CN101474153A - Epidermal growth factor nano lipid vector preparation for skin and preparation method thereof - Google Patents
Epidermal growth factor nano lipid vector preparation for skin and preparation method thereof Download PDFInfo
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- CN101474153A CN101474153A CNA2009100448553A CN200910044855A CN101474153A CN 101474153 A CN101474153 A CN 101474153A CN A2009100448553 A CNA2009100448553 A CN A2009100448553A CN 200910044855 A CN200910044855 A CN 200910044855A CN 101474153 A CN101474153 A CN 101474153A
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Abstract
The invention relates to a nano lipide carrier preparation, specifically a nano lipide carrier preparation which contains epidermal growth factor used on the skin and a preparation method thereof. The nano lipide carrier preparation which contains the epidermal growth factor used on the skin contains 0.02-5mg of epidermal growth factor, 2-20g of lipide material, 0.5-10g of emulsifier, 0.01-2g of antioxidizer, 0.01-1.5g of bacteriostat, 0.02-5g of percutaneous absorption accelerant, 0.3-15g of wetting agent and the rest of pure water based on 100mL of nano lipide carrier preparation. The nano lipide carrier preparation containing the epidermal growth factor has good skin physiological compatibility, can improve the placing stability of the epidermal growth factor, effectively promote the percutaneous absorption of the epidermal growth factor and improve the maintaining effect of the epidermal growth factor for the skin.
Description
Technical field
The present invention relates to a kind of nano lipid vector preparation, more specifically, relate to a kind of skin nano lipid vector preparation and preparation method thereof that contains epidermal growth factor (EGF).
Background technology
The skin of human body is vulnerable to the effect of multiple factors such as nature environment, atmosphere, radiation and sustains damage, and therefore, skin needs protection especially and the skin that is hurt is repaired.
Traditional skin nursing only is confined to the method that oil film is carried out lid or kept physics such as moisture content.Nowadays, along with development of life science, people have grasped epidermis cell aging and biochemical process thereof.Therefore, skin protection theory begins to turn to the nursing of cellular level.Meanwhile, development along with biology, skin physiology, many natural high activity materials that have the aging that delays or suppress skin and recovery or repair functions such as skin trauma have been it is found that, as superoxide dismutase (SOD), hyaluronic acid (HA), epidermal growth factor (Epidermal Growth Factor is called for short EGF) etc.Extra nutrition or the stimulation of epidermis cell given in this bionical nursing at the cell level, fundamentally keeps the skin natural health by the metabolism of cell own, started the new ideas of biological skin protection.
From human urine, extracted first in 1975 and obtain hEGF (hEGF).Adopting the biotechnology gene recombinaton nineties, promptly, carrying out engineering bacterium fermentation, make hEGF after purified again, the lyophilizing, be called the gene recombinaton hEGF by select producing bacterial strain.HEGF is as a kind of strong augmentor, has multiple biological activity, it can quicken the reparation of epidermis wounds such as cornea, skin, promote application on human skin epithelial cell, corneal epithelial cell and mammal epithelial cell growth, strengthen the protein of epidermis cell, the effects such as synthetic and cellular metabolism of DNA, RNA.Add hEGF in the preparation for external application to skin and can repair the skin damage cell, promote the generation of the new cell of skin, increase the content of other endogenous somatomedin simultaneously, promote emiocytosis hyaluronic acid and glycoprotein, rationally adjust skin texture, delaying decrepitude of skin reduces wrinkle, and has brightening, keeps effect such as moist, the soft and high resilience of skin.Because hEGF is one of the heat of finding at present, biologically active polypeptide that absolute acid stability is the highest, and the half-life is longer, therefore, the preparation for external application to skin that contains hEGF has the vast market potentiality.
At present, bibliographical information is arranged, hEGF is made dosage forms such as hydrogel, aqueous solution, common Emulsion, but because the hEGF molecular weight is bigger, hEGF poor stability in these dosage forms, and disperse matrix does not have tangible absorption facilitation, causes the preparation transdermal effect not good, and the degree of absorbing of effective ingredient is very low.
In order to overcome above-mentioned shortcoming, the present invention is prepared into the skin nano lipid vector preparation with epidermal growth factor.Nano-lipid carrier is the second filial generation submicron drug-loading system that solid lipid nanoparticle grows up that continues in recent years, and it has characteristics such as physical stability height, slow-releasing as dermatologic thing carrier.And because this body structure of lipid has similarity highly with the human skin lipid, so it has the keratodermatitis of increasing permeability, organizes advantages such as affinity is strong, biological degradability good, avirulence, so nano-lipid carrier has been used for the research of skin carrier drug-supplying system more and more widely.
Summary of the invention
The object of the present invention is to provide a kind of epidermal growth factor nano lipid vector preparation for skin, said preparation EGF when storing can be present in wherein steadily in the long term, and EGF is absorbed in the skin when using.
Another object of the present invention is to provide a kind of preparation method of above-mentioned epidermal growth factor nano lipid vector preparation for skin.
For achieving the above object, the present invention adopts following technical scheme:
Epidermal growth factor nano lipid vector preparation for skin of the present invention, in the 100mL nano lipid vector preparation, it consists of:
Epidermal growth factor 0.02～5mg
Matrix material 2～20g
Emulsifying agent 0.5～10g
Antioxidant 0.01～2g
Antibacterial 0.01～1.5g
Percutaneous absorption enhancer 0.02～5g
Wetting agent 0.3～15g
Surplus is a pure water.
In the preferred embodiment of the invention, in the 100mL nano lipid vector preparation, it consists of:
Epidermal growth factor 0.05～2mg
Matrix material 2～15g
Emulsifying agent 1～8g
Antioxidant 0.01～0.5g
Antibacterial 0.01～0.5g
Percutaneous absorption enhancer 0.05～3g
Wetting agent 0.5～10g
Surplus is a water.
Wherein, described epidermal growth factor is selected among hEGF, M-EGF, rabbit epidermal growth factor and the pig's epidermal growth factor, and preferred hEGF.
But described matrix material is the natural or synthetic lipid of external preparation for skin, can be in the following matrix material one or more: fatty glyceride, for example tripalmitin, tristerin, behenic acid is single, double, the mixture with triglycerides thing, the Palmic acid tristerin, and chain length is at C
8-C
10Between fatty glyceride (be called for short MCT); Fatty acid, for example stearic acid, Palmic acid, oleic acid, linoleic acid; Waxiness, for example hexadecanol, octadecanol, cetyl palmitate, vaseline, paraffin; Sterin, for example cholesterol; Crude vegetal, for example soybean oil, Oleum Ricini, safflower oil, olive oil; Vitamin, for example vitamin E, vitamin A, vitamin ester is a kind of and composition thereof.
Described emulsifying agent can be in the following emulsifying agent one or more: phospholipid, as soybean phospholipid, lecithin, hydrogenated phospholipid; Poloxalkol is as poloxamer; The fatty acid Pyrusussuriensis is smooth; Polysorbate is as tween (Tween) 60, Tween 80; Polyoxyethylene fatty acid ester; Polyoxyethylene aliphatic alcohol ether; Polyoxyethylene castor oil; Sorbitan fatty acid ester; And lanonol.Wherein emulsifying agent is preferably one or more in phospholipid, Tween 80 and the polyoxyethylene castor oil.
Described antioxidant can be tocopherol, vitamin C, tert-butyl group hydroxyanisol, 2, a kind of or its mixture in the external preparation for skin antioxidant commonly used such as 5-ditertbutylparacresol, nor-dihydro traumatic acid, propyl gallate.
Described antibacterial is one or more the mixture in Benzalkonii Chloridum, benzalkonium bromide, methyl hydroxybenzoate, ethyl hydroxybenzoate, propylparaben, chlorobutanol and the sorbic acid.
Described wetting agent is one or more the mixture in glycerol, propylene glycol, hyaluronic acid and sodium salt thereof and the chitosan.
Described Percutaneous absorption enhancer can be in the following chemical compound one or more: organic solvent, for example ethanol, propylene glycol, ethyl acetate and dimethylformamide etc.; Laurocapram and homologue thereof; Cutin is preserved moisture and softening agent, as carbamide, salicylic acid and pyrrolidone; Terpenes is as menthol, Camphora, limonene.Wherein, described Percutaneous absorption enhancer is preferably one or more in propylene glycol, laurocapram, carbamide, salicylic acid and the menthol.
The preparation method of epidermal growth factor nano lipid vector preparation for skin of the present invention is as follows:
Step 1: EGF is dissolved in a certain amount of pure water forms water, can choose wantonly at aqueous phase and add emulsifying agent and wetting agent; Matrix material and emulsifiers dissolve are formed oil phase in ethyl acetate or dichloromethane, in oil phase, can choose adding antioxidant and Percutaneous absorption enhancer wantonly;
Step 2: under shear conditions, the water that will contain EGF slowly adds in the oil phase, stirs into colostrum with high-shear homogenizing machine;
Step 3: colostrum is put decompression removal ethyl acetate or dichloromethane in the rotary evaporator;
Step 4: carry out high pressure homogenize, add antibacterial and remaining ingredient, obtain skin EGF nano-lipid carrier.
According to the present invention, epidermal growth factor nano lipid vector preparation for skin of the present invention for ease of transportation and storage, can further pass through spray drying or lyophilization, obtains powder body or dried frozen aquatic products.Powder body that obtains like this or dried frozen aquatic products adopt normal saline to be mixed with suitable concentration in use, can be applied on the skin.
The invention has the advantages that:
(1) nano-lipid carrier provided by the invention can with the EGF parcel wherein be avoided the influence of external environment to EGF, improves the shelf-stability of EGF.
(2) matrix material in the nano-lipid carrier and skin have physiological compatibility preferably, and particle diameter less (about 200nm), can by with cuticular fusion, mechanism such as penetrate, EGF is transmitted in the skin, make EGF effectively performance to the repair of Skin Cell.
(3) nano-lipid carrier itself has the effect that Skin Cell was preserved moisture, activated to advantages of good skin.
Description of drawings
Fig. 1 is the stripped transdermal photo of the hEGF nano-lipid carrier (B) of reference substance solution (A) and embodiment 5 fluorescein sodium labellings.
Fig. 2 is the hEGF nano-lipid carrier of embodiment 2 and hEGF normal saline solution at 4 ℃ shelf-stability experimental result picture.
The specific embodiment
The present invention is further elaborated below in conjunction with specific embodiment, but the present invention is not limited to these embodiment.
Among the embodiment, employed hEGF purchases in Sichuan China and steps the development in science and technology company limited below, and M-EGF is purchased the bio tech ltd in west, Shanghai Tang.
Embodiment 1
Table 1 has provided the composition and the content thereof of the epidermal growth factor nano lipid vector preparation for skin of embodiment 1-4, and has provided envelop rate, the granulometry result of preparation.
The composition of table 1 embodiment 1-4 preparation and content thereof, envelop rate, granulometry result
1. the preparation of hEGF nano-lipid carrier:
According to the composition that provides embodiment 1 in the table 1, take by weighing hEGF 0.2mg and be dissolved in the 500 μ L pure water, obtain water 1; Myrj 45 (S-40) 1.5g, glycerol 2g are dissolved in the surplus pure water, obtain water 2; Matrix material Palmic acid tristerin 4g, soybean phospholipid 2g, tocopherol 0.05g are dissolved in the 3mL dichloromethane, obtain oil phase; Under shear conditions, water 1 and water 2 are slowly added in the oil phase, stir 1min and become colostrum; Colostrum is put in the rotary evaporator, and dichloromethane is removed in 30 ℃ of decompressions; Then, adopt the pressure homogenizing of homogenizer with 500bar, add Benzalkonii Chloridum 0.01g, salicylic acid 0.5g obtains skin hEGF nano lipid vector preparation; After carry out lyophilization and get dried frozen aquatic products.
2. assay: it is an amount of to get hEGF nano-lipid carrier dried frozen aquatic products, adds normal saline and redissolves, and with the triton x-100 breakdown of emulsion, employing hEGF test kit is measured with the double-antibody sandwich euzymelinked immunosorbent assay (ELISA) after suitable dilution.Promptly respectively by specification adds testing sample, one anti-, enzyme labelled antibody, zymolyte and stop buffer, and with microplate reader in 450nm place mensuration trap, draw EGF concentration in the testing sample by the drawing standard curve calculation.
3. entrapment efficiency determination: adopt ultrafiltration to measure the envelop rate of hEGF nano-lipid carrier.Get hEGF nano-lipid carrier dried frozen aquatic products and add the normal saline redissolution in right amount, put (mw10,000) in the ultrafiltration pipe, the centrifugal 15min of 4500rpm gets ultrafiltrate through suitably adopting the hEGF test kit to measure the concentration of the hEGF that dissociates with euzymelinked immunosorbent assay (ELISA) after the dilution.Other gets the hEGF nano-lipid carrier by the operation down of content assaying method item, measures the total concentration of hEGF in nano-lipid carrier.Computational envelope rate as follows:
C
Always: the total concentration of hEGF in nano-lipid carrier
C
Free: the Cf of hEGF in the ultrafiltrate
4. granularity and particle size distribution: get hEGF nano-lipid carrier dried frozen aquatic products and add normal saline in right amount and redissolve, mean diameter and particle size distribution (representing with polydispersity coefficient) adopt the particle size analyzer of dynamic light scattering principle to measure.
The measurement result of content, envelop rate, mean diameter and particle size distribution is as shown in table 1.The result shows that the hEGF nano-lipid carrier content of the present invention's preparation is higher, does not promptly almost destroy the three dimensional structure of hEGF; The envelop rate height can effectively be wrapped in hEGF in the lipid core of nanoparticle; Granularity suits and is evenly distributed, and helps the nano-lipid carrier percutaneous and absorbs.
5. stability study-accelerated test: getting hEGF nano-lipid carrier dried frozen aquatic products, is 40 ℃ in temperature, and relative humidity is to place 6 months in 75% the climatic chamber, respectively at 0,1,2,3, the sampling in June detects.The situation of change of indexs such as the character before and after the investigation test specimen, content, envelop rate, particle diameter, particle size distribution the results are shown in Table 2.The result shows, the hEGF nano-lipid carrier dried frozen aquatic products of embodiment 1 preparation each index in 6 months accelerated test put procedure has no significant change, and illustrates that this sample is stable.
Table 2 embodiment 1 sample accelerated test result
Embodiment 2
According to the composition that provides embodiment 2 in the table 1, take by weighing hEGF 0.5mg and be dissolved in the 500 μ L pure water, obtain water 1; With hyaluronate sodium 0.3g, poloxamer 188 2g are dissolved in the surplus pure water, obtain water 2; With matrix material tripalmitin 6g, MCT 2g, polyoxyethylene (35) Oleum Ricini 3.5g is dissolved in the 3mL dichloromethane, obtains oil phase; Under shear conditions, water 1 and water 2 are slowly added in the oil phase, stir 1min and become colostrum; Colostrum is put in the rotary evaporator, and dichloromethane is removed in 30 ℃ of decompressions; Then, adopt the pressure homogenizing of homogenizer with 500bar, adding chlorobutanol 0.01g, carbamide 0.1g, vitamin C 0.1g obtain skin hEGF nano lipid vector preparation.
The measurement result of content, envelop rate, mean diameter and particle size distribution that makes the hEGF nano-lipid carrier is as shown in table 1.
Stability study: get the hEGF nano-lipid carrier of embodiment 2, in 4 ℃ of placements; It is an amount of that other gets the hEGF material powder, is to contain the hEGF concentration solution identical with nano-lipid carrier, 4 ℃ of placements with the physiological saline solution dilution.Sampling detects, and investigates the situation of change of test specimen content, the results are shown in Figure 2.The result shows, the less stable of hEGF normal saline solution is placed after 60 days for 4 ℃, and content only is 8.7%; The nano-lipid carrier of embodiment 2 preparations can effectively improve the stability of hEGF owing to hEGF can be wrapped in the lipid core of nanoparticle.
Embodiment 3
According to the composition that provides embodiment 3 in the table 1, take by weighing Mus EGF 1.0mg and be dissolved in the 500 μ L pure water, obtain water 1; Chitosan is dissolved in the excess water that contains acetic acid 1.5%, obtains water 2; With matrix material oleic acid 2.5g, stearic acid 6g, hexadecanol 2g, Tween80 3g, lecithin 1.5g, laurocapram 1g is dissolved in the 3mL dichloromethane, obtains oil phase; Under shear conditions, water 1 and water 2 are slowly added in the oil phase, stir 1min and become colostrum; Colostrum is put in the rotary evaporator, and dichloromethane is removed in 30 ℃ of decompressions; Carry out high pressure homogenize then, add nor-dihydro traumatic acid, sorbic acid, obtain skin Mus EGF nano lipid vector preparation; After carry out spray drying and get the spray powder end.
The measurement result that makes content, envelop rate, mean diameter and particle size distribution that Mus EGF nano-lipid carrier spray powder end records after normal saline redissolves is as shown in table 1.
Embodiment 4
According to the composition that provides embodiment 4 in the table 1, take by weighing hEGF 0.05mg and be dissolved in the 500 μ L pure water, obtain water 1; Hyaluronic acid 0.8g is dissolved in the surplus pure water, obtains water 2; With matrix material cholesterol 2g, olive oil 1g, soybean phospholipid 5g, polyoxyethylene (35) Oleum Ricini 0.5g is dissolved in the 3mL dichloromethane, obtains oil phase; Under shear conditions, water 1 and water 2 are slowly added in the oil phase, stir 1min and become colostrum; Colostrum is put in the rotary evaporator, and dichloromethane is removed in 30 ℃ of decompressions; Carry out high pressure homogenize then, add tert-butyl group hydroxyanisol, methyl hydroxybenzoate, menthol obtain skin hEGF nano lipid vector preparation; After carry out lyophilization and get dried frozen aquatic products.
The measurement result that makes content, envelop rate, mean diameter and particle size distribution that hEGF nano-lipid carrier dried frozen aquatic products records after normal saline redissolves is as shown in table 1.
Embodiment 5
1. prepare fluorescently-labeled hEGF nano-lipid carrier:
According to the composition that provides embodiment 5 in the table 3, take by weighing hEGF 0.3mg, fluorescein sodium 2g is dissolved in the 1mL pure water, obtains water 1; Myrj 45 (S-40) 1.5g, hyaluronate sodium 0.6g are dissolved in the surplus pure water, obtain water 2; Matrix material Palmic acid tristerin 3g, olive oil 0.5g, soybean phospholipid 3g, laurocapram 1g are dissolved in the 3mL dichloromethane, obtain oil phase; Under shear conditions, water 1 and water 2 are slowly added in the oil phase, stir 1min and become colostrum; Colostrum is put in the rotary evaporator, and dichloromethane is removed in 30 ℃ of decompressions; Carry out high pressure homogenize, adding vitamin C, propylparaben obtain skin hEGF nano lipid vector preparation; After carry out lyophilization and get dried frozen aquatic products.
2. the measurement result that makes content, envelop rate, mean diameter and particle size distribution that hEGF nano-lipid carrier dried frozen aquatic products records after normal saline redissolves is as shown in table 3.
The composition of table 3 embodiment 5-6 preparation and content thereof, envelop rate, granulometry result
3. the stripped transdermal test of hEGF nano-lipid carrier:
Contrast liquid preparation: getting fluorescein sodium and hEGF is an amount of, is the solution that contains fluorescein sodium 2wt%, contains hEGF 3 μ g/mL, liquid in contrast with the isoosmotic pH7.5 phosphate buffer of physiology (PBS) dissolved dilution.
The test liquid preparation: the hEGF nano-lipid carrier dried frozen aquatic products of getting embodiment 5 preparations is an amount of, is the nano-lipid carrier colloid solution that contains hEGF 3 μ g/mL with the isoosmotic pH7.5PBS solution dilution of physiology, as test liquid.
The BALB/c-nu/nu nude mouse is cutd open from skin of abdomen with 75% alcohol wipe, and the percutaneous absorption test begins in the 2h cuing open behind skin.Skin is cut to 1.5cm * 1.5cm size, is put into, put a filter paper, get reference substance and need testing solution respectively and drop on the skin surface filter paper at skin surface with on the wetted filter paper of PBS.Test is carried out in tool lid culture dish, leaves standstill under the room temperature lucifuge environment.
The skin of 2h is left standstill in taking-up, takes off surperficial filter paper, rinses out unabsorbed fluorescein sodium with PBS.Cut from skin central authorities with scalpel, after wrapping up with freezing embedding medium, make frozen section with freezing microtome, section is put under the fluorescence inverted microscope and is observed, and takes and amplifies 40 times photo.
Experimental result as shown in Figure 1, Fig. 1 is the hEGF nano-lipid carrier (B) of reference substance solution (A) and the embodiment 5 fluorescein sodium labellings transdermal photo that exsomatizes.The result shows after reference substance solution is put nude mice skin 2h, only have horny layer of epidermis that fluorescence is arranged; After the test liquid that contains the hEGF nano-lipid carrier of fluorescein sodium labelling was put nude mice skin surface 2h, fluorescence all appearred in horny layer of epidermis and skin corium; Experimental result explanation nano-lipid carrier has the effect that strengthens the medicine skin absorbs that is wrapped, and is the ideal carrier of hEGF.
Embodiment 6:
According to the composition that provides embodiment 6 in the table 3, take by weighing hEGF 0.3mg and be dissolved in the 1mL pure water, obtain water 1; Myrj 45 (S-40) 1.5g, hyaluronate sodium 0.6g are dissolved in the surplus pure water, obtain water 2; Matrix material Palmic acid tristerin 3g, olive oil 0.5g, soybean phospholipid 3g, laurocapram 1g are dissolved in the 3mL dichloromethane, obtain oil phase; Under shear conditions, water 1 and water 2 are slowly added in the oil phase, stir 1min and become colostrum; Colostrum is put in the rotary evaporator, and dichloromethane is removed in 30 ℃ of decompressions; Carry out high pressure homogenize, adding vitamin C, propylparaben obtain skin hEGF nano lipid vector preparation.
The measurement result of content, envelop rate, mean diameter and particle size distribution that makes the hEGF nano-lipid carrier is as shown in table 3.
Skin irritation Journal of Sex Research repeatedly: with the rabbit is animal model, is divided into 2 groups at random, 4 every group.Before the test tame rabbit back spinal column both sides dorsal body setae is cut, the unhairing scope respectively is 3cm * 3cm.
Prepare for test agent: the hEGF nano lipid vector preparation of getting embodiment 6 is an amount of, is the nano-lipid carrier colloid solution that contains hEGF 3 μ g/mL with the normal saline dilution.
Lose hair or feathers and got the 0.5mL test liquid in back 24 hours and spread upon on the side skin in the administration district, opposite side is smeared normal saline solution, smears every day 1 time, continuously 14d.Since second day, answer cropping before smearing at every turn, and remove residual sample with normal saline.Investigate the zest of hEGF nano-lipid carrier with medicine-feeding part erythema, edema scoring after smearing 1h to skin at every turn.The results are shown in Table 4.
The result shows, the hEGF nano-lipid carrier is to the skin nonirritant, and test sample group rabbit skin smoothness is good than matched group, skin irritation intensity comments part to be lower than the normal saline group, illustrate that the hEGF nano-lipid carrier has initiatively maintenance effect to skin, can effectively prevent the pachylosis phenomenon that environmental factorss such as water evaporates, mechanical force cause.
Table 4 embodiment 6 samples are to rabbit skin irritation result of the test repeatedly
Claims (10)
1, a kind of epidermal growth factor nano lipid vector preparation for skin, in the 100mL nano lipid vector preparation, it consists of:
Epidermal growth factor 0.02～5mg
Matrix material 2～20g
Emulsifying agent 0.5～10g
Antioxidant 0.01～2g
Antibacterial 0.01～1.5g
Percutaneous absorption enhancer 0.02～5g
Wetting agent 0.3～15g
Surplus is a pure water.
2, epidermal growth factor nano lipid vector preparation for skin according to claim 1 is characterized in that, in the 100mL nano lipid vector preparation, it consists of:
Epidermal growth factor 0.05～2mg
Matrix material 2～15g
Emulsifying agent 1～8g
Antioxidant 0.01～0.5g
Antibacterial 0.01～0.5g
Percutaneous absorption enhancer 0.05～3g
Wetting agent 0.5～10g
Surplus is a water.
3, epidermal growth factor nano lipid vector preparation for skin according to claim 1 and 2 is characterized in that, described epidermal growth factor is selected among hEGF, M-EGF, rabbit epidermal growth factor and the pig's epidermal growth factor.
4, epidermal growth factor nano lipid vector preparation for skin according to claim 3 is characterized in that, described epidermal growth factor is the hEGF.
5, according to claim 1,2 or 4 described epidermal growth factor nano lipid vector preparation for skin, it is characterized in that described matrix material is selected from one or more in fatty glyceride, fatty acid, waxiness, sterin, crude vegetal and the vitamin.
6, epidermal growth factor nano lipid vector preparation for skin according to claim 5 is characterized in that, described fatty glyceride is: tripalmitin, tristerin, behenic acid is single, double, the mixture with triglycerides thing, the Palmic acid tristerin, and perhaps chain length is at C
8-C
10Between fatty glyceride;
Described fatty acid is stearic acid, Palmic acid, oleic acid or linoleic acid;
Described waxiness is hexadecanol, octadecanol, cetyl palmitate, vaseline or paraffin;
Described sterin is a cholesterol;
Described crude vegetal is soybean oil, Oleum Ricini, safflower oil or olive oil;
Described vitamin is a kind of or its mixture of vitamin E, vitamin A, vitamin ester.
7, according to claim 1,2,4 or 6 described epidermal growth factor nano lipid vector preparation for skin, it is characterized in that, described emulsifying agent can be in the following emulsifying agent one or more: phospholipid, and described phospholipid comprises soybean phospholipid, lecithin and hydrogenated phospholipid; Poloxalkol, described poloxalkol are poloxamer; The fatty acid Pyrusussuriensis is smooth; Polysorbate, described Polysorbate comprises polysorbate60 and Tween 80; Polyoxyethylene fatty acid ester; Polyoxyethylene aliphatic alcohol ether; Polyoxyethylene castor oil; Sorbitan fatty acid ester; And lanonol;
Described antioxidant is tocopherol, vitamin C, tert-butyl group hydroxyanisol, 2, a kind of or its mixture in 5-ditertbutylparacresol, nor-dihydro traumatic acid and the propyl gallate;
Described antibacterial is a kind of or its mixture in Benzalkonii Chloridum, benzalkonium bromide, methyl hydroxybenzoate, ethyl hydroxybenzoate, propylparaben, chlorobutanol and the sorbic acid;
Described wetting agent is one or more the mixture in glycerol, propylene glycol, hyaluronic acid and sodium salt thereof and the chitosan;
Described Percutaneous absorption enhancer is selected from one or more in the following chemical compound: organic solvent, and described organic solvent comprises ethanol, propylene glycol, ethyl acetate and dimethylformamide; Laurocapram and homologue thereof; Cutin is preserved moisture and softening agent, and described cutin is preserved moisture and softening agent comprises carbamide, salicylic acid and pyrrolidone; Terpenes, described terpenes comprises menthol, Camphora and limonene.
8, epidermal growth factor nano lipid vector preparation for skin according to claim 7 is characterized in that, described emulsifying agent is selected from one or more in phospholipid, Tween 80 and the polyoxyethylene castor oil.
9, epidermal growth factor nano lipid vector preparation for skin according to claim 7 is characterized in that, described Percutaneous absorption enhancer is one or more in propylene glycol, laurocapram, carbamide, salicylic acid and the menthol.
10, the preparation method of each described epidermal growth factor nano lipid vector preparation for skin among a kind of claim 1-9, this method step is as follows:
Step 1: epidermal growth factor is dissolved in a certain amount of pure water forms water, can choose wantonly at aqueous phase and add emulsifying agent and wetting agent; Matrix material and emulsifiers dissolve are formed oil phase in ethyl acetate or dichloromethane, in oil phase, can choose adding antioxidant and Percutaneous absorption enhancer wantonly;
Step 2: under shear conditions, the water that will contain epidermal growth factor slowly adds in the oil phase, stirs into colostrum with high-shear homogenizing machine;
Step 3: colostrum is put decompression removal ethyl acetate or dichloromethane in the rotary evaporator;
Step 4: carry out high pressure homogenize, add antibacterial and remaining ingredient, obtain the skin epidermal growth factor nano lipid vector.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102106820A (en) * | 2010-11-26 | 2011-06-29 | 深圳市金因生物技术有限公司 | Epidermal growth factor nanolipid carrier preparation and preparation method thereof |
| CN102166167A (en) * | 2011-04-01 | 2011-08-31 | 刘京花 | Thickening and water retaining agent and preparation method thereof |
| CN102166167B (en) * | 2011-04-01 | 2013-02-13 | 山东乐丰生物科技有限公司 | Thickening and water retaining agent and preparation method thereof |
| CN103182070A (en) * | 2013-04-12 | 2013-07-03 | 江苏迪沃生物制品有限公司 | External composition, and preparation and application thereof |
| CN103182070B (en) * | 2013-04-12 | 2014-02-12 | 江苏迪沃生物制品有限公司 | External composition, and preparation and application thereof |
| CN104287995A (en) * | 2014-10-20 | 2015-01-21 | 江苏三特生物科技有限公司 | Cytokine nanostructure lipid carrier and preparation method thereof |
| WO2023077338A1 (en) * | 2021-11-04 | 2023-05-11 | 深圳市维琪科技股份有限公司 | Hexapeptide derivative and cosmetic composition or pharmaceutical composition and use thereof |
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