CN113244456A

CN113244456A - Active filler for resisting aging around eyes and preparation method thereof

Info

Publication number: CN113244456A
Application number: CN202110603068.9A
Authority: CN
Inventors: 贺激光; 李�杰; 季子云
Original assignee: Metso Hangzhou Medical Technology Co ltd
Current assignee: Metso Hangzhou Medical Technology Co ltd
Priority date: 2021-05-31
Filing date: 2021-05-31
Publication date: 2021-08-13

Abstract

The invention discloses an active filler for resisting aging around eyes, which belongs to the technical field of medical cosmetology and aging resistance, and is characterized in that hyaluronic acid or a composition part thereof, sugar, alkali and normal saline/distilled water are adopted; the active filler prepared by the invention is easy to prepare, namely can be prepared immediately after use, and is simple and convenient to operate. The filling can be finished at one time without need of refilling, and the gel can be prepared immediately when the filling is not enough, and has excellent viscoelasticity. When the medical liquid is injected into eyes of a human body in a medical operation, the medical liquid has good elasticity like muscle tissues of the human body, and meanwhile, the good viscosity can ensure that fillers injected into the human body can be fully bonded with the human body, so that the continuity is improved.

Description

Active filler for resisting aging around eyes and preparation method thereof

Technical Field

The invention belongs to the technical field of medical beauty treatment and anti-aging, and particularly relates to an active filler for resisting aging around eyes and a preparation method thereof.

Background

Human skin tissue maintains its structure through an extracellular matrix containing proteins such as collagen, elastin, or the like and glycosaminoglycans, but when soft tissue defects occur due to external impact, disease, aging, or the like, tissue augmentation, for example, soft tissue augmentation has been used for medical and cosmetic purposes. This enhancement is accomplished by orthopedic surgery or by injecting biological tissue or synthetic polymer chemicals into the area to increase and expand the volume of the soft tissue to repair and modify its shape in a non-surgical manner. Then, a substance, which is a component similar to skin tissue and is inserted into a specific site to expand soft tissue, thereby cosmetically expanding the volume of the cheek, lip, breast, hip, etc. and for anti-wrinkle or contour correction by reducing skin fine lines and deep lines, is called a soft tissue bulking material, and is generally called a dermal filler. The first generation dermal fillers originally developed with respect to such fillers include products prepared by extracting animal proteins derived from animals, i.e., cattle or pigs, such as Zyderm and Zyplast, and cosmoperm or Cosmoplast using human collagen, etc., but they have been rarely used recently due to the short duration of effect and inconvenience of skin sensitization test one month before surgery. The second generation filler is hyaluronic acid (hereinafter also referred to as 'HA') filler, HAs a longer duration of effect than collagen filler and is composed of polysaccharides (N-acetyl-D-glucosamine and D-glucuronic acid) similar to human body components, and thus HAs less side effects and is easy to handle and remove, and can maintain moisture, volume and elasticity of the skin by sucking water, thus having suitable advantages as a skin filler. However, hyaluronic acid itself shows a short half-life in the human body, only a few hours, and thus is limited in application, and thus studies have been made to increase the half-life (internal durability) by crosslinking. For example, U.S. patent discloses a hyaluronic acid derivative crosslinked using Divinylsulfone (DVS) as a crosslinking agent, the hydrogel form of which has been marketed under the trade name, and U.S. patent No. 5,827,937 discloses a method for preparing a crosslinked product of a hyaluronic acid derivative using a polyfunctional epoxy compound as a crosslinking agent, wherein the crosslinked product of hyaluronic acid in the form of hydrogel prepared using 1, 4-butanediol diglycidyl ether (BDDE) as a crosslinking agent has been approved by the U.S. FDA and can be used globally as a tissue-reinforcing filler. Such crosslinked hyaluronic acid fillers include fillers made of a single phase (single-phase HA fillers) and fillers made of a dual phase (dual-phase HA fillers). Single phase hyaluronic acid fillers are prepared using homogeneous liquid-like hydrogels comprising cross-linked hyaluronic acid and thus generally have low elasticity and high cohesion. Therefore, when the single-phase hyaluronic acid filler is injected into the skin, it is unlikely to deviate from the injection site, but there are problems in that the injection form cannot be maintained for a long time and the shape (form) retention time after the operation is only about 2 months.

The biphasic hyaluronic acid bulking agent is prepared by non-crosslinking crosslinked hyaluronic acid particles alone or in close proximity to a fluid.

Hyaluronic acid (untreated non-crosslinked hyaluronic acid (linear HA)) is mixed and thus generally HAs high elasticity and low cohesiveness. Therefore, when the biphasic HA filler is injected, its shape can be maintained for a long time, but there is a problem in that the possibility of deviation from the injection site is high.

Among the aging of many body tissues, the aging of eyes is most remarkable particularly because eyes are exposed to air for a long time and eyes of a person need to be used frequently, and aging is faster due to staying up night, fatigue, and the like.

In conclusion, the injection of the filler is an important way for delaying hand aging of human beings in the future, and is a research direction of the medical cosmetology industry, and therefore, the active filler for resisting aging around eyes and the preparation method thereof are provided.

Disclosure of Invention

The invention aims to provide an active filler for resisting aging around eyes and a preparation method thereof, which adopts hyaluronic acid or a composition part thereof, sugar, alkali, normal saline/distilled water; the active filler prepared by the invention is easy to prepare, namely can be prepared immediately after use, and is simple and convenient to operate. The infusion can be completed in one step without need of additional infusion, and can be immediately prepared when the infusion is not enough.

The purpose of the invention can be realized by the following technical scheme:

an active filler for resisting aging around eyes is composed of the following raw materials in parts by weight: 10-15 parts of hyaluronic acid or a composition thereof, 30-40 parts of sugar, 5-10 parts of alkali and 20-30 parts of normal saline/distilled water; 50-80 parts of oil solution, 5-8 parts of cross-linked hyaluronic acid microspheres, 10-25 parts of cross-linking agent and 30-50 parts of plasticizer;

the preparation method of the active filler comprises the following steps:

step S1, crosslinking the hyaluronic acid by mixing in a reaction chamber: hyaluronic acid or a composition thereof, alkali and water to obtain an aqueous solution;

step S2, adding the aqueous solution obtained in the step S1 into an oil solution containing an emulsifier, and fully emulsifying to obtain an emulsion;

step S3, crosslinking the emulsion at a crosslinking temperature by using a crosslinking agent, removing an oil solution after crosslinking, and performing post-treatment to obtain crosslinked hyaluronic acid microspheres;

step S4, dissolving hyaluronic acid or a composition thereof in water to obtain hyaluronic acid gel;

step S5, adding the crosslinked hyaluronic acid microspheres or the crosslinked hyaluronic acid microspheres and other effective components into the hyaluronic acid gel obtained in the step S4, uniformly stirring, subpackaging and drying;

step S6, filling the hyaluronic acid gel prepared in step S5 into a syringe, and then sterilizing to prepare an active filler for anti-aging around the eyes.

As a further technical scheme of the invention: the composition comprises the following components in parts by weight: 11-13 parts of hyaluronic acid or a composition thereof, 35-40 parts of sugar, 6-9 parts of alkali and 25-30 parts of normal saline/distilled water; 70-80 parts of oil solution, 6-8 parts of cross-linked hyaluronic acid microspheres, 18-25 parts of cross-linking agent and 36-50 parts of plasticizer.

As a further technical scheme of the invention: the composition comprises the following components in parts by weight: 11 parts of hyaluronic acid or a composition thereof, 35 parts of sugar, 6 parts of alkali and 25 parts of physiological saline/distilled water; 70 parts of oil solution, 6 parts of cross-linked hyaluronic acid microspheres, 18 parts of cross-linking agent and 36 parts of plasticizer.

As a further technical scheme of the invention: the oil solution is composed of an emulsifier and a matrix, wherein the matrix comprises vegetable oil, mineral oil, silicone oil, liquid paraffin, dodecane, n-octane or cyclohexane, the hydrophilic-hydrophobic balance value of the emulsifier is 6, and sorbitan monooleate or sorbitan monostearate is adopted.

As a further technical scheme of the invention: the sugar is xylose, sucrose, maltose, lactose, glucose, glucosamine, glucuronic acid, rhamnose, mannose, fucose, arabinose, acetylglucosamine, inositol, trehalose, isomalt, xylitol, erythritol or two or more thereof.

As a further technical scheme of the invention: the cross-linking agent is one or more selected from the group consisting of: butanediol diglycidyl ether (1, 4-butanediol diglycidyl ether: BDDE), ethylene glycol diglycidyl ether (EGDGE), hexanediol diglycidyl ether (1, 6-hexanediol diglycidyl ether), propylene glycol diglycidyl ether, polypropylene glycol diglycidyl ether, polytetramethylene glycol diglycidyl ether, neopentyl glycol diglycidyl ether, polyglycerol polyglycidyl ether, diglycerol polyglycidyl ether, glycerol polyglycidyl ether, trimethylpropane polyglycidyl ether, bisglycidoxyethylene (1,2- (bis (2, 3-epoxypropoxy) ethylene), pentaerythritol polyglycidyl ether and sorbitol polyglycidyl ether.

As a further technical scheme of the invention: the hyaluronic acid or its composition is hyaluronic acid, sodium carboxymethylcellulose, vinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohol, polyvinylpyrrolidone or their mixture.

A preparation method of an active filler for resisting aging around eyes comprises the following steps:

As a further technical scheme of the invention: the aqueous solution in step S1 requires sonication for 5 to 15 minutes.

As a further technical scheme of the invention: the active filler obtained in the step S6 needs to be pH-controlled to check whether its value is between 6.5 and 7.5.

As a further technical scheme of the invention: the filler was inserted into the cartridge of the syringe, which was sterilized in an autoclave at 121 ℃ for 16 minutes.

The invention has the beneficial effects that:

1. the filler produced by the present invention has a high pulling power, not only has a low possibility of deviating from an injection site and an advantage that its shape can be maintained for a long time, but also can minimize problems that may be caused when the filler is injected, for example, difficulties in a doctor's operation due to high injection force or pain of a patient, by exhibiting a low injection force different from a conventional filler having a high pulling power, and thus, it can be used as a filler for repairing soft tissues such as cheek, lip, breast, hip, etc., or expanding volume, anti-wrinkle by reducing fine and deep wrinkles of skin, or contour correction, particularly suitable for anti-aging filling of the eye.

2. The present design incorporates a sugar as a buffering agent, is close to the ingredients of the human body, and can deliver cross-linked hyaluronic acid (hyaluronic acid filler substance) into the skin or the skin by a simple method, and the swelling property of the cross-linked hyaluronic acid is improved after the delivery, thereby exerting an excellent wrinkle-improving effect.

3. The preparation is easy, and the preparation is carried out immediately after use, and the operation is simple and convenient. The infusion can be completed in one step without need of additional infusion, and can be immediately prepared when the infusion is not enough.

Detailed Description

The technical solutions of the present invention will be described clearly and completely with reference to the following embodiments, and it should be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

the preparation method of the active filler comprises the following steps:

The oil solution consists of an emulsifier and a matrix, wherein the matrix comprises vegetable oil, mineral oil, silicone oil, liquid paraffin, dodecane, n-octane or cyclohexane, the hydrophilic-hydrophobic balance value of the emulsifier is 6, and sorbitan monooleate or sorbitan monostearate is adopted.

Wherein the sugar is xylose, sucrose, maltose, lactose, glucose, glucosamine, glucuronic acid, rhamnose, mannose, fucose, arabinose, acetylglucosamine, inositol, trehalose, isomalt, xylitol, erythritol or two or more thereof.

Wherein the cross-linking agent is one or more selected from the group consisting of: butanediol diglycidyl ether (1, 4-butanediol diglycidyl ether: BDDE), ethylene glycol diglycidyl ether (EGDGE), hexanediol diglycidyl ether (1, 6-hexanediol diglycidyl ether), propylene glycol diglycidyl ether, polypropylene glycol diglycidyl ether, polytetramethylene glycol diglycidyl ether, neopentyl glycol diglycidyl ether, polyglycerol polyglycidyl ether, diglycerol polyglycidyl ether, glycerol polyglycidyl ether, trimethylpropane polyglycidyl ether, bisglycidoxyethylene (1,2- (bis (2, 3-epoxypropoxy) ethylene), pentaerythritol polyglycidyl ether and sorbitol polyglycidyl ether.

Wherein the hyaluronic acid or its composition is hyaluronic acid, sodium carboxymethylcellulose, vinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohol, polyvinylpyrrolidone or their mixture.

The invention also discloses a preparation method of the active filler for resisting aging around eyes, which comprises the following steps:

Wherein the aqueous solution in step S1 requires sonication for 5 to 15 minutes.

Wherein the active filler obtained in step S6 needs to be pH-controlled to check whether its value is between 6.5 and 7.5.

Wherein the filler is inserted into a cartridge of a syringe, said cartridge being sterilized in an autoclave at 121 ℃ for 16 minutes.

Example 1:

an active filler for resisting aging around eyes is prepared from the following components in parts by weight: 15 parts of hyaluronic acid or a composition thereof, 40 parts of sugar, 10 parts of alkali and 30 parts of normal saline/distilled water; 80 parts of oil solution, 8 parts of cross-linked hyaluronic acid microspheres, 25 parts of cross-linking agent and 50 parts of plasticizer.

The oil solution consists of an emulsifier and a matrix, wherein the matrix is formed by mixing vegetable oil, mineral oil and silicone oil, and the mixing ratio is 1: 1: 1, the hydrophilic-hydrophobic balance value of the emulsifier is 6, and sorbitan monooleate is adopted.

Wherein, the sugar is formed by mixing lactose and glucose, and the mixing proportion is 1: 1.

wherein the cross-linking agent is formed by mixing ethylene glycol diglycidyl ether (EGDGE), hexanediol diglycidyl ether (1, 6-hexanediol diglycidyl ether) and propylene glycol diglycidyl ether according to the mixing ratio of 2: 1: 1.

the hyaluronic acid or the composition thereof is prepared by mixing hyaluronic acid, sodium carboxymethylcellulose and sodium carboxymethylcellulose, wherein the mixing ratio is 2: 2: 1.

step S1, crosslinking the hyaluronic acid by mixing in a reaction chamber: 15 parts of hyaluronic acid or a composition thereof, 10 parts of alkali and 30 parts of normal saline/distilled water to obtain an aqueous solution, and carrying out ultrasonic treatment on the aqueous solution for 5 to 15 minutes;

step S2, adding the aqueous solution obtained in the step S1 into 80 parts of oil solution containing an emulsifier, and fully emulsifying to obtain an emulsion;

step S6, the hyaluronic acid gel prepared in step S5 is filled into a syringe, the cartridge is sterilized in an autoclave at 121 ℃ for 16 minutes, and the active filler for anti-aging around the eyes is prepared, and the obtained active filler needs to be pH-controlled and checked to have a pH value of 7.1.

Example 2:

an active filler for resisting aging around eyes is prepared from the following components in parts by weight: 10 parts of hyaluronic acid or a composition thereof, 30 parts of sugar, 5 parts of alkali and 20 parts of normal saline/distilled water; 50 parts of oil solution, 5 parts of cross-linked hyaluronic acid microspheres, 10 parts of cross-linking agent and 30 parts of plasticizer.

step S1, crosslinking the hyaluronic acid by mixing in a reaction chamber: 10 parts of hyaluronic acid or a composition thereof, 5 parts of alkali and 20 parts of normal saline/distilled water to obtain an aqueous solution, and carrying out ultrasonic treatment on the aqueous solution for 5 to 15 minutes;

step S2, adding the aqueous solution obtained in the step S1 into 50 parts of oil solution containing an emulsifier, and fully emulsifying to obtain an emulsion;

step S6, the hyaluronic acid gel prepared in step S5 is filled into a syringe, the cartridge is sterilized in an autoclave at 121 ℃ for 16 minutes, and the active filler for anti-aging around the eyes is prepared, and the obtained active filler needs to be pH-controlled and checked to have a pH value of 6.9.

Example 3:

an active filler for resisting aging around eyes is prepared from the following components in parts by weight: 11 parts of hyaluronic acid or a composition thereof, 35 parts of sugar, 6 parts of alkali and 25 parts of physiological saline/distilled water; 70 parts of oil solution, 6 parts of cross-linked hyaluronic acid microspheres, 18 parts of cross-linking agent and 36 parts of plasticizer.

step S1, crosslinking the hyaluronic acid by mixing in a reaction chamber: 11 parts of hyaluronic acid or a composition thereof, 6 parts of alkali and 25 parts of normal saline/distilled water to obtain an aqueous solution, and carrying out ultrasonic treatment on the aqueous solution for 5 to 15 minutes;

step S2, adding the aqueous solution obtained in the step S1 into 70 parts of oil solution containing an emulsifier, and fully emulsifying to obtain an emulsion;

Comparative example 4:

an active filler for resisting aging around eyes is prepared from the following components in parts by weight: 5 parts of hyaluronic acid or a composition thereof, 50 parts of sugar, 10 parts of alkali and 50 parts of physiological saline/distilled water; 50 parts of oil solution, 5 parts of cross-linked hyaluronic acid microspheres, 10 parts of cross-linking agent and 30 parts of plasticizer.

step S1, crosslinking the hyaluronic acid by mixing in a reaction chamber: 5 parts of hyaluronic acid or a composition thereof, 10 parts of alkali and 50 parts of normal saline/distilled water to obtain an aqueous solution, and carrying out ultrasonic treatment on the aqueous solution for 5 to 15 minutes;

step S6, the hyaluronic acid gel prepared in step S5 is filled into a syringe, the cartridge is sterilized in an autoclave at 121 ℃ for 16 minutes, and the active filler for anti-aging around the eyes is prepared, and the obtained active filler needs to be pH-controlled and checked to have a pH value of 8.5.

And (3) performance detection: the active fillers prepared in examples 1-3 were injected into a vehicle, which may be artificial skin or other animal tissue similar to artificial skin, and the following performance tests were performed:

analysis was performed using a rheometer. For comparison with the fillers of the present invention, the data for comparison include elasticity, complex viscosity and concentration:

	example 1	Example 2	Example 3	Comparative example 4
					Elasticity	520	518	560	420
Complex viscosity	7.9	7.8	8.2	5.5
					Concentration of	23	25	27	17

It is understood that the body fillers prepared in examples 1 to 3 exhibit excellent viscoelasticity. When the medical filler is injected into the eyes of a human body in a medical operation, the medical filler has good elasticity like the muscle tissue of the human body, and meanwhile, the filler injected into the human body can be fully bonded with the human body due to good viscosity, so that the continuity is improved.

Comparative example 4 does not sample the raw materials according to the standard, so the overall performance of the obtained product has larger defects compared with examples 1-3, and the materials need to be mixed according to the strict requirements when the product is formally produced and used.

The preferred embodiments of the invention disclosed above are intended to be illustrative only. The preferred embodiments are not intended to be exhaustive or to limit the invention to the precise embodiments disclosed. Obviously, many modifications and variations are possible in light of the above teaching. The embodiments were chosen and described in order to best explain the principles of the invention and the practical application, to thereby enable others skilled in the art to best utilize the invention. The invention is limited only by the claims and their full scope and equivalents.

Claims

1. The active filler for resisting aging around eyes is characterized by comprising the following raw materials in parts by weight: 10-15 parts of hyaluronic acid or a composition thereof, 30-40 parts of sugar, 5-10 parts of alkali and 20-30 parts of normal saline/distilled water; 50-80 parts of oil solution, 5-8 parts of cross-linked hyaluronic acid microspheres, 10-25 parts of cross-linking agent and 30-50 parts of plasticizer;

the preparation method of the active filler comprises the following steps:

2. The active filler for resisting aging around the eyes as claimed in claim 1, which is prepared from the following components in parts by weight: 11-13 parts of hyaluronic acid or a composition thereof, 35-40 parts of sugar, 6-9 parts of alkali and 25-30 parts of normal saline/distilled water; 70-80 parts of oil solution, 6-8 parts of cross-linked hyaluronic acid microspheres, 18-25 parts of cross-linking agent and 36-50 parts of plasticizer.

3. The active filler for resisting aging around the eyes as claimed in claim 1, which is prepared from the following components in parts by weight: 11 parts of hyaluronic acid or a composition thereof, 35 parts of sugar, 6 parts of alkali and 25 parts of physiological saline/distilled water; 70 parts of oil solution, 6 parts of cross-linked hyaluronic acid microspheres, 18 parts of cross-linking agent and 36 parts of plasticizer.

4. The active bulking agent for periocular anti-aging according to claim 3, wherein the oil solution is composed of an emulsifier and a base, the base comprises vegetable oil, mineral oil, silicone oil, liquid paraffin, dodecane, n-octane or cyclohexane, the emulsifier has a hydrophilic-hydrophobic equilibrium value of 6, and sorbitan monooleate or sorbitan monostearate is used.

5. The active bulking agent for periocular anti-aging according to claim 1, wherein the sugar is xylose, sucrose, maltose, lactose, glucose, glucosamine, glucuronic acid, rhamnose, mannose, fucose, arabinose, acetylglucosamine, inositol, trehalose, isomalt, xylitol, erythritol or two or more thereof.

6. The active filler for periocular anti-aging according to claim 1, characterized in that the cross-linking agent is one or more selected from the group consisting of: butanediol diglycidyl ether (1, 4-butanediol diglycidyl ether: BDDE), ethylene glycol diglycidyl ether (EGDGE), hexanediol diglycidyl ether (1, 6-hexanediol diglycidyl ether), propylene glycol diglycidyl ether, polypropylene glycol diglycidyl ether, polytetramethylene glycol diglycidyl ether, neopentyl glycol diglycidyl ether, polyglycerol polyglycidyl ether, diglycerol polyglycidyl ether, glycerol polyglycidyl ether, trimethylpropane polyglycidyl ether, bisglycidoxyethylene (1,2- (bis (2, 3-epoxypropoxy) ethylene), pentaerythritol polyglycidyl ether and sorbitol polyglycidyl ether.

7. The active filler for anti-aging around the eyes as claimed in claim 1, wherein the hyaluronic acid or the composition thereof is selected from hyaluronic acid, sodium carboxymethyl cellulose, vinyl pyrrolidone-vinyl acetate copolymer, polyvinyl alcohol, polyvinyl pyrrolidone, or a mixture of two or more thereof.

8. A preparation method of an active filler for resisting aging around eyes is characterized by comprising the following steps:

9. The method as claimed in claim 8, wherein the aqueous solution of step S1 is subjected to ultrasonic treatment for 5-15 min.

10. The method of claim 8, wherein the active filler obtained in step S6 is subjected to pH control to check whether its value is between 6.5 and 7.5.