CN117137810A

CN117137810A - Polylactic acid/metal-doped nanohydroxyapatite composite sunscreen microspheres and preparation method thereof

Info

Publication number: CN117137810A
Application number: CN202310805691.1A
Authority: CN
Inventors: 韩颖超; 林锶
Original assignee: Wuhan University of Technology WUT
Current assignee: Wuhan University of Technology WUT
Priority date: 2023-07-03
Filing date: 2023-07-03
Publication date: 2023-12-01

Abstract

The invention discloses polylactic acid/metal doped nano hydroxyapatite composite sun-proof microspheres and a preparation method thereof. The composite sun-proof microsphere takes polylactic acid as an organic matrix material and metal doped nano-hydroxyapatite as a ceramic phase, so that metal doped nano-hydroxyapatite particles are dispersed in, wrapped by or compounded and fixed on the surface of the polylactic acid microsphere to form a micro-nano composite structure; wherein the size distribution of the composite sun-proof microsphere is 1-150 mu m, and the metal doped nano hydroxyapatite accounts for 0.1-30wt% of the polylactic acid. The PLA/M-nHAP composite sun-screening microsphere structurally has light reflection and scattering effects, the M-nHAP ceramic phase on the components has good ultraviolet absorption function, the micro-nano composite structure effectively improves the ultraviolet absorption performance of the composite microsphere, and the physical blocking and chemical absorption dual effects can cooperatively realize the good ultraviolet sun-screening function and can be used for preparing sun-screening products.

Description

Polylactic acid/metal doped nano hydroxyapatite composite sun-screening microsphere and preparation method thereof

Technical Field

The invention relates to the technical field of sun-proof cosmetics, in particular to polylactic acid/metal doped nano hydroxyapatite composite sun-proof microspheres and a preparation method thereof.

Background

The skin is used as the largest organ of human body, and can resist the invasion of external bad environment or harmful substances. It has been found that exposure to ultraviolet light over time can cause numerous problems in skin such as erythema, pigmentation, photoaging, skin cancer, and the like. Therefore, it is important to make sun protection measures.

Common organic sunscreens include phenones, cinnamic acid esters, para-aminobenzoic acid and derivatives thereof, but the phenones are toxic to corals and cause damage to the marine ecosystem; the use amount of cinnamic acid esters is large, but the sun protection performance and the light stability are not high; para aminobenzoic acid and its derivatives are liable to cause adverse reactions such as photosensitive reaction, contact dermatitis, etc., and cannot be added excessively. Ceramic sunscreens are relatively safe compared with organic matters, and nano titanium dioxide, zinc oxide and the like are common in the ceramic sunscreens which are used more. The ceramic sun-screening agent has the advantages of wide-spectrum sun-screening, high stability and high safety for shielding UVB and UVA. However, the ceramic sun-screening agent has the defects of larger refractive index, unnatural white produced when the ceramic sun-screening agent is smeared on the face, and thereby the appearance is influenced, the phenomenon is greatly lightened when the size of the ceramic sun-screening agent is reduced to the nanometer level, but a new problem appears at the same time, nano titanium dioxide and zinc oxide are discharged into water, the water quality is polluted, the development of organisms such as sea urchins and the like is negatively influenced, and nano ceramic particles have potential risks of pore blockage, respiratory tract absorption, free radical formation induction and the like.

The construction of the composite sun-proof microsphere by adopting a mode of compounding the macromolecule and the nano ceramic particles is an effective way for solving the problems. At present, a polymerization method is generally adopted to construct the composite sun-proof microsphere, so that the production process is complex, and the risk of residues exists. Meanwhile, compared with a simple nano ceramic particle sun-screening agent, the sun-screening performance of the composite sun-screening microsphere can be obviously reduced due to the lower doping amount of the nano ceramic particles.

Disclosure of Invention

The invention aims to overcome the technical defects, and provides polylactic acid/metal doped nano hydroxyapatite composite sun-screening microspheres and a preparation method thereof, which solve the technical problems that the preparation method of the composite sun-screening microspheres in the prior art is complex and the sun-screening performance is obviously reduced.

In a first aspect, the invention provides a polylactic acid/metal doped nano-hydroxyapatite composite sun-screening microsphere, which takes polylactic acid as an organic matrix material and metal doped nano-hydroxyapatite particles as a ceramic phase, so that the metal doped nano-hydroxyapatite particles are dispersed, wrapped in or compounded and fixed on the surface of the polylactic acid microsphere to form a micro-nano composite structure; wherein the size distribution of the composite sun-proof microsphere is 1-150 mu m, and the metal doped nano hydroxyapatite accounts for 0.1-30wt% of the polylactic acid.

In a second aspect, the invention provides a preparation method of polylactic acid/metal doped nano hydroxyapatite composite sun-screening microspheres, which comprises the following steps:

s1, uniformly dispersing soluble phosphate, soluble calcium salt and soluble doped metal salt into water, and then preparing metal doped nano-hydroxyapatite by a coprecipitation method-hydrothermal method;

s2, preparing the polylactic acid/metal doped nano hydroxyapatite composite sun-proof microsphere by an emulsion solvent volatilization method or a Pickering emulsification technology.

In a third aspect, the present invention provides a cosmetic sunscreen composition comprising the polylactic acid/metal doped nano-hydroxyapatite composite sunscreen microspheres described above.

Compared with the prior art, the invention has the beneficial effects that:

the PLA/M-nHAP composite sun-screening microsphere structurally has light reflection and scattering effects, the M-nHAP ceramic phase on the component has good ultraviolet absorption function, the micro-nano composite structure effectively improves the ultraviolet absorption performance of the composite microsphere, and the physical blocking and chemical absorption dual effects can cooperatively realize the good ultraviolet sun-screening function; the PLA/M-nHAP composite sun-screening microsphere has broad-spectrum sun-screening effect, is safe, stable, non-irritating and environment-friendly, is a novel sun-screening agent with excellent performance, and can be used for preparing sun-screening products.

Drawings

FIG. 1 shows XRD patterns of Fe-nHAP prepared in examples 1 and 2;

FIG. 2 is an ultraviolet absorption spectrum of Fe-nHAP prepared in examples 1 and 2;

FIG. 3 is an XRD spectrum of Fe-nHAP prepared in examples 2, 3 and 4;

FIG. 4 is an ultraviolet absorption spectrum of Fe-nHAP prepared in examples 2, 3, and 4;

FIG. 5 is an XRD spectrum of Fe-nHAP prepared in examples 5, 6 and 7;

FIG. 6 is an ultraviolet absorption spectrum of Fe-nHA prepared in examples 5, 6 and 7;

FIG. 7 is a transmission electron microscope image of Fe-nHAP prepared in examples 2, 5, 6, and 7;

FIG. 8 is a scanning electron microscope image of PLA/Fe-nHAP composite microspheres prepared in examples 7 and 8, the magnification of example 7 being 100, the magnification of example 8 being 2000;

FIG. 9 is a scanning electron microscope image of PLA/Fe-nHAP composite microspheres prepared in example 7 at a magnification of 2000;

FIG. 10 is a plot of particle size distribution statistics of PLA/Fe-nHAP composite microspheres prepared in examples 7 and 8;

FIG. 11 is a scanning electron microscope image of PLA/Fe-nHAP composite microspheres prepared in examples 9 and 10;

FIG. 12 is a graph showing the particle size distribution of PLA/Fe-nHAP composite microspheres prepared in examples 9 and 10;

FIG. 13 is a scanning electron microscope image of PLA/Fe-nHAP composite microspheres prepared in examples 11 and 12;

FIG. 14 is a graph showing the particle size distribution of PLA/Fe-nHAP composite microspheres prepared in examples 11 and 12;

FIG. 15 is a scanning electron microscope image of PLA/Fe-nHAP composite microspheres prepared in example 13;

FIG. 16 is a particle size distribution diagram of PLA/Fe-nHAP composite microspheres prepared in example 13;

FIG. 17 is an ultraviolet absorption spectrum of PLA/Fe-nHAP composite microspheres prepared in example 13;

FIG. 18 is a scanning electron microscope image of pure PLA microspheres prepared in examples 14 and 15;

FIG. 19 is a graph showing the particle size distribution of pure PLA microspheres prepared in examples 14 and 15;

FIG. 20 is an ultraviolet absorbance spectrum of pure PLA microspheres prepared in examples 14 and 15;

FIG. 21 is a scanning electron microscope image of PLA/Fe-nHAP composite microspheres prepared in example 16;

FIG. 22 is an ultraviolet absorption spectrum of PLA/Fe-nHAP composite microspheres prepared in examples 16 and 17;

FIG. 23 is a scanning electron microscope image of PLA/Fe-nHAP composite microspheres prepared in examples 17 and 18;

FIG. 24 is a mapping scan of PLA/Fe-nHAP composite microspheres prepared in example 17;

FIG. 25 is an ultraviolet absorption spectrum of PLA/Fe-nHAP composite microspheres prepared in examples 17 and 18;

FIG. 26 is a fluorescent staining chart of living and dead Fe-nHAP coculture cells in application example 1;

FIG. 27 is a graph showing a model of a guinea pig model for phototoxicity test of Fe-nHAP nanoparticles in application example 3;

FIG. 28 is a graph showing a model of a New Zealand rabbit tested for multiple skin irritation by Fe-nHAP in application example 4;

FIG. 29 is an ultraviolet absorption spectrum of Fe-nHAP and a commercial sunscreen agent in application example 5;

FIG. 30 is an ultraviolet absorption spectrum of Fe-nHAP and its composite microsphere in application example 6.

Detailed Description

The present invention will be described in further detail with reference to the drawings and examples, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.

In a first aspect, the invention provides a polylactic acid/metal doped nano-hydroxyapatite composite sun-screening microsphere (PLA/M-nHAP), wherein the composite sun-screening microsphere takes polylactic acid (PLA) as an organic matrix material and metal doped nano-hydroxyapatite (M-nHAP) particles as a ceramic phase, so that the M-nHAP particles are dispersed, wrapped in or compounded and fixed on the surface of the PLA microsphere to form a micro-nano composite structure; the size distribution of the composite sun-proof microsphere is 1-150 mu M, and the mass content of the ceramic phase M-nHAP occupying the matrix PLA of the machine is 0.1-30wt%.

The invention realizes the ultraviolet sun-proof effect by cooperation of physical separation and chemical absorption based on the light reflection and scattering effects of the micro-nano composite structure of the PLA and the M-nHAP composite microsphere and the ultraviolet absorption functions of the M-nHAP ceramic phase component. Meanwhile, the inventor finds that M-nHAP is dispersed and wrapped in PLA matrix and has better sun-screening performance than the composite sun-screening microsphere formed by compositing and fixing on the surface of PLA matrix. The reasons for this may be: the M-nHAP nano particles are dispersed and wrapped in the composite microsphere, so that physical shielding can be realized on the surface, ultraviolet absorption is increased in the microsphere through the nano particles, and the micro-nano composite structure is favorable for improving uniform dispersion of the M-nHAP particles in a matrix and fully playing the ultraviolet absorption function of the M-nHAP particles, so that the sun-proof effect of the sun-proof microsphere is synergistically improved.

In this embodiment, the size distribution of the composite sunscreen microspheres is 20 μm to 140 μm, and the average particle size is 40 μm to 60 μm; the ceramic phase M-nHAP occupies 10-30wt% of the mass of the organic matrix PLA, and further 20-30wt%. In the range of the size distribution and the average particle size, the ultraviolet absorption performance of the composite sun-screening microsphere after the composite sun-screening microsphere wraps M-nHAP particles with the content of 20 percent is equivalent to that of pure M-nHAP, and the sun-screening effect can be reduced excessively on the premise of ensuring safety, stability, no stimulation and environmental friendliness.

In the embodiment, the metal M is one or more of Fe, zn and Mn; the molar percentage R of the metal M doping is 0.3 to 20wt% (r=m/(ca+m)), preferably 7 to 10wt%.

In some embodiments of the invention, the metal M is Fe and the M-nHAP particles have a morphology of rods, a length of 20-600nm and a diameter of 10-55nm.

In this embodiment, the molecular weight of polylactic acid is 0.5 to 30 ten thousand, and more preferably 10 ten thousand.

s1, uniformly dispersing soluble phosphate, soluble calcium salt and soluble doped metal salt into water, and then preparing nano ceramic particles M-nHAP by a coprecipitation method-hydrothermal method;

The composite sun-proof microsphere adopts an emulsion solvent volatilization method and Pickering emulsification technology to construct a micro-nano composite structure of the PLA/Fe-nHAP sun-proof microsphere, and the preparation method is simple and does not have residue risk. The invention can realize the dispersion and wrapping of M-nHAP particles in PLA microballoons or the compounding and fixing of the M-nHAP particles on the PLA microballoons, the size of the compound microballoons can be adjusted between 1 mu M and 150 mu M according to the requirement, and the mass content of the ceramic phase M-nHAP occupying matrix PLA can be adjusted within 0.1 to 30wt percent according to the requirement.

In this embodiment, the soluble phosphate is diammonium phosphate or disodium phosphate, the soluble calcium salt is calcium chloride or calcium nitrate, and the soluble doped metal salt is a hydrochloride or nitrate of the soluble doped metal. It will be appreciated by those skilled in the art that the soluble phosphate salts, soluble calcium salts, soluble doped metal salts herein also include their corresponding hydrates.

In this embodiment, in step S1, the molar ratio of Ca+M to P is 1.6 to 1.8.

In this embodiment, in step S1, the temperature of the reaction is 37 to 150 ℃, preferably 150 ℃; the reaction time is 0.5 to 5 hours, preferably 3 hours.

In this embodiment, step S1 specifically includes:

s11, dissolving soluble phosphate into water to obtain a reaction solution A; wherein, the concentration of the soluble phosphate in the reaction solution A is 0.001-0.05mol/L, and further 0.01-0.03mol/L;

s12, dissolving soluble calcium salt and soluble doped metal salt into water to obtain a reaction solution B; wherein, the total concentration of Ca+M in the reaction solution B is 0.01-0.1mol/L, and further 0.03-0.07mol/L;

s13, adding the reaction solution A into the reaction solution B, regulating the pH value to 9-10, stirring and reacting for 0.5-1h, transferring the precursor solution into a reaction kettle for crystallization treatment, and centrifuging, washing and freeze-drying to obtain the nano ceramic particles M-nHAP.

In this embodiment, in step S2, the preparation of the polylactic acid/metal doped nano-hydroxyapatite composite sunscreen microspheres by a Pickering emulsification technique includes:

S21A, dissolving polylactic acid in an organic solvent to prepare a pure polylactic acid solution; wherein, in the pure polylactic acid solution, the concentration of the pure polylactic acid solution is 0.1 to 10 weight percent, and the organic solvent is methylene dichloride;

S22A, uniformly dispersing nano ceramic particles M-nHAP into water to prepare M-nHAP aqueous suspension; wherein, in the M-nHAP aqueous suspension, the concentration of the M-nHAP is 0.01 to 0.1 weight percent;

S23A, adding a pure polylactic acid solution into an M-nHAP aqueous suspension, uniformly mixing the pure polylactic acid solution and the M-nHAP aqueous suspension, fully volatilizing an organic solvent, and centrifuging, washing and freeze-drying to obtain the polylactic acid/metal doped nano hydroxyapatite composite sun-proof microsphere; wherein the mass content of the M-nHAP is 0.1-30wt%, further 10-30wt% and further 20-30wt% of the polylactic acid; uniformly mixing the pure polylactic acid solution and the M-nHAP aqueous suspension by adopting a liquid phase homogenizer, and fully volatilizing the organic solvent; further, the homogenizing speed is 500-4500rpm, and the homogenizing time is 5-100min.

It should be noted that the order of steps S21A and S22A is not limited in the present invention, and those skilled in the art may choose according to the actual situation.

In this embodiment, in step S2, the preparation of the polylactic acid/metal doped nano-hydroxyapatite composite sunscreen microspheres by the emulsion solvent evaporation method includes:

S21B, dissolving polylactic acid in an organic solvent to prepare a pure polylactic acid solution, and then uniformly dispersing nano ceramic particles M-nHAP into the pure polylactic acid solution to prepare a polylactic acid mixture containing the M-nHAP; wherein, in the pure polylactic acid solution, the concentration of the pure polylactic acid solution is 0.1 to 10 weight percent, and the organic solvent is methylene dichloride; in the polylactic acid mixture containing the M-nHAP, the mass content of the M-nHAP in the polylactic acid is 0.1-30wt%, further 10-30wt% and further 20-30wt%; uniformly dispersing nano ceramic particles M-nHAP into a pure polylactic acid solution in an ice water bath ultrasonic mode, wherein the time of the ice water bath ultrasonic is 5-100min;

S22B, dissolving polyvinyl alcohol (PVA) into water to prepare a PVA solution; wherein, in the PVA solution, the concentration of PVA is 1-10mg/ml; dissolving polyvinyl alcohol into water by stirring 0.5-2 h at 70-100 ℃ after mixing the polyvinyl alcohol and the water, and cooling to room temperature to prepare a PVA solution;

S23B, adding the polylactic acid mixture containing M-nHAP into the PVA solution, uniformly mixing the polylactic acid mixture and the PVA solution, fully volatilizing the organic solvent, and centrifuging, washing and freeze-drying to obtain the polylactic acid/metal doped nano hydroxyapatite composite sun-screening microsphere; uniformly mixing the polylactic acid mixture containing M-nHAP and the PVA solution by adopting a constant-speed stirrer, and fully volatilizing the organic solvent; further, the stirring speed is 500-4500rpm, and the stirring time is 3-12h.

It should be noted that the order of steps S21B and S22B is not limited in the present invention, and those skilled in the art may choose according to the actual situation.

Example 1

1.78g of disodium hydrogen phosphate dihydrate is weighed and dissolved in 500ml of deionized water to obtain a reaction solution A (the concentration is 0.02 mol/L); 2.43g of calcium chloride dihydrate and 0.033g of ferrous chloride tetrahydrate are weighed and dissolved in 500ml of deionized water to obtain a reaction solution B (the total concentration of Ca+Fe is 0.0334mol/L, and Fe/(Ca+Fe) is 1%); adding the reaction solution A into the reaction solution B, regulating the pH to about 9.5, stirring and reacting for 1h, transferring the precursor solution into a reaction kettle for crystallization treatment, reacting for 3h at 37 ℃ to synthesize Fe-nHAP, and centrifuging, washing and freeze-drying to obtain Fe-nHAP powder. The powder produced was a HAP phase (FIG. 1) and had a high UV absorption in the 200-400nm range (FIG. 2).

Example 2

The difference compared to example 1 is only that Fe-nHAP was synthesized by reacting at 150℃for 3 hours. The nano powder has good crystallinity (figure 1) and good ultraviolet absorption performance in the range of 200-400nm (figures 2, 3 and 4). Fe-nHAP has a rod shape with a length of 40-160nm and a diameter of 10-40nm (FIG. 7, table 1).

As is evident from the comparison of examples 1-2, increasing the reaction temperature is more advantageous in improving the crystallinity and ultraviolet absorption properties of Fe-nHAP.

Example 3

The difference compared to example 2 is only that Fe-nHAP was synthesized by reacting at 150℃for 0.5 h. Has ultraviolet absorption performance in 200-400nm range (figures 3 and 4).

Example 4

The difference compared to example 3 is only that Fe-nHAP was synthesized by reacting at 150℃for 5 hours. The nano powder has good crystallinity and higher ultraviolet absorption performance in the range of 200-400nm (figures 3 and 4).

As is clear from the comparison of examples 2 to 4, increasing the reaction time within a certain range is advantageous for improving the crystallinity and ultraviolet absorption performance of Fe-nHAP, but the ultraviolet absorption performance tends to decrease when the reaction time is too high.

Example 5

Compared with example 4, the difference is that Fe/(Ca+Fe) is 0.3%, fe-nHAP is synthesized by reacting for 3 hours at 150 ℃, TEM observation powder is in a rod shape, the length is 20-180nm, the diameter is 10-45nm, and the ultraviolet absorption performance is better in the range of 200-400nm (figures 5, 6, 7 and table 1).

Example 6

The difference compared to example 5 is only that Fe/(Ca+Fe) is 10%. The metal ion doping ratio of the nano powder is 10%, the ultraviolet absorption performance is excellent in the range of 200-400nm, the maximum absorption can reach 1.5, the nano particles are rod-shaped, the length is 20-600nm, and the diameter is 15-55nm (figures 5, 6, 7 and table 1).

Example 7

In comparison with example 6, fe-nHAP was produced only in that Fe/(Ca+Fe) was 7%. The nanoparticles were rod-shaped with a length of 8.44-129.58nm and a diameter of 9.4-30nm (FIGS. 5, 6, 7, table 1). Dispersing 0.16g of the synthesized Fe-nHAP powder into 800ml of water, and uniformly dispersing for 5min by ultrasonic treatment to obtain Fe-nHAP water suspension (wherein the mass percentage of the ceramic powder is 0.02 wt%); dissolving 0.8g of polylactic acid with molecular weight of 10 ten thousand into 80ml of dichloromethane, and stirring to prepare polylactic acid solution (wherein the mass percentage of the polylactic acid is controlled to be 1 wt%); and (3) pouring the polylactic acid solution into the Fe-nHAP aqueous suspension, mixing, homogenizing at 500rpm for 1h, volatilizing dichloromethane, centrifuging, washing, and freeze-drying to obtain PLA/Fe-nHAP composite microspheres, wherein the Fe-nHAP is coated on the surfaces of the microspheres, and the size distribution of the composite microspheres is 20-140 mu m (figures 8, 9 and 10).

As can be seen from comparison of examples 2, 5, 6 and 7, the improvement of the iron ion doping amount is more beneficial to the improvement of the crystallinity and the ultraviolet absorption performance of Fe-nHAP; when the doping amount of the iron ions is increased to 7%, the doping amount of the iron ions is continuously increased, so that the ultraviolet absorption performance is not greatly improved; meanwhile, when the iron ion doping amount is 7%, the obtained Fe-nHAP has the smallest particle size, and is more beneficial to the preparation of the composite microsphere with polylactic acid in the later stage.

Example 8

The difference compared to example 7 is only that the homogenization is carried out for 1h at 4500 rpm. Fe-nHAP is coated on the surface of the microsphere, and the size of the composite microsphere is distributed between 1 and 5 mu m (figures 8 and 10).

As can be seen from the comparison of examples 7-8, increasing the homogenization speed over a range is advantageous in reducing the size of the PLA/Fe-nHAP composite microsphere.

Example 9

The difference compared to example 8 is only that the homogenization is carried out for 5min at 3000 rpm. Fe-nHAP is coated on the surface of the microsphere, and the size of the composite microsphere is distributed between 3 and 10 mu m (figures 11 and 12).

Example 10

The difference compared to example 9 is only that the homogenization is carried out for 100min at 3000 rpm. Fe-nHAP is coated on the surface of the microsphere, and the size of the composite microsphere is distributed between 2 and 14 mu m (figures 11 and 12).

As is evident from the comparison of examples 9 to 10, the adjustment of the homogenization time within a certain range has little effect on the particle size of the composite microsphere.

Example 11

In comparison with example 10, the only difference is that 0.08g of Fe-nHAP powder was weighed, and the mass percentage of the ceramic powder in the aqueous suspension was 0.01wt%; homogenizing at 3000rpm for 1 hr during microsphere preparation. Fe-nHAP is coated on the surface of the microsphere, and the size of the composite microsphere is distributed between 1 and 11 mu m (FIGS. 13 and 14).

Example 12

The difference compared with example 11 is that 0.8g of Fe-nHAP powder was weighed, the mass percentage of the ceramic powder in the aqueous suspension was 0.1wt%, the Fe-nHAP was coated on the surface of the microspheres, and the composite microsphere size distribution was 2-6. Mu.m (FIGS. 13, 14).

Example 13

The difference compared with example 12 is only that 0.16g of Fe-nHAP powder was weighed and dispersed in water. Fe-nHAP is coated on the surface of the microsphere, the size of the composite microsphere is distributed at 2-7 mu m, and the composite microsphere has an ultraviolet shielding effect (figures 15, 16 and 17).

As is evident from the comparison of examples 11 to 13, the mass ratio of Fe-nHAP powder to polylactic acid was increased within a certain range, which was advantageous for reducing the particle size of the composite microspheres.

Example 14

Weighing 5g of polylactic acid, stirring and dissolving in 100ml of dichloromethane to prepare a solution A; placing polyvinyl alcohol into ultrapure water, stirring at 80 ℃ for about 1h, and cooling to obtain a polyvinyl alcohol solution (the concentration is 5 mg/ml); the solution A was poured into a polyvinyl alcohol solution and stirred at 1000rpm for 5 hours, and then centrifuged, washed and freeze-dried to obtain pure PLA microspheres with an average size of 51.29 μm, which have a weak ultraviolet shielding effect (FIGS. 18, 19 and 20).

Example 15

The difference compared with example 14 is that pure PLA microspheres having an average particle diameter of 4.21 μm (FIGS. 18, 19, 20) were obtained with extremely weak ultraviolet shielding effect by stirring at 4500rpm for 5 hours.

As can be seen from a comparison of examples 14-15, increasing the particle size of the pure PLA microspheres is beneficial for increasing the UV shielding effect, but the UV shielding effect is still poor.

Example 16

Compared with example 14, the method is only different in that 0.005g of Fe-nHAP powder prepared in example 7 is weighed and dispersed into the solution A, and the solution A is subjected to ultrasonic treatment for 30min for uniform dispersion and mixing, so that a polylactic acid mixture containing Fe-nHAP (the mass content of the Fe-nHAP is 0.1% of that of the polylactic acid) is obtained; and the polylactic acid mixture containing Fe-nHAP is poured into a polyvinyl alcohol solution (the concentration is 5 mg/ml) and stirred for 5 hours at 1000rpm, and then the PLA/Fe-nHAP composite microsphere is obtained through centrifugation, washing and freeze drying, and the Fe-nHAP is wrapped in the microsphere (figures 21 and 22).

Example 17

The difference compared with example 16 is only that 1g of the Fe-nHAP powder prepared in example 7 was weighed and the mass content of Fe-nHAP was 20% of that of polylactic acid. The prepared microsphere has a smoother surface, nano particles are coated in the microsphere, the size of the composite microsphere is 20-70 mu m, fe-nHAP particles are coated in the microsphere, and the Fe-nHAP particles are uniformly dispersed in a PLA microsphere matrix to form a micro-nano composite structure, and the ultraviolet shielding effect of the composite microsphere is good (figures 22, 23 (b), 24 and 25 (b)).

As can be seen from the comparison of examples 16 to 17, the improvement of the doping amount of Fe-nHAP is beneficial to the improvement of the ultraviolet shielding effect of the composite microsphere.

Example 18

The difference from example 17 was that the composite microspheres having an average particle diameter of 4.2 μm were obtained by stirring at 4500rpm for 5 hours, and the Fe-nHAP was encapsulated in the microspheres, thereby exhibiting a light ultraviolet shielding effect (fig. 23 (a) and 25 (a)).

As can be seen from the comparison of examples 17-18, increasing the particle size of the PLA/Fe-nHAP composite microsphere is also more beneficial to improving the ultraviolet shielding effect.

Application example 1

Cells were seeded one day in advance into 24-well plates (cell density 5≡10) ⁴ ) After attachment, co-cultivation was performed with a basal medium of nano-ceramic particles (example 7) at a concentration of 200. Mu.g/ml. After 1 day of culture, fluorescent staining (AM and PI solution are added for 5-10 min) is carried out, and then living and dead fluorescent imaging of the nano ceramic particles is observed. The green color covered the entire field of view, the cells were grown over the entire plate, and almost no red color was observed. The seeded cells were in a normal growth state (fig. 26). The nano ceramic particles synthesized by the invention have good cell compatibility.

Application example 2

The mercury, lead, arsenic and cadmium contents in the sample are respectively detected by adopting a cold atomic absorption method, a graphite furnace atomic absorption spectrophotometry, a hydride atomic fluorescence spectrophotometry, a flame atomic absorption spectrophotometry and the like. Meanwhile, detecting the total number of mould and saccharomycetes, heat-resistant escherichia coli, staphylococcus aureus and pseudomonas aeruginosa after enrichment and separation. Experimental methods nine tests were performed on the Fe-nHAP powder of example 7 using cosmetic safety Specification 2015. The detection of the nano ceramic particles can observe that the contents of mercury, lead, arsenic and cadmium are respectively 0.002, 0.05, 0.01 and 0.18 mg/kg which are far lower than the detection limit standard, and the total number of colonies, staphylococcus aureus, pseudomonas aeruginosa, mold, saccharomycetes and heat-resistant coliform are not detected (table 2).

Application example 3

Skin phototoxicity was tested according to cosmetic safety Specification (2015 edition) with 4 dehairing areas (see FIG. 29), each dehairing area being approximately 2 cm X2 cm. Dehairing area 1: after 0.2g of Fe-nHAP powder of example 7 sufficiently wetted with ultra-pure water was applied for 30 minutes, it was covered with aluminum foil and fixed with tape so as to be in a dark state; dehairing area 2: after 0.2g of the Fe-nHAP powder of example 7 sufficiently wetted with ultra-pure water was applied for 30 minutes, irradiation was performed with UVA; dehairing area 3: covering with aluminum foil, and fixing with adhesive tape to make it in dark state; dehairing area 4: skin reactions were observed with UVA irradiation at 1, 24, 48 and 72 hours, respectively, and scored according to the scoring criteria for skin irritation response. The results indicated that the sample 1h, 24 h, 48 h, 72h was phototoxic to guinea pig skin (fig. 27).

Application example 4

Removing hair from skin at two sides of animal spine, wherein the hair removal range is 3 cm ×3× 3 cm, moistening and smearing 0.5g of Fe-nHAP powder ultrapure water of example 7 on right skin, and the smearing area is 2.5 cm ×2.5 cm; the left side was coated with ultrapure water as a control, and the skin irritation response was scored after continuous coating of 14d 1 time per day. The samples are smeared for 14 days for multiple skin irritation tests, so that no great difference can be observed between the experimental part of New Zealand rabbits and the control sample, the skin is smooth and unbroken, no adverse reaction occurs, and no irritation of the nano ceramic particles to the skin is shown (figure 28).

Application example 5

Comparing the ultraviolet absorption intensity of the Fe-nHAP nano ceramic particles prepared in the embodiment 7 with that of commercial titanium oxide and zinc oxide nano ceramic particles, wherein the three ultraviolet absorption intensities are relatively close, and the Fe-nHAP nano ceramic particles have relatively strong ultraviolet absorption capacity; and the Fe-nHAP ultraviolet absorption intensity in the 360-400nm band was higher than that of commercial titanium dioxide (FIG. 29).

Application example 6

The Fe-nHAP nano ceramic particles prepared in the example 7 are compared with the PLA/Fe-nHAP composite microsphere prepared in the example 17 in terms of ultraviolet absorption intensity, and the ultraviolet absorption intensity of the Fe-nHAP nano ceramic particles and the PLA/Fe-nHAP composite microsphere are similar and are obviously higher than that of pure PLA microsphere. The ultraviolet absorption performance of the microspheres of example 17 after wrapping 20% of Fe-nHAP was equivalent to the ultraviolet absorption effect of pure Fe-nHAP of example 7, demonstrating that the micro-nano composite structure and composition of the PLA/Fe-nHAP composite microspheres synergistically enhanced the ultraviolet absorption function (FIG. 30).

TABLE 1 Length and Wide particle diameter statistics of Fe-nHAP prepared in examples 2, 5, 6 and 7

TABLE 2 nine tests of Fe-nHAP heavy metals and colonies in application example 3

In summary, compared with the prior art, the invention has the beneficial effects that:

(1) Based on endogenous substances and components of human bodies, novel apatite-based ceramic sunscreens are developed to replace or reduce the use of nano zinc oxide, titanium dioxide and the like, reduce the potential harm to skin, and avoid the defects of large irritation, easy allergy, unfriendly environment and the like of the traditional chemical sunscreens;

(2) The polymer microspheres are utilized to realize the effective fixation of the nano ceramic sun-screening agent, reduce the risk of pore blockage and reduce the pollution to water;

(3) The ultraviolet blocking physical sun-screening effect can be provided by utilizing the light reflection and scattering effects of the composite microsphere, the chemical sun-screening effect can be generated based on the ultraviolet absorption function of the nano ceramic particles, the micro-nano composite structure is beneficial to improving the uniform dispersion of the nano ceramic particles in the matrix, the ultraviolet absorption function of the nano ceramic particles is fully exerted, and the ultraviolet absorption performance of the composite microsphere is effectively improved by the synergistic effect of the components and the micro-nano composite structure. The dual effects of ultraviolet blocking physical sun protection and ultraviolet absorbing chemical sun protection are beneficial to improving sun protection effect, further reducing the dosage of chemical sun protection agents and reducing toxic effects on skin and harm to environment;

(4) The sun-proof microsphere micro-nano composite structure has the advantages of broad-spectrum sun-proof effect, safety, stability, no stimulation, environmental friendliness and the like.

The above-described embodiments of the present invention do not limit the scope of the present invention. Any other corresponding changes and modifications made in accordance with the technical idea of the present invention shall be included in the scope of the claims of the present invention.

Claims

1. The polylactic acid/metal doped nano-hydroxyapatite composite sun-screening microsphere is characterized in that the composite sun-screening microsphere takes polylactic acid as an organic matrix material, and metal doped nano-hydroxyapatite particles are ceramic phase, so that the metal doped nano-hydroxyapatite particles are dispersed, wrapped in or compounded and fixed on the surface of the polylactic acid microsphere to form a micro-nano composite structure; wherein the size distribution of the composite sun-proof microsphere is 1-150 mu m, and the metal doped nano hydroxyapatite accounts for 0.1-30wt% of the polylactic acid.

2. The polylactic acid/metal doped nano hydroxyapatite composite sun protection microsphere according to claim 1, wherein the size distribution of the composite sun protection microsphere is 20-140 μm, and the average particle size is 40-60 μm; the metal doped nano hydroxyapatite accounts for 10-30wt% of the polylactic acid.

3. The polylactic acid/metal doped nano hydroxyapatite composite sun-screening microsphere according to claim 1, wherein the doped metal M is one or more of Fe, zn and Mn; the mole percentage of the doping metal M accounting for Ca+M is 0.3-20wt%.

4. The polylactic acid/metal doped nano-hydroxyapatite composite sun-screening microsphere according to claim 1, wherein the doped metal M is Fe, and the morphology of the metal doped nano-hydroxyapatite particles is rod-shaped, the length is 20-600nm, and the diameter is 10-55nm; the molecular weight of polylactic acid is 0.5-30 ten thousand.

5. A method for preparing the polylactic acid/metal doped nano-hydroxyapatite composite sun-screening microspheres according to any one of claims 1 to 4, comprising the following steps:

s1, uniformly dispersing soluble phosphate, soluble calcium salt and soluble doped metal salt into water, and then preparing metal doped nano-hydroxyapatite particles by a coprecipitation method-hydrothermal method;

6. The method for preparing polylactic acid/metal doped nano-hydroxyapatite composite sun-screening microspheres according to claim 5, wherein in the step S1, the soluble phosphate is diammonium hydrogen phosphate or disodium hydrogen phosphate, the soluble calcium salt is calcium chloride or calcium nitrate, and the soluble doped metal salt is soluble doped metal hydrochloride or nitrate; the molar ratio of Ca+M to P is 1.6-1.8; the reaction temperature is 37-150 ℃ and the reaction time is 0.5-5h.

7. The method for preparing polylactic acid/metal doped nano hydroxyapatite composite sun-screening microspheres according to claim 5, wherein step S1 specifically comprises:

s11, dissolving soluble phosphate into water to obtain a reaction solution A; wherein, the concentration of the soluble phosphate in the reaction solution A is 0.001-0.05mol/L;

s12, dissolving soluble calcium salt and soluble doped metal salt into water to obtain a reaction solution B; wherein, the total concentration of Ca+M in the reaction solution B is 0.01-0.1mol/L;

s13, adding the reaction solution A into the reaction solution B, regulating the pH value to 9-10, stirring and reacting for 0.5-1h, transferring the precursor solution into a reaction kettle for crystallization treatment, and centrifuging, washing and freeze-drying to obtain the metal doped nano hydroxyapatite particles.

8. The method for preparing the polylactic acid/metal doped nano-hydroxyapatite composite sun-blocking microspheres according to claim 5, wherein in step S2, preparing the polylactic acid/metal doped nano-hydroxyapatite composite sun-blocking microspheres by a Pickering emulsification technology comprises:

S22A, uniformly dispersing metal doped nano-hydroxyapatite particles into water to prepare metal doped nano-hydroxyapatite aqueous suspension; wherein, in the metal doped nano-hydroxyapatite aqueous suspension, the concentration of the metal doped nano-hydroxyapatite is 0.01 to 0.1 weight percent;

S23A, adding a pure polylactic acid solution into a metal doped nano hydroxyapatite aqueous suspension, uniformly mixing the pure polylactic acid solution and the metal doped nano hydroxyapatite aqueous suspension, fully volatilizing an organic solvent, and centrifuging, washing and freeze-drying to obtain polylactic acid/metal doped nano hydroxyapatite composite sun-screening microspheres; wherein, a liquid phase homogenizer is adopted to uniformly mix the pure polylactic acid solution and the metal doped nano hydroxyapatite aqueous suspension, the organic solvent is fully volatilized, the homogenizing speed is 500-4500rpm, and the homogenizing time is 5-100min.

9. The method for preparing the polylactic acid/metal doped nano-hydroxyapatite composite sun-blocking microspheres according to claim 5, wherein in step S2, the preparing the polylactic acid/metal doped nano-hydroxyapatite composite sun-blocking microspheres by an emulsion solvent evaporation method comprises:

S21B, dissolving polylactic acid in an organic solvent to prepare a pure polylactic acid solution, and then uniformly dispersing metal-doped nano-hydroxyapatite particles into the pure polylactic acid solution to prepare a polylactic acid mixture containing the metal-doped nano-hydroxyapatite; wherein, in the pure polylactic acid solution, the concentration of the pure polylactic acid solution is 0.1 to 10 weight percent, and the organic solvent is methylene dichloride;

S22B, dissolving polyvinyl alcohol into water to prepare a polyvinyl alcohol solution; wherein, in the polyvinyl alcohol solution, the concentration of the polyvinyl alcohol is 1-10mg/ml;

S23B, adding the polylactic acid mixture containing the metal doped nano hydroxyapatite into a polyvinyl alcohol solution, uniformly mixing the polylactic acid mixture and the polyvinyl alcohol solution, fully volatilizing an organic solvent, and centrifuging, washing and freeze-drying to obtain the polylactic acid/metal doped nano hydroxyapatite composite sun-screening microsphere; wherein, a constant-speed stirrer is adopted to uniformly mix the polylactic acid mixture containing the metal doped nano hydroxyapatite and the polyvinyl alcohol solution, and the organic solvent is fully volatilized, the stirring speed is 500-4500rpm, and the stirring time is 3-12h.

10. A cosmetic sunscreen composition comprising the polylactic acid/metal doped nano-hydroxyapatite composite sunscreen microspheres of any one of claims 1-4.