CN110507551A - The preparation method of the rush infiltration re-surface intensive wrinkle correct preparation of acetyl-containing hexapeptide -8 - Google Patents
The preparation method of the rush infiltration re-surface intensive wrinkle correct preparation of acetyl-containing hexapeptide -8 Download PDFInfo
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Abstract
The invention discloses a kind of preparation methods of the rush infiltration re-surface intensive wrinkle correct preparation of acetyl-containing hexapeptide -8; ingredient is by carbomer U2020,1; 3- butanediol, glycerol, Sodium Hyaluronate, methyl polyethers -10, polyvinyl alcohol, disodium ethylene diamine tetraacetate, niacinamide, aminomethyl propanol, 1,2- hexylene glycol, hydroxyapatite, chemical enhancers, Argireline solution or the acetyl group hexapeptide for the liposomal being prepared using Argireline solution, water are formed.The re-surface intensive wrinkle correct preparation that the present invention is prepared can further promote the Cutaneous permeation of Argireline.
Description
Technical field
The invention belongs to cosmetics essence fields, and in particular to one kind is adopted using Argireline as principle active component
With the preparation method for the re-surface intensive wrinkle correct preparation that permeation enhancers pentanediol, EPDM147 and liposomal promote to seep.
Background technique
Esthetics polypeptide has high activity as one kind, has natural availability, selectively acting mode and low side effect
The active constituent of incidence is effective against the aging of skin, and the use in cosmetics is always in steady-state growth.
A kind of ingredient of the Argireline as famous anti-aging product, is mainly used for desalinating expression in cosmetics
Line.It belongs to neurotransmitter peptide for inhibiting again, by inhibiting the release of neurotransmitter acetylcholine, to reduce the contraction of muscle,
To reach the generation for reducing dynamic line, expression line.It has the mechanism of action similar with botulic neurotoxin, can mould
The N-terminal structure of imitative corpusculum related protein, competes its position in SNARE compound with corpusculum related protein, to adjust
The formation of SNARE compound reduces the release of acetylcholine, achievees the effect that relax one's muscles.With botulic neurotoxin phase
Than Argireline can interfere the formation and stability of compound, will not generate irreversible destruction, and show its pole
The huge advantage of low toxicity (2000mg/kg), it is highly-safe, it can use daily, therefore its star for becoming anti-wrinkle product
Ingredient.
It is useful effect in skin, Argireline must reach target position with enough concentration, and skin itself
Sizable barrier characteristics limit its infiltration in skin, and the functioning efficiency that polypeptide reaches skin targets position reduces.For
Polypeptide is improved to the repairing effect of skin, has studied the penetration that a variety of effective ways pass through skin to reinforce polypeptide, such as
The saturating method of chemical enhancement, liposomal method, physical technique method etc..
The common strategy of the saturating method of chemical enhancement is optimization of C/C composites, increases the lipophilicity of peptide in conjunction with polypeptide and chemistry or raw is added
Object dressing agent, to reduce stratum corneum barrier function.Ideal penetrating agent should meet the following conditions: nontoxic, no sensitization；Have fast
The effect of speed, duration are predictable；One-way flow；It is compatible with auxiliary material and preparation；Its attribute meets the requirement of cosmetic material.
Polypeptide is encapsulated in liposomal delivery system by liposomal method.Polypeptide transmits Shi Qijie by liposomal
Structure and activity are protected well, stability improve, Increased Plasma Half-life, into deep skin after can achieve slow release
Effect.Using liposome as the advantages of transdermal carrier has: by changing the intercellular lipid in skin layer, enhancing as infiltration
Agent plays a role；As lasting and slow release warehouse；With making adjustments the speed limit envelope barrier of systemic Absorption, thus can provide by
The transdermal delivery system of control.Cation lipid forms double-layer structure in aqueous system, hydrophobic lipid tail portion is embedded to internal.
These double-deck curvature form spherical structure, wherein inside and outside space retains water, and double-layer of lipoid boundary has hydrophobicity.
Traditional method for preparing lipidosome mainly has film dispersion method, alcohol injection, reverse evaporation etc., preparation flow
Phosphatide membrane material first substantially is dissolved with organic solvents such as ethyl alcohol, phospholipid bilayer tunic is obtained, film is then subjected to hydration process,
Organic solvent is removed finally by modes such as rotary evaporations, to obtain the different liposome suspension of particle size.
Summary of the invention
The technical problem to be solved in the present invention is to provide the rush of Argireline to permeate re-surface intensive wrinkle correct preparation, passes through addition
The mode of permeation enhancers pentanediol, EPDM147 and liposomal increases the percutaneous permeability of Argireline, improves it
In the action activity of deep skin.
In order to solve the above-mentioned technical problem, the preparation method of the rush infiltration re-surface intensive wrinkle correct preparation of acetyl-containing hexapeptide -8, with
Lower step:
1), ingredient:
100 parts of raw materials consist of the following compositions:
0.015~0.025 part of carbomer U2020 (difficult soluble macromolecular substance, that is, card wave U2020), 1,3-BDO
2.5~3.5 parts, 3.5~4.5 parts of glycerol, 0.015~0.025 part of Sodium Hyaluronate, methyl polyethers -10 2.5~3.5
Part, 1.5~2.5 parts of polyvinyl alcohol, 0.08~0.12 part of disodium ethylene diamine tetraacetate, 0.010~0.014 part of niacinamide, ammonia first
0.4~0.6 part of base propyl alcohol, 0.4~0.6 part of 1,2- hexylene glycol, 0.4~0.6 part of hydroxyapatite, 1~6 part of chemical enhancers,
The second of 1~5 part of Argireline solution or the liposomal being prepared using 1~5 part of Argireline solution
Acyl group hexapeptide (that is, liposome suspension of cladding Argireline), surplus is water；
The concentration of Argireline is (1000 ± 100) ppm in the Argireline solution；
Above-mentioned part is parts by weight；
2), carbomer U2020 is added to uniform stirring (stirring to card in the mixed liquor of 1,3 butylene glycol and glycerol composition
Wave nurse U2020 is without agglomeration)；
3), Sodium Hyaluronate, methyl polyethers -10, polyvinyl alcohol, disodium ethylene diamine tetraacetate are dissolved in the water,
And with above-mentioned steps 2) gains are uniformly mixed, be heated to (80 ± 5) DEG C again uniform stirring mixing (20 ± 5) minute；
4), by above-mentioned steps 3) mixed gains are cooled to (70 ± 5) DEG C, niacinamide is added；Continue cool to (60
± 5) aminomethyl propanol, 1.2- hexylene glycol, hydroxyapatite and the saturating agent of chemical enhancement DEG C, is added；(45 ± 5) DEG C are cooled to,
The acetyl group hexapeptide of Argireline aqueous solution or the liposomal being prepared using Argireline solution is added,
After mixing evenly, essence preparation is obtained.
The improvement of the preparation method of rush infiltration re-surface intensive wrinkle correct preparation as acetyl-containing hexapeptide -8 of the invention: chemistry promotees
Penetration enhancer is at least one of pentanediol, EPDM147.
The further improvement of the preparation method of rush infiltration re-surface intensive wrinkle correct preparation as acetyl-containing hexapeptide -8 of the invention,
100 parts of raw materials consist of the following compositions:
0.02 part of carbomer U2020,3 parts of 1,3 butylene glycol, 4 parts of glycerol, 0.02 part of Sodium Hyaluronate, methyl are poly-
3 parts of ether -10,2 parts of polyvinyl alcohol, 0.1 part of disodium ethylene diamine tetraacetate, 0.012 part of niacinamide, 0.5 part of aminomethyl propanol, 1,
0.5 part of 2- hexylene glycol, 0.5 part of hydroxyapatite, 1~6 part of chemical enhancers, 1~5 part of Argireline solution or utilize 1
The acetyl group hexapeptide for the liposomal that~5 parts of Argireline solution is prepared, surplus are water.
The further improvement of the preparation method of rush infiltration re-surface intensive wrinkle correct preparation as acetyl-containing hexapeptide -8 of the invention,
The preparation method of the acetyl group hexapeptide of liposomal the following steps are included:
1., according to Argireline solution: total rouge material (lecithin+cholesterol)=3:(10 ± 1), cholesterol: lecithin
Rouge=1:(6 ± 1), emulsifier: total rouge material=1:(30 ± 3), lecithin: ethyl alcohol=1:(20 ± 2) mass ratio, first weigh ovum
Phosphatide, cholesterol, ethyl alcohol and emulsifier are mixed to form mixed liquor；
Total rouge material is made of lecithin and cholesterol；
2., first mixed liquor is evaporated under reduced pressure to removing ethyl alcohol, the mixing of Argireline solution is then added, obtains rouge
The acetyl group hexapeptide of plastid cladding --- the liposome suspension of cladding Argireline.
The further improvement of the preparation method of rush infiltration re-surface intensive wrinkle correct preparation as acetyl-containing hexapeptide -8 of the invention,
The emulsifier is polysorbas20.
The further improvement of the preparation method of rush infiltration re-surface intensive wrinkle correct preparation as acetyl-containing hexapeptide -8 of the invention,
The step 2. in, be added Argireline solution after prior to 50~60 DEG C rotary evaporation 4~6 minutes, then at 22~28 DEG C
Ultrasonic (15 ± 5) minute.
The method that the present invention is combined using chemical enhancers and liposomal prepares the rush infiltration of Argireline
Re-surface intensive wrinkle correct.This essence preparation in addition to the active, the cosmetic skin raw material based on the raw material used, including solvent, protect
Humectant, preservative, thickener etc., selected raw material are safe and non-stimulating property raw material, and additive amount recommends additive amount range in raw material
It is interior.
The liposome suspension of Argireline is coated obtained by the present invention (that is, utilizing Argireline solution
The acetyl group hexapeptide for the liposomal being prepared) it is centrifuged under the conditions of 2000rpm/min, 30min and does not occur lamination.
Its shelf-stability under the conditions of 4 DEG C is preferable.
The present invention uses the saturating agent of chemical enhancement for pentanediol and EPDM147.Pentanediol contains hydrophilic and lipophilic group simultaneously,
It can be improved the transparency of system in cosmetics essence preparation, and since it is with amphiphilic, help to improve active constituent
Permeability in skin.EPDM147 has effects that moisturizing and cutin-softening, reduces its barrier ability and promotes active constituent
Infiltration.
The present invention includes the acetyl group hexapeptide preparation of liposomal, and by using chemical enhancers and liposomal
The method combined is successfully prepared the rush that Argireline is main active and permeates re-surface intensive wrinkle correct preparation, can be improved
Action activity of the Argireline in deep skin.
The present invention provides a kind of preparation methods of the rush infiltration re-surface intensive wrinkle correct of Argireline.Promote infiltration by addition
The mode of agent pentanediol, EPDM147 and liposomal increases the percutaneous permeability of Argireline, improves it in skin
The action activity of deep layer.Saturating agent pentanediol of the chemical enhancement that the present invention uses etc. have it is amphiphilic, it is transparent to help to improve system
Degree and active constituent permeability.And liposome is as transdermal carrier, has the advantages that controllable, sustained release, stable.
The method that the present invention is combined by using the saturating agent of chemical enhancement and liposomal, by the acetyl of liposomal
Base hexapeptide is added in the system containing permeation enhancers.Compared with simple lipid body cladding process, it can further promote acetyl group six
The Cutaneous permeation of peptide -8 is conducive to it and is absorbed into skin and is discharged with depot forms, improves its distribution in skin.
Specific embodiment
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention
Rather than it limits the scope of the invention.In addition, it should also be understood that, after reading the content taught by the present invention, those skilled in the art
Member can make various changes or modifications the present invention, and such equivalent forms equally fall within the application the appended claims and limited
Range.
The preparation method of example 1, the acetyl group hexapeptide of liposomal:
1), according to Argireline solution: total rouge material (lecithin+cholesterol)=3:10, cholesterol: lecithin=1:
6, emulsifier (polysorbas20): total rouge material=1:30, lecithin: ethyl alcohol=1:20 mass ratio, first weigh lecithin, cholesterol,
Ethyl alcohol and polysorbas20, are placed in a beaker, and are uniformly mixed, until obtaining the solution of uniform system.
The concentration of Argireline is 1000ppm in the Argireline solution；
Cholesterol, lecithin are conventional known substance, such as cholesterol is CAS:57-88-5；
2) conventional Ultrasound about 15 minutes in supersonic wave cleaning machine, are placed the beaker, keep system dispersedly more uniform.Then
Mixed liquor is depressurized to (pressure of 0.1Mpa) to evaporate about 15 minutes under the conditions of 60 DEG C, to remove ethyl alcohol.When shape in walls of beaker
When at one layer of uniform film, Argireline solution (containing concentration 1000ppm Argireline) is poured into flask, after
Continuous rotary evaporation (55 DEG C) about 5 minutes, form apparent Liposomal suspensions.By Liposomal suspensions water-bath (25 DEG C) conventional Ultrasound 15
Minute is to get the acetyl group hexapeptide for arriving liposomal --- the liposome suspension of cladding Argireline.
The acetyl group hexapeptide of liposomal used in following example 1 1~14 is to utilize 3g Argireline
The acetyl group hexapeptide for the liposomal that solution is prepared according to above-mentioned 1 the method for example --- cladding Argireline
Liposome suspension.
Embodiment 1,
100g raw material is by following weight at being grouped as: 0.02g carbomer U2020,3g 1,3 butylene glycol, 4g glycerol,
0.02g Sodium Hyaluronate, 3g methyl polyethers -10,2g polyvinyl alcohol, 0.1g disodium ethylene diamine tetraacetate, 0.012g nicotinoyl
Amine, 0.5g aminomethyl propanol, 0.5g 1,2- hexylene glycol, 0.5g hydroxyapatite, 1g Argireline solution (contain
1000ppm Argireline), surplus is water (that is, the dosage of water is 85.348g)；
Preparation method is specific as follows:
1) 0.02g carbomer U2020, is weighed, is placed in 3g 1,3-BDO and 4g glycerol and dissolves, be evenly stirred until nothing
Agglomeration.
2) 0.02g Sodium Hyaluronate, 3g methyl polyethers -10,2g polyvinyl alcohol and 0.1g ethylenediamine tetra-acetic acid, are weighed
Disodium is dissolved in 85.348g water, and step 1) gains are added after mixing, is heated to 80 DEG C 20 points of uniform stirring mixing again
Clock (ensures without agglomeration)；
3) step 2) gains, are cooled to 70 DEG C, 0.012g niacinamide is added, when continuing cool to 60 DEG C, are added
0.5g aminomethyl propanol, 0.5g 1,2- hexylene glycol and 0.5g hydroxyapatite；≤ 45 DEG C are continued cool to, 1g acetyl group is added
- 8 solution of hexapeptide (contains 1000ppm Argireline), obtains essence preparation after mixing evenly.
Embodiment 2,
1) 0.02g carbomer U2020, is weighed, is placed in 3g 1,3-BDO and 4g glycerol and dissolves, be evenly stirred until nothing
Agglomeration.
2) 0.02g Sodium Hyaluronate, 3g methyl polyethers -10,2g polyvinyl alcohol and 0.1g ethylenediamine tetra-acetic acid, are weighed
Disodium is dissolved in 83.348g water, and step 1) gains are added after mixing, is heated to 80 DEG C 20 points of uniform stirring mixing again
Clock (ensures without agglomeration)；
3) step 2) gains, are cooled to 70 DEG C, 0.012g niacinamide is added.When continuing cool to 60 DEG C, it is added
0.5g aminomethyl propanol, 0.5g 1,2- hexylene glycol and 0.5g hydroxyapatite.When continuing cool to 45 DEG C or less, 3g second is added
- 8 solution of acyl group hexapeptide (contains 1000ppm Argireline), obtains essence preparation after mixing evenly.
Embodiment 3,
1) 0.02g carbomer U2020, is weighed, is placed in 3g 1,3-BDO and 4g glycerol and dissolves, be evenly stirred until nothing
Agglomeration.
2) 0.02g Sodium Hyaluronate, 3g methyl polyethers -10,2g polyvinyl alcohol and 0.1g ethylenediamine tetra-acetic acid, are weighed
Disodium is dissolved in 81.348g water, and step 1) gains are added after mixing, is heated to 80 DEG C 20 points of uniform stirring mixing again
Clock (ensures without agglomeration)；
3) step 2) gains, are cooled to 70 DEG C, 0.012g niacinamide is added.When continuing cool to 60 DEG C, it is added
0.5g aminomethyl propanol, 0.5g 1,2- hexylene glycol and 0.5g hydroxyapatite.When continuing cool to 45 DEG C or less, 5g second is added
- 8 solution of acyl group hexapeptide (contains 1000ppm Argireline), obtains essence preparation after mixing evenly.
Embodiment 4
1) 0.02g carbomer U2020, is weighed, is placed in 3g 1,3-BDO and 4g glycerol and dissolves, be evenly stirred until nothing
Agglomeration.
2) 0.02g Sodium Hyaluronate, 3g methyl polyethers -10,2g polyvinyl alcohol and 0.1g ethylenediamine tetra-acetic acid, are weighed
Disodium is dissolved in 82.348g water, and step 1) gains are added after mixing, is heated to 80 DEG C 20 points of uniform stirring mixing again
Clock (ensures without agglomeration)；
3) step 2) gains, are cooled to 70 DEG C, 0.012g niacinamide is added, when continuing cool to 60 DEG C, are added
0.5g aminomethyl propanol, 0.5g 1,2- hexylene glycol, 0.5g hydroxyapatite and 1g chemical enhancers pentanediol.Continue to cool down
It when to 45 DEG C or less, is added 3g Argireline solution (contain 1000ppm Argireline), is after mixing evenly to obtain
Essence preparation.
Embodiment 5
1) 0.02g carbomer U2020, is weighed, is placed in 3g 1,3-BDO and 4g glycerol and dissolves, be evenly stirred until nothing
Agglomeration.
2) 0.02g Sodium Hyaluronate, 3g methyl polyethers -10,2g polyvinyl alcohol and 0.1g ethylenediamine tetra-acetic acid, are weighed
Disodium is dissolved in 80.348g water, and step 1) gains are added after mixing, is heated to 80 DEG C 20 points of uniform stirring mixing again
Clock (ensures without agglomeration)；
3) step 2) gains, are cooled to 70 DEG C, 0.012g niacinamide is added；When continuing cool to 60 DEG C, it is added
0.5g aminomethyl propanol, 0.5g 1,2- hexylene glycol, 0.5g hydroxyapatite and 3g chemical enhancers pentanediol.Continue to cool down
It when to 45 DEG C or less, is added 3g Argireline solution (contain 1000ppm Argireline), is after mixing evenly to obtain
Essence preparation.
Embodiment 6
1) 0.02g carbomer U2020, is weighed, is placed in 3g 1,3-BDO and 4g glycerol and dissolves, be evenly stirred until nothing
Agglomeration.
2) 0.02g Sodium Hyaluronate, 3g methyl polyethers -10,2g polyvinyl alcohol and 0.1g ethylenediamine tetra-acetic acid, are weighed
Disodium is dissolved in 78.348g water, and step 1) gains are added after mixing, is heated to 80 DEG C 20 points of uniform stirring mixing again
Clock (ensures without agglomeration)；
3) step 2) gains, are cooled to 70 DEG C, 0.012g niacinamide is added.When continuing cool to 60 DEG C, it is added
0.5g aminomethyl propanol, 0.5g 1,2- hexylene glycol, 0.5g hydroxyapatite and 5g chemical enhancers pentanediol.Continue to cool down
It when to 45 DEG C or less, is added 3g Argireline solution (contain 1000ppm Argireline), is after mixing evenly to obtain
Essence preparation.
Embodiment 7
1) 0.02g carbomer U2020, is weighed, is placed in 3g 1,3-BDO and 4g glycerol and dissolves, be evenly stirred until nothing
Agglomeration.
2) 0.02g Sodium Hyaluronate, 3g methyl polyethers -10,2g polyvinyl alcohol and 0.1g ethylenediamine tetra-acetic acid, are weighed
Disodium is dissolved in 82.348g water, and step 1) gains are added after mixing, is heated to 80 DEG C 20 points of uniform stirring mixing again
Clock (ensures without agglomeration)；
3) step 2) gains, are cooled to 70 DEG C, 0.012g niacinamide is added.When continuing cool to 60 DEG C, it is added
0.5g aminomethyl propanol, 0.5g 1,2- hexylene glycol, 0.5g hydroxyapatite and 1g chemical enhancers EPDM147.Continue to cool down
It when to 45 DEG C or less, is added 3g Argireline solution (contain 1000ppm Argireline), is after mixing evenly to obtain
Essence preparation.
Embodiment 8
1) 0.02g carbomer U2020, is weighed, is placed in 3g 1,3-BDO and 4g glycerol and dissolves, be evenly stirred until nothing
Agglomeration.
2) 0.02g Sodium Hyaluronate, 3g methyl polyethers -10,2g polyvinyl alcohol and 0.1g ethylenediamine tetra-acetic acid, are weighed
Disodium is dissolved in 80.348g water, and step 1) gains are added after mixing, is heated to 80 DEG C 20 points of uniform stirring mixing again
Clock (ensures without agglomeration)；
3) step 2) gains, are cooled to 70 DEG C, 0.012g niacinamide is added.When continuing cool to 60 DEG C, it is added
0.5g aminomethyl propanol, 0.5g 1,2- hexylene glycol, 0.5g hydroxyapatite and 3g chemical enhancers EPDM147.Continue to cool down
It when to 45 DEG C or less, is added 3g Argireline solution (contain 1000ppm Argireline), is after mixing evenly to obtain
Essence preparation.
Embodiment 9
1) 0.02g carbomer U2020, is weighed, is placed in 3g 1,3-BDO and 4g glycerol and dissolves, be evenly stirred until nothing
Agglomeration.
2) 0.02g Sodium Hyaluronate, 3g methyl polyethers -10,2g polyvinyl alcohol and 0.1g ethylenediamine tetra-acetic acid, are weighed
Disodium is dissolved in 78.348g water, and step 1) gains are added after mixing, is heated to 80 DEG C 20 points of uniform stirring mixing again
Clock (ensures without agglomeration)；
3) step 2) gains, are cooled to 70 DEG C, 0.012g niacinamide is added.When continuing cool to 60 DEG C, it is added
0.5g aminomethyl propanol, 0.5g 1,2- hexylene glycol, 0.5g hydroxyapatite and 5g chemical enhancers EPDM147.Continue to cool down
It when to 45 DEG C or less, is added 3g Argireline solution (contain 1000ppm Argireline), is after mixing evenly to obtain
Essence preparation.
Embodiment 10
1) 0.02g carbomer U2020, is weighed, is placed in 3g 1,3-BDO and 4g glycerol and dissolves, be evenly stirred until nothing
Agglomeration.
2) 0.02g Sodium Hyaluronate, 3g methyl polyethers -10,2g polyvinyl alcohol and 0.1g ethylenediamine tetra-acetic acid, are weighed
Disodium is dissolved in 77.348g water, and step 1) gains are added after mixing, is heated to 80 DEG C 20 points of uniform stirring mixing again
Clock (ensures without agglomeration)；
3) step 2) gains, are cooled to 70 DEG C, 0.012g niacinamide is added.When continuing cool to 60 DEG C, it is added
0.5g aminomethyl propanol, 0.5g 1,2- hexylene glycol, 0.5g hydroxyapatite and 3g pentanediol and 3g EPDM147.Continue cold
When but to 45 DEG C or less, it is added 3g Argireline solution (containing 1000ppm Argireline), after mixing evenly to obtain the final product
To essence preparation.
1g Argireline solution in embodiment 1 is changed to and utilizes 3g Argireline solution system by embodiment 11
The acetyl group hexapeptide of liposomal made of standby, and the dosage of water is accordingly adjusted, so that the sum of ingredient is still 100g.Its
It is remaining to be equal to embodiment 1.
" 3g Argireline solution " in embodiment 5 is changed to and " utilizes 3g Argireline solution by embodiment 12
Liposomal acetyl group hexapeptide ", the dosage of chemical enhancers pentanediol is still 3g；And the dosage of water is accordingly adjusted, from
And the sum of making ingredient still is 100g.Remaining is equal to embodiment 5.
Chemical enhancers in embodiment 12 are changed to EPDM147 3g by pentanediol 3g by embodiment 13, remaining is equal to
Embodiment 12.
Chemical enhancers in embodiment 12 are changed to " pentanediol 1.5g+EPDM147 by pentanediol 3g by embodiment 14
1.5g, remaining is equal to embodiment 12.
Table 1, permeation enhancers concentration gradient and concentration of liposomes table (embodiment 1-14)
Experiment, according to GB/T 27818-2011 (chemicals skin absorber outer test method) the method to above-mentioned reality
It applies example 1~implementation 14 permeance property to be detected, acquired results such as the following table 2~table 6:
Table 2, various concentration Argireline permeate situation table (embodiment 1-3) at 6h
| Embodiment | Argireline concentration (ppm) | 6h unit area Percutaneous permeability (μ g) | Infiltration coefficient |
| 1 | 10 | 2.256 | 0.2669 |
| 2 | 30 | 8.482 | 0.6553 |
| 3 | 50 | 14.621 | 1.5310 |
Infiltration situation table (embodiment 2,4-6) of the Argireline at 6h when table 3, different pentanediol concentration
| Embodiment | Pentanediol concentration (%) | 6h unit area Percutaneous permeability (μ g) | Infiltration coefficient |
| 2 | 0 | 8.482 | 0.6553 |
| 4 | 1 | 10.998 | 0.6738 |
| 5 | 3 | 15.206 | 1.2690 |
| 6 | 5 | 10.747 | 0.9652 |
Infiltration situation table (embodiment 2,7-9) of the Argireline at 6h when table 4, difference EPDM concentration
| Embodiment | EPDM concentration (%) | 6h unit area Percutaneous permeability (μ g) | Infiltration coefficient |
| 2 | 0 | 8.482 | 0.6553 |
| 7 | 1 | 9.480 | 0.6637 |
| 8 | 3 | 13.655 | 1.1762 |
| 9 | 5 | 10.706 | 0.9425 |
Infiltration situation table (embodiment 10) of the Argireline at 6h when table 5, combination bleeding agent
Infiltration situation table (embodiment of the Argireline at 6h when table 6, liposome and liposome and penetrating agent combine
2、11-14)
Comparative example 1, by the Argireline in example 1 " preparation method of the acetyl group hexapeptide of liposomal " step 1)
Solution: total rouge material (lecithin+cholesterol) is changed to " 3:15 " by " 3:10 ", remaining is equal to example 1.
Comparative example 2, by the Argireline in example 1 " preparation method of the acetyl group hexapeptide of liposomal " step 1)
Solution: total rouge material (lecithin and cholesterol) is changed to " 3:5 " by " 3:10 ", remaining is equal to example 1.
Comparative example 3, by the cholesterol in example 1 " preparation method of the acetyl group hexapeptide of liposomal " step 1): lecithin
Rouge is changed to " 1:12 " by " 1:6 ", remaining is equal to example 1.
Comparative example 4, by the cholesterol in example 1 " preparation method of the acetyl group hexapeptide of liposomal " step 1): lecithin
Rouge is changed to " 1:3 " by " 1:6 ", remaining is equal to example 1.
Comparative test " will utilize 3g Argireline solution, be prepared according to 1 the method for example in embodiment 14
Liposomal acetyl group hexapeptide " be changed to respectively " using 3g Argireline solution, according to 1/ comparative example 2/ of comparative example
The acetyl group hexapeptide for the liposomal that 3/ comparative example of comparative example, 4 the method is prepared "；Remaining is equal to embodiment 14.
It is as shown in table 7 below with the Comparative result of embodiment 14.
Infiltration coefficient of the acetyl group hexapeptide at 6h of table 7, the liposomal being prepared using distinct methods
The above list is only a few specific embodiments of the present invention for finally, it should also be noted that.Obviously, this hair
Bright to be not limited to above embodiments, acceptable there are many deformations.Those skilled in the art can be from present disclosure
All deformations for directly exporting or associating, are considered as protection scope of the present invention.
Claims (6)
1. the preparation method of the rush infiltration re-surface intensive wrinkle correct preparation of acetyl-containing hexapeptide -8, it is characterised in that the following steps are included:
1), ingredient:
100 parts of raw materials consist of the following compositions:
0.015~0.025 part of carbomer U2020,2.5~3.5 parts of 1,3 butylene glycol, 3.5~4.5 parts of glycerol, Sodium Hyaluronate
0.015~0.025 part, -10 2.5~3.5 parts of methyl polyethers, 1.5~2.5 parts of polyvinyl alcohol, disodium ethylene diamine tetraacetate
0.08~0.12 part, 0.010~0.014 part of niacinamide, 0.4~0.6 part of aminomethyl propanol, 0.4~0.6 part of 1,2- hexylene glycol,
0.4~0.6 part of hydroxyapatite, 1~6 part of chemical enhancers, 1~5 part of Argireline solution or the second using 1~5 part
The acetyl group hexapeptide for the liposomal that -8 solution of acyl group hexapeptide is prepared, surplus are water；
The concentration of Argireline is (1000 ± 100) ppm in the Argireline solution；
Above-mentioned part is parts by weight；
2) uniform stirring into 1,3 butylene glycol and glycerol, is added in carbomer U2020；
3), Sodium Hyaluronate, methyl polyethers -10, polyvinyl alcohol, disodium ethylene diamine tetraacetate are dissolved in the water, and with
Above-mentioned steps 2) gains are uniformly mixed, it is heated to (80 ± 5) DEG C again uniform stirring mixing (20 ± 5) minute；
4), by above-mentioned steps 3) mixed gains are cooled to (70 ± 5) DEG C, niacinamide is added；Continue cool to (60 ± 5)
DEG C, aminomethyl propanol, 1.2- hexylene glycol, hydroxyapatite and the saturating agent of chemical enhancement is added；It is cooled to (45 ± 5) DEG C, is added
The acetyl group hexapeptide of Argireline aqueous solution or the liposomal being prepared using Argireline solution, stirring
After uniformly, essence preparation is obtained.
2. the preparation method of the rush infiltration re-surface intensive wrinkle correct preparation of acetyl-containing hexapeptide -8 according to claim 1, feature
Be: the chemical enhancers are at least one of pentanediol, EPDM147.
3. the preparation method of the rush infiltration re-surface intensive wrinkle correct of Argireline according to claim 1 or 2, it is characterised in that
100 parts of raw materials consist of the following compositions:
0.02 part of carbomer U2020,3 parts of 1,3 butylene glycol, 4 parts of glycerol, 0.02 part of Sodium Hyaluronate, methyl polyethers -10
3 parts, 2 parts of polyvinyl alcohol, 0.1 part of disodium ethylene diamine tetraacetate, 0.012 part of niacinamide, 0.5 part of aminomethyl propanol, 1,2- oneself two
0.5 part of alcohol, 0.5 part of hydroxyapatite, 1~6 part of chemical enhancers, 1~5 part of Argireline solution utilize 1~5 part
The acetyl group hexapeptide for the liposomal that Argireline solution is prepared, surplus are water.
4. the preparation method of the rush infiltration re-surface intensive wrinkle correct of any Argireline according to claim 1~3, feature
Be the preparation method of the acetyl group hexapeptide of liposomal the following steps are included:
1., according to Argireline solution: total rouge material=3:(10 ± 1), cholesterol: lecithin=1:(6 ± 1), emulsifier:
Total rouge material=1:(30 ± 3), lecithin: ethyl alcohol=1:(20 ± 2) mass ratio, first weigh lecithin, cholesterol, ethyl alcohol and cream
Agent is mixed to form mixed liquor；
Total rouge material is made of lecithin and cholesterol；
2., first mixed liquor is evaporated under reduced pressure to removing ethyl alcohol, the mixing of Argireline solution is then added, obtains liposome
The acetyl group hexapeptide of cladding --- the liposome suspension of cladding Argireline.
5. the preparation method of the rush infiltration re-surface intensive wrinkle correct of Argireline according to claim 4, it is characterised in that: institute
Stating emulsifier is polysorbas20.
6. the preparation method of the rush infiltration re-surface intensive wrinkle correct of Argireline according to claim 4 or 5, feature exist
In: the step 2. in, prior to 50~60 DEG C rotary evaporation 4~6 minutes after Argireline solution are added, then at 22~28
DEG C ultrasound (15 ± 5) minute.
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