CN107595884A - A kind of head hair follicle vascular endothelial growth factor accelerator - Google Patents
A kind of head hair follicle vascular endothelial growth factor accelerator Download PDFInfo
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- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 title claims abstract description 33
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Abstract
The present invention discloses a kind of head hair follicle vascular endothelial growth factor accelerator, it includes fullerene oil, amino fullerene water solution, the polyhydroxylated fullerene aqueous solution one or more, the accelerator can effectively facilitate expression of the VEGFR 2 at head hair follicle position, so as to play a part of promoting hair growth, hair growth, safely and effectively, have no side effect, it is uneasy to recur, especially androgenetic alopecia, alopecia areata, alopecia seborrheica effect are become apparent from.
Description
Technical field
The present invention relates to field of medicaments, more particularly, to a kind of head hair follicle vascular endothelial growth factor accelerator.
Background technology
At present, hair follicle research Main way be Effect of Mutual Regulation between the true epidermis of hair follicle, be related to multiple genes, growth because
Son, form generation molecule families and signal path etc. as：TGF (TGF), fibroblast growth factor (FGF)/
Wnt paths, BMP families, and EGF, vascular endothelial growth factor, stem cell factor etc..These families
Race, the factor are all made up of mediator and nuclear factor etc. in corresponding acceptor, part, kytoplasm.
Growth of discovered in recent years vascular endothelial growth factor (VEGF) family to hair follicle has regulating and controlling effect, and
Find there is vegf expression on hair papilla cell, hair follicle external root sheath cell in growth period hair follicle.Growth period perifollicolar
Blood vessel is remarkably reinforced, into catagen after the blood vessel of perifollicolar start to degenerate, and stand-down, then vascularization phenomenon stopped, this
Phenomenon is relevant with external root sheath cell VEGF expression.VEGF family members are specific positioned at vascular endothelial cell by combining
Vegf receptor mediation capillary proliferation, the enhancing effect such as vasopermeability and endothelial cell proliferation, vegf receptor are divided into VEGFR-
1st, VEGFR-2 and VGEGFR-3, VEGF propagation is mainly mediated by VEGFR-2 in endothelial cell.Because VEGF is only growing
Expressed in the hair follicle of phase, and weaken in the hairy cyst vegf expression of androgenetic alopecia and patients with alopecia areata and even disappear, this
Suggest that our androgenetic alopecias and alopecia areata are likely to relevant with the horizontal reductions of VEGF, so if local hair can be raised
Tumour VEGF is horizontal, will be expected to treat androgenetic alopecia and alopecia areata, is taken off at present by FDA approval external curing androgenetics
A kind of local topical medicine minoxidil of hair can effectively suppress trichomadesis and promote hair regeneration, but minoxidil is existing
The method of hair growth works, and slow, side effect is big.Therefore a kind of rapid-action, small medicine urgent problem of toxic side effect.
The content of the invention
In order to solve the above-mentioned technical problem, the present invention provides a kind of head hair follicle vascular endothelial growth factor and promoted
Agent, while can promoting the VEGFR-2 to express, the fast and effective and safe function of playing hair growth.
The present invention is achieved through the following technical solutions：
A kind of head hair follicle vascular endothelial growth factor accelerator, comprising fullerene oil, amino fullerene water solution,
The polyhydroxylated fullerene aqueous solution.
Accelerator of the present invention can treat hair follicle vascular endothelial growth factor and decline caused alopecia.
Accelerator of the present invention can raise hair follicle blood vessel endothelial cell growth factor VEGF content, especially raise
Hair follicle blood vessel endothelial cell growth factor VEGF R-2 contents.
Alopecia of the present invention includes androgenetic alopecia, alopecia areata, preferably alopecia seborrheica, androgenetic alopecia and spot
It is bald.
In accelerator of the present invention, the fullerene oil is the combination of fullerene and oil, and wherein fullerene is in fullerene
In oil
Concentration is 0.01-20mg/ml.
Further preferably, fullerene concentration 0.1mg/mL-15mg/mL in the fullerene oil.
Further preferably, fullerene concentration 1-10mg/ml in the fullerene oil.
Fullerene of the present invention is empty fullerene and/or metal fullerene.Including but not limited to fullerene C2n、M@
C2n、M2@C2n、MA@C2n、M3N@C2n、M2C2@C2n、M2S@C2n、M2O@C2nAnd MxA3-xN@C2nAny of, wherein, M and A are equal
For metallic element, the M and A are selected from any one in Sc, Y and lanthanide element；30≤n≤60；0≤x≤3.
Further preferably described fullerene selection C60、C70、C76、C84, Gd@C82, SC3N@C80One or more of mixing
Thing.
Described oil includes but is not limited to the extract of vegetable seeds, flower, rhizome etc., such as olive oil, soybean oil, Asia
Flaxseed oil, prinsepia utilis royle oil, rapeseed oil, Sweet Almond Oil, sunflower oil, safflower seed oil, grape-kernel oil, evening primrose oil, Common Borage seed
Oil, Angelica oil, oil of ginger, SIMMONDSIA CHINENSIS SEED OIL, walnut oil, avocado oil, mango oil, castor oil, apricot kernel oil, shea butter, fructus rosae
Oil, coconut oil, palm oil, cavings oil, wheat-germ oil, pot marigold oil, aloe, palm oil, Sweet Almond Oil, corn oil, Portugal
One or more of mixture such as grape seed oil.Further preferred fullerene oil is fullerene olive oil.
The preparation of the fullerene oil：After fullerene end is sufficiently mixed uniformly with oil, it is placed in ball mill, ultrasound, stirs
Mix, heat, fullerene is fully dissolved in oil, be filtrated to get fullerene oil.
Further preferably, fullerene powder is carried out ball milling and refines 0.05-1 μm by step (1), then by the fullerene after refinement
Powder is mixed with oil, is placed in ball mill 500-1000 revs/min, ball milling 8-20h, obtains fullerene oil suspension, then
Fullerene oil suspension is heated to 40-60 DEG C, nitrogen protection, after stirring 12-72h, centrifugation, filtering, it is molten to obtain fullerene oil
Liquid.
Further preferably, fullerene powder ball milling is refined 0.05-1 μm by step (1), after being sufficiently mixed uniformly with oil, is put
500-700 revs/min in ball mill, ball milling 6-10h, fullerene oil suspension is obtained, suspension is then heated to 40-50
DEG C ultrasound, nitrogen protection, agitating and heating 10-15h, make fullerene fully be dissolved in grease type auxiliary material, centrifuge, are filtrated to get richness
Strangle alkene oil.
Amino fullerene of the present invention is to be prepared by the following method:
(a) Amine Solutions are mixed with solid fullerene, be stirred at room temperature or heating stirring counterflow condition under carry out it is anti-
Should, wherein, organic amine includes at least one of ethylenediamine, propylamine, Propanolamine, p-phenylenediamine and diethanol amine；Solid fullerene
Including empty fullerene C2n, metal fullerene M@C2n、M2@C2n、MA@C2n、M3N@C2n、M2C2@C2n、M2S@C2n、M2O@C2nWith
MxA3-xN@C2nAt least one of, wherein, M and A are independently selected from Sc, Y and lanthanide element, 30≤n≤60,0≤
x≤3。
(b) solution rotating for obtaining step (a) is dried, and the remaining solid after Rotary drying is dissolved with dilute acid soln, its
In, dilute acid soln is inorganic acid solution, and the concentration of dilute acid soln is 0.5~1.5mmol/L.
(c) pH value for the solution that regulating step (b) obtains is 4~6, and the electrical conductivity dialysed to solution is less than 1 μ s/cm.
(d) solution obtained using anion exchange resin process step (c), the electrical conductivity dialysed to solution are less than 1 μ s/
cm。
The polyhydroxylated fullerene is prepared by following methods：By solid fullerene and hydrogenperoxide steam generator and alkali soluble
Liquid hybrid reaction, wherein, it is water-soluble that aqueous slkali includes sodium hydrate aqueous solution, potassium hydroxide aqueous solution and TBAH
At least one of liquid, solid fullerene include empty fullerene C2n、M@C2n、M2@C2n、MA@C2n、M3N@C2n、M2C2@C2n、M2S@
C2n、M2O@C2nAnd MxA3-xN@C2nAt least one of, wherein, M and A are independently selected from Sc, Y and lanthanide element, and 30
≤ n≤60,0≤x≤3；The content of alkali is 8~15wt% in the aqueous slkali；Based on the gross mass of the hydrogenperoxide steam generator,
The content of hydrogen peroxide is 20~40wt% in the hydrogenperoxide steam generator；Hydrogen peroxide described in the mixed solution and institute
The volume ratio for stating aqueous slkali is 7:(1~4)；The reaction is carried out under heating stirring processing, the heating stirring processing
Heating-up temperature be 50~80 degrees Celsius, stir speed (S.S.) be 600~1500rpm/min, and the time is 15~36 hours, to by institute
The mixed solution for stating reaction carries out purification processes.
Further preferably, the preparation of polyhydroxylated fullerene is obtained by following methods：
(a) sodium hydroxide for being 40% by aqueous hydrogen peroxide solution and weight/mass percentage composition that weight/mass percentage composition is 30%
Solution is 7 according to volume ratio:3 add 100mL round-bottomed flasks, add 200mg fullerene solids, use magnetic stirrer
24h, temperature：70 DEG C, rotating speed：1000r/min, filtering, retain filtrate.
(b) filtrate is added in centrifuge tube, adds the ethanol that excessive concentration is 95%.Precipitated by collected after centrifugation,
Centrifugal rotational speed：10000r/min, centrifugation time：4min, precipitation is dissolved in water.
(c) solution for obtaining (b) step carries out dialysis treatment, and the electrical conductivity dialysed to solution is less than 1 μ s/cm.
(d) solution after dialysis is freeze-dried, to obtain polyhydroxylated fullerene solid.Freeze temperature：- 29 DEG C, vacuum
Degree：55Pa, freeze-drying time：48h.
A kind of application method of head hair follicle vascular endothelial growth factor accelerator of the present invention：Fullerene oil can apply
Smear, amino fullerene water solution, the polyhydroxylated fullerene aqueous solution are smeared or gastric infusion mode.
A kind of head hair follicle vascular endothelial growth factor accelerator of the present invention can be used for health products or medicine or food
Or one of active ingredient of skin care item or hair care product, composition is formed with pharmaceutically acceptable carrier or with Chinese medical extract,
Its amount of filling is 0.01-99.99%.
The present invention also provides above-mentioned accelerator and is preparing promotion head hair follicle vascular endothelial growth factor expression medicine
Middle application.Described accelerator is preparing the application in treating androgenetic alopecia medicine.
Compared with prior art, the present invention has the advantages that：
Fullerene olive oil, amino fullerene, polyhydroxylated fullerene can effectively facilitate VEGFR-2 at head hair follicle position
Expression, so as to play the purpose for promoting hair growth, hair growth, safely and effectively, have no side effect, it is uneasy to recur, it is especially right
Androgenetic alopecia, alopecia areata, alopecia seborrheica effect become apparent from, and are come into force once week effective.
Brief description of the drawings
Fig. 1 shows the amino fullerene infrared absorption according to embodiment 1 in amino fullerene of the present invention and embodiment 2
Spectrum.
Fig. 2 shows the amino fullerene electron-beam probe according to amino fullerene embodiment 1 of the present invention and embodiment 2
Analysis result.
Fig. 3 is shown is hydrated particle diameter according to the amino fullerene of amino fullerene embodiment 1 of the present invention and embodiment 2
(Fig. 3 a) and zeta current potentials (Fig. 3 b).
Fig. 4 shows the C prepared according to embodiment 1 in polyhydroxylated fullerene of the present invention60(O)5(OH)12FTIR.
Fig. 5 shows the C prepared according to polyhydroxylated fullerene embodiment 1 of the present invention60(O)5(OH)12X-ray photoelectron energy
Compose C1s peak matched curves.
Fig. 6 shows the C prepared according to polyhydroxylated fullerene embodiment 1 of the present invention60(O)5(OH)12Hydration particle diameter (Fig. 3 a)
With zeta current potentials (Fig. 3 b).
Fig. 7 is according to test example one of the present invention：C60- olive oil group Western Blot detections VEGFR-2 contains spirogram.
Fig. 8 is the test example one according to the present invention：C60- olive oil group RT-PCR detection detections VEGFR-2 contains spirogram, wherein
A：C60- olive oil；B：Olive oil；C：Minoxidil；D：Physiological saline.
Fig. 9 is mouse VEGFR-2, Western the Blot detection levels according to the test example diaminourea fullerene of the present invention
Figure.
Figure 10 be according to the present invention test example diaminourea fullerene mouse VEGFR-2, RT-PCR detection level figure, its
Middle A：Amino fullerene；B minoxidils；C；Physiological saline.
Figure 11 is contained according to mouse VEGFR-2, Western the Blot detections of the test example trihydroxy fullerene of the present invention
Spirogram.
Figure 12 be according to the present invention test example trihydroxy fullerene mouse VEGFR-2, RT-PCR detection level figure, its
Middle A：Polyhydroxylated fullerene；B minoxidils；C：Physiological saline.
Embodiment
The embodiment of the present invention is described in detail below, it is to be understood that protection scope of the present invention is not
Limited by embodiment.
Embodiment fullerene oil
The C70 fullerenes of embodiment 1 oil
Fullerene powder C70 is subjected to ball milling and refines 0.05-1 μm, then by the fullerene powder 1g and soybean oil after refinement
20g is mixed, and is placed in ball mill 500 revs/min, ball milling 8h, obtains fullerene oil suspension, then fullerene oil is suspended
Liquid is heated to 40 DEG C, nitrogen protection, after stirring 12h, centrifugation, filtering, obtains fullerene oil solution.
The C60 fullerenes of embodiment 2 oil
Fullerene powder C60 is subjected to ball milling and refines 0.05-1 μm, then by the fullerene powder 5g and soybean oil after refinement
100g is mixed, and is placed in ball mill 700 revs/min, ball milling 12h, obtains fullerene oil suspension, then fullerene oil is mixed
Suspension is heated to 50 DEG C, nitrogen protection, after stirring 24h, centrifugation, filtering, obtains fullerene oil solution.
The C76 fullerenes of embodiment 3 oil
Fullerene powder C76 is subjected to ball milling and refines 0.05-1 μm, then by the fullerene powder 0.1 after refinement and blue or green bur
Oily 10g is mixed, and is placed in ball mill 1000 revs/min, ball milling 20h, obtains fullerene oil suspension, then fullerene is oily
Suspension is heated to 60 DEG C, nitrogen protection, after stirring 36h, centrifugation, filtering, obtains fullerene oil solution.
The Gd@C82 fullerenes of embodiment 4 oil
Fullerene powder Gd@C82 are subjected to ball milling and refine 0.05-1 μm, then by the fullerene powder 10g and olive after refinement
Olive oil 40g is mixed, and is placed in ball mill 500-1000 revs/min, ball milling 8-20h, obtains fullerene oil suspension, then will
Fullerene oil suspension is heated to 40-60 DEG C, nitrogen protection, after stirring 12-72h, centrifugation, filtering, obtains fullerene oil solution.
The C60 fullerenes of embodiment 5 oil
Fullerene powder C60 is subjected to ball milling and refines 0.05-1 μm, then by the fullerene powder 3g and olive oil after refinement
30g is mixed, and is placed in ball mill 500 revs/min, ball milling 80h, obtains fullerene oil suspension, then fullerene oil is mixed
Suspension is heated to 40 DEG C, nitrogen protection, after stirring 12h, centrifugation, filtering, obtains fullerene oil solution.
The C70 fullerenes of embodiment 6 oil
Fullerene powder C60 is subjected to ball milling and refines 0.05-1 μm, then by the fullerene powder 3g and olive oil after refinement
30g is mixed, and is placed in ball mill 500 revs/min, ball milling 80h, obtains fullerene oil suspension, then fullerene oil is mixed
Suspension is heated to 40 DEG C, nitrogen protection, after stirring 12h, centrifugation, filtering, obtains fullerene oil solution.
The C76 fullerenes of embodiment 7 oil
Fullerene powder C76 is subjected to ball milling and refines 0.05-1 μm, then by the fullerene powder 3g and olive oil after refinement
20g is mixed, and is placed in ball mill 500 revs/min, ball milling 80h, obtains fullerene oil suspension, then fullerene oil is mixed
Suspension is heated to 40 DEG C, nitrogen protection, after stirring 12h, centrifugation, filtering, obtains fullerene oil solution.
The C60 fullerenes of embodiment 8 oil
Fullerene powder C60 is subjected to ball milling and refines 0.05-1 μm, then by the fullerene powder 5g and olive oil after refinement
25g is mixed, and is placed in ball mill 500 revs/min, ball milling 80h, obtains fullerene oil suspension, then fullerene oil is mixed
Suspension is heated to 40 DEG C, nitrogen protection, after stirring 12h, centrifugation, filtering, obtains fullerene oil solution.
The C70 fullerenes of embodiment 9 oil
Fullerene powder C70 is subjected to ball milling and refines 0.05-1 μm, then by the fullerene powder 1g and olive oil after refinement
15g is mixed, and is placed in ball mill 500 revs/min, ball milling 80h, obtains fullerene oil suspension, then fullerene oil is mixed
Suspension is heated to 40 DEG C, nitrogen protection, after stirring 12h, centrifugation, filtering, obtains fullerene oil solution.
Embodiment amino fullerene
Embodiment 1：Prepare C60(EDA)9
(a) 50mL ethylenediamines (analyzing pure, traditional Chinese medicines reagent) are added into 100mL conical flask with cover, adds 50mg solid fowlers
Alkene C60(purity：99%, Xiamen good fortune is taken in the fresh material Science and Technology Ltd.), magnetic stir bar is added, is stirred using magnetic stirring apparatus
Mix 24h (temperature：Room temperature, rotating speed：1000r/min), using solvent filter (volume：1L, filter sizes：200nm, Jin Tenggong
Department) reactant is filtered after obtain brown-red solution.The composition of solution does not participate in the ethylenediamine and C of reaction mainly60(EDA)9。
(b) solution for obtaining (a) step is added in 250ml round-bottomed flask, reuses Rotary Evaporators (model：IKA
RV10basic) by filtrate Rotary drying (temperature completely：70 degrees Celsius, rotating speed：80r/min).By watery hydrochloric acid (concentration：1mol/
L) it is added in round-bottomed flask, vibration flask makes the thing that is evaporated on its inwall be dissolved in watery hydrochloric acid, and it is molten to obtain brownish red clarification
Liquid.
(c) solution for obtaining (b) step uses the NaOH aqueous solution (concentration：10mol/L) neutralization pH test paper is detected as weak
Acid (pH is 5 or so), exists with chlorination salt form to ensure excessive ethylenediamine, can fully be removed in follow-up dialysis step
Go.Solution, which is fitted into bag filter (cutoff 3500) and is put into ultra-pure water, after neutralizing dialyses, and dialyses to the electricity of ultra-pure water
Conductance is less than 1 μ s/cm.
(d) solution after (c) step is dialysed is flowed through equipped with anion exchange resin (Ambersep900 (OH), Yi Nuokai
Reagent Company) chromatographic column, be repeated 3 times.Solution loading bag filter (cutoff 3500) after ion exchange is put into super
Dialysis dialysis to the electrical conductivity of ultra-pure water is less than 1 μ s/cm in pure water.Solution is in the brownish red clarified.
Brown-red solution is dripped on silver mirror, tested after natural drying for infrared spectrum (IR).As shown in figure 1, sample
(- NH is absorbed in 3300nm or so infrared signature2Stretching vibration absworption peak) prove that ethylenediamine is bonded to the carbon of fullerene
Cage, while also prove second two in the change of 800-1500nm infrared signatures absorption (C-C and C=C stretching vibration peak on carbon cage)
Amine has been bonded on carbon cage.Sample solution is dripped in being stained with the electron probe platform of carbonaceous conductive glue, electricity is used for after natural drying
Beamlet probe analysis (EPMA), shown in test result such as Fig. 2 (a), CN elements are only existed in the sample after anion exchange
(H can not be detected), the ethylenediamine for illustrating bonding are present with bulk form rather than with chlorination salt form.Sample solution is straight
Connect for dynamic light scattering (DLS) test, as shown in figure 3, its be hydrated particle diameter 100nm or so and surface it is positively charged, be adapted to
By cell capture, phagocytosis.Sample is freeze-dried for CHN elementary analyses (EA), selects 2 positions in the sample at random, point
Analysis the results are shown in Table 1, by N：C ratio can determine that its chemical composition is C60(EDA)9.By adjusting ethylenediamine and richness in (a) step
The reaction time of alkene is strangled, the quantity of the ethylenediamine of bonding can be regulated and controled, obtains C60(EDA)n, n=5-9.
Table 1：C60(EDA)9Elementary analysis result
Embodiment 2：Prepare Gd@C82(EDA)8
Reaction condition and step with embodiment 1, except that, using 50mg metal fullerene Gd@C82Solid is (pure
Degree：99%, Xiamen good fortune is taken in the fresh material Science and Technology Ltd.) substitute C60.Final obtain contains Gd@C82(EDA)8Clarification brownish black
Solution.Composition detection is carried out to the product of acquisition using method of testing and condition in the same manner as in Example 1, as shown in figure 1,
Infrared signature of the sample in 3300nm or so absorbs (- NH2Stretching vibration absworption peak) prove that ethylenediamine is bonded to fullerene
Carbon cage, while 800-1500nm infrared signatures absorb (C-C and C=C stretching vibration peak on carbon cage) change also prove
Ethylenediamine has been bonded on carbon cage.Sample solution is dripped in being stained with the electron probe platform of carbonaceous conductive glue, used after natural drying
Analyze (EPMA) in electron-beam probe, shown in test result such as Fig. 2 (b), only existed in the sample after anion exchange C,
N, Gd elements (H can not be detected), the ethylenediamine for illustrating bonding are present with bulk form rather than with chlorination salt form.By sample
Product solution is directly used in dynamic light scattering (DLS) test, as shown in figure 3, it is hydrated particle diameter in 100nm or so and surface positively charged
Lotus, it is adapted to by cell capture, phagocytosis.Sample is freeze-dried for CHN elementary analyses (EA), selects 2 in the sample at random
Position, analysis result are shown in Table 2, by N：C ratio can determine that its chemical composition is Gd@C82(EDA)8.By adjust ethylenediamine and
In the reaction time of metal fullerene, the quantity of the ethylenediamine of bonding can be regulated and controled, obtain Gd@C82(EDA) n, n=6-8.Use
Gd in inductively coupled plasma atomic emission spectrum (ICP-AES) test sample3+Ion concentration (uses concentrated nitric acid processing sample
Product, by the Gd acidolysis in sample into Gd3+Ion), it may be determined that sample concentration in solution.
Table 2：Gd@C82(EDA)8Elementary analysis result
Embodiment 3：Prepare Cm(EDA)9(m=70,76,78,84)
Reaction condition and step with embodiment 1, except that, using 50mg C70、C76、C78Or C84Solid is (pure
Degree：99%, Xiamen good fortune is taken in the fresh material Science and Technology Ltd.) substitute C60。
Embodiment 4：Prepare M@C82(EDA)8(M=Y, Ho, Lu)
Reaction condition and step with embodiment 1, except that, using 50mg Y@C82、Ho@C82Or Lu@C82Gu
Body (purity：99%, Xiamen good fortune is taken in the fresh material Science and Technology Ltd.) substitute C60。
Embodiment 5：Prepare M3N@C80(EDA)8(M=Sc, Y, Lu)
Reaction condition and step with embodiment 1, except that, using 50mg Sc3N@C80、Y3N@C80Or Lu3N@
C80Solid (purity：99%, Xiamen good fortune is taken in the fresh material Science and Technology Ltd.) substitute C60。
Embodiment polyhydroxylated fullerene
Embodiment 1：Prepare C60Fullerol
(a) by hydrogen peroxide (analysis pure, the be purchased from traditional Chinese medicines reagent) aqueous solution and 3mL that 7mL weight/mass percentage compositions are 30%
The sodium hydroxide (analyzing pure, traditional Chinese medicines reagent) that weight/mass percentage composition is 40% adds 100mL round-bottomed flasks, adds 200mg fowlers
Alkene C60Solid (purity：99%, Xiamen good fortune is taken in the fresh material Science and Technology Ltd.), add magnetic stir bar (model：B200), make
With magnetic stirrer 24h (temperature：70 DEG C, rotating speed：1000r/min), using solvent filter (volume：1L, filter membrane hole
Footpath：200nm, Jin Teng company) it is filtrated to get brown yellow solution.
(b) solution for obtaining (a) step is added in 50ml centrifuge tube, adds the ethanol that excessive concentration is 95%
(analyzing pure, traditional Chinese medicines reagent).By centrifuging (rotating speed：10000r/min, time：Upper strata colourless solution 4min) is removed afterwards, will be received
The precipitation of collection is dissolved in ultra-pure water, obtains yellow clear solution.
(c) solution that (b) step obtains is fitted into bag filter (cutoff 3500) be put into ultra-pure water and dialyse, thoroughly
Analyse to the electrical conductivity of ultra-pure water and be less than 1 μ s/cm, obtain yellow solution.
(d) solution after (c) step is dialysed is fitted into 50mL plastic centrifuge tubes, dry using freezing is put into after liquid nitrogen frozen
(temperature is freeze-dried in dry machine：- 29 DEG C, vacuum：55Pa, time：48h), obtained yellow solid is loaded into brown sample
It is standby in bottle.
Solid sample is dissolved in into ultra-pure water to drip again on silver mirror, tested after natural drying for infrared spectrum (IR), such as Fig. 4
Shown, sample absorbs (- OH stretching vibration absworption peak) in 3400nm or so infrared signature proves that hydroxyl is bonded to carbon cage；
Belong to the feature of Fullerene Carbon cage in 800-1500nm infrared signatures absorption (C-C and C=C stretching vibration peak on carbon cage) simultaneously
Vibration absorption peak；Eigen vibration peak be 1750nm-1 belong to-C=O stretching vibrations, this be due to-C-OH over oxidations or
Caused by pinacol rearrangement.Solid sample is directly used in X-ray photoelectron spectroscopic analysis, as shown in figure 5, to C members in sample
Plain photoelectron spectroscopy carries out swarming fitting, and the peak that bond energy is 284.68eV belongs to C-C and C=C, and bond energy is 285.91eV peak category
In C-O, bond energy is that 288.58eV peak belongs to C=O, can determine that the chemical composition of sample is C60 (O) according to integral area5
(OH)12.Sample solution is directly used in dynamic light scattering (DLS) test, as shown in fig. 6, sample is hydrated particle diameter in 145nm or so
And surface is negatively charged, can be present in steadily in the long term in the aqueous solution.Solid sample is used for CHN elementary analyses (EA), taken
Two random sites (1# and 2#) carry out elementary analysis in sample.It the results are shown in Table 3.C content in table 3 can be to sample
In Fullerol quantified.
Table 3：C60Fullerol elementary analysis result
By adjusting hydrogen peroxide and C in (a) step60Reaction temperature and the reaction time, the hydroxyl of bonding can be regulated and controled
Quantity (C60(O)5(OH)n, n=16-30).
Embodiment 2：Prepare Cn (n=70,76,78,84) Fullerol
Preparation method and preparation condition with embodiment 1, except that, in step (a), C is respectively adopted70、C76、C78
And C84Substitute C60。
Embodiment 3：Prepare metal fullerene M@C82Fullerol
Preparation method and preparation condition are the same as embodiment 1.Except that in step (a), Y@C are respectively adopted82、Ho@
C82And Lu@C82Substitute C60。
Embodiment 4：Prepare M3N@C80Fullerol
Preparation method and preparation condition are the same as embodiment 1.Except that in step (a), Y is respectively adopted3N@C82、
Sc3N@C82And Lu3N@C82Substitute C60。
Test example
Test example one：C57BL/6 black rats are 8 weeks big, will be by 1 after etherization：The rosin heating paraffin of 1 ratio mixing
Mouse back is applied to after thawing, is peelled off after its cooling is hardened, is pulled out all amortization period hairs, induce the growth of high level of synchronization
Phase hair development, the hair follicle and the growth period hair follicle that spontaneously forms morphologically indifference.Its back hair growth is complete after 9 days
Entirely.Mouse is divided into 4 groups, respectively C60- olive oil group, olive oil group, minoxidil group, physiological saline group, daily backside
After smearing 150 microlitres, 14 days, mouse back skin is taken, VEGFR-2 contents are detected using Western Blot and RT-PCR method.
As a result：Fig. 7 Western Blot detections are as can be seen that C is smeared at back60Mouse VEGFR-2 contents apparently higher than
Other groups；Fig. 8 RT-PCR detections are as can be seen that C is smeared at back60Mouse, VEGFR-2 contents are apparently higher than other groups.
Conclusion：The accelerator of the fullerene oil of the present invention can raise VEGFR-2 contents, hair growth, swash for male
The plain alopecia of source property and alopecia areata positive effect are better than minoxidil.
Test example two：C57BL/6 black rats are 8 weeks big, will be by 1 after etherization：The rosin heating paraffin of 1 ratio mixing
Mouse back is applied to after thawing, is peelled off after its cooling is hardened, is pulled out all amortization period hairs, induce the growth of high level of synchronization
Phase hair development, the hair follicle and the growth period hair follicle that spontaneously forms morphologically indifference.Its back hair growth is complete after 9 days
Entirely.Mouse is divided into 3 groups, respectively amino fullerene group, minoxidil group, physiological saline group, it is micro- that daily back smears 150
Rise, after 14 days, take mouse back skin, VEGFR-2 contents are detected using Western Blot and RT-PCR method.As a result：It is attached
Fig. 9, the Western Blot detections of amino fullerene group are as can be seen that the mouse VEGFR-2 that amino fullerene is smeared at back contains
Measure apparently higher than other groups；Accompanying drawing 10：As can be seen that the mouse of amino fullerene is smeared at back, VEGFR-2 contains for RT-PCR detections
Measure apparently higher than other groups.
Conclusion：The amino fullerene accelerator of the present invention can raise VEGFR-2 contents, hair growth, swash for male
The plain alopecia of source property and alopecia areata positive effect are better than minoxidil.
Test example three：C57BL/6 black rats are 8 weeks big, will be by 1 after etherization：The rosin heating paraffin of 1 ratio mixing
Mouse back is applied to after thawing, is peelled off after its cooling is hardened, is pulled out all amortization period hairs, induce the growth of high level of synchronization
Phase hair development, the hair follicle and the growth period hair follicle that spontaneously forms morphologically indifference.Its back hair growth is complete after 9 days
Entirely.Mouse is divided into 3 groups, respectively polyhydroxylated fullerene group, minoxidil group, physiological saline group, it is micro- that daily back smears 150
Rise, after 14 days, take mouse back skin, VEGFR-2 contents are detected using Western Blot and RT-PCR method.As a result：It is attached
Figure 11 explanations：Western Blot detection as can be seen that back smear polyhydroxylated fullerene mouse VEGFR-2 contents apparently higher than
Other groups；Accompanying drawing 12 illustrates：As can be seen that the mouse of polyhydroxylated fullerene is smeared at back, VEGFR-2 contents are obvious for RT-PCR detections
Higher than other groups.
Conclusion：The polyhydroxylated fullerene accelerator of the present invention can raise VEGFR-2 contents, hair growth, swash for male
The plain alopecia of source property and alopecia areata positive effect are better than minoxidil.
The description of the foregoing specific illustrative embodiment to the present invention is to illustrate and the purpose of illustration.These descriptions
It is not wishing to limit the invention to disclosed precise forms, and it will be apparent that according to above-mentioned teaching, can be much changed
And change.The purpose of selecting and describing the exemplary embodiment is that explain that the certain principles of the present invention and its reality should
With so that those skilled in the art can realize and utilize the present invention a variety of exemplaries and
Various chooses and changes.The scope of the present invention is intended to be limited by claims and its equivalents.
Claims (10)
1. a kind of head hair follicle vascular endothelial growth factor accelerator, it is characterised in that it is rich that it includes fullerene oil, amino
It is one or more of to strangle aqueous solution, the polyhydroxylated fullerene aqueous solution.
2. a kind of head hair follicle vascular endothelial growth factor accelerator as claimed in claim 1, it is characterised in that described
Accelerator can treat hair follicle vascular endothelial growth factor and decline caused alopecia.
3. a kind of head hair follicle vascular endothelial growth factor accelerator as claimed in claim 1, it is characterised in that described
Accelerator can raise hair follicle blood vessel endothelial cell growth factor VEGF content.
4. a kind of head hair follicle vascular endothelial growth factor accelerator as claimed in claim 3, it is characterised in that described
Accelerator can raise hair follicle blood vessel endothelial cell growth factor VEGF R-2 contents.
5. a kind of head hair follicle vascular endothelial growth factor accelerator as claimed in claim 2, it is characterised in that described
Alopecia includes androgenetic alopecia, alopecia areata, alopecia seborrheica.
6. a kind of head hair follicle vascular endothelial growth factor accelerator as claimed in claim 1, it is characterised in that described
Fullerene oil, wherein fullerene concentration in fullerene oil is 0.01-20mg/ml；It is rich in the further preferred fullerene oil
Strangle alkene concentration 0.1mg/mL-15mg/mL；Further preferably, fullerene concentration 1-10mg/ml in the fullerene oil.
7. a kind of head hair follicle vascular endothelial growth factor accelerator as claimed in claim 1, it is characterised in that described
Amino fullerene is to be prepared by the following method：
(a) Amine Solutions are mixed with solid fullerene, be stirred at room temperature or heating stirring counterflow condition under reacted, its
In, organic amine includes at least one of ethylenediamine, propylamine, Propanolamine, p-phenylenediamine and diethanol amine；Solid fullerene includes sky
Heart fullerene C2n, metal fullerene M@C2n、M2@C2n、MA@C2n、M3N@C2n、M2C2@C2n、M2S@C2n、M2O@C2nAnd MxA3-xN@
C2nAt least one of, wherein, M and A are independently selected from Sc, Y and lanthanide element, 30≤n≤60,0≤x≤3；
(b) solution rotating for obtaining step (a) is dried, and the remaining solid after Rotary drying is dissolved with dilute acid soln, wherein, it is dilute
Acid solution is inorganic acid solution, and the concentration of dilute acid soln is 0.5~1.5mmol/L；
(c) pH value for the solution that regulating step (b) obtains is 4~6, and the electrical conductivity dialysed to solution is less than 1 μ s/cm；
(d) solution obtained using anion exchange resin process step (c), the electrical conductivity dialysed to solution are less than 1 μ s/cm.
8. a kind of head hair follicle vascular endothelial growth factor accelerator as claimed in claim 1, it is characterised in that described
Polyhydroxylated fullerene is prepared by following methods：By solid fullerene and hydrogenperoxide steam generator and aqueous slkali hybrid reaction,
Wherein, aqueous slkali include sodium hydrate aqueous solution, potassium hydroxide aqueous solution and the TBAH aqueous solution at least it
One, solid fullerene includes empty fullerene C2n、M@C2n、M2@C2n、MA@C2n、M3N@C2n、M2C2@C2n、M2S@C2n、M2O@C2n
And MxA3-xN@C2nAt least one of, wherein, M and A are independently selected from Sc, Y and lanthanide element, 30≤n≤60, and 0
≤x≤3；The content of alkali is 8~15wt% in the aqueous slkali；Based on the gross mass of the hydrogenperoxide steam generator, the peroxide
The content for changing hydrogen peroxide in hydrogen solution is 20~40wt%；Hydrogen peroxide described in the mixed solution and the aqueous slkali
Volume ratio be 7:(1~4)；The reaction is carried out under heating stirring processing, the heating temperature of the heating stirring processing
Spend for 50~80 degrees Celsius, stir speed (S.S.) is 600~1500rpm/min, and the time is 15~36 hours, to by the reaction
The mixed solution carries out purification processes.
9. accelerator as claimed in claim 1 is in promotion head hair follicle vascular endothelial growth factor expression medicine is prepared
Application.
10. accelerator as claimed in claim 1 is preparing the application in treating androgenetic alopecia medicine.
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| WO2009114089A2 (en) * | 2008-03-03 | 2009-09-17 | Luna Innovations Incorporated | Using fullerenes to enhance and stimulate hair growth |
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| CN106265115A (en) * | 2016-10-09 | 2017-01-04 | 中国科学院化学研究所 | Water-soluble fullerenes derivates application in promoting hair growth |
| CN107555418A (en) * | 2016-06-30 | 2018-01-09 | 中国科学院化学研究所 | Amino fullerene and preparation method thereof |
| CN107556166A (en) * | 2016-06-30 | 2018-01-09 | 中国科学院化学研究所 | Polyhydroxylated fullerene and preparation method thereof |
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| WO2009114089A2 (en) * | 2008-03-03 | 2009-09-17 | Luna Innovations Incorporated | Using fullerenes to enhance and stimulate hair growth |
| CN102898542A (en) * | 2012-10-23 | 2013-01-30 | 郑州大学 | Water-soluble fullerene and application thereof |
| CN104997646A (en) * | 2015-07-09 | 2015-10-28 | 北京福纳康生物技术有限公司 | Oil-soluble fullerene solution and preparation method thereof |
| CN107555418A (en) * | 2016-06-30 | 2018-01-09 | 中国科学院化学研究所 | Amino fullerene and preparation method thereof |
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