阅读说明：本技术 一种五味子木脂素柔性脂质体乳液及其制备方法 (Schisandra chinensis lignan flexible liposome emulsion and preparation method thereof ) 是由 刘俊霞 闫峰 于 2021-10-08 设计创作，主要内容包括：本发明涉及脂质体制备领域,具体涉及一种五味子木脂素柔性脂质体乳液及其制备方法,该五味子木脂素柔性脂质体乳液,由以下质量百分比的原料制备而成：油相为23.3%、促透剂0.17%,乳化剂0.88%、保湿剂0.18%、黄原胶0.18%、柔性脂质体16.87%、苯氧乙醇0.50%、加水相至100%。本发明所得的五味子木脂素柔性脂质体乳液具有安全无毒、柔韧性能好、渗透性能强等特点,对皮肤有很强的亲和力。(The invention relates to the field of liposome preparation, in particular to a schisandra lignan flexible liposome emulsion and a preparation method thereof, wherein the schisandra lignan flexible liposome emulsion is prepared from the following raw materials in percentage by mass: 23.3 percent of oil phase, 0.17 percent of transdermal enhancer, 0.88 percent of emulsifier, 0.18 percent of humectant, 0.18 percent of xanthan gum, 16.87 percent of flexible liposome, 0.50 percent of phenoxyethanol and 100 percent of water phase. The schisandra lignan flexible liposome emulsion obtained by the invention has the characteristics of safety, no toxicity, good flexibility, strong permeability and the like, and has strong affinity to skin.)

1. The schisandra lignan flexible liposome emulsion is characterized by being prepared from the following raw materials in percentage by mass: 23.3 percent of oil phase, 0.17 percent of transdermal enhancer, 0.88 percent of emulsifier, 0.18 percent of humectant, 0.18 percent of xanthan gum, 16.87 percent of flexible liposome, 0.50 percent of phenoxyethanol and 100 percent of water phase; wherein the flexible liposome is prepared by the following steps:

precisely measuring 1 mL of fructus Schisandrae lignin, and preparing tween-80 into 10 mg/mL with anhydrous ethanol^-1As a solution of tween-80: adding appropriate amount of Tween-80 solution, 120 mg of cholesterol and 600 mg of soybean lecithin at a ratio of soybean lecithin =1:6, fixing the volume to 25 mL with absolute ethyl alcohol, ultrasonically dissolving for 5-10 min, rotationally evaporating in 55 ℃ water bath to form a film layer, adding appropriate amount of water phase, and performing hydration ultrasonic treatment until the film completely falls off to obtain the flexible lipidAnd (3) suspension of the body.

2. The schisandra lignan liposome emulsion of claim 1, wherein the oil phase is prepared by mixing beeswax and liquid paraffin according to a mass ratio of 1: 3.

3. The schisandra lignan flexible liposome emulsion of claim 1, wherein the aqueous phase is phosphate buffered saline with pH = 7.0.

4. The schisandra lignan flexible liposome emulsion of claim 1, wherein the penetration enhancer is propylene glycol or azone.

5. The schisandra lignan liposome emulsion of claim 1, wherein the emulsifier is tween-80 and the emulsifier OP is mixed at a mass ratio of 1: 5.

6. The schisandra lignan flexible liposome emulsion of claim 1, wherein the humectant is prepared by mixing sodium hyaluronate and sorbitol at a mass ratio of 1: 3.

7. The method for preparing the schisandra lignan liposome emulsion of any one of claims 1 to 6, wherein the method comprises the following steps: the method comprises the following steps: weighing oil phase and water phase, respectively heating to 80 deg.C until completely melted, adding water phase into oil phase, emulsifying for about 5 min with high speed homogenizer, cooling to 40 deg.C, adding liposome and essence, stirring again to mix well, and cooling to room temperature to obtain fructus Schisandrae lignanoid flexible liposome emulsion.

Technical Field

The invention relates to the field of liposome preparation, in particular to a schisandra lignan flexible liposome emulsion and a preparation method thereof.

Background

Schisandra chinensis, commonly known as "Schisandra chinensis", is a plant of Schisandraceae, Schisandra chinensisSchisandra chinensis(Turcz.) dried ripe fruit of Baill. The lignans are main active substances and have the capabilities of obviously eliminating free radicals and inhibiting lipid peroxidation.

The liposome is a liposome colloidal particle, wherein phospholipid forms a closed vesicle containing one or more layers of phospholipid membranes in water and forms a bilayer membrane structure. Despite the many advantages of liposome drug loading, unmodified liposomes still have certain limitations.

Disclosure of Invention

In order to solve the problems, the invention provides the schisandra lignan flexible liposome emulsion and the preparation method thereof, and the obtained flexible liposome emulsion has the characteristics of safety, no toxicity, good flexibility, strong permeability and the like, and has strong affinity to skin.

The schisandra lignan flexible liposome emulsion is prepared from the following raw materials in percentage by mass: 23.3 percent of oil phase, 0.17 percent of transdermal enhancer, 0.88 percent of emulsifier, 0.18 percent of humectant, 0.18 percent of xanthan gum, 16.87 percent of flexible liposome, 0.50 percent of phenoxyethanol and 100 percent of water phase; wherein the flexible liposome is prepared by the following steps: precisely measuring 1 mL of fructus Schisandrae lignanoid, and preparing tween-80 into 10 mg/mL with anhydrous ethanol^-1As a solution of tween-80: adding a proper amount of Tween-80 solution, 120 mg of cholesterol and 600 mg of soybean lecithin into the soybean lecithin at the ratio of 1:6, fixing the volume to 25 mL by using absolute ethyl alcohol, ultrasonically dissolving for 5-10 min, rotationally evaporating in a water bath at 55 ℃ to form a film layer, adding a proper amount of water phase, and carrying out hydration ultrasonic treatment until the film completely falls off to obtain the flexible liposome suspension.

Further, the oil phase is prepared by mixing beeswax and liquid paraffin according to the mass ratio of 1: 3.

Further, the aqueous phase is phosphate buffer at pH = 7.0.

Further, the penetration enhancer is propylene glycol or azone.

Further, the emulsifier is obtained by mixing Tween-80 and an emulsifier OP according to the mass ratio of 1: 5.

Further, the humectant is prepared by mixing sodium hyaluronate and sorbitol according to the mass ratio of 1: 3.

The invention also provides a preparation method of the schisandra lignan flexible liposome emulsion, which comprises the following steps:

weighing oil phase and water phase, respectively heating to 80 deg.C until completely melted, adding water phase into oil phase, emulsifying for about 5 min with high speed homogenizer, cooling to 40 deg.C, adding liposome and essence, stirring again to mix well, and cooling to room temperature to obtain fructus Schisandrae lignanoid flexible liposome emulsion.

The invention has the following beneficial effects: the obtained Schisandra chinensis lignan flexible liposome emulsion has the characteristics of safety, no toxicity, good flexibility, strong permeability and the like, and has strong affinity to skin.

The obtained schisandra lignan flexible liposome emulsion meets the specified standard of cosmetic industry QB/T1857-2013 skin-moistening cream, and lays a material foundation for the wide application of schisandra lignan.

Drawings

FIG. 1 is a chromatogram of a mixed standard of Schisandra chinensis;

note: 1-schizandrol A; 2-schizandrol B; 3-deoxyschizandrin; 4-Schisandrin B.

FIG. 2 is a schizandrin A standard curve.

Detailed Description

In order that the objects and advantages of the invention will be more clearly understood, the invention is further described in detail below with reference to examples. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

Test data

Reagent

Schizandrol A control (MUST-20082908, institute of Others of Chinese academy of sciences); beeswax (20201020, Tianjin chemical Co., Ltd.); liquid paraffin (20171010, Tanjia chemical Co., Ltd.); azone (20181206, Hengxuan growth trade Co., Ltd.); propylene glycol (20040312, Shenyang new space chemical plant); tween-80 (2017111035, tianjin, remote chemical agents ltd); emulsifier OP (20190508, Jinan engineering, Inc.); sorbitol (20180302, Tianjin chemical Co., Ltd.); sodium hyaluronate (HA 200730, guangyu biotechnology limited, qingzhou); xanthan gum (20200710, Lorentz Biotechnology, Inc. of Tianjin); phenoxyethanol (20201215, Pander trade International Co., Ltd.)

2 method of experiment

2.1 preparation method of Flexible Liposome and emulsion

Precisely measuring 1 mL of fructus Schisandrae lignanoid, and preparing tween-80 into 10 mg/mL with anhydrous ethanol^-1After the solution of (a), the ratio of tween-80: adding 120 mg of cholesterol and 600 mg of soybean lecithin according to the ratio of soybean lecithin =1:6, fixing the volume to 25 mL by absolute ethyl alcohol, ultrasonically dissolving for 5-10 min, rotationally evaporating in a water bath at 55 ℃ to form a film layer, adding a proper amount of phosphate buffer (pH = 7.0) for hydration and ultrasonic treatment until the film completely falls off, and obtaining the flexible liposome suspension.

According to the literature, the oil phase content is 15-30%, the transdermal enhancer content is 0.1-0.3%, the emulsifier content is 1-3%, the humectant content is 1-5%, the xanthan gum content is 0.1-0.2%, the phenoxyethanol content is 0.5-1%, the flexible liposome content is 15-20%, and the water phase is added to 100%.

The oil and water phases were weighed and heated to 80 ℃ separately until complete melting. Adding the water phase into the oil phase, emulsifying for about 5 min with a high speed homogenizer, cooling to 40 deg.C, adding liposome and essence, stirring again to mix well, and cooling to room temperature. Namely the schisandra lignan flexible liposome emulsion.

Method for measuring content

2.2.1 establishment of chromatographic conditions

Column Hyperil-C18(10 μm, 4.6X 250 mm), mobile phase: water (A) -methanol (B), the elution ratio is 0-35 min, and the concentration is 68% B; 35-40 min, 68-100% B; 40-48 min, 100-100% B; 48-52 min, 100-68% B; 52 to 60min, 68-68% of B, and the flow rate is 1 mL/min^-1The column temperature is 35 ℃, the detection wavelength is 254 nm, and the injection volume is 10 mu L.

2.2.2 drawing of Standard Curve

Precisely measuring standard schizandrol A5 mg, and preparing with methanol to give a concentration of 0.5 mg/mL^-1The control solution of (4). Control solutions (0.05, 0.1, 0.15, 0.2, 0.25 mg/mL) were prepared with different concentration gradients^-1) And then standby. And (3) passing the reference substance solutions with different concentration gradients through a 0.22-micron microporous filter membrane, respectively injecting 10 mu L of sample according to 2.2.1 chromatographic conditions, recording peak areas, and drawing a standard curve by taking the concentration of the reference substance as a horizontal coordinate and the peak area as a vertical coordinate.

2.2.3 sample assay

Taking three batches of flexible liposome emulsion, precisely measuring 0.5 g, placing in a 10 mL volumetric flask, adding methanol, performing ultrasonic treatment for 10 min, fixing volume to obtain sample solution, introducing 10 μ L of sample according to 2.2.1 chromatographic conditions, recording chromatogram, and calculating sample content by adopting a standard curve method.

Study of emulsion formulation

2.3.1 Single factor investigation

The oil phase, the emulsifier, the xanthan gum and the liposome have obvious influence on the experimental result through a pre-experiment, so that the oil phase, the emulsifier, the xanthan gum and the liposome are used as orthogonal experimental objects;

2.3.2 design of orthogonal experiments

As can be seen from a single factor, A: oil phase content ratio, B: emulsifier content ratio, C: amount of xanthan gum, D: the amount of liposomes used, as a subject of investigation, was 3 levels for each factor, based on L₉(3⁴) An orthogonal test table is used for designing an experiment, centrifugal separation at 2000 r/min for 30 min is used as a test condition, and a sedimentation volume ratio (F is more than or equal to 0.9) is used as a test index.

Stability survey

Under the preferred formulation, 3 batches of the emulsion were prepared and evaluated for sensory, pH, centrifugation, cold, heat resistance, and particle size, respectively.

Results and data

3.1 drawing of Standard Curve

The chromatographic peak of the schisandra chinensis mixed standard substance is shown in figure 1 by the chromatographic conditions of item 2.2.1.

Standard curve Y =21056X +4.19 (R) of schizandrol A²= 0.9938) as shown in FIG. 2, indicating that in the range of 0.05-0.25 mg. mL^-1The linear relationship within the concentration range is good.

Results of single factor experiments

3.2.1 screening results for oil phase ratio

The results of the single factor investigation of the oil phase ratio are shown in table 1 below.

Table 1 oil phase ratio examination results

The data in the table show that the oil phase ratio of the experimental optimization is 1:3, 1:4 and 1: 5.

3.2.2 screening results for emulsifier ratio

The results of the single factor examination of the emulsifier ratio are shown in table 2.

Table 2 emulsifier ratio test results

According to the data in the table, the ratio of the emulsifiers optimally investigated in the experiment is 1:3, 1:4 and 1: 5.

3.2.3 screening results for humectant ratio

The results of the single factor examination of the humectant ratio are shown in table 3.

Table 3 humectant proportion test results

The data in the table show that the humectant has no significant effect on the stability of the emulsion and therefore is not considered a factor in the orthogonal experiments.

3.2.4 investigation of amount of Xanthan Gum

The results of the single factor examination of xanthan gum are shown in table 4.

Table 4 investigation of xanthan gum usage

The data in the table show that the amount of the stabilizer optimized and considered in the experiment is 0.18%, 0.20% and 0.22%.

3.2.5 examination of liposome dosage

Results of single factor examination of liposomes are shown in table 5.

TABLE 5 examination of liposome dosage

The data in the table show that the optimized liposome dosage for this experiment is 15.25%, 16.87% and 18.64%.

Orthogonal design

From the single factor results, screening for levels of orthogonality is shown in Table 6 using L₉(3⁴) Orthogonal tables were used to screen the optimal emulsion preparation recipe.

TABLE 6 orthogonal test factor horizon

The orthogonal test table is shown in table 7.

TABLE 7 results of orthogonal experiments

The sequence of the indexes influencing the finished product investigation in 4 factors is A obtained from the orthogonal test result table of Table 7>D>B>C, determining the optimized prescription A according to the formula₁B₃C₂D_1，Namely an oil phase: the ratio of beeswax to liquid paraffin is 1: 3; emulsifier: tween-80 emulsionThe agent OP is 1: 5; the dosage of the liposome is 16.87%; the xanthan gum is used in an amount of 0.18%.

Determination of content

The results of the content measurement are shown in Table 8.

TABLE 8 results of content measurement

3.5 stability test results

The results of the tests of organoleptic physicochemical properties of the test products, as specified in the industrial standard QB/T29665-2013 skin care lotions, are shown in Table 9.

Table 9 stability test results

The foregoing is only a preferred embodiment of the present invention, and it should be noted that those skilled in the art can make various improvements and modifications without departing from the principle of the present invention, and these improvements and modifications should also be construed as the protection scope of the present invention.