KR20030021707A - O/o/w multiple emulsion containing minoxidil - Google Patents

Abstract

PURPOSE: A process of preparing an oil-in-oil-in-water multiple emulsion system containing minoxidil as a hair growth effective component is provided. Whereby, the multiple emulsions have excellent dispersion stability and avoid precipitation problems of minoxidil particles generated in an aqueous phase. CONSTITUTION: The O/O/W multiple emulsions are prepared by the following process; dissolving minoxidil in oil to produce an inner oil phase; dispersing the inner oil phase in an outer oil phase containing an O/O emulsifier to produce an O/O emulsion; and emulsifying the O/O emulsion in water containing the O/W emulsifier. The weight ratio of the minoxidil to the inner oil phase is 0.05:1 to 0.3:1 and the volume ratio of the inner oil phase to the outer oil phase and the O/O emulsion to water is 0.05:1 to 1.2:1 and 0.1:1 to 1:1 respectively.

Description

O / O / Ｗ multi-emulsion containing minoxidil and preparation method thereof {O / O / Ｗ MULTIPLE EMULSION CONTAINING MINOXIDIL}

The present invention relates to an O / O / W multiple emulsion containing minoxidil, which is an active ingredient of wool, and a preparation method thereof.

Since minoxidil was approved by the US Food and Drug Administration in 1979 as an oral antihypertensive drug, minoxidil began to be used as a hair regrowth agent by coincidence of hirsutism as a side effect in clinical trials as an antihypertensive drug. As a drug in 1997, a 5% formulation was approved by the US Food and Drug Administration as a drug in 1997 [ Fragrance Journal , 2, 33-37 (2000)]. In 153 patients with crown-type male baldness, clinical trials over 24 months with 2% and 3% minoxidil solutions confirmed hair growth promotion after 12 months of treatment and most patients between 12 and 24 months. The bald area in radically decreased or no longer enlarged. In other words, it has been demonstrated that minoxidil has the effect of treating and preventing male baldness. J. Am. Acad. Dermatol , 16, 711-718 (1982).

Minoxidil is currently developed as a topical formulation and used to treat male alopecia. Conventionally, the minoxidil solution using propylene glycol, ethanol, water and the like as an aqueous solvent has been used as a general solution for minoxidil.

Although the external solution of minoxidil has been proved to have a wool effect, minoxidil has a very low solubility in water of 0.2%. Therefore, when present at a higher concentration in the aqueous phase, the minoxidil particles are precipitated. it's difficult.

Therefore, the present invention solves the problem of precipitation of the minoxidil particles generated in the aqueous phase is a situation that the liquid formulation containing minoxidil with good dispersion stability is urgently needed.

In order to solve the above problems, the present invention is to provide an O / O / W multi-emulsion emulsion having a good dispersion stability, minoxidil, derivatives or salts thereof for the hair regrowth as an active ingredient.

It is still another object of the present invention to provide an O / O / W multiple emulsion comprising minoxidil, a derivative thereof or a salt thereof as an active ingredient including minoxidil as an active ingredient.

1 is an optical micrograph of an octanoic acid / silicone oil / water multiple emulsion containing minoxidil.

The present invention relates to an O / O / W multiple emulsion containing minoxidil, a derivative thereof or a salt thereof having good dispersion stability, in order to solve the precipitation problem of minoxidil particles generated in an aqueous phase, and a method for preparing the same. .

More specifically, the present invention contains minoxidil, consisting of water, an oil phase dispersed in the water, an internal oil phase dispersed in the oil phase, and minoxidil, a derivative thereof, or a salt thereof contained in the internal oil phase. To an O / O / W multiple emulsion.

The present invention also prepares an inner oil phase by dissolving minoxidil in an inner oil, dispersing the inner oil phase in an outer oil phase containing an O / O emulsifier, to prepare an O / O emulsion, and in water containing an O / W emulsifier. It provides a method for producing an O / O / W multiple emulsion containing minoxidil comprising the step of emulsifying the O / O emulsion. In one example of the invention, minoxidil-containing O / O / W multiple emulsions may be prepared as follows. Minoxidil is dissolved in an oil that can form the internal oil phase of the O / O / W emulsion (hereinafter referred to as the internal oil phase). It is then added to an external oil phase containing an emulsifier (hereinafter referred to as O / O emulsifier) which has a function of forming an O / O emulsion, and emulsified in a homogenizer to prepare an O / O emulsion. Then, the O / O emulsion prepared as described above is added to water containing an emulsifier (hereinafter referred to as O / W emulsifier) which has a function of forming an O / W emulsion, and emulsified in a homogenizer to obtain O / O emulsion. Prepare O / W multiple emulsions.

The minoxidil compound included as an active ingredient in O / O / W in the present invention is intended to include hair minoxidil, salts thereof and derivatives thereof. The weight ratio of minoxidil to the internal oil is 0.05: 1-0.3: 1, more preferably 0.1: 1-0.25: 1, most preferably 0.1 / 1-0.2 / 1. If the weight ratio of minoxidil to internal oil is lower than the above range, the amount of minoxidil in the final multi-emulsion emulsion is too small and if it is higher than the above range, there is a fear that minoxidil is precipitated due to solubility limitation.

In addition, the internal oil of the present invention may be used a natural or synthetic oil having a high solubility of minoxidil without mixing with the external oil phase, and more preferably octanoic acid.

The external oil is polydimethyl siloxane (viscosity: 1.5 x 10-6 m2 / s to 2.5 x 10-1 m2 / s, trade name: DC Fluid 200 (Dow Corning), Abil 10, Abil K03 (Goldschmidt) ), Rhodorsil 47 V 10, Silbione 70047 V 10, Silbion 70047 V 100, Silbion 70047 V 300 (Rhone Poulenc), Silicone Oil L45 (Union Carbide), and sweet almond oil. oil, avocado oil, castor oil, olive oil, jojoba oil, sunflower oil, sunflower oil, sesame oil ), Ground nut oil, raisinseed oil, soba oil, rapeseed oil, safflower oil, coconut oil, corn oil oils, hazelnut oil, palm oil, vegetable or animal oils such as apricot-kernel oil, miners such as liquid paraffin Oil, Caprylic / Capric triglycerides three rod may be used (caprylic / capric triglycerides) and triglyceryl three rod synthetic oils, and fatty acid triglycerides, such as sera (triglycerides, C10-C18) Degas.

When preparing the O / O emulsion of the first stage, the volume ratio of the inner oil phase to the outer oil phase is 0.05: 1-1.2: 1, preferably 0.1: 1-1: 1, most preferably 0.2: 1 to 0.8 / 1 If the volume ratio of the inner oil phase to the outer oil phase is lower than the above range, the content of minoxidil in the final multi-emulsion emulsion is too small and if it is higher than the above range, no stable O / O emulsion is formed and phase-inversion occurs.

When preparing the O / O / W emulsion of the second stage, the volume ratio of the O / O emulsion to the aqueous phase is 0.1: 1-1: 1, preferably 0.2: 1-0.8: 1, most preferably 0.3: 1- 0.7: 1. If the volume ratio is lower than this range, the content of minoxidil in the final multiple emulsion emulsion is too small, and if it is higher than this range, phase-inversion occurs, so that a stable O / O / W multiple emulsion is not formed.

In one example of the invention, the O / O emulsifier may be a surfactant having a span 40, span 65, span 85, soy lecithin or HLB (hydrophilic lipophilic balance) number of 3-8.

O / W emulsifiers usable in the present invention include polyvinyl alcohol (PVA), gelatin (gelatin), polysorbate 80, sodium alginate, sodium oleate, methyl cellulose (methyl) cellulose, albumin, sodium dodecyl sulfate, sodium lauryl sulfate, polysorbate 20, Pluronic-F68, or 8 Surfactants having an HLP number of −16 and the like.

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

Examples 1-4: Preparation of O / O Emulsions Containing Minoxidil

According to the composition shown in Table 1, minoxidil was dissolved in octanoic acid and then cyclomethicone dimethicone copolyol (CDC, Dow Corning 3225C) or dimethylsiloxane containing span 65 ( dimethylsiloxane, 104CS, Dow Corning 3225C) or Oliver oil was added to emulsify at 2000 rpm in a homogenizer (Robo Mics, Tokushu Kika) to prepare an O / O emulsion. Table 1 shows the composition (the numerical unit is weight percent).

division Minoxidil Octanoic acid Dimethyl siloic acid (104CS) Oliver Oil CDC Span65 Example 1 8 42 49 - One - Example 2 8 42 49 - - One Example 3 8 42 - 49 One - Example 4 8 42 - 49 - One

Examples 5-8: Preparation of O / O / W Multiple Emulsions Containing Minoxidil

According to the composition of the following Table 2, the O / O emulsion containing the minoxidil prepared in Examples 1 and 3 water containing polysorbate 20 (polysorbate 20), Pluronic-F68 (Pluronic-F68) After addition to the emulsification at 2000rpm in a homogenizer (Robo Mics, Tokushu Kika) to prepare an O / O / W multiple emulsion containing minoxidil.

In Examples 5 and 6, the O / O emulsion prepared in Example 1 was used, and in Examples 7 and 8, multiple emulsions were prepared using the O / O emulsion prepared in Example 3, respectively. In addition, the optical micrograph of the minoxidil octanoic acid / silicon oil / water multiple emulsion prepared according to an embodiment of the present invention is shown in FIG.

Comparative Example 1-2: Preparation of Multiple Emulsions and Dispersions Containing Minoxidil

As shown in Table 2 (the numerical unit is weight percent), in the comparative example, minoxidil was added and dispersed in water in the same manner as the minoxidil content (3.2%) in the multiple emulsion of Example 5-8.

division O / O Emulsion of Example 1 O / O Emulsion of Example 3 Minoxidil water Polysorbate 20 Pluronic-F68 Example 5 40 - - 59 One - Example 6 40 - - 59 - One Example 7 - 40 - 59 One - Example 8 - 40 - 59 - One Comparative Example 1 - - 3.2 95.8 One - Comparative Example 2 - - 3.2 95.8 - One

Example 9-10 Stability With Time

In order to evaluate the phase stability over time of the multi-emulsion prepared according to Examples 5 and 7, the multi-emulsion was stored at room temperature and 40 ° C. for 90 days and the results are shown in Table 3. %being)

Comparative Example 3-4: Tightness

In order to evaluate the phase stability of the minoxidil aqueous dispersion prepared in Comparative Examples 1 and 2 over time, it was stored at room temperature and 40 ℃ for 90 days and the results are shown in Table 3.

division Multiple Emulsions of Example 5 Multiple Emulsions of Example 7 Dispersion of Comparative Example 1 Dispersion of Comparative Example 2 Room temperature stability stability Sedimentation Sedimentation 40 ℃ stability stability Sedimentation Sedimentation

As shown in Table 3, at room temperature and 40 ° C., the multi-emulsion of the example remained stable without the minoxidil precipitated, but the minoxidil precipitated the dispersion of the comparative example. Therefore, it is possible to solve the problem of precipitation of the minoxidil particles generated in the aqueous phase by preparing the O / O / W multiple emulsion containing minoxidil as in the present invention.

The present invention provides an O / O / W multiple emulsion containing minoxidil as an active ingredient and a method for preparing the same, which provides an excellent minoxidil emulsion having a dispersion stability that solves the problem of precipitation of minoxidil particles generated in an aqueous phase.

Claims (9)

O / O containing minoxidil, consisting of water, an external oil phase dispersed in the water, an internal oil phase dispersed in the external oil phase, and hair regrowth minoxidil, a derivative thereof or a salt thereof contained in the internal oil phase. O / W multiple emulsions. The multiple emulsion of claim 1 wherein the weight ratio of minoxidil to the internal oil phase is 0.05: 1 to 0.3: 1. 2. The multiple emulsion of claim 1 wherein the volume ratio of the inner oil phase to the outer oil phase is 0.05: 1-1.2: 1. The multiple emulsion of claim 1 wherein the volume ratio of the O / O emulsion to water is 0.1: 1 to 1: 1. The multi-emulsion of claim 1, wherein the oil included in the inner oil phase is selected from the group consisting of natural oil and synthetic oil having high solubility of minoxidil without mixing with the external oil phase. The multi-emulsion of claim 1, wherein the oil contained in the external oil phase is selected from the group consisting of polydimethyl siloxane, silicone oil, natural oil, mineral oil, triglyceride and fatty acid triglyceride. Dissolve minoxidil in oil to prepare an internal oil phase, and disperse the internal oil phase in an external oil phase containing an O / O emulsifier to prepare an O / O emulsion, and the O / O emulsion in water containing an O / W emulsifier. A method for preparing an O / O / W multiple emulsion containing minoxidil according to any one of claims 1 to 6, comprising the step of emulsifying. 8. The method of claim 7, wherein said O / O emulsifier is selected from the group consisting of span 40, span 65, span 85, soy lecithin, and surfactants having a hydrophilic lipophilic balance (HLB) number of 3-8. According to claim 7, wherein the O / W emulsifier is polyvinyl alcohol (PVA), gelatin (gelatin), polysorbate 80, sodium alginate, sodium oleate, methyl cellulose ( methyl cellulose, albumin, sodium dodecyl sulfate, sodium lauryl sulfate, polysorbate 20, Pluronic-F68, and The surfactant having a HLP number of 8-16.