Background technique
Chitosan is to be obtained by shrimp, crab shell through a series of processing, nontoxic, tasteless, is widely used to food, medicine etc.
In industry, chitosan has immunoregulatory activity, can effectively facilitate wound healing.Appropriate shell is such as added in cream kind cosmetics
Glycan can increase the immunity that human body causes infection to bacterium, fungi, hinder opportunistic pathogen growth, not but not draw to damaged skin
Play infection, moreover it is possible to promote its healing, eliminates facial dermatosis, meanwhile, when chitosan is used for make-up and beauty, it is easy to form protection skin
Film, moisture absorption, water retention can make skin become soft, wet, ductility good.In addition, chitosan also can be with formalin
Mixing, prepares the cosmetics containing formalin, and cosmetics obtained have good bactericidal effect.
Salicylic acid, be otherwise known as septichen, is a kind of fat-soluble organic acid.Salicylic acid is widely used, for example,
It can be used as the standard reagent of alkalimetry and iodometric titrationiodimetry titration;Be used as in rubber industry antiscorching agent and production ultraviolet absorbing agent and
Foaming agent;Additive is used as in certain faintly acid electrolyte, it is also possible to make the complexing agent of plating or chemical plating;It can be used as makeup
Savor preservative use;As the raw material of medical industry, it is used to prepare aspirin, sodium salicylate, salicylamide, ethoxybenzamide, water
The drugs such as poplar acid phenenyl ester, Niclosamide;It can be used to reduce the long-term concurrent cardiopathic risk of diabetic in clinical test;
Salicylic acid is widely used in external application and smears in class drug, and salicylic acid is all used in many skin nursing products, can be played soft
The effects of changing cutin, sterilization, treatment acne.But salicylic poorly water-soluble, so that its application effect is restricted, and salicylic acid
Irritation is stronger, cannot directly and skin contact.
γ-aminobutyric acid (γ-aminobutyric acid, abbreviation GABA) is distributed widely in green vegetables, rice, Chinese herbal medicine, beans
In the animal and plant bodies such as category, it is a kind of important inhibitory neurotransmitter, participates in a variety of metabolic activities, it is living with high physiology
Property.In addition to be currently known can reduce blood pressure, improve liver function, prevention of arterial hardening, headstroke, prevention and treatment dreaminess disease, lose
It sleeps, promotes to loosen, pain of releiving, promote compressive resistance, eliminate fatigue, keep mental state gentle outer, cranial nerve cell can also be adjusted
Function has the function that invigorating brain and relieving mental uneasiness, promotes brain blood circulation, and prevention senile dementia and lifestyle disease, also
Active oxygen is removed, prevents blood vessel and cell senescence, and improve the absorptivity of nutritional ingredient, especially hard substance, and keep seeking
Support equilibrium;In addition to this, γ-aminobutyric acid also has the problem of anti-oxidant, anti-aging, maintenance endure external pressure to the fullest extent skin, together
When have the function of releiving pressure, loosen nerve, can permeate rapidly and go deep into skin cuticula, reform microgroove, it is concave-convex for repairing
Mixed and disorderly flesh line has extraordinary effect.
Ionic liquid is to be made of organic cation and inorganic (or organic) anion, be in room temperature (or near room temperature)
The salt of liquid condition, commonly known as ionic liquid at room temperature or room temperature molten salt, thermal stability is good and solvability is strong, together
When can also enhance the physiological activity of ion itself, cause the extensive concern of researcher in recent years.γ-aminobutyric acid is one
The common ionic liquid starting material of kind, if γ-aminobutyric acid can be prepared by alkaloids such as the organic acids such as salicylic acid or matrines
Ionic liquid will be expected to obtain the active material that physiological activity is strong and dissolubility is good.
Therefore, it is expected to enhance salicylic dissolubility if γ-aminobutyric acid and salicylic acid are prepared into ionic liquid, then
Chitosan, which is wrapped in γ-aminobutyric acid salicylic acid ionic liquid, can further decrease irritation caused by salicylic acid.
Summary of the invention
The first technical problem to be solved by the present invention is: providing a kind of dissolubility good and mild to skin chitosan
Wrap up the salicylic preparation method of γ-aminobutyric acid.
Second technical problem to be solved by this invention is: providing a kind of package of chitosan made from above method γ-
Aminobutyric acid salicylic acid.
Third technical problem to be solved by this invention is: providing a kind of above-mentioned chitosan package γ-aminobutyric acid water
The application of poplar acid.
In order to solve above-mentioned first technical problem, the technical solution adopted by the present invention are as follows: a kind of chitosan package γ-ammonia
The salicylic preparation method of base butyric acid, comprising the following steps:
S1, according to solid-to-liquid ratio 1mg:(1~5) ratio of mL, add chitosan into glacial acetic acid solution, chitosan be made
Aqueous solution, wherein the mass percentage concentration of the glacial acetic acid of the glacial acetic acid solution is 1~3%;
S2, under stiring, γ-aminobutyric acid salicylic acid ionic liquid is added dropwise to dropwise in the chitosan aqueous solution,
And chitosan package γ-aminobutyric acid salicylic acid is obtained after standing at room temperature.
Further, the preparation method of the γ-aminobutyric acid salicylic acid ionic liquid, comprising the following steps:
S201, under hypoxemia, normal temperature environment, γ-aminobutyric acid is added into solvent, be made γ-aminobutyric acid solution;
The γ-aminobutyric acid salicylic acid is obtained after adding salicylism reaction in S202, Xiang Suoshu γ-aminobutyric acid solution
Ionic liquid.
Further, the solvent is water.
Further, in the step S202, γ-aminobutyric acid and salicylic molar ratio are 1:(0.8~1.2);It is excellent
Selection of land, the molar ratio are 1:(0.9~1.1).
Further, in the step S202, the reaction temperature after adding salicylic acid is 15~30 DEG C;Preferably, described
Reaction temperature is 20~25 DEG C;Most preferably 20 DEG C.
Further, in the step S202, the reaction time is 9~16h, preferably 12~13h.
The beneficial effects of the present invention are: chitosan made from the present invention program wraps up γ-aminobutyric acid salicylic acid in oil
Good dissolubility is all had in system or water solvent;Irritation caused by salicylic acid can be reduced by chitosan package, together
When can also play the role of sustained release so that effect is more longlasting, meanwhile, chitosan package γ-aminobutyric acid salicylic acid obtained is same
When the physiological action with chitosan, salicylic acid and γ-aminobutyric acid, all have good application in cosmetics and field of medicaments
Prospect;Solvent used in the present invention program is usual vehicle, and reaction condition is mild and easy to operate, and synthesis step is succinct,
Convenient post-treatment, chitosan package γ-aminobutyric acid salicylic acid encapsulation ratio obtained are high.
In order to solve above-mentioned second technical problem, the technical solution adopted by the present invention are as follows: one kind passes through above method system
The chitosan obtained wraps up γ-aminobutyric acid salicylic acid.
In order to solve above-mentioned third technical problem, the technical solution adopted by the present invention are as follows: a kind of above-mentioned chitosan package
Application of the γ-aminobutyric acid salicylic acid in cosmetics.
Further, the raw material for preparing of the cosmetics is grouped as by the group of following weight percent:
Deionized water: surplus
AVC:0.1-0.3wt%
HA:0.05-0.2wt%
PEG-26 glycerin ether: 1-5wt%
Glycerol: 1-5wt%
Glycine betaine: 1-8wt%
Dipropylene glycol: 2-15wt%
WSK-1:1-6wt%
Chitosan wraps up γ-aminobutyric acid salicylic acid ionic liquid: 1-10wt%
Niacinamide: 0.5-2wt%
1,2- hexylene glycol: 0.2-1wt%
A631:0.1-1wt%
ENNACOMPLEX 261:1-5wt%
PEG-60 rilanit special: 0.01-0.05wt%;
Wherein, in the ENNACOMPLEX 261 containing hamamelis leaf extract, European horse-chestnut seed extract and
Arnica extract.
The technical solution adopted by the present invention further include: a kind of above-mentioned chitosan package γ-aminobutyric acid salicylic acid is being made up
Application in the preparation of product.
Further, it is described application the following steps are included:
1) in deionized water by AVC and HA complete wetting, and homogeneous to disperse completely, add PEG-26 glycerin ether,
Glycerol, glycine betaine, dipropylene glycol are warming up to 80~90 DEG C, middling speed homogeneous 3-5min, 20~40min of insulated and stirred;
2) step 1) gains are cooled to 35~45 DEG C, WSK-1 are added under stiring, chitosan wraps up gamma-amino fourth
Sour water poplar acid ion liquid, niacinamide, 1,2- hexylene glycol, A631 and 261;
3) by PEG-60 rilanit special, heating stirring and is added to step 2) and is made to transparent under 35~45 DEG C of environment
Mixture in, cooling i.e. obtain containing chitosan package the salicylic cosmetics of γ-aminobutyric acid.
Further, the mixing speed of the middling speed homogeneous is 3000~5000rpm.
The beneficial effects of the present invention are: there is good antioxygen added with chitosan package γ-aminobutyric acid salicylic acid
Change property, lasting moisture retention, and it is mild to skin, non-stimulated or irritation is small.
Specific embodiment
To explain the technical content, the achieved purpose and the effect of the present invention in detail, it is explained below in conjunction with embodiment.
A kind of embodiment of the present invention 1 are as follows: salicylic preparation method of chitosan γ-aminobutyric acid, comprising the following steps:
(1) preparation of γ-aminobutyric acid salicylic acid ionic liquid: package weighs 1.03g γ-aminobutyric acid (10mmol),
20mL deionized water is added, is passed through N2(inert gas can also be used) makes reaction whole process in N2It is carried out under atmosphere, by reaction vessel
Be placed in room temperature water-bath, reaction temperature made to be maintained at 25 DEG C, by reaction vessel shading treatment, guarantee reaction under the conditions of being protected from light into
Row.It weighs 1.38g salicylic acid (10mmol), γ-aminobutyric acid is 1:1 with salicylic molar ratio, a small amount of repeatedly quickly (usual
It is advisable with being added in 3~5 2min, in the present embodiment, divides 4 times and salicylic acid is added in solution) it is added in reaction vessel, it protects
Demonstrate,prove N2Atmosphere and reaction real time temperature are 0-5 DEG C.After addition, ice salt bath is removed, in the case where room temperature is protected from light inert gas conditions
React 12h.
(2) chitosan package γ-aminobutyric acid bigcatkin willow acid preparation process is as follows:
According to the ratio of solid-to-liquid ratio 1mg:4mL, the ice second that mass concentration is 1% is added chitosan under magnetic stirring
In acid solution, chitosan aqueous solution is obtained.It is water-soluble that γ-aminobutyric acid salicylic acid is added dropwise to chitosan dropwise under magnetic stirring
In liquid, mixing speed 700r/min, and stand at room temperature obtain for 24 hours chitosan package γ-aminobutyric acid salicylic acid from
Sub- liquid.The encapsulation rate for measuring sample is 85.12%.
The embodiment of the present invention 2 are as follows: one kind wraps up the salicylic cosmetics of γ-aminobutyric acid containing chitosan, and preparation is former
Expect composed of the following components: deionized water: 76.25wt%;AVC:0.13wt%;HA (middle molecule): 0.05wt%;PEG-26 is sweet
Oily ether: 1.2wt%;Glycerol: 2.3wt%;Glycine betaine: 3.2wt%;Dipropylene glycol: 4.5wt%;WSK-1:3.3wt%;Shell is poly-
Sugar package γ-aminobutyric acid salicylic acid ionic liquid: 4wt%;Niacinamide: 0.78wt%;1,2- hexylene glycol: 0.42wt%;
A631:0.24wt%;261:3.6wt%;RH-60:0.03wt%.
Specific preparation process is as follows:
1) in deionized water by AVC and HA (middle molecule) complete wetting, and homogenous disperse is complete in homogenizer, homogeneous
Speed of agitator is 3000r/min, adds PEG-26 glycerin ether, glycerol, glycine betaine, dipropylene glycol, is warming up to 85 DEG C, middling speed is equal
Matter 3min, homogeneous mixing speed are 4000r/min and insulated and stirred 30min.
2) step 1 gains are cooled to 40 DEG C, WSK-1 are added in magnetic agitation, chitosan wraps up gamma-amino
Butyric acid salicylic acid ionic liquid, niacinamide, 1,2- hexylene glycol, A631,261.
3) by RH-60, heating stirring and is added into step 2 mixture to transparent under 40 DEG C of environment, and cooling obtains
Chitosan wraps up γ-aminobutyric acid salicylization cosmetic.
The embodiment of the present invention 3 are as follows: one kind wraps up the salicylic cosmetics of γ-aminobutyric acid containing chitosan, and preparation is former
Expect composed of the following components: deionized water: 64.38wt%;AVC:0.22wt%;Molecule in HA: 0.14wt%;PEG-26 glycerol
Ether: 2.1wt%;Glycerol: 3.5wt%;Glycine betaine: 4.5wt%;Dipropylene glycol: 8.2wt%;WSK-1:4.7wt%;Chitosan
Wrap up γ-aminobutyric acid salicylic acid ionic liquid: 6wt%;Niacinamide: 1.1wt%;1,2- hexylene glycol: 0.54wt%;A631:
0.6wt%;261:4wt%;RH-60:0.02wt%.
Specific preparation process is as follows:
1) homogenous disperse is complete in deionized water by molecule complete wetting in AVC and HA, and in homogenizer, and homogeneous stirs
Mixing revolving speed is 4000r/min, adds PEG-26 glycerin ether, glycerol, glycine betaine, dipropylene glycol, is warming up to 85 DEG C, middling speed homogeneous
3min, homogeneous mixing speed 5000r/min and insulated and stirred 30min.
2) step 1 gains are cooled to 40 DEG C, WSK-1 are added in magnetic agitation, chitosan wraps up gamma-amino
Butyric acid salicylic acid ionic liquid, niacinamide, 1,2- hexylene glycol, A631,261.
3) by RH-60, heating stirring and is added into step 2 mixture to transparent under 40 DEG C of environment, and cooling obtains
Chitosan wraps up γ-aminobutyric acid salicylization cosmetic.
The embodiment of the present invention 4 are as follows: one kind wraps up the salicylic cosmetics of γ-aminobutyric acid containing chitosan, and preparation is former
Expect composed of the following components: deionized water: 52.64wt%;AVC:3wt%;Molecule in HA: 0.18wt%;PEG-26 glycerin ether:
4.4wt%;Glycerol: 4.2wt%;Glycine betaine: 7.6wt%;Dipropylene glycol: 11wt%;WSK-1:5wt%;Chitosan wraps up γ-
Aminobutyric acid salicylic acid ionic liquid: 7.1wt%;Niacinamide: 1.6wt%;1,2- hexylene glycol: 0.67wt%;A631:
0.58wt%;261:2wt%;RH-60:0.03wt%.
Specific preparation process is as follows:
1) homogenous disperse is complete in deionized water by molecule complete wetting in AVC and HA, and in homogenizer, and homogeneous stirs
Mixing revolving speed is 4000r/min, adds PEG-26 glycerin ether, glycerol, glycine betaine, dipropylene glycol, is warming up to 85 DEG C, middling speed homogeneous
3min, homogeneous mixing speed 6000r/min and insulated and stirred 30min.
2) step 1 gains are cooled to 40 DEG C, WSK-1 are added in magnetic agitation, chitosan wraps up gamma-amino
Butyric acid salicylic acid ionic liquid, niacinamide, 1,2- hexylene glycol, A631,261.
3) by RH-60, heating stirring and is added into step 2 mixture to transparent under 40 DEG C of environment, and cooling obtains
Chitosan wraps up γ-aminobutyric acid salicylization cosmetic.
Comparative example 1:
Cosmetics preparation step is same as Example 2, " chitosan wraps up γ-aminobutyric acid salicylic acid ionic liquid:
4wt% " is changed to " γ-aminobutyric acid salicylic acid ionic liquid: 4wt% ".
Comparative example 2:
Cosmetics preparation step is same as Example 2, " chitosan wraps up γ-aminobutyric acid salicylic acid ionic liquid:
4wt% " is changed to " chitosan: 4wt% ".
Cosmetics made from above-described embodiment 2~4 and comparative example 1~2 are taken to carry out antioxygenic property, irritation or moisturizing effect
The various aspects such as fruit compare.
1) inoxidizability is tested:
Cosmetics made from Example 2~4 and reference examples 1 carry out the test of DPPH free radical scavenging activity, and (operating procedure is pressed
According to routine operation well known in the art), the results are shown in Table 1:
Influence of 1 different formulations of table to DPPH free radical scavenging activity
From table 1 it follows that by chitosan package γ-aminobutyric acid salicylization cosmetic ratio without chitosan packet
The cosmetics wrapped up in have higher DPPH free radical scavenging activity (being promoted to 1.5 times or more), the gamma-amino wrapped up by chitosan
The salicylic inoxidizability of butyric acid is remarkably reinforced.
2) irritation is tested:
By analyzing IL-1 α, LTB4 or the PGE2 that are discharged by Normal human epidermal's horn cell (NHEK), cosmetics are evaluated
To the effect of the inhibition of the reaction of the shallow-layer epithelial cell of board inflammatory conditions.Cell is the horn cell system (HL60) in people source,
By the cell the penicillin of the L-Glutamine, 50U/mL that are supplemented with 2mmol, the streptomysin of 50 μ g/mL and 10% tire
It is cultivated in RPMI 1640 (Life Technologies) culture medium of cow's serum (FCS), which operates at 37 DEG C and 5%
CO2Under conditions of carry out.
It, will be thin in the presence of phorbol exters and calcium ion carrier A 23187 (Sigma number C752) for IL-1 α
Born of the same parents' preincubation 24 hours.
For LTB4, in the presence of arachidonic acid and calcium ion carrier A 23187 (Sigma number C752),
By cell preincubation 24 hours.
For PEG2, in the presence of phorbol exters, by cell preincubation 24 hours.
With identical but containing the cosmetics for being tested (embodiment 2~4 and reference examples 1) cultures after culture medium culture
Base replacement.
At the end of the new incubation period (15min, 37 DEG C), supernatant is collected and in discharged into culture medium
The amount of IL-1 α, LTB4 or PGE2 carry out elisa assay (R and d system kit, number DE0275).
For each test, the control of cosmetics not to be tested is carried out, test result is as follows shown in table 2:
2 irritation test result table of table
|
IL-1α |
LTB4 |
PGE2 |
Embodiment 2 |
- 22% |
- 26% |
- 40% |
Embodiment 3 |
- 23% |
- 20% |
- 44% |
Embodiment 4 |
- 17% |
- 30% |
- 50% |
Comparative example 1 |
15% |
12% |
18% |
Data in table 2 are relative on control IL-1 α, the LTB4 of cosmetics not to be tested or the yield of PGE2
Increment rate or slip.
Under identical experiment condition, containing chitosan package γ-aminobutyric acid salicylic acid ionic liquid cause IL-1 α,
The yield of LTB4 or PGE2 is decreased obviously, and the γ-aminobutyric acid salicylic acid ionic liquid not being wrapped then has in various degree
Growth, it is indicated above that the γ-aminobutyric acid salicylic acid ionic liquid irritation after the present invention program wraps up drops significantly
It is low.
3) moistening effect is tested:
5 volunteers are chosen to test, the age be 30~50 women, first using can how Asia SC-D8F-03 type skin
The skin of face moisture value of moisture tester measurement volunteer utilizes SPSS10.0 using the cosmetics of embodiment 2, comparative example 2
Software statistics analyze data, obtain moisture of skin average value (P < 0.05), volunteer are then in same working environment, relatively
Humidity is 20%, in the environment that temperature is 28 DEG C;Respectively at initially, for 24 hours with 48h when measurement test group and control group volunteer
Skin of face moisture value, as shown in table 3.
3 moistening effect test result table of table
As can be seen that being enclosed with the chitosan of γ-aminobutyric acid salicylic acid ionic liquid compared to simple from upper table 3
Chitosan, more preferably, and after 48h, moisture retention rate is substantially better than uses simple chitosan to moistening effect.
In conclusion being wrapped up γ-aminobutyric acid salicylic acid ionic liquid by chitosan, it is added in cosmetics
Cosmetics obtained can be made all to be increased dramatically in various physiological activity such as moisturizing, anti-oxidant, and the present invention is real
It is smaller to the irritation of skin to apply cosmetics made from a scheme.
The above description is only an embodiment of the present invention, is not intended to limit the scope of the invention, all to utilize this hair
Equivalents made by bright description are applied directly or indirectly in relevant technical field, are similarly included in this hair
In bright scope of patent protection.