CN115282336A

CN115282336A - Polysaccharide mixed gel containing aliphatic polyester microspheres as well as preparation method and application thereof

Info

Publication number: CN115282336A
Application number: CN202211030526.5A
Authority: CN
Inventors: 陈亮; 牛睿
Original assignee: Zhejiang Tianyan Biotechnology Co ltd
Current assignee: Zhejiang Tianyan Biotechnology Co ltd
Priority date: 2022-08-26
Filing date: 2022-08-26
Publication date: 2022-11-04

Abstract

The invention relates to a mixed gel containing aliphatic polyester microsphere polysaccharide, a preparation method and application thereof. The mass fraction ratio of the polyester microsphere, the polysaccharide disperse phase, the emulsifier and the anesthetic (added according to the condition) is (5% -40%) (15% -30%) (0.1% -5%) (1%). The invention is characterized in that polyester microspheres coated by mixed aliphatic are prepared, and finally the gel with good dispersibility and strong stability is prepared by regulating the proportion of the polyester microspheres, polysaccharide dispersed phase, emulsifier and anesthetic. The synthetic method is simple to operate and easy to industrialize, the addition of the aliphatic polyester microspheres prolongs the gel period, the stability is stronger, the added polysaccharide dispersant and anesthetic respectively solve the problem of residue of the crosslinking agent of the injected gel and the pain caused by injection, and the prepared gel has the advantages of long filling period, good dispersibility and no pain.

Description

Polysaccharide mixed gel containing aliphatic polyester microspheres as well as preparation method and application thereof

Technical Field

The invention relates to a mixed gel containing aliphatic polyester microsphere polysaccharide and a preparation method thereof.

Background

With the rapid development of biological material science, beauty technology is favored by people, and more filling materials are applied to tissue filling and medical beauty (facial shaping). Filling beauty is a non-surgical cosmetic method of injecting biological material into the dermis or beneath the skin to reduce wrinkles or shaping of the skin. At present, facial soft tissue filling materials mainly comprise non-autologous tissue injections, such as Hyaluronic Acid (HA), polycaprolactone (PCL), polylactic acid (PLA), and the like. Polyester materials are often used as dermal fillers and are often in the form of particles or microspheres. The skin filler prepared from aliphatic polyester has certain effects on treating facial lipoatrophy related to human immunodeficiency virus and removing wrinkles and filling pits of normal people. However, the development of the filler is restricted by the problems of degradability and dispersibility of the filler.

Patent CN201410438010 discloses a polylactic acid microsphere and sodium hyaluronate mixed gel for injection and a preparation method thereof, which solves the problem of HA gel degradation but remembers that the addition of HA cross-linking increases the safety risk of the gel. The CN112807486 patent discloses a scheme of dispersing aliphatic polyester microspheres in polysaccharide solution, but because the components of the microspheres are fat soluble and the dispersant is water soluble, the mutual solubility of the two is not good, and the microspheres cannot be uniformly dispersed in the dispersed phase for a long time and are easy to settle. However, the degradation cycle of the gel mainly comprising HA is short, multiple injections are required, and the addition of the aliphatic polyester microparticles can cause the problems of poor dispersibility of the filler product, easy agglomeration to form large particles, coagulation and the like, cause needle blockage during injection and often cause pain, and the problems of poor dispersibility and stability in the aliphatic polyester material need to be solved urgently.

Disclosure of Invention

The invention aims to solve the problems that a filling material prepared from aliphatic polyester has poor dispersibility, is easy to agglomerate to form large particles, generates coagulation and the like, and provides a preparation method of a polysaccharide mixed gel containing aliphatic polyester microspheres, so as to obtain the polysaccharide mixed gel containing aliphatic polyester microspheres, which has the advantages of uniform dispersion, long period, stability and pain reduction.

The technical purpose of the invention is realized by the following technical scheme: the mixed polysaccharide gel containing fatty polyester microsphere is synthesized through the steps of synthesizing fatty coated polyester microsphere, and controlling the adding ratio of polyester microsphere, polysaccharide dispersing phase, emulsifier and anesthetic.

Preferably, the polysaccharide mixed gel contains aliphatic polyester microspheres, wherein the polyester microspheres are single polymers of PLA, PGA and PCL or copolymers between the single polymers, and the particle size of the polyester microspheres is 5-200um.

Preferably, the polysaccharide dispersed phase of the fatty polyester microsphere polysaccharide mixed gel is a single aqueous solution of guar gum, carboxymethyl cellulose, hydroxypropyl methyl cellulose and alginate, or a compound aqueous solution of two or more than two kinds of the polysaccharide dispersed phase.

Preferably, the gel mixture contains the aliphatic polyester microsphere polysaccharide, and the emulsifier is phospholipid, polyvinyl alcohol, cyclodextrin, TW-80, polyoxyethylene castor oil derivative, poloxamer and other single components, or two or more of the components can be used in a compounding way.

Preferably, the gel comprises an aliphatic polyester microsphere polysaccharide mixed gel, and the anesthetic is a single component such as lidocaine, procaine and tetracaine, or two or more of the components can be used in combination.

Preferably, the polysaccharide mixed gel contains aliphatic polyester microsphere, and the molecular weight of the polyester microsphere is 30000-300000 daltons.

Preferably, the mixed gel contains aliphatic polyester microsphere polysaccharide, wherein the mass fraction ratio of the polyester microsphere, the polysaccharide disperse phase, the emulsifier and the anesthetic (added according to the situation) is (5% -40%) (15% -30%) (0.1% -5%): 1%.

A preparation method of a polysaccharide mixed gel containing aliphatic polyester microspheres comprises the following steps:

the method comprises the following steps: dissolving mixed fatty glyceride in a solvent to prepare a 0.3-5% solution, adding 5-40% polyester microspheres into the solution to disperse the microspheres, stirring the obtained mixed solution at 1000-2000 r/min for 20-30min, and forming a stable suspension a at normal temperature.

Step two: and (3) carrying out suction filtration on the obtained suspension a, separating microspheres from the solution, and drying the microspheres in a normal-temperature blast box to obtain the polyester microspheres b wrapped by the mixed fatty glyceride.

Step three: dissolving a certain dispersant in water, wherein the mass fraction of the dispersant is 15-30%, adding the obtained polyester microspheres b coated with the mixed fatty glyceride, stirring for 30-60min at 1000-2000 r/min, and forming a stable suspension c at normal temperature.

Step four: gradually dripping 0.1-5% of emulsifier into the suspension c, keeping stirring at 1000-2000 r/min, adding anesthetic with mass fraction of 1% after 10-20min, and mixing the solution uniformly. The temperature is kept above 20 ℃ during stirring, and the aliphatic polyester microsphere polysaccharide mixed gel is obtained.

Step five: and finally, filling and sterilizing: filling into disposable syringe or penicillin bottle, and sterilizing with 115-125 deg.C steam in sterilizing pot for 15-30min to obtain uniform gel containing fatty polyester microsphere polysaccharide.

The utility model provides an application of mixed gel of fatty polyester microballon polysaccharide, it is leading-in through the leading-in beauty instrument injection of electronic micropin, and the leading-in beauty instrument of electronic micropin includes the shell, the first backup pad of inner wall fixedly connected with of shell, the fixed surface of first backup pad is connected with the division board, be provided with injection liquid chamber and installation cavity in the shell, install the suction pump in the injection liquid intracavity, the output of suction pump is connected with the drain pipe, the drain pipe runs through first backup pad, drain pipe and first backup pad fixed connection, install the motor in the installation cavity, the output fixedly connected with pivot of motor, the pivot runs through first backup pad, the pivot is connected with first backup pad rotation, the output of pivot is connected with the liquid box through elevating system, drain pipe and liquid box sliding connection, the drain pipe communicates with liquid box inner chamber each other with the liquid box inner chamber, the bottom of liquid box is provided with the micropin, and during the use, starts the motor drive pivot and rotates, and under elevating system's effect, the rotation of pivot drives the liquid box and is reciprocating motion, starts the suction pump when starting the motor, with the leading-in liquid box of injection liquid in the injection liquid chamber, then from the micropin cavity of injection liquid, this injection liquid can realize the leading-in the beauty instrument, has improved automatic efficiency that adds.

As a preferable scheme of the present invention, the inner wall of the housing is symmetrically provided with first sliding grooves, the outer wall of the liquid box is symmetrically and fixedly connected with first sliding blocks, the first sliding blocks correspond to the first sliding grooves one to one, and the first sliding blocks are slidably connected in the corresponding first sliding grooves.

As a preferable scheme of the present invention, the lifting mechanism includes a cam fixedly connected to an output end of the rotating shaft, a second support plate is fixedly connected to an inner wall of the housing, a moving plate is disposed on a surface of the second support plate, the moving plate penetrates through the second support plate, the moving plate is slidably connected to the second support plate, an upper end of the moving plate abuts against the cam, a first connecting plate is fixedly connected to the surface of the moving plate, a first spring is fixedly connected between the first connecting plate and the second support plate, and a bottom of the moving plate is fixedly connected to the liquid cartridge.

As a preferable scheme of the present invention, a concave plate is fixedly connected to a surface of the moving plate, a first rotating rod is rotatably connected to an inner wall of the concave plate, a rotating wheel is fixedly connected to an outer wall of the first rotating rod, and the rotating wheel is slidably connected to the cam.

As a preferable scheme of the present invention, one side of the moving plate is connected to a balance plate through a second connecting plate, the bottom of the balance plate is fixedly connected to a first vertical plate, the first vertical plate is fixedly connected to the liquid box, and a telescopic mechanism is disposed between the balance plate and the second supporting plate.

As a preferable scheme of the present invention, the telescopic mechanism includes an outer tube fixedly connected to the bottom of the second support plate, an inner rod is slidably connected to an inner wall of the outer tube, and a second spring is disposed between the outer tube and the balance plate.

As a preferable scheme of the present invention, a rack is fixedly connected to a side wall of the first connecting plate, a first gear is engaged and connected to a side wall of the rack, second vertical plates are symmetrically and fixedly connected to a surface of the second support plate, a second rotating rod is rotatably connected between the two second vertical plates, the second rotating rod is fixedly connected to the first gear, a second gear is fixedly connected to an outer wall of the second rotating rod, a third gear is engaged and connected to a bottom of the second gear, a third rotating rod is fixedly connected to a surface of the third gear, a stirring blade is fixedly connected to a bottom of the third rotating rod, and the stirring blade is located in an inner cavity of the liquid box.

As a preferable scheme of the present invention, the third rotating rod penetrates through the second support plate, the third rotating rod is rotatably connected to the second support plate, the third rotating rod is slidably connected to the liquid box, and the second gear and the third gear are both bevel gears.

Advantageous effects

1. The preparation method takes aliphatic polyester and polysaccharide as dispersing agents and adds anesthetic to synthesize mixed gel, systematically researches the influence of the proportion of polyester microspheres, polysaccharide dispersed phases, emulsifier and anesthetic on the dispersibility and stability of the mixed gel containing the aliphatic polyester microsphere polysaccharide, and obtains the preparation method provided by the invention;

2. the addition of the aliphatic polyester-containing microspheres solves the problems that the existing gel mainly comprising HA HAs short degradation period and needs to be injected for many times; meanwhile, the problem of residue of the crosslinking agent for the injectable gel which mainly comprises crosslinked HA is solved by taking soluble cellulose and chitosan as dispersed phases; the problem of uneven dispersion of the original microspheres in the flowing phase is solved by adding the emulsifier; the addition of anesthetic reduces the pain sensation of irritation to the tissue upon injection. The fatty polyester microsphere obtained by the invention has moderate particle size, good hydrophilicity and suspension property, is easy to inject and has small irritation to subcutaneous tissues, and the degradation of the fatty polyester microsphere or particle can provide nutrition. The mixed gel prepared by the invention has good stability, is easy to disperse uniformly, can reduce subcutaneous nodules and reduce pain, and has good application prospect in the fields of facial filling and tissue repair;

3. when injection is introduced, the starting motor drives the rotating shaft to rotate, the rotating shaft drives the cam to rotate, the cam and the moving plate are matched with each other, the moving plate is driven to move by the rotation of the cam, the moving plate is convenient to move by the mutual matching between the first sliding groove and the first sliding block, meanwhile, the moving range of the liquid box can be limited, the moving plate drives the liquid box to move, the moving plate is convenient to move and reset by the design of the first spring, the suction pump is started while the starting motor is started, the injection in the injection cavity is introduced into the liquid box, and then the injection is introduced into skin from the cavity of the microneedle, so that the beauty instrument can realize automatic injection adding, and the working efficiency is improved;

4. under the linking effect of first linkage plate, the rack is driven to remove in the removal of movable plate, the removal of rack drives first gear and rotates, the rotation of first gear drives the second bull stick and rotates, the rotation of second bull stick drives the second gear and rotates, the rotation of second gear drives the third gear and rotates, the rotation of third gear drives the third bull stick and rotates, thereby make the stirring leaf rotate, the circulation of the injection liquid of liquid box inner chamber with higher speed, through the design to the balance plate, conveniently maintain the balance of liquid box at the removal in-process, through the mutually supporting between outer tube and interior pole, make things convenient for balance plate and movable plate synchronous motion, through the design to the second spring, make things convenient for the removal and the reseing of balance plate.

Additional aspects and advantages of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention.

Drawings

FIG. 1 is a schematic perspective view of the present invention;

FIG. 2 is a schematic diagram of a first perspective view of an internal structure of a housing according to an embodiment of the invention;

FIG. 3 is an enlarged view of the structure at A in FIG. 2 according to the present invention;

FIG. 4 is a second perspective view of the internal structure of the housing in accordance with the exemplary embodiment of the present invention;

FIG. 5 is an enlarged view of the structure at B in FIG. 4 according to the present invention;

fig. 6 is a partial perspective view of the present invention.

The numbering in the figures illustrates:

1. a housing; 2. a first support plate; 3. a partition plate; 4. an injection liquid cavity; 5. a suction pump; 6. a liquid outlet pipe; 7. a motor; 8. a rotating shaft; 9. a liquid cartridge; 10. microneedles; 11. a first chute; 12. a first slider; 13. a mounting cavity; 14. a cam; 15. a concave plate; 16. a first rotating lever; 17. a rotating wheel; 18. moving the plate; 19. a second support plate; 20. a first spring; 21. a first connector tile; 22. a second connector tile; 23. a balance plate; 24. a first vertical plate; 25. an outer tube; 26. an inner rod; 27. a second spring; 28. a rack; 29. a first gear; 30. a second vertical plate; 31. a second rotating rod; 32. a second gear; 33. a third gear; 34. a third rotating rod; 35. stirring the leaves.

Example 1

The mass fraction ratio of the components of the mixed gel containing the aliphatic polyester microsphere polysaccharide is shown in table 1. The specific operation steps are as follows:

the method comprises the following steps: 5g of mixed fatty glyceride and 6g of polylactic acid are mixed and dissolved to disperse the microspheres, the obtained mixed solution is stirred for 20-30min at 1000-2000 r/min, and a stable suspension a can be formed at normal temperature.

Step three: and adding 5.36g of the obtained polyester microspheres b coated with the mixed fatty glyceride into 3.39g of the dispersing agent, stirring for 30-60min at 1000-2000 r/min, and forming a stable suspension c at normal temperature, wherein the suspension c is marked as A.

Step four: gradually dripping 0.54g emulsifier into the suspension c, keeping stirring at 1000-2000 r/min, and adding 0.18g anesthetic after 10-20min until the solution is uniformly mixed. The temperature is kept above 20 ℃ during stirring, and the mixed gel of the aliphatic polyester microsphere polysaccharide is obtained and is marked as B.

Table 1 mass fractions of the ingredients of the gel described in example 1

The above samples A and B were observed, and the results are shown in FIG. 1, in which FIG. 1 is a graph showing the state of dispersion of the sample in example 1 after it was vigorously shaken and then left for a certain period of time. The results show that after mixing, the polymer microspheres a are dispersed in the medium; with increasing time, the polymer microspheres form a stable suspension and a coagulation phenomenon is observed. And B, standing for a period of time, and observing under an optical microscope, wherein the result shows that the polymer microspheres are not aggregated and are well dispersed.

In this embodiment, application of fatty polyester microsphere polysaccharide mixed gel is provided, the injection and introduction of the cosmetic apparatus are performed by an electric microneedle introduction device, referring to fig. 1-2, which includes a housing 1, a first support plate 2 is fixedly connected to an inner wall of the housing 1, a partition plate 3 is fixedly connected to a surface of the first support plate 2, an injection cavity 4 and an installation cavity 13 are provided in the housing 1, the injection cavity 4 and the installation cavity 13 are conveniently separated by the design of the partition plate 3, a suction pump 5 is installed in the injection cavity 4, an output end of the suction pump 5 is connected with a liquid outlet pipe 6, the liquid outlet pipe 6 penetrates through the first support plate 2, the liquid outlet pipe 6 is fixedly connected with the first support plate 2, a motor 7 is installed in the installation cavity 13, an output end of the motor 7 is fixedly connected with a rotating shaft 8, the rotating shaft 8 penetrates through the first support plate 2, the rotating shaft 8 is rotatably connected with the first support plate 2, an output end of the rotating shaft 8 is connected with a liquid box 9 through a lifting mechanism, the liquid outlet pipe 6 is slidably connected with the liquid box 9, the inner cavity of the liquid box 6 is mutually communicated with an inner cavity of the liquid box 9, a microneedle injection pump is automatically started under the action of the rotating shaft 8, and the rotating shaft of the rotating shaft 7, the rotating shaft is capable of driving the rotating shaft to drive the liquid injection pump to perform reciprocating motion of the liquid injection cavity, and then the microneedle injection pump to improve the microneedle injection efficiency of the microneedle injection cavity.

Referring to fig. 1-2, the inner wall of the housing 1 is symmetrically provided with first sliding grooves 11, the outer wall of the liquid box 9 is symmetrically and fixedly connected with first sliding blocks 12, the first sliding blocks 12 correspond to the first sliding grooves 11 one to one, the first sliding blocks 12 are slidably connected in the corresponding first sliding grooves 11, and the first sliding grooves 11 and the first sliding blocks 12 are matched with each other, so that the liquid box 9 can be moved conveniently, and meanwhile, the moving range of the liquid box 9 can be limited.

Referring to fig. 2-3, the lifting mechanism includes a cam 14 fixedly connected to an output end of the rotating shaft 8, a second supporting plate 19 is fixedly connected to an inner wall of the housing 1, a moving plate 18 is disposed on a surface of the second supporting plate 19, the moving plate 18 penetrates through the second supporting plate 19, the moving plate 18 is slidably connected to the second supporting plate 19, an upper end of the moving plate 18 abuts against the cam 14, a first connecting plate 21 is fixedly connected to a surface of the moving plate 18, a first spring 20 is fixedly connected between the first connecting plate 21 and the second supporting plate 19, and a bottom of the moving plate 18 is fixedly connected to the liquid box 9.

Referring to fig. 3, a concave plate 15 is fixedly connected to the surface of the moving plate 18, a first rotating rod 16 is rotatably connected to the inner wall of the concave plate 15, a rotating wheel 17 is fixedly connected to the outer wall of the first rotating rod 16, and the rotating wheel 17 is slidably connected to the cam 14, so that the moving plate 18 is driven to move by the rotation of the cam 14 through the mutual matching between the rotating wheel 17 and the cam 14.

Referring to fig. 4-5, one side of the moving plate 18 is connected to a balance plate 23 through a second connecting plate 22, the balance plate 23 is designed to facilitate maintaining the balance of the liquid box 9 during moving, a first vertical plate 24 is fixedly connected to the bottom of the balance plate 23, the first vertical plate 24 is fixedly connected to the liquid box 9, and a telescopic mechanism is disposed between the balance plate 23 and the second supporting plate 19.

Referring to fig. 5, the telescoping mechanism includes an outer tube 25 fixedly connected to the bottom of the second support plate 19, an inner rod 26 is slidably connected to an inner wall of the outer tube 25, the outer tube 25 and the inner rod 26 are matched with each other to facilitate the balance plate 23 and the moving plate 18 to move synchronously, a second spring 27 is disposed between the outer tube 25 and the balance plate 23, and the second spring 27 is designed to facilitate the movement and the resetting of the balance plate 23.

Referring to fig. 6, a rack 28 is fixedly connected to a side wall of the first engaging plate 21, a first gear 29 is engaged and connected to a side wall of the rack 28, second vertical plates 30 are symmetrically and fixedly connected to a surface of the second supporting plate 19, a second rotating rod 31 is rotatably connected between the two second vertical plates 30, the second rotating rod 31 is fixedly connected to the first gear 29, a second gear 32 is fixedly connected to an outer wall of the second rotating rod 31, a third gear 33 is engaged and connected to a bottom of the second gear 32, a third rotating rod 34 is fixedly connected to a surface of the third gear 33, a stirring blade 35 is fixedly connected to a bottom of the third rotating rod 34, the stirring blade 35 is located in an inner cavity of the liquid box 9, the moving of the moving plate 18 drives the rack 28 to move under the engaging action of the first engaging plate 21, the moving of the rack 28 drives the first gear 29 to rotate, the rotating rod 31 is driven to rotate by the rotating of the first gear 29, the rotating rod 31 drives the second gear 32 to rotate, the rotating rod 32 drives the third gear 33 to rotate, the rotating rod 33 drives the third gear 34 to rotate, so as to accelerate the rotation of the liquid in the inner cavity 9, and the liquid to circulate through the liquid.

Referring to fig. 6, the third rotating rod 34 penetrates through the second supporting plate 19, the third rotating rod 34 is rotatably connected with the second supporting plate 19, the third rotating rod 34 is slidably connected with the liquid box 9, the second gear 32 and the third gear 33 are both bevel gears, and the second gear 32 and the third gear 33 are limited in shape, so that the stirring blade 35 can work normally.

During use, the starting motor 7 drives the rotating shaft 8 to rotate, the rotation of the rotating shaft 8 drives the cam 14 to rotate, the rotating wheel 17 is matched with the cam 14, the cam 14 rotates to drive the moving plate 18 to move, the first sliding groove 11 is matched with the first sliding block 12, the moving plate 18 moves to drive the liquid box 9 to move, the balance of the liquid box 9 in the moving process is conveniently maintained through the design of the balance plate 23, the balance plate 23 and the moving plate 18 are convenient to move synchronously through the matching of the outer tube 25 and the inner rod 26, the balance plate 23 is convenient to move and reset through the design of the second spring 27, the suction pump 5 is started while the motor 7 is started, the injection in the injection cavity 4 is guided into the liquid box 9 and then guided into skin from the cavity of the microneedle 10, the instrument can automatically add the injection, the working efficiency is improved, the moving of the moving plate 18 simultaneously drives the rack 28 to move, the rack 28 moves to drive the first gear 29 to rotate, the second rotating rod 31 is matched with the second gear 32, and the third rotating rod 34 is convenient to rotate, and the injection is convenient to circulate in the third rotating rod 34 and rotate.

Example 2

the method comprises the following steps: 5g of mixed fatty glyceride and 8g of polylactic acid are mixed and dissolved to disperse the microspheres, the obtained mixed solution is stirred for 20-30min at 1000-2000 r/min, and a stable suspension a can be formed at normal temperature.

Step two: and (3) carrying out suction filtration on the obtained suspension a, separating the microspheres from the solution, and drying the microspheres in a normal-temperature blast box to obtain the polyester microspheres b coated by the mixed fatty glyceride.

Step three: 6.58g of the obtained polyester microspheres b coated with the mixed fatty glyceride are added into 2.89g of the dispersing agent, stirred for 30-60min at 1000-2000 r/min, and a stable suspension c is formed at normal temperature and is marked as A.

Step four: gradually dripping 0.39g of emulsifier into the suspension c, keeping stirring at 1000-2000 r/min, and adding 0.18g of anesthetic after 10-20min until the solution is uniformly mixed. The temperature is kept above 20 ℃ during stirring, and the mixed gel of the aliphatic polyester microsphere polysaccharide is obtained and is marked as B.

Table 2 mass fractions of ingredients of the gel described in example 2

The same observation as in example 1 was made for the above samples a and B, and the results showed that the mixed a polymer microspheres dispersed in the medium at a slow speed; as time goes on, the polymeric microspheres form a suspension but are dispersed completely and a coagulation phenomenon is observed. And B, after standing for a period of time, observing under an optical microscope, and showing that the polymer microspheres are dispersed more and have poor dispersibility. The PLA polyester microspheres are too much to be dispersed completely, so that coagulation phenomenon occurs.

Example 3

Step three: and adding 1.03g of the obtained polyester microspheres b coated by the mixed fatty glyceride into 7.58g of the dispersing agent, stirring for 30-60min at 1000-2000 r/min, and forming a stable suspension c at normal temperature, wherein the suspension c is marked as A.

Step four: gradually dripping 1.03g of emulsifier into the suspension c, keeping stirring at 1000-2000 r/min, and adding 0.18g of anesthetic after 10-20min until the solution is uniformly mixed. The temperature is kept above 20 ℃ during stirring, and the mixed gel of the aliphatic polyester microsphere polysaccharide is obtained and is marked as B.

Table 3 mass fractions of the ingredients of the gel described in example 3

The same observations as in example 1 were made for samples a and B above and showed that the mixed a polymeric microspheres rapidly dispersed throughout the medium; with increasing time, the polymeric microspheres form a stable suspension. And B, after standing for a period of time, observing under an optical microscope, and showing that the polymer microspheres have good dispersibility.

Example 4

Step three: and 4.84g of the obtained polyester microspheres b coated with the mixed fatty glyceride are added into 3.55g of the dispersing agent, stirred for 30-60min at 1000-2000 r/min, and a stable suspension c is formed at normal temperature and is marked as A.

Step four: gradually dripping 1.13g of emulsifier into the suspension c, keeping stirring at 1000-2000 r/min, and adding 0.18g of anesthetic after 10-20min until the solution is uniformly mixed. The temperature is kept above 20 ℃ during stirring, and the mixed gel of the aliphatic polyester microsphere and the polysaccharide is obtained and marked as B.

Table 4 mass fractions of the ingredients of the gel described in example 4

The same observations as in example 1 were made for samples a and B above and showed that the mixed a polymeric microspheres were dispersed in the medium; with time, the polymer microspheres form a suspension but aggregation occurs. And B, after standing for a period of time, observing under an optical microscope, and displaying that the polymer has no aggregation and coagulation phenomena and good dispersibility.

Example 5

The mass fraction ratio of the components of the mixed gel containing the aliphatic polysaccharide microsphere polysaccharide is shown in table 1. The specific operation steps are as follows:

Step three: and (3) adding 5.67g of the obtained polyester microspheres b coated by the mixed fatty glyceride into 4.15g of the dispersing agent, stirring for 30-60min at 1000-2000 r/min, and forming a stable suspension c at normal temperature, wherein the suspension c is marked as A.

Step four: and c, keeping stirring at 1000-2000 r/min for suspension liquid c, and adding 0.18g of anesthetic until the solution is uniformly mixed. The temperature is kept above 20 ℃ during stirring, and the mixed gel of the aliphatic polyester microsphere polysaccharide is obtained and is marked as B.

Table 5 mass fractions of the ingredients of the gel described in example 5

The same observations as in example 1 were made for samples a and B above and showed that the mixed a polymeric microspheres slowly dispersed in the medium; with the increase of time, the polymer microspheres form a suspension, and an aggregation phenomenon appears and is unstable. And B, after standing for a period of time, observing under an optical microscope, and showing that the state is not changed and is not improved.

The comparison is made as follows from example 1 to example 5, see table 6:

table 6 properties of the gels described in examples 1-5.

Comparison of example 1 with example 5 shows that the addition of the emulsifier makes the polyester microspheres disperse better and no aggregation occurs. The ratio of the polyester microspheres in example 1 to example 2 is very important, and the proper amount provides the best dispersion effect, and the best is 30%.

In conclusion, the mass fraction ratio of the polyester microspheres, the polysaccharide dispersed phase, the emulsifier and the anesthetic (added according to the situation) is 30 percent to 22 percent to 3 percent to 1 percent. The addition of the aliphatic polyester microspheres and the emulsifier prolongs the stable period, so that the original microspheres are more uniformly dispersed in the flowing phase; the addition of anesthetic reduces injection pain. The finally obtained preparation method is simple to operate and easy to industrialize, and the prepared gel has long filling period, good dispersibility and no pain.

The present embodiment is only for explaining the present invention, and it is not limited to the present invention, and those skilled in the art can make modifications of the present embodiment without inventive contribution as needed after reading the present specification, but all of them are protected by patent law within the scope of the claims of the present invention.

Detailed Description

The following describes embodiments of the present invention in detail.

The following examples respectively adopt the following raw materials: the polyester microspheres are single polymers of PLA, PGA and PCL or copolymers between every two of the single polymers, and the particle size is controlled to be 5-200um; the polysaccharide dispersion phase is guar gum, hydroxypropyl methylcellulose and alginate single aqueous solution, or two or more compound aqueous solutions; the emulsifier is phospholipid, polyvinyl alcohol, cyclodextrin, TW-80, polyoxyethylene castor oil derivative, poloxamer, etc., or two or more of the components can be used in combination. The anesthetic is single component such as lidocaine, procaine, and tetracaine, or two or more of them can be used in combination. The embodiment selects polylactic acid PLA, carboxymethyl cellulose as polysaccharide dispersant and lidocaine as anesthetic.

Claims

1. The mixed gel is characterized by comprising polyester microspheres, polysaccharide disperse phase, emulsifier and anesthetic which is added optionally.

2. The polysaccharide mixed gel containing aliphatic polyester microspheres according to claim 1, wherein the order of synthesizing the mixed gel is to synthesize the aliphatic encapsulated polyester microspheres first, and the adding ratio of the polyester microspheres, the polysaccharide dispersed phase, the emulsifier and the anesthetic (added as the case may be) is controlled.

3. The polysaccharide mixed gel containing the aliphatic polyester microspheres and the polysaccharide thereof according to claim 1, wherein the polyester microspheres are single polymers of PLA, PGA and PCL or copolymers between every two of the single polymers, and the particle size of the polyester microspheres is 5-200um.

4. The polysaccharide mixed gel containing the aliphatic polyester microsphere polysaccharide according to claim 1, wherein the polysaccharide dispersed phase is a single aqueous solution of guar gum, carboxymethyl cellulose, hydroxypropyl methyl cellulose and alginate, or a compound aqueous solution of two or more of the above.

5. The mixed gel containing the aliphatic polyester microsphere polysaccharide according to claim 1, wherein the emulsifier is a single component such as phospholipid, polyvinyl alcohol, cyclodextrin, TW-80, polyoxyethylene castor oil derivative, poloxamer and the like, or two or more of the components can be used in a compound way.

6. The mixed gel containing the aliphatic polyester microsphere polysaccharide as claimed in claim 1, wherein the anesthetic is single component such as lidocaine, procaine and tetracaine, or two or more of the components can be used in combination.

7. The polysaccharide mixed gel containing the aliphatic polyester microspheres is characterized in that the molecular weight of the polyester microspheres is 30000-300000 daltons, and the proportion of the polyester microspheres in the mixed gel is 5% -40%; the mass fraction of the dispersed phase is between 15 and 30 percent.

8. The mixed gel containing the aliphatic polyester microsphere polysaccharide as claimed in claim 4, wherein the mass fraction of the emulsifier is 0.1-5%, and the mass fraction of the anesthetic is 1%.

9. The preparation method of the mixed gel containing the aliphatic polyester microsphere polysaccharide is characterized by comprising the following preparation processes:

(1) Dissolving mixed fatty glyceride in a solvent to prepare a 0.3-5% solution, adding 5-40% polyester microspheres into the solution to disperse the microspheres, stirring the obtained mixed solution at 1000-2000 r/min for 20-30min, and forming a stable suspension a at normal temperature;

(2) Carrying out suction filtration on the obtained suspension a, separating microspheres from the solution, and drying the microspheres in a normal-temperature blast box to obtain polyester microspheres b coated by mixed fatty glyceride;

(3) Dissolving a certain dispersant in water, adding the obtained polyester microspheres b coated with the mixed fatty glyceride, stirring for 30-60min at 1000-2000 r/min, and forming a stable suspension c at normal temperature;

(4) Gradually dripping emulsifier into the suspension c, keeping stirring at 1000-2000 r/min, and adding a certain amount of anesthetic after 10-20min until the solution is uniformly mixed;

keeping the temperature above 20 ℃ during stirring to obtain the mixed gel of the aliphatic polyester microsphere polysaccharide;

(5) Filling and sterilizing: filling into disposable syringe or penicillin bottle, and sterilizing with 115-125 deg.C steam in sterilizing pot for 15-30min to obtain uniform gel containing fatty polyester microsphere polysaccharide.

10. The application of the polysaccharide mixed gel containing the aliphatic polyester microsphere is characterized in that: leading-in through the leading-in beauty instrument injection of electronic micropin, the leading-in beauty instrument of electronic micropin includes shell (1), the first backup pad of inner wall fixedly connected with (2) of shell (1), fixed surface of first backup pad (2) is connected with division board (3), be provided with injection liquid chamber (4) and installation cavity (13) in shell (1), install suction pump (5) in injection liquid chamber (4), the output of suction pump (5) is connected with drain pipe (6), drain pipe (6) run through first backup pad (2), drain pipe (6) and first backup pad (2) fixed connection, install motor (7) in installation cavity (13), the output fixedly connected with pivot (8) of motor (7), pivot (8) run through first backup pad (2), pivot (8) are connected with first backup pad (2) rotation, the output of pivot (8) is connected with liquid box (9) through the mechanism that goes up and down, drain pipe (6) and liquid box (9) sliding connection, liquid box (6) inner chamber and liquid box (9) intercommunication each other the microneedle (10).