KR20080038710A - Epidermal emulsion composition for treating a bald containing minoxidil and tretinoin - Google Patents

Abstract

A composition for growing hair comprising minoxidil and tretinoin is provided to help absorption of active ingredients by forming a film using a film forming agent and improve skin permeability by using a skin absorption promoting agent having affinity to sebum. An epidermal emulsion composition for growing hair comprises: 2.0-5.0 wt.% of minoxidil; 0.01-0.03 wt.% of tretinoin; 0.1-2.0 wt.% of an absorption promoting agent; 0.3-5.0 wt.% of a film forming agent; 85.0-94.0 wt.% of a dissolution supplement; and 0.05-2.0 wt.% of an additive. Further, the dissolution supplement is selected from a group consisting of ethyl alcohol, glycerin, propylene glycol, Cremophor RH40 or a mixture thereof.

Description

Epidermal Emulsion Composition for Treating a bald Containing Minoxidil and tretinoin}

Figure 1. Photograph before applying the comparative example according to the present invention to the BDF1 mouse in which the male hair loss environment was formed by applying the testosterone 4.0% by weight solution once a week for one week after hair removal on the back.

Figure 2. Photograph before applying the Example according to the present invention to the BDF1 mouse in which the male hair loss environment was formed by applying the testosterone 4.0% by weight solution once a week for 1 week after hair removal on the back.

Figure 3. BDF1 mouse photograph taken three weeks after the application of the comparative example according to the present invention.

Figure 4. BDF1 mouse picture taken three weeks after application of the embodiment according to the present invention.

The present invention provides a pharmaceutical composition containing minoxidil and tretinoin, using the film forming agent to help the absorption of the active ingredient through the film formation, and improved skin permeability by using a skin absorption accelerator having affinity with oil sebum. The present invention relates to an emulsion composition for hair growth and a method for preparing the same.

More specifically, the present invention provides an external emulsion comprising minoxidil and tretinoin as active ingredients, and a dissolution aid and other additives (stabilizer, preservative) selected from the group consisting of ethyl alcohol, propylene glycol, glycerin or mixtures thereof. It relates to a composition that can be used for hair growth by providing and a method for producing the same.

Minoxidil (2,4-diamino-6-piperidinopyrimidine-3-oxide), a compound of the present invention, was originally approved by the US Food and Drug Administration as a therapeutic agent for oral hypertension, followed by treatment of severe hypertension with vasodilators. It has been found that hair growth, thickening and pigmentation are observed in oral administration patients, and 2%, 3%, and 5% concentrations of minoxidil have been developed for topical application. It is used for treatment.

Another compound of the invention, tretinoin (or all-trans retinoic acid or vitamin A acid), is a drug used for vulgar acne, a skin disease. This drug is a vitamin A synthetic derivative made from vitamin A as a raw material. It is used not only for the treatment of acne, but also for the treatment of pigments such as blemishes and blemishes, and is known to have anti-aging function to remove wrinkles.

In addition, tretinoin has recently been used with minoxidil to increase the absorption of minoxidil, increase epithelial cells in the scalp area, regenerate the skin and hair follicles, and invigorate new vitality. It has also been shown to reduce the levels of testosterone (DHT), which inhibits DHT from further damage to hair follicles.

Many prescription drugs currently on the market are minoxidil single solution formulations, and hair loss patients have to apply a minoxidil-containing formulation after applying a tretinoin-containing solution. Therefore, in the present invention, the convenience of the hair loss patient was increased by changing the two drugs into a stable formulation.

In addition, a minoxidil solution using propylene glycol, ethanol, water, and the like as an aqueous solvent, which has a high solubility with respect to minoxidil, has been used as a conventional solution of minoxidil. However, there is a problem in that the skin permeability is extremely reduced because there is no affinity with sebum which is an oil component surrounding the hair follicles of the skin. Therefore, in the present invention, by using a skin absorption accelerator having affinity with oil component sebum to promote absorption of minoxidil and tretinoin, it was possible to improve poor skin permeability and reproducible skin absorption effect which was a problem of the conventional formulation.

In addition, in the present invention, by activating by selecting and adding a group consisting of hydroxypropyl methyl cellulose, methyl cellulose, propyl cellulose, polypropylene, polymethyl methacrylate, or a mixture thereof, which forms a film to maximize absorption, The components of minoxidil and tretinoin are distributed on the scalp for a long time to help effectively reach and function to the desired skin tissue, thereby completing the present invention.

Accordingly, the present invention solves the inconvenience of using the minoxidil-containing agent and tretinoin-containing agent separately, improves poor skin permeability, which is a problem of the existing formulations, and more powerful minoxidil and tretinoin by continuous distribution and effective permeation through film formation. The purpose is to make a composition for external emulsion hair growth containing.

In order to achieve the above object, the composition for external emulsion hair growth according to the present invention may contain minoxidil and tretinoin as active ingredients and may include an absorption accelerator, a film forming agent, a dissolution aid and an additive.

The hair growth composition is minoxidil 2.0 to 5.0% by weight relative to the total weight of the composition; Tretinoin is 0.01% to 0.03% by weight based on the total weight of the composition; The absorption accelerator is 0.1% to 2.0% by weight based on the total weight of the composition; The film forming agent is 0.3% to 5.0% by weight based on the total weight of the composition; The dissolution aid is 85.0% to 94.0% by weight based on the total weight of the composition; And 0.05 wt% to 2.0 wt% with respect to the total weight of the composition.

The absorption accelerator is octyldodecyl myristate, octyl dodecyl lactate, octyl dodecyl ercaate, octyl dodecyl oleate, octyledolic acid lysoleate, isostearic acid, Myristic acid isocetyl, myristic acid isopropyl, myristic acid butyl, myristic acid cetyl, It may be selected from the group consisting of myristic acid decyl, myristic acid myristyl or mixtures thereof.

The film forming agent may be selected from the group consisting of hydroxypropyl methyl cellulose, methyl cellulose, propyl cellulose, polypropylene, polymethyl methacrylate or a mixture thereof.

The dissolution aid may be selected from the group consisting of ethyl alcohol, glycerin, propylene glycol, cremophor RH40 or mixtures thereof.

The additive is selected from the group consisting of Kollidon VA64 as a stabilizer, citric acid, sodium lactate, sodium acetate, lactic acid, glacial acetic acid or adipic acid as a stabilizer, Butyl Hydroxy Anisole (hereinafter BHA), Butyl Hydroxy Toluene (hereinafter as BHT), tocopherol or ascorbic acid.

Hereinafter, the present invention will be described in detail.

In the present invention, as active ingredient, minoxidil may comprise 2.0% to 5.0% by weight based on the total weight. If it contains more than 5.0% by weight, it may affect the cardiovascular system due to overdose and cause excessive blood pressure drop. If it contains less than 2.0% by weight, the expected hair growth effect may not be obtained.

As another active ingredient in the present invention, tretinoin is included 0.01% to 0.03% by weight, more preferably 0.025% by weight based on the total weight. When used in less than 0.01% by weight it is difficult to expect the effect, even when used in excess of 0.03% by weight does not show a synergistic effect due to the increase in content, and may be accompanied by side effects such as redness, itching, peeling of the skin when used in excess . When tretinoin is used, it increases the absorption of minoxidil, increases epithelial cells in the scalp area, regenerates skin and hair follicles, and reduces the level of dehydrotestosterone (DHT), which prevents this DHT from causing further damage to hair follicles. Giving effect.

Absorption accelerators octyldodecyl myristate, octyl dodecyl lactate, octyl dodecyl ercaate, octyl dodecyl oleate, octyledolic acid ricinoleate, isocetyl myristate, isocetyl myristate, isopropyl myristic acid It is selected from the group consisting of butyl myristic acid, myristic acid cetyl, myristic acid decyl, myristic acid myristyl, or a mixture thereof, and may include 0.1% to 2.0% by weight based on the total weight of the present composition. . If it contains more than 2.0% by weight, it may cause problems in the stability of the preparation, such as a layer is formed over time after the preparation of the preparation, when containing less than 0.1% by weight it is difficult to expect the role as the desired absorption accelerator.

The film-forming agent according to the present invention is selected from the group consisting of hydroxypropyl methyl cellulose, methyl cellulose, propyl cellulose, polypropylene, polymethyl methacrylate or mixtures thereof, and 0.3 wt% based on the total weight of the composition of the present invention. To 5.0 wt%. Addition of more than 5.0% by weight affects the viscosity of the composition and causes a pulling of the skin upon application. If less than 0.3% by weight, it is difficult to expect the distribution duration through the film forming effect.

As a dissolution aid according to the present invention, a mixture of ethyl alcohol, glycerin, propylene glycol and cremophor RH40 may be included in an amount of 85.0 wt% to 94.0 wt% based on the total weight. Ethyl alcohol and glycerin serve as solubilizers and dissolution aids for minoxidil, and propylene glycol and cremophor RH40 serve as solubilizers and dissolution aids for tretinoin and octyldodecyl myristate. When added in excess of 94.0% by weight may affect the viscosity of the composition of the present invention, it may cause discomfort such as stickiness in use, and the problem of stability due to separation of the oil layer and the water layer. If less than 85.0% by weight of the main component is difficult to dissolve.

The stabilizer according to the present invention is selected from the group consisting of Kollidon VA64, pH adjusting agent, citric acid, sodium lactate, sodium acetate, lactic acid, glacial acetic acid or adipic acid, and as an antioxidant is a group consisting of BHT, BHA, tocopherol or ascorbic acid It may be selected from, and may be included in the 0.05 wt% to 2.0 wt% based on the total weight of the composition.

Hereinafter, the present invention will be described in more detail with reference to the following examples and comparative examples. However, the following examples are merely examples and the scope of the present invention is not limited thereto.

EXAMPLE

Minoxidil and tretinoin-containing external emulsion hair growth composition was prepared according to the composition of Table 1 below.

 Table 1

Ingredient Name content Minoxidil 3 g Tretinoin 25mg Ethyl alcohol 47 g glycerin 18g Cremophor RH40 14 g Propylene glycol 12 g Octyldodecyl Myristate 1 g Kollidon VA64 1 g Citric acid 0.3 g BHT 50 mg Hydroxypropyl methylcellulose 2.3g Distilled water 100ml with proper amount

According to each of the above compositions, minoxidil was prepared using ethyl alcohol and glycerin as a dissolving agent, tretinoin was prepared at 50 ° C. using Cremophor RH40 and propylene glycol as a dissolving agent, and the two prepared solutions were slowly mixed. Was completed.

Comparative Example 1

Except for octyldodecyl myristate in the composition of the above example, the composition for hair growth of the comparative example was prepared by the same composition and preparation method.

Comparative Example 2

Except for tretinoin in the composition of the above example, the composition for hair growth of the comparative example was prepared by the same composition and preparation method.

Comparative Example 3

Except for the hydroxypropyl methyl cellulose in the composition of the Example was prepared a composition for hair growth of the comparative example in the same composition and preparation method.

Comparative Example 4

Except for octyldodecyl myristate and hydroxypropyl methylcellulose in the composition of the above Example, the composition for hair growth of Comparative Example 4 was prepared by the same composition and preparation method.

Comparative Example 5

Except for tretinoin and hydroxypropyl methylcellulose in the composition of the above example, the composition for hair growth of Comparative Example 5 was prepared by the same composition and preparation method.

[Test Example 1]

The above embodiment according to the present invention was confirmed the stability of the two active ingredients minoxidil and tretinoin over the storage period under the conditions of room temperature, refrigeration and acceleration, the results are shown in Table 2 below.

[Table 2]

Example  content (%) Storage period / Preservation Room temperature cold storage Acceleration Minoxidil Tretinoin Minoxidil Tretinoin Minoxidil Tretinoin 1 week 99.8 100.1 99.5 99.9 99.7 99.6 4 Weeks 99.8 100.2 99.4 99.7 99.5 99.6 8 Weeks 99.6 99.9 99.2 99.8 99.4 99.3 12 Weeks 99.6 99.8 99.3 99.7 99.4 99.5

(Content was converted into% compared to 0 weeks)

As can be seen in Table 2, when the composition of the present invention according to the present invention was confirmed to be stable at room temperature, refrigeration and acceleration conditions.

[Test Example 2]

For the Example according to the present invention, the skin absorption promoting effect of the minoxidil component of octyldodecyl myristate was confirmed and the results are shown in Table 3 below.

Table 3

Minoxidil  Cumulative Skin Penetration (㎍ / ㎠) 3 hours later 6 hours later 12 hours Example 8.2 20.6 30.5 Comparative Example 1 6.9 14.3 21.8 Comparative Example 4 7.4 15.8 23.2

Note: Cumulative skin permeation of minoxidil (㎍ / ㎠) = concentration of sample solution (㎍ / mL) X total volume of cells (mL) X (1 / cell inlet area (㎠))

As can be seen from the results of Table 3, the composition of the present invention shows excellent skin permeability compared to Comparative Example 1 and Comparative Example 4. In addition, Comparative Example 1 was found to show an increased absorption of about 1.31 times or more after 12 hours, when comparing the Example according to the present invention.

[Test Example 3]

For the examples of the present invention, the hair growth and wool effects were confirmed through comparison with minoxidil alone.

The test was conducted after depilation of the back hairs of BDF1 mice (4 weeks old) and application of testosterone 4.0% by weight solution once a week to form a male hair loss environment (see FIGS. 1 and 2). It was applied twice a day for 3 weeks to check the hair growth and wool effect.

Through the above test, it can be seen that the combined use of tretinoin (see Fig. 4) is more effective for wool and hair growth than the use of minoxidil alone (see Fig. 3). Removed the convenience and improved the ease of use.

[Test Example 4]

In the present invention, the absorption of minoxidil was confirmed by increasing the sustained distribution time through the use of the film forming agent of minoxidil and tretinoin, and the results are shown in Table 4 below.

Table 4

Minoxidil  Cumulative Skin Penetration (㎍ / ㎠) 3 hours later 6 hours later 12 hours Example 8.1 20.4 30.3 Comparative Example 3 7.8 19.3 28.7 Comparative Example 5 7.2 15.6 23.1

Note: Cumulative skin permeation of minoxidil (㎍ / ㎠) = concentration of sample solution (㎍ / mL) X total volume of cells (mL) X (1 / cell inlet area (㎠))

As can be seen from the results of Table 4, the embodiment according to the present invention showed a better result than when the film forming agent was excluded (Comparative Example 3), which is octyldode as a skin absorption accelerator. It showed a better effect than the addition of only sil myristate (Comparative Example 5).

The external emulsion formulation of the present invention contains minoxidil and tretinoin as active ingredients and contains a skin absorption accelerator having an affinity with oil sebum for increasing absorption, thereby promoting skin absorption of minoxidil component and thus excellent in terms of hair growth and wool. It shows activity, forms a film, and distributes the active ingredient to the scalp for a long time. In addition, it is manufactured with tretinoin to improve the patient's convenience by eliminating the need to apply separately. In addition, it is an emulsion composition for external hair regrowth having the advantage that there is no change in properties even when stored with an appropriate additive and the content is not reduced.

Although the present invention has been described in detail with reference to specific examples described, it will be apparent to those skilled in the art that various modifications and variations are possible within the scope and spirit of the present invention, and such modifications and modifications are set forth in the appended claims. It is natural to belong.

Claims (6)

As an external emulsion hair growth composition, A composition for hair growth comprising minoxidil and tretinoin as active ingredients and comprising an absorption accelerator, a film forming agent, a dissolution aid and an additive. The method of claim 1, Minoxidil is 2.0% to 5.0% by weight based on the total weight of the composition; Tretinoin is 0.01% to 0.03% by weight based on the total weight of the composition; The absorption accelerator is 0.1% to 2.0% by weight based on the total weight of the composition; The film forming agent is 0.3% to 5.0% by weight based on the total weight of the composition; The dissolution aid is 85.0% to 94.0% by weight based on the total weight of the composition; And The additive is 0.05% to 2.0% by weight based on the total weight of the composition; Regrowth composition comprising a. The method according to claim 1 and 2, The absorption accelerator is octyldodecyl myristate, octyl dodecyl lactate, octyl dodecyl ercaate, octyl dodecyl oleate, octyledolic acid lysoleate, isostearic acid, Myristic acid isocetyl, myristic acid isopropyl, myristic acid butyl, myristic acid cetyl, A composition for hair regrowth, characterized in that it is selected from the group consisting of myristic acid decyl, myristic acid myristyl or mixtures thereof. The method according to claim 1 and 2, The film-forming agent is a hair growth composition, characterized in that selected from the group consisting of hydroxypropyl methyl cellulose, methyl cellulose, propyl cellulose, polypropylene, polymethyl methacrylate or a mixture thereof. The method according to claim 1 and 2, The dissolution aid is selected from the group consisting of ethyl alcohol, glycerin, propylene glycol, Cremophor RH40 or a mixture thereof. The method according to claim 1 and 2, The additive as Kollidon VA64 as a stabilizer; pH adjusting agent is selected from the group consisting of citric acid, sodium lactate, sodium acetate, lactic acid, glacial acetic acid or adipic acid; Hair growth composition, characterized in that selected from the group consisting of BHT, BHA, tocopherol or ascorbic acid as an antioxidant.

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