KR100522381B1 - Use of L-Lysine in Hair Loss Treatment - Google Patents

Abstract

The present invention provides the use of L-lysine in the provision of a medicament for the prevention and treatment of human hair loss, in particular resting hair loss. In addition, the present invention provides a kit having a plurality of independent containers each containing one or more combination active agents for treating hereditary hair loss, which kit includes minoxidil, antiandrogen, 5α-reductase inhibitor, aromatase inhibitor. And L-lysine and one or more additional active agents selected from corticosteroids.

Description

Use of L-lysine in the treatment of hair loss

The present invention provides a medicament for the prevention and treatment of human hair loss, in particular telogen effluvium. The present invention further provides a kit for use in combination therapy for the treatment of genetic hair loss.

Hair loss in the scalp can be divided into three groups, which can occur at any point in time to each individual in one or a combination of these groups.

1. Hair loss due to a decrease in the number of hairs per unit area (cm ² );

2. hair loss by reducing the diameter of the hair; And

3. Hair loss due to an increase in the number of hairs in the resting phase or an increase in the period (latency) between the end of the resting period and the beginning of the next growth phase.

It is normal for hair loss to freeze every day. There is a natural variation in the hair cycle that causes the amount of hair lost in the scalp to change on a daily basis. Therefore, it is important to establish whether there is a problem causing excessive hair loss and whether the individual is aware of his or her normal daily loss.

Most human hairs have a survival cycle between 1000 and 2000 days (between 2 3/4 years and 5 1/2 years), followed by a short pause lasting about 100 days. During most of the survival cycle, hair is in the growing phase called the anagen phase. As new hair grows in the hair follicles, the existing hair (pause hair) becomes loose and is usually removed when brushing, combing, or washing the hair. This cycle continues as long as the metabolism of the hair is not disturbed. Since most of the lost hair is at rest, hair loss in the scalp is observed after 10 to 12 weeks.

As a result of this procedure, a normal person with 100,000 hairs loses about 100 hairs per day from the scalp, and a person with 150,000 hairs loses about 150 daily. These values are based on a 1000-day cycle, and the value is cut in half when the 2000-day cycle is used. The hair grows about 0.33 mm every day, up to 33 cm in 1000-day cycles, and 66 cm in 2000-day cycles.

Most instantaneous and temporary effects on the hair cycle also affect hair loss, but do not heal themselves and respond specifically. Because an individual does not know his or her normal hair loss rate, it is sometimes difficult to determine whether the natural hair loss rate is increased or excessive hair loss is reduced. However, if there really is a problem, such as that seen with nutrient imbalances, the result is a reduction in hair volume. This is because a long-term effect on the hair cycle caused a significant change in the total hair abundance.

Many women are aware of the increase in daily hair loss by seeing more hair on the brush, comb or floor of the bathroom. It is important to consider unoptimized hair growth where increased hair loss is a primary feature if there are no obvious causes, for example, if you have been ill within the last three months, have taken medications known to cause hair loss, or have no cause, such as pregnancy. Do.

The problem of increased hair loss (pause hair loss) and unoptimized hair growth affects mainly women in menstrual years and can coexist with other hair loss disorders based on either hormones or nutrients. Hair loss under these conditions is the result of an increase in the amount of resting hair lost in the scalp. In addition, hair loss may include a reduction in the length of the grown hair.

Increased hair loss results from excessive amounts of resting hair. Increased hair loss of this type can usually be determined by measuring the ratio of hair in the growing phase to hair in the resting phase. In a chronic state, an increase in hair loss may not be detected as the growth-to-rest ratio exhibits a plateau effect. However, the result is an increase in the number of hairs that cannot grow to a given length. Women often complain of a reduced amount of hair that can be pinned, shaved or bundled compared to before. The measurement variable for identifying this aspect is usually the amount of hair below 30 mm.

To date, no treatment has been found to be successful in preventing and treating human hair loss. In particular, no reliable therapies have been found to treat human hair loss. Surprising findings are known to show significant increases in hair growth in patients with alopecia, especially resting alopecia, when treating with the essential amino acid lysine. Pharmaceutical compositions for treating hair loss comprising lysine in combination with other components are disclosed in US 5,470,876, US 5,133,958, US 5,122,369 and DE-A-3118882. However, none of the above documents discloses the use of L-lysine as an active ingredient in the prevention or treatment of resting hair loss.

The present invention provides the use of L-lysine in the manufacture of a medicament for preventing and treating human hair loss, wherein the L-lysine does not exist in complex form with a transition metal, and the medicament comprises one or more of the following substances: I never do that:

(Iii) a combination of trigonelline and vitamin B6;

(Ii) a combination of divalent iron, fentonic acid, and methionine;

(Iii) Garlic oil or garlic extract.

In particular, L-lysine is particularly used in the manufacture of a medicament for the treatment of resting hair loss in humans.

The present invention also provides a pharmaceutical composition comprising L-lysine used to prevent or treat hair loss in humans, wherein the L-lysine is not present in complex form with the transition metal, and the medicament comprises one or more of the following substances: Does not contain more than:

(Iii) a combination of trigonelline and vitamin B6;

(Ii) a combination of divalent iron, fentonic acid, and methionine;

(Iii) Garlic oil or garlic extract.

The composition of the present invention is particularly used to treat resting hair loss in humans.

A study comprising administering L-lysine of the present invention to a woman with increased hair loss has shown a marked increase in hair growth. The growth of the hair is characterized by an increase in the proportion of growing hair, a decrease in the proportion of resting hair, an increase in the length of the grown hair (which can be seen as a decrease in the proportion of hair less than 30 mm), and the amount of hair lost from the scalp. It seems to include a reduction.

Typically, L-lysine is administered at 200 to 2000 mg in a daily dose, and more preferably 500 to 1500 mg per day in an oral dosage form, eg, 500 mg once, twice or three times daily. . L-lysine is a salt such as, for example, perus sulfate, perus fumarate, perus gluconate, perus succinate, perus glycine sulfate, other chelate iron compounds or iron in chelate form (one dose of iron component) To typically 14 mg to 300 mg); Vitamin C (the same amount as the iron component); And other essential ingredients such as vitamin B ₁₂ (the daily dose is usually 6 μg to 200 μg).

L-lysine may conveniently be administered orally in the form of tablets, capsules, granules, powders, mixtures, suspensions, or syrups. These formulations may be prepared by conventional methods and, if desired, L-lysine may be mixed with conventional additives such as excipients, binders, disintegrants, lubricants, corrective agents, solubilizers, suspension aids, emulsifiers, or coating agents.

The inventors have found that the administration of lysine to a patient results in a dramatic increase in conventional therapeutic efficiency in genetic hair loss. A concept that includes many conditions that are variously called common baldness, female baldness, the spread of hair loss, and male baldness).

Accordingly, another aspect of the present invention is to provide a kit having a plurality of independent containers each containing one or more complex therapeutically active agents for treating hereditary hair loss, which kit includes minoxidil, antiandrogen, 5α-reductase. L-lysine and one or more additional active agents selected from inhibitors, aromatase inhibitors, and corticosteroids.

The present invention also provides therapeutic compounds for the treatment of hereditary hair loss comprising L-lysine and one or more additional active agents selected from minoxidil, antiandrogens, 5 α -reductase inhibitors, aromatase inhibitors and corticosteroids.

Examples of representative antiandrogens that can be used in the present invention include, for example, cyproterone acetate, spyronollactone, hydroxyprogesterone acetate, and flutamide, which can be prepared for oral and topical administration. do. Type I, type II, or mixed type 5 α -reductase inhibitors of type I and type II can be used (eg, finasteride is present). A representative example of a suitable corticosteroid is dexamethasone.

In a preferred embodiment, the kit comprises L-lysine and at least one additional active agent selected from minoxidil and at least one antiandrogen, wherein the antiandrogen is preferably from cyproterone acetate, spyronolactone and hydroxyprogesterone acetate. Is selected. In a particularly preferred embodiment, the kit comprises L-lysine prepared for oral administration and minoxidil prepared for topical application.

Administration with conventional hereditary hair loss treatments such as minoxidil and antiandrogens has shown a significant improvement in treatment efficiency. The reason for such improvement in efficiency is unknown at present.

Typically, L-lysine is administered in a dose of 200 mg to 2000 mg, preferably 500 to 1500 mg in a single dose, for example, in the form of once, twice, or three times orally, for example, 500 mg per day. Is administered. Conventional genetic hair loss treatments such as topical application of minoxidil to the scalp are also administered simultaneously.

The surprising effect of L-lysine in the treatment of various forms of hair loss is illustrated in the following examples.

Resting hair loss treatment in women

Eight women received oral administration of 500 mg of L-lysine once, twice, or three times daily over a 16 week period (total daily dosages of 500 mg to 1500 mg). Women who participated in the treatment program underwent various biochemical tests before the start of the program and after 16 weeks of treatment. Detailed inspection items and the results (average values) are shown in Table 1 below.

The effect of administration of L-lysine on hair growth was determined by measuring three scalp hair parameters. These variables are the percentage of hair in the growing phase, the percentage of hair in the resting phase, and the percentage of hair less than or equal to 300 mm in length. These three variables are measured using known bio-assays for unit area trichograms (Rushton et al., British Journal of Dermatology, 1990, 123 , 187-197; Rushton et al., Clinical and Experimental Dermatology, 1991, 16 , 188-192; and Rushton et al., Clinical Endocrinology, 1992, 36 , 421-427). The values obtained before and after 16 weeks of experiment are shown in Table 2 below.

Table 1

Variables determined on the basis of blood before and after 16 weeks of experiment in eight female patients suffering increased hair loss (average obtained = 8). Statistical significance is assessed by the Student's t-test on the paired samples.

TABLE 2

Hair parameters determined before and after 16 weeks of study in 8 female patients suffering increased hair loss (average obtained = 8). Statistical significance is assessed using the Wilcoxon signed rank test.

The results shown in Table 2 clearly demonstrate that administration of L-lysine resulted in an increase in the proportion of growing hair and a corresponding decrease in the proportion of resting hair in women suffering from resting hair loss. In addition, the percentage of hair less than 30 mm in length was significantly reduced.

The results shown in Table 1 show that there was no significant change in the level of hemoglobin, serum ferritin, or serum zinc in the blood between initiation and termination of treatment. Therefore, it is reasonable to conclude that the significant increase in hair growth observed after L-lysine in women with resting hair loss is not due to increased levels of iron or zinc in the blood as a result of L-lysine. Seems to be.

Additional effects on women with low iron or zinc levels during resting hair loss were observed as shown in the experiment below.

Groups of women with chronic resting hair loss who were treated for reduced iron levels with serum ferritin concentrations below 40 ng / ml did not increase serum ferritin sufficiently despite ingesting iron additives containing 50-100 mg of iron per day. However, a significant increase (P <0.002) of serum ferritin concentrations was observed when 1.0 g to 1.5 g of L-lysine additives were added to these women's usual iron additives daily (Table 3).

TABLE 3

In Table 4 below the serum zinc concentrations for the female group (n = 10) with base concentrations of 11.8 μmol / L or less, eg, within 10% of the lower limit of normal, are shown. The average concentration of baseline for this group is 10.28 μmol / L (range from 9.0 μmol to 11.7 μmol / L). Each woman was treated with daily additives with L-lysine (1 g to 1.5 g) for 16 weeks, after which the mean serum zinc concentration increased to a significant (P <0.01) level, resulting in 13.78 μmol / L (11.6). To 17.4 μmol / L).

TABLE 4

Treatment of Women With Hereditary Hair Loss

The effect of lysine administration on the efficiency of conventional treatment for hereditary hair loss was examined as follows.

Women with sufficient iron levels (eg, serum ferritin levels above 40 mg / ml) at the beginning of the experiment and who were suffering from hereditary hair loss were divided into four groups.

The first group (17) received minoxidil in the form of topical formulations containing 3% by weight minoxidil.

The second group (15 patients) received minoxidil in the form of topical formulations containing 3% by weight minoxidil and oral antiandrogens selected from cyproterone acetate, hydroxyprogesterone and spylonolactone. The first two antiandrogens were administered with ethynylestradiol or oral contraceptives. The particular antiandrogen administered was selected based on clinical needs.

The third group (eight) received minoxidil in the form of topical formulations containing 3% by weight minoxidil and 500 mg to 1500 mg L-lysine (administered orally) per day.

The fourth group (13) consisted of minoxidil and oral antiandrogen in the form of topical formulations containing 3% by weight minoxidil (administered as in the second group), and 500-1500 mg of L-lysine (oral administration daily) Received multiple treatments. The results of the experiments are shown in Table 5 below.

TABLE 5

The results in Table 5 suggest that the administration of L-lysine in combination with conventional treatments such as topical administration of minoxidil and / or oral administration of antiandrogens for the treatment of hereditary hair loss improved the efficiency of known treatments.

When L-lysine is administered to treat resting hair loss in humans according to the present invention, a representative daily therapeutic regimen includes the following substances:

200 mg to 2000 mg L-lysine per day;

14 mg to 300 mg of iron element;

14 mg to 300 mg of vitamin C; And

3 μg to 24 μg of vitamin B _12.

Typically L-lysine can be administered as a tablet or capsule containing the following components:

200 mg L-lysine;

14 mg of vitamin C;

14 mg of iron (Perus glycine sulfate); And

3 μg of vitamin B _12.

Typically, 200 mg of L-lysine tablets are administered six times a day during periods of severe hair loss, four times a day in chronic periods, and twice a day as a maintenance dose.

Claims (15)

A medicament for preventing and treating hair loss in humans comprising L-lysine, wherein the L-lysine is not present in the form of a complex with a transition metal, The agent comprises (i) a combination of trigonelline and vitamin B ₆ ;             (Ii) a combination of divalent iron, pantothenic acid, and methionine;             (Iii) A medicament for preventing and treating hair loss, characterized in that it does not contain at least one of garlic oil or garlic extract. The method of claim 1, L-lysine is the only active agent for preventing and treating hair loss. Drugs for the prevention and treatment of resting phase hair loss in humans comprising L-lysine. The method of claim 3, L-lysine daily content 200 mg to 2000 mg; And One or more of the following ingredients: (i) an iron compound selected from the group consisting of ferrous sulfate, ferrous fumarate, ferrous gluconate, ferrous succinate, ferrous glycine sulfate, and other chelate iron compounds, wherein Content of 14 mg to 300 mg; (ii) 14 mg to 300 mg of vitamin C daily content; And (iii) vitamin B ₁₂ daily content 3 μg to 24 μg Papillary hair loss prevention and treatment agent comprising a. In the pharmaceutical composition used to prevent or treat resting hair loss in humans, L-lysine content 200 mg to 2000 mg; And One or more of the following ingredients: (i) an iron compound selected from the group consisting of ferrous sulfate, ferrous fumarate, ferrous gluconate, ferrous succinate, ferrous glycine sulfate, and other chelate iron compounds, wherein the iron content in elemental form is from 14 mg to 300 mg; (ii) 14 mg to 300 mg of vitamin C; And (iii) 3 μg to 24 μg of vitamin B ₁₂ Pharmaceutical composition for the treatment of resting phase hair loss comprising a. A kit for treating hereditary hair loss comprising a plurality of independent containers, each of the containers containing an activator for the treatment of hereditary hair loss, wherein the kit is from the group consisting of L-lysine and minoxidil and antiandrogen. A kit comprising the additional activator selected. The method of claim 6, And wherein said antiandrogen is selected from the group consisting of cyproterone acetate, spyronollactone, and methoxy progesterone acetate. The method of claim 7, wherein And wherein said antiandrogen is formulated for oral administration. The method of claim 6, A kit comprising L-lysine and minoxidil. The method of claim 9, And the minoxidil is formulated for topical application. A therapeutic combination for treating hereditary hair loss comprising L-lysine and an additional active agent selected from the group consisting of minoxidil and antiandrogen. The method of claim 11, The anti-androgen is a therapeutic combination selected from the group consisting of cyproterone acetate, spyronolactone, and hydroxyprogesterone acetate. The method of claim 12, The therapeutic combination wherein the antiandrogen is formulated for oral administration. The method of claim 11, Therapeutic compounds comprising L-lysine and minoxidil. The method of claim 14, The therapeutic compound wherein said minoxidil is formulated for topical application.