Hair loss abstract
The use of the polyamine known as spermidine, i.e., N-(3-aminopropyl)
tetraminethylenediamine, as an active principle in the preparation
of a composition for pharmaceutical or dietetic use in man for combating
hair loss is disclosed.
Hair loss claims
1. Use of spermidine as an active principle in the preparation
of a composition for pharmaceutical or dietetic use in man to combat
hair loss.
2. Use of spermidine according to claim 1, to combat hair loss
in the case of the pathology known as telogenic defluvium.
3. Use of spermidine according to claim 2, to reduce the telogenic
phase in the growth cycle of the hair.
4. Use of spermidine according to claim 1, to make the hair robust.
5. Composition for pharmaceutical or dietetic use to be administered
to man to combat hair loss, characterized in that it comprises spermidine,
methionine, vitamin C, polyphenols, vitamin E, calcium pantothenate,
zinc (as amino acid chelate), vitamin B.sub.6, copper (as amino
acid chelate), folic acid and biolin.
6. Composition according to claim 5, characterized in that it comprises:
6 Methionine 300.00 mg Vitamin C 90.00 mg Polyphenols from Vitis
vinifera 5.00 mg Vitamin E 15.00 mg Calcium pantothenate 9.00 mg
Zinc (as amino acid chelate) 7.50 mg Vitamin B.sub.6 2.00 mg Copper
(as amino acid chelate) 1.25 mg Spermidine 0.50 mg Folic acid 0.15
mg Biotin 0.05 mg
7. Composition for pharmaceutical or dietetic use to be administered
to man to combat hair loss, characterized in that it is formulated
for oral administration and comprises an oral vehicle and spermidine
as active principle.
8. Lotion of balm to be applied to the human scalp to make the
hair robust and to reduce hair loss characterized in that it comprises
spermidine as active principle.
Hair loss description
[0001] The present invention relates to a novel use of the polyamine
known as spermidine, i.e. N-(3-aminopropyl)tetramethylenediamine.
[0002] It is known in the literature that compounds belonging to
the class of aliphatic polyamines play a deciding role in controlling
the biological mechanisms of growth, division and differentiation
of cells and proliferation of animal tissues.
[0003] The polyamines in question essentially comprise the compounds
putrescine, spermine and spermidine. The latter compound, i.e. N-(3-aminopropyl)tetramethylenediamine,
owes its name to the fact that it was first discovered in human
sperm. In reality, it is present in virtually all the bodily fluids
(blood, saliva, tears and milk). It was subsequently also found
in many foods of both animal origin (meat, fish, eggs, milk and
cheese) and plant origin (fruit and vegetables). It is of particularly
high concentration in human milk (on average about 600 micrograms
in milk over 24 hours), where it plays an important role for the
newborn. Specifically, in the newborn, the mucosae of the digestive
tract are not fully formed and spermidine, taken up with the milk,
promotes the growth of the epithelium of the gastric and intestinal
mucosa.
[0004] Spermidine is therefore an important factor in the growth
and proliferation of cells.
[0005] According to the present invention, it has now been found,
surprisingly, that a preparation containing spermidine, administered
orally to man, results in a stimulation of the hair bulbs with consequent
promotion of hair growth, in particular in the case of a pathological
hair loss such as that known as telogenic defluvium, characterized
by a state of suffering of the hair bulb, leading to an abnormal
and excessive loss of hair.
[0006] One subject of the present invention is, thus, the use of
spermidine as an active principle in the preparation of a composition
for pharmaceutical or dietetic use in man to combat pathological
hair loss, in particular in the case of telogenic defluvium.
[0007] A subject of the present invention is also a composition
for pharmaceutical or dietetic use to be administered to man to
combat pathological hair loss, characterized in that it comprises
spermidine as active principle.
[0008] To understand the characteristics and advantages of the
invention more clearly, an experimental study from which they are
derived will now be described in greater detail.
[0009] To this end, a few fundamental notions regarding the phases
of growth of a hair should first be presented. The growth cycle
of hair consists essentially of three phases, during which the hair
follicle passes from periods of intense growth to periods of quiescence
and then of involution. These three phases are: the anagenic phase,
i.e. the phase of hair growth, during which there are a number of
changes in the dermal papilla in which the cells undergo intense
metabolic activity.
[0010] The hairs grow 0.3-0.4 mm per day. The hairs are not all
in the same growth phase, but rather they alternate. The anagenic
phase lasts from 3 to 6 years.
[0011] The catagenic phase is the phase of involution lasting from
2 to 3 weeks, during which the hair follicle undergoes profound
morphological and metabolic changes. The lower segment is lost,
the length of the follicle is reduced by about a third, the bulb
decreases in size, the melanocytes stop producing pigment and the
papilla becomes atrophic:
[0012] the hair falls out.
[0013] Finally, the telogenic phase is the resting phase, during
which the hair follicle is completely inactive. The hair is inside
the hair follicle, held by weak intercellular bonds that cause it
to stay in the scalp until the start of the new anagenic phase and
sometimes even for several successive phases. The telogenic phase
lasts from 2 to 4 months.
[0014] Every day about 50 hairs die and fall out, and, under normal
conditions, are immediately replaced by new members, since the follicles
have mutually synchronized life cycles such that the total volume
of hairs remains virtually unchanged. In this way, total exchange
of the hairs takes place every 2-6 months.
[0015] The concept of telogenic defluvium was first introduced
by Kligman in 1961. Before that time, it was difficult to distinguish
the causes of excessive hair loss (owing to metabolic disturbances,
intoxication or infection) from the other more general forms of
alopecia.
[0016] The diagnosis of telogenic defluvium is made by taking into
consideration the growth phases of the hair. When, for various reasons,
the anagenic and telogenic phases are altered (and this may take
place in both senses: either they are excessively faster or excessively
slower than the norm), this results in the phenomenon of telogenic
defluvium, which is distinguished by excessive hair loss and by
profound morphological alterations in the hair.
[0017] The factors that can lead to an imbalance in the hair cycles,
with consequent onset of telogenic defluvium, may be: particular
physiological conditions (pregnancy), prolonged states of stress
and anxiety, use of certain drugs such as, for example, bromocryptine,
cimetidine, levodopa, etretinate, lithium, pyridostigmine, propanolol
and anti-thyroid drugs, non-balanced diets and deficiencies in vitamins
and minerals.
[0018] The morphological alterations in the hair during telogenic
defluvium may be a microscopically visible destructuring of the
shaft, with a consequent reduced mechanical tensile strength and
reduced elasticity; alterations in the trichogram; mineral deficiencies,
or histological alterations in the hair bulb.
Clinical Study
[0019] This controlled, randomized double-blind study was performed
according to the present invention by means of the protocols below.
[0020] Sixty volunteers of both sexes and ranging between 18 and
60 years old were divided into three groups of 20 individuals each,
all having the same level of pathology, i.e. telogenic defluvium
existing for at least 2 months.
[0021] Some of these individuals were treated for 60 days with
one capsule a day of a composition of the invention, according to
the following scheme:
[0022] Group 1: 20 individuals treated with a composition of the
invention containing spermidine alone (0.50 mg per capsule).
[0023] Group 2: 20 individuals treated with a composition of the
invention according to Example 1 described later (spermidine 0.50
mg per capsule).
[0024] Group 3: 20 individuals treated with a placebo, in capsules.
[0025] The parameters evaluated were the following:
[0026] A) General dermatological visit.
[0027] B) Microscopic evaluation of the shaft of the hairs (diameter
and possible structural changes in the hair).
[0028] C) Trichogram, i.e. evaluation of the bulbs in the anagenic
(growth) phase, catagenic (involutive stasis) phase, telogenic (pathological
precocious hair loss) phase and exogenic (physiological loss of
hairs since they are replaced with new hairs).
[0029] D) Haematochemical analysis.
[0030] E) Pull test (mechanical tensile strength of the hair).
[0031] F) Wash test (count of the hairs lost after washing with
shampoo).
[0032] G) Possible side effects.
[0033] These parameters were evaluated at time T.sub.0 (before
the start of the treatment); at time T.sub.1 (at the end of the
60 days of treatment); and finally at time T.sub.2 (30 days after
stopping the administration).
[0034] The results were as follows:
[0035] A) The dermatological visit revealed an appreciable and
significant reduction in the hair loss and an improvement in the
structure of the shaft in the groups of patients 1 and 2 compared
with the placebo group 3.
[0036] B) Microscopic evaluation of the shaft The diameter of the
hair shaft increases quite substantially in groups 1 and 2, whereas
it remains virtually unchanged in the placebo group 3.
[0037] C) The trichogram is the parameter that, together with the
wash test, gave the most interesting results. In this regard, reference
is made to the diagrams of FIGS. 1 and 2 in the attached drawings.
These show the trichogram of the anagenic and telogenic phases at
times T.sub.0 (before the start of the treatment); at time T.sub.1
(at the end of the 60 days of treatment); and finally at time T.sub.2
(30 days after stopping the administration) for the individuals
of the three groups, 1 (grey column), 2 (black column) and 3 (pale
column). The percentage of hairs in the anagenic phase (FIG. 1)
and in the telogenic phase (FIG. 2) for the treated individuals
belonging to the three groups under consideration is shown on the
y-axis, and the said times T are shown on the x-axis, under which
are tabulated the said percentages found.
[0038] Specifically, the microscopic analysis of the state of the
bulb reveals that the number of bulbs in the anagenic phase increases
significantly in Groups 1 and 2 and, in parallel, in the same Groups,
the telogenic phase decreases significantly. In contrast, in the
placebo group 3, the anagenic and telogenic phases are not significantly
changed.
[0039] In particular, a 17.2% increase in the anagenic phase at
T.sub.2 relative to T.sub.0 (with an 8.1% increase at T.sub.1) was
found in Group 1.
[0040] A 20.2% increase in the anagenic phase at T.sub.2 relative
to T.sub.0 (with an 8.12% increase at T.sub.1) was found in Group
2.
[0041] A 7.79% increase in the anagenic phase at T.sub.2 relative
to T.sub.0 (with a 2.7% increase at T.sub.1) was found in Group
3. The change of about 7.79% in the anagenic phase from T.sub.0
to T.sub.2 in the placebo group is comparable to the cyclic changes
that take place within the hair bulbs.
[0042] In parallel, the telogenic phase decreased by:
[0043] 6.76% at T.sub.2 (9.1% at T.sub.1) in Group 1
[0044] 27.7% at T.sub.2 (9.6% at T.sub.1) in Group 2
[0045] 4.16% at T.sub.2 in Group 3, for which, however, an increase
in the telogenic phase (of about 1.88%) is actually found at T.sub.1.
[0046] D) The haematochemical analyses gave values within the norm
for all the Groups 1, 2 and 3.
[0047] E) Pull test:
[0048] The mechanical tensile strength of the hair increased significantly
in Groups 1 and 2, whereas it remained virtually unchanged in the
placebo Group 3.
[0049] F) Wash test. This test makes it possible not only to quantify
the number of hairs lost after shampooing, but also, by means of
a suitable microscopic analysis, to evaluate the phase of the cycle
in which the bulb was found when the hair fell out: pathological
loss (telogenic) or phase of physiological exchange (exogenic).
[0050] The test results are given in the graph of FIG. 3 in the
attached drawings. In this graph, the number of hairs lost during
washing for the individuals of the three groups mentioned above
is given on the y-axis, and the said times T [T.sub.0 (before starting
the treatment); T.sub.1 (at the end of the 60 days of treatment);
T.sub.2 (30 days after stopping the administration)] are given on
the x-axis, under which are tabulated the values found.
[0051] As may be seen, the number of hairs lost in the wash test
decreases significantly for the treatment process in Groups 1 and
2 (solid lines), whereas it remains unchanged in the placebo Group
3 (dashed line in the graph).
[0052] In addition, by analysing the bulbs of the lost hairs, the
following important observation was made. In Group 3 treated with
placebo, more than 90% of the lost hairs were in the telogenic phase
(pathological loss) and only 3% were in the exogenic phase (physiological
loss).
[0053] In Groups 1 and 2 this ratio changes, since the hairs in
the exogenic phase are 33% in Group 1 and 46% in Group 2, with a
consequent reduction in the hairs in the telogenic phase, which
was found to be 63% in Group 1 and 52% in Group 2.
[0054] Thus, in Groups 1 and 2, among the lost hairs, there was
a significant decrease in the percentage of hairs in the telogenic
phase (pathological loss) and a proportionate increase in the percentage
of hairs in the exogenic phase (physiological loss by exchange).
[0055] G) The side effects were mild and all disappeared as the
treatment continued, taking care to take the capsule during the
main meal, at T.sub.1.
[0056] According to the present invention, it was thus experimentally
found that the oral administration to man of a composition containing
spermidine, preferably combined with other components such as methionine,
bioflavonoids, vitamins and mineral salts, is capable of slowing
down and stopping excessive hair loss in the case of telogenic defluvium,
and simultaneously of improving the strength and general health
of the hair.
[0057] The pull test demonstrated that spermidine, either in unmodified
form or combined with other micro-nutrients, increases the mechanical
tensile strength of the hair.
[0058] The trichogram and the wash test made it possible to demonstrate
large variations arising in the hair bulb following treatments with
spermidine in unmodified form or combined with other active components.
Not only is the number of hairs lost after washing substantially
reduced, but also, among those lost, the number in the telogenic
phase (pathological loss) is substantially decreased when compared
with the number in the exogenic phase (loss by physiological exchange).
Thus, the treatment with spermidine in unmodified form or with spermidine
combined with other micro-nutrients has substantially modified the
cycle of the hair altered by the telogenic defluvium pathology,
returning it to the normal values of physiological exchange.
[0059] For the use of spermidine according to the present invention,
it is convenient to formulate it in compositions preferably for
oral use, and preferably as a dietetic product. It may also be formulated
in compositions for topical use on the scalp.
[0060] A number of examples, not intended to be limiting, of compositions
according to the invention will now be described.
EXAMPLE 1
Dietetic Composition for Making the Hair Robust and Reducing Hair
Loss
[0061]
1 Sealed rigid plant capsules Each capsule contains: Active principles
Methionine 300.00 mg Vitamin C 90.00 mg Polyphenols from Vitis vinifera
5.00 mg Vitamin E 15.00 mg Calcium pantothenate 9.00 mg Zinc (as
amino acid chelate) 7.50 mg Vitamin B.sub.6 2.00 mg Copper (as amino
acid chelate) 1.25 mg Spermidine 0.50 mg Folic acid 0.15 mg Biotin
0.05 mg Excipients Hydroxypropylmethylcellulose 110.00 mg Talc 21.00
mg Magnesium stearate 6.50 mg Colloidal silica 2.85 mg Natural colorants
2.50 mg
EXAMPLE 2
Dietetic Composition for Making the Hair Robust and Reducing Hair
Loss
[0062]
2 Packets to be dissolved in water Each packet contains: Active
principles Methionine 300.00 mg Vitamin C 90.00 mg Polyphenols from
Vitis vinifera 20.00 mg Vitamin E 15.00 mg Calcium pantothenate
9.00 mg Zinc (as amino acid chelate) 7.50 mg Beta-carotene 4.20
mg Vitamin B.sub.6 2.00 mg Copper (as amino acid chelate) 1.25 mg
Spermidine 0.50 mg Folic acid 0.30 mg Biotin 0.15 mg Excipients
Maltodextrin 2 000.00 mg Sodium citrate 350.00 mg Citric acid monohydrate
200.00 mg Flavourings 160.00 mg Colloidal silica 65.00 mg Aspartame
30.00 mg Acesulfame K 7.00 mg Natural colorants 3.50 mg
EXAMPLE 3
Cosmetic Attack Lotion (initial treatment) for Making the Hair
Robust and Reducing Hair Loss
[0063]
3 In ampules Each ampule of 10 ml of solution contains: Active
principles Spermidine 2 mg Catechin and quercetin complex 40 mg
Methylsulphonylmethane 400 mg Azeoglycine (potassium azeloyl diglycinate)
300 mg Sunflower oil and rosemary oil 5 mg Menthyl lactate 25 mg
Calcium pantothenate 16 mg Biotin 0.15 mg Excipients Ethyl alcohol
4.0 ml Fragrance 5.0 mg Natural colorants 0.2 mg Purified water
qs 10 ml
EXAMPLE 4
Cosmetic Maintenance Lotion (continuation of treatment) for Making
the Hair Robust and Reducing Hair Loss
[0064]
4 In bottles 100 ml of solution contain: Active principles Spermidine
5 mg Catechin and quercetin complex 200 mg Methylsulphonylmethane
2 000 mg Azeoglycine (potassium azeloyl diglycinate) 3 000 mg Sunflower
oil and rosemary oil 50 mg Menthyl lactate 250 mg Calcium pantothenate
80 mg Biotin 1.5 mg Excipients Ethyl alcohol 35 ml Natural colorants
900 mg Fragrance 50 mg Purified water qs 100 ml
EXAMPLE 5
Cosmetic Balm for Making the Hair Robust and Reducing Hair Loss
[0065]
5 In bottles 100 ml of balm contain: Active principles Spermidine
10 mg Catechin and quercetin complex 400 mg Methylsulphonylmethane
4 000 mg Azeoglycine (potassium azeloyl diglycinate) 3 000 mg Sunflower
oil and rosemary oil 50 mg Menthyl lactate 250 mg Calcium pantothenate
80 mg Biotin 1.5 mg Excipients Cetearyl alcohol 5 000 mg PEG-15
cocopolyamine 5 000 mg Oat protein hydrolysate 3 000 mg Glycerol
3 000 mg Cetyl alcohol 2 000 mg Quaternium-52 1 000 mg Phenoxyethanol
300 mg Methyl-ethyl-propyl para-oxybenzoates 200 mg Fragrance 500
mg Colorants 1 000 mg Purified water qs 100 ml |