CN105030658A - Cosmetic pharmaceutical - Google Patents

Abstract

The invention belongs to the technical field of pharmaceutical or medical instruments and discloses a cosmetic pharmaceutical. The cosmetic pharmaceutical is characterized by being made from cross-linked sodium hyaluronate, normal saline and pH regulator. The pH regulator in gel is made from the sodium hyaluronate; stability experimental studies show that the gel using the sodium hyaluronate as the pH regulator has better stability. The cross-linked sodium hyaluronate which is purified is made by adding water, adding L-aspartic acid and allowing ethanol precipitation; the purified cross-linked sodium hyaluronate is made into the gel having better quality; BDDE (butane dioldiglycidyl ether) content of the gel is less than 0.5ug/g, and protein quality thereof in mass percentage is less than 0.1%.

Description

A kind of medicine of beautification function

Technical field

The invention belongs to medicine or medical beautifying technique field, be specifically related to a kind of medicine containing cross-linking hyaluronic acid sodium.

Background technology

Hyaluronate sodium is humans and animals skin, vitreous body, the important component of joint lubrication liquid and cartilaginous tissue, it is repeated to be formed by connecting by (1-β-4) D-glucuronic acid and (1-β-3) N-acetyl group-D-aminoglucose dissacharide units, due to the effect of hydrogen bond between monosaccharide on hyaluronic acid straight chain axle, the screw cylindrical structure of hyaluronan molecule spatially in rigidity, the inner side of post produces strongly hydrophilic owing to there is a large amount of hydroxyls, and the hydrone that hyaluronan molecule is combined is locked in its Double helix column structure, moisture is not easily run off, therefore there is special water retention, water holding capacity in theory can up to 500ml/g, be described as desirable nature moisturizing factor.With age, the minimizing of HA in body, oral can HA in added body containing hyaluronic health product, there is the effect such as slow down aging and moist skin, be widely used in countries such as Japan, the U.S..Hyaluronic acid has good physicochemical property and biocompatibility.But it is subject to the zymolysis of hyaluronidase in vivo and degrades rapidly, and retention time is shorter, needs duplicate injection just can reach curative effect.Cross-linked-hyaluronic acid is that hyaluronate sodium modifies the high-molecular gel with 3-D solid structure obtained through cross-linking agents, can make up the shortcomings such as hyaluronate sodium retention time is short, still has good biocompatibility and effect simultaneously.

The customary preparation methods of cross-linking sodium hyaluronate gel is uniformly mixed in alkaline solution hyaluronate sodium and cross-linking agent, makes the incompatible preparation of chemical bond between hyaluronic acid macromolecular chain by cross-linking agent.But cross-linking agent used remains in organism and easily causes inflammatory reaction.The cross-linking agent removed in jel product is also a large problem at present, the method of the most frequently used removal or reduction cross-linking agent residual quantity comprises dialysis or cleans with water or buffer solution, but these class methods all cannot effectively be removed or reduce content of crosslinking agent, and the cycle is long, not easily realizes commercial production.Separately have one, if the hyaluronic acid solids that preparation is crosslinked, the conventional method removing cross-linking agent is the sedimentation method, with organic solvent cleaning, cross-linking sodium hyaluronate gel is precipitated, but the method still cannot remove residual free cross-linking agent completely.Domestic a lot of patent (CN101759881, CN101502677, CN1590444, CN102558600 etc.) is all use hyaluronate sodium and cross-linking agent 1,4-butanediol diglycidyl ether (hereinafter referred to as BDDE) reacts obtained gel in alkaline solution, its Patent CN101759881 discloses BDDE and is cross-linked HA and prepares medical cross-linking sodium hyaluronate gel derivative product, although retention time is long in the gelinite of preparation, biocompatibility good, remove cycle long, the very difficult residual quantity removed completely or reduce cross-linking agent of cross-linking agent.

Summary of the invention

For these reasons, applicant is being found by research: be cross-linked the cross-linking hyaluronic acid sodium prepared through BDDE, after adding ASPARTIC ACID after employing adds water, the cross-linking hyaluronic acid sodium of purification is obtained after alcohol settling, it is more outstanding that cross-linking hyaluronic acid sodium after purification is prepared into gel quality, in this gel, BDDE content is less than 0.5 μ g/g, and wherein protein quality percentage composition is less than 0.1%.Applicant studies cross-linking sodium hyaluronate gel agent, obtains a kind of new gel, and in this gel, pH adjusting agent adopts hyaluronic acid, and stability test research shows, adopts hyaluronic acid to have better stability as the gel of pH adjusting agent.

The present invention is achieved through the following technical solutions.

A medicine for beautification function, this medicine is prepared from by cross-linking hyaluronic acid sodium, normal saline and pH adjusting agent.

The medicine of preferred cosmetic effect, wherein cross-linking hyaluronic acid sodium 15-25 weight portion, normal saline 975-985 weight portion.

Cross-linking hyaluronic acid sodium described above is that hyaluronate sodium is cross-linked through BDDE and prepares.

In medicine described above, BDDE content is greater than zero and is less than 0.5 μ g/g.

In medicine described above, protein quality percentage composition is less than 0.1%.

PH adjusting agent described above is hyaluronic acid, and cross-linking hyaluronic acid sodium and hyaluronic weight ratio are 3-5: 1.

Medicine described above is gel.

The preparation method of gel described above is:

(1) cross-linking hyaluronic acid sodium purification

Get cross-linking hyaluronic acid sodium, add water for injection, be heated to 35 DEG C-45 DEG C, add cross-linking hyaluronic acid sodium weight 0.35-0.45 ASPARTIC ACID doubly, stir, add the 7.5-9 dehydrated alcohol doubly of cross-linking hyaluronic acid sodium weight, be cooled to 5 DEG C-10 DEG C, retain precipitation, lyophilization, obtains the cross-linking hyaluronic acid sodium after purification;

(2) preparation preparation

Get the cross-linking hyaluronic acid sodium after purification, add normal saline, add hyaluronic acid mix homogeneously, cross 100 eye mesh screens, 121 DEG C of moist heat sterilizations 30 minutes, fill, to obtain final product.

Crosslinking agent B DDE of the present invention is: BDDE.

Hyaluronate sodium (No. CAS: 9067-32-7) described above obtains from bacterial fermentation; Cross-linking hyaluronic acid sodium take hyaluronate sodium as raw material, is cross-linked prepares through BDDE; Hyaluronic acid, hyaluronate sodium and cross-linking hyaluronic acid sodium are provided by Taiwan Hekang Biological SCi. & Tech. Co., Ltd..

Or prepared by following method: get hyaluronic acid and add (pH=12.5) in 0.1N sodium hydroxide solution, get crosslinking agent B DDE (1,4 butanediol glycidyl ethers) add 95% alcoholic solution, add in hyaluronic acid aqueous slkali, under the environment of 30 DEG C, carry out 20 hours cross-linking reactions, after reaction after fragmentation, with 50% ethanol purge, then wash with water, concentrated, lyophilization, obtains cross-linking hyaluronic acid sodium.

Other raw materials are provided by Beijing Meidi Kangxin Pharmaceutical Technology Co., Ltd.

Following test is in repeatedly creative experimental basis, the concluding test that the technical scheme protected according to the present invention is carried out.

One, purification process research

Test method 1: cross-linking hyaluronic acid sodium purification: get cross-linking hyaluronic acid sodium 10g, add water for injection 1L, be heated to 40 DEG C, add the ASPARTIC ACID of 4g, stir, add 80g dehydrated alcohol, be cooled to 8 DEG C, retain precipitation, lyophilization, obtains the cross-linking hyaluronic acid sodium 9.3g after purification;

Get the cross-linking hyaluronic acid sodium 2g after purification, add normal saline 98g, add 0.5g hyaluronic acid mix homogeneously, cross 100 eye mesh screens, 121 DEG C of moist heat sterilizations 30 minutes, fill, obtains 100.

Test method 2: the sodium hydrate aqueous solution 20ml of preparation 1%, adds crosslinking agent B DDE0.2g, after mix homogeneously, add 2.0g hyaluronate sodium, after stirring, put into 4 DEG C of refrigerators and leave standstill 48h.Then, then put into 40 DEG C of water-baths, after heating 2h, take out the gel being cut into quality 1g, put into PBS buffer, expand dialysis 8h, and obtain cross-linking sodium hyaluronate gel, concentration is 20mg/ml.

Test method 3: get sodium hydrate aqueous solution and 50 μ L cross-linking agent 1 that 5.0ml concentration is 0.5M, 4-butanediol diglycidyl ether, both mix homogeneously, add hyaluronate sodium 0.9g under magnetic stirring, stir after within 5 minutes, being placed in the constant water bath box of temperature controllable 50 DEG C of reaction 1h, react 3 days at 20 DEG C again, after reaction terminates, the 0.1M phosphate buffered solution soaking and washing repeatedly that 100mLpH is 7.0 is added in gained reactant, to make to obtain pH < 7.5 and physiologically acceptable osmotic pressure value, drain away the water, collect gel, by 150 object screen clothes, then sterilizing, cross-linking sodium hyaluronate gel product can be obtained.

Test method 4: cross-linking hyaluronic acid sodium purification: get cross-linking hyaluronic acid sodium 10g, add water for injection 1L, be heated to 40 DEG C, add the Pidolidone of 4.3g, stir, add 80g dehydrated alcohol, be cooled to 8 DEG C, retain precipitation, lyophilization, obtains the cross-linking hyaluronic acid sodium 9.3g after purification;

Get the cross-linking hyaluronic acid sodium 2g after purification, add normal saline 98g, add 0.5g hyaluronic acid mix homogeneously, cross 100 eye mesh screens, 121 DEG C of moist heat sterilizations 30 minutes, fill, obtains 100.

Test method: get above-mentioned different tests method gel, by the following method, detect BDDE content and protein content in gel, result of the test is in table 1.

The method of inspection:

Protein content analysis:

1 principle

Forint phenol test solution can with the protein generation colored reaction in solution, and its shade is directly proportional to the concentration of protein.

2 equipment

Analytical balance, ultraviolet spectrophotometer or suitable equipment, vortex mixer or suitable equipment.

3 solution preparations

3.1 reagent A: take 1.0g hydrated copper sulfate (CuSO ₄5H ₂o), be dissolved in water and be diluted to 100ml.

3.2 reagent B: take 2.0g sodium potassium tartrate hydrate (KNaC ₄h ₄o ₆4H ₂o), be dissolved in water and be diluted to 100mL.

3.3 reagent C: take 25.0g natrium carbonicum calcinatum and 5.0g sodium hydroxide, be diluted to 250mL after being dissolved in water.

3.4 reagent D: before use, mix the reagent A of equivalent and reagent B.

3.5 reagent E: before use, by 1 part of reagent D and 10 parts of reagent C mixing.

3.6 reagent F: before use, get forint phenol test solution (Folin-phenol test solution) and carry out 10 times of dilutions.

Note: test agents useful for same is analytical pure.

The preparation of 4 standard solution

4.1 precisions take and are about 50mg through the vacuum drying bovine serum albumin reference substance of phosphorus pentoxide, are dissolved in water and are diluted to 250ml, (about 200 μ g/ml).

4.2 precisions pipette above-mentioned standard solution 1.0ml, 2.0ml, 4.0ml, 5.0ml, 10.0ml, are diluted to 100ml (concentration is about 2 μ g/ml, 4 μ g/ml, 8 μ g/ml, 10 μ g/ml, 20 μ g/ml).

5 steps

5.1 get 2ml test sample inserts in Potter-Elvehjem Tissue Grinders, and reciprocal even power is exerted pressure, and is that it enters bulb, and suction pipe sucking-off bulb content is pre-treatment sample.Through pre-treatment sample homogenizing, thoroughly, still possess viscoelasticity clearly, there is good circulation, facilitate sampler to the extraction of sample and dilution.

5.2 precisions pipette above-mentioned each standard solution 1.0ml, and blank tube precision pipettes distilled water 1.0ml, and sample cell precision takes sample 1.0g.By hyaluronate sodium quality in formula (1) calculation sample pipe, represent with microgram.

By hyaluronate sodium quality in formula (1) calculation sample pipe, represent with microgram.

${\mathrm{\&rho;}}_1=\frac{m\&times;c}{d}\&times;{10}^3...\left(1\right)$

In formula:

M-hyaluronic acid sodium gel quality, unit is gram (g);

C mono-hyaluronate sodium indicates mass concentration, and unit is milligram every milliliter (mg/ml);

D mono-hyaluronic acid sodium gel density is 1.01g/ml;

5.3 add reagent E 1.0ml in above-mentioned each pipe, and through the mixing of vortex agitator, room temperature places 10min.Add 3.0ml reagent F, after vortex mixer mixing, place 10min 50 DEG C of water-baths, measure absorbance in 750nm place.

6 results calculate

Use return law of the straight line result of calculation, computing formula about calculates hyaluronate sodium protein content ρ by (B.2) ₃(mass fraction):

${\mathrm{\&rho;}}_3(\%)=\frac{{\mathrm{\&rho;}}_2}{{\mathrm{\&rho;}}_1}\&times;100...(B.2)$

In formula:

ρ ₁hyaluronate sodium quality in-sample cell, unit is microgram (μ g);

ρ ₂protein quality in-sample cell, unit is microgram (μ g).

The BDDE determination of residual amount:

1 Cleaning Principle

1, epoxide in 4-butanedioldiglycidylether (BDDE) is under alkalescence and 1-Phenylethanone. environment, quantitative nucleophilic substitution can be there is with Nicotinamide (nicotiamide/niacin amide), and under acid condition, generate hyperfluorescence material (λ ex=370nm/ λ em=430nm), and fluorescence intensity is directly proportional to its content.Thus the fluorescence intensity by detecting product can measure the BDDE residual quantity in cross-linked hyaluronic acid gel.

2 major experimental instrument and reagents

Instrument

-fluorescence spectrophotometer luminance meter

-microbalance

-thermostatic water bath

Reagent

3 preparation of reagents

2.0mg/mLBDDE standard substance storage liquid:

Get 100mgBDDE to put in 50ml volumetric flask, add after PBS is settled to 50ml and mix, for subsequent use.

125mmole/L niacin amide solution:

Precision takes 0.763g niacin amide and puts in 50ml volumetric flask and be settled to 50ml with PBS, mixes for subsequent use.

15% acetophenone solution (V/V ethanol):

Pipette 1.5ml acetophenone solution to put in 10ml volumetric flask, add dehydrated alcohol and be settled to 10ml, mix for subsequent use.

1mol/LKOH solution:

Precision takes 5.62g potassium hydroxide, is dissolved in 15ml pure water and (is placed on ice face), put in 100ml volumetric flask, and then be settled to 100ml with pure water.Mixing is kept in tool plug bottle and leaves standstill 24 hours, and it is for subsequent use to get the supernatant.

4 experimental procedures

(1). by BDDE standard substance storing solution, pipette appropriate storing solution respectively and be diluted to 8.0, 4.0, 2.0, 1.0, 0.5the BDDE standard solution (for Criterion district line) of μ g/mL.

(2). pipette above-mentioned 5 kinds of concentration standard solution and each 200 μ L of test specimen, add the 125mmol/L niacin amide solution mixing of 100 μ L, water-bath 120min at 37 DEG C.

(3). add 15% acetophenone solution of 1mL and the 1mol/L potassium hydroxide solution of 1mL respectively, mixing ice bath 10min.

(4). add 5mL formic acid, 5min under 60 DEG C of water-baths, with being placed on cooled on ice 5min.

(5). room temperature leaves standstill 10 ~ 15min.

(6). measure fluorescent value (excitation wavelength: 370nm, emission wavelength: 430nm) with fluorescence spectrophotometer luminance meter

Table 1 different tests method obtains gel and compares

Conclusion (of pressure testing): from above-mentioned result of the test, test 2 groups of gel BDDE residual quantities to test 4 groups and be greater than 1 μ g/g, test 2 groups, test 3 histone matter content and be greater than 0.1%, and test group of the present invention (testing 1 group) BDDE residual quantity and protein content very low, there is better safety.

Two, preparation research

Cross-linking hyaluronic acid sodium purification: get cross-linking hyaluronic acid sodium 100g, adds water for injection 10L, is heated to 40 DEG C, adds the ASPARTIC ACID of 40g, stir, add 800g dehydrated alcohol, be cooled to 8 DEG C, retain precipitation, lyophilization, obtains the cross-linking hyaluronic acid sodium 93.3g after purification;

Test 1 group: get the cross-linking hyaluronic acid sodium 2g after purification, add normal saline 98g, add 0.5g hyaluronic acid mix homogeneously, cross 100 eye mesh screens, 121 DEG C of moist heat sterilizations 30 minutes, fill, obtains 100.

Test 2 groups: get the cross-linking hyaluronic acid sodium 2g after purification, add normal saline 98g, add 0.66gPBS buffer mix homogeneously, cross 100 eye mesh screens, 121 DEG C of moist heat sterilizations 30 minutes, fill, obtains 100.

Test method: get above-mentioned gel, place 3 months under being placed on 2 DEG C of-8 DEG C of dry environments, measure the hyaluronic acid sodium content of different tests group gel, result of the test is in table 2.

Hyaluronate sodium assay:

1 principle

After hyaluronate sodium hydrolysis, glucuronic acid and the effect of carbazole reagent produce reddish violet, and the shade of generation is directly proportional to glucuronic acid content.

2 equipment

Analytical balance, Scroll-tupe blender, purple spectrophotometer.

3 solution preparations

3.14.6M HCl

Get the hydrochloric acid 46ml of 37%, adding distil water standardize solution is in 100ml volumetric flask.

3.2 volume fractions are the carbazole ethanol of 0.1%

Take 0.1g carbazole, add dehydrated alcohol 100mL and dissolve.Move in dark-brown bottle, store at 4 DEG C, effect duration is 12 months.

3.3 glucuronic acids (GA) standard solution

Accurately take 10mg glucuronic acid in 100ml volumetric flask, be diluted to scale, shake up, store at 4 DEG C.

3.40.025mol/L sodium tetraborate sulfuric acid solution

Take sodium tetraborate (Na ₂b ₄o ₇.10H ₂o) 9.54g, adds in 1L concentrated sulphuric acid, adds a cover.Variable interval is shaken, until sodium tetraborate dissolves completely.4 DEG C of storages, effect duration is 12 months.

Note: test agents useful for same is analytical pure.

The preparation of 4 samples

4.1 test sample process

Accurately take in 0.52 ± 0.02g sample holding test tubes.Prepare a Duplicate Samples.Add the hydrochloric acid 1.0ml of 4.6M in the sample to which.Tool plug mixes, 65-75 DEG C of water-bath 2h.Test tube at least will be shaken four times in water-bath process.

The dilution of 4.2 samples

Sample is transferred in 100ml volumetric flask, uses distilled water standardize solution.Magnetic stirrer sample, spends the night.

5 steps

5.1 prepare glucal standard acid solution series by table.

Operating level liquid (1mg/ml): 100ml distilled water dissolves 100mgD-glucuronic acid, can keep stablizing 6 months at 4 DEG C.

Standard solution (100 μ g/ml): dilute 5ml storage standard liquid respectively to 50ml with water, use front Extemporaneous.

Working standard liquid: the glucal acid solution 5ml of preparation standard concentration.

Working standard liquid (ì g/ml)	Standard solution (ml)	Water (ml)
			70	3.5	1.5
60	3.0	2.0
			50	2.5	2.5
40	2.0	3.0
			30	1.5	3.5

5.2 get each working solution of 0.5ml and dilute sample liquid respectively to (three repetitions) in other test tube.The each test tube of titer series is placed in ice-water bath together with sample cell, and in every pipe, add four canopies acid sodium sulphuric acid 2.5ml (storing at least 2h before using at 4 DEG C) lentamente with acid buret, limit edged shakes up.Finish rear mixing and be placed in after boiling water bath boils 20min and take out, be cooled to room temperature.All add carbazole alcoholic solution 0.1ml in each test tube, fully after mixing, be placed in room temperature (10-30 DEG C) 2h.Compare (in a test tube, adding 0.5ml water) with No. 0 pipe, with the light absorption value of each standard pipe in spectrophotometric determination 530nm place and sample cell.

5.3 draw absorbance-D glucuronic acid concentration curve (coefficient of determination, r with titer ²>=0.995) concentration of glucuronic acid in sample cell, is checked according to the linear regression of standard curve.

6. result calculates:

Hyaluronic concentration is calculated by formula

$\mathrm{HA}(\mathrm{mg}/\mathrm{ml})=\frac{\mathrm{Cs}}{\mathrm{Ws}\&CenterDot;1000}\&CenterDot;100\&CenterDot;\frac{401.3}{194.1}$

In formula:

Cs-directrix curve calculates the equal concentration of product (μ g/ml) of the D glucuronic acid in three dilute sample solution;

Ws-weighs the weight (g, 1g=1ml) of gel

Table 2 different tests group hyaluronate sodium comparision contents

Conclusion (of pressure testing): above-mentioned result of the test shows, the present invention adopts hyaluronic acid to adjust as pH and is prepared into gel, hyaluronate sodium changes of contents is very little, and when adopting the gel 3 months of phosphate buffer, hyaluronic acid sodium content reduces 11.2%, absolutely proves that invention formulation prescription has scientific meaning.

Preparation embodiment

Embodiment 1

(1) cross-linking hyaluronic acid sodium purification

Get cross-linking hyaluronic acid sodium 1000g, add water for injection 100L, be heated to 45 DEG C, add the ASPARTIC ACID of 450g, stir, add the dehydrated alcohol of 900g, be cooled to 10 DEG C, retain precipitation, lyophilization, obtains the cross-linking hyaluronic acid sodium 909.2g after purification;

(2) preparation preparation: preparation prescription: cross-linking hyaluronic acid sodium 25g, normal saline 985g, hyaluronic acid 8.3g.

Get the cross-linking hyaluronic acid sodium after purification, add normal saline, add hyaluronic acid mix homogeneously, cross 100 eye mesh screens, 121 DEG C of moist heat sterilizations 30 minutes, fill, obtains 1000.

Embodiment 2

(1) cross-linking hyaluronic acid sodium purification

Get cross-linking hyaluronic acid sodium 1000g, add water for injection 100L, be heated to 35 DEG C, add the ASPARTIC ACID of 450g, stir, add the dehydrated alcohol of 9000g, be cooled to 5 DEG C, retain precipitation, lyophilization, obtains the cross-linking hyaluronic acid sodium 913.4g after purification;

(2) preparation preparation: preparation prescription: cross-linking hyaluronic acid sodium 15g, normal saline 975g, hyaluronic acid 3g.

Get the cross-linking hyaluronic acid sodium after purification, add normal saline, add hyaluronic acid mix homogeneously, cross 100 eye mesh screens, 121 DEG C of moist heat sterilizations 30 minutes, fill, obtains 1000.。

Embodiment 3

(1) cross-linking hyaluronic acid sodium purification

Get cross-linking hyaluronic acid sodium 1000g, add water for injection 100L, be heated to 38 DEG C, add the ASPARTIC ACID of 365g, stir, add 795g dehydrated alcohol, be cooled to 6 DEG C, retain precipitation, lyophilization, obtains the cross-linking hyaluronic acid sodium 922.3g after purification;

(2) preparation preparation: preparation prescription: cross-linking hyaluronic acid sodium 18g, normal saline 978g, hyaluronic acid 4g.

Get the cross-linking hyaluronic acid sodium after purification, add normal saline, add hyaluronic acid mix homogeneously, cross 100 eye mesh screens, 121 DEG C of moist heat sterilizations 30 minutes, fill, obtains 1000.

Embodiment 4

(1) cross-linking hyaluronic acid sodium purification

Get cross-linking hyaluronic acid sodium 1000g, add water for injection 100L, be heated to 43 DEG C, add the ASPARTIC ACID of 435g, stir, add the dehydrated alcohol of 850g, be cooled to 8 DEG C, retain precipitation, lyophilization, obtains the cross-linking hyaluronic acid sodium after purification;

(2) preparation preparation: preparation prescription: cross-linking hyaluronic acid sodium 23g, normal saline 983g, hyaluronic acid 8g.

Get the cross-linking hyaluronic acid sodium after purification, add normal saline, add hyaluronic acid mix homogeneously, cross 100 eye mesh screens, 121 DEG C of moist heat sterilizations 30 minutes, fill, obtains 1000.

Described embodiment includes but not limited to above-mentioned.

Claims (8)

1. a medicine for beautification function, is characterized in that this medicine is prepared from by cross-linking hyaluronic acid sodium, normal saline and pH adjusting agent.

2. the medicine of a kind of beautification function according to claim 1, wherein cross-linking hyaluronic acid sodium 15-25 weight portion, normal saline 975-985 weight portion.

3. the medicine of a kind of beautification function according to claim 1 and 2, wherein cross-linking hyaluronic acid sodium is that hyaluronate sodium is cross-linked through BDDE and prepares.

4. the medicine of a kind of beautification function according to claim 1 and 2, in its Chinese medicine, BDDE content is greater than zero and is less than 0.5 μ g/g.

5. the medicine of a kind of beautification function according to claim 1 and 2, in its Chinese medicine, protein quality percentage composition is less than 0.1%.

6. the medicine of a kind of beautification function according to claim 1, wherein pH adjusting agent is hyaluronic acid, and cross-linking hyaluronic acid sodium and hyaluronic weight ratio are 3-5: 1.

7. the medicine of a kind of beautification function according to claim 1 and 2, is characterized in that medicine is gel.

8. the medicine of a kind of beautification function according to claim 1 and 2, wherein the preparation method of gel is:

(1) cross-linking hyaluronic acid sodium purification

Get cross-linking hyaluronic acid sodium, add water for injection, be heated to 35 DEG C-45 DEG C, add cross-linking hyaluronic acid sodium weight 0.35-0.45 ASPARTIC ACID doubly, stir, add the 7.5-9 dehydrated alcohol doubly of cross-linking hyaluronic acid sodium weight, be cooled to 5 DEG C-10 DEG C, retain precipitation, lyophilization, obtains the cross-linking hyaluronic acid sodium after purification;

(2) preparation preparation

Get the cross-linking hyaluronic acid sodium after purification, add normal saline, add hyaluronic acid mix homogeneously, cross 100 eye mesh screens, 121 DEG C of moist heat sterilizations 30 minutes, fill, to obtain final product.