KR20040076400A - Hair care composition containing minoxidal and surfactant cmposite particles - Google Patents

Abstract

PURPOSE: A hair care composition containing minoxidil and surfactant composite particles and a preparation method thereof are provided to improve phase stability, remaining of minoxidil in skin and hair growing effect. CONSTITUTION: The method for preparing the hair care composition comprises the steps of: mixing 5 to 35 wt.% of minoxidil, 0.5 to 35 wt.% of surfactant, 0.1 to 10 wt.% of moisturizer and water, and pulverizing the mixture and dispersing pulverized mixture at ultra-high pressure, wherein the surfactant is bipolar surfactant or cationic surfactant; the surfactant is selected from distearyldimethylammonium chloride, stearyl trimethylammonium methosulfate, stearyltrimethylammonium chloride, stearyldimethylbenzylammonium chloride, docosyltrimethylammonium methosulfate, docosyltrimethylammonium chloride, docosyldimethylbenzylammonium chloride, didocosyldimethylammonium chloride, lauryldiethylbenzylammonium chloride, lauryltrimethylammonium bromide, distearylmethylhydroxymethyl chloride, cetyltrimethylammonium chloride, N-stearyl-N,N,N-tri(polyoxyethylene)ammonium chloride, cetyltriethylammonium bromide and stearyldimethylammonium chloride; and the moisturizer is selected from dibutyl phthalate, gelatin, glycerin, soluble collagen, sorbitol, sodium 2-pyrrolidone-5-carboxylate, polyethylene glycol, octadecan-2-ol, caprylic triglyceride, capric triglyceride, propane-1,2-diol, triethylene glycol, nonoxynol-9, panthenol and propylene glycol.

Description

Hair composition containing minoxidil / surfactant composite particles {HAIR CARE COMPOSITION CONTAINING MINOXIDAL AND SURFACTANT CMPOSITE PARTICLES}

[TECHNICAL FIELD OF THE INVENTION]

The present invention relates to a hair composition containing a minoxidil / surfactant composite particle, and more specifically, to a minoxidil / surfactant complex, which is characterized by mixing minoxidil, a surfactant, a moisturizer and water, and pulverizing the same. It relates to a particle production method and a hair composition comprising the minoxidil / surfactant composite particles.

[Private Technology]

Minoxidil was approved by the US Food and Drug Administration as an oral antihypertensive drug in 1979, followed by hirsutism as a side effect in clinical trials as a hypertension drug. As a drug sold in 1997, a 5% formulation was approved by the US Food and Drug Administration as a drug sold in 1997 ( Fragrance Journal , 2, 33-37 (2000)).

153 patients with crown-type male baldness were tested for 24 months with 2% and 3% minoxidil solutions and found to promote hair growth after 12 months of treatment. The bald area was radically reduced in the patient or the bald area was no longer enlarged. Minoxidil is currently sold as Rogaine, a product dissolved in 2% and 5% ethanol / propylene glycol / water mixed solvents.

Although the external solution of minoxidil has been proved to have a wool effect, the hair composition for washing with minoxidil, for example, a composition such as shampoo and rinse, has a low skin residue because minoxidil is washed out by washing. Therefore, minoxidil is difficult to expect a wool effect in the hair composition for washing, minoxidil is a low solubility in water 0.2%, so when applied to shampoo and rinse at relatively high concentrations such as 1%, 2%, 3% It is difficult to maintain the stability of the composition, such as the minoxidil particles precipitate.

Meanwhile, previous studies on adsorption and residual properties of specific substrates such as fibers, hair, and skin of surfactants have been conducted. Certain surfactants, in particular cationic surfactants, have high adsorptive power to the surface of negatively charged substrates such as fibers, hair, and skin due to electrostatic attraction and persistence after cleaning. Therefore, there has been a previous study to increase the residual of the active ingredient by encapsulating the active ingredient such as silicone and sunscreen in a vesicle composed of the cationic surfactant itself as a fabric softener or a cationic surfactant (US 5,874,105). ).

An object of the present invention is to provide a composition for hair with high scalability of minoxidil.

It is another object of the present invention to provide a hair composition having excellent phase stability of minoxidil.

In addition, an object of the present invention is to provide a hair cleaning composition having a high concentration of minoxidil with excellent dispersion stability and excellent wool effect even after rinsing.

It is also an object of the present invention to provide a method for improving scalp persistence and phase stability of minoxidil.

The present invention provides a method for producing minoxidil / surfactant composite particles, characterized in that the minoxidil, surfactant, moisturizer and water are mixed, and pulverized.

In another aspect, the present invention provides a minoxidil / surfactant composite particles prepared by the above method.

In addition, the present invention provides a hair cleaning composition comprising the minoxidil / surfactant composite particles.

Hereinafter, the present invention will be described in more detail.

The present invention relates to a process for preparing minoxidil in the form of surfactants and multiparticulates to improve scalp persistence and phase stability of minoxidil.

The method for producing minoxidil / surfactant composite particles provided by the present invention is to mix minoxidil, a surfactant, a moisturizing agent, and water, and to grind it to ultra high pressure dispersion treatment.

Minoxidil uses what is usually sold.

The surfactant serves as a dispersion stabilizer of the minoxidil particles and at the same time serves as a binder to allow the minoxidil to remain on the scalp after rinsing. The surfactant may be used as one or more selected from the group consisting of anionic, cationic, nonionic and amphoteric surfactants. Anionic surfactants include alkyl sulphates, alkyl ether sulphates, alkaryl sulphonates, alkanoyl isethionates, alkyl succinates, and alkyl sulfates. Alkyl sulphosuccinates, N-alkoylsarcosinates, alkyl phosphates, alkyl ether phosphates, alkyl ether carboxylates, alpha-olefin sulfates (alpha-olefin sulphonates) and salt compounds thereof. The alkyl and acyl groups mentioned above are unsaturated having 8 to 18 carbon atoms. Alkyl ether sulphates, alkyl ether phosphates and alkyl carboxylates each contain 1-10 ethylene oxide or propylene oxide per molecule. It is desirable to have.

In addition, the anionic surfactant salt compound is sodium (sodium), magnesium (magnesium), ammonium, mono-, di-, tri- ethanolamine salt (mono-, di-, tri-ethanolamine) salt in the anionic surfactant It includes, preferably oleyl succinate (sodium oleyl succinate), lauryl sulphosuccinate, ammonium lauryl sulphate, sodium dodecylbenzene sulphonate ), Dodecylbenzenesulfonic acid triethanolamine salt (triethanolamine dodecylbenzene sulphonate), sodium cocoyl isethionate, sodium lauroyl isethionate and sodium N-lauryl salcosinate (sodium N-lauryl sarcosinate). Most preferably sodium lauryl sulphate, triethanolamine lauryl sulphate, triethanolamine monolauryl phosphate, sodium lauryl ether sulphate, ethylene Oxides are 1-3), at least one selected from the group consisting of ammonium lauryl sulphate and sodium lauryl ether sulphate (the number of ethylene oxide is 1-3).

As the cationic surfactant, a quaternary ammonium salt having the following formula may be used.

Formula

In the above formula, one or two of R ₁ , R ₂ , R ₃ , and R ₄ are linear alkyl or branched alkyl, or hydroxy alkyl group (C ₈ C ₂₂ ), and the rest are carbon atoms. Is an alkyl group having 1 to 3, a hydroxy alkyl group, a benzyl group or a poly oxyethylene group;

X is an alkyl sulfate group having halogen atoms or 1-2 carbon atoms.

Preferred cationic surfactants include distearyldimethylammonium chloride, stearyl trimethylammonium methosulfate, stearyltrimethylammonium chloride, stearyldimethylbenzyl ammonium chloride, stearyldimethylbenzylammonium chloride, Docosyltrimethylammonium methosulfate, docosyltrimethylammonium chloride, docosyldimethylbenzylammonium chloride, didocosyldimethylammonium chloride, lauryldiethylbenzyl chloride lauryldiethylbenzylammonium chloride, lauryltrimethylammonium bromide, distearylmethylhydroxymethyl chloride, cetyl tree chloride Cetyltrimethylammonium chloride, N-stearyl-N, N, N-tri (polyoxyethylene) ammonium salt (N-stearyl-N, N, N-tri (polyoxyethylene) ammonium chloride), brominated cetyltriethylammonium salt (cetyltriethylammonium bromide) and stearyldimethylammonium chloride.

The nonionic surfactant may be selected from primary or secondary fatty alcohols (C ₈ -C ₁₈ , straight or branched chains) or of phenols and alkylene oxides (ethylene oxides having mainly 6-30 ethylene oxide groups). Condensation reaction products, other alkyl polyglycosides, mono-, di-alkyl alkanol amides and coco mono-isopropanolamides isopropanolamide).

The amphoteric surfactants include alkyl amine oxides, alkyl betaines, alkyl amidorpopyl betaines, alkyl sulphobetaines, and alkyl glycinates. alkyl glycinates, alkyl carboxyglycinates, alkyl amphopropionates, alkyl amphoglycinates and alkyl amidopropyl hydorxylsultaines The carbon number of the alkyl and acyl group is preferably 8-19. More preferred amphoteric surfactants are lauryl amine oxide, cocodimethyl sulphopropyl betaine, lauryl betaine, cocamidopropyl betaine and sodium cocam Popprionate (sodium cocamphopripionate).

The moisturizing agent dissolves minoxidil by supplying water to minoxidil, thereby increasing the bioavailability of minoxidil to improve wool efficacy. Typical moisturizers that can be used include dibutyl phthalate, gelatin, glycerin, soluble collagen, sorbitol, sodium 2-pyrrolidone-5-carboxylate (sodium 2) -pyrrolidone-5-carboxylate, polyethylene glycol, octadecan-2-ol, caprylic triglyceride, capric triglyceride, propane Propane-1,2-diol, triethylene glycol, nonoxynol-9, panthenol and propylene glycol.

In the method for preparing minoxidil / surfactant composite particles of the present invention, the mixing content of minoxidil composition including minoxidil, surfactant, humectant and water is 5 to 35 wt% of minoxidil, 0.5 to 35 wt% of surfactant, 0.1 to 10 Weight percent moisturizer and residual water. The most preferred mixing content is 10 to 25% by weight minoxidil, 0.1 to 30% by weight surfactant, 1.0 to 8% by weight humectant and residual water.

If the amount of minoxidil and surfactant included in the minoxidil composition is lower than the above range, it is difficult to prepare a shampoo containing a high amount of minoxidil, that is, 1%, 2%, or 3% due to the problems of the general shampoo manufacturing process, and the minoxidil and the surfactant When the content of is higher than the above range, it is difficult to disperse with a mechanical dispersion device. In addition, if the content of the moisturizer is lower than the above range can not provide sufficient moisture to the scalp, if it is higher than the above range the phase of the final hair composition mixed with minoxidil / surfactant composite particles may be separated.

More specific minoxidil / surfactant manufacturing method is a colloid mill (mixing minoxidil, surfactant, moisturizer and distilled water, preliminary stirring at 50 to 65 ℃ for a certain time, using the friction of the grinding stone rotating at high speed ( colloid mill, a roll mill that uses the compression force between the rolls by rotating several metal rolls in succession, an ultrasonic sonicator that uses the pulverization of ultrasonic energy, and a fluid at high pressure through a small orifice. Ultra-high pressure dispersion device (Microfluidizer, Microfluidics Corp., USA) using shear stress, collision energy, and cavitation generated by effluent, Ultra Turrax, Janke and Kunkel, Germany, Nanojet, Nonojet Engineering , Germany), Brogli, Italy or its corresponding minoxidil / surfactant suitability using a mechanical dispersing device. It is to prepare a combined particle.

The present invention also provides a composition for hair comprising minoxidil / surfactant composite particles prepared as mentioned above. The concentration of minoxidil in the hair composition may be 0.1 to 5% by weight, preferably 0.5 to 4% by weight, most preferably 1 to 3% by weight. When the minoxidil / surfactant composite particles are added to the hair composition, the application temperature may be 20 to 70 ° C., preferably 30-60 ° C., and most preferably 40-50 ° C. At a temperature lower than the temperature range, minoxidil / surfactant composite particles are not well dispersed in the liquid liquid composition for hair, and when applied at a temperature higher than the temperature range, minoxidil may precipitate in the final liquid liquid composition.

The composition for hair comprising the minoxidil / surfactant composite particles of the present invention may further add a wool adjuvant to improve wool efficacy. Wool supplements include scalp diseases, fatty acids, vegetable and animal oils such as olive and emu oils, arginine, cysteine, green tea, polysorbate 80, and progesterone. ), Saw palmetto extract, saw palmetto extract, trichosaccaride, vitamin B6, zinc (zinc) and gamma linoic acid (gamma linoic acid) can be used for selection. The scalp disease treatment agent is ketoconazole (Ketoconazole), zinc pyrithione (zinc pyrithione), selenium (Selenium), sulfur (Sulfur), pyroctone olamine (piroctone olamine) therapeutic agents for dandruff, triclosan, chlorec Treatment of bacterial infections such as chlorhexidine, salicylic acid, and povidone-iodine, and sadness, such as Lindane, malathion, permethrin, and pyrethrin Pedoriasis treatments such as pediculosis and coal tar may be used. In addition, the hair composition of the present invention may further include an excipient according to the intended use. Examples of excipients are liquid paraffin, stearyl alcohol, glycerin and the like.

Hair composition of the present invention can be prepared in liquid, powder, tablets, sprays, emulsifiers, creams and emulsions, it is preferable to prepare differently depending on the intended use. The hair composition can be used for the purpose of washing the hair, and can be applied to all kinds of other uses used for the hair. Representatives applicable are shampoos, rinses, treatments, hair packs, hair sprays, hair mousses, hair gels, hair creams, hair tonics and hair essences.

Hair composition comprising the minoxidil / surfactant composite particles of the present invention has the following advantages.

First, it has excellent dispersibility and phase stability. Dispersion of the pure minoxidil particles prepared by grinding and homogenization by a mechanical method without using a surfactant in the hair composition causes the minoxidil particles to settle within a few days. However, the minoxidil / surfactant composite particles prepared by mechanically dispersing minoxidil together with a surfactant acting as a dispersant and a binder are well dispersed in the hair composition and are stable without prolonged precipitation.

Secondly, minoxidil has excellent skin retention after rinsing. In the case of the hair composition containing pure minoxidil particles prepared without using a surfactant, the minoxidil residue on the skin is low because minoxidil is easily washed off by rinsing. However, in the case of the hair composition containing the minoxidil composite particle suspension, the residual amount of minoxidil is high even after rinsing. This is because a surfactant that acts as a binder increases the adsorption of minoxidil and skin.

Third, the wool effect is excellent after rinsing. A hair composition containing pure minoxidil particles prepared without using a surfactant has little wool effect because minoxidil is easily washed off by rinsing. On the other hand, the hair composition containing the minoxidil / surfactant composite particles prepared in the present invention exhibits an excellent wool effect since minoxidil remains in the skin even after rinsing. Moisturizers used with minoxidil also provide moisture to the minoxidil particles remaining in the scalp to dissolve minoxidil, resulting in increased bioavailability of minoxidil and enhancement of wool effects. In addition, the wool supplement is added to alleviate the hair loss symptoms caused by the scalp disease to increase the wool effect or to act physically, biochemically and microbiologically exhibits wool and hair loss prevention effect.

Fourth, it is easy to use. Existing minoxidil solution has to be applied to the scalp at a given time, but the hair composition containing the minoxidil / surfactant composite particles of the present invention is a daily life, that is, in the form of a composition for hair such as shampoo and rinse Minoxidil coating effect can be obtained by simple trituration.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention, and it will be apparent to those skilled in the art that the scope of the present invention is not limited to these examples.

Example 1-8 Preparation of Minoxidil / Anionic Surfactant Composite Particles

The minoxidil / anionic surfactant composite particles of Examples 1 to 8 were prepared in the composition of Table 1 below (unit: wt%). As anionic surfactant, sodium lauryl ether sulphate (SLES, two ethylene oxide waters), sodium lauryl sulphate (SLS) were used, and puffylene glycol and glycerin were used as moisturizing agents.

Minoxidil, anionic surfactant, moisturizer and distilled water were mixed to a total of 1 kg in the composition ratio of Table 1 and then stirred at 60 ℃ for about 1 hour. The stirring solution was treated once with 1000 bar pressure using an ultra-high pressure dispersion device (M-110EH Microfluidizer Processors) to prepare minoxidil / anionic surfactant composite particles. In the ultra-high pressure dispersing device, since foam is generated a lot during the manufacturing process of the multiparticulates, 4-5 drops of oryl alcohol was added as an antifoaming agent.

division Minoxidil Sodium Lauryl Sulfate Ether (SLES) Sodium Lauryl Sulfate (SLS) Propylene glycol glycerin water Example 1 14 5 - 1.5 - up to100 Example 2 14 10 - 3.0 - Example 3 14 5 - - 1.5 Example 4 14 10 - - 3.0 Example 5 14 - 5 1.5 - Example 6 14 - 10 3.0 - Example 7 14 - 5 - 1.5 Example 8 14 - 10 - 3.0

Example 9-20: Preparation of minoxidil / nonionic surfactant composite particles

The minoxidil / nonionic surfactant composite particles of Examples 9 to 20 were prepared by mixing minoxidil, a nonionic surfactant, a humectant, and water in the composition ratios shown in Table 2 in the same manner as in Example 1 (unit is wt%). ). Span60, tween60, and Pluronic P85 were used as nonionic surfactants, and fluorene glycol and glycerin were used as moisturizers.

division Minoxidil Span60 Twin 60 Pluronic P85 Propylene glycol glycerin water Example 9 14 5 - - 1.5 - Up to 100 Example 10 14 10 - - 3.0 - Example 11 14 5 - - - 1.5 Example 12 14 10 - - - 3.0 Example 13 14 - 5 - 1.5 - Example 14 14 - 10 - 3.0 - Example 15 14 - 5 - - 1.5 Example 16 14 - 10 - - 3.0 Example 17 14 - - 5 1.5 - Example 18 14 - - 10 3.0 - Example 19 14 - - 5 - 1.5 Example 20 14 - - 10 - 3.0

Example 21-28 Preparation of Minoxidil / Amphoteric Surfactant Composite Particles

The minoxidil / amphoteric surfactant composite particles of Examples 21 to 28 were prepared in the same manner as in Example 1 by mixing minoxidil, an amphoteric surfactant, a humectant, and water in the composition ratios shown in Table 3 below (unit is wt%). ). Cocamidopropyl betaine and sodium cocamphopripionate were used as amphoteric surfactants, and flophylene glycol and glycerin were used as moisturizing agents.

division Minoxidil Cocamidopropyl Betaine Sodium Cocampo Prepionate Propylene glycol glycerin water Example 21 14 5 - 1.5 - up to 100 Example 22 14 10 - 3.0 - Example 23 14 5 - - 1.5 Example 24 14 10 - - 3.0 Example 25 14 - 5 1.5 - Example 26 14 - 10 3.0 - Example 27 14 - 5 - 1.5 Example 28 14 - 10 - 3.0

Examples 29-40: Preparation of minoxidil / cationic surfactant composite particles

The minoxidil / cationic surfactant composite particles of Examples 29 to 40 were prepared in the same manner as in Example 1 by mixing minoxidil, a cationic surfactant, a humectant, and water in the composition ratios shown in Table 4 below (unit is wt%). ). As cationic surfactants, stearyltrimethylammonium chloride, behenyltrimethylammonium chloride, and distearyldimethylammonium chloride were used as moisturizing agents. Used.

Minoxidil Stearyl Trimethyl Ammonium Salt Behenyl trimethyl ammonium chloride Distearyl dimethyl ammonium chloride Propylene glycol glycerin water Example 29 14 5 - - 1.5 - up to 100 Example 30 14 10 - - 3.0 - Example 31 14 5 - - - 1.5 Example 32 14 10 - - - 3.0 Example 33 14 - 5 - 1.5 - Example 34 14 - 10 - 3.0 - Example 35 14 - 5 - - 1.5 Example 36 14 - 10 - - 3.0 Example 37 14 - - 5 1.5 - Example 38 14 - - 10 3.0 - Example 39 14 - - - - 1.5 Example 40 14 - - - - 3.0

Comparative Example 1-4: Preparation of minoxidil single particle

Minoxidil single particles were prepared by grinding only by mechanical methods without using a surfactant. To a total of 1 kg in the composition ratio of Table 5 was stirred for about 1 hour at 60 ℃ (unit is weight%). Puffylene glycol and glycerin were used as humectants. The stirring solution was treated once at 1000 bar pressure with an ultra-high pressure dispersion device (M-110EH Microfluidizer Processors) to prepare pure minoxidil single particles.

division Minoxidil Propylene glycol glycerin water Comparative Example 1 14 1.5 - up to 100 Comparative Example 2 14 3.0 - Comparative Example 3 14 - 1.5 Comparative Example 4 14 - 3.0

Experiment 1: Characterization of Minoxidil Composite Particles

Zeta potential and size of the minoxidil / surfactant composite particles of Examples 1 to 40 and the minoxidil single particle of Comparative Examples 1 to 4 were measured using a Zeta Plus device (Zeta Plus, Brookhaven Instruments Co.), and the results are shown in the table. 6 is shown.

division Average size (㎛) Zeta Potential (mV) Composite Particles of Example 1 6.0 -30.1 Composite Particles of Example 5 5.4 -32.3 Composite Particles of Example 9 5.7 -3.4 Composite Particles of Example 13 6.3 -3.0 Composite Particles of Example 17 6.6 -5.2 Composite Particles of Example 21 5.5 +1.5 Composite Particles of Example 25 6.0 +0.6 Composite Particles of Example 29 5.3 +43.0 Composite Particles of Example 33 5.4 +45.8 Composite Particles of Example 37 6.2 +44.1 Single particle of Comparative Example 1 7.2 -3.0 Single particle of Comparative Example 2 6.9 -2.7

In Table 6, the average size of the particles is about 5-7 μm, and the zeta potential is different for each particle. Zeta potential is a value that reflects the surface properties of the particles. That is, the composite particles of Example 1 and Example 5 using anionic surfactants showed negative (-) zeta potential values, and the composite particles of Examples 29, 22 and 37 using cationic surfactants were positive (+) zeta. Potential values are shown.

Examples 41-44: Preparation of Shampoos Containing Minoxidil / Anionic Surfactant Composite Particles

The composite particles of Examples 1 and 5 were added to the hair composition, and then mixed at 35-40 ° C. with a stirrer (rotational speed: 300-400 rpm) to prepare a uniform liquid composition. It is shown in Table 7 (weight%) (unit is weight%).

division Hair cleaning composition Example 1 Example 5 water Betaine SLES SLS CDE Example 41 up to 100 One 20 5 One 7.14 - Example 42 One 20 5 One 14.28 - Example 43 One 20 5 One - 7.14 Example 44 One 20 5 One - 14.28 * Betaine: cocamidopropyl betaine * SLES: sodium lauryl sulfate ether (2 ethylene oxide, 12 carbon atoms) * SLS: sodium lauryl sulfate salt (12 carbon atoms) * CDE: coconut diethanolamide (coconut diethanolamide)

Example 45-50: Preparation of Shampoo Including Minoxidil / Nonionic Surfactant Composite Particles

The nonionic composite particles of Examples 9, 13 and 17 were added to the hair composition, and then mixed at 35-40 ° C. with a stirrer (rotational speed: 300-400 rpm) to prepare a uniform liquid composition. Composition and composition ratio of the shampoo is shown in Table 8 (unit is weight%).

division Hair cleaning composition Example 9 Example 13 Example 17 water Betaine SLES SLS CDE Example 45 Up to 100 One 20 5 One 7.14 - - Example 46 One 20 5 One 14.28 - - Example 47 One 20 5 One - 7.14 - Example 48 One 20 5 One - 14.28 - Example 49 One 20 5 One - - 7.14 Example 50 One 20 5 One - - 14.28

Examples 51-54: Preparation of Shampoos Containing Minoxidil / Amphoteric Surfactant Composite Particles

The amphoteric multiparticulates of Examples 21 and 25 were added to the hair composition, followed by mixing at 35-40 ° C. with a stirrer (rotational speed: 300-400 rpm) to prepare a uniform liquid composition. Composition and composition ratio of the shampoo is shown in Table 9 (unit is weight%).

division Hair cleaning composition Example 21 Example 25 water Betaine SLES SLS CDE Example 51 Up to 100 One 20 5 One 7.14 - Example 52 One 20 5 One 14.28 - Example 53 One 20 5 One - 7.14 Example 54 One 20 5 One - 14.28

Examples 55-60 Preparation of Shampoos Containing Minoxidil / Cationic Surfactant Composite Particles

The cationic composite particles of Examples 29, 33 and 37 were added to the hair composition, followed by mixing at 35-40 ° C. with a stirrer (rotational speed: 300-400 rpm) to prepare a uniform liquid composition. Composition and composition ratio of the shampoo is shown in Table 10 (unit is weight%).

division Hair cleaning composition Example 29 Example 33 Example 37 water Betaine SLES SLS CDE Example 55 Up to 100 One 20 5 One 7.14 - - Example 56 One 20 5 One 14.28 - - Example 57 One 20 5 One - 7.14 - Example 58 One 20 5 One - 14.28 - Example 59 One 20 5 One - - 7.14 Example 60 One 20 5 One - - 14.28

Comparative Example 5-8: Preparation of Shampoo Containing Minoxidil Single Particles

The minoxidil single particles of Comparative Example 1 and Comparative Example 3 were added to the hair composition, followed by mixing at 35-40 ° C. with a stirrer (rotational speed: 300-400 rpm) to prepare a uniform liquid composition. Composition and composition ratio of the shampoo is shown in Table 11 (% by weight).

division Hair cleaning composition Comparative Example 1 Comparative Example 3 water Betaine SLES SLS CDE Comparative Example 5 up to 100 One 20 5 One 7.14 - Comparative Example 6 One 20 5 One 14.28 - Comparative Example 7 One 20 5 One - 7.14 Comparative Example 8 One 20 5 One - 14.28

Experiment 2: Time-lapse stability of shampoo

Phase stability over time of the hair cleaning composition comprising minoxidil / surfactant composite particles was confirmed.

The stability of the shampoos of Examples 41 to 61 and the shampoos of Comparative Examples 5 to 8 were observed at room temperature or 40 ° C. for 90 days, and the stability of the shampoos was observed.

division Shampoo with minoxidil / anionic surfactant composite particles Example 41 Example 43 Room temperature stability stability 40 ℃ stability stability

In Table 12, both the shampoos of Example 41 and Example 43 where minoxidil was applied 1% were stable.

division Shampoo with Minoxidil / Nonionic Surfactant Composite Particles Example 45 Example 47 Example 49 Room temperature stability stability stability 40 ℃ stability stability stability

In Table 13, the minoxidil composite particles were all stable for 90 days at room temperature regardless of the concentration, and at 40 ° C., the shampoos of Example 45, Example 47, and Example 49 where minoxidil was applied at 1% were stable.

division Shampoo with minoxidil / amphoteric surfactant composite particles Example 51 Example 52 Example 53 Example 54 Room temperature stability stability stability stability 40 ℃ stability stability stability stability

In Table 14, minoxidil composite particles were stable regardless of temperature and application concentration.

division Shampoo with Minoxidil / Cationic Surfactant Composite Particles Example 55 Example 56 Example 57 Example 58 Example 59 Example 60 Room temperature stability stability stability stability stability stability 40 ℃ stability stability stability stability stability stability

In Table 15, both the shampoos with 1% and 2% minoxidil applied at room temperature and 40 ° C. showed good phase stability.

division Shampoo with Minoxidil Single Particle Comparative Example 5 Comparative Example 6 Comparative Example 7 Comparative Example 8 Room temperature Sedimentation Sedimentation Sedimentation Sedimentation 40 ℃ Sedimentation Sedimentation Sedimentation Sedimentation

When minoxidil single particles were used as the hair cleansing composition, as shown in Table 16, minoxidil was precipitated due to precipitation of minoxidil at 1% or 2% of minoxidil stored at 40 ° C. at room temperature, resulting in poor phase stability.

Experiment 3: Minoxidil Residual Verification

Hairless mice were slaughtered after cervical spine, and their back skin was removed and used for the experiment. Place two metal rings (inner diameter 15 mm, height 10 mm) on one skin such as thinned and tacked, and 0.5 ml per metal ring of the sample diluted with minoxidil with distilled water so that the minoxidil concentration is 1%. Was added. After 2 minutes, the sample was removed and rinsed three times with 1 ml of distilled water, and then the skin inside the ring treated with the sample was punched out 3 per metal ring, that is, 6 per sample, with a 6 mm biopsy punch. In order to quantify the amount of minoxidil adsorbed on the skin obtained by punching, put the punched skin into a microtube, add 0.5 ml of ethanol and leave for 24 hours, then take a certain amount of ethanol and measure the amount of minoxidil by using HPLC Analyzed. The results are shown in Table 17.

Minoxidil 1% Residual amount (㎍ / mm ² ) Minoxidil 2% Residual amount (㎍ / mm ² ) Amphoteric composite particles Example 51 1.34 Example 52 3.02 Example 53 1.47 Example 54 3.13 Cationic Composite Particles Example 55 1.65 Example 56 4.40 Example 57 1.55 Example 58 4.25 Example 59 1.89 Example 60 4.80 Minoxidil Single Particle Comparative Example 5 0.37 Comparative Example 6 0.79 Comparative Example 7 0.35 Comparative Example 8 0.65

As a result of measuring the residual skin of minoxidil, when minoxidil 1% was applied, the minoxidil made of the amphoteric and cationic complex particles had excellent skin retention, and the skin of minoxidil prepared from the anionic and nonionic composite particles. Persistence was similar to minoxidil single particles. In addition, when 2% minoxidil was applied, the multiparticulates of the present invention showed higher skin residuality than the minoxidil single particle.

Experiment 4: Verification of Wool Effect of Shampoo with Minoxidil

Six-week-old female C57BL6 mice were purchased, purified for one week, observed for general symptoms, and then healthy were selected for the experiment. The environmental conditions of the feeding room were 23 ℃ and the lighting time was 12 hours from 7 am to 7 pm, and the feed and water were freely fed. The hair removal of the back hair was performed using a hair clipper (clipper) one day before the start of the experiment.

A sample (minoxidil concentration 1%) was applied to the depilated C57BK6 mice, and washed 2 minutes later with running water for 10 seconds. Sample treatment was performed once per day, 5-6 times per week for 30 days from the day after hair removal. After 30 days from the start of the experiment, the animals were photographed by anesthesia with pentobarbital.

Table 18 shows the wool effect on the basis of the area of hair restoration, where the hair recovery area is the ratio of the area where hair growth occurred after 30 days of hair growth compared to the area after hair removal:

-: Recovery area is less than 10% +: Recovery area is 10-30%,

++: Recovery Area 30-70% +++: Recovery Area 70-100%

division Minoxidil 1% Wool effect (%) Minoxidil 2% Wool effect (%) Amphoteric composite particles Example 51 - Example 52 + Example 53 - Example 54 + Cationic Composite Particles Example 55 + Example 56 ++ Example 57 + Example 58 ++ Example 59 + Example 60 ++ Minoxidil Single Particle Comparative Example 5 - Comparative Example 6 - Comparative Example 7 - Comparative Example 8 -

As shown in Table 18, the wool effect was not observed after rinsing in the case of the shampoo to which the anionic and nonionic composite particles were applied, and there was no wool effect in the case of 1% of the minoxidil in the shampoo to which the amphoteric composite particles were applied. However, at 2%, wool effect was observed. In the shampoo to which the cationic composite particles were applied, the wool effect was observed even when the minoxidil content was 1%, and the wool effect was good at 2%. On the other hand, in the case of a shampoo applied with pure minoxidil single particles, no wool effect was observed.

Example 61 Preparation of Rinse with Minoxidil Anionic Composite Particles

The composition mixed in the composition ratio (wt%) of Table 19 was mixed at 35-40 ° C. with a stirrer (rotational speed: 200-300 rpm) to prepare a uniform composition.

division Rinse composition comprising minoxidil / anionic surfactant complex particles Example 61 Example 62 Example 63 Example 64 Example 65 Example 67 Behenyltrimethyl ammonium chloride 0.3 0.3 0.3 0.3 0.3 0.3 Floating paraffin 1.5 1.5 1.5 1.5 1.5 1.5 Stearyl alcohol 5 5 5 5 5 5 glycerin One One One One One One Cetyl Trimethyl Ammonium Chloride 5 5 5 5 5 5 Silicone Oil (Dow Corning, 2-1691 Emulsion) 2 2 2 2 2 2 Anionic Composite Particles of Example 1 7.14 14.28 21.42 - - - Anionic Composite Particles of Example 5 - - - 7.14 14.28 21.42 water 78.06 70.92 63.78 78.06 70.92 63.78 Minoxidil final concentration in the rinse composition One % 2 % 3% One % 2 % 3%

Examples 67-75: Rinse preparation with minoxidil nonionic multiparticulates applied

Rinse was prepared by mixing nonionic composite particles at each concentration in the compositions except Example 1 and Example 5 of the compositions described in Table 19.

Examples 67, 68 and 69 used the nonionic multiparticulates of Example 9 at 7.14 wt%, 14.28 wt% and 21.42 wt%, respectively, and Examples 70, 71 and 72 were the nonionic multiparticulates of Example 13 And 7.14 wt%, 14.28 wt% and 21.42 wt%, respectively, and Examples 73, 74 and 75 use 7.14%, 14.28% and 21.42% of the nonionic multiparticulates of Example 17, respectively.

Example 76-81: Rinse Preparation with Minoxidil Amphoteric Multiparticulates

Rinsing was prepared by mixing amphoteric multiparticulates in each composition in the compositions except for Examples 1 and 5 in the compositions described in Table 19.

Examples 76, 77 and 78 used the amphoteric multiparticulates of Example 21 at 7.14%, 14.28% and 21.42% by weight, respectively, and Examples 79, 80 and 81 were the amphoteric multiparticulates of Example 25 At 7.14 wt%, 14.28 wt% and 21.42 wt%, respectively.

Example 82-90: Rinse Preparation with Minoxidil Cationic Composite Particles

Rinsing was prepared by mixing cationic composite particles at each concentration in the compositions except for Examples 1 and 5 in the compositions described in Table 19.

Examples 82, 83 and 84 mix the cationic multiparticulates of Example 29 at 7.14%, 14.28% and 21.42% by weight, respectively, and Examples 85, 86 and 87 are the cationic multiparticulates of Example 33 And 7.14%, 14.28% and 21.42% by weight, respectively, and Examples 88, 89, and 90 are 7.14%, 14.28%, and 21.42%, respectively.

Comparative Example 9-14: Rinse Preparation with Minoxidil Single Particles

Rinse preparation with minoxidil nonionic composite particles

Comparative Examples 9, 10, and 11 were prepared by mixing the minoxidil single particles of Comparative Example 1 with 7.14 wt%, 14.28 wt%, and 21.42 wt% of the compositions described in Table 19, except for Examples 1 and 5, respectively. In the same manner, Comparative Examples 12, 13, and 14 were prepared using the minoxidil single particles of Comparative Example 3 at 7.14 wt%, 14.28 wt%, and 21.42 wt%, respectively.

Experiment 5: Stability of Rinse with Time

The phase stability of the rinse was observed while the rinses of Examples 61 to 96 were stored at room temperature or 40 ° C. As a result, minoxidil did not precipitate and maintained a stable phase.

Experiment 6: Verifying Minoxidil Residuals in Rinse

Minoxidil skin persistence was measured by the method described in Experiment 3, and the results are shown in Table 20 below.

Minoxidil skin residual amount (㎍ / mm ² ) according to minoxidil concentration Minoxidil 1% Minoxidil 2% Minoxidil 3% Amphoteric composite particles Example 76 1.54 Example 77 3.82 Example 78 4.32 Example 79 1.47 Example 80 3.53 Example 81 4.43 Cationic Composite Particles Example 82 2.75 Example 83 4.85 Example 84 6.48 Example 85 2.77 Example 86 4.76 Example 87 6.39 Example 88 2.89 Example 89 4.55 Example 90 6.75 Minoxidil Single Particle Comparative Example 9 0.74 Comparative Example 10 1.53 Comparative Example 11 2.62 Comparative Example 12 0.87 Comparative Example 13 1.65 Comparative Example 14 2.78

As shown in Table 20, the minoxidil skin residual amount was significantly higher than when minoxidil was prepared in the form of cationic or amphoteric multiparticulates compared to using minoxidil single particle. In the case of the rinse applied with the cation composite particles, the minoxidil residue was the highest. Experiment 7: Verification of Wool Effect of Rinse Containing Minoxidil

In the same manner as in Experiment 4 to verify the wool effect of the rinse. The results are shown in Table 21 below.

Wool Effect According to Minoxidil Concentration Minoxidil 1% Minoxidil 2% Minoxidil 3% Amphoteric composite particles Example 76 - Example 77 + Example 78 ++ Example 79 - Example 80 + Example 81 ++ Cationic Composite Particles Example 82 - Example 83 ++ Example 84 +++ Example 85 + Example 86 ++ Example 87 +++ Example 88 + Example 89 ++ Example 90 +++ Minoxidil Single Particle Comparative Example 9 - Comparative Example 10 + Comparative Example 11 + Comparative Example 12 - Comparative Example 13 Comparative Example 14 +

As shown in Table 21, in the case of the amphoteric composite particles, the minoxidil content in the shampoo had no wool effect in the case of 1%, but in 2% and 3%, the wool effect was observed. In the case of cationic composite particles, the wool effect was minimal when the minoxidil content was 1%, but the wool effect was good at 2% and 3%. On the other hand, in the case of the rinse containing pure minoxidil single particles, no wool effect was observed in 1%, and a slight wool effect was observed in 2% and 3%.

Examples 91-94 and Comparative Example 15 Preparation of Minoxidil Wool Sampu Containing Scalp Disease Agent

The cationic minoxidil composite particle of Example 29 was mixed with a shampoo containing zinc pyrithion, an anti-dandruff component, and triclosan, a therapeutic agent for bacterial infection, and then agitated at about 35-40 ° C. 300-400 rpm) to prepare a uniform liquid composition with a minoxidil content of 2%. Table 22 shows the composition of the hair cleaning composition and the content of the cationic minoxidil composite particles. The composition in Table 22 is weight percent and the balance is water.

division Hair cleaning composition (% by weight) Zinc Pity Triclosan Betaine SLES SLS CDE Example 29 Example 91 0.25 - One 20 5 One 14.28 Example 92 0.50 - One 20 5 One 14.28 Example 93 - 0.25 One 20 5 One 14.28 Example 94 - 0.50 One 20 5 One 14.28 Comparative Example 15 - - One 20 5 One 14.28

Examples 95-98 Preparation of Minoxidil Wool Shampoo Containing Fatty Acids

Cationic minoxidil composite particles of Example 29 were added to a shampoo containing saturated unsaturated fatty acids such as octadeonic acid and stearic acid, followed by stirring at about 35-40 ° C. (rotational speed: 300 -400 rpm) to prepare a uniform liquid composition with a minoxidil content of 2%. Table 23 shows the composition of the hair cleaning composition and the content of the cationic minoxidil composite particles. The composition in Table 23 is given in weight percent and the balance is water.

division Hair cleaning composition Octadenic acid Stearic acid Betaine SLES SLS CDE Example 29 Example 95 0.5 - One 20 5 One 14.28 Example 96 1.0 - One 20 5 One 14.28 Example 97 - 0.5 One 20 5 One 14.28 Example 98 - 1.0 One 20 5 One 14.28

Example 99-102 Preparation of Minoxidil Wool Shampoo with Oil

The cationic minoxidil composite particles of Example 29 were added to a hair composition containing vegetable and animal oils such as olive oil and emu oil, and then mixed with a stirrer (rotational speed: 300-400 rpm) at about 35-40 ° C. A uniform liquid composition of 2% was prepared. Table 24 shows the composition of the hair cleaning composition and the content of the cationic minoxidil composite particles.

division Hair cleaning composition Olive oil Emu oil Betaine SLES SLS CDE Example 29 Example 99 0.5 - One 20 5 One 14.28 Example 100 1.0 - One 20 5 One 14.28 Example 101 - 0.5 One 20 5 One 14.28 Example 102 - 1.0 One 20 5 One 14.28

Experiment 8: Verification of Wool Effect of Minoxidil Shampoo Containing Wool Supplement

The wool effect of the minoxidil shampoo containing the wool auxiliary component as described in Experiment 4 was carried out, and the results are shown in Table 25 below.

division Wool effect Example 92 +++ Example 94 ++ Example 96 +++ Example 98 ++ Example 100 +++ Example 102 +++ Comparative Example 15 ++ -: Recovery area 10% or less, +: Recovery area 10-30% ++: Recovery area 30-70%, +++: Recovery area 70-100%

As shown in Table 25, in comparison to the shampoo containing only the cationic minoxidil composite particles of Comparative Example 15, the shampoo to which the wool auxiliary component is additionally added, that is, zinc pyrithione, octenoic acid, olive oil, emu oil The shampoo wool effect of Example 92, Example 96, Example 100, and Example 102 added as a result was excellent.

As mentioned above, the minoxidil complex factor prepared by the method for preparing minoxidil / surfactant complex factor of the present invention is excellent in phase stability, skin retention, and wool effect of high concentration of minoxidil, and can be used in addition to conventional hair products. Easy to use

Claims (9)

Minoxidil, surfactant, moisturizer and water is mixed, it is milled to the ultra-high pressure dispersion process characterized in that the minoxidil / surfactant composite particle production method. The minoxidil / interface of claim 1, wherein the minoxidil / surfactant composite particle comprises 5 to 35 wt% minoxidil, 0.5 to 35 wt% surfactant, 0.1 to 10 wt% moisturizer and balance water. Method for preparing active compound particles. The method of claim 1, wherein the surfactant is an amphoteric surfactant or a cationic surfactant. The method of claim 1, wherein the surfactant is distearyl dimethyl ammonium chloride, stearyl trimethylammonium methosulfate, stearyltrimethyl ammonium chloride, stearyldimethylbenzyl ammonium chloride, docosyltrimethylammonium methosulfate, docosyltrimethylammonium chloride , Docosyldimethylbenzyl ammonium chloride, didocosyldimethylammonium chloride, lauryldiethylbenzylammonium chloride, lauryltrimethylammonium chloride, distearylmethylhydroxymethyl salt, cetyltrimethylammonium chloride, N-stearyl-N chloride A method for producing minoxidil / surfactant composite particles, wherein N, N-triammonium salt, cetyltriethylammonium bromide and stearyldimethylammonium chloride are selected from at least one member. The method of claim 1, wherein the humectant is dibutyl phthalate, gelatin, glycerin, soluble collagen, sorbitol, sodium 2-pyrrolidone-5-carboxylate, polyethylene glycol, octadecan-2-ol, caprylic triglycere A method for producing minoxidil / surfactant composite particles, wherein at least one selected from the group consisting of reed, capric triglyceride, propane-1,2-diol, triethylene glycol, nonoxynol-9, panthenol, and flothylene glycol. Minoxidil / surfactant composite particles prepared by the method according to any one of claims 1 to 5. Hair composition comprising the minoxidil / surfactant composite particles of claim 6. According to claim 7, wherein the hair composition is a composition for hair containing minoxidil 0.1 to 5% by weight. The method of claim 7, wherein the hair composition is used for treating scalp diseases, fatty acids, vegetable oils, animal oils, arginine, cysteine, green tea, polysorbate 80, progesterone, sopalmeto extract, tricosaccharide, vitamin B6, zinc and gamma Hair composition further comprises a wool adjuvant selected from the group consisting of linoic acid.