CN108419431A - Including having enclosed cosmetics and preparation method thereof of the multi-layer nano particle of natural insoluble drug as preservative substance - Google Patents
Including having enclosed cosmetics and preparation method thereof of the multi-layer nano particle of natural insoluble drug as preservative substance Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
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- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
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- A—HUMAN NECESSITIES
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Abstract
The present invention relates to a kind of cosmetics including preservative substance, in more detail, the multi-layer nano particle for having enclosed natural insoluble drug of the cosmetics not only maintains a certain size of 0.001 40nm after the preparation, a certain size of 0.001 40nm can be maintained long-time preserves and steadily maintains medicament contg, preservative substance as liquid cosmetic will not precipitate when using, including above-mentioned multi-layer nano particle is achieved excellent long-term preservability as preservative substance.
Description
Technical field
The present invention relates to a kind of cosmetics including preservative substance, more particularly it relates to a kind of comprising enclosed
The cosmetics that the multi-layer nano particle of natural insoluble drug makes long-term preservability excellent as preservative substance.
Background technology
There is many natural of pharmaceutical active can be played in human body in the natural materials that can be obtained from animals and plants
Drug.Its frankincense (mastic) that can illustrate, myrrh, flavonoids, propolis, allicin, Glucosamine, omega aliphatic acid (Omega
Fatty acid) etc..Above-mentioned frankincense inhibits or kills the fertility of helicobacter pylori and has alleviation effects to peptic ulcer.On
Stating myrrh, there is anti-inflammatory analgesic effect, above-mentioned flavonoids to have allergic reaction alleviation effects.Further, above-mentioned propolis has
Strengthen immunity and antioxidant effect, above-mentioned allicin have the effect of sterilization, improve blood circulation and prevent diabetes, above-mentioned ammonia
Base glucose mitigates arthritic symptom, and above-mentioned omega aliphatic acid (Omega fatty acid) has improvement blood pressure and cholesterol
The effect of numerical value.
Even if above-mentioned natural drug has foregoing excellent therapeutic effect, but its major part has for slightly solubility
Standby lower solubility.Therefore, lower bioavilability (bioavailability) is showed when being put into raw body and is being increased
It is molten to meet difficulty.Therefore people have studied a variety of cosmetics methods of the solubilising for above-mentioned natural insoluble drug, but
Its effect is minimum so far or its application is restricted.
Recently, during the nano-particle using amphipathy macromolecule is actively studied in drug delivery system field.On
Amphipathy macromolecule is stated since hydrophobicity block and hydrophily block coexist and by feat of intermolecular hydrophobicity on aqueous solution
The physics cohesive force of interaction, van der Waals (van der waals) strength etc forms the nanometer set of unique structure
Body.This is because hydrophobicity block shows the tendency of self cohesion in order to reduce its contact with water to the greatest extent, so agglomerate
Hydrophobicity aggregate then form fine field (core), outside then allows hydrophily block to wrap up and form macromolecule micelle
(micelle), to improve the solubility to whole aqueous solution.The macromolecule micelle forms tens of to hundreds of nanometers sizes
Core and its internal enclosed insoluble drug and be able to as the insoluble drug for showing low solubility and low raw body absorptivity
Solubilized dosage form and be widely used.
However, if it is the cosmetics for high molecular nanometer particles being suitable for natural insoluble drug, due to natural
Insoluble drug can mutually coagulate being not dissolved in water and viscosity height and be distributed in water after being emulsified with the time
It is poly-, therefore particle size changes or medicament contg reduces and is difficult to maintain a certain size and medicament contg for a long time, to
It is more difficult to carry out cosmetics with enclosing natural insoluble drug, although people have persistently carried out many researchs to the problem, according to
So satisfactory achievement is obtained not yet.
The present invention then people for stable pharmacy cosmetics can be maintained to carry out having enclosed natural insoluble drug
Following content is found that during exploitation, also that is, the present invention's includes the multi-layer nano grain for having enclosed natural insoluble drug
Son as preservative substance cosmetics not only after being prepared for above-mentioned multi-layer nano particle, can be with low preservation for a long time
A certain size is maintained in the size of 40nm or so and steadily maintains medicament contg, will not be formed when liquid cosmetic is made
Precipitation, increases the solubility of natural insoluble drug and is improved bioavilability, therefore being capable of long-term preservation sheet easily
Invention comprising having enclosed the cosmetics of the multi-layer nano particle of natural insoluble drug as preservative substance, so as to complete
Invention.
Invention content
Present invention seek to address that the problems of the cosmetics based on the prior art, the object of the present invention is to provide a kind of length
Phase excellent in stability comprising having enclosed the cosmetics of the multi-layer nano particle of natural insoluble drug as preservative substance.
In order to achieve the above object, the present invention discloses a kind of cosmetics including preservative substance, and the toiletry bag is containing enclosed
For the multi-layer nano particle of natural insoluble drug as preservative substance, above-mentioned preservative substance includes having enclosed natural slightly solubility medicine
The multi-layer nano particle of object, the multi-layer nano particle include：
First core, including 1 parts by weight of natural insoluble drug and glycol (glycol) system for being indicated with following chemical formula 1
Close object 0.5-10 parts by weight；Second core includes poloxamer (poloxamer) the compound 0.5- indicated with following chemical formula 2
50 parts by weight, the polyoxyether indicated with following chemical formula 3 (polyoxy ether) based compound are indicated with following chemical formula 4
Polyoxy castor oil (polyoxy castor oil) based compound 0.5-10 parts by weight；And third core, including natural polymer
0.1-10 parts by weight；
[chemical formula 1]
Wherein, in above-mentioned chemical formula 1,
R1 is hydrogen or methyl；
R2 is hydrogen or tetrahydrofuran base (tetrahydrofuranyl)；And n is 1 to 200 integer；
[chemical formula 2]
Wherein, in above-mentioned chemical formula 2,
L, m and p is 1 to 200 integer respectively；
[chemical formula 3]
Wherein, in above-mentioned chemical formula 3,
It is singly-bound or double bond；
X, y and z is 1 to 100 integer respectively；And
[chemical formula 4]
Wherein, in above-mentioned chemical formula 4,
It is singly-bound or double bond；
A, a', a ", b, b', b ", c, c' and c " are 1 to 200 integer respectively；And
D, d' and d " are 0 to 200 integer respectively.
The present invention discloses a kind of comprising having enclosed the change of the multi-layer nano particle of natural insoluble drug as preservative substance
The preparation method of cosmetic, this method include the following steps：Step 1, the glycol based compound indicated with above-mentioned chemical formula 1, with
Poloxamer compound that above-mentioned chemical formula 2 indicates, the polyoxyether based compound that is indicated with above-mentioned chemical formula 3 or with above-mentioned chemistry
The polyoxy castor oil based compound and natural insoluble drug that formula 4 indicates are mixed and add at heat or ultrasonic
Reason；And step 2, it adds natural polymer in the mixture of above-mentioned steps 1 and is stirred.
The cosmetics of the present invention disclosed as previously mentioned are contained in cosmetics having enclosed harmless day
The multi-layer nano particle of right insoluble drug improves the long-term preservability of cosmetics as the preservative substance of active ingredient.
Description of the drawings
Fig. 1 be show the present invention comprising having enclosed the multi-layer nano particle of natural insoluble drug as preservative substance
The figure of the structure of multi-layer nano particle included in cosmetics.
Fig. 2 be in order to using prepared by embodiment 3 comprising enclosed the multi-layer nano particle of natural insoluble drug as
The liquid cosmetic of preservative substance is packed into transparent phial and is clapped whether confirming precipitation after 2 months with naked eyes
The photo taken the photograph.
Fig. 3 is in order to which the liquid cosmetic comprising natural insoluble drug prepared by comparative example 2 is packed into transparent small medicine
Bottle and the photo shot whether confirming precipitation after 2 months with naked eyes.
Fig. 4 be using prepared by embodiment 3 comprising having enclosed the multi-layer nano particle of natural insoluble drug as anti-corrosion
Curve graph shown in the time-based particle size variation of the liquid cosmetic of substance.
Fig. 5 is the time-based particle the liquid cosmetic comprising natural insoluble drug prepared by comparative example 2
Curve graph shown in size variation.
Fig. 6 is to show that being used as comprising the multi-layer nano particle for having enclosed natural insoluble drug prepared by embodiment 3 is prevented
The liquid cosmetic of rotten substance curve graph of the distribution map of multi-layer nano particle and average-size after 6 months.
Fig. 7 is to show the liquid cosmetic comprising natural insoluble drug prepared by comparative example 2 particle after 6 months
Distribution map and average-size curve graph.
Fig. 8 be according to lapse of time measure prepared by the embodiment of the present invention 3 comprising having enclosed natural insoluble drug
Above-mentioned natural insoluble drug changes of contents of the multi-layer nano particle as the liquid cosmetic of preservative substance after the song that shows
Line chart.
Specific implementation mode
The present invention is illustrated below in conjunction with the accompanying drawings.
[comprising cosmetics of the multi-layer nano particle of natural insoluble drug as preservative substance have been enclosed]
The present invention discloses a kind of cosmetics including multi-layer nano particle as preservative substance, and the present invention is including the first core
And second the micella of core enclose third core, above-mentioned first core includes 1 parts by weight of natural insoluble drug and with 1 table of following chemical formula
The glycol based compound 0.5-10 parts by weight shown；
Above-mentioned second core includes the poloxamer compound 0.5-50 parts by weight indicated with following chemical formula 2, " with followingization
The polyoxyether based compound or the polyoxy castor oil based compound 0.5-10 weight indicated with following chemical formula 4 that formula 3 indicates
Part "；
Above-mentioned third core includes natural polymer 0.1-10 parts by weight；
[chemical formula 1]
(in above-mentioned chemical formula 1,
R1 is hydrogen or methyl；
R2 is hydrogen or tetrahydrofuran base；And
N is 1 to 200 integer)；
[chemical formula 2]
(in above-mentioned chemical formula 2,
L, m and p is 1 to 200 integer respectively)；
[chemical formula 3]
(in above-mentioned chemical formula 3,
It is singly-bound or double bond；
X, y and z is 1 to 100 integer respectively)；And
[chemical formula 4]
(in above-mentioned chemical formula 4,
It is singly-bound or double bond；
A, a', a ", b, b', b ", c, c' and c " are 1 to 200 integer respectively；And
D, d' and d " are 0 to 200 integer respectively).
The following detailed description of the above-mentioned cosmetics of the present invention.
In the cosmetics of the present invention, above-mentioned natural insoluble drug can be the natural insoluble drug list of more difficult solubilising
It solely or is used in mixed way, it is highly preferred that frankincense (mastic), myrrh, flavonoids, propolis, allicin, Glucosamine, omega
Aliphatic acid etc. is used alone or as a mixture, and most preferably, frankincense is used alone, but not limited thereto.
It is as follows with the glycol based compound that following chemical formula 1 indicates in the cosmetics of the present invention：
[chemical formula 1]
In above-mentioned chemical formula 1,
R1 is hydrogen or methyl；
R2 is hydrogen or tetrahydrofuran base；And
N is 1 to 200 integer
Preferably,
Above-mentioned R1 and R2 be simultaneously hydrogen either R1 is methyl and R2 is hydrogen or R1 is hydrogen and R2 is tetrahydrofuran base；And
N is 5 to 50 integer.
The effect of the glycol based compound indicated with above-mentioned chemical formula 1 is the natural insoluble drug of dissolving.Above-mentioned glycol system
Compound can use polyethylene glycol, propylene glycol, tetraethylene glycol (tetraglycol) etc., it is preferable that use polyethylene glycol.
Moreover, the glycol based compound indicated with above-mentioned chemical formula 1 can and Tetrahydrofurfuryl polyethylene glycol ether
(Glycofurol), polysorbate (Polysorbate), cremophor (Cremophor), -15 hydroxy stearic acid of polyethylene glycol
It is used after the mixing such as ester (Solutol HS 15).
Preferably, relative to the glycol based compound of 1 parts by weight of natural insoluble drug indicated with above-mentioned chemical formula 1
Content is 0.5-10 parts by weight, it is highly preferred that its content is 2-8 parts by weight.
The content of the glycol based compound indicated with above-mentioned chemical formula 1 relative to 1 parts by weight of natural insoluble drug is low
The dispersion of natural insoluble drug is imperfect if 0.5 parts by weight and more difficult release drug, if content is higher than 10 parts by weight
The problem of particle size increases will occur.
It is as follows with the poloxamer compound that following chemical formula 2 indicates in the cosmetics of the present invention：
[chemical formula 2]
In above-mentioned chemical formula 2,
L, m and p is 1 to 200 integer respectively
Preferably,
L, m and p is 10 to 150 integer respectively.
The poloxamer compound indicated with above-mentioned chemical formula 2 is formed micella and is able to above-mentioned glycol based compound institute is molten
The natural insoluble drug of solution is enclosed inside micella.The poloxamer compound indicated with above-mentioned chemical formula 2 can use pool Lip river
Husky nurse 68, poloxamer 88, poloxamer 108, Pluronic/Lutrol F 44, poloxamer 184, poloxamer 185, poloxamer
188, poloxamer 237, Pluronic/Lutrol F 108, poloxamer188 etc., it is preferable that use PLURONICS F87.
Preferably, relative to the poloxamer compound of 1 parts by weight of natural insoluble drug indicated with above-mentioned chemical formula 2
Content be 0.5-50 parts by weight, more electedly, content be 3-20 parts by weight.Relative to 1 parts by weight of natural insoluble drug
The poloxamer compound indicated with above-mentioned chemical formula 2 content less than natural slightly solubility will occur if 0.5 parts by weight
The problem of particle size increases will occur if being higher than 50 parts by weight for the problem of drug comparatively fast precipitates, content.
In the cosmetics of the present invention, the polyoxyether based compound that is indicated with following chemical formula 3 or with 4 table of following chemical formula
The polyoxy castor oil based compound shown is as follows：
[chemical formula 3]
(in above-mentioned chemical formula 3,
It is singly-bound or double bond；
X, y and z is 1 to 100 integer respectively)；And
[chemical formula 4]
(in above-mentioned chemical formula 4,
It is singly-bound or double bond；
A, a', a ", b, b', b ", c, c' and c " are 1 to 200 integer respectively；And
D, d' and d " they are 0 to 200 integer respectively)
Preferably,
X, y and z is 1 to 50 integer respectively；
A, a', a ", b, b', b ", c, c' and c " are 1 to 100 integer respectively；And
D, d' and d " are 0 to 100 integer respectively.
The polyoxyether based compound indicated with above-mentioned chemical formula 3 or the polyoxy castor oil system indicated with above-mentioned chemical formula 4
It closes object and plays the effect for increasing solubility on aqueous solution.The polyoxyether based compound indicated with above-mentioned chemical formula 3 can 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) spermaceti
Base ether (brij56), polyoxyethylene (20) cetyl ether (brij58), polyoxyethylene (2) stearyl ether (polyoxyl-2-
Stearyl Ether) (brij72), polyoxyethylene (10) stearyl ether (brij76), polyoxyethylene (2) oleyl ether
(polyoxyl-2-oleyl ether) (brij93), polyoxyethylene (10) oleyl ether (brij97), polyoxyethylene (20) oil base
Ether (brij98) etc. is used alone or as a mixture, it is preferable that uses polyoxyethylene (20) cetyl ether (brij58).
Moreover, the polyoxy castor oil based compound indicated with above-mentioned chemical formula 4 can be 5 castor oil (Polyoxy of polyoxy
5Castor Oil), 9 castor oil of polyoxy, 15 castor oil of polyoxy, 35 castor oil of polyoxy, 40 castor oil of polyoxy, 60 castor oil of polyoxy,
Polyoxy Wart Fix, 200 castor oil of polyoxy, 40 rilanit special of polyoxy, 60 rilanit special of polyoxy, 100 hydrogenated castor of polyoxy
Oil, 200 rilanit special of polyoxy etc. are used alone or as a mixture, it is preferable that use 15 castor oil of polyoxy.
It is further preferred that the polyoxyether based compound that is indicated with above-mentioned chemical formula 3 or indicating poly- with following chemical formula 4
HLB (Hydrophile-Lipophile Balance) value of oxygen castor oil based compound uses 5-20 ranges, it is highly preferred that making
With 10-20 ranges.
Further still, it is preferred that the polyoxy indicated with above-mentioned chemical formula 3 relative to 1 parts by weight of natural insoluble drug
Ether based compound or the polyoxy castor content indicated with above-mentioned chemical formula 3 are 0.5-10 parts by weight, are weighed it is highly preferred that content is 2-8
Measure part.Relative to the polyoxyether based compound of 1 parts by weight of natural insoluble drug indicated with above-mentioned chemical formula 3 or with above-mentionedization
The content for the compound that formula 4 indicates is less than the effect that can not show increase solubility if 0.5 parts by weight and therefore sends out
The problem of raw natural insoluble drug comparatively fast precipitates will indicate poly- higher than if 10 parts by weight because of with above-mentioned chemical formula 3
Oxygen ether based compound or the polyoxy castor oil based compound that is indicated with above-mentioned chemical formula 4 and show toxicity.
In the cosmetics of the present invention, above-mentioned natural polymer wraps up the surface of above-mentioned micella and is enhanced above-mentioned enclosed
The stability of the micella of natural insoluble drug.Above-mentioned natural polymer can use alginic acid, chitosan, Arabic gum, Portugal
Glycan, dextrin, gel, polyacrylic acid, general stream Buddhist nun gram (Pluronic) acid, methylcellulose, ethyl cellulose, hydroxy ethyl fiber
Element, hydroxypropyl cellulose, carboxymethyl cellulose or its salt etc., it is preferable that use alginic acid or mosanom.
Preferably, it is 0.1-20 parts by weight relative to the above-mentioned natural polymer content of 1 parts by weight of natural insoluble drug.
It includes the micella of natural insoluble drug that above-mentioned natural polymer content can occur if being less than 0.1 parts by weight to be enclosed
The problem of stating natural polymer, content will be precipitated higher than that can occur without the natural polymer for wrapping micella if 20 parts by weight
The problem of.
In the cosmetics of the present invention, above-mentioned cosmetics further comprise tension adjustment to increase the stability of micella
Device, mentioned strain adjuster can use sorbierite, mannitol, xylitol, lactose, glucose, dextrose, sodium chloride, chlorination
Potassium, carbomer, abundant mesh connect (Pemulen) etc., it is preferable that use sodium chloride or potassium chloride.
Preferably, it is 1-20 parts by weight relative to the content of the mentioned strain adjuster of 1 parts by weight of natural insoluble drug,
It is highly preferred that content is 5-15 parts by weight.Mentioned strain adjuster content can not play enough if being less than 1 parts by weight
Power regulating effect can allow the concentration of natural insoluble drug to reduce and reduce drug efficiency higher than 20 parts by weight.
Moreover, the cosmetics of the present invention further include that acidity adjustment is adjusted at the pH for being suitable as the acidity that cosmetics use
Agent, above-mentioned pH adjusting agent can then use pH adjusting agent usually used in the art, it is preferable that use citric acid, apple
Tartaric acid, lactic acid, humic acid, glycolic, acetic acid, hydrochloric acid, hydrobromic acid, sulfuric acid etc., it is highly preferred that using hydrochloric acid, sodium hydroxide etc..
Further, cosmetics of the invention can use the excipient of at least more than one, such as can be used for cosmetics
Starch, calcium carbonate, sucrose, lactose, D-sorbite, dextrose, dextrates, xylitol, microcrystalline cellulose etc..
Moreover, the cosmetics of the present invention can use the lubricant of at least more than one, such as it can be used for the tristearin of cosmetics
Sour magnesium talcum, Ludox (colloidal silica), stearic acid, iron oxide, sodium stearyl fumarate etc..
As previously mentioned, observation result of the cosmetics after it have passed through 2 months of the present invention be still do not precipitate it is saturating
Bright liquid phase and be able to confirm which improve the sedimentation problem of cosmetics (please referring to experimental example 1)
Moreover, multi-layer nano particle contained by the cosmetics of the present invention maintains during 0-6 months, about 40nm's is certain big
It is small and do not change in particle size, thus it is confirmed that particle size can maintain a certain size for a long time and improve
Long-term safety (please referring to experimental example 2) about form
Further, multi-layer nano particle contained by cosmetics of the invention is still distributed in about 20nm- after six months
The measured value of the range of 180nm sizes and the average-size of these particles is 38.1nm.Whereby, above-mentioned multi-layer nano particle exists
It has passed through after making and particle size still allowed within 6 months to maintain a certain size for a long time and be able to confirm the length improved about form
Phase safety (please refers to experimental example 3).
Moreover, multi-layer nano particle contained by the cosmetics of the present invention allows above-mentioned natural insoluble drug during 0-6 months
Content maintain about 100% always, thus it is confirmed that above-mentioned natural insoluble drug content for a long time do not become
Change ground to maintain certain content and improve the long-time stability (please referring to experimental example 4) for physical property
Therefore, the multi-layer nano particle for having enclosed natural insoluble drug of the invention allows including with 1 table of above-mentioned chemical formula
First core of the glycol based compound and natural slightly solubility substance that show is enclosed the poloxamer including being indicated with above-mentioned chemical formula 2
Compound, " the polyoxyether based compound indicated with above-mentioned chemical formula 3 or the polyoxy castor oil system indicated with above-mentioned chemical formula 4
The micella that 0.001-30nm sizes are formed after second core of conjunction object ", is then sealed by the third core including above-mentioned natural polymer again
Enter and be able to maintain the particle size of 0.001-40nm for a long time, is increased almost without drug loss and includes its makeup
The solubility of product, moreover it is possible to improve stability.
[comprising having enclosed the preparation side of the multi-layer nano particle of natural insoluble drug as the cosmetics of preservative substance
Method]
It includes to have enclosed the multi-layer nano particle of above-mentioned natural insoluble drug as preservative substance that the present invention, which provides a kind of,
Cosmetics preparation method, this method includes the following steps：Step 1, the glycol system chemical combination indicated with following chemical formula 1
Object, the poloxamer compound indicated with following chemical formula 2, " the polyoxyether based compound or following indicated with following chemical formula 3
State the polyoxy castor oil based compound of the expression of chemical formula 4 " and naturally insoluble drug is mixed and is heated or surpassed
Sonicated；And
Step 2, it adds natural polymer in the mixture of above-mentioned steps 1 and is stirred.
[chemical formula 1]
(in above-mentioned chemical formula 1,
R1 is hydrogen or methyl；
R2 is hydrogen or tetrahydrofuran base；And
N is 1 to 200 integer)；
[chemical formula 2]
(in above-mentioned chemical formula 2,
L, m and p is 1 to 200 integer respectively)；
[chemical formula 3]
(in above-mentioned chemical formula 3,
It is singly-bound or double bond；And
X, y and z is 1 to 100 integer respectively)；And
[chemical formula 4]
(in above-mentioned chemical formula 4,
It is singly-bound or double bond；
A, a', a ", b, b', b ", c, c' and c " are 1 to 200 integer respectively；And
D, d' and d " they are 0 to 200 integer respectively)
The following detailed description of the above-mentioned preparation method of the present invention.
First, in the preparation method of the above-mentioned cosmetics of the present invention, step 1 is indicating sweet with above-mentioned chemical formula 1
Alcohol based compound, the poloxamer compound indicated with above-mentioned chemical formula 2, " the polyoxyether system chemical combination indicated with above-mentioned chemical formula 3
Object or the polyoxy castor oil based compound indicated with above-mentioned chemical formula 4 " and natural insoluble drug are mixed and are added
The step of heat or ultrasonic processing.
Specifically, above-mentioned steps 1 are indicated the glycol based compound indicated with above-mentioned chemical formula 1, with above-mentioned chemical formula 2
Poloxamer compound, " the polyoxyether based compound indicated with above-mentioned chemical formula 3 or the polyoxy indicated with above-mentioned chemical formula 4
Castor oil based compound " and natural insoluble drug carry out heating or ultrasonication and are formed enclosed after being mixed
The micella of the 0.001-30nm sizes of the glycol based compound and natural insoluble drug that are indicated with above-mentioned chemical formula 1.For shape
At above-mentioned micella, the method for being heated to mentioned component or carrying out ultrasonication can be used, but not limited thereto.
In the preparation process in accordance with the present invention, above-mentioned natural insoluble drug can be the natural insoluble drug of more difficult solubilising
It is used alone or as a mixture, it is highly preferred that frankincense (mastic), myrrh, flavonoids, propolis, allicin, Glucosamine, Europe rice
Gal aliphatic acid etc. is used alone or as a mixture, and most preferably, frankincense is used alone, but not limited thereto.
In the preparation process in accordance with the present invention, the effect of the glycol based compound indicated with above-mentioned chemical formula 1 is that dissolving is above-mentioned
Natural insoluble drug.Preferably, the glycol based compound indicated with above-mentioned chemical formula 1 uses polyethylene glycol, propylene glycol, four sweet
Alcohol etc., it is highly preferred that using polyethylene glycol.Moreover, the glycol based compound indicated with above-mentioned chemical formula 1 can and tetrahydrofuran
Make after the mixing such as polyglycol ether, polysorbate, cremophor, -15 hydroxy stearic acid ester of polyethylene glycol (Solutol HS15)
With.
Preferably, relative to the glycol based compound of 1 parts by weight of natural insoluble drug indicated with above-mentioned chemical formula 1
Content is 0.5-10 parts by weight, it is highly preferred that content is 2-8 parts by weight.
In the preparation process in accordance with the present invention, the poloxamer compound indicated with above-mentioned chemical formula 2 is formed micella and is able to
The natural insoluble drug that the glycol based compound indicated with above-mentioned chemical formula 1 is dissolved is enclosed inside micella.Preferably, on
It states poloxamer compound and uses poloxam 68, poloxamer 88, poloxamer 108, Pluronic/Lutrol F 44, poloxamer
184, poloxamer 185, PLURONICS F87, poloxamer 237, Pluronic/Lutrol F 108, poloxamer188 etc., it is highly preferred that making
Use PLURONICS F87.
It is further preferred that the poloxamer indicated with above-mentioned chemical formula 2 relative to 1 parts by weight of natural insoluble drug
The content of compound is 0.5-50 parts by weight, it is highly preferred that content is 3-20 parts by weight.
In the preparation method of the above-mentioned cosmetics of the present invention, above-mentioned steps 2 are that a kind of mixture in above-mentioned steps 1 adds
The step of adding natural polymer and being stirred.
Specifically, above-mentioned steps 2 in order to improve natural insoluble drug solubility and stability and in above-mentioned steps 1
The prepared micella for having enclosed natural insoluble drug adds natural polymer and wraps up above-mentioned micella with natural polymer
Surface, to be able to that the nano-particle of multilayer (multilayer) is made.
In the preparation process in accordance with the present invention, above-mentioned natural polymer wraps up the surface of above-mentioned micella and enhances on aqueous solution
Stability.Above-mentioned natural polymer can use alginic acid, chitosan, Arabic gum, glucan, dextrin, gel, polyacrylic acid,
General stream Buddhist nun gram (Pluronic) acid, methylcellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl are fine
Dimension element or its salt etc., it is preferable that use alginic acid or mosanom.
Preferably, it is 0.1-10 weight relative to the content of the above-mentioned natural polymer of 1 parts by weight of natural insoluble drug
Part.
As previously mentioned, the present invention's includes to have enclosed the multi-layer nano particle of natural insoluble drug as preservative substance
The preparation method of cosmetics particle size after it have passed through 6 months still maintains less than the size of 40nm and is able to maintain for a long time
Certain particle size, therefore learn that it can improve long-term safety (please referring to experimental example 2 and experimental example 3) for form
Moreover, the present invention comprising having enclosed the makeup of the multi-layer nano particle of natural insoluble drug as preservative substance
The preparation method of product is enclosed the content of above-mentioned natural insoluble drug of above-mentioned multi-layer nano particle after it have passed through 6 months
About 100% ground does not maintain alternatively for a long time, it is known that improves and (please refers to experimental example to the long-time stability of physical property
4)
Therefore, of the invention comprising having enclosed makeup of the multi-layer nano particle of natural insoluble drug as preservative substance
The preparation method of product can make the particle size for having 0.001-40nm and maintain certain particle size transitivity for a long time
Multi-layer nano particle, it is above-mentioned comprising having enclosed the multi-layer nano particle of natural insoluble drug as preservative substance making
It can be efficiently used when liquid cosmetic, solid, cosmetic.
With reference to embodiment, comparative example and experimental example, the present invention will be described in detail.
But following embodiments, comparative example and experimental example are only the illustration of the present invention, must not be present disclosure
It is limited to following embodiments, comparative example and experimental example.
<Embodiment 1>Including having enclosed cosmetics 1 of the multi-layer nano particle as preservative substance of natural insoluble drug
Preparation
(1) preparation of liquid cosmetic
Frankincense (mastic, 100mg, frankincense gum (HR-50850), importer：Han Bi essence Co., Ltd., source area：
Greece), polyethylene glycol (PEG-400,125mg), PLURONICS F87 (500mg) and -20 cetyl ether of polyoxyethylene (250mg)
After being mixed and said mixture being heated to 50 DEG C, mosanom (2% aqueous solution, 1000mg) is added and stirs that packet is made
Include the liquid cosmetic for the multi-layer nano particle for having enclosed natural insoluble drug.
(2) preparation of solid, cosmetic
Allow liquid cosmetic prepared by above-mentioned (1) is dry and is made including having enclosed natural insoluble drug under reduced pressure
Multi-layer nano particle solid, cosmetic.
<Embodiment 2>Including having enclosed cosmetics 2 of the multi-layer nano particle as preservative substance of natural insoluble drug
Preparation
In addition in above-described embodiment 1 use polyethylene glycol (PEG-400,250mg) instead of polyethylene glycol (PEG-400,
Other than 125mg), remaining is all carried out in the same way.
<Embodiment 3>Including having enclosed cosmetics 3 of the multi-layer nano particle as preservative substance of natural insoluble drug
Preparation
In addition in above-described embodiment 1 use polyethylene glycol (PEG-400,500mg) instead of polyethylene glycol (PEG-400,
Other than 125mg), remaining is all carried out in the same way.
<Embodiment 4>Including having enclosed cosmetics 4 of the multi-layer nano particle as preservative substance of natural insoluble drug
Preparation
In addition in above-described embodiment 1 use polyethylene glycol (PEG-400,750mg) instead of polyethylene glycol (PEG-400,
Other than 125mg), remaining is all carried out in the same way.
<Embodiment 5>Including having enclosed cosmetics 5 of the multi-layer nano particle as preservative substance of natural insoluble drug
Preparation
In addition to using -15 castor oil of polyoxy (250mg) instead of -20 cetyl ether of polyoxyethylene in above-described embodiment 3
Other than (250mg), remaining is all carried out in the same way.
<Embodiment 6>Including having enclosed cosmetics 6 of the multi-layer nano particle as preservative substance of natural insoluble drug
Preparation
In addition in above-described embodiment 3 use PLURONICS F87 (250mg) instead of PLURONICS F87 (500mg) with
Outside, remaining is all carried out in the same way.
<Embodiment 7>Including having enclosed cosmetics 7 of the multi-layer nano particle as preservative substance of natural insoluble drug
Preparation
In addition in above-described embodiment 3 use PLURONICS F87 (750mg) instead of PLURONICS F87 (500mg) with
Outside, remaining is all carried out in the same way.
<Embodiment 8>Including having enclosed cosmetics 8 of the multi-layer nano particle as preservative substance of natural insoluble drug
Preparation
In addition in above-described embodiment 3 use PLURONICS F87 (1500mg) instead of PLURONICS F87 (500mg) with
Outside, remaining is all carried out in the same way.
<Embodiment 9>Including having enclosed cosmetics 9 of the multi-layer nano particle as preservative substance of natural insoluble drug
Preparation
In addition to using -20 cetyl ether of polyoxyethylene (125mg) instead of -20 whale of polyoxyethylene in above-described embodiment 3
Other than cerul ether (250mg), remaining is all carried out in the same way.
<Embodiment 10>Including having enclosed cosmetics of the multi-layer nano particle of natural insoluble drug as preservative substance
10 preparation
In addition to using -20 cetyl ether of polyoxyethylene (500mg) instead of -20 whale of polyoxyethylene in above-described embodiment 3
Other than cerul ether (250mg), remaining is all carried out in the same way.
<Embodiment 11>Including having enclosed cosmetics of the multi-layer nano particle of natural insoluble drug as preservative substance
11 preparation
In addition to using -20 cetyl ether of polyoxyethylene (750mg) instead of -20 whale of polyoxyethylene in above-described embodiment 3
Other than cerul ether (250mg), remaining is all carried out in the same way.
<Embodiment 12>Including having enclosed cosmetics of the multi-layer nano particle of natural insoluble drug as preservative substance
12 preparation
In addition in above-described embodiment 3 use methylcellulose (1000mg) instead of mosanom (2% aqueous solution,
Other than 1000mg), remaining is all carried out in the same way.
<Embodiment 13>Including having enclosed cosmetics of the multi-layer nano particle of natural insoluble drug as preservative substance
13 preparation
In addition to using PLURONICS F87 (125mg) and methylcellulose (1000mg) instead of pool in above-described embodiment 3
Other than Luo Shamu 188 (500mg) and mosanom (2% aqueous solution, 1000mg), remaining is all carried out in the same way.
<Embodiment 14>Including having enclosed cosmetics of the multi-layer nano particle of natural insoluble drug as preservative substance
14 preparation
In addition in above-described embodiment 3 use PLURONICS F87 (125mg) instead of PLURONICS F87 (500mg) with
Outside, remaining is all carried out in the same way.
<Embodiment 15>Including having enclosed cosmetics of the multi-layer nano particle of natural insoluble drug as preservative substance
15 preparation
In addition to using -15 castor oil of polyoxy (250mg) instead of -20 cetyl of polyoxyethylene in 14 step of above-described embodiment
Other than ether (250mg), remaining is all carried out in the same way.
<Embodiment 16>Including having enclosed cosmetics of the multi-layer nano particle of natural insoluble drug as preservative substance
16 preparation
In addition in above-described embodiment 3 use mosanom (2% aqueous solution, 500mg) instead of mosanom (2% aqueous solution,
Other than 1000mg), remaining is all carried out in the same way.
<Embodiment 17>Including having enclosed cosmetics of the multi-layer nano particle of natural insoluble drug as preservative substance
17 preparation
In addition in above-described embodiment 3 use mosanom (2% aqueous solution, 750mg) instead of mosanom (2% aqueous solution,
Other than 1000mg), remaining is all carried out in the same way.
<Embodiment 18>Including having enclosed cosmetics of the multi-layer nano particle of natural insoluble drug as preservative substance
18 preparation
In addition in above-described embodiment 3 use PLURONICS F87 (2000mg) instead of PLURONICS F87 (500mg) with
Outside, remaining is all carried out in the same way.
<Embodiment 19>Including having enclosed cosmetics of the multi-layer nano particle of natural insoluble drug as preservative substance
19 preparation
In addition in above-described embodiment 3 use PLURONICS F87 (2500mg) instead of PLURONICS F87 (500mg) with
Outside, remaining is all carried out in the same way.
<Comparative example 1>The preparation of liquid cosmetic 1 including natural insoluble drug
Frankincense (100mg), polyethylene glycol (PEG-400,500mg) and PLURONICS F87 (500mg) are mixed and
Said mixture is heated to be prepared for after 50 DEG C include the particle for having enclosed natural insoluble drug liquid cosmetic.
<Comparative example 2>The preparation of liquid cosmetic 2 including natural insoluble drug
Frankincense (100mg), polyethylene glycol (PEG-400,500mg), PLURONICS F87 (500mg) and polyoxyethylene -20
Cetyl ether (250mg) is mixed and said mixture is heated to be prepared for after 50 DEG C of said mixtures to include enclosed
The liquid cosmetic of the particle of natural insoluble drug.
<Comparative example 3>The preparation of liquid cosmetic 3 including natural insoluble drug
In addition in above-described embodiment 3 use polyethylene glycol (PEG-400,30mg) instead of polyethylene glycol (PEG-400,
Other than 500mg), remaining is all carried out in the same way.
<Comparative example 4>The preparation of liquid cosmetic 4 including natural insoluble drug
In addition in above-described embodiment 3 use PLURONICS F87 (30mg) instead of PLURONICS F87 (500mg) other than,
Remaining is all carried out in the same way.
<Comparative example 5>The preparation of liquid cosmetic 5 including natural insoluble drug
In addition to using -20 cetyl ether of polyoxyethylene (30mg) instead of -20 spermaceti of polyoxyethylene in above-described embodiment 3
Other than base ether (250mg), remaining is all carried out in the same way.
Following table 1 shows the reaction condition of above-described embodiment 1 to 19 and comparative example 1 to 5 in a capsule.
[table 1]
<Experimental example 1>Assessment includes the precipitation of the liquid cosmetic for the multi-layer nano particle for having enclosed natural insoluble drug
Whether
In order to compare and assess the present invention liquid cosmetic precipitation whether, prepared by above-described embodiment 1 to 19
Cosmetics and comparative example 1 to 5 prepared by cosmetics carry out following experiments so as to visually observe its whether occur based on when
Between precipitation.
Specifically, preparing transparent phial (vial) and the embodiment 1 for respectively pouring into 10ml in each phial arrives
The cosmetics prepared by cosmetics and comparative example 1 to 5 prepared by 19, then pour into after distilled water (20ml) is dissolved at once and
To visually observe and the result is shown in following table 2 after 2 months.Especially, the cosmetics prepared by embodiment 3 and
Cosmetics prepared by comparative example 2 shoot photo and with photo illustration in Fig. 2 to Fig. 3 after it have passed through 2 months.
[table 2]
(in above-mentioned table 2, × indicate the situation precipitated, although △ indicates not occur to precipitate opaque feelings
Shape, zero indicates that precipitation and opaque situation occurs.)
Fig. 2 is in order to the liquid for including the multi-layer nano particle for having enclosed natural insoluble drug prepared by embodiment 3
The photo that state cosmetics are packed into transparent phial and are shot whether confirming precipitation after 2 months with naked eyes.
Fig. 3 is in order to the liquid cosmetic for including the particle for having enclosed natural insoluble drug prepared by comparative example 2
The photo for being packed into transparent phial and being shot whether confirming precipitation after 2 months with naked eyes.
As shown in table 2, the liquid cosmetic prepared by above-described embodiment 1 to 19 after preparation at once and after 2 months
The state not precipitated is also at when observation.In contrast to this, prepared by comparative example 1, comparative example 2, comparative example 3 and comparative example 5
Although observation result liquid cosmetic is observed after preparation at once when is the transparent liquid phase not precipitated, after 2 months
Observe the opaque liquid phase precipitated, the liquid cosmetic prepared by comparative example 4 is then observed after preparation impermeable at once
Bright liquid phase then observes the opaque liquid phase precipitated after 2 months.
Moreover, as shown in the photo of Fig. 2 to Fig. 3, the liquid makeup comprising natural polymer prepared by above-described embodiment 3
Product are also the transparent liquid phase not precipitated even across observation result when being observed after 2 months, prepared by above-mentioned comparative example 2 not
Including the liquid cosmetic of natural polymer then observes the opaque liquid phase for being mixed with precipitation after 2 months.
Therefore, cosmetics of the invention are enclosed comprising poloxamer compound, poly- due to above-mentioned natural insoluble drug
The multi-layer nano particle of oxygen ether based compound or polyoxy castor oil based compound and natural polymer and dissolved on aqueous solution,
To learn the sedimentation problem for improving above-mentioned natural insoluble drug.
<Experimental example 2>The size of the time-based multi-layer nano particle for having enclosed natural insoluble drug is analyzed and long-term
Stability assessment
In order to understand the liquid for including the multi-layer nano particle for having enclosed natural insoluble drug prepared by above-described embodiment 3
Prepared by state cosmetics and above-mentioned comparative example 2 comprising enclosed natural insoluble drug particle liquid cosmetic based on
The particle size of time changes, to use dynamic light scattering (DLS；Dynamic light scattering) method analyzer
Device (manufacturer：PhotalOtsuka electronics, model name：ELS-Z it includes envelope) to measure prepared by embodiment 3
Entered the liquid cosmetic of the multi-layer nano particle of natural insoluble drug and prepared by comparative example 2 comprising having enclosed natural difficulty
The particle size of the liquid cosmetic of the particle of soluble drug and its result with graphical representations in Fig. 4 to Fig. 5.
Fig. 4 is the liquefied for including the multi-layer nano particle for having enclosed natural insoluble drug prepared by embodiment 3
Curve graph shown in the time-based particle size variation of cosmetic.
Fig. 5 is the base the liquid cosmetic comprising the particle for having enclosed natural insoluble drug prepared by comparative example 2
The curve graph shown in particle size variation in the time.
Please refer to Fig. 4 to Fig. 5's as a result, the liquid cosmetic comprising natural polymer prepared by embodiment 3 multilayer
Nano-particle maintains a certain size of about 40nm during 0-6 months and does not change in particle size.However,
Although the particle of the liquid cosmetic not comprising natural polymer prepared by comparative example 2 maintains about during 0-1 months
The size of 40nm, but after 1 month size start to increase and in the size for increasing to about 100nm after 6 months.
Therefore, cosmetics of the invention are enclosed comprising poloxamer compound, poly- due to above-mentioned natural insoluble drug
The multi-layer nano particle of oxygen ether based compound or polyoxy castor oil based compound and natural polymer and make particle size it is long-term
A certain size is maintained, to learn the long-term safety improved about form.
<Experimental example 3>Average-size analysis and the long-time stability of the multi-layer nano particle of natural insoluble drug are enclosed
Assessment
It is commented after being analyzed for the multi-layer nano particle average size for having enclosed natural insoluble drug to the present invention
Estimate long-time stability, uses the analytical instrument (manufacturer that can be analyzed from the particle size of 30nm or more：
PhotalOtsuka electronics, model name：ELS-Z) with dynamic light scattering (DLS；Dynamic light
Scattering) method measures being received comprising the multilayer for having enclosed natural insoluble drug prepared by embodiment 3 after six months
The liquid cosmetic of rice corpuscles and the liquid cosmetic for including the particle for having enclosed natural insoluble drug prepared by comparative example 2
Particle distribution map and average-size and its result is shown in Fig. 6 to Fig. 7.
Fig. 6 is the liquid for including the multi-layer nano particle for having enclosed natural insoluble drug shown prepared by embodiment 3
Cosmetics curve graph of the distribution map of multi-layer nano particle and average-size after 6 months.
Fig. 7 is the liquid cosmetic warp comprising the particle for having enclosed natural insoluble drug shown prepared by comparative example 2
The curve graph of the distribution map of particle and average-size after crossing 6 months.
As shown in Figures 6 and 7, the multilayer of the liquid cosmetic comprising natural polymer prepared by above-described embodiment 3 is received
It is 38.1nm that rice corpuscles, which is distributed in about 20nm-180nm ranges and measures the average-size of these particles,.In contrast to this,
The particle of the liquid cosmetic not comprising natural polymer prepared by comparative example 2 be then distributed in about 45nm-315nm ranges and
And the average-size for measuring these particles is 108.9nm.
From the above it is found that the above-mentioned multilayer of the liquid cosmetic comprising natural polymer prepared by embodiment 3 is received
Rice corpuscles average 38.1nm is still maintained after 6 months a certain size.
Therefore, cosmetics of the invention are enclosed comprising poloxamer compound, poly- due to above-mentioned natural insoluble drug
The multi-layer nano particle of oxygen ether based compound or polyoxy castor oil based compound and natural polymer and make particle size it is long-term
The state that mean size is less than 40nm is maintained, to learn the long-term safety improved about form.
<Experimental example 4>Including enclosed the liquid cosmetic of the multi-layer nano particle of natural insoluble drug based on the time
Natural insoluble drug content analysis and long-time stability assessment
In order to understand the liquid cosmetic comprising the multi-layer nano particle for having enclosed natural insoluble drug of the invention
Time-based natural insoluble drug changes of contents, using butanol as solvent and with GC (Gas chromatography, GC
Agilent 6890N) analyzed after its result with graphical representations in Fig. 8.
Fig. 8 be according to lapse of time measure prepared by the embodiment of the present invention 8 comprising having enclosed natural insoluble drug
The curve graph shown after the above-mentioned natural insoluble drug changes of contents of the liquid cosmetic of multi-layer nano particle.
As shown in figure 8, the above-mentioned natural insoluble drug during 0-6 months of the liquid cosmetic prepared by embodiment 8
Content maintains always about 100%.
Therefore, cosmetics of the invention do not occur alternatively maintaining centainly to contain due to the content of above-mentioned natural insoluble drug
It measures and learns the long-time stability improved for physical property.
At the same time, being used as comprising the multi-layer nano particle for having enclosed natural insoluble drug for constituting as previously mentioned is anti-
The cosmetics of rotten substance can be included in the cosmetic composition based on known technology, each ratio of components individually or in a mixed manner
Rate then can be appropriately configured according to its judgement progress by those skilled in the art.
Moreover, the cosmetics of the present invention can be used as the active ingredient of following cosmetics, which being distinguished into
Adornment water, toner, essence dew, emulsion, lotion, creams, moisturizing spraying, makeup remover or facial mask the types such as emulsion.Also that is, it is above-mentioned
The cosmetics of type classify according to dosage form and include the cosmetics of the present invention as active ingredient and can also be comprising for being made
The various carrier components of each dosage form.
Preferably, it is ointment, creams using the cosmetics of the present invention as the dosage form of effect ingredient and prepared cosmetics
Or if gel, above-mentioned carrier components can utilize animal origin, plant fiber, wax, paraffin, starch, tragacanth, cellulose to spread out
More than one substance in biology, polyethylene glycol, silicon, bentonite, silica, talcum or zinc oxide.
Moreover, using the present invention cosmetics as active ingredient and the dosage form of prepared cosmetics be pulvis or spraying
If agent, above-mentioned carrier components can be used a certain in lactose, talcum, silica, aluminium hydroxide, calcium silicates or Silon
A above substance, especially, dosage form be spray if can also use fluorochlorohydrocarbon, propane/butane or dimethyl ether in some with
On propellant.
At the same time, using the cosmetics of the present invention as active ingredient and the dosage form of prepared cosmetics for solution or
If emulsion, above-mentioned carrier components can use solvent, cosolvent or emulsifier.In more detail, above-mentioned carrier components can
To be water, ethyl alcohol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, Ergol, propylene glycol, 1,3- butyl glycols
Some above substance in the aliphatic ester of oil, glycerine aliphatic (acid) ester, polyethylene glycol or sorbitan.
At the same time, using the present invention cosmetics as active ingredient and the dosage form of prepared cosmetics be suspension
If, above-mentioned carrier components can use some above substance in following substance：The liquid of water, ethyl alcohol or propylene glycol etc
Diluent；The suspending agent of ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitol ester etc；Crystallite
Property cellulose；Inclined aluminium hydroxide；Bentonite；Agar or tragacanth.
Moreover, using the cosmetics of the present invention as active ingredient and the dosage form of prepared cosmetics is containing surface-active
If the makeup remover of agent, above-mentioned carrier components can use sulphated fatty alcohol, sulfate fatty alcohol ether, sulfosuccinic acid list
Ester, isethionate, imidazolidine derivatives, methyl tauride, sarcosinate, fatty acid amide ether sulfate, alkyl acyl
Amine glycine betaine, fatty alcohol, fatty glyceride, fatty diglycollic amide, plant oil, flax acid derivative or ethyoxyl are sweet
Some above substance in oil and fat acid esters.
According to the above, the carrier of mentioned kind according to the purposes of prepared cosmetics and can with various groups of composition and division in a proportion and
Cosmetics (active ingredient as the prepared cosmetics plays a role) mixing of the present invention, the preferred combination about this respect
Than can suitably apply well known technology.
It is illustrated previously in conjunction with the preferred embodiment of the present invention, but the present invention is not limited to above-described embodiments, originally
Technical staff in technical field that the present invention belongs to can be real in the range of not departing from the gist of the invention by above-described embodiment
Existing various change.
Claims (11)
1. a kind of comprising having enclosed the cosmetics of the multi-layer nano particle of natural insoluble drug as preservative substance, above-mentioned anti-corrosion
Substance includes the multi-layer nano particle for having enclosed natural insoluble drug, which is characterized in that the multi-layer nano particle includes：
First core, including 1 parts by weight of natural insoluble drug and the glycol based compound 0.5-10 weights that are indicated with following chemical formula 1
Measure part；
Second core includes the poloxamer compound 0.5-50 parts by weight indicated with following chemical formula 2, with 3 table of following chemical formula
The polyoxyether based compound shown or the polyoxy castor oil based compound 0.5-10 parts by weight indicated with following chemical formula 4；And
Third core, including natural polymer 0.1-10 parts by weight,
[chemical formula 1]
Wherein, in above-mentioned chemical formula 1,
R1 is hydrogen or methyl；
R2 is hydrogen or tetrahydrofuran base；And
The integer that n is 1 to 200；
[chemical formula 2]
Wherein, in above-mentioned chemical formula 2,
L, m and p is respectively 1 to 200 integer；
[chemical formula 3]
Wherein, in above-mentioned chemical formula 3,
It is singly-bound or double bond；X, y and z is respectively 1 to 100 integer；And
[chemical formula 4]
Wherein, in above-mentioned chemical formula 4,
It is singly-bound or double bond；
A, a', a ", b, b', b ", c, c' and c " are respectively 1 to 200 integer；And d, d' and d " are respectively 0 to 200 integer.
2. according to claim 1 includes to have enclosed the multi-layer nano particle of natural insoluble drug as preservative substance
Cosmetics, which is characterized in that
Above-mentioned natural insoluble drug is selected from frankincense (mastic), myrrh, flavonoids, propolis, allicin, Glucosamine and Europe rice
One or more of gal aliphatic acid.
3. according to claim 1 includes to have enclosed the multi-layer nano particle of natural insoluble drug as preservative substance
Cosmetics, which is characterized in that
It is selected from one or more of polyethylene glycol, propylene glycol and tetraethylene glycol with the glycol based compound that above-mentioned chemical formula 1 indicates.
4. according to claim 1 includes to have enclosed the multi-layer nano particle of natural insoluble drug as preservative substance
Cosmetics, which is characterized in that
The glycol based compound indicated with above-mentioned chemical formula 1 further mixing selected from Tetrahydrofurfuryl polyethylene glycol ether, polysorbate,
It is used after one or more of -15 hydroxy stearic acid ester of cremophor and polyethylene glycol (Solutol HS 15) substance.
5. according to claim 1 includes to have enclosed the multi-layer nano particle of natural insoluble drug as preservative substance
Cosmetics, which is characterized in that
It is selected from poloxam 68, poloxamer 88, poloxamer 108, pool with the poloxamer compound that above-mentioned chemical formula 2 indicates
Luo Shamu 124, poloxamer 184, poloxamer 185, PLURONICS F87, poloxamer 237, Pluronic/Lutrol F 108 and pool Lip river are husky
One or more of nurse 407.
6. according to claim 1 includes to have enclosed the multi-layer nano particle of natural insoluble drug as preservative substance
Cosmetics, which is characterized in that
It is selected from polyoxyethylene (4) lauryl ether (brij30), polyoxy second with the polyoxyether based compound that above-mentioned chemical formula 3 indicates
Alkene (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 poly-
One or more of ethylene oxide (20) oleyl ether (brij98).
7. according to claim 1 includes to have enclosed the multi-layer nano particle of natural insoluble drug as preservative substance
Cosmetics, which is characterized in that
It is selected from 5 castor oil of polyoxy, 9 castor oil of polyoxy, 15 castor of polyoxy with the polyoxy castor oil based compound that above-mentioned chemical formula 4 indicates
Sesame oil, 35 castor oil of polyoxy, 40 castor oil of polyoxy, 60 castor oil of polyoxy, polyoxy Wart Fix, 200 castor oil of polyoxy, polyoxy
In 40 rilanit specials, 200 rilanit special of 60 rilanit special of polyoxy, 100 rilanit special of polyoxy and polyoxy it is a kind of with
On.
8. according to claim 1 includes to have enclosed the multi-layer nano particle of natural insoluble drug as preservative substance
Cosmetics, which is characterized in that
Above-mentioned natural polymer is selected from alginic acid, chitosan, Arabic gum, glucan, dextrin, gel, polyacrylic acid, general stream Buddhist nun gram
(Pluronic) acid, methylcellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose and carboxymethyl cellulose；And
One or more of its salt.
9. according to claim 1 includes to have enclosed the multi-layer nano particle of natural insoluble drug as preservative substance
Cosmetics, which is characterized in that
In above-mentioned multi-layer nano particle the first core and the second karyomorphism at 0.001-30nm sizes micella.
10. according to claim 1 includes to have enclosed the multi-layer nano particle of natural insoluble drug as preservative substance
Cosmetics, which is characterized in that
Above-mentioned multi-layer nano particle has the particle size of 0.001-40nm.
11. a kind of including the preparation side for having enclosed cosmetics of the multi-layer nano particle of natural insoluble drug as preservative substance
Method, which is characterized in that
Include the following steps：
Step 1, the glycol based compound indicated with following chemical formula 1, the poloxamer chemical combination indicated with following chemical formula 2
Object, the polyoxyether based compound indicated with following chemical formula 3 or the polyoxy castor oil based compound indicated with following chemical formula 4,
And natural insoluble drug is mixed and carries out heating or ultrasonication；And
Step 2, it adds natural polymer in the mixture of above-mentioned steps 1 and is stirred,
[chemical formula 1]
Wherein, in above-mentioned chemical formula 1,
R1 is hydrogen or methyl；
R2 is hydrogen or tetrahydrofuran base；And
The integer that n is 1 to 200；
[chemical formula 2]
Wherein, in above-mentioned chemical formula 2,
L, m and p is respectively 1 to 200 integer；
[chemical formula 3]
Wherein, in above-mentioned chemical formula 3,
It is singly-bound or double bond；
X, y and z is respectively 1 to 100 integer；And
[chemical formula 4]
Wherein, in above-mentioned chemical formula 4,
It is singly-bound or double bond；
A, a', a ", b, b', b ", c, c' and c " are respectively 1 to 200 integer；And
D, d' and d " are respectively 0 to 200 integer.
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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| Publication Number | Publication Date |
|---|---|
| CN108419431A true CN108419431A (en) | 2018-08-17 |
| CN108419431B CN108419431B (en) | 2021-02-12 |
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| CN201680034178.5A Active CN108419431B (en) | 2016-12-05 | 2016-12-05 | Cosmetic containing multilayer nanoparticles encapsulating natural poorly-soluble drug as antiseptic substance and method for producing same |
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| WO (1) | WO2018105756A1 (en) |
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| KR20100025427A (en) * | 2008-08-27 | 2010-03-09 | 한국화학연구원 | Pharmaceutical compositions, formulations and absorption of talniflumate extended release tablets |
| KR20150000337A (en) * | 2013-06-24 | 2015-01-02 | 한국화학연구원 | Liquid formulation having micelles that encapsulate immunosuppressant |
| 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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| KR101025641B1 (en) * | 2008-06-18 | 2011-03-30 | 한국콜마 주식회사 | Self-microemulsified mastic composition and capsule containing the composition |
| KR101601954B1 (en) * | 2014-02-07 | 2016-03-10 | (주)에이씨티 | Method for preparation of poor soluble materials containingnanoparticle for cosmetic composition |
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| KR20100025427A (en) * | 2008-08-27 | 2010-03-09 | 한국화학연구원 | Pharmaceutical compositions, formulations and absorption of talniflumate extended release tablets |
| KR20150000337A (en) * | 2013-06-24 | 2015-01-02 | 한국화학연구원 | Liquid formulation having micelles that encapsulate immunosuppressant |
| 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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