CN110812253A - Hyaluronic acid gel for water light injection and use method thereof - Google Patents
Hyaluronic acid gel for water light injection and use method thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/04—Dispersions; Emulsions
- A61K8/042—Gels
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/91—Injection
Abstract
The invention discloses a hyaluronic acid gel for water light injection, wherein the hyaluronic acid gel is disulfide-bond cross-linked hyaluronic acid, and the content of hyaluronic acid in the gel is not more than 10 mg/mL. The cross-linked hyaluronic acid gel has unique advantages when being used for hydro-optic injection, is easy to inject through a micro needle head of a hydro-optic needle, can realize good uniform distribution on a subcutaneous superficial layer, and does not generate a bulge phenomenon; meanwhile, the skin moisturizing cream has a moisturizing effect for a longer time than that of uncrosslinked hyaluronic acid, and can effectively improve skin quality.
Description
Technical Field
The invention relates to the field of biomedicine, in particular to a hyaluronic acid gel for water light injection and a using method of the hyaluronic acid gel for water light injection.
Background
In recent years, medical beauty treatment industry at home and abroad is rapidly developed, and various new beauty treatment technologies are researched and developed. The water light injection is one of the most extensive medical beauty treatment projects developed at home and abroad at present, can effectively solve the problem that skin care products used on the body surface are not easy to be absorbed through an epidermal barrier, can quickly and effectively supply water and nourishment to the skin, and can effectively improve the skin quality and delay senility. Water light injection originated from mesoderm therapy (Mesotherapy) proposed by Michal pitor in 1952 by the french physician, with the idea of injecting a trace of therapeutic substance topically and superficially; decades of efforts have been made to develop the current water laser needle technology. The water light injection precisely penetrates a plurality of extremely fine needle heads into the subcutaneous part by about 1-2 mm through a negative pressure technology, and the repairing substance is directly conveyed into the space between epidermis and dermis or dermis layer through the epidermis layer, so that the problem that effective ingredients in the skin care product cannot effectively penetrate the epidermis barrier is solved.
Hyaluronic acid, also known as hyaluronic acid, is an inherent acidic mucopolysaccharide in the human body, is commonly applied to various skin care products, is a super-strong moisturizer naturally existing in the skin of the human body, and can maintain 1000 times of the water content of the hyaluronic acid per se. The moisture level of the skin is closely related to the content and molecular weight of hyaluronic acid, and the hyaluronic acid with high molecular weight has stronger water retention performance. With the increase of age and the disruption of daily active oxygen radicals, endogenous hyaluronic acid in the skin is degraded and lost, and the water retention function is gradually weakened, so that various skin aging symptoms such as dryness, roughness, darkness, relaxation, wrinkles and the like are caused (Stern et al, Clinics in Dermatology 2008,26: 106-.
The supplement of exogenous hyaluronic acid is an important measure for improving skin quality, delaying aging symptoms and recovering young state. However, hyaluronic acid applied to the skin surface is hardly absorbed efficiently due to the epidermal barrier, and particularly high molecular weight hyaluronic acid having superior moisturizing ability. The hyaluronic acid injected by water light can directly penetrate through the epidermis barrier, and the hyaluronic acid can be immediately supplemented on the superficial layer of the skin, so that the effects of quickly supplementing water and moisturizing are realized, and the ultimate aim of improving the skin quality is fulfilled. The current water light injection mainly replenishes exogenous hyaluronic acid by superficial injection and also properly contains other repair nutrients. CN106074213A discloses a hyaluronic acid gel for water light injection, which comprises 10-30 parts of sodium hyaluronate, 0.5-3 parts of glycerol, 0.5-1.5 parts of mannitol, 1-9 parts of pH regulator and 25-45 parts of isotonic regulator. CN 105233270a discloses a pharmaceutical composition for water light therapy and its application, which comprises: 0.01-0.5 wt% of high molecular weight sodium hyaluronate, 0.01-0.3 wt% of medium molecular weight sodium hyaluronate, 0.01-1 wt% of low molecular weight sodium hyaluronate, 0.01-1 wt% of oligomeric sodium hyaluronate, 0.01-5 wt% of collagen, 0.05-1.8 wt% of an auxiliary agent, recombinant human epidermal growth factor and the balance of water, wherein the concentration of the recombinant human epidermal growth factor is 0.5-10 mu g/ml; the molecular weight of the high molecular weight sodium hyaluronate is 130-200 kilodaltons, the molecular weight of the medium molecular weight sodium hyaluronate is 50-100 kilodaltons, the molecular weight of the low molecular weight sodium hyaluronate is 5-30 kilodaltons, and the molecular weight of the oligomeric sodium hyaluronate is 3000-8000 daltons.
However, under the action of hyaluronidase in vivo, hyaluronic acid is rapidly degraded into small molecular fragments which enter body fluid circulation and are absorbed and metabolized, and the function of locally moisturizing skin is lost; in skin, hyaluronic acid has a half-life of less than 1 day (Laurent et al, Exp Physiol 1991,76: 695-. Therefore, although the water light injection can quickly supplement hyaluronic acid on local skin, the water injection can only supplement water and keep moisture in a short time, and the long-term effects of improving skin quality, delaying aging, recovering young state and the like are difficult to realize. For example, the results of Amin et al (Dermatol Surg 2006,32: 1467-.
Cross-linking modifications to retard the degradation and absorption of hyaluronic acid in vivo, e.g. 1, 4-butanediol diglycidyl ether (BDDE) cross-linked hyaluronic acid gels: (
Etc.) can be degraded and absorbed for more than 6 months under the skin, and is widely used for wrinkle injection filling. However, current crosslinked hyaluronic acid gel products are high in content (generally not less than 20mg/mL) (Edsman et al, Dermatol Surg 2012,38:1170-1179), i.e., generally not more than 98% in water content (water content of about 49 times the weight of the crosslinked hyaluronic acid itself), and poor in moisturizing performance; in addition, the cross-linked hyaluronic acid gel products also have higher gel strength, can be used after being crushed into granules, have higher extrusion force, and are difficult to perform superficial layer injection through a water smooth needle with a very fine needle head; in addition, these crosslinked hyaluronic acid gel products have poor fluidity, cannot be uniformly distributed on the superficial layer of water light injection, are easily swelled, and cannot be degraded and disappear in a short period of time. Therefore, there are many limitations in the use of current crosslinked hyaluronic acid gel products for water light injection.
Disclosure of Invention
In order to solve the problem that the maintenance time of the moisturizing effect is short due to degradation and absorption of the hyaluronic acid injected by water light in the prior art, and simultaneously solve the problem that the crosslinked hyaluronic acid gel is not suitable for water light injection although the degradation and absorption time is long in the prior art, the application provides the disulfide bond crosslinked hyaluronic acid gel for water light injection, which has longer degradation and absorption time and longer moisturizing maintenance time than the existing hyaluronic acid, has low impurity toxicity, is suitable for water light injection, does not generate the swelling phenomenon easily generated by the existing crosslinked hyaluronic acid gel product, and can effectively improve the skin quality through water light injection.
The invention is realized by the following technical scheme:
a hyaluronic acid gel for water light injection, wherein the hyaluronic acid is disulfide-bond-crosslinked hyaluronic acid, and the content thereof in hyaluronic acid is not more than 10 mg/mL.
In the present invention, the content of disulfide-bond crosslinked hyaluronic acid is expressed as the weight (mg/mL) of crosslinked hyaluronic acid contained in a unit volume of disulfide-bond crosslinked hyaluronic acid gel. The content of the cross-linked hyaluronic acid for water light injection is preferably 4-8 mg/mL, and particularly preferably 5.5-7 mg/mL.
Compared with the content of the current cross-linked hyaluronic acid gel product (generally not less than 20mg/mL), the content of the disulfide bond cross-linked hyaluronic acid gel for water light injection is low, and is only less than 50% of the content of the current cross-linked hyaluronic acid gel product; therefore, the disulfide bond cross-linked hyaluronic acid gel for the hydro-optical injection has lower strength and better fluidity, is easy to inject through the ultra-fine needle of the hydro-optical needle and realizes uniform distribution on the subcutaneous superficial layer. In addition, the disulfide bond cross-linked hyaluronic acid gel for water light injection has a water content of not less than 99% (99 times and more of the weight of disulfide bond cross-linked hyaluronic acid) and can further absorb and retain water to about 1000 times of the weight of disulfide bond cross-linked hyaluronic acid, so that the disulfide bond cross-linked hyaluronic acid gel for water light injection has a water retention capacity similar to that of non-cross-linked hyaluronic acid.
In the present invention, the disulfide bond cross-linked hyaluronic acid gel for water light injection according to the present invention can be prepared by a method similar to that disclosed in the prior art patent document CN 101721349a by the applicant of the present invention. The preparation method realizes disulfide bond crosslinking through the oxidation of the hyaluronic acid sulfhydrylation derivative aqueous solution under the oxidation action of oxygen (oxygen in air and/or dissolved oxygen in the aqueous solution), has the advantages of no need of adding a crosslinking agent, water as a byproduct, simple production process, no impurity and the like, and avoids the complex process of the current crosslinked hyaluronic acid gel product and potential toxic and side effects caused by the residual crosslinking agent.
As well known to those skilled in the art, in the current preparation process of crosslinked hyaluronic acid gel products, soaking dialysis is conventionally used for purification, that is, the gel after crosslinking reaction is soaked in a large amount of water or buffered saline solution to remove impurities such as residual crosslinking agent in the crosslinked gel by dialysis; the purification process requires the cross-linked gel to have higher strength, so the current cross-linked hyaluronic acid gel products all have higher strength and are not suitable for water light injection application. In contrast, in the present invention, the above-mentioned method for preparing the disulfide-bond cross-linked hyaluronic acid gel for water light injection does not require a purification process, and is particularly suitable for preparing a cross-linked gel having a low strength and a certain fluidity, and is suitable for water light injection use.
In the present invention, the disulfide-bond cross-linked hyaluronic acid gel for water light injection according to the present invention can be prepared using thiol-modified hyaluronic acid derivatives disclosed in the applicant's prior art patent document CN 102399295 a. The sulfhydryl derivatives of hyaluronic acid better keep the initial structure, physiological function and biocompatibility of hyaluronic acid, can realize effective disulfide bond crosslinking, and delay metabolism absorption in vivo, thus having longer water replenishing and moisturizing maintaining time than non-crosslinked hyaluronic acid.
The hyaluronic acid of the present invention may be in the form of a salt thereof (e.g., sodium salt, potassium salt, zinc salt, calcium salt, etc.) and/or a derivative thereof (e.g., carboxymethylated hyaluronic acid, acetylated hyaluronic acid, etc.).
In the present invention, the thiol-modified hyaluronic acid derivative refers to a thiol-containing hyaluronic acid derivative, which can be prepared by thiol-modification of hyaluronic acid, and also includes thiol-modified derivatives prepared by further thiol-modification of various hyaluronic acid derivatives. The side chain carboxyl, side chain hydroxyl, reducing end group and the like of hyaluronic acid or a salt or a derivative thereof are usually active functional groups capable of being subjected to thiol modification, and various methods for preparing thiol-modified hyaluronic acid derivatives disclosed in the prior documents such as WO 2009/006780a1 can be used for preparing the thiol-modified hyaluronic acid derivatives of the present invention.
In the present invention, thiol-modified derivatives of hyaluronic acid with various thiol contents can be used to prepare the disulfide-bond cross-linked hyaluronic acid gel for water light injection according to the present invention. The content of the sulfydryl groups is expressed as micromole (mu mol/g) of the sulfydryl groups contained in each gram of the thiol-modified hyaluronic acid derivative, the preferable content of the sulfydryl groups is 10-50 mu mol/g, and the particularly preferable content of the sulfydryl groups is 20-40 mu mol/g.
It is still another object of the present invention to provide a method for using the disulfide-bond cross-linked hyaluronic acid gel for water light injection.
When the content of the disulfide bond cross-linked hyaluronic acid gel for water light injection is low (generally less than 4 mg/mL), the water light injection can be directly carried out by adopting a water light injection mode well known by the technical personnel in the field, such as Derma
The water light injection instrument (demanga) and the like performs water light injection through a five-needle or nine-needle and other extremely fine negative pressure needle heads. However, when the content of the disulfide-bond cross-linked hyaluronic acid gel for water light injection is high (such as 4-10 mg/mL), the pushing force for directly performing water light injection is high, and at this time, the disulfide-bond cross-linked hyaluronic acid gel can be properly diluted to a low content (generally less than 4 mg/mL) before water light injection, so that the water light injection can be smoothly performed. The dilution process can be carried out in two-way or three-way joint connected injectors, wherein one injector is filled with the disulfide bond cross-linked hyaluronic acid gel for water light injection, the other injector is filled with physiological saline, buffer solution isosmotic with body fluid or nutrient active substance solution (such as solution containing growth factors, amino acids, vitamins and the like), and the two injectors are pushed and extruded to realize physical dilution and mixing. In addition to the supplementation of hyaluronic acid, the current water light injection usually also needs to be supplemented with other repair nutrients properly; this demand can conveniently be realized through above-mentioned physics hybrid process to realize synergistic effect such as water light injection moisturizing.
The invention has the beneficial effects that:
the disulfide bond cross-linked hyaluronic acid gel for the water injection overcomes the defects of the current cross-linked hyaluronic acid gel product for the water injection, has lower content and better fluidity, is easy to inject through the superfine needle of a water needle, can realize good uniform distribution on the subcutaneous superficial layer, and does not generate the swelling phenomenon; meanwhile, the skin moisturizing cream has a moisturizing effect for a longer time than that of uncrosslinked hyaluronic acid, and can effectively improve skin quality.
The disulfide bond cross-linked hyaluronic acid gel for water light injection can be conveniently prepared from thiol derivatives of hyaluronic acid, has the advantages of no need of adding a cross-linking agent, simple preparation process, no impurities and the like, and can avoid the complex process of the current cross-linked hyaluronic acid gel product and toxic and side effects caused by the residual cross-linking agent.
In addition, the disulfide-bond cross-linked hyaluronic acid gel for water light injection can be conveniently and physically mixed with other nutritional active substances before use so as to realize the synergistic effect of water light treatment.
Drawings
FIG. 1 Effect of disulfide-bond Cross-Linked sodium hyaluronate gel on skin Water content after hydro-light injection
Figure 2 effect of disulfide-bond cross-linked sodium hyaluronate gel on skin elasticity after hydro-light injection.
Figure 3 effect of disulfide-bond cross-linked sodium hyaluronate gel on skin wrinkle depth after hydro-light injection.
Detailed Description
Embodiments of the present invention will be described in detail below with reference to examples, but those skilled in the art will appreciate that the following examples are only illustrative of the present invention and should not be construed as limiting the scope of the present invention.
Example 1: preparation of disulfide-bond crosslinked hyaluronic acid gel
The thiol-modified hyaluronic acid derivative is prepared by using sodium hyaluronate with a molecular weight of 180KDa as a raw material and adopting a method reported by Shu and the like (Shu and the like, Biomacromolecules 2002,3: 1304-plus 1311), wherein the thiol contents of the thiol-modified hyaluronic acid derivative are 24 mu mol/g, 38 mu mol/g and 57 mu mol/g respectively.
Dissolving the thiol-modified hyaluronic acid derivative to obtain 10mL of water solution, wherein the content of the water solution is 3mg/mL, 4mg/mL, 5.5mg/mL, 6.5mg/mL, 7mg/mL, 8mg/mL and 10 mg/mL; adjusting the pH value of the solution to 7.4, sterilizing, filtering, and transferring into a 25ml sterile glass container; keeping for 4 weeks at room temperature, sealing and standing, and allowing the solution to lose fluidity and form disulfide bond crosslinked hydrogel.
Example 2: evaluation of injectability of disulfide-bond crosslinked hyaluronic acid gel
By Derma
(demanga) 2 generation water light injection apparatus, the gel prepared in example 1 was tested for injectability through a conventional water light injection needle (nine needles) with the following test results:
when the content of the cross-linked hyaluronic acid is 3mg/mL and 4mg/mL, the injectability is good generally; and the content is more than or equal to 5.5mg/mL, so that the injection is difficult to carry out by a water light injection instrument.
Example 3: evaluation of injectability of disulfide-bond crosslinked hyaluronic acid gel after dilution
The gels prepared in example 1 (the contents of the cross-linked hyaluronic acid were 5.5mg/mL, 6.5mg/mL, 7mg/mL, 8mg/mL and 10mg/mL, respectively; the thiol content of the thiolated derivative was 38. mu. mol/g) were diluted by physical mixing with physiological saline in the volume ratios of 1:1, 1:1.5 and 1: 2. The dilution process was performed in two syringes connected by a connector, one syringe containing the gel (1mL) prepared in example 1 and the other syringe containing a suitable volume of physiological saline (1mL, 1.5mL, 3mL), and the two syringes were physically diluted and mixed by pushing back and forth 60 to 80 times.
By Derma
(demanga) 2 generation water light injection instrument, and the injectability of the diluted gel through a conventional water light injection needle (nine needles) is tested, and the test results are as follows:
when the content is diluted to be less than or equal to 4mg/mL, the injection can be realized through a water light injection instrument; the lower the content after dilution, the better the injectability. And the current crosslinked hyaluronic acid gel products (
Etc.) has high strengthAnd the particle size is larger, and even if the dilution is carried out according to the volume ratio of higher times under the same condition, the injection needle head is still easy to block.
Example 4: evaluation of Water absorption and Water retention Properties of disulfide bond Cross-Linked hyaluronic acid gel
The gel prepared in example 1 and normal saline are physically mixed and diluted according to the volume ratio of 1:2 by adopting the same dilution process as example 3, then the gel is placed into a glass bottle and stands for 1 hour at room temperature, and no obvious layering phenomenon of a water phase and a gel phase is observed, so that the gel has good water absorption and retention performance (about 1000 times of the self weight of the cross-linked hyaluronic acid).
Example 5: evaluation of injectability of disulfide-bond crosslinked hyaluronic acid gel after dilution
The gel prepared in example 1 (content: 6.5 mg/mL; mercapto group content of the mercapto derivative: 57. mu. mol/g) was physically mixed and diluted with 5 kinds of aqueous solutions (containing 0.5mg/mL of vitamin C, vitamin B2, arginine, lysine and glutamine, respectively) in the volume ratios of 1:1 and 1:2, respectively, by the same mixing and diluting procedure as in example 3. By Derma
(demanga) 2 generation water light injection instrument, testing the injectability of the gel after each dilution through a conventional water light injection needle (nine needles); test results show that the gel after dilution has good injectability.
Example 6: preparation of disulfide-bond crosslinked hyaluronic acid gel
The thiol-modified hyaluronic acid derivative is prepared by using 300KDa and 1,500KDa molecular weight sodium hyaluronate as raw material and adopting the method reported by Shu et al (Shu et al, Biomacromolecules 2002,3:1304-1311), and the thiol contents of the thiol-modified hyaluronic acid derivative are 33 mu mol/g and 40 mu mol/g respectively.
Dissolving the thiol-modified hyaluronic acid derivative to obtain 10mL of water solution, wherein the content of the water solution is 3mg/mL, 4mg/mL, 5.5mg/mL, 6.5mg/mL, 7mg/mL, 8mg/mL and 10 mg/mL; adjusting the pH value of the solution to 7.4, sterilizing, filtering, and transferring into a 25ml sterile glass bottle; keeping for 4 weeks at room temperature, sealing and standing, and allowing the solution to lose fluidity and form disulfide bond crosslinked hydrogel.
Example 7: injectable properties of disulfide-bond cross-linked hyaluronic acid gels
By Derma
(dammar) 2 generation water light injection apparatus, the gel prepared in example 6 was tested for injectability through a conventional water light injection needle (nine needles). The test results of this example show that: when the content is 3mg/mL and 4mg/mL, the injectability is better generally; and the concentration is more than or equal to 5.5mg/mL, so that the injection is difficult to carry out by a water light injection instrument.
Example 8: evaluation of injectability of disulfide-bond crosslinked hyaluronic acid gel after dilution
The gel prepared in example 6 (contents: 5.5mg/mL, 6.5mg/mL, 7mg/mL, 8mg/mL and 10mg/mL, respectively) was physically mixed and diluted with physiological saline in volume ratios of 1:1, 1:1.5 and 1: 2. The dilution procedure was the same as in example 3.
By Derma(demanga) 2 generation water light injection instrument, and testing the injectability of the diluted gel through a conventional water light injection needle (nine needles). The test results of this example show that the injection performance is good when the injection is diluted to a content of less than or equal to 4 mg/mL.
Example 9: evaluation of Effect of Water light injection of disulfide bond Cross-Linked hyaluronic acid gel
8 healthy volunteers (4 in test group and 4 in control group) were selected for facial water light injection (Derma) respectively
2 generation water light injection instrument, conventional nine-needle water light injection needle).
The samples used in the test groups were: 2mL of the gel prepared in example 1 (crosslinked hyaluronic acid content: 6.5 mg/mL; thiol content of the thiolated derivative: 38. mu. mol/g) was mixed with 3mL of physiological saline and diluted before use in the same manner as in example 3; the total volume of the sample was 5mL, and the final content of the cross-linked sodium hyaluronate was 2.6 mg/mL. The control used the same volume of the same concentration of non-crosslinked sodium hyaluronate in water (molecular weight 1.5 MDa).
Skin moisture content test and improvement test of wrinkles and skin elasticity were performed at the same site at different time points after facial water light injection, respectively.
The relative increase (%) of skin moisture before and after injection was measured using a skin moisture meter, the relative increase (%) of skin elasticity before and after injection was measured using a skin elasticity meter, and the relative decrease in average depth of wrinkles before and after injection was evaluated using a rapid three-dimensional imaging system.
The test results of this example are shown in FIGS. 1-3. Compared with a non-crosslinked hyaluronic acid control, the disulfide-bond crosslinked hyaluronic acid gel has better water light treatment effect and longer maintenance time; meanwhile, no swelling phenomenon is found in all test objects in the treatment group, which shows that the disulfide bond cross-linked hyaluronic acid gel has good fluidity and can be uniformly distributed on the superficial layer of water light injection.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the embodiments, and any other changes, modifications, combinations, substitutions and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents and are included in the scope of the present invention.
Claims (10)
1. A hyaluronic acid gel for use in water light injection, characterized in that the hyaluronic acid is disulfide-bond-crosslinked hyaluronic acid, and wherein the content of disulfide-bond-crosslinked hyaluronic acid is not more than 10 mg/mL.
2. The hyaluronic acid gel for water light injection according to claim 1, wherein the content of the disulfide-bond cross-linked hyaluronic acid is between 4 and 8 mg/mL.
3. The hyaluronic acid gel for water light injection according to claim 2, wherein the content of the disulfide-bond cross-linked hyaluronic acid is between 5.5 and 7 mg/mL.
4. The hyaluronic acid gel for water light injection according to claim 1, wherein the crosslinked hyaluronic acid gel for water light injection is prepared by thiolating derivatives of hyaluronic acid.
5. The hyaluronic acid gel for water light injection according to claim 4, wherein the thiol content of the thiol-modified derivative of hyaluronic acid is between 10 and 50 μmol/g.
6. The hyaluronic acid gel for water light injection according to claim 5, wherein the thiol content of the thiol-modified derivative of hyaluronic acid is between 20 and 40 μmol/g.
7. The method for using the hyaluronic acid gel for water light injection according to any of claims 1-6, wherein the disulfide-bond crosslinked hyaluronic acid gel is diluted with a diluent by physical mixing until the content of the disulfide-bond crosslinked hyaluronic acid is not more than 4mg/mL before use.
8. The method for using the hyaluronic acid gel for water light injection according to claim 7, wherein the diluent is physiological saline or a buffered saline solution isotonic with body fluid.
9. The method of using the hyaluronic acid gel for water light injection according to claim 7, wherein the diluent contains a nutritional active substance.
10. The method for using the hyaluronic acid gel for water light injection according to claim 9, wherein the nutraceutically active substance is an amino acid, a vitamin or a growth factor.
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| CN111498822A (en) * | 2020-05-25 | 2020-08-07 | 四川大学 | Functional fibrosis hybrid gel and preparation method and application thereof |
| WO2021077683A1 (en) * | 2019-10-23 | 2021-04-29 | 常州百瑞吉生物医药有限公司 | Hyaluronic acid gel for hyaluronic acid injection and use method for hyaluronic acid gel |
| WO2021077681A1 (en) * | 2019-10-23 | 2021-04-29 | 常州百瑞吉生物医药有限公司 | Hyaluronic acid gel composition for water optoinjection, and preparation method therefor |
| CN115671030A (en) * | 2021-07-21 | 2023-02-03 | 杭州协合医疗用品有限公司 | Melanocyte-containing sodium hyaluronate hydrogel capable of being injected by water light needle, preparation method and application |
| CN117298355A (en) * | 2023-11-28 | 2023-12-29 | 常州百瑞吉生物医药股份有限公司 | Coated hyaluronic acid gel composition and preparation method and application thereof |
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| CN108261341A (en) * | 2018-02-12 | 2018-07-10 | 苏州纳晶医药技术有限公司 | Two-component is used to correct the long-acting water laser accunputure agent of whitening of wrinkle of skin |
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| CN110812253A (en) * | 2019-10-23 | 2020-02-21 | 常州百瑞吉生物医药有限公司 | Hyaluronic acid gel for water light injection and use method thereof |
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| WO2021077683A1 (en) * | 2019-10-23 | 2021-04-29 | 常州百瑞吉生物医药有限公司 | Hyaluronic acid gel for hyaluronic acid injection and use method for hyaluronic acid gel |
| WO2021077681A1 (en) * | 2019-10-23 | 2021-04-29 | 常州百瑞吉生物医药有限公司 | Hyaluronic acid gel composition for water optoinjection, and preparation method therefor |
| CN111498822A (en) * | 2020-05-25 | 2020-08-07 | 四川大学 | Functional fibrosis hybrid gel and preparation method and application thereof |
| CN115671030A (en) * | 2021-07-21 | 2023-02-03 | 杭州协合医疗用品有限公司 | Melanocyte-containing sodium hyaluronate hydrogel capable of being injected by water light needle, preparation method and application |
| CN117298355A (en) * | 2023-11-28 | 2023-12-29 | 常州百瑞吉生物医药股份有限公司 | Coated hyaluronic acid gel composition and preparation method and application thereof |
| CN117298355B (en) * | 2023-11-28 | 2024-03-08 | 常州百瑞吉生物医药股份有限公司 | Coated hyaluronic acid gel composition and preparation method and application thereof |
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