CN108419431B - Cosmetic containing multilayer nanoparticles encapsulating natural poorly-soluble drug as antiseptic substance and method for producing same - Google Patents
Cosmetic containing multilayer nanoparticles encapsulating natural poorly-soluble drug as antiseptic substance and method for producing same Download PDFInfo
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Abstract
The present invention relates to a cosmetic containing a preservative, and more particularly, to a cosmetic in which a natural poorly soluble drug-encapsulated multilayer nanoparticle maintains a constant size of 0.001 to 40nm after preparation, maintains a constant size of 0.001 to 40nm even after long-term storage, stably maintains a drug content, and does not precipitate even when used as a preservative for a liquid cosmetic, and which can realize excellent long-term storage stability by containing the multilayer nanoparticle as a preservative.
Description
Technical Field
The present invention relates to a cosmetic containing a preservative, and more particularly, to a cosmetic containing a multilayered nanoparticle in which a natural poorly soluble drug is encapsulated as a preservative and having excellent long-term storage stability.
Background
Among natural substances obtainable from animals and plants, there are many natural drugs that exhibit pharmaceutical activity in the human body. As examples thereof, frankincense (mastic), poultice, flavonoid, propolis, allicin, glucosamine, Omega fatty acid (Omega fat acid) and the like can be given. The Olibanum has effect in inhibiting or killing helicobacter pylori reproduction to relieve peptic ulcer. The powder has antiinflammatory and analgesic effects, and the flavonoid has anaphylaxis relieving effect. Further, the propolis has immunity enhancing and antioxidant effects, the allicin has bactericidal, blood circulation improving and diabetes preventing effects, the glucosamine alleviates arthritis symptoms, and the Omega fatty acid (Omega fatty acid) has blood pressure and cholesterol value improving effects.
Even though the above natural drugs have excellent pharmaceutical effects as described above, most of them are poorly soluble and have low solubility. Therefore, it shows low bioavailability when administered into a living body and suffers from difficulty in solubilization. Therefore, many cosmetic methods for solubilizing the above natural poorly soluble drugs have been studied, but the effect thereof has been extremely small or the application thereof has been limited so far.
Recently, the field of drug delivery systems has actively been studied for nanoparticles using amphiphilic macromolecules. The amphiphilic polymer forms a nano-aggregate with a unique structure on an aqueous solution by virtue of hydrophobic interaction between molecules and physical agglutination force such as van der waals (van der waals) force because of coexistence of the hydrophobic block and the hydrophilic block. This is because the hydrophobic blocks tend to self-aggregate in order to minimize contact with water, and the hydrophobic aggregates thus aggregated form fine domains (core), and the hydrophilic blocks are wrapped around the hydrophobic blocks to form polymer micelles (micelles), thereby improving the solubility in the entire aqueous solution. The polymer micelle forms a core having a size of several tens to several hundreds nanometers and has a poorly soluble drug enclosed therein, and thus the polymer micelle is widely used as a solubilizer for poorly soluble drugs that exhibit low solubility and low bioabsorption rate.
However, if the polymer nanoparticles are applied to a cosmetic containing a natural poorly soluble drug, the natural poorly soluble drug is insoluble in water and has a high viscosity, and the natural poorly soluble drug is dispersed in water after emulsification, and therefore, the natural poorly soluble drug is aggregated with time, and the particle size changes or the drug content decreases, so that it is difficult to maintain a certain size and drug content for a long time, and thus it is difficult to make a cosmetic containing a natural poorly soluble drug into a cosmetic.
The present inventors have found that, in the course of developing a pharmaceutical cosmetic composition which can maintain stability even when a natural poorly soluble drug is encapsulated, a cosmetic composition comprising a multilayer nanoparticle in which a natural poorly soluble drug is encapsulated as a preservative can maintain a certain size and stably maintain a drug content even after long-term storage, does not form a precipitate even when the cosmetic composition is prepared as a liquid cosmetic composition, and can increase the solubility of a natural poorly soluble drug to improve bioavailability, and thus can easily store a cosmetic composition comprising a multilayer nanoparticle in which a natural poorly soluble drug is encapsulated as a preservative for a long period of time, thereby completing the present invention.
Disclosure of Invention
The present invention is intended to solve various problems of cosmetics based on the prior art, and an object of the present invention is to provide a cosmetic containing multilayered nanoparticles in which a natural poorly soluble drug is encapsulated as a preservative with excellent long-term stability.
In order to achieve the above object, the present invention discloses a cosmetic comprising a preservative substance, the cosmetic comprising a multilayered nanoparticle in which a natural poorly soluble drug is encapsulated as the preservative substance, the preservative substance comprising a multilayered nanoparticle in which a natural poorly soluble drug is encapsulated, the multilayered nanoparticle comprising:
a first core including 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 chemical formula 1; a second core including 0.5 to 50 parts by weight of a poloxamer (poloxamer) compound represented by the following chemical formula 2, 0.5 to 10 parts by weight of a polyoxyether (polyoxyether) compound represented by the following chemical formula 3, or a polyoxycastor oil (polyoxy castor oil) compound represented by the following chemical formula 4; and a third core comprising 0.1-10 parts by weight of a natural polymer;
[ chemical formula 1]
Wherein, in the above chemical formula 1,
r1 is hydrogen or methyl;
r2 is hydrogen or tetrahydrofuranyl (tetrahydrofuranyl); and
n is an integer from 1 to 200;
[ chemical formula 2]
Wherein, in the above chemical formula 2,
l, m and p are each an integer of 1 to 200;
[ chemical formula 3]
Wherein, in the above chemical formula 3,
-is a single or double bond;
x, y and z are each an integer of 1 to 100; and
[ chemical formula 4]
Wherein, in the above chemical formula 4,
-is a single or double bond;
a. a ', a ", b ', b", c ' and c "are integers of 1 to 200, respectively; and
d. d 'and d' are integers of 0 to 200, respectively.
The present invention discloses a method for preparing a cosmetic containing multilayered nanoparticles in which a natural poorly soluble drug is encapsulated as a preservative, the method comprising the steps of: a step 1 of mixing a glycol-based compound represented by the above chemical formula 1, a poloxamer compound represented by the above chemical formula 2, a polyoxyetheric compound represented by the above chemical formula 3 or a polyoxyricinoleic compound represented by the above chemical formula 4, and a natural poorly soluble drug and performing heating or ultrasonic treatment; and a step 2 of adding a natural polymer to the mixture of the step 1 and stirring the mixture.
As described above, the cosmetic of the present invention contains a preservative substance containing as an active ingredient a multilayered nanoparticle in which a natural poorly soluble drug that is harmless to the human body is encapsulated, and thus the long-term storage stability of the cosmetic is improved.
Drawings
Fig. 1 is a diagram showing the structure of a multilayer nanoparticle contained in a cosmetic containing the multilayer nanoparticle in which a natural poorly soluble drug is encapsulated as a preservative of the present invention.
Fig. 2 is a photograph taken to load the liquid cosmetic composition containing the multilayered nanoparticles encapsulating the natural poorly soluble drug as the antiseptic substance prepared in example 3 into a vial and to visually confirm whether or not the precipitation has occurred after 2 months.
Fig. 3 is a photograph taken in order to load the liquid cosmetic containing a natural poorly soluble drug prepared in comparative example 2 into a vial and confirm whether or not precipitation has occurred with the naked eye after 2 months have elapsed.
FIG. 4 is a graph showing the change of particle size over time of the liquid cosmetic composition containing as a preservative substance the multilayered nanoparticles encapsulating a natural poorly soluble drug prepared in example 3.
Fig. 5 is a graph showing the change in particle size over time of the liquid cosmetic containing a natural poorly soluble drug prepared in comparative example 2.
Fig. 6 is a graph showing the distribution and average size of the multilayered nanoparticles after 6 months in the liquid cosmetic containing the multilayered nanoparticles encapsulating a natural poorly soluble drug as a preservative prepared in example 3.
Fig. 7 is a graph showing a distribution graph and an average size of particles after 6 months for the liquid cosmetic containing a natural poorly soluble drug prepared in comparative example 2.
Fig. 8 is a graph showing changes in the content of the natural poorly soluble drug in a liquid cosmetic containing the natural poorly soluble drug encapsulated multi-layered nanoparticles as a preservative prepared in example 3 of the present invention, measured with elapsed time.
Detailed Description
The present invention will be described in detail with reference to the accompanying drawings.
[ cosmetics comprising multilayered nanoparticles encapsulating natural poorly-soluble drugs as antiseptic substance ]
The invention discloses a cosmetic comprising multilayer nanoparticles as antiseptic, wherein the invention comprises micelle comprising a first core and a second core, wherein the first core comprises 1 weight part of natural indissolvable drug and 0.5-10 weight parts of glycol compound represented by the following chemical formula 1;
the second core comprises 0.5-50 parts by weight of poloxamer compound represented by chemical formula 2, 0.5-10 parts by weight of polyoxyetheric compound represented by chemical formula 3 or polyoxyricinic oil compound represented by chemical formula 4;
the third core comprises 0.1-10 parts by weight of natural polymer;
[ chemical formula 1]
(in the above-mentioned chemical formula 1,
r1 is hydrogen or methyl;
r2 is hydrogen or tetrahydrofuranyl; and
n is an integer of 1 to 200);
[ chemical formula 2]
(in the above-mentioned chemical formula 2,
l, m and p are each an integer of 1 to 200);
[ chemical formula 3]
(in the above-mentioned chemical formula 3,
-is a single or double bond;
x, y and z are each an integer of 1 to 100); and
[ chemical formula 4]
(in the above-mentioned chemical formula 4,
-is a single or double bond;
a. a ', a ", b ', b", c ' and c "are integers of 1 to 200, respectively; and
d. d' and d "are integers of 0 to 200, respectively).
The above cosmetic of the present invention will be described in detail.
In the cosmetic of the present invention, the natural poorly soluble drug may be used alone or in combination with a natural poorly soluble drug which is difficult to solubilize, more preferably, frankincense (massic), a powder, a flavonoid, propolis, allicin, glucosamine, omega fatty acid, and the like are used alone or in combination, and most preferably, frankincense is used alone, but not limited thereto.
In the cosmetic of the present invention, the glycol-based compound represented by the following chemical formula 1 is as follows:
[ chemical formula 1]
In the above-described chemical formula 1,
r1 is hydrogen or methyl;
r2 is hydrogen or tetrahydrofuranyl; and
n is an integer of 1 to 200
Preferably, the first and second electrodes are formed of a metal,
r1 and R2 are both hydrogen, or R1 is methyl and R2 is hydrogen, or R1 is hydrogen and R2 is tetrahydrofuranyl; and
n is an integer of 5 to 50.
The glycol-based compound represented by the above chemical formula 1 functions to dissolve a natural poorly soluble drug. The glycol compound may be polyethylene glycol, propylene glycol, tetraethylene glycol (tetraglycol), etc., and preferably polyethylene glycol is used.
The glycol compound represented by the above chemical formula 1 may be used in combination with Glycofurol (Glycofurol), Polysorbate (Polysorbate), Cremophor (Cremophor), polyethylene glycol-15 hydroxystearate (Solutol HS15), and the like.
The content of the glycol-based compound represented by the above chemical formula 1 is preferably 0.5 to 10 parts by weight, more preferably 2 to 8 parts by weight, relative to 1 part by weight of the natural poorly soluble drug.
When the content of the glycol-based compound represented by the above chemical formula 1 is less than 0.5 part by weight based on 1 part by weight of the natural poorly-soluble drug, the dispersion of the natural poorly-soluble drug is incomplete and the drug is difficult to be released, and when the content is more than 10 parts by weight, the problem of an increase in particle size occurs.
In the cosmetic of the present invention, the poloxamer compound represented by the following chemical formula 2 is as follows:
[ chemical formula 2]
In the above-described chemical formula 2,
l, m and p are each an integer of 1 to 200.
Preferably, the first and second electrodes are formed of a metal,
l, m and p are each an integer of 10 to 150.
The poloxamer compound represented by chemical formula 2 forms micelles, and the natural poorly soluble drug dissolved in the glycol compound is encapsulated in the micelles. The poloxamer compound represented by chemical formula 2 may use poloxamer 68, poloxamer 88, poloxamer 108, poloxamer 124, poloxamer 184, poloxamer 185, poloxamer 188, poloxamer 237, poloxamer 338, poloxamer 407, etc., preferably, poloxamer 188.
Preferably, the poloxamer compound represented by chemical formula 2 is contained in an amount of 0.5 to 50 parts by weight, more preferably 3 to 20 parts by weight, based on 1 part by weight of the natural poorly soluble drug. When the content of the poloxamer compound represented by chemical formula 2 is less than 0.5 parts by weight based on 1 part by weight of the natural poorly soluble drug, the natural poorly soluble drug is precipitated relatively quickly, and when the content is more than 50 parts by weight, the particle size is increased.
In the cosmetic of the present invention, the polyoxyether-based compound represented by the following chemical formula 3 or the polyoxycastor oil-based compound represented by the following chemical formula 4 is as follows:
[ chemical formula 3]
(in the above-mentioned chemical formula 3,
-is a single or double bond;
x, y and z are each an integer of 1 to 100); and
[ chemical formula 4]
(in the above-mentioned chemical formula 4,
-is a single or double bond;
a. a ', a ", b ', b", c ' and c "are integers of 1 to 200, respectively; and
d. d' and d "are integers of 0 to 200, respectively).
Preferably, the first and second electrodes are formed of a metal,
x, y and z are each an integer of 1 to 50;
a. a ', a ", b ', b", c ' and c "are integers of 1 to 100, respectively; and
d. d 'and d' are each an integer of 0 to 100.
The polyoxyetheric compound represented by the above chemical formula 3 or the polyoxyricinoleic compound represented by the above chemical formula 4 exhibits an effect of increasing solubility in an aqueous solution. The polyoxyethylene Ether compound represented by the above chemical formula 3 may be polyoxyethylene (4) lauryl Ether (brij30) (polyoxyl-4-lauryl Ether), polyoxyethylene (23) lauryl Ether (brij35), polyoxyethylene (2) cetyl Ether (polyoxyl-2-cetyl Ether) (brij52), polyoxyethylene (10) cetyl Ether (brij56), polyoxyethylene (20) cetyl Ether (brij58), polyoxyethylene (2) Stearyl Ether (polyoxyl-2-stearylether) (brij72), polyoxyethylene (10) Stearyl Ether (brij76), polyoxyethylene (2) oleyl Ether (polyoxyl-2-oleylether) (brij93), polyoxyethylene (10) oleyl Ether (brij97), polyoxyethylene (20) oleyl Ether (brij98), etc., alone or in combination, preferably polyoxyethylene (20) cetyl Ether (brij 58).
The Polyoxy Castor Oil compound represented by chemical formula 4 may be Polyoxy 5Castor Oil (Polyoxy 5Castor 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, or the like, singly or in combination, and preferably Polyoxy 15 Castor Oil is used.
Further, the HLB (Hydrophile-Lipophile Balance) value of the polyoxyether compound represented by chemical formula 3 or the polyoxycastor oil compound represented by chemical formula 4 is preferably in the range of 5 to 20, more preferably in the range of 10 to 20.
Further, the polyoxyethylene ether compound represented by chemical formula 3 or the polyoxy castor represented by chemical formula 3 is preferably contained in an amount of 0.5 to 10 parts by weight, more preferably 2 to 8 parts by weight, based on 1 part by weight of the natural poorly soluble drug. When the content of the polyoxyether-based compound represented by chemical formula 3 or the compound represented by chemical formula 4 is less than 0.5 part by weight relative to 1 part by weight of the natural poorly-soluble drug, the effect of increasing solubility is not exhibited and thus the natural poorly-soluble drug is rapidly precipitated, and when the content is more than 10 parts by weight, toxicity is exhibited due to the polyoxyether-based compound represented by chemical formula 3 or the polyoxycastor oil-based compound represented by chemical formula 4.
In the cosmetic of the present invention, the natural polymer coats the surface of the micelle to enhance the stability of the micelle in which the natural poorly soluble drug is encapsulated. The natural polymer may be alginic acid, chitosan, gum arabic, dextran, dextrin, gelatin, polyacrylic acid, Pluronic acid, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose or salts thereof, and preferably alginic acid or sodium alginate.
Preferably, the natural polymer is contained in an amount of 0.1 to 20 parts by weight based on 1 part by weight of the natural poorly-soluble drug. When the content of the natural polymer is less than 0.1 part by weight, the micelle containing the natural poorly-soluble drug cannot be encapsulated in the natural polymer, and when the content is more than 20 parts by weight, the natural polymer not encapsulating the micelle precipitates.
In the cosmetic of the present invention, the cosmetic further comprises a tension regulator for increasing the stability of micelles, and the tension regulator may be sorbitol, mannitol, xylitol, lactose, glucose, dextrose, sodium chloride, potassium chloride, carbomer, Pemulen (Pemulen), or the like, and preferably, sodium chloride or potassium chloride is used.
Preferably, the content of the above-mentioned tension adjuster is 1 to 20 parts by weight, more preferably 5 to 15 parts by weight, relative to 1 part by weight of the natural poorly soluble drug. When the content of the tension adjuster is less than 1 part by weight, a sufficient tension adjusting effect cannot be exerted, and when the content is more than 20 parts by weight, the concentration of the natural poorly soluble drug is lowered to decrease the drug efficacy.
The cosmetic of the present invention further includes a pH adjuster for adjusting the acidity to an acidity suitable for use as a cosmetic, and the pH adjuster may be a pH adjuster generally used in the art, preferably citric acid, malic acid, lactic acid, humic acid, glycolic acid, acetic acid, hydrochloric acid, hydrobromic acid, sulfuric acid, and the like, and more preferably hydrochloric acid, sodium hydroxide, and the like.
Furthermore, the cosmetic of the present invention can use at least one excipient such as starch, calcium carbonate, sucrose, lactose, sorbitol, dextrose, dextrates, xylitol, microcrystalline cellulose, and the like, which are used in cosmetics.
In addition, the cosmetic of the present invention may use at least one lubricant, for example, magnesium stearate talc, colloidal silica (colloidal silica), stearic acid, iron oxide, sodium stearyl fumarate, and the like, which are cosmetically acceptable.
As described above, the observation that the cosmetic of the present invention was still a transparent liquid phase without precipitation after 2 months was confirmed to improve the precipitation of the cosmetic (see Experimental example 1)
Further, the multilayered nanoparticles contained in the cosmetic of the present invention maintain a certain size of about 40nm for 0 to 6 months without change in particle size, and thus it was confirmed that the particle size can be maintained for a long time to improve the long-term safety with respect to morphology (see experimental example 2)
Still further, the cosmetics of the present invention contain multi-layered nanoparticles still distributed in the size range of about 20nm to 180nm after 6 months and the average size of these particles is measured to be 38.1 nm. Accordingly, it was confirmed that the multi-layered nanoparticles maintain a certain particle size for a long time after 6 months from the production thereof, and the long-term safety of the morphology was improved (see experimental example 3).
Further, since the multi-layered nanoparticles contained in the cosmetic of the present invention maintain the content of the natural poorly soluble drug at about 100% for 0 to 6 months, it was confirmed that the long-term stability of physical properties was improved by maintaining the content of the natural poorly soluble drug at a constant content without changing the content for a long time (see example 4)
Therefore, the multilayered nanoparticle having a natural poorly soluble drug encapsulated therein according to the present invention forms a micelle having a size of 0.001 to 30nm by encapsulating a first core including the glycol-based compound represented by the above chemical formula 1 and the natural poorly soluble substance in a second core including the poloxamer compound represented by the above chemical formula 2, the polyoxyetheric compound represented by the above chemical formula 3, or the polyoxyricinic compound represented by the above chemical formula 4, and then encapsulates the second core including the natural polymer in a third core, thereby maintaining the particle size of 0.001 to 40nm for a long time, increasing the solubility of cosmetics including the same with little loss of the drug, and improving the stability.
[ method for producing cosmetic preparation comprising multilayer nanoparticles encapsulating natural poorly-soluble drug as antiseptic substance ]
The present invention provides a method for producing a cosmetic containing, as a preservative, the multilayered nanoparticles in which the natural poorly soluble drug is encapsulated, the method comprising the steps of: a step 1 of mixing a glycol-based compound represented by the following chemical formula 1, a poloxamer compound represented by the following chemical formula 2, a polyoxyetheric compound represented by the following chemical formula 3 or a polyoxyricinoleic compound represented by the following chemical formula 4, and a natural poorly soluble drug, and performing heating or ultrasonic treatment; and
and 2, adding natural polymer into the mixture obtained in the step 1 and stirring.
[ chemical formula 1]
(in the above-mentioned chemical formula 1,
r1 is hydrogen or methyl;
r2 is hydrogen or tetrahydrofuranyl; and
n is an integer of 1 to 200);
[ chemical formula 2]
(in the above-mentioned chemical formula 2,
l, m and p are each an integer of 1 to 200);
[ chemical formula 3]
(in the above-mentioned chemical formula 3,
-is a single or double bond; and
x, y and z are each an integer of 1 to 100); and
[ chemical formula 4]
(in the above-mentioned chemical formula 4,
-is a single or double bond;
a. a ', a ", b ', b", c ' and c "are integers of 1 to 200, respectively; and
d. d' and d "are integers of 0 to 200, respectively).
The above-mentioned production process of the present invention is explained in detail below.
First, in the method for producing the cosmetic of the present invention, step 1 is a step of mixing a glycol-based compound represented by chemical formula 1, a poloxamer compound represented by chemical formula 2, a polyoxyether-based compound represented by chemical formula 3 or a polyoxycastor oil-based compound represented by chemical formula 4, and a natural poorly soluble drug, and performing heating or ultrasonic treatment.
Specifically, in the step 1, the glycol compound represented by the chemical formula 1, the poloxamer compound represented by the chemical formula 2, the polyoxyetheric compound represented by the chemical formula 3 or the polyoxyricinoleic compound represented by the chemical formula 4, and the natural poorly-soluble drug are mixed, and then heated or sonicated to form micelles having a size of 0.001 to 30nm, in which the glycol compound represented by the chemical formula 1 and the natural poorly-soluble drug are encapsulated. In order to form the micelles, a method of heating or ultrasonic treatment of the above components may be used, but the present invention is not limited thereto.
In the preparation method of the present invention, the natural poorly soluble drug may be used alone or in combination with a natural poorly soluble drug that is difficult to solubilize, more preferably, mastic (boswellia), powder, flavonoid, propolis, allicin, glucosamine, omega fatty acid, etc., and most preferably, mastic is used alone, but not limited thereto.
In the preparation method of the present invention, the glycol-based compound represented by the above chemical formula 1 functions to dissolve the above natural poorly soluble drug. Preferably, polyethylene glycol, propylene glycol, tetraethylene glycol, etc. are used as the glycol-based compound represented by the above chemical formula 1, and more preferably, polyethylene glycol is used. The glycol compound represented by the above chemical formula 1 may be used in combination with glycofurol, polysorbate, cremophor, polyethylene glycol-15 hydroxystearate (Solutol HS15), and the like.
The content of the glycol-based compound represented by the above chemical formula 1 is preferably 0.5 to 10 parts by weight, more preferably 2 to 8 parts by weight, relative to 1 part by weight of the natural poorly soluble drug.
In the preparation method of the present invention, the poloxamer compound represented by chemical formula 2 forms micelles, and the natural poorly soluble drug dissolved in the glycol compound represented by chemical formula 1 is encapsulated in the micelles. Preferably, poloxamer 68, poloxamer 88, poloxamer 108, poloxamer 124, poloxamer 184, poloxamer 185, poloxamer 188, poloxamer 237, poloxamer 338, poloxamer 407, etc. are used as the above poloxamer compound, and poloxamer 188 is more preferably used.
Also, the poloxamer compound represented by chemical formula 2 is preferably contained in an amount of 0.5 to 50 parts by weight, more preferably 3 to 20 parts by weight, based on 1 part by weight of the natural poorly soluble drug.
In the method for preparing the cosmetic of the present invention, the step 2 is a step of adding a natural polymer to the mixture of the step 1 and stirring the mixture.
Specifically, in step 2, in order to improve the solubility and stability of the natural poorly soluble drug, a natural polymer is added to the micelle in which the natural poorly soluble drug is encapsulated prepared in step 1, and the surface of the micelle is coated with the natural polymer, thereby preparing a multilayered (multilayered) nanoparticle.
In the preparation method of the present invention, the natural polymer coats the surface of the micelle to enhance the stability in an aqueous solution. The natural polymer may be alginic acid, chitosan, gum arabic, dextran, dextrin, gelatin, polyacrylic acid, Pluronic acid, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose or salts thereof, and preferably alginic acid or sodium alginate.
Preferably, the content of the natural polymer is 0.1 to 10 parts by weight relative to 1 part by weight of the natural poorly-soluble drug.
As described above, the method for producing a cosmetic comprising as a preservative a multilayered nanoparticle in which a natural poorly soluble drug is encapsulated, according to the present invention, maintains a particle size of less than 40nm for a long period of time after 6 months, and thus it is found that long-term safety can be improved with respect to morphology (see Experimental examples 2 and 3)
Further, in the method for producing a cosmetic containing as a preservative substance a multilayered nanoparticle in which a natural poorly soluble drug is encapsulated according to the present invention, it is found that the content of the natural poorly soluble drug encapsulated in the multilayered nanoparticle is maintained to be approximately 100% after 6 months, and the long-term stability with respect to physical properties is improved (see example 4)
Therefore, the method for producing a cosmetic containing as a preservative substance a multilayered nanoparticle in which a natural poorly soluble drug is encapsulated can produce a multilayered nanoparticle having a particle size of 0.001 to 40nm and maintaining a constant particle size and physical properties for a long period of time, and can be effectively used for producing a liquid cosmetic or a solid cosmetic containing as a preservative substance the multilayered nanoparticle in which a natural poorly soluble drug is encapsulated.
The present invention will be described in detail below with reference to examples, comparative examples and experimental examples.
However, the following examples, comparative examples and experimental examples are merely illustrative of the present invention and the contents of the present invention should not be limited to the following examples, comparative examples and experimental examples.
< example 1> preparation of cosmetic 1 comprising multilayered nanoparticles encapsulating natural poorly soluble drug as antiseptic substance
(1) Preparation of liquid cosmetic
Olibanum (100mg, mastic gum (HR-50850), imported from Korea essence Co., Ltd., Greek), polyethylene glycol (PEG-400, 125mg), poloxamer 188(500mg) and polyoxyethylene-20 cetyl ether (250mg) were mixed, and the mixture was heated to 50 deg.C, and then sodium alginate (2% aqueous solution, 1000mg) was added thereto and stirred to prepare a liquid cosmetic comprising multilayered nanoparticles in which a natural poorly soluble drug was encapsulated.
(2) Preparation of solid cosmetic
The liquid cosmetic prepared in (1) above was dried under reduced pressure to prepare a solid cosmetic comprising multilayer nanoparticles in which a natural poorly soluble drug was encapsulated.
< example 2> preparation of cosmetic 2 comprising multilayered nanoparticles encapsulating natural poorly soluble drug as antiseptic substance
The same procedure was followed, except that polyethylene glycol (PEG-400, 250mg) was used instead of polyethylene glycol (PEG-400, 125mg) in example 1 above.
< example 3> preparation of cosmetic 3 comprising multilayered nanoparticles encapsulating natural poorly soluble drug as antiseptic substance
The same procedure was followed, except that polyethylene glycol (PEG-400, 500mg) was used in place of polyethylene glycol (PEG-400, 125mg) in example 1.
< example 4> preparation of cosmetic 4 comprising multilayered nanoparticles encapsulating natural poorly soluble drug as antiseptic substance
The same procedure was followed, except that polyethylene glycol (PEG-400, 750mg) was used in place of polyethylene glycol (PEG-400, 125mg) in example 1.
< example 5> preparation of cosmetic 5 comprising multilayered nanoparticles encapsulating natural poorly soluble drug as antiseptic substance
The procedure was carried out in the same manner as in example 3 except that polyoxy-15 castor oil (250mg) was used in place of polyoxyethylene-20 cetyl ether (250 mg).
< example 6> preparation of cosmetic 6 containing multilayered nanoparticles encapsulating natural poorly soluble drug as antiseptic substance
The same procedure was followed, except that poloxamer 188(250mg) was used instead of poloxamer 188(500mg) in example 3 above.
< example 7> preparation of cosmetic 7 comprising multilayered nanoparticles encapsulating natural poorly soluble drug as antiseptic substance
The same procedure was followed, except that poloxamer 188(750mg) was used instead of poloxamer 188(500mg) in example 3 above.
< example 8> production of cosmetic 8 comprising multilayered nanoparticles encapsulating natural poorly soluble drug as antiseptic substance
The same procedure was followed, except that poloxamer 188(1500mg) was used instead of poloxamer 188(500mg) in example 3 above.
< example 9> preparation of cosmetic 9 containing multilayered nanoparticles encapsulating natural poorly soluble drug as antiseptic substance
The procedure was carried out in the same manner as in example 3 except that polyoxyethylene-20 cetyl ether (125mg) was used in place of polyoxyethylene-20 cetyl ether (250 mg).
< example 10> production of cosmetic 10 comprising multilayered nanoparticles encapsulating natural poorly-soluble drug as antiseptic substance
The procedure was carried out in the same manner as in example 3 except that polyoxyethylene-20 cetyl ether (500mg) was used in place of polyoxyethylene-20 cetyl ether (250 mg).
< example 11> production of cosmetic 11 comprising multilayered nanoparticles encapsulating natural poorly-soluble drug as antiseptic substance
The procedure was carried out in the same manner as in example 3 except that polyoxyethylene-20 cetyl ether (750mg) was used in place of polyoxyethylene-20 cetyl ether (250 mg).
< example 12> production of cosmetic 12 containing multilayered nanoparticles encapsulating natural poorly soluble drug as antiseptic substance
The procedure was carried out in the same manner as in example 3 above except that methylcellulose (1000mg) was used instead of sodium alginate (2% aqueous solution, 1000 mg).
< example 13> production of cosmetic 13 containing multilayered nanoparticles encapsulating natural poorly-soluble drug as antiseptic substance
The procedure was carried out in the same manner as in example 3 except that poloxamer 188(125mg) and methylcellulose (1000mg) were used instead of poloxamer 188(500mg) and sodium alginate (2% aqueous solution, 1000 mg).
< example 14> preparation of cosmetic 14 containing multilayered nanoparticles encapsulating natural poorly soluble drug as antiseptic substance
The same procedure was followed, except that poloxamer 188(125mg) was used instead of poloxamer 188(500mg) in example 3 above.
< example 15> preparation of cosmetic 15 comprising multilayered nanoparticles encapsulating natural poorly soluble drug as antiseptic substance
The procedure was carried out in the same manner as described above except that polyoxy-15 castor oil (250mg) was used instead of polyoxyethylene-20 cetyl ether (250mg) at the step of example 14.
< example 16> production of cosmetic 16 comprising multilayered nanoparticles encapsulating natural poorly soluble drug as antiseptic substance
The same procedure was followed except that sodium alginate (2% aqueous solution, 500mg) was used in place of sodium alginate (2% aqueous solution, 1000mg) in example 3 above.
< example 17> production of cosmetic 17 comprising multilayered nanoparticles encapsulating natural poorly-soluble drug as antiseptic substance
The same procedure was followed except that sodium alginate (2% aqueous solution, 750mg) was used in place of sodium alginate (2% aqueous solution, 1000mg) in example 3 above.
< example 18> preparation of cosmetic 18 containing multilayered nanoparticles encapsulating natural poorly soluble drug as antiseptic substance
The same procedure was followed, except that poloxamer 188(2000mg) was used instead of poloxamer 188(500mg) in example 3 above.
< example 19> production of cosmetic 19 comprising multilayered nanoparticles encapsulating natural poorly soluble drug as preservative
The same procedure was followed, except that poloxamer 188(2500mg) was used instead of poloxamer 188(500mg) in example 3 above.
< comparative example 1> preparation of liquid cosmetic 1 comprising natural poorly soluble drug
Liquid cosmetic comprising particles encapsulating natural poorly soluble drugs is prepared by mixing Olibanum (100mg), polyethylene glycol (PEG-400, 500mg) and poloxamer 188(500mg) and heating the mixture to 50 deg.C.
< comparative example 2> preparation of liquid cosmetic 2 comprising natural poorly soluble drug
Liquid cosmetic comprising particles encapsulating natural poorly soluble drugs is prepared by mixing Olibanum (100mg), polyethylene glycol (PEG-400, 500mg), poloxamer 188(500mg) and polyoxyethylene-20 cetyl ether (250mg), and heating the mixture to 50 deg.C.
< comparative example 3> preparation of liquid cosmetic 3 comprising natural poorly soluble drug
The same procedure was followed, except that polyethylene glycol (PEG-400, 30mg) was used in place of polyethylene glycol (PEG-400, 500mg) in example 3 above.
< comparative example 4> preparation of liquid cosmetic 4 comprising natural poorly soluble drug
The same procedure was followed, except that poloxamer 188(30mg) was used instead of poloxamer 188(500mg) in example 3 above.
< comparative example 5> preparation of liquid cosmetic 5 comprising natural poorly soluble drug
The procedure was carried out in the same manner as in example 3 except that polyoxyethylene-20 cetyl ether (30mg) was used in place of polyoxyethylene-20 cetyl ether (250 mg).
The following table 1 schematically shows the reaction conditions of the above examples 1 to 19 and comparative examples 1 to 5.
[ Table 1]
< Experimental example 1> evaluation of whether or not precipitation of a liquid cosmetic comprising multilayered nanoparticles encapsulating a natural poorly soluble drug occurs
In order to compare and evaluate whether the liquid cosmetics according to the present invention were precipitated, the following experiments were performed on the cosmetics prepared in the above examples 1 to 19 and the cosmetics prepared in the comparative examples 1 to 5 so as to visually observe whether time-based precipitation occurred.
Specifically, transparent vials (visual) were prepared and 10ml of each of the cosmetics prepared in examples 1 to 19 and the cosmetics prepared in comparative examples 1 to 5 were poured into each vial, and then distilled water (20ml) was poured for dissolution and then observed with the naked eye immediately after 2 months 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 2 months and are illustrated in fig. 2 to 3 as photographs.
[ Table 2]
(in the above Table 2, X represents a case where no precipitation occurred, Delta represents a case where no precipitation occurred but was opaque, and O represents a case where precipitation occurred and was opaque.)
Fig. 2 is a photograph taken to load the liquid cosmetic composition containing the multilayered nanoparticles encapsulating a natural poorly soluble drug prepared in example 3 into a vial and to visually confirm whether or not precipitation has occurred after 2 months have elapsed.
Fig. 3 is a photograph taken to load the liquid cosmetic composition containing particles encapsulating a natural poorly soluble drug prepared in comparative example 2 into a vial and visually confirm whether or not precipitation has occurred after 2 months have elapsed.
As shown in Table 2, the liquid cosmetics prepared in examples 1 to 19 were not precipitated immediately after the preparation and observed after 2 months. In contrast, the liquid cosmetics prepared in comparative examples 1, 2, 3 and 5 showed a clear liquid phase without precipitation when observed immediately after the preparation, but a non-clear liquid phase with precipitation was observed after 2 months, while the liquid cosmetics prepared in comparative example 4 showed a non-clear liquid phase immediately after the preparation and a non-clear liquid phase with precipitation was observed after 2 months.
As shown in the photographs of fig. 2 to 3, the liquid cosmetic containing a natural polymer prepared in example 3 was observed to be a transparent liquid phase without precipitation even after 2 months, and the liquid cosmetic containing no natural polymer prepared in comparative example 2 was observed to be an opaque liquid phase mixed with precipitation after 2 months.
Therefore, the cosmetic of the present invention is known to improve the problem of precipitation of the natural poorly soluble drug by encapsulating the natural poorly soluble drug in a multilayer nanoparticle containing a poloxamer compound, a polyoxyetheric compound or a polyoxyricinoleic compound, and a natural polymer and dissolving the same in an aqueous solution.
< Experimental example 2> analysis of size and evaluation of Long-term stability of multilayered nanoparticles encapsulating Natural poorly soluble drugs on the basis of time
In order to understand the time-based particle size change of the liquid cosmetic containing the natural poorly soluble drug-encapsulated multi-layered nanoparticles prepared in example 3 and the liquid cosmetic containing the natural poorly soluble drug-encapsulated particles prepared in comparative example 2, the particle sizes of the liquid cosmetic containing the natural poorly soluble drug-encapsulated multi-layered nanoparticles prepared in example 3 and the liquid cosmetic containing the natural poorly soluble drug-encapsulated particles prepared in comparative example 2 were measured with an analytical instrument (manufacturer: photographic otsuka electronics, model name: ELS-Z) using the Dynamic Light Scattering (DLS) method, and the results thereof are graphically shown in fig. 4 to 5.
FIG. 4 is a graph showing the change in particle size over time of the liquid cosmetic composition containing the multilayered nanoparticles encapsulating a natural poorly soluble drug prepared in example 3.
Fig. 5 is a graph showing the change in particle size over time of the liquid cosmetic composition containing particles encapsulating a natural poorly soluble drug prepared in comparative example 2.
Referring to the results of fig. 4 to 5, the multilayered nanoparticles of the liquid cosmetic comprising a natural polymer prepared in example 3 maintained a certain size of about 40nm for 0-6 months without change in particle size. However, the particles of the liquid cosmetic prepared in comparative example 2, which did not include the natural polymer, maintained a size of about 40nm during 0-1 month, but began to increase in size after 1 month and increased to a size of about 100nm after 6 months.
Therefore, the cosmetic of the present invention has been found to improve the long-term safety of the form by encapsulating the natural poorly soluble drug in a multilayered nanoparticle containing a poloxamer compound, a polyoxyetheric compound or a polyoxyricinoleic compound, and a natural polymer so that the particle size is maintained at a constant size for a long period of time.
< Experimental example 3> average size analysis and evaluation of Long-term stability of multilayered nanoparticles having natural poorly soluble drugs Encapsulated therein
In order to evaluate the long-term stability after analyzing the average size of the multilayered nanoparticles encapsulating a natural poorly soluble drug according to the present invention, the distribution and average size of the particles of the liquid cosmetic comprising the multilayered nanoparticles encapsulating a natural poorly soluble drug prepared in example 3 and the liquid cosmetic comprising the particles encapsulating a natural poorly soluble drug prepared in comparative example 2 were measured by Dynamic Light Scattering (DLS) method after 6 months using an analyzer (manufacturer: Phototsuka electronics, model name: ELS-Z) capable of analyzing from a particle size of 30nm or more, and the results are shown in FIGS. 6 to 7.
Fig. 6 is a graph showing the distribution and average size of the multilayered nanoparticles after 6 months in the liquid cosmetic containing the multilayered nanoparticles in which the natural poorly soluble drug is encapsulated prepared in example 3.
Fig. 7 is a graph showing a distribution and an average size of particles of the liquid cosmetic composition containing the particles in which the natural poorly soluble drug is encapsulated, prepared in comparative example 2, after 6 months.
As shown in fig. 6 and 7, the multi-layered nanoparticles of the liquid cosmetic including a natural polymer prepared in the above example 3 were distributed in the range of about 20nm to 180nm and the average size of the particles was measured to be 38.1 nm. In contrast, the particles of the liquid cosmetic prepared in comparative example 2, which did not include the natural polymer, were distributed in the range of about 45nm to 315nm and the average size of the particles was measured to be 108.9 nm.
From the above results, it can be seen that the multilayered nanoparticles of the liquid cosmetic including a natural polymer prepared in example 3 maintain a certain size of 38.1nm in average after 6 months.
Therefore, the cosmetic of the present invention has been found to improve the long-term safety of the form by encapsulating the natural poorly soluble drug in a multilayer nanoparticle containing a poloxamer compound, a polyoxyetheric compound or a polyoxyricinoleic compound, and a natural polymer so that the particle size is maintained at an average size of less than 40nm for a long period of time.
< Experimental example 4> analysis of content of natural poorly soluble drug and evaluation of long-term stability of liquid cosmetic containing multilayered nanoparticles in which natural poorly soluble drug is encapsulated over time
In order to understand the change in the content of the natural poorly soluble drug over time in the liquid cosmetic composition of the present invention containing the multilayered nanoparticle in which the natural poorly soluble drug is encapsulated, the results of analysis using GC (Gas chromatography) with butanol as a solvent are shown in fig. 8 as a graph.
Fig. 8 is a graph showing changes in the content of the natural poorly soluble drug in a liquid cosmetic containing the multilayered nanoparticle in which the natural poorly soluble drug is encapsulated, prepared in example 8 of the present invention, measured with lapse of time.
As shown in fig. 8, the content of the natural poorly soluble drug was maintained at about 100% for 0-6 months in the liquid cosmetic prepared in example 8.
Therefore, the cosmetic of the present invention has been found to have improved long-term stability with respect to physical properties by maintaining a constant content of the natural poorly soluble drug without changing the content.
Meanwhile, the cosmetic composition comprising the multilayered nanoparticles encapsulating a natural poorly soluble drug as a preservative substance, which is configured as described above, may be included in a cosmetic composition based on a known technique alone or in a mixed manner, and the respective composition ratios may be appropriately set by those skilled in the art according to the judgment.
Furthermore, the cosmetic of the present invention can be used as an active ingredient of cosmetics classified into types of lotions, toilet lotions, essence lotions, emulsions, milky lotions, creams, moisturizing sprays, makeup remover oils, emulsions for face masks, and the like. That is, the above-mentioned kinds of cosmetics contain the cosmetics of the present invention as an active ingredient according to the classification of dosage forms and can further contain various carrier ingredients for preparing each dosage form.
Preferably, when the cosmetic of the present invention is used as an active ingredient and the form of the prepared cosmetic is an ointment, cream or gel, the carrier component may be one or more of animal fiber, plant fiber, wax, paraffin, starch, tragacanth, cellulose derivative, polyethylene glycol, silicon, bentonite, silica, talc or zinc oxide.
In addition, when the cosmetic of the present invention is used as an active ingredient and the form of the prepared cosmetic is a powder or a spray, one or more of lactose, talc, silica, aluminum hydroxide, calcium silicate, and polyamide powder can be used as the carrier component, and in particular, one or more of chlorofluorocarbon, propane/butane, and dimethyl ether can be used as the spray.
Meanwhile, when the cosmetic of the present invention is used as an active ingredient and the form of the prepared cosmetic is a solution or an emulsion, a solvent, a cosolvent or an emulsifier may be used as the carrier component. More specifically, the carrier component may be at least one selected from water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1, 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, and fatty acid ester of sorbitan.
Meanwhile, when the cosmetic of the present invention is used as an active ingredient and the form of the prepared cosmetic is a suspension, any one or more of the following substances may be used as the carrier component: liquid diluents such as water, ethanol or propylene glycol; suspending agents such as ethoxylated isostearyl alcohols, polyoxyethylene sorbitol esters and polyoxyethylene sorbitol esters; microcrystalline cellulose; aluminum metahydroxide; bentonite; agar or tragacanth.
When the cosmetic of the present invention is used as an active ingredient and the form of the prepared cosmetic is a surfactant-containing makeup remover oil, the carrier component may be at least one of sulfated fatty alcohol, sulfated fatty alcohol ether, sulfosuccinic acid monoester, isethionate, imidazoline derivative, methyltaurate, sarcosinate, fatty acid amide ether sulfate, alkylamide betaine, fatty alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, linolenic acid derivative, and ethoxylated glycerol fatty acid ester.
From the above, the above-mentioned types of carriers can be mixed with the cosmetic of the present invention (which functions as an active ingredient of the prepared cosmetic) at various combination ratios depending on the use of the prepared cosmetic, and known techniques can be appropriately applied to the preferred combination ratio in this regard.
The foregoing description has been made with reference to the preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and those skilled in the art to which the present invention pertains can implement various changes in the above embodiments without departing from the gist of the present invention.
Claims (11)
1. A cosmetic comprising, as an antiseptic substance, a multilayered nanoparticle in which a natural poorly soluble drug is encapsulated, the multilayered nanoparticle comprising:
a first core including 1 part by weight of a natural poorly soluble drug and 0.5 to 10 parts by weight of a glycol-based compound represented by the following chemical formula 1;
a second core including 0.5 to 50 parts by weight of a poloxamer compound represented by the following chemical formula 2, 0.5 to 10 parts by weight of a polyoxyetheric compound represented by the following chemical formula 3, or a polyoxyricinoleic compound represented by the following chemical formula 4; and
the third core comprises 0.1 to 10 weight parts of natural polymer,
[ chemical formula 1]
Wherein, in the above chemical formula 1,
r1 is hydrogen or methyl;
r2 is hydrogen or tetrahydrofuranyl; and
n is an integer from 1 to 200;
[ chemical formula 2]
Wherein, in the above chemical formula 2,
l, m and p are each an integer of 1 to 200;
[ chemical formula 3]
Wherein, in the above chemical formula 3,
-is a single or double bond; x, y and z are each an integer of 1 to 100; and
[ chemical formula 4]
Wherein, in the above chemical formula 4,
-is a single or double bond;
a. a ', a ', b ', c ' and c ' are integers of 1 to 200, respectively; and d, d 'and d' are each an integer of 0 to 200.
2. The cosmetic preparation comprising as a preservative substance a multilayered nanoparticle encapsulating a natural poorly soluble drug according to claim 1,
the natural insoluble medicine is selected from more than one of Olibanum, Myrrha, flavonoid, propolis, allicin, glucosamine and omega fatty acid.
3. The cosmetic preparation comprising as a preservative substance a multilayered nanoparticle encapsulating a natural poorly soluble drug according to claim 1,
the glycol-based compound represented by the above chemical formula 1 is selected from one or more of polyethylene glycol, propylene glycol and tetraethylene glycol.
4. The cosmetic preparation comprising as a preservative substance a multilayered nanoparticle encapsulating a natural poorly soluble drug according to claim 1,
the glycol compound represented by the above chemical formula 1 is further mixed with at least one selected from the group consisting of glycofurol, polysorbate, cremophor and polyethylene glycol-15 hydroxystearate (Solutol HS15) and used.
5. The cosmetic preparation comprising as a preservative substance a multilayered nanoparticle encapsulating a natural poorly soluble drug according to claim 1,
the poloxamer compound represented by chemical formula 2 is selected from one or more of poloxamer 68, poloxamer 88, poloxamer 108, poloxamer 124, poloxamer 184, poloxamer 185, poloxamer 188, poloxamer 237, poloxamer 338 and poloxamer 407.
6. The cosmetic preparation comprising as a preservative substance a multilayered nanoparticle encapsulating a natural poorly soluble drug according to claim 1,
the polyoxyethylene ether compound represented by chemical formula 3 is selected from one or more of polyoxyethylene (4) lauryl ether (brij30), polyoxyethylene (23) lauryl ether (brij35), polyoxyethylene (2) cetyl ether (brij52), polyoxyethylene (10) cetyl ether (brij56), polyoxyethylene (20) cetyl ether (brij58), polyoxyethylene (2) stearyl ether (brij72), polyoxyethylene (10) stearyl ether (brij76), polyoxyethylene (2) oleyl ether (brij93), polyoxyethylene (10) oleyl ether (brij97), and polyoxyethylene (20) oleyl ether (brij 98).
7. The cosmetic preparation comprising as a preservative substance a multilayered nanoparticle encapsulating a natural poorly soluble drug according to claim 1,
the polyoxy castor oil compound represented by the chemical formula 4 is at least one selected from polyoxy 5castor 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, and polyoxy 200 hydrogenated castor oil.
8. The cosmetic preparation comprising as a preservative substance a multilayered nanoparticle encapsulating a natural poorly soluble drug according to claim 1,
the natural polymer is selected from alginic acid, chitosan, acacia, dextran, dextrin, gelatin, polyacrylic acid, Pluronic acid, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose and carboxymethylcellulose; and salts thereof.
9. The cosmetic preparation comprising as a preservative substance a multilayered nanoparticle encapsulating a natural poorly soluble drug according to claim 1,
the first core and the second core in the multilayer nanoparticle form a micelle having a size of 0.001-30 nm.
10. The cosmetic preparation comprising as a preservative substance a multilayered nanoparticle encapsulating a natural poorly soluble drug according to claim 1,
the multilayer nanoparticles have a particle size of 0.001-40 nm.
11. A method for producing a cosmetic containing a multilayered nanoparticle in which a natural poorly soluble drug is encapsulated as a preservative,
comprises the following steps:
a step 1 of mixing a glycol-based compound represented by the following chemical formula 1, a poloxamer compound represented by the following chemical formula 2, a polyoxyetheric compound represented by the following chemical formula 3 or a polyoxyricinoleic compound represented by the following chemical formula 4, and a natural poorly soluble drug, and performing heating or ultrasonic treatment; and
step 2, adding natural polymer into the mixture obtained in the step 1 and stirring the mixture,
[ chemical formula 1]
Wherein, in the above chemical formula 1,
r1 is hydrogen or methyl;
r2 is hydrogen or tetrahydrofuranyl; and
n is an integer from 1 to 200;
[ chemical formula 2]
Wherein, in the above chemical formula 2,
l, m and p are each an integer of 1 to 200;
[ chemical formula 3]
Wherein, in the above chemical formula 3,
-is a single or double bond;
x, y and z are each an integer of 1 to 100; and
[ chemical formula 4]
Wherein, in the above chemical formula 4,
-is a single or double bond;
a. a ', a ', b ', c ' and c ' are integers of 1 to 200, respectively; and
d. d 'and d' are integers of 0 to 200, respectively.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/KR2016/014164 WO2018105756A1 (en) | 2016-12-05 | 2016-12-05 | Cosmetics comprising multi-layer nanoparticles having natural insoluble medicine encapsulated therein as preservative, and method for producing said cosmetics |
| KR20160164049 | 2016-12-05 |
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| KR101025641B1 (en) * | 2008-06-18 | 2011-03-30 | 한국콜마 주식회사 | Self-microemulsified mastic composition and capsule containing the composition |
| KR101018894B1 (en) * | 2008-08-27 | 2011-03-04 | 근화제약주식회사 | Pharmaceutical compositions, formulations and absorption of Talniflumate extended release tablets |
| KR101515982B1 (en) * | 2013-06-24 | 2015-05-04 | 한국화학연구원 | Liquid formulation having micelles that encapsulate immunosuppressant |
| KR101601954B1 (en) * | 2014-02-07 | 2016-03-10 | (주)에이씨티 | Method for preparation of poor soluble materials containingnanoparticle for cosmetic composition |
| KR101698809B1 (en) * | 2015-09-21 | 2017-01-24 | 한국화학연구원 | Pharmaceutical formulation containing multilayer nanoparticle that encapsulate poorly water soluble natural drug and preparation method thereof |
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