JP2005314323A - Hair growth formulation - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a hair growth formulation which contains minoxidil and has a high hair growth effect and an excellent application texture. <P>SOLUTION: The hair growth formulation is one containing minoxidil, propylene glycol, and a volatile solvent, wherein the propylene glycol is contained in an amount larger than 5 times and smaller than 10 times (in terms of a mass ratio) that of the minoxidil. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a hair restorer composition having a high hair growth effect comprising minoxidil as an active ingredient.

  While minoxidil (chemical name: 6- (1-piperidinyl) -2,4-pyrimidinediamine-3-oxide) has a peripheral vasodilatory action, it is used as an oral antihypertensive for the treatment of hypertension, Hairy as a side effect has attracted attention, and indication as a hair restorer has also been proposed (for example, US Pat. No. 4,139,619, US Pat. No. 4,695,812). Since then, studies on the optimal concentration of minoxidil in hair growth agents (for example, “Study on the optimal concentration of a topical preparation of minoxidil for male pattern baldness in double-blind studies by Katsuyuki Takeda I” (clinical medicine, 1992, No. 1) Vol. 8, No. 7, pp. 1597-1623) and Katsuyuki Takeda et al. “Study on the usefulness of minoxidil 1% lotion and 2% lotion for long-term external use for male pattern baldness” (Progress in Medicine) 1992, Vol. 12, No. 7, p.1553-1565)), and some minoxidil-containing hair restoration agents are already commercially available (for example, 1% minoxidil). Containing RiUP (registered trademark) (made by Taisho Pharmaceutical Co., Ltd.), Rogaine containing 5% minoxidil (Phama Made ia & Upjoin)).

  The dosage forms of minoxidil-containing hair restorers that have been studied to date have been widely applied to lotions, jellies, ointments, creams, sprays, aerosols, tonics, etc. Propylene glycol is widely used as a solvent.

US Pat. No. 4,139,619 US Pat. No. 4,695,812 Clinical Medicine, 1992, Vol. 8, No. 7, p. 1597-1623 Progress in Medicine, 1992, Vol. 12, No. 7, p. 1553-1565

  By the way, the improvement of the hair-growth effect in these minoxidil-containing hair-growth agents has been carried out mainly by increasing the amount of minoxidil used in the hair-growth agent. However, the amount of propylene glycol used has not been studied in detail, and is only appropriately selected according to each dosage form. Since it is known that contact dermatitis due to the action of propylene glycol is slightly concerned (see Non-Patent Documents 1 and 2 above), in the above-mentioned commercially available hair restorer, propylene glycol is less than minoxidil. It is used in a mass ratio of 10 times.

  The inventors thought that the hair-growth effect could be changed by propylene glycol which has not been studied so far. Accordingly, an object of the present invention is to provide a hair-restoring agent having a high hair-growth effect in which the hair-growth effect of minoxidil is sufficiently exerted, and having an excellent usability.

  As a result of intensive studies, the inventors have unexpectedly discovered that the amount of propylene glycol changes the transdermal absorbability of minoxidil and affects the hair growth effect of minoxidil. And in the hair restorer composition containing a minoxidil, propylene glycol, and a volatile solvent, the above-mentioned subject is achieved by adjusting propylene glycol to a quantity ratio of more than 5 times and less than 10 times with respect to minoxidil. As a result, it was discovered that a hair-growth agent with high hair-growth effect and excellent usability was obtained, and the present invention was completed. As far as this specification is concerned, the term “volatile solvent” is a compound that is compatible with propylene glycol and dissolves minoxidil in a mixture with propylene glycol, and the boiling point of the compound alone is low. It means a compound that is 100 ° C. or lower, or a mixture of such compounds. In the present invention, the volatile solvent is preferably selected from the group consisting of ethanol, water, and a mixture of ethanol and water from the viewpoint of the feeling of use of the hair restorer composition.

  If the propylene glycol is contained in the hair growth composition in an amount of 5 times or less by mass ratio with respect to minoxidil, a hair growth composition showing a sufficiently high hair growth effect cannot be obtained. According to the study by the inventors, when the amount of propylene glycol is small, the hair-growth effect decreases because minoxidil is rapidly absorbed into the body immediately after applying the hair-growth composition on the skin such as the scalp. Is considered to be the cause. In other words, it is considered that the hair growth effect of minoxidil is fully exhibited only after minoxidil is absorbed into the body slowly to some extent. Moreover, when propylene glycol is contained in a mass ratio of 10 times or more with respect to minoxidil in the hair restorer composition, an improvement in the hair restore effect is no longer desired, and when the hair restorer is applied to the scalp, etc. The feeling of use is reduced due to stickiness. Furthermore, there is concern about the development of contact dermatitis as described above.

  The reason why minoxidil is rapidly absorbed in the body when the amount of propylene glycol is small is considered as follows. When the hair restorer composition is applied onto the skin, the volatile solvent in the mixture of propylene glycol and mincedil dissolving minoxidil preferentially evaporates immediately after application. As a result, minoxidil is present on the skin mainly dissolved in propylene glycol. When the amount of propylene glycol is small, minoxidil is locally present at a very high concentration on the skin surface, and it is considered that the transdermal absorbability of minoxidil is greatly increased. The rapid absorption of minoxidil into the body is also concerned about the influence on the circulatory system, considering that minoxidil acts as a hypotensive agent as described above.

  In the hair restorer composition of the present invention, it is particularly preferable that propylene glycol is contained in an amount of more than 7 times and less than 10 times by mass ratio with respect to minoxidil.

  In the hair restorer composition of the present invention, it is desirable that minoxidil is contained in an amount of 0.1 to 7 g with respect to 100 mL of the hair restorer composition. When the content of minoxidil is less than the above range, the hair-growth effect is insufficient. In addition, the higher the content of minoxidil, there is concern about the influence of minoxidil on the circulatory system.

  The dosage form of the hair restorer composition of the present invention is not particularly limited, but it is preferably a lotion agent or a jelly agent particularly when the minoxidil content is as high as 3 to 7 g with respect to 100 mL of the composition.

  According to the present invention, there is provided a hair restorer having a high hair-growth effect in which the hair-growth effect of minoxidil is sufficiently exhibited. Moreover, the hair restorer excellent in the usability | use_condition at the time of applying to a scalp etc. is provided.

  The hair restorer composition of the present invention contains at least propylene glycol and a volatile solvent in addition to minoxidil as a hair restorer active ingredient.

  In the hair restorer composition of the present invention, minoxidil is blended so as to be in the range of 0.1 to 7 g, preferably 0.5 to 6 g, particularly preferably 1 to 5 g, per 100 mL of the hair restorer composition. desirable. A sufficient hair-growth effect can be obtained within this range.

  In the hair growth composition of the present invention, propylene glycol is in a mass ratio with respect to minoxidil in a range of more than 5 times and less than 10 times, preferably more than 6 times and less than 10 times, particularly preferably more than 7 times. It is blended so that it is less than 10 times more. If the blending ratio of propylene glycol to minoxidil is smaller than the above range, a hair restorer composition exhibiting a sufficiently high hair restoring effect cannot be obtained, and if it is more than the above range, an improvement in hair restoring effect is no longer desired. When a hair restorer is applied to the scalp, etc., it becomes sticky and the feeling of use decreases.

  Examples of the volatile solvent blended in the hair restorer composition of the present invention include ethanol, water, propyl alcohol, isopropyl alcohol, s-butyl alcohol, and t-butyl alcohol. From the viewpoint of the feeling of use when the hair restorer is applied to the scalp and the like, the volatile solvent is preferably selected from the group consisting of ethanol, water, and a mixture of ethanol and water.

  The hair restorer composition of the present invention is prepared by blending minoxidil, propylene glycol, and a volatile solvent as hair restoration active ingredients at the blending ratio as described above. The dosage form of the hair restorer composition of the present invention is not particularly limited, and a lotion agent, jelly agent, tonic agent, ointment, cream agent, spray agent, aerosol agent and the like can be adopted, but in particular the content of minoxidil Is a lotion agent or jelly agent when it is relatively high at 3 to 7 g per 100 mL of the composition. In accordance with these dosage forms, the hair growth composition of the present invention includes a moisturizer, preservative, surfactant, gelling agent, pH in addition to the essential components of minoxidil, propylene glycol, and volatile solvent. A regulator, an antioxidant, a refreshing agent, a solubilizing agent, an emulsion stabilizer, a pressure-sensitive adhesive, a fragrance, and the like can be appropriately blended within a range not impairing the effects of the present invention.

  As humectants, glycerin, diglycerin, 1,3-butanediol, sodium hyaluronate, chondroitin sulfate, etc. can be used, and as preservatives, parabens, benzoates, etc. can be used, As the surfactant, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, glycerin fatty acid ester, propylene glycol fatty acid ester and the like can be used. Hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxyvinyl polymer, etc. can be used as gelling agents, and triethanolamine, diisopropanolamine, citric acid, lactic acid, phosphoric acid, etc. can be used as pH adjusters. Can do. Dibutylhydroxytoluene, sodium pyrosulfite, tocophenol, sodium edetate, isopropyl gallate and the like can be used as the antioxidant, and menthol, peppermint oil, camphor and the like can be used as the cooling agent. As a solubilizer, diisopropyl adipate, isopropyl myristate, γ-cyclodextrin, and the like can be used.

  The hair growth agent of the present invention further includes other conventional medicinal ingredients such as vasodilators (carpronium chloride, benzyl nicotinate, ginseng extract, vitamin E acetate, etc.), metabolic activators (panthenol, pantothenic acid and derivatives thereof, etc. ), Antihistamines (diphenhydramine hydrochloride, isothipentyl hydrochloride, etc.), anti-inflammatory agents (guaiazulene, glycyrrhetinic acid, etc.), keratolytic agents (urea, salicylic acid, etc.), fungicides (chlorhexidine gluconate, isopropylmethylphenol, hinokitiol, piroctone olamine) Etc.), vitamins (retinol acetate, pyridoxine hydrochloride, ascorbic acid, biotin, etc.) can also be incorporated within a range not impairing the effects of the present invention.

  The hair restorer composition of the present invention is used by applying an appropriate amount to the skin surface about once or twice a day.

  EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

1. Measurement of blood concentration A hair growth solution was prepared by blending each compound with the composition shown in Table 1 below.

Table 1: Composition of hair growth solution

  The blood concentration of minoxidil was measured using Wistar male rats (7 weeks old). On the day before the test, the back was shaved with an animal clipper and used. 500 μL of the hair-growth solution shown in Table 1 was applied to the back of the shaved rat (about 4 × 6 cm), and blood was collected after a predetermined time (1, 2, 4, 8 hours) after application to obtain serum.

  The obtained serum sample was subjected to solid phase extraction with a pretreated column and quantified by high performance liquid chromatography.

  FIG. 1 shows the measurement results. From FIG. 1, it can be seen that as the ratio of the propylene glycol content to the minoxidil content in the hair growth composition increases, the transient increase in the blood concentration of minoxidil is suppressed.

2. Confirmation test of hair growth effect Each compound was mix | blended with the composition shown in the following Tables 2-4, and the hair growth lotion agent was prepared.

  A test for confirming the hair-growth effect was performed using C3H / HeN male mice (7 weeks old). After the mouse was anesthetized, the back was shaved. From the next day after shaving, 100 μL of the lotions shown in Tables 2 to 4 were applied to the back of the mouse twice a day (morning and afternoon). The hair-growth effect was evaluated by the percentage of hair growth individuals (%) 66 days after the start of application. Tables 2 to 4 summarize the percentage of hair growth individuals (%) calculated by the following formula.

Hair growth individual ratio (%) = number of hair growth individuals in each group × 100 / number of cases in each group

Table 2: Lotion preparation composition and evaluation results

Table 3: Lotion preparation composition and evaluation results

Table 4: Lotion preparation composition and evaluation results

  From Tables 2 to 4, the proportion of propylene glycol content in the lotion tends to increase as the proportion of the propylene glycol content to the minoxidil content increases (the hair growth effect increases), but the propylene glycol content of minoxidil content It can be seen that when the ratio to the ratio is 10 times, the hair-growth effect is rather lowered. Furthermore, it can be seen that when the hair-growing composition (lotion) of the present invention is used, good results with a hair growth individual ratio of 80% or more are obtained.

  Regarding Examples 3 to 8, Controls 2 and 3, and Comparative Example 3, in addition to the evaluation based on the above-mentioned hair growth individual ratio (%), the hair growth site area was also evaluated. Tables 3 and 4 summarize the hair growth site areas 66 days after the start of application.

  From Tables 3 and 4, when using a lotion preparation containing 5 g of minoxidil in an amount of 3 g based on 100 mL of the composition, the hair growth area was increased. I understand that. Further, in the case of a lotion preparation containing 3 g of minoxidil per 100 mL of the composition, the hair growth site area increases as the ratio of the propylene glycol content to the minoxidil content increases. In the case of a lotion preparation containing 5 g per 100 mL of the product, the maximum hair growth area was observed in the lotion preparation with a ratio of propylene glycol content to minoxidil content of 7.5 times, and further contained propylene glycol. It can be seen that as the ratio of the amount to the minoxidil content increases, the hair growth site area rather decreases.

3. Usability Confirmation Test Each compound was blended with the composition shown in Table 5 below to prepare a lotion preparation.

Table 5: Composition of lotion

  About the lotion preparations of these Examples and Comparative Examples, the feeling of use was evaluated by 10 male subjects in their 20s to 50s. In the evaluation method, 0.5 mL of the lotion preparation of the example was applied to the right side of the head and the lotion preparation of the comparative example was applied to the left side. The evaluation items were a sticky feeling immediately after application of the lotion agent, a sticky feeling after 5 minutes of application, and the dryness, and the sensory evaluation was performed in the following five stages.

Evaluation criteria Stickiness
5: Pretty sticky
4: Slightly sticky
3: Normal
2: Slightly smooth
1: It is quite smooth and dry
5: Very difficult to dry
4: Slightly difficult to dry
3: Normal
2: Slightly easy to dry
1: Pretty easy to dry Table 6 below shows the average of the evaluation of 10 subjects. It has been clarified that the hair restorer composition of the present invention is excellent in the feeling of use.

Table 6: Evaluation results

4). Formulation example The lotion agent and jelly agent by the hair restorer composition of this invention shown in the following Table 7 were manufactured.

Table 7-1: Composition of lotion

Table 7-2: Composition of jelly agent

It is the figure which showed the time change of the blood concentration of minoxidil.

Claims (3)

A hair restorer composition comprising minoxidil, propylene glycol, and a volatile solvent,
A hair restorer composition comprising propylene glycol in an amount of more than 5 times and less than 10 times by mass ratio with respect to minoxidil.   A hair restorer composition comprising propylene glycol in an amount of more than 7 times and less than 10 times by weight with respect to minoxidil.   The hair restorer composition according to claim 1 or 2, wherein minoxidil is contained in an amount of 0.1 to 7 g with respect to 100 mL of the hair restorer composition.

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