Composition for treating hair loss containing minoxidil

Abstract

This application relates to a hair loss treatment composition comprising minoxidil or a pharmaceutically acceptable salt thereof, wherein the skin permeability of minoxidil can be improved by including a lipid-soluble transdermal absorption enhancer.

Description

Technical Field

[0001] The present invention relates to a composition for hair loss treatment containing minoxidil.

Background Art

[0002] Hair loss treatment agents are mainly under development in oral dosage forms containing finasteride or dutasteride as the main component, or liquid dosage forms containing minoxidil as the main component. Among them, the liquid dosage form treatment agents are in the form of a solution in which a skin penetration enhancer, an antioxidant, a surfactant, a humectant, a pH adjuster, etc. are dissolved in water and / or ethanol in order to increase the stability of the active ingredient and the skin permeability. <​​​​​​​​​​​​​​​​​​The present invention relates to a pharmaceutical composition comprising minoxidil or a pharmaceutically acceptable salt thereof, and a lipid-soluble skin permeability enhancer. The composition of the present invention may further contain a surfactant. The pharmaceutical composition according to the present invention can be used for the treatment of hair loss in the form of a foam aerosol formulation.

[0006] The composition of the present invention may further contain one or more solvents selected from the group consisting of water and ethanol. Preferably, volatile ethanol is used as the solvent, and water may optionally be included (for example, less than 70% by weight of the total weight of the composition).

[0007] In the composition of the present invention, the lipid-soluble skin permeability enhancer is preferably a propylene glycol fatty acid ester. In the present invention, propylene glycol monocaprylate, propylene glycol dicaprylate / dicaplate, propylene glycol monolaurate, propylene glycol monooleate, propylene glycol monostearate, and the like can be preferably used as the propylene glycol fatty acid ester. Most preferably, propylene glycol monocaprylate is used.

[0008] In the present invention, the skin penetration enhancer may be included in an amount of 0.01 to 15% by weight, preferably 0.1 to 12% by weight, relative to the total weight of the composition.

[0009] Preferred surfactants in the present invention are sorbitan esters (e.g., sorbitan stearate, polysorbate (polyoxyethylene sorbitan fatty acid ester), or polyoxyethylene alkyl ether), which may be included in the composition in an amount of 0.01 to 10% by weight, preferably 0.1 to 7% by weight, relative to the total weight of the composition.

[0010] Furthermore, the composition of the present invention may further contain one or more of a wetting agent, a pH adjuster, and an antioxidant.

[0011] Any commonly used wetting agent (e.g., glycerin, sodium hyaluronate, mannitol, xylitol, etc.) may be used as the wetting agent in the present invention, but glycerin is preferred. The wetting agent may be included in an amount of 0.1 to 5% by weight relative to the total weight of the composition of the present invention.

[0012] Any commonly used pH adjusting agent can be used as the pH adjusting agent in the present invention, preferably an organic acid such as citric acid or lactic acid. The pH adjusting agent may be included in an amount of 0.1 to 5% by weight relative to the total weight of the composition of the present invention.

[0013] Any commonly used antioxidant can be used as the antioxidant in the present invention, preferably butylhydroxytoluene (BHT). The antioxidant may be included in an amount of 0.1 to 5% by weight relative to the total weight of the composition of the present invention.

[0014] The pharmaceutical composition according to the present invention is used for the treatment of hair loss and can be formulated into a liquid formulation or a foam aerosol formulation. [Effects of the Invention]

[0015] The pharmaceutical composition according to the present invention exhibits excellent skin permeability. [Brief explanation of the drawing]

[0016] [Figure 1] This graph shows the cumulative amount of skin permeation per unit area over 24 hours when the composition according to the present invention is applied. [Modes for carrying out the invention]

[0017] Hereinafter, for the purpose of facilitating the understanding of the present invention, the present invention will be described in detail based on examples. However, the following examples are merely illustrative of the content of the present invention, and the idea and scope of the present invention are not limited by the following examples in any sense. The examples of the present invention are provided to more fully explain the present invention to those with average knowledge in the industry.

[0018] Example 1: Production of Composition Compositions of Example 1 and Comparative Examples 3 to 6 were respectively produced according to the components and contents shown in Table 1 below.

[0019] [Table 1]

[0020] Specifically, among the above components, the remaining components excluding the LPG component as the propellant were mixed to produce an emulsion. After filling this emulsion into a foam aerosol container, the LPG as the propellant was pressure-filled into this container to produce a foam aerosol preparation.

[0021] Experimental Example 1: Evaluation of Fluidity The fluidity of the composition of Example 1 and a currently commercially available minoxidil-containing liquid therapeutic agent (Comparative Example 2) was evaluated by the following method.

[0022] On an inclined plane having a 10° inclination, a PET film with one surface silica-coated and having a release force was overlaid to form an inclined path for evaluating fluidity. 1 g each of the composition of Example 1 and the composition of Comparative Example 2 was applied to the upper part of the corresponding inclined path, and the time taken to flow 5 cm was measured. Each fluidity evaluation was performed 5 times, and the corresponding results are as shown in Table 2.

[0023] [Table 2]

[0024] As can be seen from the results in Table 2 above, Example 1 does not flow on an inclined surface, thus improving the ease of use compared to Comparative Example 2. That is, when the composition according to the present invention is applied to the hair on the scalp, the medicinal composition does not flow, so the medicinal effect is exerted continuously, and daily life is not interfered with after application.

[0025] Experimental Example 2: Evaluation of Artificial Skin Permeability The skin permeability of the compositions of Example 1 and Comparative Examples 3-6, as well as a currently marketed minoxidil-containing topical drug for hair loss treatment (Comparative Example 2), was evaluated using the following method.

[0026] Strat-M as an artificial skin TM Using a membrane (transdermal diffusion test membrane, Milipole), 1 mL each of the compositions from Example 1 and Comparative Examples 2-6 was applied to each donor compartment. The skin permeability test was performed three times for each (n=3), and the skin permeability test conditions using a Franz diffusion cell were as follows.

[0027] - Diffusion area: 1.767 cm² 2 -Sample Loading: 1 mL each of the compositions for Example 1 and Comparative Examples 2-6. - Receiver compartment: 7 mL of phosphate buffered saline (PBS) (pH 7.4) - Stirring speed 600 rpm -Temperature: 32℃ - Sample collection: 200 μl samples were collected from each receiver compartment at 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 18 hours, and 24 hours, and then 200 μl of the phosphate buffer was added to each.

[0028] The amount of minoxidil present in the sample taken was analyzed by high performance liquid chromatography (HPLC) analysis. The HPLC analysis was carried out under the following conditions:

[0029] <HPLC Conditions> - Column: Hypersil Gold C18 (250x4.6 mm, 5 μm) - Column temperature: 40 °C - Mobile phase: methanol: water: acetic acid = 700:300:10 (sodium doxsylate 3.0 g / L, perchloric acid → pH 3.0) - Flow rate: 1.0 mL / min - Detection: 254 nm - Sample injection volume: 10 μl

[0030] The analysis results are as shown in Table 3 and Figure 1 below.

[0031]

Table 3

[0032] As can be seen from the results of Table 3 above, in Example 1 according to the present invention, the skin permeation concentration was very high compared to the comparative example.

[0033] From the above results, it can be seen that propylene glycol monocaprylate has a significantly superior skin permeation promoting effect compared to other skin permeation promoters (propylene glycol, glyceryl monooleate, sorbitan monooleate).

[0034] From the above experiments, the minoxidil-containing preparation according to the present invention does not flow on an inclined surface, so the ease of use is ensured and improved percutaneous permeation of minoxidil is shown.

Industrial Applicability

[0035] The minoxidil-containing composition according to the present invention is excellent in skin permeability and is useful as a hair loss treatment agent.

Claims

1. Minoxidil or a pharmaceutically acceptable salt thereof, A pharmaceutical composition containing a lipid-soluble transdermal absorption enhancer.

2. The pharmaceutical composition according to claim 1, wherein the lipid-soluble transdermal absorption enhancer is a propylene glycol fatty acid ester.

3. The pharmaceutical composition according to claim 2, wherein the propylene glycol fatty acid ester is selected from one or more of the group consisting of propylene glycol monocaprylate, propylene glycol dicaprylate / dicaplate, propylene glycol monolaurate, propylene glycol monooleate, and propylene glycol monostearate.

4. The pharmaceutical composition according to claim 2, wherein the propylene glycol fatty acid ester is selected from the group consisting of propylene glycol monocaprylate and propylene glycol monolaurate, one or more of these.

5. The pharmaceutical composition according to claim 1 or 2, further comprising a surfactant.

6. The pharmaceutical composition according to claim 5, wherein the surfactant is selected from one or more of the group consisting of sorbitan esters, polysorbates, and polyoxyethylene alkyl ethers.

7. The pharmaceutical composition according to claim 5, wherein the surfactant is selected from one or more of the group consisting of sorbitan stearate, polysorbate 60, and polyoxyethylene lauryl ether.

8. The pharmaceutical composition according to claim 1, wherein the solvent is water, ethanol, or a mixture of water and ethanol.

9. The pharmaceutical composition according to claim 1, further comprising one or more surfactants, wetting agents, pH adjusters, and antioxidants.

10. The pharmaceutical composition according to claim 1 or 2, wherein the pharmaceutical composition is a liquid formulation and is for the treatment of hair loss.

11. The pharmaceutical composition according to claim 1 or 2, wherein the pharmaceutical composition is a foam aerosol formulation and is for the treatment of hair loss.

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