Method of treating hair growth disorder, such as female pattern of hair loss, and compositions applied therein

FIELD: medicine.

SUBSTANCE: invention refers to cosmetology and represents method of treating hair loss involving introduction to an indigent person of an amount of alkyl ester of nicotinic acid with alkyl group with direct chain or branched chain containing approximately 6 to 22 CH2 groups in sufficient to decrease or to terminate hair loss in said person.

EFFECT: invention provides stimulation of hair follicle with favourable therapeutic effect for hair growth disorder, such as female alopecia.

8 cl, 2 ex, 2 tbl, 2 dwg

 

A RELATED APPLICATION

This application claims priority in accordance with the application serial number 60/693716 filed June 24, 2005, included as a reference.

The technical FIELD TO WHICH the INVENTION RELATES.

This invention relates to methods for treating disorders such as hair loss, characterized by loss of hair (alopecia). It also refers to increasing the amount of NAD in the hair follicles, thus increasing the energy in these tissues, which in turn leads to increased growth, fullness, thickness and overall quality of the hairline. Even more specifically, the invention relates to the treatment of these conditions in women.

BACKGROUND AND PRIOR art

Baldness female type (alopecia) affects approximately 20 million women. Hair loss begins with puberty and progresses throughout life. Difficult is early detection of the condition that is unfavorable, because early diagnosis and treatment is essential to achieve optimal therapy. While the nature of the hair loss varies considerably, reducing the amount of hair on the top of the hair as usual. The real measure of a characteristic hair loss in women is expanding partial line or is anaysis pony tail. Typically, daily hair loss is quantitatively less than 100-125 hairs; however, hair follicles, which come in telogen phase, will not come again in anagennao growth phase, which leads to a slow connection, the loss of active follicles. Treatment options for this condition are limited and include hair transplants, additional stimulation by hormones and Minoxidil, a drug that affects calcium homeostasis. See, Li et al., J Invest Dermatol, 117(6): 1594-1600 (2001). Topical 2% Minoxidil are the only approved drug therapies for this condition.

Limited treatment options available, when alopecia in women has led to the search of other tools that can provide a beneficial effect in this state. A potential candidate for the stimulation of hair growth is Niacin (nicotinic acid). The studies identified several possible mechanisms, suggesting that nicotinic acid may have a beneficial impact on state data. The main biologically active form of Niacin nicotinamide of adenindinucleotide (ABOVE) plays a key role in energy metabolism in cells, and hair follicle has high energy requirements (Jacobson, et al., J Photochem Photobiol B 63 (1-3):141-7 (2001)). OVER also which is a substrate for enzymes included in the maintenance of genome integrity (Jacobson, et al., Trends Biochem Sci, 24(11):415-417 (1999)) and calcium homeostasis (Lee, Curr. Mol. Med., 4(3):227-237 (2004)). Additionally, it was shown that the skin contains receptors Niacin, which stimulate the release of leptin (Kim, et al., J. Invest. Dermatol., 119:347 (2002)), and regulators downstream in the metabolic pathway of leptin included in the homeostasis of the skin (Komuves, et., J. Invest Dermatol, 115(3):361-367 (2000)) and the cycle of the hair follicle (Sano, et al., EMBO J. 18(17):4657-4668 (1999)). While Niacin or other form of vitamin, Niacinamide, have the potential for conversion to ABOVE, the receptor for nicotinic acid is responsible only for Niacin (Tunaru et al., Nat. Med., 9(3):352-355 (2003)).

While Niacin has the potential to provide beneficial effect on the skin and scalp, delivery of Niacin per se is not suitable in substantial amounts, because it causes intense vasodilation at the site of use, and its physical properties do not allow to reach the long residence time in the skin. This has led to the development of meesterdokument, a derivative of Niacin, which has an impact on the delivery of the cells of the skin without vasodilation and generates a time, allowing the transformation in the ABOVE (Jacobson, et al., J. Invest. Dermatol., 114:849 (2000) and U.S. patent No. 6337065, which are both incorporated by reference) and the stimulation of re is of aptara nicotinic acid (Tunaru, et al., supra). It is shown that meesterdokument triggers epidermal differentiation, leading to a strong increase in the integrity of the skin barrier (Jacobson, et al., in Alberts, et al., Fundamentals of Cancer Prevention (Srpinger, 2005, pgs. 139-160)). Another derivative of Niacin, actiniaria, stimulates blood flow and oxygen delivery to tissue. (See, for example, U.S. Patent No. 6924299, incorporated by reference in its entirety. Patent '299, however, in this patent does not mention the application of the described compounds in the context of hair growth or treatment of disorders of hair growth or any related conditions).

The characteristic of the invention, thus, relates to a method of treating disorders of hair growth, such as typical baldness or alopecia in women, by introducing one or more alilovic esters of nicotinic acid. In some cases, the introduction of one of these compounds will be sufficient, while in other cases it will be desirable introduction mixtures of two or more of them in the composition or structure.

When two or more of these alilovic esters of nicotinic acid used in the compositions, such compositions are also characteristic of this invention.

Additional features of the invention and its implementation will be clear from the discussion which follows.

The INVENTION

The invention relates to components is the way, used to stimulate hair follicles, resulting from the favorable effect of treatment of disorders of hair growth, such as alopecia, especially in women. Methods of treatment of the relevant population groups are also a sign of the invention.

Compositions, in their broadest aspect, contain at least two alilovic ester of nicotinic acid. The first is alkilany ester of nicotinic acid, which delivers Niacin in cells, particularly in cells of the hair follicle, without vasodilation, where alkilany ester of nicotinic acid has sufficient time to convert to Niacin without adverse effect vasodilation.

Second alkilany ester of nicotinic acid is an ester, which stimulates blood flow and therefore oxygen delivery to the cells.

First alkilany ester of nicotinic acid is preferably a compound where the alkyl fragment contains at least 11 carbon residue and to 22 carbon residue, i.e. alkalemia esters C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21 and C22. Second alkilany ester nicotinic acid is a compound in which an alkyl group is shorter than in the first connection, and preferably represents alkilany ether C6, C7, C8, C9 or C10.

More preference is sustained fashion, the compositions contain a first alkilany ester of nicotinic acid, where the alkyl fragment contains from 11 to 16 carbon atoms, and the second fragment is from 8 to 10 carbon atoms. Most preferably, the composition contains C14 alkilany ester of nicotinic acid and C8 alkilany ester of nicotinic acid. Optionally the composition may include ingredients such as shown in U.S. Patent No. 6337065, U.S. Patent No. 6464942 and/or U.S. Patent No. 6924299, which are included as references.

Any one of the first and second alilovic esters of nicotinic acid, as described above, can be used separately or they can be incorporated into the composition as described above. When used separately, may be any alkilany ester of nicotinic acid with alkyl fragment from about 8 carbons to about 16 carbons, with the C8 and/or C14 alkalemia esters of nicotinic acid are particularly preferred. When used in combination, such as a composition of two or more alilovic esters of nicotinic acid, the preferred compositions are as described above.

BRIEF DESCRIPTION of DRAWINGS

Figa and 1B are pictures of “before and after”, which show the effect of the compositions of the invention on the growth of hair.

Figure 2 shows the data of Table 2 in the graphics is the form.

A DETAILED DESCRIPTION of the PREFERRED embodiments

EXAMPLE 1

Sixty women aged 20-80, who have gone through the procedure with informed consent and had alopecia female type (type of Ludwig I-III) (Ludwig et al., Br. J. Dermatol., 97(3):247-254 (1977))were detected in 6-month pilot study using double-blind, placebo-controlled method. The subjects are statistically distributed in the placebo group (20, only the environment) and the active group (40, medium containing 0.5% of octylaniline and 5.0% of meesterdokument). Pre-packaged foods Packed in identical containers. Trisiloxane and Dimethicone were the main components of the composition. Because the active substances are substances derived vitamins, as placebo, and active preparations are classified as cosmetics in accordance with the recommendations of the FDA.

At baseline the subjects was given a one-month supply assigned to the study product. The first dose was applied at the research center nurse. Subjects were instructed to apply the formula on the night of 6 measured doses on the scalp, as follows: one drop on the right top, left top part of the scalp, right middle top of the head, the left middle top of the head, right n the life, the lower left part of the scalp. If the head was cleaned, the study drug was applied after shampooing. All subjects were provided with the same shampoo. Frequent hair washing was out independently. Subjects were asked to maintain the appearance of the style, color and Perm their hair throughout the study.

Subjects returned at monthly intervals to assess the increase in amount of hair, irritation of the scalp or other adverse events, and to obtain a product. They were asked to wash your hair with shampoo in the morning before the test and avoid products for hair styling. Subjects were also asked to evaluate the appearance of their hair. To assess the completeness of hair applied a standardized photograph because of increased fullness hair within a 6-month study is not generally found as a researcher and subjects. At baseline, month 3 and month 6 pictures of the top of the scalp, with hair combed from the top, like the spokes of a wheel, and a Central parting with your hair, gently combed on both sides of the head. These images were obtained with a double, and one set was provided to the subjects for personal comparison, while the second set remained at the research center. A standardized 35 mm photography was done on the source the level after 2, 4 and 6 months as follows: type of crown with hair combed from the top, the view from the top with the hair, divided by a Central parting, view of the head from front to image the top of the hair line. Image of the head of the subject was obtained from 3-point tripod specifically designed for pictures with hair loss. The evaluation was completed upon receipt of the photos after 6 months, as this was the minimum time to detect changes of the fullness of the hair.

Of the total number of entities registered in the study, 32 of the 40 active and 12 of the 20 placebo subjects completed the study. Relatively high drop-out is typical for studies of weight/hair growth, but it is interesting to note that in the proportion of twice the number of subjects in the placebo group withdrew from the study. There were no reports of serious adverse events, and mild adverse events included 9 messages abrasions, about 2 burns hairline, 12 of itch in the hairline, 4 reported redness hairline and 7 reports of eye irritation. These events occurred in the placebo group and the active group, which indicates that volatile environment, not the active ingredients was a source of irritation.

At the output of the research were obtained from the evaluation of researchers, assessment of the subjects and photographic evaluation. Statistical pictures on Polaroid and evaluation of the subjects showed a positive trend, but did not reach statistical significance with p value equal to 0.05, which was not unexpected for a 6-month study. Key evaluation was based on a standardized 35 mm photographs that were assessed valuation method blindly to evaluate improvement "completeness" of hair. Each set of images was distributed on a scale from minus 1 for reduced "completeness" of the hair, zero for no change or plus 1 to increase the "completeness" of hair. These data are summarized in Table 1. Data comparison of placebo and active groups show increased benefit to active groups with a p value equal to 0.04, as analyzed in accordance with the one-parameter test Mann-Whitney for non-parametric data. The placebo effect observed in this study, it is not unusual for studies of the fullness of the hair. Example of effect of derivatives of nicotinic acid on thinning hair, as documented by 35 mm photography at baseline and after 6 months of use, shown in figure 1.

Table 1
Assessment of the impact of derivatives of nicotinic acid on baldness female type
GroupCol. entitiesThe scoring of hair growth. Col. subjects (% of total)A value of p#
ReductionWithout change.Increase
Placebo20*(12)1(8%)7(59%)4(33%)---
Active40*(32)2(6%)8(25%)22(69%)0,04
* the number of entities registered in the study
the number of subjects who completed the study
#active compared with placebo for one-parameter test Mann-Whitney
active, containing 0.5% of octylaniline and 5.0% of meesterdokument

EXAMPLE 2

This example describes how to use alilovic esters of nicotinic acid of the invention improves energy status of the hair follicle, by increasing them in sod is Rania ABOVE.

Hair samples were taken from subjects exposed to treatment composition of Example 1 and tested for the content ABOVE, and the DNA content using methods recognized in this area. The results are shown below in Table 2 and figure 2.

/tr>
Table 2
SubjectABOVE-DNA Pmol/ng. Initial levelABOVE-DNA Pmol/ng. 7 daysChange % change
10,1360,1940,05843
20.104 gof) 0.1570,05351
30,0800,1370,05771
40,1070,1320,02523
50,0620,0850,02337
60,0690,0720,00451
70,0790,1030,02531
Average0,0910,1260,03537
p=0,005

These results clearly show that alkalemia esters of nicotinic acid increases the number ABOVE in the hair follicles. To put it another way, increasing the energy content of the follicles and increase, as you can see, are quite significant.

The above disclosure presents various features of the invention that relate to compositions used for treating disorders of hair loss, such as typical baldness, and the application of these compositions. The compositions contain a first alkilany ester of nicotinic acid in which the alkyl chain of the ester, which may be branched or straight chain and contains from 10 to 22 CH2groups. Especially pre who is respectful alkilany ester of nicotinic acid, in which the alkyl chain contains 14 CH2groups, i.e. meesterdokument.

Second alkilany ester nicotinic acid is a compound in which an alkyl group that may be branched or straight chain, containing from 1 to 10 CH2groups, preferably with from 6 to 10 CH2groups. Especially preferred is alkilany ester of nicotinic acid with a straight chain octylaniline.

Two alilovic ester nicotinic acid combined in the composition, optionally together with a carrier, which may be a water, detergent or any other standard media applicable for application to the scalp.

Compositions of the invention can be presented in any form that is suitable for introduction of substances into the scalp. Representative, but in no way exclusive examples of such forms are soluble shampoos for local use, rinses, sprays, emulsions, creams, sprays, lotions, gels, etc.

The composition is applied by coating them on the scalp, such as by washing, massage, etc. Preferably, the composition was applied at least once a day, preferably in a dose of from about 0.01% to about 10% of the components, the more PR doctitle from approximately 0.1% to approximately 5% m/o for each component in the day. Can be used various dosing regimens.

An additional characteristic of the invention is a method of treating disorders, which is the loss of hair, through the introduction of a number Olkiluoto ester of nicotinic acid with alkyl group with a straight chain of from about 6 to about 22, and preferably from about 8 to about 16 carbon atoms in a quantity sufficient to reduce, reduce the degree or other treatment of hair loss. As was shown above, the data alkalemia esters of nicotinic acid cause an increase vnutrimolekulyarnogo content of NAD+, as manifested in the increased ratio of NAD+/DNA in hair follicles. Thus, this in turn leads to an increase vnutrimolekulyarnogo energy content, which may be the reason for the decrease in hair loss.

Can be used one or more alilovic esters of nicotinic acid with alkyl chains of C8 and C14 they are especially preferred.

Also part of the invention is a method of increasing the thickness or "weight" of existing hair by applying compositions of the invention. Watched the data show that the use of these compositions in addition to reducing hair loss leads to an increase in "completeness" and/or thickness of the hair.

Other aspects of the invention will be clear to a skilled practitioner in this area, and there is no need to put them in the description.

The terms and expressions which have been used are used as terms of description and not of limitation, there is no intention to apply such terms and expressions to exclude any equivalents shown and described signs or parts thereof, it is recognized that within the scope of legal protection of the invention various modifications are possible.

1. A method of treating hair loss, comprising the administration to a subject in need this number Olkiluoto ester of nicotinic acid with alkyl group with straight chain or branched chain, containing from about 6 to about 22 CH2groups in a quantity sufficient to reduce or to stop hair loss the specified entity.

2. The method according to claim 1, wherein said alkilany ester nicotinic acid is octylaniline.

3. The method according to claim 1, wherein said alkilany ester nicotinic acid is meesterdokument.

4. The method according to claim 1, comprising the introduction of this Olkiluoto ester of nicotinic acid in a quantity sufficient to increase vnutrimolekulyarnykh levels ABOVE+in the hair follicles of the specified entity.

5. Ways who according to claim 1, includes introduction:
i) first Olkiluoto ester of nicotinic acid, the alkyl fragment of which is straight or branched chain containing from 11 to 22 CH2groups, and more
ii) a second Olkiluoto ester of nicotinic acid, the alkyl fragment of which is straight or branched chain containing from 1 to 10 CH2groups.

6. The method according to claim 5, in which
(i) represents meesterdokument, and
(ii) is octylaniline.

7. The method according to claim 1, in which the specified subject is a woman.

8. The method according to claim 1, wherein said subject suffers from alopecia.



 

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FIELD: medicine.

SUBSTANCE: drug preparation for toxicosis relief in early pregnancy exhibiting immune corrective, diuretic action contains yellow bedstraw tincture produced under certain conditions.

EFFECT: drug preparation effectively relieves toxicosis in early pregnancy.

4 cl, 1 tbl

FIELD: technological processes.

SUBSTANCE: ground birch bark is extracted by diethyl ether with separation of betulenol. Then birch bark residue is extracted by water with hydraulic module of 1:15-20 at the temperature of 95-100°C for 1.5-2.0 hours. Produced solution of water soluble substances is concentrated down to 1/3 of initial volume, saturated with sodium chloride, and produced residue is separated by filtration, filtrate is thrice extracted by ethyl acetate and concentrated down to 1/12-1/15 of initial volume, dissolved with chloroform, and proanthocyanidins are extracted.

EFFECT: invention makes it possible to achieve the specified purpose.

1 ex

FIELD: medicine.

SUBSTANCE: external skin preparation contains as active components a ferrous compound and a compound chosen from 5-aminolevulin acid, salt of 5-aminolevulin acid, ester of 5-aminolevulin acids, ester of salt of 5-aminolevulin acids, N-acyl-5-aminolevulin acids, salts of N-acyl-5 aminolevulin acid and ester of N-acyl-5-aminolevulin acid. The ferrous compound is chosen from iron (II) citrate, sodium-iron citrate, ammonium-iron citrate, iron acetate, iron oxalate, iron (II) succinate, sodium-iron succinate and citrate, iron (II) pyrophosphate, iron (III) pyrophosphate, heme iron, iron dextrane, iron lactate, iron (II) gluconate, sodium-iron diethylene triaminepentaacetate, ammonium-iron diethylene triaminepentaacetate, ethylenediaminetetraacetate sodium-iron ethylene aminpentaacetate, ammonium-iron ethylene aminpentaacetate, iron triethylene tetraamine, sodium-iron dicarboxymehtyl glutamate and ammonium-iron dicarboxymehtyl glutamate.

EFFECT: improved skin look, prevention or reduction of roughness, dryness, wrinkles, flabbiness, and pigment spots, efficient for atopic dermatitis.

16 cl, 2 ex, 2 dwg

FIELD: medicine.

SUBSTANCE: paste for oral cleansing contains: silicon dioxide, glycerine, PEG 400, xylite, disodium EDTA, papain, lysozyme, lactulose, sodium carboxymethyl cellulose, Carbomer, ribonuclease, Lydasa, sodium lauroyl sarcosinate, sodium lauroyl sulphate, cocamidopropyl betaine, reduced glutathione, camomile extract, parsley extract, grapeseed extract, glycospheres (liposomes), tetrapotassium pyrophosphate, tetrasodium pyrophosphate, disodium pyrophosphate, sodium saccharinate, citric acid, sodium citrate, spruce extract, sage extract, chondroitin sulphate, betaine, aminofluoride, sodium fluoride, sodium methyl paraben, sodium propyl paraben, the titanium dioxide, an aromatiser, polyvinylpyrrolidone, demineralised water in the certain ratio.

EFFECT: high-effective product prevents development of herpetic stomatitis, moistens oral cavity, restores damaged parodentium tissues, and reduces formation of dental deposit on the tooth surface.

9 tbl, 5 ex

FIELD: medicine, oncology, amino acids.

SUBSTANCE: invention relates, in particular, to the development of an antitumor preparation based on natural substances. Invention relates to an amino acid preparation comprising at least one modified essential amino acid obtained by treatment of amino acid by ultraviolet radiation (UV) at wavelength 250-350 nm for 12-80 h at temperature 15-30oC or with ozone at temperature 15-25oC. The modified amino acid has no toxicity for health cells. Also, invention relates to a method for preparing such preparation. Invention provides the development of an antitumor preparation based on modified amino acids and expanded assortment of antitumor preparations being without cytotoxicity for normal cells.

EFFECT: valuable medicinal antitumor properties of preparation.

8 cl, 4 tbl, 2 dwg, 4 ex

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