WO2014201618A1

WO2014201618A1 - Use of xanthan gum in preparation of injectable beauty products

Info

Publication number: WO2014201618A1
Application number: PCT/CN2013/077374
Authority: WO
Inventors: 凌沛学; 韩冠英; 王桂兰; 宋志刚; 邵华荣; 朱希强; 刘飞; 颜震; 窦茜茜; 侯重文
Original assignee: 山东省生物药物研究院
Priority date: 2013-06-18
Filing date: 2013-06-18
Publication date: 2014-12-24
Also published as: CN105338988B; CN105338988A

Abstract

Provided is a use of xanthan gum in the preparation of injectable beauty products for filling in wrinkles, fine lines, sagging skin and/or scars, and an injectable beauty product containing xanthan gum used for filling in wrinkles, fine lines, sagging skin and/or scars.

Description

Use of xanthan gum in preparing injection beauty products

The invention belongs to the technical field of medicine, and relates to the use of xanthan gum in preparing an injection cosmetic product and an injection cosmetic product containing xanthan gum. Background technique

With the advancement of biomaterial science and clinical medicine, the plastic surgery industry has continued to develop from minimally invasive non-surgical beauty. Injection beauty refers to a method of injecting a specific bio-filling material or preparation into a target site that needs to be repaired and remodeled according to different injection routes to achieve a young and beautiful natural beauty. The injection beauty operation is simple, the damage is small, and the recovery is fast.

Currently, dermal fillers have been approved by the US FDA as a medical device to fill facial wrinkles. These products can be used to inject deep or deep dermis to repair moderate or deep skin wrinkles, wrinkles or scars. It is widely used in clinical practice to eliminate wrinkles, lip augmentation, rhinoplasty, chin chin, brocade and various dent fillings.

Filling materials can be classified into non-biological materials and biological materials according to their sources. Non-biological dermal fillers are not biodegradable and have permanent filling properties, mainly including silica gel, polymethyl methacrylate, polyacrylamide, hydroxyphosphorus δ, etc., which remain in the body for a long time and cannot be completely removed. The reaction rate is higher and less used for facial skin filling. Biomaterials are biodegradable, with short durations, some only a few months, but the incidence of adverse events is low, relative to ^. It mainly includes products such as protein, hyaluronic acid, and autologous cells. ^^ Protein products are divided into human and non-human sources. Human source materials are limited in source, expensive, and have the risk of transmitting hepatitis B and HIV. Non-human sources are human heterologous proteins, which are prone to occur. Rejection, resulting in excessive and complications. Autologous cell products take more autologous tissue cells, the patient suffers, and the cell proliferation is slow, and it is effective after a long time after injection, and multiple injections are required. At present, there are many hyaluronic acid fillers. Hyaluronic acid is a substance existing in the human body. It has good histocompatibility, no allergic reaction, and non-heating. Source, not carcinogenic, causing (Falcone SJ, Doerfler AM, Berg R A. Dermal Fillers: Types, Indications, and Complications. Dermatol Surg, 2007,

33:136-143). Since naturally extracted hyaluronic acid is easily degraded by enzymes and free radicals in the body, the half-life in tissues is only 1-2 days, so hyaluronic acid products used as dermal fillers are mostly cross-linked or modified transparent. Acidic preparation. At present, there are four different cross-linking agents in the international market. According to the chemical material safety assessment report, these cross-linking agents are irritating or even toxic to the skin. The FDA requires that the concentration of residual cross-linking agent in the dermal filler must be lower than the endangered. Under the standard of human body (Chen, Ling Peixue. Research on transparent quality: skin filler i^H. Chinese Journal of Biochemicals, 2011, 32(3): 248-251).

In recent years, the clinical application research of injectable cosmetic orthopedic materials has developed rapidly, and new products have been reported more and more, and the search for biomaterials with high viscoelasticity, better stability and longer lasting as a skin filler has been used for injection beauty. Become a research hotspot.

Xanthan gum is a black rot of Xanthomonas {Xanthomonas

Fermentation of an extracellular heteropolysaccharide, relative molecular mass of 2xl0 ⁶ ~ 2xl0 ^7, the basic structure is composed of repeating pentasaccharide units, this unit consists of two D- glucose, D- mannose, and two 1 D-glucuronic acid composition. The primary structure of the xanthan gum molecule consists of a D-glucose backbone linked to a ?-1,4 bond and a side chain of a trisaccharide unit, the side chains of which are alternately linked by D-mannose and D-glucuronic acid. The mannose at the end of the partial side chain is linked to a pyruvate group at the 4th and 6th positions, while the mannose partially linked to the main chain is acetylated at the C-6 position; the secondary structure is the side chain through the hydrogen bond A double helix or a multi-helical structure formed by winding a main chain; a tertiary structure is a network structure in which a secondary structure is composed of non-covalent bonds.

Currently, xanthan gum is widely used in food, medicine, cosmetics, petroleum, textile and papermaking (Garcia-Ochoa F, Santos VE, Casas JA, et al. Xanthan gum: production, recovery, and properties. Biotechnol Adv, 2000, 18(7): 549-579). However, no reports of xanthan gum for the preparation of cosmetic products have been reported. Summary of the invention

The inventors of the present invention have surprisingly found that xanthan gum can be used in a large number of experiments. The present invention has been completed by preparing a cosmetic product, particularly an injection cosmetic product which can be used for preparing wrinkles, fine lines, epidermal depressions and/or scars.

A first aspect of the invention relates to the use of xanthan gum in the preparation of an injection cosmetic product filled with wrinkles, fine lines, epidermal depressions and/or scars.

The use according to the first aspect of the invention, wherein the content of xanthan gum in the injection cosmetic product is from 0.25 w/v% to 10 w/v%, preferably, the content of the xanthan gum is 0.5 w/v% ~8.0 w/v%, more preferably, the xanthan gum is 0.5 w/v% to 5 w/v%, for example, 1 w/v% to 5 w/v%, 2 w/v%~ 5 w/v%.

The use according to the first aspect of the invention, wherein the xanthan gum has an average relative molecular mass of from 2 to 20 million, preferably from 3 to 10 million.

The use according to the first aspect of the invention, wherein the injection cosmetic product has a viscosity of from 100 to 2000 Pa s, preferably from 300 to 1000 Pa's. The degree can be measured by methods well known in the art. In an embodiment of the invention, the degree data is determined using a rotational rheometer (Malvern Kinexus, Britain) at a shear rate of 0.1 s" ¹ .

The use according to the first aspect of the invention, wherein the injection cosmetic product has a pH of 5.5 to 8.5, preferably a pH of 6.0 to 8.0, more preferably a pH of 7.0 to 7.4.

Use according to the first aspect of the invention, wherein the injection cosmetic product is a liquid preparation or formulation. When the content of xanthan gum in the product is low (<2%), it is a liquid state with good fluidity. At this time, the product is a liquid preparation; as the concentration of xanthan gum in the product increases, the viscosity of the solution increases, and the fluidity deteriorates. , to become a viscous gel state, the product at this time can be regarded as a gel preparation.

The use according to the first aspect of the invention, wherein the injection cosmetic product further comprises a biocompatible solvent, and optionally other physiologically acceptable raw and auxiliary ingredients.

The use according to the first aspect of the invention, wherein the biocompatible solvent is a sterile, pyrogen-free, isotonic aqueous solution, preferably the sterile, non-pyrogenic, isotonic aqueous solution is selected from the group consisting of sterile, non-pyrogenic physiological saline, Isotonic glucose solution, isotonic borate buffer, isotonic phosphate buffer, isotonic citrate buffer, isotonic tartrate buffer, isotonic lactate buffer, etc. One or several of osmium carbonate buffer and isotonic acetate buffer (for example, two or three Kind)

In an embodiment of the invention, the isotate buffer ^! An isotonic buffer system consisting of disodium hydrogen phosphate, sodium dihydrogen phosphate, and sodium chloride; the isotonic borate buffer is an isotonic buffer system consisting of boric acid, borax, and sodium chloride.

The use according to the first aspect of the present invention, wherein the raw material component is selected from one or both of a glycan and a local anesthetic; preferably, the hyaluronic acid, chondroitin sulfate, and quercetin sulfate Or one or more of heparan sulfate, keratan sulfate, heparin, wherein the content of the glycan in the injection cosmetic product is 0.125 w/v% to 10 w/v%, preferably, the poly The sugar is from 0.25 w/v% to 5.0 w/v%, more preferably, the glycan is from 0.5 w/v% to 3.0 w/v%, from 0.5 w/v% to 1.0 w/v% or lw. /v%~3 w/v%.

The local anesthetic is selected from one or more of lidocaine, procaine, bupivacaine, tetracaine, ropivacaine, and salts thereof. The amount of the local anesthetic is the usual dosage in the art, for example, the concentration is about 0.1 w/v% to about 5.0 w/v% of the injection cosmetic product.

According to the use of the first aspect of the invention, the injection cosmetic product is for intradermal injection or subcutaneous injection. A second aspect of the invention relates to an injection cosmetic product for filling wrinkles, fine lines, epidermal depressions and/or scars, wherein the injection cosmetic product contains xanthan gum.

An injection cosmetic product according to a second aspect of the present invention, wherein the content of xanthan gum in the injection cosmetic product is from 0.25 w/v% to 10 w/v%, preferably, the content of the xanthan gum is 0.5 w/ v%~8.0 w/v%, more preferably, the x-ray of the xanthan gum is 0.5 w/v%~5 w/v%, for example, 1 w/v%~5 w/v%, 2 w/v%~5 w/v%.

The injection cosmetic product according to the second aspect of the invention, wherein the xanthan gum has an average molecular weight of from 2 to 20 million, preferably from 3 to 10,000,000.

An injection cosmetic product according to the second aspect of the invention, wherein the injection cosmetic product has a viscosity of from 100 to 2000 Pa s, preferably from 300 to 1000 Pa's. Anyone known in the art can be used. Method for determining viscosity, in an embodiment of the invention, the viscosity data is using a rotational rheometer

( Malvern Kinexus, Britain ) was measured at a shear rate of 0.1 s" ¹ .

An injection cosmetic product according to a second aspect of the invention, wherein the injection cosmetic product has a pH of 5.5 to 8.5, preferably, a pH of 6.0 to 8.0, more preferably a pH of 7.0 to 2 according to the second aspect of the invention An injection cosmetic product, wherein the injection cosmetic product is a liquid preparation or a gel preparation.

An injection cosmetic product according to the second aspect of the invention, wherein the injection cosmetic product further comprises a biocompatible solvent, and optionally other physiologically acceptable raw and auxiliary ingredients.

An injection cosmetic product according to the second aspect of the present invention, wherein the biocompatible solvent is a sterile, pyrogen-free, isotonic aqueous solution, preferably the sterile, non-pyrogenic, isotonic aqueous solution is selected from the group consisting of a sterile, non-pyrogenic physiology Saline, isotonic glucose solution, isotonic borate buffer, isotonic phosphate buffer, isotonic citrate buffer, isotonic tartrate buffer, isotonic lactate buffer One or more of isotonic carbonate buffer and isotonic acetate buffer.

An injection cosmetic product according to a second aspect of the present invention, wherein the prosthetic material is one or two selected from the group consisting of amino glycans and local anesthetics; preferably, the amino polysaccharide is selected from the group consisting of hyaluronic acid and sulfuric acid. One or several of chondroitin, quercetin sulfate, heparan sulfate, keratan sulfate, heparin, wherein the content of the aminoglycan in the injection cosmetic product is 0.125 w/v% to 10 w/v% Preferably, the content is from 0.25 w/v% to 5.0 w/v%, and more preferably, the glycan is from 0.5 w/v% to 3.0 w/v%, 0.5 w/v% to 1.0. w/v%^ 1 w/v%~3 w/v%. The anesthetic is selected from one or more of lidocaine, procaine, bupivacaine, tetracaine, ropivacaine, and salts thereof. The amount of the local anesthetic is conventionally used in the art, for example, at a concentration of from about 0.1 w/v% to about 5.0 w/v% of the injection cosmetic product.

An injection cosmetic product according to the second aspect of the invention, the injection cosmetic product for intradermal administration Injection or subcutaneous injection. A third aspect of the invention relates to the use of the injection cosmetic product according to any one of the second aspects of the invention for the preparation of a cosmetic injection for filling wrinkles, fine lines, epidermal depressions and/or scars. A fourth aspect of the invention relates to a cosmetic method for filling wrinkles, fine lines, epidermal depressions and/or scars, the method comprising the step of injecting a cosmetic product containing xanthan gum; preferably, the cosmetic product containing xanthan gum is The invention relates to an injection cosmetic product according to any of the second aspects of the invention.

A cosmetic method according to a fourth aspect of the present invention, wherein the content of xanthan gum in the cosmetic product is from 0.25 w/v% to 10 w/v%, preferably, the content of the xanthan gum is 0.5 w/v% ~8.0 w/v%, more preferably, the xanthan gum is 0.5 w/v% to 5 w/v%, for example, 1 w/v% to 5 w/v%, 2 w/v%~ 5 w/v%.

The cosmetic method according to the fourth aspect of the present invention, wherein the xanthan gum has an average relative molecular mass of 2 to 20,000,000, preferably 3 to 10,000,000.

The cosmetic method according to the fourth aspect of the invention, wherein the injection cosmetic product has a viscosity of 100 to 2000 Pa s, preferably 300 to 1000 Pa's. The degree can be measured by methods well known in the art. In an embodiment of the invention, the degree data is determined using a rotational rheometer (Malvern Kinexus, Britain) at a shear rate of 0.1 s" ¹ .

The cosmetic method according to the fourth aspect of the present invention, wherein the injection cosmetic product has a pH of from 5. 5 to 8. 5, preferably, a pH of from 6.8 to 8.0, more preferably, a pH of 7 ·0 ~ 7.4.

A cosmetic method according to the fourth aspect of the invention, wherein the injection cosmetic product is a liquid preparation or a gel preparation.

A cosmetic method according to the fourth aspect of the present invention, wherein the injection cosmetic product further comprises a biocompatible solvent, and optionally other physiologically acceptable raw and auxiliary ingredients.

A cosmetic method according to the fourth aspect of the present invention, wherein the biocompatible solvent is a sterile, pyrogen-free, isotonic aqueous solution, preferably, the sterile, non-pyrogenic, isotonic aqueous solution is selected from the group consisting of sterile, non-pyrogenic physiological saline. Isotonic glucose solution, isotonic borate buffer, isotonic phosphate Buffer, isotonic citrate buffer, isotonic tartrate buffer, isotonic lactate buffer, isotonic carbonate buffer and isotonic acetate buffer One or several.

A cosmetic method according to the fourth aspect of the present invention, wherein the raw material component is one or more selected from the group consisting of a glycan and a local anesthetic; preferably, the amino polysaccharide is selected from the group consisting of hyaluronic acid and chondroitin sulfate Or one or more of quercetin sulfate, heparan sulfate, keratan sulfate, heparin, wherein the content of the polysaccharide in the injection cosmetic product is 0.125 w/v% to 10 w/v%, preferably The glycan is 0.25 w/v% to 5.0 w/v%, and more preferably, the glycan is 0.5 w/v% to 3.0 w/v%, 0.5 w/v% to 1.0 w. /v% or 1 w/v%~3 w/v%. The anesthetic is selected from one or more of lidocaine, procaine, bupivacaine, tetracaine, ropivacaine, and salts thereof. The amount of the local anesthetic is conventionally used in the art, for example, at a concentration of from about 0.1 w/v% to about 5.0 w/v% of the injected cosmetic product.

According to the cosmetic method of the fourth aspect of the invention, the injection cosmetic product is used for intradermal injection or subcutaneous injection.

In the present invention, the xanthan gum is produced by fermentation of Xanthomonas oryzae, and the molecular weight of xanthan gum is determined by a multi-angle laser 3⁄4 (Wyatt Technology, DAWN EOS) combined with 'permeation chromatography. Under the same conditions, the viscosity of the xanthan gum solution increases with the increase of its molecular weight.

In the present invention, the wrinkles, fine lines, skin depressions and scars respectively mean that the embossed lines formed by the human skin due to aging or being affected by the external environment are called wrinkles. Fine lines are a kind of wrinkles. The linear aging of human muscles and the long-term contraction of eye muscles are called fine lines. Epidermal depression refers to a narrow surface depression or a depressed scar formed by a series of physiological or pathological factors, which are caused by defects in the dermis and subcutaneous tissues of the skin. Scars are external to normal skin and narrow tissue caused by various traumas

It is an inevitable outcome of the human wound repair process. In the present invention, the cosmetic product includes a medicine, a preparation, and the like for cosmetic use. In the present invention, the injection cosmetic product refers to a product that achieves a cosmetic effect by injecting a drug or a preparation; in an embodiment of the present invention, the injection is performed, for example, by intradermal injection or subcutaneous injection. Advantageous effects of the invention

The invention proves that the xanthan gum has good biocompatibility, safety, high viscoelasticity and good gel formation when used for preparing cosmetic products; and its property is stable, and it is not easy to be degraded in the preparation process and in the human body, and no cross-linking is required. If injected into the skin, it can be stably stored for a long time without change and degradation, prolonging its action time. Meanwhile, xanthan gum solution is a typical pseudoplastic fluid, which has a very low viscosity at high shear rate, enabling it to It is easy to inject through a fine needle into the skin, and has a high viscosity and elasticity at a low shear rate, so that it can be injected into the skin to form a gel with certain emphasis, which can exist stably for a long time without migration or dispersion.

The invention also shows that xanthan gum belongs to polysaccharides and has similar properties to polysaccharides such as chondroitin sulfate and hyaluronic acid, but xanthan gum is not easily degraded by enzymes and free radicals in the body, and has better stability. The filling effect lasts for a long time and is superior to the existing similar products in the field of cosmetic filling. Compared with cross-linked hyaluronic acid products, xanthan gum can be stably stored for a long time without cross-linking, and avoids damage to human body caused by the use of cross-linking agent; compared with collagen products, xanthan gum is derived from microbial fermentation. Reduces the risk of allergic reactions to collagen and the infection of animals or human infectious diseases; compared with autologous cell products, xanthan gum has the same advantages as collagen and cross-linked hyaluronic acid products, that is, it has the effect of timely shaping Immediately after the injection, the filling effect is maintained for a certain period of time, without multiple injections, which is more conducive to the physician to meet the patient's requirements for shaping the filling site.

In summary, the present invention uses xanthan gum as a main component for the preparation of a cosmetic product for the first time, and the results show that xanthan gum can increase the tissue volume and effectively reduce or eliminate skin wrinkles, fine lines, epidermal depressions and scars in a certain period of time, and achieve beauty. Or the purpose of shaping. DRAWINGS

Fig.1 Comparison of viscosity of different concentrations of xanthan gum with shear rate

Figure 2 Rheology of Examples 5, 7, and 8 and commercially available cross-linked hyaluronic skin fillers: Elastiic modulus (G') and Viscous modulus (G") Comparison

Figure 3 Example 3: Gross observation of subcutaneous injection into the back of rats

Figure 4 Example 1 Histological observation of subcutaneous injection into the back of rats

Figure 5 Example 5 Histological observation of xanthan gum injection into the back of the guinea pig. Figure 6 Example 8 Histological observation of xanthan gum injection into the back of the guinea pig head.

The embodiments of the present invention are described in detail below with reference to the embodiments of the present invention, but it is understood that the following examples are only intended to illustrate the invention and should not be construed as limiting the scope of the invention. If no specific conditions are specified in the examples, they are carried out according to the general conditions or the conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products that can be obtained commercially. The xanthan gum is derived from the fermentation production of Xanthomonas oryzae var. chinensis, and the purified xanthan gum raw material obtained by purification and purification is prepared by reference method ( Han G, Wang Q Ling P, et al. Preparation of Xanthan gum injection and its protective effect on articular cartilage in the development of osteoarthritis [J]. Carbohydr Pofym, 2012, 87(2): 1837-1842. )„ The main preparation steps include crude preparation of xanthan gum, crude dissolution, diatom Soil adsorption, sterilization filtration, enzymatic hydrolysis, activated carbon adsorption, carbon removal filtration, microfiltration membrane fine filtration, alcohol precipitation, drying and refined products. Osmotic pressure reference osmolality determination method (Chinese Pharmacopoeia 2010 edition two appendix DCG Determination: Example 1: An injection cosmetic product containing 0.5% xanthan gum

Group

Ingredient

Xanthan gum (average molecular weight 5 million) 0.5 g

Hyaluronic acid 0.5g Sodium dihydrogen phosphate 0.16 g Disodium hydrogen phosphate 0.756 g Sodium chloride 0.411 g Water for injection to 100 mL pH 7.33 Osmotic pressure 300 mOsmol/L Example 2: Injectable beauty product containing 2% xanthan gum

Group

Ingredients added xanthan gum (average molecular weight ⁵ million) 2 g boric acid 1.166 g borax 0.114 g sodium chloride 0.220 g water for injection added to 100 mL pH 7.1 osmotic pressure 296 mOsmol / L Example 3: - 3% containing yellow Original rubber injection beauty products

Group

Ingredients added xanthan gum (average molecular weight ⁵ million) 3 g

Sodium dihydrogen phosphate 0.16 g Disodium hydrogen phosphate 0.756 g Sodium chloride 0.411 g Water for injection Add to 100 mL pH 7.33 Osmotic pressure 300 mOsmol/L Example 4: An injection cosmetic product containing 4% xanthan gum

Group

Ingredients added amount of xanthan gum (average molecular weight 3 million) 4 g Chondroitin sulfate 0.5g

Sodium dihydrogen phosphate 0.16 g Disodium hydrogen phosphate 0.756 g Sodium chloride 0.411 g Water for injection Add to 100 mL pH 7.8

Osmotic pressure 305 mOsmol/L Example 5: A painless injection cosmetic product containing 1% xanthan gum

Group

Ingredients Adding amount Xanthan gum (average molecular weight 8 million) 1 g

Sodium dihydrogen phosphate 0.16 g Disodium hydrogen phosphate 0.756 g Sodium chloride 0.411 g Lidocaine hydrochloride 0.3 g Water for injection Add to 100 mL pH 6.8

Osmotic pressure 290 mOsmol/L Example 6: a painless injection cosmetic product containing 2% xanthan gum

Group

Ingredients Adding amount Xanthan gum (average molecular weight 8 million) 2 g

Boric acid 1.166 g Borax 0.114 g Sodium chloride 0.220 g Procaine hydrochloride 0.3 g Water for injection Add to 100 mL pH 7.1

Osmotic pressure 305 mOsmol/L Example 7: A painless injection cosmetic product containing 3% xanthan gum

Ingredient

Xanthan gum (average molecular weight 10 million) 3 g

Chondroitin sulfate 1 g

Sodium dihydrogen phosphate 0.16 g

Disodium hydrogen phosphate 0.756 g

Sodium chloride 0.411 g

Procaine hydrochloride 0.3 g

Water for injection added to 100 mL

pH 6.2

Osmotic pressure 282 mOsmol/L Example 8: a painless injection cosmetic product containing 5% xanthan gum

Group

Ingredient

Xanthan gum (average molecular weight 10 million) 5 g

Sodium dihydrogen phosphate 0.16 g

Disodium hydrogen phosphate 0.756 g

Sodium chloride 0.411 g

Lidocaine Hydrochloride 0.3 g

Water for injection added to 100 mL

pH 7.8

Osmotic pressure 303 mOsmol/L Experimental example

I. Determination of rheological properties

1. Comparison of viscosity and shear rate of different concentrations of xanthan gum solution

Method:

Based on the composition of Example 3 (all components except xanthan gum), a series of different concentrations of xanthan gum (1% ~ 5%) solution were prepared using a rotary rheometer ( Malvern Kinexus, Britain ) , 20mm flat plate, shear rate 0.1 s" ¹ ~ 1000 s" ¹ , different Concentration of xanthan gum solution! The ML changes with shear rate (see Figure 1).

Result:

The curve of the degree of xanthan gum solution as a function of shear rate exhibits the characteristics of a typical pseudoplastic fluid. The higher the concentration of xanthan gum, the larger the solution. The xanthan gum solution has a very low viscosity at high shear rates, and the resistance when using a fine needle push is small and easy to inject.

2. Comparison of the rheological parameters of the elastic cross-linked hyaluronic skin fillers of Examples 5, 7, and 8 and the comparison of Elastiic modulus (G, ) and Viscous modulus (G")

Method:

Using Examples 5, 7, and 8 with commercially available cross-linked hyaluronic skin filler (Resylane, lot: 9137, Q-Med, Uppsala, Sweden), using a rotary rheometer (Malvern Kinexus. Britain), 20mm plate The frequency is 0.1 Hz ~ 10 Hz, and the relationship between the rheological parameters (Elastiic modulus, G, ) and the Viscous modulus (G") is compared (see Figure 2).

Result:

The product of the embodiment of the invention has obvious viscoelasticity, and the elastic modulus G of the experimentally determined frequency range is always higher than the viscous modulus G", and a gel having a certain strength can be formed at a low shear rate. It has higher viscosity and elasticity. The gel strength of Example 5 is weaker than that of crosslinked hyaluronic acid, and the gel strength of Example 7 is similar to that of crosslinked hyaluronic acid. The strength of Example 8 is stronger than that of crosslinked hyaluronic acid. It shows that the xanthan gum injection beauty products with different viscoelasticity and strength can be provided by changing the product group, which can cover a wide range of products and can meet the market demand for different kinds of products.

1. Short-term animal experiments:

Method:

Thirty-two female Sprague-Dawley rats, weighing 210 ± 15 g, were randomly divided into 4 groups (n=8): control group, injected with normal saline; group A, injected with product of example 1; group B, injected with product of example 2; Group C, the product of Example 3 was injected. After anesthesia, prepare the skin and disinfect. A little point was taken on the left and right sides of the back of the rat, and the subcutaneous injection was performed at a dose of 0.5 ml and 0.25 ml, respectively. The control group was injected with the same amount of normal saline at the same site.

(1) General observation: Rats' activities and eating conditions, regular observation of the injection site outside the skin without redness, oozing and other inflammatory reactions;

(2) Detection of blood biochemical indicators: On the 5th day before the sample ^, each rat was statically Ji^ k, and the blood biochemical baseline parameters were detected; on the 3rd, 7th, 21st and 42th days after the injection, each group randomly took 2 Only rats, anesthesia, cardiac puncture, Jk ^ blood biochemical indicators. Blood biochemical indicators include total cholesterol (TC), total protein (TP), albumin (ALB), urea nitrogen (BUN), total bilirubin (TBIL), creatinine (CR), triglycerides (TG), and blood glucose ( GLU), creatine phosphokinase (CK) and gamma-glutamyltransferase (GGT).

(3) Histological observation: On days 3, 7, 21 and 42 after the injection, the rats were weighed, sacrificed by cardiac puncture, dissected, and the presence of the implant was observed as described above.

The implanted samples and adjacent tissues were taken as specimens, stained with hematoxylin-eosin (hereinafter referred to as HE), and the morphology of the tissues around the injection site was observed under an optical microscope (Nikon ECLIPSE E600, Japan).

Heart, brain, liver, spleen, lung, kidney and thymus were excised, weighed and stored in 4% formaldehyde solution, sectioned and histologically observed under light microscope.

Result:

(1) The activity and eating status of the rats showed no redness, swelling, no exudate, and normal weight gain at each injection site, and there was no significant difference from the control.

(2) The blood biochemical indicators of the rats were the same as those of the control, and there were no signs of systemic toxicity.

(3) After 42 days, all implants remained at the injection site and did not migrate or disperse (see Figure 3). The xanthan gum implant is surrounded by a very thin capsule (see Figure 4), no acute inflammatory response, no granulation and lymphocyte aggregation, no obvious pathological changes in the surrounding tissue of the 3⁄4V, rat heart and brain Pathological sections of liver, spleen, lung, kidney and thymus showed no obvious pathological changes. It indicates that the implant has good biocompatibility.

2. Long-term animal experiments: method:

Female Hartley guinea pigs 40, weighed, anesthetized, prepared on the left and right sides of the regular back, disinfected. A total of 10 implantation sites were selected on the left and right sides of each guinea pig, and the enamel marks were drawn respectively. Among them, the xanthan gum product was injected at 6 points (the product of Example 5 was 2 points, and the product of Example 7 was 2 points. Example 8 product 2 points); Positive control 2 points, injection of commercially available cross-linked hyaluronic acid skin narrow filling agent (Run Baiyan, lot: 12021801, Huaxi Freda Biomedical Co., Ltd.); At 2 points, saline was injected. The injection sites of different samples were randomized. One and a half of the guinea pigs were injected intradermally with 0.05 ml per point, and the other half of the guinea pigs were injected subcutaneously with 0.2 ml per point.

Observation indicators:

(1) General observation: The activity and eating of guinea pigs, the appearance of skin at each injection site, whether there is redness, oozing and other inflammatory reactions.

(2) Histological observation: On the 3rd day, 1 week, 2 weeks, 4 weeks, 9 weeks, 13 weeks, 26 weeks and 52 weeks after the injection, 5 guinea pigs were randomly selected, weighed, anesthetized, opened the skin. , to observe the survival of the implant.

The samples and adjacent tissues were taken as specimens, and stained with HE. The morphology of the tissues around the injection site was observed under an optical microscope.

(3) Evaluation: The method of evaluating the degree of inflammatory response by the method of reference (Piacquadio D, Jarcho M, Goltz R. Evaluation of hylan b gel as a soft-tissue augmentation implant material. J Am Acad Dermatol, 1997, 36:544-549) And the extent of retention of the implant. The degree of inflammation j1⁄2 is divided into 0 to 4 grades, that is, 0 = no inflammation j1⁄2, 1 = very little, 2 = slight, 3 = medium, 4 = severe. Implant retention is divided into 0~4 grades, ie, 0=no persistence, 1=24% to 1%, 2=49% to 25%, 3=74% to 50%, 4=100% to 75% .

Result:

(1) After all the guinea pigs were injected, no red, swollen, no exudate was observed, and the guinea pigs were active and eating normally.

(2) Observed within 4 weeks after injection, the original characters of Huangyuan gum file were consistent with the positive control. The visual shape was always good, no dispersion, good hand feeling, good elasticity, and the xanthan gum implant was not sticky with the surrounding tissue. No, no vascular proliferation, no significant changes in surrounding tissues. HE staining showed that a week after the injection, a very thin envelope was observed around the xanthan gum, and no inflammatory cells invaded. At 2 weeks, fibroblast proliferation and cell infiltration were observed around the xanthan gum implant (inflammation response was assessed as grade 2). At 4 weeks, the inflammatory response around the xanthan gum implant was slightly reduced compared to 2 weeks, and the envelope was slightly thickened (see Figures 5 and 6). At 9 weeks, inflammatory infiltration of the reticular dermis and adipose tissue around the xanthan gum remained (inflammation response was assessed as grade 1), similar to the previous table. At 13 weeks, the inflammatory infiltration around the xanthan gum implant was significantly reduced. The implant of Example 5 was significantly reduced (clinical evaluation retention level 1), indicating that the product retention time was shorter when the xanthan gum content was lower; the implants of Examples 7 and 8 were still relatively complete, light touch It can be seen that there is no obvious degradation.

(3) At 26 weeks, there was no obvious inflammatory infiltration around the streaks of Examples 7 and 8, the stowage was intact, surrounded by fibroproliferative tissue; the degradation of the implant of Example 5 disappeared, and the implant site and The surrounding organization is no different. Implant residues at weeks 26 and 52 are shown in Table 1. Table 1 Long-term test results Example 7 Example 8 Cross-linked hyaluronic acid ( «= 10 ) ( «= 10 ) ( «= 10 )

26 weeks 52 weeks 26 weeks 52 weeks 26 weeks 52 weeks Inflammation Degree:

Level 0 10 10 10 10 10 10

Level 1 0 0 0 0 0 0

Level 2 0 0 0 0 0 0

Level 3 0 0 0 0 0 0

Level 4 0 0 0 0 0 0 Number of items 8 6 10 9 9 8

The degree of material retention is 3, 2, 4, 3, 4, 3, and 3, and the results of short-term and long-term animal experiments show that xanthan gum has good biocompatibility, no obvious inflammatory reaction, and is non-toxic to animal organs. A safe injection of cosmetic filling material. The xanthan gum injection beauty product can be stably stored in the skin for a long time, and the skin filling effect is obvious. Although specific embodiments of the invention have been described in detail, those skilled in the art will understand. Various modifications and alterations of the details are possible in light of the teachings of the invention. The full scope of the invention is given by the appended claims and any equivalents thereof.

Claims

1. Use of xanthan gum in the preparation of injectable cosmetic products for filling wrinkles, fine lines, epidermal depressions and/or scars.

2. An injection cosmetic product for filling wrinkles, fine lines, epidermal depressions and/or scars, characterized in that the injection cosmetic product contains xanthan gum.

3. The use of claim or the injection cosmetic product of claim 2, wherein the content of xanthan gum in the injection cosmetic product is from 0.25 w/v% to 10 w/v%, preferably, the content of the xanthan gum More preferably, the content of the xanthan gum is from 0.5 w/v% to 5 w/v%, for example, from 1 w/v% to 5 w/v%, and more preferably from 0.5 w/v% to 8.0 w/v%. 2 w/v%~5 w/v%.

4. The use of the claims or the injection cosmetic product of claim 2, wherein the xanthan gum has an average relative molecular mass of from 2 to 20 million, preferably from 3 to 10 million.

5. The use of claim or the injection cosmetic product of claim 2, wherein the injection cosmetic product has a viscosity of from 100 to 2000 Pas, preferably from 300 to 1000 Pa's.

6. The use of claim or the injection cosmetic product of claim 2, wherein the injection cosmetic product has a pH of 5.5 to 8.5, preferably a pH of 6.0 to 8.0, more preferably a pH of 7.0 to 7.4.

7. The use of claim or the injection cosmetic product of claim 2, wherein the injection cosmetic product is a liquid formulation or a gel formulation.

8. The use of claim or the injection cosmetic product of claim 2, wherein the injection cosmetic product further comprises a biocompatible solvent, and optionally other physiologically acceptable originals Excipient ingredients.

9. The use or injection cosmetic product of claim 8 wherein said biocompatible solvent is a sterile, pyrogen-free, isotonic aqueous solution, preferably said sterile, non-pyrogenic, isotonic aqueous solution is selected from the group consisting of sterile, pyrogen-free Saline, isotonic glucose solution, isotonic borate buffer, isotonic phosphate buffer, isotonic citrate buffer, isotonic tartrate buffer, isotonic lactate buffer One or several of liquid, isotonic carbonate buffer and isotonic acetate buffer.

10. The use or injection cosmetic product according to claim 8, wherein the auxiliary material is one or two of a polysaccharide, a local anesthetic; preferably, the hyaluronic acid, chondroitin sulfate, sulfuric acid One or several of dermatan, heparan sulfate, keratan sulfate, heparin, selected from the group consisting of lidocaine, procaine, bupivacaine, tetracaine, ropivacaine, and One or several of the salts.

11. Use of the claim or an injection cosmetic product of claim 2, the injectable cosmetic product for intradermal or subcutaneous injection.

12. Use of an injection cosmetic product according to any of claims 2-11 for the preparation of a cosmetic injection for filling wrinkles, fine lines, epidermal depressions and/or scars.

13. A cosmetic method for filling wrinkles, fine lines, epidermal depressions and/or scars, the method comprising the step of injecting a cosmetic product containing xanthan gum; preferably, the cosmetic product containing xanthan gum refers to rights The injection cosmetic product of any of 2-11 is claimed.