
D0
D+3
Table 3 shows that the percentage of the hairs in the anagenic, catagenic and telogenic
phases (mean for the number of participants) were 74.6%, 20.9% and 4.5% before treatment
began. By way of reference the literature gives distribution values for these 3 phases of
>80%, 9 - 17% and 1 - 5% for healthy hair.
- 18 -
CAPIGEN™ SP
Table 3:
Pre-treatment phototrichograms
Subjects
Anagenic phase
(growth)
Catagenic phase
(growth stopped)
Telogenic phase
(loss)
1
84%
14%
2%
2
3
46%
69%
40%
26%
14%
5%
4
87%
11%
2%
5
80%
20%
0%
6
7
94%
63%
6%
21%
0%
16%
8
68%
28%
4%
9
82%
18%
0%
10
73%
25%
2%
After 3 months of application, these percentages had changed in 10 out of 10 cases
(tables 4 and 5) and hair health had improved. There was, therefore, a reduction in
the catagenic phases 20.9 to 13.6% (resting) and of the telogenic phase from 4.5
to 0.9% (hair loss) and an increase in the anagenic phase from 74.6 to 85.5%
growth.
Table 4:
After-treatment phototrichograms
Subjects
Anagenic phase
(growth)
Catagenic phase
(growth stopped)
Telogenic phase
(loss)
1
2
90 %
59 %
10 %
39 %
0%
2%
3
75 %
25 %
0%
4
95 %
5%
0%
5
90 %
10%
0%
6
97 %
3%
0%
7
89 %
11%
0%
8
84 %
12%
4%
9
85 %
12%
3%
10
91 %
9%
0%
- 19 -
CAPIGEN™ SP
Table 5:
Percentage of hair in anagenic phases
Before
After
10
10
Mean
74.60
85.50
Standard deviation
13.87
11.16
Number of values
T
=
Significant difference
4.67
p ≤ 0.01
Table 6:
Percentage of hair in telogenic phases
Before
After
10
10
Mean
25.40
14.50
Standard deviation
13.87
11.16
Number of values
T
=
Significant difference
4.67
p ≤ 0.01
The use of a lotion containing 10% of CAPIGEN™ for 11 weeks results a
significant improvement in the state of the hair in all the volunteers. The
increase in the percentage of hairs in the anagenic phase was 15%, p <0.01.
Abnormal hair loss was markedly reduced.
The macrophotographs also revealed two other significant parameters: increase in
apparent hair volume and the hair regrowth rate.
The apparent regrowth rate of the hair expresses the number of hairs as well as their
thickness and length per cm2 of scalp.
Tables 6 and 7 also show that the CAPIGEN™-based treatment produced a major increase
in the apparent hair volume and the hair regrowth rate.
- 20 -
CAPIGEN™ SP
Table 7:
Apparent hair volume variation - CAPIGEN™
on 3 days
Before treatment
Subjects
1
2
3
4
5
6
7
8
9
10
on 3 days
At the end of treatment
7742.00
1192.00
2673.00
4279.00
5795.00
4528.00
5659.00
1762.00
7234.00
3612.00
8164.00
4115.00
7584.00
6515.00
8794.00
7021.00
10602.00
7278.00
5642.00
9572.00
Before
After
10
10
Mean
4447.60
7528.70
Standard deviation
2200.85
1891.18
Number of values
T
=
Significant difference
4.0
p ≤ 0.01
The increase in the apparent hair volume was 69%
Table 8:
Hair regrowth rate variation - CAPIGEN™
Subjects
on 3 days
Before treatment
on 3 days
At the end of treatment
1
2
3
4
5
6
7
8
9
10
9.82
1.20
5.00
7.90
10.72
6.14
9.75
4.85
13.25
5.89
10.06
5.41
10.74
9.27
12.28
8.52
12.77
8.52
8.04
13.31
- 21 -
CAPIGEN™ SP
Before
After
10
10
Mean
7.45
9.90
Standard deviation
3.52
2.45
Number of values
T
=
Significant difference
2.36
p ≤ 0.042
The hair regrowth increased by 33%
The apparent hair volume increased by 69% and the hair regrowth rate by 33%.
Since these parameters are related, it can be concluded that the number of hairs
per cm2 of scalp was increased and that the hair density was therefore greater
CAPIGEN™ treatment.
- 22 -
CAPIGEN™ SP
Example of changes on the apparent hair volume and fair regrowth rate
(digitalized macrophotographs)
Before treatment D0
Before treatment D + 3
At the end of treatment D’0
At the end of treatment D’ + 3
NB: It is remarkable to note that the lengthening of the spots correspond to the lengthening
of the hair.
- 23 -
CAPIGEN™ SP
4.
COSMETIC INTEREST OF CAPIGEN™ SP
The state of health of the hair and scalp depends not only on genetic factors but also on a
number of intrinsic parameters (age, diet, stress, lifestyle, environment). A poor condition of
the hair, reflected by excessive hair loss; is often related to seborrhea deregulation.
The results of the clinical evaluation of the tests described above are significant:
Tests performed with CAPIGEN™ parabens version.
The use of a lotion containing 10% CAPIGEN™ for an 11-week treatment period helped to
remedy the causes (seborrhea) and symptoms (hair loss) of hair problems.
•
The clinical observation detected a reduction in hair loss and normalization of
the excessive or insufficient greasiness of the hair.
•
The kinetic determination of seborrhea using Sebutape revealed a reduction of
sebaceous activity by 62%.
•
The percentage of anagenic hairs was increased by 15% (mean value rising
from 75 to 86%).
•
The apparent hair volume rose by more than 69%.
•
The hair regrowth rate increased by 33%.
CAPIGEN™ therefore made it possible:
- to eliminate premature and/or excessive hair loss,
- to promote hair regrowth,
- to regulate sebum secretion and therefore excessive oiling of the hair.
In this way CAPIGEN™ helps to restore the vigor andstrength of the hair.
We recommend CAPIGEN™ should be used:
- either as vials containing 5 - 15% for intensive treatment,
- or as a lotion or hair cream containing 3 - 7% for maintenance care.
- 24 -
CAPIGEN™ SP
5.
PHYSICO-CHEMICAL PROPERTIES AND ANALYSIS
(Provisional values given by way of indication)
5.1.
Specifications
Appearance
:
clear to slightly opalescent liquid
Color
:
yellow to orange yellow
pH
:
4.8 - 6.3
Specific gravity (20°C)
:
1.030 - 1.050
Refractive index (25°C)
:
1.350 - 1.370
Water content (K. Fischer) (%)
:
75 - 85
Proteins content (Biuret) (%)
:
0.35 - 0.65
Total combined yeasts/molds count
:
<100 cfu/g
Molds and yeasts
:
<10 cfu/g
5.2.
Analysis
5.2.1. Gravimetric assay of sulfur : 0.5 - 0.7%
5.2.2. Assay of amino acids
After pre-derivation and passing over a chromatography column (Applied Biosystem). The
high concentration of homotaurine interferes with the analysis and causes column saturation
problems. We therefore carried out the analysis on the bacterial filtrate alone, before the
homotaurine was added.
Amino acids
% / Total
Aspartic acid
5.5
Glutamic acid
14.0
Asparagine
5.25
Serine
3.67
Glycine
33.85
Arginine
1.18
Alanine
9.6
Proline
12.2
Tyrosine
0.5
Valine
2.3
Methionine
0.5
Cysteine
0.27
Isoleucine
1.3
Leucine
2.85
Phenylalanine
1.06
Lysine
3.88
- 25 -
CAPIGEN™ SP
5.2.3. Detection of peptide fragments by thin-layer chromatography
Plate
:
Cellulose (Merck)
Eluant
:
n-Propanol /Water 2:1
Duration
:
7 hours
Revelation
:
Ninhydrin
Deposit
:
20 drops
Result:
Front
of solvent
} Homotaurine
Deposit
- 26 -
CAPIGEN™ SP
5.2.4. Assay of the sulfomucopolysaccharides
Titration method with cetyl-pyridinium chloride (1 g/l).
Dilute 5 ml of CAPIGEN™ in 50 ml of water.
Take 5.0 ml of this stock solution and to it add 20 ml of distilled water and adjust the pH to
7.0 with a 2 M solution of sodium acetate. The cetyl-pyridinium chloride solution is added
using a burette.
The solution gradually becomes cloudy, then milky and finally opaque. Addition of another
one or two drops results in complete coagulation and a fairly clear supernatant appears.
Calculation of the percentage of sulfomucopolysaccharides:
V x 503.3 x 50 x 100
% =
358 x 2 x 5 x ts
where:
V
:
volume of the solution of cetyl-pyridinium chloride (in ml)
503.3 :
molecular weight of sulfomucopolysaccharide (daltons)
358
:
molecular weight of cetyl-pyridinium chloride (daltons)
ts
:
test sample (5 ml)
The
stochiometrics
require
2
moles
of
sulfomucopolysaccharide.
- 27 -
cetyl-pyridinium
chloride
per
mole
of
CAPIGEN™ SP
REFERENCES
1.
ACKERMAN A.B., MOSCHELLA, S.L., PILLSBURY, D.M., HURLEY, H.Z.,
Dermatology, 1975, eds. SAUNDERS et Cie, Philadelphia.
2.
KUSHIKU K., FURUKAWA T., Ganryu Aminosan, 1985, 8, p. 329-35.
3.
TSUNOO S., HORISAKA K., YAMAGUCHI A., ADACHI K., UMEZAWA O., 1972, US
Patent 3658966.
4.
KAMEYA T., KUZUTANI F., 1974, Jap. Patent 49041186.
5.
KIKUNO M., KOBAYASHI M., SUZUKI Y., NEKABA I., 1975, Jap. Patent 50010371.
6.
COOK E., TAMAKA K., FUJII A., 1977, Fr Patent 2321285.
7.
COOK E., TAMAKA K., FUJII A., 1975, US Patent 3920833.
- 28 -
ACTIVE INGREDIENTS
Sederma SAS
29, rue du Chemin Vert
F-78612 Le Perray en Yvelines
Tel ++ 33 1 34 84 10 10
Fax ++ 33 1 34 84 11 30
sederma@sederma.fr
www.sederma.fr
Sederma, Inc.
300-A Columbus Circle
Edison, NJ 08837 USA
Tel ++ (732) 692 1652
Fax ++ (732) 417 0804
sederma-usa@croda.com
www.crodausa.com
Sederma GmbH
Herrenpfad-Süd 33
41334 Nettetal Germany
Tel ++ 49 21 57 817318
Fax ++ 49 21 57 817361
sederma@sederma.de
www.sederma.fr
Sederma © 2012
member of Croda International Plc.