CN103755981A - Hydrogel used as skin filling material and preparation method thereof - Google Patents
Hydrogel used as skin filling material and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a hydrogel used as a skin filling material and a preparation method thereof. Skin filling materials such as white wax, silicon resin, a saline water bag, and silica gel have defects of generating chronic inflammation, lump, and tissue damage to tissues, are poor in biocompatibility, and are incapable of meeting the recovering requirement. The preparation method comprises the steps: adding a chitosan solution in a human-like collagen protein solution, stirring for reacting, adding a hyaluronic acid solution, stirring for reacting, adding a crosslinking agent, and stirring for reacting; and heating by adopting a constant-temperature water bath to prepare the hydrogel, wherein a human-like collagen protein is produced by a genetically engineered bacterium BL21 high-density fermentation. The hydrogel provided by the invention is prepared by adopting two methods of self-assembling and physical/chemical crosslinking, and has the advantages of better stability and high biological value, is capable of preventing trauma of surgical operation and reducing patient pain, thereby actually realizing the advantage of skin filling.
Description
Technical field
the present invention relates to a kind of hydrogel, be specifically related to a kind of hydrogel as skin packing material and preparation method thereof.
Background technology
Hydrogel is a kind of macromolecule network system, and character is soft, can keep certain shape, can absorb a large amount of water.The tissue that human body face beauty and shaping mainly contains and revise wrinkle, improve face contour, fill and lead up depressed scar or lip, reparation is injured etc., be applicable to human tissue structure, its require hydrogel do not absorb, do not come off, not cracked, under the environment of disperse, can keep well moisture, have good viscosity, elasticity and pliability.When hydrogel is transplanted to after organism, because degree of tissue damage is different, be difficult to meet the effect of repairing; When hydrogel is expelled to after organism, if hydrogel is environment sensitive type, such as responsive to temperature type, be at room temperature colloidal sol shape, when temperature reaches after human body temperature, hydrogel can form gel, can maintain form and have good biocompatibility.Therefore, injection type hydrogel is as tissue filling material, and its research, development and application have immeasurable market outlook.Prepare method that hydrogel is conventional and have two kinds of chemically crosslinked and physical crosslinkings.Self-assembling technique becomes the focus of research gradually in technical field of biological material, can be by the specific biological reactive force between biomolecules, interaction between hydrophobic, interaction of hydrogen bond and electrostatic interaction from simple to complex, the spontaneous process of disorder to order.Therefore, adopting Human-like Collagen, chitosan and hyaluronic acid is raw material, and application self-assembly and chemical/physical crosslinking technological are prepared hydrogel, are successfully applied to tissue renovation material.
Following three developmental stage have been gone through in the development of hydrogel: first-generation product is with Chinese wax injection, fat transfer, silicone resin, plastic sponge etc.; S-generation product be take gel and is planted into body as main, as bag of saline, silicon gel, prosthese etc.All there is the defect that tissue is produced to chronic inflammatory diseases, lump and damaged tissue in above two series products, and gel do not have good biocompatibility with tissue, so can not fully meet the requirement of body.Third generation product injection aquagel has also obtained development to a certain degree as a kind of good packing material, although overcome the shortcoming of tissue injury, it also can not accomplish to meet completely the requirement of reparation.
Summary of the invention
The object of this invention is to provide a kind of hydrogel as skin packing material and preparation method thereof, in conjunction with self-assembly and the crosslinked two kinds of methods preparation of physical/chemical, have more biocompatibility, the higher skin packing material of security.
The technical solution adopted in the present invention is:
A preparation method who is used as the hydrogel of skin packing material, is characterized in that:
By following steps, realized:
Step 1: take Human-like Collagen and be dissolved in distilled water, then in Human-like Collagen solution, add chitosan solution, the mass ratio that makes Human-like Collagen and chitosan is (1～6): 5, and temperature of reaction is controlled as-4～0 ℃, reacts 0.5～1h under agitation condition;
Step 2: add hyaluronic acid solution, the mass ratio of hyaluronic acid and chitosan is (0.1～0.4): 1, it is 20～30 ℃ that temperature of reaction is controlled, and under agitation condition, reacts 0.2～0.5h;
Step 3: add cross-linking agent solution, the mass ratio of linking agent and chitosan is (6～8): 1, temperature of reaction is controlled as-4～0 ℃, reacts 0.5～1h under agitation condition;
Step 4: reaction solution is put in to 1h in 37 ℃ of thermostat water baths, makes hydrogel.
In step 1, Human-like Collagen is the Human-like Collagen that genetic engineering bacterium BL21 high density fermentation is produced.
In step 1, chitosan is that deacetylation is more than 90% chitosan, and quality volume fraction is 40mg/mL.
In step 2, hyaluronic acid is other hyaluronic acid of medical grade, and molecular weight is 1000000Da, and the massfraction of hyaluronic acid solution is 2%.
In step 3, linking agent is that β-Phosphoric acid glycerol esters is received, α-Sodium Glycerophosphate or α, and β-Phosphoric acid glycerol esters is received, and the massfraction of cross-linking agent solution is 40%.
Hydrogel prepared by the preparation method of described a kind of hydrogel as skin packing material.
The present invention has the following advantages:
A kind of hydrogel as skin packing material involved in the present invention, by chitosan, hyaluronic acid and Human-like Collagen combine the skin packing material of making, the Human-like Collagen of producing with genetic engineering bacterium BL21 high density fermentation, chitosan and hyaluronic acid are raw material, adopt the crosslinked two kinds of methods of self-assembly and physical/chemical to make, have and have good stability, biological value is high, can avoid the advantage of operating wound and minimizing patient's pain, thereby really realize the advantage that skin is filled, and hydrogel varies with temperature the transition process that realizes sol-gel, finally reach the object that strengthens skin elasticity and beauty treatment.
Accompanying drawing explanation
Fig. 1 is the infrared spectrogram of hydrogel.
In figure, transverse axis is wave number (cm
-1), the longitudinal axis is transmitance (%), and Line 1 is that β-Phosphoric acid glycerol esters is received curve, and No. 2 lines are hyaluronic acid curve, and No. 3 lines are hydrogel curve, and No. 4 lines are Human-like Collagen curve, and No. 5 lines are chitosan curve.
Fig. 2 is the x-ray photoelectron energy spectrogram of hydrogel.
In figure, transverse axis is in conjunction with can (eV), and the longitudinal axis is counting (s), and Line 1 is that β-Phosphoric acid glycerol esters is received curve, and No. 2 lines are hydrogel curve, and No. 3 lines are hyaluronic acid curve, and No. 4 lines are chitosan curve, and No. 5 lines are Human-like Collagen curve.
Fig. 3 is the sample drawing of hydrogel.
In figure, A, B, C are the photo figure of self-assembly fiber, the colloidal sol figure that D is hydrogel, and E is hydrogel is glue figure, the photo figure that F is hydrogel.
Fig. 4 is the scanning electron microscope (SEM) photograph of self-assembly fiber and hydrogel.
In figure, No. 1 scanning electron microscope (SEM) photograph (amplifying 250 times) that is hydrogel, No. 2 scanning electron microscope (SEM) photographs (amplifying 100 times) that are hydrogel, No. 3 scanning electron microscope (SEM) photographs (amplifying 250 times) that are blend fiber, No. 4 scanning electron microscope (SEM) photographs (amplifying 100 times) that are blend fiber.
Fig. 5 is that hydrogel is injected in the subcutaneous figure of mouse.
In figure, A is injected in the figure of mouse after subcutaneous one week, B is injected in the figure of mouse after subcutaneous 2 weeks, C is injected in the figure of mouse after subcutaneous 6 weeks, D is injected in the figure of mouse after subcutaneous 10 minutes, E is the figure that is injected in the hydrogel that mouse takes out after subcutaneous 10 minutes, and F is the figure that hydrogel takes out from centrifuge tube, and G is the figure of hydrogel plastic in centrifuge tube.
Fig. 6 is that hydrogel is injected in the transmission electron microscope picture of mouse after subcutaneous.
In figure, A(first week), B(second week), C(is the 6th week) be the transmission electron microscope picture of control group (injecting normal saline), embodiment 1(D, G, J, M), embodiment 2(E, H, K, N), embodiment 3(F, I, L, O) and be the transmission electron microscope picture of hydrogel.Be injected in mouse subcutaneous rear respectively the 1st, 2,6,12 weeks sampling, D, E, F are first week, G, H, I are second week, J, K, L are the 3rd week, M, N, O are 4th week.In figure, 1 represents collegen filament, and 2 represent scavenger cell, and 3 represent neutrophil leucocyte, and 4 represent inoblast, and 5 represent fibrocyte, and 6 represent that fat drips, and 7 represent cell paste, and 8 represent inflammatory cell.
Fig. 7 is that hydrogel is injected in the immunohistochemical methods figure of mouse after subcutaneous.
In figure, A(first week), B(second week), C(the 6th week), D(is the 12 week) be the control group immunohistochemical methods figure of (not adding the dyeing of CD68 monoclonal antibody), embodiment 1(E, F, G, H), embodiment 2(I, J, Q, L), embodiment 3(M, N, O, P) be the hydrogel immunohistochemical methods figure of (adding the dyeing of CD68 monoclonal antibody).Be injected in mouse subcutaneous rear respectively the 1st, 2,6,12 weeks sampling, E, I, M are first week, F, J, N are second week, G, Q, O are the 6th week, H, L, P are the 12 week.T represents tissue, and G represents hydrogel, g-t representative tissue and hydrogel interface, and FC represents adipocyte, PC represents pigment cell.
Fig. 8 is that hydrogel is injected in the H & E colored graph of mouse after subcutaneous.
In figure, embodiment 1(A, E, I, J), embodiment 2(B, F, G, K), embodiment 3(C, D, H, L) be the H & E colored graph of hydrogel.Be injected in mouse subcutaneous rear respectively the 1st, 2,6,12 weeks sampling, A, B, C are first week, E, F, D are second week, I, G, H are the 6th week, J, K, L are the 12 week.
Fig. 9 is reaction principle procedure chart of the present invention.
Embodiment
Below in conjunction with embodiment, the present invention will be described in detail.
A kind of hydrogel as skin packing material involved in the present invention, Human-like Collagen, chitosan and hyaluronic acid that the genetic engineering bacterium BL21 high density fermentation of take is produced are raw material, adopt self-assembling technique to form self-assembly fiber, then by linking agent, carry out chemically crosslinked, under-4 ℃ of stirrings, carry out physical crosslinking again, after reaction finishes, reaction solution is put into the static 10-30 minute of placement at 37 ℃, prepare hydrogel.
What the Human-like Collagen in raw material adopted is the Human-like Collagen of being produced by genetic engineering bacterium BL21 high density fermentation, compare with the collagen protein extracting from animal source, it has good water solubility, low rejection, virus-free hidden danger, the remarkable advantage that structure and human body self collagen albumen are extremely approaching.In addition, animal source collagen protein also can be used as raw material and manufactures hydrogel.Chitosan itself has good biocompatibility and degradability, can be applicable to field of tissue engineering technology.Hyaluronic acid can directly be prepared hydrogel for injection fillers by linking agent, and it has good biocompatibility, but its degraded is than very fast.
And, Human-like Collagen, chitosan and hyaluronic acid itself have good biocompatibility and degradability, itself there is no temperature sensitive character, by self-assembling technique and the crosslinked hydrogel preparing of chemical/physical, there is temperature sensitivity, at room temperature be colloidal sol shape, can be expelled to and will fill position, when hydrogel spontaneous formation gel under human body temperature environment, its stability is high, does not absorb, do not come off, not cracked, there is good viscosity, elasticity and pliability, and there is good biocompatibility, be suitable for tissue filling.
Concrete preparation method is as follows:
Step 1: take Human-like Collagen and be dissolved in distilled water, then in Human-like Collagen solution, add chitosan solution, the mass ratio that makes Human-like Collagen and chitosan is (1～6): 5, and temperature of reaction is controlled as-4～0 ℃, under agitation condition, reacts 0.5～1h.
Wherein, Human-like Collagen is the Human-like Collagen that genetic engineering bacterium BL21 high density fermentation is produced; Chitosan is that deacetylation is more than 90% chitosan, and quality volume fraction is 40mg/mL.
Step 2: add hyaluronic acid solution, the mass ratio of hyaluronic acid and chitosan is (0.1～0.4): 1, it is 20～30 ℃ that temperature of reaction is controlled, and under agitation condition, reacts 0.2～0.5h.
Wherein, hyaluronic acid is other hyaluronic acid of medical grade, and molecular weight is 1000000Da, and the massfraction of hyaluronic acid solution is 2%.
After above-mentioned Human-like Collagen, chitosan and three kinds of mixed with polymers of hyaluronic acid, its aqueous systems can be spontaneous in solution by self-assembly, form blend fiber, its motivating force is that polycation and polyanion are by electrostatic adhesion interaction, interaction of hydrogen bond and hydrophobic interaction, the aqueous systems of each multipolymer does not have separately the character of heat-sensitive gel, and this can only be dissolved in the water within the scope of 1-50 ℃ simultaneously.
Step 3: add cross-linking agent solution, the mass ratio of linking agent and chitosan is (6～8): 1, temperature of reaction is controlled as-4～0 ℃, under agitation condition, reacts 0.5～1h.
Wherein, linking agent is that β-Phosphoric acid glycerol esters is received, α-Sodium Glycerophosphate or α, and β-Phosphoric acid glycerol esters is received, and the massfraction of cross-linking agent solution is 40%.
Add linking agent to carry out chemically crosslinked, under-4～0 ℃ of condition, stir and carry out physical crosslinking (freeze-thawing process implementation), adopt physical/chemical to carry out association response in conjunction with crosslinked method.Reacted aqueous systems has temperature correspondence, can spontaneous formation hydrogel under body temperature.
Step 4: reaction solution is put in to 1h in 37 ℃ of thermostat water baths, makes hydrogel.
Embodiment 1:
Step 1: take Human-like Collagen and be dissolved in distilled water, then add chitosan solution in Human-like Collagen solution, the mass ratio that makes Human-like Collagen and chitosan is 1:5, temperature of reaction is controlled as-4 ℃, under agitation condition, reacts 0.5h.
Wherein, Human-like Collagen is the Human-like Collagen that genetic engineering bacterium BL21 high density fermentation is produced; Chitosan is that deacetylation is more than 90% chitosan, and quality volume fraction is 40mg/mL.
Step 2: add hyaluronic acid solution, the mass ratio of hyaluronic acid and chitosan is 0.1:1, it is 20 ℃ that temperature of reaction is controlled, and under agitation condition, reacts 0.2h.
Wherein, hyaluronic acid is other hyaluronic acid of medical grade, and molecular weight is 1000000Da, and the massfraction of hyaluronic acid solution is 2%.
Step 3: add cross-linking agent solution, the mass ratio of linking agent and chitosan is 6:1, temperature of reaction is controlled as-40 ℃, under agitation condition, reacts 0.5h.
Wherein, linking agent is that β-Phosphoric acid glycerol esters is received, and the massfraction of cross-linking agent solution is 40%.
Step 4: reaction solution is put in to 1h in 37 ℃ of thermostat water baths, makes hydrogel.
Embodiment 2:
Step 1: take Human-like Collagen and be dissolved in distilled water, then add chitosan solution in Human-like Collagen solution, the mass ratio that makes Human-like Collagen and chitosan is 3:5, temperature of reaction is controlled as-2 ℃, under agitation condition, reacts 0.5h.
Wherein, Human-like Collagen is the Human-like Collagen that genetic engineering bacterium BL21 high density fermentation is produced; Chitosan is that deacetylation is more than 90% chitosan, and quality volume fraction is 40mg/mL.
Step 2: add hyaluronic acid solution, the mass ratio of hyaluronic acid and chitosan is 0.2:1, it is 25 ℃ that temperature of reaction is controlled, and under agitation condition, reacts 0.3h.
Wherein, hyaluronic acid is other hyaluronic acid of medical grade, and molecular weight is 1000000Da, and the massfraction of hyaluronic acid solution is 2%.
Step 3: add cross-linking agent solution, the mass ratio of linking agent and chitosan is 7:1, temperature of reaction is controlled as-2 ℃, under agitation condition, reacts 0.5h.
Wherein, linking agent is α-Sodium Glycerophosphate, and the massfraction of cross-linking agent solution is 40%.
Step 4: reaction solution is put in to 1h in 37 ℃ of thermostat water baths, makes hydrogel.
Embodiment tri-:
Step 1: take Human-like Collagen and be dissolved in distilled water, then add chitosan solution in Human-like Collagen solution, the mass ratio that makes Human-like Collagen and chitosan is 6:5, it is 0 ℃ that temperature of reaction is controlled, and under agitation condition, reacts 1h.
Wherein, Human-like Collagen is the Human-like Collagen that genetic engineering bacterium BL21 high density fermentation is produced; Chitosan is that deacetylation is more than 90% chitosan, and quality volume fraction is 40mg/mL.
Step 2: add hyaluronic acid solution, the mass ratio of hyaluronic acid and chitosan is 0.4:1, it is 30 ℃ that temperature of reaction is controlled, and under agitation condition, reacts 0.5h.
Wherein, hyaluronic acid is other hyaluronic acid of medical grade, and molecular weight is 1000000Da, and the massfraction of hyaluronic acid solution is 2%.
Step 3: add cross-linking agent solution, the mass ratio of linking agent and chitosan is 8:1, it is 0 ℃ that temperature of reaction is controlled, and under agitation condition, reacts 1h.
Wherein, linking agent is α, and β-Phosphoric acid glycerol esters is received, and the massfraction of cross-linking agent solution is 40%.
Step 4: reaction solution is put in to 1h in 37 ℃ of thermostat water baths, makes hydrogel.
The product of above embodiment is carried out to Infrared spectroscopy, x-ray photoelectron power spectrum, scanning electron microscope analysis, sample observation, TEM (transmission electron microscope) analysis, immunohistochemical analysis and H & E staining analysis, and its analytical results is as follows:
1, the Infrared spectroscopy of hydrogel packing material as shown in Figure 1, with pure Human-like Collagen, chitosan, hyaluronic C=O absorption peak (1644 cm
-1, 1644 cm
-1, 1646 cm
-1) compare the C=O(1619cm of hydrogel
-1) absorption peak generation blue shift, and at 1413 cm
-1there is new absorption peak at place, is the absorption peak of the C-N stretching vibration of amido linkage (RCONHR ').In hydrogel spectrogram, 1619 cm
-1with 2625 cm
-1place's absorption peak is newly-generated ammonium salt (RNH
2 +) absorption peak.
2, as shown in Figure 2, in N spectrum, there is new N at 399.31eV place in conjunction with generating to the X-ray photoelectron spectroscopic analysis of hydrogel packing material.In C spectrum, at the C of 287.85eV place, in conjunction with comparing and reduce with pure chitosan, compare increase with pure hyaluronic acid; At the C of 286.2eV place in conjunction with comparing all and reduce with hyaluronic acid with pure chitosan.Thereby proof has new amido linkage (RCONHR ') and ammonium salt (RNH
2 +) generate.
3, as shown in Figure 3, self-assembly fiber is well-regulated and arranges the sample of hydrogel packing material.Hydrogel is colloidal sol at ambient temperature, under body temperature condition, forms gel, and is the oyster white gel that is similar to jelly shape.
4, as shown in Figure 4, self-assembly fiber is well-regulated and arranges the scanning electron microscope analysis of hydrogel packing material.Hydrogel is the vesicular structure of three-dimensional network shape, arranges more regular.
5, hydrogel packing material is injected in the subcutaneous analysis of mouse as shown in Figure 5, is present in mouse subcutaneous at first week hydrogel; It is subcutaneous that second week hydrogel is present in mouse, slightly some degraded; The 6th week residual small portion of hydrogel, major part has been degraded.After taking out with from test tube after hydrogel packing material is injected in subcutaneous 10 minutes of mouse and takes out, compare, all become the milky hydrogel that is similar to jelly shape.
6, hydrogel packing material is injected in the TEM (transmission electron microscope) analysis of mouse after subcutaneous as shown in Figure 6, the hydrogel that embodiment mono-, two and three prepares has collegen filament and cell paste, the same with the analytical results of blank group (A, B, C), histocompatibility is good.
7, hydrogel packing material be injected in the immunohistochemical analysis of mouse after subcutaneous as shown in Figure 7, the hydrogel that embodiment mono-, two and three prepares, inflammatory reaction is minimum.
8, hydrogel packing material be injected in the H & E staining analysis of mouse after subcutaneous as shown in Figure 8, the hydrogel that embodiment mono-, two and three prepares, degradable and speed are slow.
The hydrogel packing material that the present invention makes shows for the experimentation on animals of the female ICR mouse that grows up: the hydrogel of preparing with self-assembly and physical/chemical crosslinking, there is good biocompatibility and histocompatibility, and degraded is slow, is suitable for tissue filling.
It is cited that content of the present invention is not limited to embodiment, and the conversion of any equivalence that those of ordinary skills take technical solution of the present invention by reading specification sheets of the present invention, is claim of the present invention and contains.
Claims (6)
1. be used as a preparation method for the hydrogel of skin packing material, it is characterized in that:
By following steps, realized:
Step 1: take Human-like Collagen and be dissolved in distilled water, then in Human-like Collagen solution, add chitosan solution, the mass ratio that makes Human-like Collagen and chitosan is (1～6): 5, and temperature of reaction is controlled as-4～0 ℃, reacts 0.5～1h under agitation condition;
Step 2: add hyaluronic acid solution, the mass ratio of hyaluronic acid and chitosan is (0.1～0.4): 1, it is 20～30 ℃ that temperature of reaction is controlled, and under agitation condition, reacts 0.2～0.5h;
Step 3: add cross-linking agent solution, the mass ratio of linking agent and chitosan is (6～8): 1, temperature of reaction is controlled as-4～0 ℃, reacts 0.5～1h under agitation condition;
Step 4: reaction solution is put in to 1h in 37 ℃ of thermostat water baths, makes hydrogel.
2. the preparation method of a kind of hydrogel as skin packing material according to claim 1, is characterized in that:
In step 1, Human-like Collagen is the Human-like Collagen that genetic engineering bacterium BL21 high density fermentation is produced.
3. the preparation method of a kind of hydrogel as skin packing material according to claim 2, is characterized in that:
In step 1, chitosan is that deacetylation is more than 90% chitosan, and quality volume fraction is 40mg/mL.
4. the preparation method of a kind of hydrogel as skin packing material according to claim 3, is characterized in that:
In step 2, hyaluronic acid is other hyaluronic acid of medical grade, and molecular weight is 1000000Da, and the massfraction of hyaluronic acid solution is 2%.
5. the preparation method of a kind of hydrogel as skin packing material according to claim 4, is characterized in that:
In step 3, linking agent is that β-Phosphoric acid glycerol esters is received, α-Sodium Glycerophosphate or α, and β-Phosphoric acid glycerol esters is received, and the massfraction of cross-linking agent solution is 40%.
6. the hydrogel that prepared by the preparation method of a kind of hydrogel as skin packing material as claimed in claim 5.
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| CN105944150A (en) * | 2016-03-25 | 2016-09-21 | 华东理工大学 | Hydrogel, artificial skin manufactured through application of hydrogel and manufacturing method of artificial skin |
| CN107189119A (en) * | 2017-07-24 | 2017-09-22 | 苏州景卓生物技术有限公司 | A kind of preparation method and applications of compound sodium hyaluronate collagen hydrogels |
| CN107638588A (en) * | 2016-07-22 | 2018-01-30 | 中央大学 | Hydrogel comprising bacterium and preparation method thereof |
| CN108939132A (en) * | 2018-07-18 | 2018-12-07 | 陕西科技大学 | A kind of high bioactivity hyaluronic acid medical film and preparation method thereof based on the modification of low immunogenicity collagen |
| CN109195642A (en) * | 2016-06-07 | 2019-01-11 | 医药研究产品有限公司 | Tissue enhancing filled compositions comprising nucleic acid, chitosan and hyaluronic acid and preparation method thereof |
| JP2019531816A (en) * | 2016-10-13 | 2019-11-07 | アラーガン、インコーポレイテッドＡｌｌｅｒｇａｎ，Ｉｎｃｏｒｐｏｒａｔｅｄ | Coacervate hyaluronan hydrogel for dermal filler applications |
| JP2021072906A (en) * | 2021-01-18 | 2021-05-13 | アラーガン、インコーポレイテッドＡｌｌｅｒｇａｎ，Ｉｎｃｏｒｐｏｒａｔｅｄ | Coacervate hyaluronan hydrogel for use in dermal filler |
| CN113384748A (en) * | 2021-04-29 | 2021-09-14 | 尚诚怡美(成都)生物科技有限公司 | Collagen dermal implant and preparation method thereof |
| CN117085174A (en) * | 2023-08-22 | 2023-11-21 | 美蔻生物药业(广州)有限公司 | Liquid dressing for medical and artistic wound care and preparation method thereof |
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| CN105944150A (en) * | 2016-03-25 | 2016-09-21 | 华东理工大学 | Hydrogel, artificial skin manufactured through application of hydrogel and manufacturing method of artificial skin |
| CN105944150B (en) * | 2016-03-25 | 2019-05-10 | 华东理工大学 | A kind of hydrogel and the artificial skin and preparation method thereof using the hydrogel |
| CN109195642B (en) * | 2016-06-07 | 2021-12-10 | 医药研究有限公司 | Filling composition for tissue enhancement comprising nucleic acid, chitosan and hyaluronic acid and preparation method thereof |
| CN109195642A (en) * | 2016-06-07 | 2019-01-11 | 医药研究产品有限公司 | Tissue enhancing filled compositions comprising nucleic acid, chitosan and hyaluronic acid and preparation method thereof |
| CN107638588A (en) * | 2016-07-22 | 2018-01-30 | 中央大学 | Hydrogel comprising bacterium and preparation method thereof |
| CN107638588B (en) * | 2016-07-22 | 2020-10-30 | 大江生医股份有限公司 | Hydrogel containing bacteria and preparation method thereof |
| JP2019531816A (en) * | 2016-10-13 | 2019-11-07 | アラーガン、インコーポレイテッドＡｌｌｅｒｇａｎ，Ｉｎｃｏｒｐｏｒａｔｅｄ | Coacervate hyaluronan hydrogel for dermal filler applications |
| CN107189119A (en) * | 2017-07-24 | 2017-09-22 | 苏州景卓生物技术有限公司 | A kind of preparation method and applications of compound sodium hyaluronate collagen hydrogels |
| CN107189119B (en) * | 2017-07-24 | 2020-06-16 | 浙江景嘉医疗科技有限公司 | Preparation method and application of composite hyaluronic acid collagen hydrogel |
| CN108939132A (en) * | 2018-07-18 | 2018-12-07 | 陕西科技大学 | A kind of high bioactivity hyaluronic acid medical film and preparation method thereof based on the modification of low immunogenicity collagen |
| JP2021072906A (en) * | 2021-01-18 | 2021-05-13 | アラーガン、インコーポレイテッドＡｌｌｅｒｇａｎ，Ｉｎｃｏｒｐｏｒａｔｅｄ | Coacervate hyaluronan hydrogel for use in dermal filler |
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Application publication date: 20140430 |