WO2018105756A1 - Cosmetics comprising multi-layer nanoparticles having natural insoluble medicine encapsulated therein as preservative, and method for producing said cosmetics - Google Patents

Abstract

The present invention relates to cosmetics comprising a preservative, more specifically to cosmetics having an excellent long-term storage characteristic by comprising multi-layer nanoparticles as a preservative, the multi-layer nanoparticles, which has natural insoluble medicine encapsulated therein, stably maintaining medicine content while maintaining a set size of 0.001-40 nm not only immediately after production but even after long-term storage, and forming no precipitates when used as a preservative for liquid cosmetics.

Description

Cosmetics and manufacturing method comprising multilayer nanoparticles containing natural poorly soluble drugs as antiseptics

The present invention relates to a cosmetic containing a preservative, and more particularly, to a field of cosmetics having excellent long-term storage, including the multi-layer nanoparticles containing a natural poorly soluble drug as an antiseptic.

Among the natural substances obtainable from animals and plants, there are a number of natural drugs with pharmacological activity in the human body. Examples include mastic, myrrh, flavonoids, propolis, allicin, glucosamine, omega fatty acids, and the like. The mastic is effective to alleviate peptic ulcer by inhibiting or killing the growth of Helicobacter pylori. In addition, the myrrh has the effect of anti-inflammatory and analgesic, the flavonoids are effective in allergy relief. Furthermore, the propolis has an increase in immunity and an antioxidant effect, the allicin has an effect of sterilization, blood circulation and diabetes prevention, the glucosamine relieves arthritis symptoms, and the omega fatty acid has an effect on improving blood pressure and cholesterol levels. have.

However, the natural drug has a low solubility since it is mostly poorly soluble, despite the excellent pharmaceutical effect as described above. Accordingly, when administered to a living body, it shows a low bioavailability and has difficulty in solubilization. Therefore, many various cosmetic methods for solubilizing the natural poorly soluble drug have been studied, but the effect is insufficient or the application is limited until now.

 Recently, research on nanoparticles using amphiphilic polymers has been actively conducted in the field of drug delivery systems. The amphiphilic polymer coexists with a hydrophobic block and a hydrophilic block to form a nanostructure having a unique structure by physical cohesion such as intermolecular hydrophobic interaction and van der waals force in an aqueous solution. This tends to cause the hydrophobic blocks to agglomerate themselves in order to minimize contact with water. The agglomerated hydrophobic aggregates form a core and a polymer micelle surrounded by a hydrophilic block on the outside to form a polymer micelle. To increase the solubility. Such polymer micelles are widely used as a formulation for solubilizing poorly soluble drugs having low solubility and low bioabsorption by forming cores of several tens to hundreds of nanometers and encapsulating poorly soluble drugs therein.

However, in the case of cosmetics in which the polymer nanoparticles are applied to a natural poorly soluble drug, the natural poorly soluble drug is not dissolved in water and is highly viscous, so that even if it is emulsified and dispersed in water, the particle size changes. It is difficult to maintain a certain size and drug content for a long time due to a decrease in the amount of drugs, and it is difficult to make cosmetics by encapsulating natural poorly soluble drugs. Therefore, many studies to improve this have been made, but there are still satisfactory results. not.

Thus, the inventors of the present invention while developing a stable pharmaceutical cosmetics even though the natural poorly soluble drugs are encapsulated, the cosmetics containing the multi-layered nanoparticles encapsulated with the natural poorly soluble drug according to the present invention as a preservative material is The drug content remains stable while maintaining a constant size of less than about 40 nm, even after prolonged storage as well as after preparation, and does not form precipitates even when manufactured in liquid cosmetics, and increases the solubility of natural poorly soluble drugs. Since the utilization rate is improved, cosmetics containing the multilayer nanoparticles containing the natural poorly soluble drug according to the present invention as antiseptics have been found to be easy to store for a long time, thereby completing the present invention.

The present invention has been made to improve the problems according to the prior art of the cosmetics, an object of the present invention is to provide a cosmetics with the preservatives of the multi-layer nanoparticles containing the natural poorly soluble drugs excellent in long-term stability.

The present invention is to realize the desired object as described above,

In cosmetics containing preservatives,

The antiseptic material,

A first core comprising 1 part by weight of a natural poorly soluble drug and 0.5-10 parts by weight of a glycol compound represented by Formula 1 below; 0.5 to 50 parts by weight of a poloxamer compound represented by Formula 2; And a second core including 0.5 to 10 parts by weight of a polyoxyether compound represented by Formula 3 or a polyoxy castor oil compound represented by Formula 4 below; And a multi-layer nanoparticle encapsulated with a natural poorly soluble drug consisting of a third core including 0.1-10 parts by weight of a natural polymer,

[Formula 1]

(In Formula 1,

R ₁ is hydrogen or methyl;

R ₂ is hydrogen or tetrahydrofuranyl; And

n is an integer from 1 to 200;

[Formula 2]

(In Formula 2,

l, m and p are independently integers from 1 to 200;

[Formula 3]

(In Chemical Formula 3,

-Is a single or double bond;

x, y and z are independently an integer from 1 to 100); And

[Formula 4]

(In Formula 4,

-Is a single or double bond;

a, a ', a ", b, b', b", c, c 'and c "are independently integers from 1 to 200; and

d, d 'and d "are independently an integer from 0 to 200.) It proposes a cosmetic comprising a multi-layer nanoparticles containing a natural poorly soluble drug as an antiseptic material,

Glycol-based compounds represented by Formula 1; Poloxamer compounds represented by Formula 2; A polyoxyether compound represented by Formula 3 or a polyoxy castor oil compound represented by Formula 4; And a natural poorly soluble drug; mixing or heating or sonicating (step 1); And a step (step 2) of adding a natural polymer to the mixture of step 1; and a step of preparing a cosmetic comprising the multilayer nanoparticles containing the natural poorly soluble drug as a preservative.

Cosmetics according to the present invention presented as described above includes a preservative material containing the multi-layered nanoparticles as an active ingredient in which natural poorly soluble drugs are harmless to the human body, it is possible to obtain the effect of improving the long-term storage of cosmetics have.

Figure 1 shows the structure of the multi-layer nanoparticles contained in the cosmetic containing a multi-layer nanoparticles containing a natural poorly soluble drug according to the present invention as an antiseptic.

2 is a photograph taken to visually check whether the liquid cosmetics containing the multi-layer nanoparticles prepared in Example 3 containing the multi-layer nanoparticles as an antiseptic in a transparent vial and precipitated after 2 months. .

3 is a photograph taken to visually check whether the liquid cosmetic containing a natural poorly soluble drug prepared in Comparative Example 2 in a transparent vial, and precipitated after 2 months.

Figure 4 is a graph showing the change in particle size over time of the liquid cosmetics containing the multi-layer nanoparticles containing the natural poorly soluble drug prepared in Example 3 as an antiseptic.

Figure 5 is a graph showing the particle size change over time of the liquid cosmetic containing a natural poorly soluble drug prepared in Comparative Example 2.

FIG. 6 is a graph showing distribution and average size of multilayer nanoparticles after 6 months of a liquid cosmetic including the multilayer nanoparticles containing the natural poorly soluble drug prepared in Example 3 as an antiseptic material.

Figure 7 is a graph showing the distribution and the average size of the particles after six months of the liquid cosmetics containing the natural poorly soluble drug prepared in Comparative Example 2.

Figure 8 is a graph showing the measurement of the change in the natural poorly soluble drug content of the liquid cosmetics containing the multi-layer nanoparticles containing the natural poorly soluble drug prepared in Example 3 as a preservative over time.

Hereinafter, described in detail with reference to the accompanying drawings of the present invention.

[Natural poorly soluble drugs Enclosed  Multilayer nanoparticles As antiseptic  Containing Cosmetics]

The present invention includes a first core comprising 1 part by weight of a natural poorly soluble drug and 0.5 to 10 parts by weight of a glycol compound represented by the following Formula 1; And

0.5 to 50 parts by weight of a poloxamer compound represented by Formula 2; And a second core including 0.5-10 parts by weight of a polyoxyether compound represented by Formula 3 or a polyoxy castor oil compound represented by Formula 4 below: a micelle comprising 0.1-10 parts by weight of a natural polymer It provides a cosmetic comprising a multi-layer nanoparticles as an antiseptic, characterized in that the encapsulated in three cores.

[Formula 1]

(In Formula 1,

R ₁ is hydrogen or methyl;

R ₂ is hydrogen or tetrahydrofuranyl; And

n is an integer from 1 to 200;

[Formula 2]

(In Formula 2,

l, m and p are independently integers from 1 to 200;

[Formula 3]

(In Chemical Formula 3,

-Is a single or double bond;

x, y and z are independently an integer from 1 to 100); And

[Formula 4]

(In Formula 4,

-Is a single or double bond;

a, a ', a ", b, b', b", c, c 'and c "are independently integers from 1 to 200; and

d, d 'and d "are independently an integer from 0 to 200).

Hereinafter, the cosmetics according to the present invention will be described in detail.

In the cosmetics according to the present invention, the natural poorly soluble drugs can be used alone or mixed with a difficult to solubilize natural, mastic (mystic), myrrh, flavonoids, propolis, allicin, glucosamine, omega fatty acid, etc. It is more preferable to use these alone or in combination, and most preferably using a mastic alone, but is not limited thereto.

In the cosmetics according to the present invention, the glycol compound represented by the following Chemical Formula 1 is as follows:

[Formula 1]

In Chemical Formula 1,

R ₁ is hydrogen or methyl;

R ₂ is hydrogen or tetrahydrofuranyl; And

n is an integer from 1 to 200.

* Preferably,

R ₁ and R ₂ are simultaneously hydrogen; R ₁ is methyl and R ₂ is hydrogen; Or R ₁ is hydrogen and R ₂ is tetrahydrofuranyl; And

n is an integer of 5-50.

The glycol compound represented by Formula 1 serves to dissolve a natural poorly soluble drug. Polyethylene glycol, propylene glycol, tetraglycol, etc. can be used for the said glycol type compound, It is preferable to use polyethylene glycol.

In addition, the glycol-based compound represented by Formula 1 may be used in combination with glycofurol, polysorbate, cremophore, Solutol HS (Solutol HS 15) and the like.

The glycol compound represented by Chemical Formula 1 is preferably contained in an amount of 0.5 to 10 parts by weight, and more preferably in an amount of 2 to 8 parts by weight, based on 1 part by weight of the natural poorly soluble drug.

When the glycol-based compound represented by the formula (1) is contained less than 0.5 parts by weight with respect to 1 part by weight of the natural poorly soluble drug, the dispersion of the natural poorly soluble drug is incomplete, it is difficult to release the drug, 10 parts by weight When contained in excess, there is a problem that the size of the particles increases.

In the cosmetics according to the present invention, the poloxamer compound represented by Formula 2 is as follows:

[Formula 2]

In Chemical Formula 2,

l, m and p are independently integers from 1 to 200.

Preferably,

l, m and p are independently integers from 10 to 150.

The poloxamer compound represented by Formula 2 may form a micelle to encapsulate a natural poorly soluble drug dissolved by the glycol compound in the micelle. As the poloxamer compound represented by Formula 2, poloxamer 68, poloxamer 88, poloxamer 108, poloxamer 124, poloxamer 184, poloxamer 185, poloxamer 188, poloxamer 237, poloxamer 338, poloxamer 407 Etc. can be used, and it is preferable to use poloxamer 188.

The poloxamer compound represented by Formula 2 is preferably contained in an amount of 0.5 to 50 parts by weight, and more preferably in an amount of 3 to 20 parts by weight, based on 1 part by weight of the natural poorly soluble drug. If the poloxamer compound represented by the formula (2) is contained less than 0.5 parts by weight with respect to 1 part by weight of the natural poorly soluble drug, a problem occurs that the natural poorly soluble drug is precipitated quickly, if the content exceeds 50 parts by weight increases There is a problem.

In the cosmetics according to the present invention, the polyoxyether compound represented by the following Chemical Formula 3 or the polyoxy castor oil compound represented by the following Chemical Formula 4 is as follows:

[Formula 3]

(In Chemical Formula 3,

-Is a single or double bond;

x, y and z are independently an integer from 1 to 100); And

[Formula 4]

(In Formula 4,

-Is a single or double bond;

a, a ', a ", b, b', b", c, c 'and c "are independently integers from 1 to 200; and

d, d 'and d "are independently an integer from 0 to 200).

Preferably,

x, y and z are independently integers from 1 to 50;

a, a ', a ", b, b', b", c, c 'and c "are independently integers from 1 to 100; and

d, d 'and d "are independently an integer of 0-100.

The polyoxyether compound represented by Formula 3 or the polyoxy castor oil compound represented by Formula 4 serves to increase solubility in aqueous solution. The polyoxyether compound represented by Chemical Formula 3 may be polyoxyl-4-lauryl ether (brij30), polyoxyl-23-lauryl ether (brij35), polyoxyl-2-cetyl ether (brij52), polyoxyl- 10-cetyl ether (brij56), polyoxyl-20-cetyl ether (brij58), polyoxyl-2-stearyl ether (brij72), polyoxyl-10-stearyl ether (brij76), polyoxyl-2-oleyl Ether (brij93), polyoxyl-10-oleyl ether (brij97), polyoxyl-20-oleyl ether (brij98) and the like can be used alone or in combination, and polyoxyl-20-cetyl ether (brij58) is used. It is desirable to.

In addition, the polyoxy castor oil-based compound represented by Formula 4 is polyoxy 5 castor oil, polyoxy 9 castor oil, polyoxy 15 castor oil, polyoxy 35 castor oil, polyoxy 40 castor oil, polyoxy 60 castor oil, Polyoxy 100 castor oil, polyoxy 200 castor oil, polyoxy 40 hydrogenated castor oil, polyoxy 60 hydrogenated castor oil, polyoxy 100 hydrogenated castor oil, polyoxy 200 hydrogenated castor oil, and the like can be used alone or in combination. Preference is given to using oxy 15 castor oil.

In addition, the HLB (Hydrophile-Lipophile Balance) value of the polyoxyether compound represented by Chemical Formula 3 or the polyoxy castor oil compound represented by the following Chemical Formula 4 is preferably in the range of 5-20, and preferably 10-20. It is more preferable to use what is a range.

Further, the polyoxyether compound represented by the formula (3) or the polyoxy castor oil compound represented by the formula (4) is preferably contained in 0.5 to 10 parts by weight, based on 1 part by weight of the natural poorly soluble drug, 2 to 8 weight It is more preferable to contain by part. When the polyoxyether-based compound represented by Formula 3 or the compound represented by Formula 4 is contained in an amount of less than 0.5 part by weight based on 1 part by weight of the natural poorly soluble drug, the effect of increasing solubility does not appear and the natural poorly soluble drug precipitates quickly. If a problem occurs, and when contained in more than 10 parts by weight, there is a problem that the toxicity caused by the polyoxyether compound represented by the formula (3) or the polyoxy castor oil compound represented by the formula (4).

In the cosmetic according to the present invention, the natural polymer serves to increase the stability of the micelle encapsulated with the natural poorly soluble drug by wrapping the surface of the micelle. Examples of the natural polymer include alginic acid, chitosan, gum arabic, dextran, dextrin, gelatin, polyacrylic acid, pluronic acid, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, and salts thereof. Can be used, it is preferable to use alginic acid or sodium alginate.

The natural polymer is preferably contained in an amount of 0.1 to 20 parts by weight based on 1 part by weight of the natural poorly soluble drug. If the natural polymer is contained less than 0.1 parts by weight, micelles containing natural poorly soluble drugs are not encapsulated in the natural polymer. If the natural polymer is contained in an amount exceeding 20 parts by weight, the natural polymer that does not surround the micelles is precipitated. have.

In the cosmetics according to the present invention, the cosmetics may further include a tension regulator for improving the stability of the micelle, the tension regulator is sorbitol, mannitol, xylitol, lactose, glucose, dextrose, sodium chloride, potassium chloride, carbo Mermer, pemulene, etc. can be used, It is preferable to use sodium chloride or potassium chloride.

The tension modifier is preferably contained in an amount of 1 to 20 parts by weight, and more preferably 5 to 15 parts by weight, based on 1 part by weight of the natural poorly soluble drug. If the tension modifier is contained in less than 1 part by weight, it is not possible to expect a sufficient tension adjustment effect, when contained in more than 20 parts by weight there is a problem that the concentration of the poorly soluble drug is reduced to reduce the efficiency of the drug.

In addition, the cosmetic product according to the present invention may further include a pH adjuster for adjusting to an acidity suitable for use as a cosmetic, the pH adjuster may be used that is commonly used in the art, citric acid, malic acid, lactic acid , Fumaric acid, glycolic acid, acetic acid, hydrochloric acid, hydrobromic acid, sulfuric acid, and the like are preferably used, and hydrochloric acid, sodium hydroxide and the like are more preferable.

Furthermore, the cosmetics according to the present invention may use at least one or more excipients, such as starch, calcium carbonate, sucrose, lactose, sorbitol, dextrose, dextrate, xylitol, microcrystalline cellulose, and the like.

In addition, the cosmetics according to the present invention can be used for cosmetics such as at least one or more lubricants, for example, magnesium styrene talc, colloidal silica, stearic acid, iron oxide, sodium stearyl fumarate.

As described above, the cosmetic according to the present invention is observed as a transparent liquid without precipitation even after 2 months has elapsed it can be seen that the problem of precipitation of cosmetics is improved (see Experimental Example 1).

In addition, the multi-layered nanoparticles included in the cosmetics according to the present invention maintain a constant size of about 40 nm for 0-6 months and do not show a change in particle size, so that the size of the particles is kept constant for a long period of time to form It can be seen that the safety is improved (see Experimental Example 2).

Furthermore, the multi-layered nanoparticles included in the cosmetics according to the present invention are distributed in the range of about 20 nm-180 nm even after 6 months, and the average size of these particles was measured to be 38.1 nm. Thus, although the multi-layer nanoparticles have passed 6 months after manufacture, it can be seen that the size of the particles is kept constant for a long time to improve the long-term safety of the shape (see Experimental Example 3).

In addition, the multilayer nanoparticles included in the cosmetic according to the present invention, the content of the natural poorly soluble drug is constantly maintained at about 100% for 0-6 months, the content of the natural poorly soluble drug is maintained for a long time unchanged It can be seen that the long-term stability to physical properties is improved (see Experimental Example 4).

Therefore, in the multilayer nanoparticles in which the natural poorly soluble drug according to the present invention is encapsulated, the first core including the glycol-based compound and the natural poorly soluble substance represented by the formula (1) is represented by the poloxamer compound (Formula 2). And a second core containing the polyoxyether compound represented by Chemical Formula 3 or the polyoxy castor oil compound represented by Chemical Formula 4 to form a micelle having a size of 0.001 to 30 nm, comprising the natural polymer. By being encapsulated once more by the third core, it is possible to maintain a particle size of 0.001-40 nm for a long time and almost no loss of drug, thereby increasing the solubility and improving the stability of the cosmetic containing it.

[ Production method for cosmetics containing multilayer nanoparticles containing natural poorly soluble drugs as antiseptics ]

The present invention is a glycol compound represented by the formula (1); A poloxamer compound represented by Formula 2 below; A polyoxyether compound represented by Formula 3 or a polyoxy castor oil compound represented by Formula 4; And a natural poorly soluble drug; mixing or heating or sonicating (step 1); And

It provides a method for producing a cosmetic comprising the multi-layer nanoparticles containing the natural poorly soluble drug is added as a preservative material comprising the step (step 2) of adding a natural polymer to the mixture of step 1.

[Formula 1]

(In Formula 1,

R ₁ is hydrogen or methyl;

R ₂ is hydrogen or tetrahydrofuranyl; And

n is an integer from 1 to 200;

[Formula 2]

(In Formula 2,

l, m and p are independently integers from 1 to 200;

[Formula 3]

(In Chemical Formula 3,

-Is a single or double bond; And

x, y and z are independently an integer from 1 to 100); And

[Formula 4]

(In Formula 4,

-Is a single or double bond;

a, a ', a ", b, b', b", c, c 'and c "are independently integers from 1 to 200; and

d, d 'and d "are independently an integer from 0 to 200).

Hereinafter, the manufacturing method according to the present invention will be described in detail.

First, in the method of manufacturing the cosmetic according to the present invention, step 1 is a glycol-based compound represented by Formula 1, a poloxamer compound represented by Formula 2, a polyoxyether compound represented by Formula 3, or the It is a step of mixing or heating or sonicating the polyoxy castor oil-based compound represented by the formula (4) and a natural poorly soluble drug.

Specifically, Step 1 is a glycol compound represented by Formula 1, a poloxamer compound represented by Formula 2, a polyoxyether compound represented by Formula 3 or a polyoxy castor oil compound represented by Formula 4 And a natural poorly soluble drug, followed by heating or ultrasonication to form a micelle having a size of 0.001-30 nm in which the glycol-based compound represented by Chemical Formula 1 and the natural poorly soluble drug are encapsulated. In order to form the micelle, a method of heating or sonicating the components may be used, but is not limited thereto.

In the preparation method according to the present invention, the natural poorly soluble drug can be used alone or mixed with a difficult to solubilize natural, mastic (mystic), myrrh, flavonoids, propolis, allicin, glucosamine, omega fatty acid It is more preferable to use these alone or in combination, and most preferably, mastic is used alone, but not always limited thereto.

In the preparation method according to the present invention, the glycol compound represented by Formula 1 serves to dissolve the natural poorly soluble drug. It is preferable to use polyethyleneglycol, propylene glycol, tetraglycol, etc., and, as for the glycol compound represented by the said Formula (1), it is more preferable to use polyethyleneglycol. In addition, the glycol-based compound represented by Formula 1 may be used in combination with glycofurol, polysorbate, cremophore, Solutol HS (Solutol HS 15) and the like.

The glycol compound represented by Chemical Formula 1 is preferably contained in an amount of 0.5 to 10 parts by weight, and more preferably in an amount of 2 to 8 parts by weight, based on 1 part by weight of the natural poorly soluble drug.

In the production method according to the present invention, the poloxamer compound represented by the formula (2) can be encapsulated in the micelle natural soluble drug dissolved by the glycol-based compound represented by the formula (1) by forming a micelle. Examples of the poloxamer compounds include poloxamer 68, poloxamer 88, poloxamer 108, poloxamer 124, poloxamer 184, poloxamer 185, poloxamer 188, poloxamer 237, poloxamer 338, and poloxamer 407. It is preferable to use poloxamer 188.

In addition, the poloxamer compound represented by Chemical Formula 2 is preferably contained in an amount of 0.5 to 50 parts by weight, and more preferably 3 to 20 parts by weight, based on 1 part by weight of the natural poorly soluble drug.

In the cosmetic preparation method according to the present invention, step 2 is a step of adding a natural polymer to the mixture of step 1 and stirring.

Specifically, the step 2 is a multi-layer by wrapping the surface of the micelle with a natural polymer by adding a natural polymer to the micelle containing the natural poorly soluble drug prepared in step 1 to improve the solubility and stability of the natural poorly soluble drug (Multilayer) nanoparticles can be prepared.

In the production method according to the invention, the natural polymer serves to increase the stability in the aqueous solution by wrapping the surface of the micelles. The natural polymer is alginic acid, chitosan, gum arabic, dextran, dextrin, gelatin, polyacrylic acid, pluronic acid, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose or salts thereof Etc. can be used, and it is preferable to use alginic acid or sodium alginate.

The natural polymer is preferably contained in 0.1 to 10 parts by weight with respect to 1 part by weight of the natural poorly soluble drug.

As described above, the cosmetic manufacturing method comprising the multi-layer nanoparticles containing the natural poorly soluble drug according to the present invention as an antiseptic, the particle size can maintain the size of less than 40 nm even after six months It can be seen that the long-term stability of the form was improved by maintaining the constant size of L for a long time (see Experimental Examples 2 and 3).

In addition, the cosmetic manufacturing method comprising the multi-layer nanoparticles containing the natural poorly soluble drug according to the invention as an antiseptic material, the content of the natural poorly soluble drug encapsulated in the multi-layer nanoparticles even after 6 months has elapsed. It can be seen that the long-term stability with respect to physical properties is improved since it is maintained for a long time in% (see Experimental Example 4).

Therefore, the method for preparing a cosmetic including the multilayer nanoparticles containing the natural poorly soluble drug according to the present invention as an antiseptic material, has a particle size of 0.001-40 nm, the multilayer of which the particle size and physical properties are maintained for a long time Nanoparticles may be prepared and may be usefully used in the preparation of liquid cosmetics and solid cosmetics containing the multilayer nanoparticles in which the natural poorly soluble drug is encapsulated.

Hereinafter, the present invention will be described in detail by Examples, Comparative Examples and Experimental Examples.

However, the following Examples, Comparative Examples and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited to the following Examples, Comparative Examples and Experimental Examples.

<Example 1> Preparation of natural I cosmetic 1, including a multi-layered nano-particles of the poorly soluble drug encapsulated in antiseptic substance

(1) Preparation of Liquid Cosmetics

Mastic (100 mg, mastic gum (HR-50850), import source: Hanbit fragrance, origin: Greece), polyethylene glycol (PEG-400, 125 mg), poloxamer 188 (500 mg) and poly Oxyl-20 cetyl ether (250 mg) was mixed and the mixture was heated to 50 ° C., followed by addition and stirring of sodium alginate (2% aqueous solution, 1000 mg) to contain multilayer nanoparticles encapsulated with a natural poorly soluble drug. Liquid cosmetics were prepared.

(2) Preparation of solid cosmetics

The liquid cosmetic prepared in (1) was dried under reduced pressure to prepare a solid cosmetic comprising multilayer nanoparticles in which a natural poorly soluble drug was enclosed.

<Example 2> Preparation of natural I cosmetic 2, including a multi-layered nano-particles of the poorly soluble drug encapsulated in antiseptic substance

Except for using polyethylene glycol (PEG-400, 250 mg) instead of polyethylene glycol (PEG-400, 250 mg) in Example 1 was carried out in the same manner.

<Example 3> Raw I in the manufacture of cosmetics, including three multi-layered nano-particles of the poorly soluble drug encapsulated in antiseptic substance

Except for using polyethylene glycol (PEG-400, 125 mg) instead of polyethylene glycol (PEG-400, 500 mg) in Example 1 was carried out in the same manner.

<Example 4> Raw I in the manufacture of cosmetics 4, including a multi-layered nano-particles of the poorly soluble drug encapsulated in antiseptic substance

Except for using polyethylene glycol (PEG-400, 750 mg) instead of polyethylene glycol (PEG-400, 125 mg) in Example 1 was carried out in the same manner.

<Example 5> Raw I in the manufacture of cosmetics 5, including a multi-layered nano-particles of the poorly soluble drug encapsulated in antiseptic substance

Except for using polyoxy-15 castor oil (250 mg) instead of polyoxyl-20 cetyl ether (250 mg) in Example 3 was carried out in the same manner.

<Example 6> Raw I in the manufacture of cosmetics 6 including a multi-layered nano-particles of the poorly soluble drug encapsulated in antiseptic substance

Except for using poloxamer 188 (250 mg) instead of poloxamer 188 (500 mg) in Example 3 was carried out in the same manner.

<Example 7> Raw I in the manufacture of cosmetics 7, including a multi-layered nano-particles of the poorly soluble drug encapsulated in antiseptic substance

Except for using poloxamer 188 (750 mg) instead of poloxamer 188 (500 mg) in Example 3 was carried out in the same manner.

<Example 8> Raw I in the manufacture of cosmetic 8 including a multi-layered nano-particles of the poorly soluble drug encapsulated in antiseptic substance

Except for using poloxamer 188 (1500 mg) instead of poloxamer 188 (500 mg) in Example 3 was carried out in the same manner.

<Example 9> Preparation of natural I cosmetic 9, including a multi-layered nano-particles of the poorly soluble drug encapsulated in antiseptic substance

Except for using polyoxyl-20 cetyl ether (125 mg) instead of polyoxyl-20 cetyl ether in Example 3 was carried out in the same manner.

< Example 10> Preparation of the cosmetics 10 including the multilayer nanoparticles containing the natural poorly soluble drug as an antiseptic

Except for using polyoxyl-20 cetyl ether (250 mg) instead of polyoxyl-20 cetyl ether (500 mg) in Example 3 was carried out in the same manner.

<Example 11> Preparation of natural I cosmetic 11 comprises a multi-layered nano-particles of the poorly soluble drug encapsulated in antiseptic substance

Except for using polyoxyl-20 cetyl ether (250 mg) instead of polyoxyl-20 cetyl ether (750 mg) in Example 3 was carried out in the same manner.

<Example 12> Preparation of natural I cosmetic 12 comprises a multi-layered nano-particles of the poorly soluble drug encapsulated in antiseptic substance

The same procedure as in Example 3 was performed except that (methyl cellulose, 1000 mg) was used instead of sodium alginate (2% aqueous solution, 1000 mg).

<Example 13> Preparation of natural I cosmetic 13 comprises a multi-layered nano-particles of the poorly soluble drug encapsulated in antiseptic substance

Except for using poloxamer 188 (125 mg) and (methyl cellulose, 1000 mg) instead of poloxamer 188 (500 mg) and sodium alginate (2% aqueous solution, 1000 mg) in Example 3 It was.

<Example 14> Preparation of natural I cosmetic 14 comprises a multi-layered nano-particles of the poorly soluble drug encapsulated in antiseptic substance

Except for using poloxamer 188 (125 mg) instead of poloxamer 188 (500 mg) in Example 3 was carried out in the same manner.

<Example 15> Preparation of natural I cosmetic 15 comprises a multi-layered nano-particles of the poorly soluble drug encapsulated in antiseptic substance

Except for using polyoxy-15 castor oil (250 mg) instead of polyoxyl-20 cetyl ether (250 mg) in Example 14 was carried out in the same manner.

<Example 16> Preparation of natural I cosmetic 16 comprises a multi-layered nano-particles of the poorly soluble drug encapsulated in antiseptic substance

The same procedure as in Example 3 was performed except that sodium alginate (2% aqueous solution, 500 mg) was used instead of sodium alginate (2% aqueous solution, 1000 mg).

<Example 17> Preparation of natural I cosmetic 17 comprises a multi-layered nano-particles of the poorly soluble drug encapsulated in antiseptic substance

Except for using sodium alginate (2% aqueous solution, 750 mg) instead of sodium alginate (2% aqueous solution, 1000 mg) in Example 3 was carried out in the same manner.

<Example 18> Preparation of natural I cosmetic 18 comprises a multi-layered nano-particles of the poorly soluble drug encapsulated in antiseptic substance

Except for using poloxamer 188 (2000 mg) instead of poloxamer 188 (500 mg) in Example 3 was carried out in the same manner.

<Example 19> Preparation of natural I cosmetic 19 comprises a multi-layered nano-particles of the poorly soluble drug encapsulated in antiseptic substance

Except for using poloxamer 188 (2500 mg) instead of poloxamer 188 (500 mg) in Example 3 was carried out in the same manner.

Comparative Example 1 Preparation of Liquid Cosmetics 1 Containing Naturally Soluble Drug

Mastic (100 mg), polyethylene glycol (PEG-400, 500 mg) and poloxamer 188 (500 mg) are mixed and the mixture is heated to 50 ° C., liquid cosmetics containing particles containing natural poorly soluble drugs. Was prepared.

Comparative Example 2 Preparation of Liquid Cosmetics 2 Containing Naturally Soluble Drug

Mastic (100 mg), polyethylene glycol (PEG-400, 500 mg), poloxamer 188 (500 mg) and polyoxyl-20 cetyl ether (250 mg) are mixed and the mixture is heated to 50 ° C. to give natural eggs. Liquid cosmetics were prepared comprising the particles containing the soluble drug.

Comparative Example 3 Preparation of Liquid Cosmetics 3 Containing Naturally Soluble Drug

Except for using polyethylene glycol (PEG-400, 500 mg) instead of polyethylene glycol (PEG-400, 30 mg) in Example 3 was carried out in the same manner.

Comparative Example 4 Preparation of Liquid Cosmetics 4 Containing Naturally Soluble Drug

Except for using poloxamer 188 (30 mg) instead of poloxamer 188 (500 mg) in Example 3 was carried out in the same manner.

Comparative Example 5 Preparation of Liquid Cosmetics 5 Containing Naturally Soluble Drug

Except for using polyoxyl-20 cetyl ether (250 mg) instead of polyoxyl-20 cetyl ether (30 mg) in Example 3 was carried out in the same manner.

Table 1 below summarizes the reaction conditions of Examples 1 to 19 and Comparative Examples 1 to 5.

	Naturally Insoluble Substances	Glycol-based compounds	Poloxamer Compound	Polyoxyl ether type / polyoxy castor oil type compound		Natural polymer
	Mastic (part by weight)	PEG-400 (parts by weight)	Poloxamer 188 (part by weight)	Polyoxyl-20 cetyl ether (part by weight)	Polyoxy-15 castor oil (part by weight)	Sodium alginate (2% aqueous solution) (parts by weight)	Methyl cellulose (parts by weight)
Example 1	One	1.25	5.00	2.50	-	10.00	-
Example 2	One	2.50	5.00	2.50	-	10.00	-
Example 3	One	5.00	5.00	2.50	-	10.00	-
Example 4	One	7.50	5.00	2.50	-	10.00	-
Example 5	One	5.00	5.00	-	2.50	10.00	-
Example 6	One	5.00	2.50	2.50	-	10.00	-
Example 7	One	5.00	7.50	2.50	-	10.00	-
Example 8	One	5.00	15.00	2.50	-	10.00	-
Example 9	One	5.00	5.00	1.25	-	10.00	-
Example 10	One	5.00	5.00	5.00	-	10.00	-
Example 11	One	5.00	5.00	7.50	-	10.00	-
Example 12	One	5.00	5.00	2.50	-	-	10.00
Example 13	One	5.00	1.25	2.50	-	-	10.00
Example 14	One	5.00	1.25	2.50	-	10.00	-
Example 15	One	5.00	1.25	-	2.50	10.00	-
Example 16	One	5.00	5.00	2.50	-	5.00	-
Example 17	One	5.00	5.00	2.50	-	7.50	-
Example 18	One	5.00	20.00	2.50	-	10.00	-
Example 19	One	5.00	25.00	2.50	-	10.00	-
Comparative Example 1	One	5.00	5.00	-	-	-	-
Comparative Example 2	One	5.00	5.00	2.50	-	-	-
Comparative Example 3	One	0.30	5.00	2.50	-	10.00	-
Comparative Example 4	One	5.00	0.30	2.50	-	10.00	-
Comparative Example 5	One	5.00	5.00	0.30	-	10.00	-

<Experimental Example 1> Raw I evaluate whether precipitation product make-up liquid containing the multi-layered nano-particles of the poorly soluble drug encapsulated

In order to comparatively evaluate the precipitation of the liquid cosmetics according to the present invention, the cosmetics prepared in Examples 1 to 19 and the cosmetics prepared in Comparative Examples 1 to 5, by visually confirming whether or not to produce precipitation over time The experiment was carried out as follows.

Specifically, a transparent vial was prepared, 10 ml of each of the cosmetics prepared in Examples 1 to 19 and the cosmetics prepared in Comparative Examples 1 to 5 were added to each vial, and distilled water (20 ml) was dissolved therein. Immediately and after 2 months, the results were visually observed and the results are shown in Table 2 below. In particular, the cosmetics prepared in Example 3 and the cosmetics prepared in Comparative Example 2 were photographed after two months have elapsed, and the results are shown in the photographs in Figs.

	Immediately after manufacture	2 months
Example 1	×	×
Example 2	×	×
Example 3	×	×
Example 4	×	×
Example 5	×	×
Example 6	×	×
Example 7	×	×
Example 8	×	×
Example 9	×	×
Example 10	×	×
Example 11	×	×
Example 12	×	×
Example 13	×	△
Example 14	×	△
Example 15	×	△
Example 16	×	×
Example 17	×	×
Example 18	×	×
Example 19	×	×
Comparative Example 1	×	○
Comparative Example 2	×	○
Comparative Example 3	×	○
Comparative Example 4	△	○
Comparative Example 5	×	○

(In Table 2 above,

× denotes that when a precipitate is produced,

Δ does not produce precipitate but is opaque,

○ means that a precipitate has been formed and is opaque.)

Figure 2 is a photograph taken to visually check whether the liquid cosmetic containing the multi-layer nanoparticles containing the natural poorly soluble drug prepared in Example 3 in a transparent vial, precipitated after 2 months.

Figure 3 is a photograph taken to visually check whether the liquid cosmetic containing the particles containing the natural poorly soluble drug prepared in Comparative Example 2 in a transparent vial, and precipitated after 2 months.

As shown in Table 2, the liquid cosmetics prepared in Examples 1 to 19 were observed in the absence of precipitation immediately after the preparation and even after 2 months. In comparison, the liquid cosmetics prepared in Comparative Examples 1, 2, 3 and 5 were observed as transparent liquids without precipitation immediately after preparation, but were observed as opaque liquids having precipitates formed thereafter, and prepared in Comparative Example 4 The liquid cosmetics were observed as non-transparent liquids immediately after preparation, and after 2 months, as opaque liquids with precipitation.

2 to 3, the liquid cosmetics containing the natural polymer prepared in Example 3 was observed as a transparent liquid without precipitation even after 2 months, the natural polymer prepared in Comparative Example 2 Liquid cosmetics containing no was observed as an opaque liquid mixed with precipitate after 2 months.

Therefore, the cosmetic according to the present invention is dissolved in an aqueous solution by encapsulating the natural poorly soluble drug in a multilayer nanoparticle containing a poloxamer compound, a polyoxyether compound or a polyoxy castor oil compound and a natural polymer to the It can be seen that the problem of precipitation has been improved.

<Experimental Example 2> with the passage of time natural I of the multi-layer nanoparticles are soluble drug encapsulated size analysis and long-term stability assessment

Particle size over time of the liquid cosmetics containing the multi-layer nanoparticles containing the natural poorly soluble drug prepared in Example 3 and the liquid cosmetics containing the particles containing the natural poorly soluble drug prepared in Comparative Example 2 To determine the change, a multi-layer encapsulated with a natural poorly soluble drug prepared in Example 3 was an analyzer (Photal Otsuka electronics, model name: ELS-Z) using a dynamic light scattering (DLS) method. The particle size of the liquid cosmetics including the nanoparticles and the liquid cosmetics including the particles containing the natural poorly soluble drug prepared in Comparative Example 2 was measured and the results are shown graphically in FIGS. 4 to 5.

Figure 4 is a graph showing the change in particle size over time of the liquid cosmetics containing the multilayer nanoparticles containing the natural poorly soluble drug prepared in Example 3.

Figure 5 is a graph showing the change in particle size over time of the liquid cosmetic containing particles containing the natural poorly soluble drug prepared in Comparative Example 2.

 4 to 5, the multilayer nanoparticles of the liquid cosmetics containing the natural polymer prepared in Example 3 maintained a constant size of about 40 nm for 0-6 months and did not show a change in particle size. However, the particles of the liquid cosmetics containing no natural polymer prepared in Comparative Example 2 maintained a size of about 40 nm for 0-1 month, but after about 6 months after the size began to increase after 1 month The size increased to 100 nm.

Therefore, the cosmetic according to the present invention is encapsulated in the multi-layer nanoparticles containing the natural soluble drug poloxamer compound, polyoxyether compound or polyoxy castor oil-based compound and natural polymer to maintain a constant size of the particles for a long time form It can be seen that the long-term safety for.

<Experimental Example 3> Raw I mean size analysis of the multi-layered nano-particles of a poorly soluble drug encapsulated and long-term stability assessment

In order to evaluate the long-term stability by analyzing the average size of the multi-layer nanoparticles encapsulated with a natural poorly soluble drug according to the present invention, an analyzer (manufacturer: Photal Otsuka electronics, model name: ELS-Z) that can be analyzed from a particle size of 30 nm or more By using dynamic light scattering (DLS) method, liquid cosmetics containing multilayered nanoparticles encapsulated with the natural poorly soluble drug prepared in Example 3 after 6 months and the natural poorly soluble drug prepared in Comparative Example 2 were encapsulated. The distribution and average size of the particles of the liquid cosmetics containing the prepared particles were measured, and the results are shown in FIGS. 6 to 7.

Figure 6 is a graph showing the distribution and the average size of the multi-layer nanoparticles after 6 months of the liquid cosmetics containing the multi-layer nanoparticles containing the natural poorly soluble drug prepared in Example 3.

Figure 7 is a graph showing the distribution and average size of the particles after six months of the liquid cosmetics containing the particles containing the natural poorly soluble drug prepared in Comparative Example 2.

As shown in Figure 6 and 7, the multi-layer nanoparticles of the liquid cosmetics containing the natural polymer prepared in Example 3 is distributed in the range of about 20 nm-180 nm, the average size of these particles is 38.1 nm Was measured. In comparison, particles of the liquid cosmetics containing no natural polymer prepared in Comparative Example 2 were distributed in the range of about 45 nm to 315 nm, and the average size of these particles was measured to be 108.9 nm. From the above results, it can be seen that the multilayer nanoparticles of the liquid cosmetics containing the natural polymer prepared in Example 3 are maintained at a constant size of 38.1 nm on average even after 6 months.

Therefore, the cosmetic according to the present invention is a long-term particle size of less than 40 nm by encapsulating the natural poorly soluble drug in a multi-layer nanoparticle containing a poloxamer compound, polyoxyether compound or polyoxy castor oil compound and a natural polymer It can be seen that the long-term safety of the form has been improved by being kept constant.

<Experiment 4> with the passage of time natural I of the liquid cosmetic containing the multi-layered nano-particles of a poorly soluble drug encapsulated natural poorly soluble drug content analysis and long-term stability assessment

In order to find out the change of the content of the natural poorly soluble drug over time of the liquid cosmetics containing the multi-layer nanoparticles encapsulated with the natural poorly soluble drug according to the present invention, butanol as a solvent to GC (Gas chromatography, GC Agilent 6890N) The results of the analysis are shown graphically in FIG. 8.

Figure 8 is a graph showing the measurement of the change in the natural poorly soluble drug content of the liquid cosmetics containing the multi-layer nanoparticles containing the natural poorly soluble drug prepared in Example 8 over time.

As shown in Figure 8, the liquid cosmetics prepared in Example 8, it can be seen that the content of the natural poorly soluble drug is constantly maintained at about 100% for 0-6 months.

Therefore, the cosmetics according to the present invention can be seen that the long-term stability of the physical properties is improved because the content of the poorly soluble drug is maintained for a long time.

In addition, cosmetics containing the multi-layered nanoparticles containing the natural poorly soluble drug of the above composition as an antiseptic material may be configured to be included alone or in a mixture in the cosmetic composition according to a known technique, each composition ratio is determined by those skilled in the art It can be configured appropriately.

In addition, the cosmetics according to the present invention can be used as an active ingredient of cosmetics that can be classified into a kind such as skin, toner, essence, emulsion, lotion, cream, face mist, cleansing or face pack emulsion. That is, the kind of cosmetics can be divided according to the dosage form as an active ingredient according to the present invention and may further comprise a variety of carrier components for forming each formulation.

Preferably, when the cosmetic according to the present invention is an active ingredient, and the formulation of the cosmetic to be prepared is a paste, cream or gel, the carrier component is animal fiber, plant fiber, wax, paraffin, starch, trakant, cellulose derivative. , Polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used.

In addition, when the cosmetic according to the present invention as an active ingredient, and the formulation of the cosmetic to be prepared is a powder or a spray, the carrier component is any one or more of lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder May be used, and in particular when the formulation is a spray, it may further comprise a propellant of any one or more of chloro fluorohydrocarbon, propane / butane or dimethyl ether.

In addition, the cosmetic according to the present invention as an active ingredient, in the case of the formulation of the cosmetic to be prepared is a solution or emulsion, the carrier component may be used as a solvent, solvating agent or emulsifying agent. More specifically, the carrier component may be selected from fatty acid esters of water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan. It can be any one or more.

In addition, when the cosmetic preparation according to the invention as an active ingredient, and the formulation of the cosmetic preparation is a suspension, the carrier component is a liquid diluent such as water, ethanol or propylene glycol, ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester And suspending agents such as polyoxyethylene sorbitan esters, microcrystalline cellulose, aluminum meta hydroxide, bentonite, agar or tracant.

In addition, when the cosmetic according to the present invention as an active ingredient, and the formulation of the cosmetic is prepared with a surfactant-containing cleansing, the carrier component is aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, already Dazolinium derivatives, methyltaurate, sarcosinate, fatty acid amide ether sulfate, alkylamidobetaine, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linolin derivatives or ethoxylated glycerol fatty acid esters The above can be used.

In connection with the above, the carrier of this kind may be mixed with cosmetics according to the present invention (which serves as an active ingredient of the cosmetics to be manufactured) in various composition ratios, and the preferred composition ratios thereof are known according to the use of the cosmetics produced. The technique can be applied as appropriate.

The above has been described with reference to a preferred embodiment of the present invention, but is not limited to the above embodiment, the person having ordinary skill in the art to which the present invention pertains through the above embodiments without departing from the gist of the present invention Can be implemented in a variety of changes.

Claims (11)

1. In cosmetics containing preservatives,

   The antiseptic material,

   A first core comprising 1 part by weight of a natural poorly soluble drug and 0.5-10 parts by weight of a glycol compound represented by Formula 1 below;

   0.5 to 50 parts by weight of a poloxamer compound represented by Formula 2; And a second core including 0.5 to 10 parts by weight of a polyoxyether compound represented by Formula 3 or a polyoxy castor oil compound represented by Formula 4 below; And

   It comprises a multi-layer nanoparticles containing a natural poorly soluble drug consisting of a third core; 0.1 to 10 parts by weight of a natural polymer,

   [Formula 1]

   

   (In Formula 1,

   R ₁ is hydrogen or methyl;

   R ₂ is hydrogen or tetrahydrofuranyl; And

   n is an integer from 1 to 200;

   [Formula 2]

   

   (In Formula 2,

   l, m and p are independently integers from 1 to 200;

   [Formula 3]

   

   (In Chemical Formula 3,

   -Is a single or double bond;

   x, y and z are independently an integer from 1 to 100); And

   [Formula 4]

   

   (In Formula 4,

   -Is a single or double bond;

   a, a ', a ", b, b', b", c, c 'and c "are independently integers from 1 to 200; and

   d, d 'and d "is independently an integer of 0 to 200.) Cosmetics comprising a multi-layer nanoparticles containing a natural poorly soluble drug is embedded as an antiseptic material.
2. The method of claim 1,

   The natural poorly soluble drug preserving the multi-layer nanoparticles encapsulated with the natural poorly soluble drug, characterized in that at least one selected from the group consisting of mastic (mystic), myrrh, flavonoids, propolis, allicin, glucosamine and omega fatty acid. Cosmetics containing as substance.
3. The method of claim 1,

   The glycol-based compound represented by the formula (1) is a cosmetic comprising a multi-layer nanoparticles encapsulated with a natural poorly soluble drug, characterized in that at least one selected from the group consisting of polyethylene glycol, propylene glycol and tetraglycol as an antiseptic material.
4. The method of claim 1,

   The glycol compound represented by the formula (1) is a natural egg, characterized in that the mixture further used at least one selected from the group consisting of glycofurol, polysorbate, cremophore and Solutol HS (Solutol HS 15) Cosmetics containing multilayer nanoparticles containing a soluble drug as an antiseptic material.
5. The method of claim 1,

   The poloxamer compounds represented by Formula 2 are poloxamer 68, poloxamer 88, poloxamer 108, poloxamer 124, poloxamer 184, poloxamer 185, poloxamer 188, poloxamer 237, poloxamer 338 and poloxamer 407. Cosmetics containing as the antiseptic substance the multilayer nanoparticles encapsulated with a natural poorly soluble drug, characterized in that it is at least one member selected from the group consisting of:
6. The method of claim 1,

   The polyoxyether compound represented by Chemical Formula 3 may be polyoxyl-4-lauryl ether (brij30), polyoxyl-23-lauryl ether (brij35), polyoxyl-2-cetyl ether (brij52), polyoxyl- 10-cetyl ether (brij56), polyoxyl-20-cetyl ether (brij58), polyoxyl-2-stearyl ether (brij72), polyoxyl-10-stearyl ether (brij76), polyoxyl-2-oleyl Multilayer nano-encapsulated natural poorly soluble drug, characterized in that at least one selected from the group consisting of ether (brij93), polyoxyl-10-oleyl ether (brij97) and polyoxyl-20-oleyl ether (brij98). Cosmetics containing particles as antiseptics.
7. The method of claim 1,

   The polyoxy castor oil-based compound represented by Formula 4 is polyoxy 5 castor oil, polyoxy 9 castor oil, polyoxy 15 castor oil, polyoxy 35 castor oil, polyoxy 40 castor oil, polyoxy 60 castor oil, polyoxy It is at least one member selected from the group consisting of 100 castor oil, polyoxy 200 castor oil, polyoxy 40 hydrogenated castor oil, polyoxy 60 hydrogenated castor oil, polyoxy 100 hydrogenated castor oil and polyoxy 200 hydrogenated castor oil Cosmetics containing multilayer nanoparticles containing poorly soluble drugs as preservatives.
8. The method of claim 1,

   The natural polymer is alginic acid, chitosan, gum arabic, dextran, dextrin, gelatin, polyacrylic acid, pluronic acid, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose and carboxymethyl cellulose; And cosmetics comprising the multilayer nanoparticles encapsulated with a natural poorly soluble drug as one or more selected from the group consisting of salts thereof as an antiseptic material.
9. The method of claim 1,

   Wherein the multi-layer nanoparticles cosmetics comprising a multi-layer nanoparticles containing the natural poorly soluble drug is characterized in that the first core and the second core to form a micelle of 0.001- 30 nm size as an antiseptic material.
10. The method of claim 1,

    Wherein the multi-layer nanoparticles cosmetic product comprising a multi-layer nanoparticles containing a natural poorly soluble drug as a preservative, characterized in that having a particle size of 0.001- 40 nm.
11. A glycol compound represented by Formula 1 below; A poloxamer compound represented by Formula 2 below; A polyoxyether compound represented by Formula 3 or a polyoxy castor oil compound represented by Formula 4; And a natural poorly soluble drug; mixing or heating or sonicating (step 1); And

    And adding and stirring the natural polymer to the mixture of step 1 (step 2);

    [Formula 1]

    

    (In Formula 1,

    R ₁ is hydrogen or methyl;

    R ₂ is hydrogen or tetrahydrofuranyl; And

    n is an integer from 1 to 200;

    [Formula 2]

    

    (In Formula 2,

    l, m and p are independently integers from 1 to 200;

    [Formula 3]

    

    (In Chemical Formula 3,

    -Is a single or double bond;

    x, y and z are independently an integer from 1 to 100); And

    [Formula 4]

    

    (In Formula 4,

    -Is a single or double bond;

    a, a ', a ", b, b', b", c, c 'and c "are independently integers from 1 to 200; and

    d, d 'and d "is an integer of 0 to 200 independently.) A cosmetic manufacturing method comprising a multi-layer nanoparticles containing natural poorly soluble drugs as an antiseptic material.

Images