阅读说明：本技术 含乙酰基六肽-8的促渗透抗皱精华制剂的制备方法 (The preparation method of the rush infiltration re-surface intensive wrinkle correct preparation of acetyl-containing hexapeptide -8 ) 是由 叶琳琳 王舒月 于 2019-09-18 设计创作，主要内容包括：本发明公开了一种含乙酰基六肽-8的促渗透抗皱精华制剂的制备方法,配料由卡波姆U2020、1,3-丁二醇、甘油、透明质酸钠、甲基葡糖聚醚-10、聚乙烯醇、乙二胺四乙酸二钠、烟酰胺、氨甲基丙醇、1,2-己二醇、羟基磷灰石、化学促渗剂、乙酰基六肽-8溶液或利用乙酰基六肽-8溶液制备而得的脂质体包覆的乙酰基六肽、水组成。本发明制备而得的抗皱精华制剂,可进一步促进乙酰基六肽-8的皮肤渗透。(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.)

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.

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.