CN103860392A - Hydrophobic solid microspheres containing epidermal growth factors and preparation method and application of microspheres - Google Patents
Hydrophobic solid microspheres containing epidermal growth factors and preparation method and application of microspheres Download PDFInfo
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- CN103860392A CN103860392A CN201410040914.0A CN201410040914A CN103860392A CN 103860392 A CN103860392 A CN 103860392A CN 201410040914 A CN201410040914 A CN 201410040914A CN 103860392 A CN103860392 A CN 103860392A
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Abstract
The invention discloses hydrophobic solid microspheres containing epidermal growth factors and a preparation method and application of the microspheres. The preparation method comprises the following steps: with polyethylene glycol porous microspheres as a protective agent, loading the epidermal growth factors; and protecting the polyethylene glycol porous microspheres loading the epidermal growth factors by paraffin through fusing and spraying. The preparation method provided by the invention has the advantages and effects that (1) polyethylene glycol with the molecular weight from 2000 to 20000 is selected as the protective agent for the epidermal growth factors; (2) the epidermal growth factors are protected by solid paraffin, and polyethylene glycol freezed powder isolates water; (3) the preparation process is simple and does not refer to chemical reactions, and is free of the generation of the three wastes and green and environment-friendly; (4) the contained epidermal growth factors are acid-resistant, alkali-resistant, light-resistant, waterproof and high-temperature-resistant; and (5) the hydrophobic solid microspheres are simple and convenient to use, and can serve as a functional additive which is added into various emulsions and cream or frost-like cosmetics by being slightly squeezed.
Description
Technical field
The invention belongs to field of functional materials, particularly a kind of hydrophobic solid microsphere containing epidermal growth factor and preparation method thereof and the application in cosmetics.
Background technology
Epidermal growth factor (Epidermal Growth Factor, be called for short EGF, CAS:62229-50-9) be the class peptide material being extensively present in mammalian body, secreted by normal cell, both without medicine class toxicity, also without immunoreation, be therefore widely used in people's burn, wound, diabetic skin ulcer, decubital ulcer, varicosis skin ulcer and corneal injury, can promote wound healing.Its effect at beauty treatment fields mainly contains: 1. skin care effect.EGF can irritate the various cells of ectoderm and entoderm origin as corneal epithelium and endotheliocyte, epidermis, skin corium cell (as fibroblast), mammary gland alveolus and Interstitial cell etc., makes its proliferation apoptosis, accelerates metabolism, reaches the effect of skin care.2. skin care.EGF can promote the biosynthesis of DNA, RNA and functional protein, can promote extracellular macromolecular synthetic (as hyaluronic acid, elastic fiber albumen etc.), increases moisture content of skin, and then increases skin elasticity, Glycerin.3. smooth away wrinkles.EGF promotes cytotrophy material to be initiatively transported in cell from extracellular, increases intracellular nutrition.Promote the functional moleculars such as skin corium emiocytosis rubber polymer fibril, polysaccharide, glycoprotein, make that subcutaneous dermal tissue is full, muscle fiber marshalling is tight, thereby reduce and smooth away wrinkles.4. repair wound.Enter cell division cycle, some critical function gene activations, expression, secretion biological activity protein etc. in active cell by irritating epidermis cell (comprising epithelial cell, the various Interstitial cell in Various Tissues source) with EGF receptors bind.Impel collagen fiber to be the linear alignment, the growth of epidermis cell fast regular in time flap coverage.After obviously accelerating beauty treatment, cosmetology and the wound healing such as other skin trauma, and keep wound surface smooth smooth, abnormal pigmentary deposit on the skin trace is reduced or disappear and reduce pigmentation.5. prevent mottle.Epidermal growth factor has stronger facilitation to the propagation of epidermis cell, youthening of epidermis cell after using, make the less accumulation such as residual that has pigment and dead cell in epidermal tissue, cutaneous manifestations is gone out and tenderly have no time in vain, eliminate the abnormal cutaneous manifestations such as mottle and pigmentation.Treatment phase and convalescent period at speckle dispelling are used EGF can effectively contain the recurrence of mottle.
But EGF is a kind of biological activity protein, place one's entire reliance upon its activity of its magical effect, does not have activated EGF like water off a duck's back.EGF can only store and use with the form of lyophilized powder at present, lyophilized powder at room temperature can be deposited 3 years its biological activitys and not change, and playing activity in solution, EGF generally can only preserve 7-10 days, therefore, if be added in cosmetics and skincare product, production and life cycle all will exceed active storage life, make EGF ineffective, so EGF is difficult to use as additive.
The Chinese patent application that is 201210532835 as application number discloses a kind of somatomedin controlled release thermosensitive hydrogel and preparation method thereof, application number is that 201210469251 Chinese patent application discloses the preparation method of a kind of Polyethylene Glycol with nerve growth factor conjugate, publication number is that the Chinese patent of CN101316618B discloses the sustained release film formulation for healing of wound that comprises epidermal growth factor, and the Chinese patent that the patent No. is ZL201110027337 discloses a kind of growth factor slow-release microsphere and preparation method thereof.These patents or patent application all do not solve the problem that keeps for a long time EGF activity.
Summary of the invention
In order to solve the deficiencies in the prior art, primary and foremost purpose of the present invention is to provide a kind of preparation method of the hydrophobic solid microsphere containing epidermal growth factor.
The hydrophobic solid microsphere containing epidermal growth factor that provides above-mentioned preparation method to prepare is provided.
A further object of the present invention is to provide the application of the above-mentioned hydrophobic solid microsphere containing epidermal growth factor in cosmetics.Hydrophobic solid microsphere containing epidermal growth factor is added in cosmetics, has long period of activity storage life (being greater than 2 years) after interpolation.
Object of the present invention is achieved through the following technical solutions: a kind of preparation method of the hydrophobic solid microsphere containing epidermal growth factor, is characterized in that comprising the steps:
(1) 10g Polyethylene Glycol is joined in 100～1000mL deionized water, at 0～45 ℃, be stirred to completely and dissolve with the speed of 200～400rpm, freezing rear lyophilizing at-80～-5 ℃, adopts freezing ball mill under-20～0 ℃ of condition, after ball milling, to cross 115 mesh sieves, obtains polyglycol porous microsphere;
At (2) 0～45 ℃, polyglycol porous 1g microsphere and 0.1～0.2g epidermal growth factor are joined in three-dimensional mixer, first stirring at low speed 1～10min under 20～600rpm, high-speed stirred 1～10min under 1200～4000rpm again, obtains the polyglycol porous microsphere containing epidermal growth factor;
At (3) 0～45 ℃, 1g is laid on vibrations conveyer belt containing the polyglycol porous microsphere of epidermal growth factor, at 70～100 ℃, use molten atomizing machine by after paraffin melting, the polyglycol porous microsphere covering containing epidermal growth factor is given in spraying, and spray parameters is 0.1g/mincm
2, be 0.5～1 second containing the polyglycol porous microsphere of epidermal growth factor in the time of staying in molten atomizing district, be then cooled to immediately 0 ℃; By 2 sprayings, obtaining cladding thickness is 25 ± 2 μ m, crosses 100 mesh sieves, both must be containing the hydrophobic solid microsphere of epidermal growth factor.
Molecular weight polyethylene glycol described in step (1) is 1800～20000 dalton, it at 45 ℃, is solid, fusing point is 49～64 ℃, be more preferably PEG-2000(white solid, 51 ± 2 ℃ of fusing points), PEG-4000(white solid, 55 ± 2 ℃ of fusing points), PEG-6000(white solid, 57 ± 2 ℃ of fusing points), PEG-8000(white solid, 60 ± 2 ℃ of fusing points), PEG-10000(white solid, 61 ± 2 ℃ of fusing points) or PEG-20000(white solid, 62 ± 2 ℃ of fusing points).
Epidermal growth factor described in step (2) is the powder body that particle diameter is less than 10nm, and mass percent is greater than 99%, commercially available, as Sigma company.
Paraffin described in step (3) is paraffin wax, pathology level, and fusing point is 60～62 ℃.
Described in step (1), freeze dryer is commercially available instrument, and model specification does not do requirement.
Described in step (1), freezing ball mill is commercially available instrument, and model specification does not do requirement.
Described in step (2), three-dimensional mixer is commercially available instrument, and model specification does not do requirement.
Described in step (3), sieve aperture shaking table is commercially available instrument, and model specification does not do requirement.
Described in step (3), molten atomizing machine is commercially available instrument, and model specification does not do requirement.
Cladding thickness described in step (3) is controlled by spraying duration.
Containing a hydrophobic solid microsphere for epidermal growth factor, prepared by above-mentioned preparation method.
The above-mentioned hydrophobic solid microsphere containing epidermal growth factor, in the application of cosmetic field, can be used as functional additive and adds in various emulsions, paste or white shape cosmetics.
The present invention has following advantage and effect with respect to prior art:
(1) nontoxic, the nonirritant of Polyethylene Glycol, has good water solublity, can be used as the protective agent of epidermal growth factor, and the different in kind according to relative molecular mass difference, from no color or smell thick liquid to waxy solid.The present invention selects the Polyethylene Glycol of molecular weight from 2000～20000, and 50 ℃ is all white solid below.
(2) adopting hard paraffin is hydrophobic protective agent, can protect the freezing powder body isolation of epidermal growth factor and Polyethylene Glycol moisture, thereby play the effect of (being greater than 2 years) of long period of activity storage life.
(3) because the hydrophobic solid microsphere containing epidermal growth factor has hydrophobicity, can be used as additive is added in various emulsions, cream, white shape class cosmetics, and can suspend and be statically placed in cosmetics, thoroughly solve epidermal growth factor and be difficult to be added on the problem in cosmetics and skincare product.
(4) preparation technology is simple, does not relate to chemical reaction, produces environmental protection without the three wastes.
(5) contained epidermal growth factor can be acidproof, alkaline-resisting, fast light, waterproof, high temperature resistant (60 ℃ following).
(6) easy to use, only need exert oneself gently, after racking containing the hydrophobic solid microsphere of epidermal growth factor, Polyethylene Glycol is absorbing environmental moisture immediately, makes epidermal growth factor soluble in water, thereby medical value occurs.
Accompanying drawing explanation
Fig. 1 is the scanning electron microscope picture containing the hydrophobic solid microsphere of epidermal growth factor prepared by embodiment 1.
The specific embodiment
Below in conjunction with embodiment and accompanying drawing, the present invention is described in further detail, but embodiments of the present invention are not limited to this.
Embodiment 1
By 10g Polyethylene Glycol (PEG-2000, white solid, 51 ± 2 ℃ of fusing points) join in 100mL deionized water, at 0 ℃, be stirred to completely and dissolve with the speed of 400rpm, freezing rear lyophilizing at-5 ℃, after adopting freezing ball mill-10 ℃ ball milling, (125 μ m), obtain polyglycol porous microsphere to mistake 115 mesh sieves.
At 0 ℃, polyglycol porous 1g microsphere and 0.1g epidermal growth factor powder body (are purchased to Sigma company; Title: EGF Epidermal cell growth factor; Character: lyophilized powder, BioReagent, suitable for cell culture; Cas number: 62229-50-9) join in three-dimensional mixer, first stirring at low speed 1min under 600rpm, then under 1200rpm high-speed stirred 1min, obtain the polyglycol porous microsphere containing epidermal growth factor.
At 0 ℃, 1g is laid on vibrations conveyer belt containing the polyglycol porous microsphere of epidermal growth factor, at 100 ℃, use molten atomizing machine by paraffin (paraffin wax, pathology level, fusing point is 60～62 ℃) after melting, the polyglycol porous microsphere covering containing epidermal growth factor is given in spraying, and spray parameters is 0.1g/mincm
2, be 0.5～1 second containing the polyglycol porous microsphere of epidermal growth factor in the time of staying in molten atomizing district, be then cooled to immediately 0 ℃.By 2 sprayings, obtaining cladding thickness is 25 ± 2 μ m, and (150 μ m), both must be containing the hydrophobic solid microsphere of epidermal growth factor to cross 100 mesh sieves.
Fig. 1 is that (scanning electron microscope is that PHILIPS company produces to the prepared scanning electron microscope (SEM) photograph containing the hydrophobic solid microsphere of epidermal growth factor of this embodiment, model: ESEMXL30, the place of production: Holland), in figure, the visible hydrophobic solid microsphere containing epidermal growth factor is spherical, large bound feet homogeneous, particle diameter is in 100～150 μ m left and right.
Embodiment 2
By 10g Polyethylene Glycol (PEG-4000, white solid, 55 ± 2 ℃ of fusing points) join in 200mL deionized water, at 5 ℃, be stirred to completely and dissolve with the speed of 300rpm, freezing rear lyophilizing at-80 ℃, after adopting freezing ball mill-20 ℃ ball milling, (125 μ m), obtain polyglycol porous microsphere to mistake 115 mesh sieves.
At 5 ℃, polyglycol porous 1g microsphere and 0.2g epidermal growth factor powder body (are purchased to Sigma company; Title: EGF Epidermal cell growth factor; Character: lyophilized powder, BioReagent, suitable for cell culture; Cas number: 62229-50-9) join in three-dimensional mixer, first stirring at low speed 2min under 500rpm, then under 2000rpm high-speed stirred 3min, obtain the polyglycol porous microsphere containing epidermal growth factor.
At 5 ℃, 1g is laid on vibrations conveyer belt containing the polyglycol porous microsphere of epidermal growth factor, at 90 ℃, use molten atomizing machine by paraffin (paraffin wax, pathology level, fusing point is 60～62 ℃) after melting, the polyglycol porous microsphere covering containing epidermal growth factor is given in spraying, and spray parameters is 0.1g/mincm
2, be 0.5～1 second containing the polyglycol porous microsphere of epidermal growth factor in the time of staying in molten atomizing district, be then cooled to immediately 0 ℃.By 2 sprayings, obtaining cladding thickness is 25 ± 2 μ m, and (150 μ m), both must be containing the hydrophobic solid microsphere of epidermal growth factor to cross 100 mesh sieves.
Embodiment 3
By 10g Polyethylene Glycol (PEG-6000, white solid, 57 ± 2 ℃ of fusing points) join in 400mL deionized water, at 15 ℃, be stirred to completely and dissolve with the speed of 200rpm, freezing rear lyophilizing at-65 ℃, after adopting freezing ball mill-15 ℃ ball milling, (125 μ m), obtain polyglycol porous microsphere to mistake 115 mesh sieves.
At 15 ℃, polyglycol porous 1g microsphere and 0.1g epidermal growth factor powder body (are purchased to Sigma company; Title: EGF Epidermal cell growth factor; Character: lyophilized powder, BioReagent, suitable for cell culture; Cas number: 62229-50-9) join in three-dimensional mixer, first stirring at low speed 4min under 300rpm, then under 2500rpm high-speed stirred 4min, obtain the polyglycol porous microsphere containing epidermal growth factor.
At 15 ℃, 1g is laid on vibrations conveyer belt containing the polyglycol porous microsphere of epidermal growth factor, at 85 ℃, use molten atomizing machine by paraffin (paraffin wax, pathology level, fusing point is 60～62 ℃) after melting, the polyglycol porous microsphere covering containing epidermal growth factor is given in spraying, and spray parameters is 0.1g/mincm
2, be 0.5～1 second containing the polyglycol porous microsphere of epidermal growth factor in the time of staying in molten atomizing district, be then cooled to immediately 0 ℃.By 2 sprayings, obtaining cladding thickness is 25 ± 2 μ m, and (150 μ m), both must be containing the hydrophobic solid microsphere of epidermal growth factor to cross 100 mesh sieves.
Embodiment 4
By 10g Polyethylene Glycol (PEG-8000, white solid, 60 ± 2 ℃ of fusing points) join in 600mL deionized water, at 25 ℃, be stirred to completely and dissolve with the speed of 400rpm, freezing rear lyophilizing at-40 ℃, after adopting freezing ball mill-10 ℃ ball milling, (125 μ m), obtain polyglycol porous microsphere to mistake 115 mesh sieves.
At 25 ℃, polyglycol porous 1g microsphere and 0.2g epidermal growth factor powder body (are purchased to Sigma company; Title: EGF Epidermal cell growth factor; Character: lyophilized powder, BioReagent, suitable for cell culture; Cas number: 62229-50-9) join in three-dimensional mixer, first stirring at low speed 5min under 200rpm, then under 3000rpm high-speed stirred 6min, obtain the polyglycol porous microsphere containing epidermal growth factor.
At 25 ℃, 1g is laid on vibrations conveyer belt containing the polyglycol porous microsphere of epidermal growth factor, at 80 ℃, use molten atomizing machine by paraffin (paraffin wax, pathology level, fusing point is 60～62 ℃) after melting, the polyglycol porous microsphere covering containing epidermal growth factor is given in spraying, and spray parameters is 0.1g/mincm
2, be 0.5～1 second containing the polyglycol porous microsphere of epidermal growth factor in the time of staying in molten atomizing district, be then cooled to immediately 0 ℃.By 2 sprayings, obtaining cladding thickness is 25 ± 2 μ m, and (150 μ m), both must be containing the hydrophobic solid microsphere of epidermal growth factor to cross 100 mesh sieves.
Embodiment 5
By 10g Polyethylene Glycol (PEG-10000, white solid, 61 ± 2 ℃ of fusing points) join in 800mL deionized water, at 35 ℃, be stirred to completely and dissolve with the speed of 300rpm, freezing rear lyophilizing at-30 ℃, after adopting freezing ball mill-5 ℃ ball milling, (125 μ m), obtain polyglycol porous microsphere to mistake 115 mesh sieves.
At 35 ℃, polyglycol porous 1g microsphere and 0.1g epidermal growth factor powder body (are purchased to Sigma company; Title: EGF Epidermal cell growth factor; Character: lyophilized powder, BioReagent, suitable for cell culture; Cas number: 62229-50-9) join in three-dimensional mixer, first stirring at low speed 8min under 100rpm, then under 3500rpm high-speed stirred 8min, obtain the polyglycol porous microsphere containing epidermal growth factor.
At 35 ℃, 1g is laid on vibrations conveyer belt containing the polyglycol porous microsphere of epidermal growth factor, at 75 ℃, use molten atomizing machine by paraffin (paraffin wax, pathology level, fusing point is 60～62 ℃) after melting, the polyglycol porous microsphere covering containing epidermal growth factor is given in spraying, and spray parameters is 0.1g/mincm
2, be 0.5～1 second containing the polyglycol porous microsphere of epidermal growth factor in the time of staying in molten atomizing district, be then cooled to immediately 0 ℃.By 2 sprayings, obtaining cladding thickness is 25 ± 2 μ m, and (150 μ m), both must be containing the hydrophobic solid microsphere of epidermal growth factor to cross 100 mesh sieves.
Embodiment 6
By 10g Polyethylene Glycol (PEG-20000, white solid, 62 ± 2 ℃ of fusing points) join in 1000mL deionized water, at 45 ℃, be stirred to completely and dissolve with the speed of 200rpm, freezing rear lyophilizing at-15 ℃, after adopting 0 ℃ of ball milling of freezing ball mill, (125 μ m), obtain polyglycol porous microsphere to mistake 115 mesh sieves.
At 45 ℃, polyglycol porous 1g microsphere and 0.2g epidermal growth factor powder body (are purchased to Sigma company; Title: EGF Epidermal cell growth factor; Character: lyophilized powder, BioReagent, suitable for cell culture; Cas number: 62229-50-9) join in three-dimensional mixer, first stirring at low speed 10min under 20rpm, then under 4000rpm high-speed stirred 10min, obtain the polyglycol porous microsphere containing epidermal growth factor.
At 45 ℃, 1g is laid on vibrations conveyer belt containing the polyglycol porous microsphere of epidermal growth factor, at 70 ℃, use molten atomizing machine by paraffin (paraffin wax, pathology level, fusing point is 60～62 ℃) after melting, the polyglycol porous microsphere covering containing epidermal growth factor is given in spraying, and spray parameters is 0.1g/mincm
2, be 0.5～1 second containing the polyglycol porous microsphere of epidermal growth factor in the time of staying in molten atomizing district, be then cooled to immediately 0 ℃.By 2 sprayings, obtaining cladding thickness is 25 ± 2 μ m, and (150 μ m), both must be containing the hydrophobic solid microsphere of epidermal growth factor to cross 100 mesh sieves.
Application Example
By the hydrophobic solid microsphere containing epidermal growth factor prepared embodiment 1～6, join in various cosmetics, after certain hour, the activity of investigation table skin growth factor.Detection method list of references (Chen Ke, Guo Di, Su Zhijian, Zheng Weidong, yellow Yadong, a fine jade. the fast detecting [J] of cosmetics Concentrations of Epidermal Growth Factor. daily chemical industry .2010,40 (1): 67-70.) carry out.
Embodiment 7
According to formula described in table 1, other raw materials are dispersed in water, be heated with stirring to 75-80 ℃, to dissolving, be cooled to 50 ℃, then add the prepared hydrophobic solid microsphere containing epidermal growth factor of embodiment 1, after stirring, obtain the brilliant white opsonic water that contains epidermal growth factor, specifically fill a prescription as shown in table 1:
Table 1. is containing the brilliant white opsonic water of epidermal growth factor
After 10 days, investigate the activity of brilliant white opsonic water Concentrations of Epidermal Growth Factor, result shows, directly in the brilliant white opsonic water of interpolation epidermal growth factor (contrast sample), the activity of epidermal growth factor is 0, and using the brilliant white opsonic water (test sample) of the present invention containing the hydrophobic solid microsphere of epidermal growth factor, the activity of its epidermal growth factor still remains unchanged.After 2 years, contain in the brilliant white opsonic water of hydrophobic solid microsphere of epidermal growth factor, the activity of its epidermal growth factor still keeps 83% activity.
Embodiment 8
According to formula described in table 2, other raw materials are dispersed in water, be heated with stirring to 75-80 ℃, to dissolving, be cooled to 50 ℃, then add the prepared hydrophobic solid microsphere containing epidermal growth factor of embodiment 2, after stirring, the shining face breast of brilliant white that obtains containing epidermal growth factor, specifically fill a prescription as shown in table 2:
Table 2. is containing the shining face breast of brilliant white of epidermal growth factor
After 10 days, investigate the activity of the shining face of brilliant white Ruzhong epidermal growth factor, result shows, directly add the shining face Ruzhong (contrast sample) of brilliant white of epidermal growth factor, the activity of epidermal growth factor is 0, and using the brilliant white shining face breast (test sample) of the present invention containing the hydrophobic solid microsphere of epidermal growth factor, the activity of its epidermal growth factor still remains unchanged.After 2 years, contain the shining face of the brilliant white Ruzhong of the hydrophobic solid microsphere of epidermal growth factor, the activity of its epidermal growth factor still keeps 93% activity.
Embodiment 9
According to formula described in table 3, other raw materials are dispersed in water, be heated with stirring to 75-80 ℃, to dissolving, be cooled to 50 ℃, then add the prepared hydrophobic solid microsphere containing epidermal growth factor of embodiment 3, after stirring, obtain containing the shining face frost of the yellow brilliant white of dispelling of epidermal growth factor, specifically fill a prescription as shown in table 3:
Table 3. is containing the shining face frost of the yellow brilliant white of dispelling of epidermal growth factor
After 10 days, the dispel activity of the shining face frost of yellow brilliant white Concentrations of Epidermal Growth Factor of investigation, result shows, directly add the shining Yan Shuanzhong (contrast sample) of the yellow brilliant white of dispelling of epidermal growth factor, the activity of epidermal growth factor is 0, and using the dispel yellow brilliant white shining face frost (test sample) of the present invention containing the hydrophobic solid microsphere of epidermal growth factor, the activity of its epidermal growth factor still remains unchanged.After 2 years, contain the shining Yan Shuanzhong of the yellow brilliant white of dispelling of the hydrophobic solid microsphere of epidermal growth factor, the activity of its epidermal growth factor still keeps 95% activity.
Embodiment 10
According to formula described in table 4, other raw materials are dispersed in water, be heated with stirring to 75-80 ℃, to dissolving, be cooled to 50 ℃, then add the prepared hydrophobic solid microsphere containing epidermal growth factor of embodiment 4, after stirring, obtain containing the yellow brilliant white facial milk cleanser of dispelling of epidermal growth factor, specifically fill a prescription as shown in table 4:
Table 4. is containing the yellow brilliant white facial milk cleanser of dispelling of epidermal growth factor
After 10 days, the dispel activity of yellow brilliant white facial milk cleanser Concentrations of Epidermal Growth Factor of investigation, result shows, directly add dispel (the contrast sample) in yellow brilliant white facial milk cleanser of epidermal growth factor, the activity of epidermal growth factor is 0, and using the dispel yellow brilliant white facial milk cleanser (test sample) of the present invention containing the hydrophobic solid microsphere of epidermal growth factor, the activity of its epidermal growth factor still remains unchanged.After 2 years, containing dispelling in yellow brilliant white facial milk cleanser of the hydrophobic solid microsphere of epidermal growth factor, the activity of its epidermal growth factor still keeps 94% activity.
Embodiment 11
According to formula described in table 5, other raw materials are dispersed in water, be heated with stirring to 75-80 ℃, to dissolving, be cooled to 50 ℃, then add the prepared hydrophobic solid microsphere containing epidermal growth factor of embodiment 6, after stirring, obtain containing the yellow brilliant white essence of dispelling of epidermal growth factor, specifically fill a prescription as shown in table 5:
Table 5. is containing the yellow brilliant white essence of dispelling of epidermal growth factor
After 10 days, the dispel activity of yellow brilliant white essence Concentrations of Epidermal Growth Factor of investigation, result shows, directly add dispel (the contrast sample) in yellow brilliant white essence of epidermal growth factor, the activity of epidermal growth factor is 0, and using the dispel yellow brilliant white essence (test sample) of the present invention containing the hydrophobic solid microsphere of epidermal growth factor, the activity of its epidermal growth factor still remains unchanged.After 2 years, containing dispelling in yellow brilliant white essence of the hydrophobic solid microsphere of epidermal growth factor, the activity of its epidermal growth factor still keeps 89% activity.
Clinic trial observation is carried out in containing after the present invention leaves standstill half a year containing the product of the hydrophobic solid microsphere of epidermal growth factor that above-described embodiment 7-11 is prepared, and compares with the product beta test effect of not adding the hydrophobic solid microsphere that contains epidermal growth factor.
The object of observation: 18～45 years old age women.Choosing face has women's 30 examples of pigementation in various degree, the problem skin such as dark yellow, dry.
Observational technique: after cleaning skin, coat the product that embodiment 7-11 prepares before sleep every night.Using continuously 28 days is a course for the treatment of.
Criterion of therapeutical effect: (1) is effective: dark yellow the disappearing of pigment reaches more than 90%, skin has the obvious whitening smooth feeling of moistening; (2) effective: pigment is dark yellow to disappear more than 50%, and skin is moist smooth compared with whitening; (3) invalid: unchanged before and after treatment.Result is as shown in table 6:
The product clinical trial result that table 6. embodiment 7-11 prepares
As can be seen from Table 6, add the present invention containing after the hydrophobic solid microsphere of epidermal growth factor, obvious effective rate obviously promotes.
Above-described embodiment is preferably embodiment of the present invention; but embodiments of the present invention are not restricted to the described embodiments; other any do not deviate from change, the modification done under spirit of the present invention and principle, substitutes, combination, simplify; all should be equivalent substitute mode, within being included in protection scope of the present invention.
Claims (7)
1. a preparation method that contains the hydrophobic solid microsphere of epidermal growth factor, is characterized in that comprising the steps:
(1) 10g Polyethylene Glycol is joined in 100～1000mL deionized water, at 0～45 ℃, be stirred to completely and dissolve with the speed of 200～400rpm, freezing rear lyophilizing at-80～-5 ℃, adopts freezing ball mill under-20～0 ℃ of condition, after ball milling, to cross 115 mesh sieves, obtains polyglycol porous microsphere;
At (2) 0～45 ℃, polyglycol porous 1g microsphere and 0.1～0.2g epidermal growth factor are joined in three-dimensional mixer, first stirring at low speed 1～10min under 20～600rpm, high-speed stirred 1～10min under 1200～4000rpm again, obtains the polyglycol porous microsphere containing epidermal growth factor;
At (3) 0～45 ℃, 1g is laid on vibrations conveyer belt containing the polyglycol porous microsphere of epidermal growth factor, at 70～100 ℃, use molten atomizing machine by after paraffin melting, the polyglycol porous microsphere covering containing epidermal growth factor is given in spraying, and spray parameters is 0.1g/mincm
2, be 0.5～1 second containing the polyglycol porous microsphere of epidermal growth factor in the time of staying in molten atomizing district, be then cooled to immediately 0 ℃; By 2 sprayings, obtaining cladding thickness is 25 ± 2 μ m, crosses 100 mesh sieves, both must be containing the hydrophobic solid microsphere of epidermal growth factor.
2. the preparation method of a kind of hydrophobic solid microsphere containing epidermal growth factor according to claim 1, is characterized in that: the molecular weight polyethylene glycol described in step (1) is 1800～20000 dalton, is solid at 45 ℃, and fusing point is 49～64 ℃.
3. the preparation method of a kind of hydrophobic solid microsphere containing epidermal growth factor according to claim 1, is characterized in that: the Polyethylene Glycol described in step (1) is PEG-2000, PEG-4000, PEG-6000, PEG-8000, PEG-10000 or PEG-20000.
4. the preparation method of a kind of hydrophobic solid microsphere containing epidermal growth factor according to claim 1, is characterized in that: the epidermal growth factor described in step (2) is the powder body that particle diameter is less than 10nm, and mass percent is greater than 99%.
5. the preparation method of a kind of hydrophobic solid microsphere containing epidermal growth factor according to claim 1, is characterized in that: the paraffin described in step (3) is paraffin wax, pathology level, and fusing point is 60～62 ℃.
6. containing a hydrophobic solid microsphere for epidermal growth factor, prepared by the preparation method described in claim 1～5 any one.
7. a kind of hydrophobic solid microsphere containing epidermal growth factor according to claim 6, in the application of cosmetic field, is characterized in that: the described hydrophobic solid microsphere containing epidermal growth factor adds in various emulsions, paste or white shape cosmetics as functional additive.
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