CN106619149A - Method for preparing nicotinamide-coated multivesicular liposomes - Google Patents

Abstract

A multivesicle liposome coated with nicotinamide is composed of phospholipid, neutral lipid, cholesterol, organic solvent, hydrophilic emulsifier, nicotinamide, amino acid, osmotic pressure regulator and deionized water. In the present invention, phospholipids, cholesterol and neutral lipids are dissolved in an organic solvent as an organic phase; nicotinamide, amino acid, osmotic pressure regulator and deionized water are uniformly mixed as an internal water phase; the homogeneous organic phase components are The inner water phase components are added to prepare W/O type primary emulsion; the hydrophilic emulsifier, amino acid, osmotic pressure regulator and deionized water are mixed and dispersed as the outer water phase; the homogeneous outer water phase components are added The W/O type primary emulsion components are homogenized, ultrasonicated, then stirred and cooled to room temperature to form a W/O/W type multiple emulsion; then the multiple emulsion is dispersed in the amino acid solution, and nitrogen gas is introduced to remove the organic solvent to obtain Suspension of multivesicular liposomes coated with niacinamide. The invention improves the stability of nicotinamide.

Description

A preparation method of multivesicular liposomes coated with nicotinamide

technical field

The invention belongs to the field of cosmetics and relates to a liposome, in particular to a multivesicle liposome coated with nicotinamide and a preparation method thereof.

Background technique

Niacinamide, a derivative of vitamin B3, is a multifunctional active substance that has attracted more and more attention in recent years. It has 6 major skin care effects: whitening, anti-aging, improving skin barrier function, moisturizing, oil control and Shrink pores, treat acne. Therefore, its application in cosmetics involves whitening products, anti-wrinkle products, moisturizing products, anti-acne products, and hair care products. However, nicotinamide is very sensitive to pH and has poor stability. In a solution with a pH value higher or lower than 6, it will be hydrolyzed to form nicotinic acid, causing skin allergies; Caking and poor stability during storage, thus limiting the widespread use of niacinamide in cosmetics.

Multivesicular liposomes (MVLs), also known as multivesicular liposomes, are a new type of liposome preparation with a special structure, and its discontinuous aqueous lumen is separated by non-concentric lipid and phospholipid membranes. , forming many tiny vesicles. MVLS particles are honeycomb-shaped, and the particle size is generally between 1-100 μm. The structure of MVLs multivesicles makes it have more encapsulating volume of water-soluble substances, and the volume of the water chamber accounts for 95% of the total particle volume. The plastid is much higher; when a vesicle ruptures, the active substance is released from the ruptured vesicle, and the intact vesicle can still maintain its original shape, so it has a good slow-release effect; the non-concentric structure of the lipid layer makes The stability of the liposome is increased, and the release time of the active substance is prolonged.

For the coating of hydrophilic substances, multivesicular liposomes are needed to coat nicotinamide in the inner water phase to form a coating carrier structure for nicotinamide. To improve the stability of nicotinamide, reduce the irritation, and then improve the activity and wide application of nicotinamide.

At present, there have been many studies on multivesicular liposome carrier technology, most of which are coated drugs used in the medical industry. The preparation process is relatively complicated, but multivesicular liposomes coated with nicotinamide and applied to Cosmetics have not yet been published.

Contents of the invention

Aiming at the above-mentioned technical problems in the prior art, the present invention provides a multivesicular liposome coated with nicotinamide and a preparation method thereof, the multivesicular liposome coated with nicotinamide and its preparation method The preparation method should solve the technical problem of poor quality of nicotinamide in the prior art.

The invention provides a multivesicular liposome coated with nicotinamide. The composition and content of the raw materials are as follows:

Phospholipids 1.0~20.0%;

Neutral lipid 1.0~10.0%;

Cholesterol 1.0~10.0%;

Organic solvent 5.0~20.0%;

Niacinamide 0.01~5.0%;

Hydrophilic emulsifier 0.1~12.0%;

Amino acid 0.1~1.0%;

Osmotic pressure regulator 2.0~8.0%;

Deionized water balance;

The phosphoric acid is lecithin, hydrogenated lecithin, soybean lecithin, phosphatidylethanolamine, distearoylphosphatidylcholine, dimyristoylphosphatidylcholine, dioleoylphosphatidylethanolamine, or dipalmitoylphosphatidylcholine One or a mixture of two or more glycerin;

The neutral lipid is glyceryl trioleate, glyceric acid, glyceryl laurate, glyceryl tricaprate, glyceryl tricaprylate, or one or a mixture of two or more of vitamin E;

The organic solvent is one or a mixture of ether, ethanol, butanol, or ethyl acetate;

The hydrophilic emulsifier is Tween 80, polyoxyethylene-polyoxypropylene block copolymer, peptide bimolecular lipophilic and hydrophilic surfactant, PEG-100 stearate, glycerol stearate, One of arachidyl alcohol and behenyl alcohol and arachidyl alcohol glucoside, cetearyl alcohol and cetearyl glucoside, fatty alcohol polyoxyethylene ether (21EO), glyceryl behenate, or cetearyl glucoside A mixture of two or more kinds;

Described amino acid is lysine, aspartic acid, serine, L-arginine, alanine, aspartic acid, glutamic acid, glycine, histidine, tryptophan, tyrosine, proline One or a mixture of two or more of amino acid, leucine, or valine;

The osmotic pressure regulator is one or a mixture of glucose, sucrose, or physiological saline.

Further, the above-mentioned multivesicular liposome coated with nicotinamide has the following raw material composition and content in terms of weight percentage:

Phospholipids 1.0%;

Neutral Lipid 1.0%;

Cholesterol 1.0%;

Organic solvent 5.0%;

Niacinamide 0.01%;

Hydrophilic emulsifier 0.1%;

Amino acid 0.1%;

Osmotic pressure regulator 2.0%;

Deionized water balance;

Described phospholipid is lecithin;

Described neutral fat is glyceryl trioleate;

Described organic solvent is ether;

Described hydrophilic emulsifier is Tween 80;

Described amino acid is lysine;

The osmotic pressure regulator is glucose.

Further, the above-mentioned multivesicular liposome coated with nicotinamide has the following raw material composition and content in terms of weight percentage:

Phospholipids 10.0%;

Neutral lipid 5.0%;

Cholesterol 5.0%;

Organic solvent 12.5%;

Niacinamide 2.5%;

Hydrophilic emulsifier 6.0%;

Amino acid 0.5%;

Osmotic pressure regulator 5.0%;

Deionized water balance;

The phospholipid is one or a mixture of hydrogenated lecithin or soybean lecithin;

Described neutral substance is glyceric acid;

Described organic solvent is ethanol;

The hydrophilic emulsifier is a polyoxyethylene-polyoxypropylene block copolymer or a mixture of one or two of PEG-100 stearate;

The amino acid is aspartic acid;

The osmotic pressure regulator is sucrose.

Further, the above-mentioned multivesicular liposome coated with nicotinamide has the following raw material composition and content in terms of weight percentage:

Phospholipids 20.0%

Neutral Lipid 10.0%;

Cholesterol 10.0%;

Organic solvent 20.0%;

Niacinamide 5.0%;

Hydrophilic emulsifier 12.0%;

Amino acid 1.0%;

Osmotic pressure regulator 8.0%;

Deionized water balance;

Described phosphoric acid is phosphatidylethanolamine;

The neutral lipid is one or a mixture of tricaprylin and vitamin E;

Described organic solvent is butanol;

The hydrophilic emulsifier is a mixture of one or two of peptide bimolecular lipophilic and hydrophilic surfactants, cetearyl alcohol and cetearyl glucoside;

The amino acid is L-arginine;

The osmotic pressure regulator is physiological saline.

The present invention also provides the above-mentioned preparation method of multivesicular liposomes coated with nicotinamide, comprising the following steps:

1) Weighing phospholipids, neutral lipids, cholesterol, organic solvents, hydrophilic emulsifiers, nicotinamide, amino acids, osmotic pressure regulators and deionized water by weight percentage;

2) dissolving phospholipids, cholesterol and neutral lipids in an organic solvent as an organic phase;

3) Prepare 1~100mmol/L amino acid solution, mix nicotinamide, 30~60% amino acid solution, 30~60% osmotic pressure regulator and 30~60% deionized water as the inner water phase;

4) Add the internal water phase obtained in step 3) into the organic phase, homogenize the organic phase components at a homogenization speed of 7200-30000rpm, and simultaneously add the internal water phase components, homogenize for 1-15min, and obtain W/ O-type primary emulsion;

5) mixing the hydrophilic emulsifier, the remaining content of the amino acid solution, the remaining content of the osmotic pressure regulator and the remaining content of deionized water as the external water phase;

6) Homogenize the outer water phase components at a homogenization speed of 7200-30000rpm, and at the same time add the W/O-type primary emulsion components prepared in step (3) to it. After homogenizing for 1-15 minutes, select the ultrasonic power of 20%- 30%, ultrasonication for 5 seconds and stop for 5 seconds, ultrasonication of the emulsion for 1 to 20 minutes, stirring until the system is uniform and cooled down to room temperature naturally to make a W/O/W multiple emulsion;

7) Configure the amino acid solution with the same concentration as in step 3), disperse the obtained multiple emulsion in the amino acid solution, wherein the volume ratio of the multiple emulsion to the amino acid solution is 5:1 to 1:5, and pass nitrogen gas to remove the multiple emulsion Organic solvent, prepared multivesicular liposome suspension coated with nicotinamide.

The effect of the amino acid solution in this step 7) is to affect the pH of the aqueous solution, regulate the surface charge of the oil-water interface phospholipid, improve the electrostatic stability of the multivesicular liposome, and reduce the removal of the organic solvent process of the multivesicular liposome by nitrogen blowing The demulsification phenomenon in the formula does not participate in the formation process of multivesicular liposomes, so the content of amino acids in the formula does not include this part.

In the present invention, phospholipids, cholesterol and neutral lipids are dissolved in an organic solvent as an organic phase; nicotinamide, amino acid, osmotic pressure regulator and deionized water are uniformly mixed as an internal water phase; the homogeneous organic phase components are The inner water phase components are added to prepare the W/O type primary emulsion; the hydrophilic emulsifier, amino acid, osmotic pressure regulator and deionized water are mixed and dispersed evenly as the outer water phase; the homogeneous outer water phase components, Add the previously prepared W/O-type primary emulsion components, homogenize and perform ultrasonication, then stir and cool to room temperature to form a W/O/W-type multiple emulsion; then disperse the multiple emulsions in the amino acid solution, and pass through nitrogen to remove multiple emulsions. The organic solvent in the emulsion obtains the multivesicular liposome suspension coated with nicotinamide.

In the present invention, a compounding scheme of suitable phospholipids, neutral lipids, cholesterol, organic solvents, amino acids, osmotic pressure regulators and deionized water is used. Adopt two-step emulsification method in the preparation process, and carry out ultrasonic, therefore, the particle diameter of the dispersed phase particle of the multivesicular liposome of final gained is relatively uniform, and its preparation process is simple, energy consumption is low, and the emulsion system formed is stable, It not only provides a suitable carrier for niacinamide, improves the stability of niacinamide, reduces its irritation to the skin, is mild to the skin, absorbs quickly, and has both functionality and beauty.

Compared with the prior art, the technical progress of the present invention is remarkable. The invention provides a suitable carrier for the coating of nicotinamide, improves the stability of nicotinamide, reduces irritation, further improves the activity and wide application of nicotinamide, and develops a non-toxic and strong action Harmless and non-irritating cosmetics containing niacinamide actives.

Description of drawings

Fig. 1 is the photomicrograph of the multivesicular liposomes coated with nicotinamide obtained in Example 1

detailed description

The present invention will be further described below through specific embodiments in conjunction with the accompanying drawings, but the present invention is not limited.

Example 1

A multivesicular liposome coated with nicotinamide, calculated by weight percentage, its raw material composition and content are as follows:

Phospholipids 1.0%;

Neutral Lipid 1.0%;

Cholesterol 1.0%;

Organic solvent 5.0%;

Niacinamide 0.01%;

Hydrophilic emulsifier 0.1%;

Amino acid 0.1%;

Osmotic pressure regulator 2.0%;

Deionized water balance;

Described phospholipid is lecithin;

Described neutral fat is glyceryl trioleate;

Described organic solvent is ether;

Described hydrophilic emulsifier is Tween 80;

Described amino acid is lysine;

The osmotic pressure regulator is glucose;

The above-mentioned preparation method of multivesicular liposomes coated with nicotinamide specifically comprises the following steps:

1) Weighing phospholipids, neutral lipids, cholesterol, organic solvents, hydrophilic emulsifiers, nicotinamide, amino acids, osmotic pressure regulators and deionized water by weight percentage;

2) dissolving phospholipids, cholesterol and neutral lipids in an organic solvent as an organic phase;

3) Prepare 1~100mmol/L amino acid solution, mix nicotinamide, 30~60% amino acid solution, 30~60% osmotic pressure regulator and 30~60% deionized water as the inner water phase;

4) Add the internal water phase obtained in step 3) into the organic phase, homogenize the organic phase components at a homogenization speed of 7200-30000rpm, and simultaneously add the internal water phase components, homogenize for 1-15min, and obtain W/ O-type primary emulsion;

5) mixing the hydrophilic emulsifier, the remaining content of the amino acid solution, the remaining content of the osmotic pressure regulator and the remaining content of deionized water as the external water phase;

6) Homogenize the outer water phase components at a homogenization speed of 7200-30000rpm, and at the same time add the W/O-type primary emulsion components prepared in step (3) to it, after homogenizing for 1-15 minutes, select the ultrasonic power of 20%- 30%, ultrasonication for 5 seconds and stop for 5 seconds, ultrasonication of the emulsion for 1 to 20 minutes, stirring until the system is uniform and cooled down to room temperature naturally to make a W/O/W multiple emulsion;

7) Configure the amino acid solution with the same concentration as in step 3), disperse the obtained multiple emulsion in the amino acid solution, wherein the volume ratio of the multiple emulsion to the amino acid solution is 5:1 to 1:5, and pass nitrogen gas to remove the multiple emulsion Organic solvent, prepared multivesicular liposome suspension coated with nicotinamide.

Example 2

A multivesicular liposome coated with nicotinamide, calculated by weight percentage, its raw material composition and content are as follows:

Phospholipids 10.0%;

Neutral lipid 5.0%;

Cholesterol 5.0%;

Organic solvent 12.5%;

Niacinamide 2.5%;

Hydrophilic emulsifier 6.0%;

Amino acid 0.5%;

Osmotic pressure regulator 5.0%;

Deionized water balance;

The phospholipid is one or a mixture of hydrogenated lecithin and soybean lecithin;

Described neutral substance is glyceric acid;

Described organic solvent is ethanol;

The hydrophilic emulsifier is one or a mixture of polyoxyethylene-polyoxypropylene block copolymer and PEG-100 stearate;

The amino acid is aspartic acid;

The osmotic pressure regulator is sucrose;

The above-mentioned preparation method of multivesicular liposomes coated with nicotinamide specifically comprises the following steps:

1) Weighing phospholipids, neutral lipids, cholesterol, organic solvents, hydrophilic emulsifiers, nicotinamide, amino acids, osmotic pressure regulators and deionized water by weight percentage;

2) dissolving phospholipids, cholesterol and neutral lipids in an organic solvent as an organic phase;

3) Prepare 1~100mmol/L amino acid solution, mix nicotinamide, 30~60% amino acid solution, 30~60% osmotic pressure regulator and 30~60% deionized water as the inner water phase;

4) Add the internal water phase obtained in step 3) into the organic phase, homogenize the organic phase components at a homogenization speed of 7200-30000rpm, and simultaneously add the internal water phase components, homogenize for 1-15min, and obtain W/ O-type primary emulsion;

5) mixing the hydrophilic emulsifier, the remaining content of the amino acid solution, the remaining content of the osmotic pressure regulator and the remaining content of deionized water as the external water phase;

6) Homogenize the outer water phase components at a homogenization speed of 7200-30000rpm, and at the same time add the W/O-type primary emulsion components prepared in step (3) to it. After homogenizing for 1-15 minutes, select the ultrasonic power of 20%- 30%, ultrasonication for 5 seconds and stop for 5 seconds, ultrasonication of the emulsion for 1 to 20 minutes, stirring until the system is uniform and cooled down to room temperature naturally to make a W/O/W multiple emulsion;

7) Configure the amino acid solution with the same concentration as in step 3), disperse the obtained multiple emulsion in the amino acid solution, wherein the volume ratio of the multiple emulsion to the amino acid solution is 5:1 to 1:5, and pass nitrogen gas to remove the multiple emulsion Organic solvent, prepared multivesicular liposome suspension coated with nicotinamide.

Example 3

A multivesicular liposome coated with nicotinamide, calculated by weight percentage, its raw material composition and content are as follows:

Phospholipids 20.0%;

Neutral Lipid 10.0%;

Cholesterol 10.0%;

Organic solvent 20.0%;

Niacinamide 5.0%;

Hydrophilic emulsifier 12.0%;

Amino acid 1.0%;

Osmotic pressure regulator 8.0%;

Deionized water 14.0%;

Described phosphoric acid is phosphatidylethanolamine;

The neutral lipid is one or a mixture of tricaprylin and vitamin E;

Described organic solvent is butanol;

The hydrophilic emulsifier is one or a mixture of peptide bimolecular lipophilic and hydrophilic surfactants, cetearyl alcohol and cetearyl glucoside;

The amino acid is L-arginine;

Described osmotic pressure regulator is physiological saline;

The above-mentioned preparation method of multivesicular liposomes coated with nicotinamide specifically comprises the following steps:

1) Weighing phospholipids, neutral lipids, cholesterol, organic solvents, hydrophilic emulsifiers, nicotinamide, amino acids, osmotic pressure regulators and deionized water by weight percentage;

2) dissolving phospholipids, cholesterol and neutral lipids in an organic solvent as an organic phase;

3) Prepare 1~100mmol/L amino acid solution, mix nicotinamide, 30~60% amino acid solution, 30~60% osmotic pressure regulator and 30~60% deionized water as the inner water phase;

4) Add the internal water phase obtained in step 3) into the organic phase, homogenize the organic phase components at a homogenization speed of 7200-30000rpm, and simultaneously add the internal water phase components, homogenize for 1-15min, and obtain W/ O-type primary emulsion;

5) mixing the hydrophilic emulsifier, the remaining content of the amino acid solution, the remaining content of the osmotic pressure regulator and the remaining content of deionized water as the external water phase;

6) Homogenize the outer water phase components at a homogenization speed of 7200-30000rpm, and at the same time add the W/O-type primary emulsion components prepared in step (3) to it. After homogenizing for 1-15 minutes, select the ultrasonic power of 20%- 30%, ultrasonication for 5 seconds and stop for 5 seconds, ultrasonication of the emulsion for 1 to 20 minutes, stirring until the system is uniform and cooled down to room temperature naturally to make a W/O/W multiple emulsion;

7) Configure the amino acid solution with the same concentration as in step 3), disperse the obtained multiple emulsion in the amino acid solution, wherein the volume ratio of the multiple emulsion to the amino acid solution is 5:1 to 1:5, and pass nitrogen gas to remove the multiple emulsion Organic solvent, prepared multivesicular liposome suspension coated with nicotinamide.

The above content is only a basic description of the concept of the present invention, and any equivalent transformation made according to the technical solution of the present invention shall belong to the protection scope of the present invention.

Claims (5)

1. a kind of many vesicles of cladding niacinamide, it is characterised in that count by weight percentage, its raw material composition and contain Amount is as follows：

Phosphatidase 1 .0 ~ 20.0%；

Neutral lipid 1.0 ~ 10.0%；

Cholesterol 1.0 ~ 10.0%；

Organic solvent 5.0 ~ 20.0%；

Niacinamide 0.01 ~ 5.0%；

Hydrophilic emulsifier 0.1 ~ 12.0%；

Amino acid 0.1 ~ 1.0%；

Osmotic pressure regulator 2.0 ~ 8.0%；

Deionized water surplus；

Described phosphoric acid be lecithin, hydrolecithin, soybean lecithin, phosphatidyl-ethanolamine, DSPC, two In dimyristoylphosphatidycholine, DOPE or DPPG one or two with On the mixture that constituted；

Described neutral lipid is olein, glyceric acid, glyceryl laurate ester, decanoin, three sad glycerine One or more mixtures for being constituted in ester or vitamin E；

Described organic solvent is by one or more mixing for constituting in ether, ethanol, butanol or ethyl acetate Thing；

Described hydrophilic emulsifier is that Tween 80, polyox-yethylene-polyoxypropylene block copolymer, peptides bimolecular oleophylic are hydrophilic Table work, PEG-100 stearates, stearine, arachidic alcohol and docosyl alcohol and arachidic alcohol glucoside, cetostearyl alcohol and whale Wax stearyl glucoside, AEO（21EO）, in Compritol 888 ATO or cetearyl glucoside one Plant or two or more constituted mixtures；

Described amino acid is lysine, asparatate, serine, L-arginine, alanine, L-aminobutanedioic acid, glutamic acid, sweet One or more mixture in propylhomoserin, histidine, tryptophan, tyrosine, proline, leucine or valine；

Described osmotic pressure regulator is one or more the mixture in glucose, sucrose or physiological saline.

2. many vesicles of a kind of cladding niacinamide as claimed in claim 1, it is characterised in that by weight percentage Calculate, its raw material composition and content are as follows：

Phosphatidase 1 .0%；

Neutral lipid 1.0%；

Cholesterol 1.0%；

Organic solvent 5.0%；

Niacinamide 0.01%；

Hydrophilic emulsifier 0.1%；

Amino acid 0.1%；

Osmotic pressure regulator 2.0%；

Deionized water surplus；

Described phosphatide is lecithin；

Described neutral grease is olein；

Described organic solvent is ether；

Described hydrophilic emulsifier is Tween 80；

Described amino acid is lysine；

Described osmotic pressure regulator is glucose.

3. many vesicles of a kind of cladding niacinamide as claimed in claim 1, it is characterised in that by weight percentage Calculate, its raw material composition and content are as follows：

Phosphatidase 1 0.0%；

Neutral lipid 5.0%；

Cholesterol 5.0%；

Organic solvent 12.5%；

Niacinamide 2.5%；

Hydrophilic emulsifier 6.0%；

Amino acid 0.5%；

Osmotic pressure regulator 5.0%；

Deionized water surplus；

Described phosphatide is the mixture of hydrolecithin or one or two compositions in soybean lecithin；

Described neutral substance is glyceric acid；

Described organic solvent is ethanol；

Described hydrophilic emulsifier is in polyox-yethylene-polyoxypropylene block copolymer or PEG-100 stearates Plant or two kinds of mixtures for being constituted；

Described amino acid is asparatate；

Described osmotic pressure regulator is sucrose.

4. many vesicles of a kind of cladding niacinamide as claimed in claim 1, it is characterised in that by weight percentage Calculate, its raw material composition and content are as follows：

Phosphatidase 2 0.0%

Neutral lipid 10.0%；

Cholesterol 10.0%；

Organic solvent 20.0%；

Niacinamide 5.0%；

Hydrophilic emulsifier 12.0%；

Amino acid/11 .0%；

Osmotic pressure regulator 8.0%；

Deionized water surplus；

Described phosphoric acid is phosphatidyl-ethanolamine；

Described neutral lipid is by one or two mixtures for constituting in tricaprylin, vitamin E；

Described organic solvent is butanol；

Described hydrophilic emulsifier is in the hydrophilic table work of peptides bimolecular oleophylic, cetostearyl alcohol and cetearyl glucoside One or two mixtures for being constituted；

Described amino acid is L-arginine；

Described osmotic pressure regulator is physiological saline.

5. a kind of preparation method of many vesicles of the cladding niacinamide described in claims 1,2,3 or 4, its feature exists In specifically including following steps：

1）Phosphatide, neutral lipid, cholesterol, organic solvent, hydrophilic emulsifier, niacinamide, amino are weighed by weight percentage Acid, osmotic pressure regulator and deionized water；

2）Phosphatide, cholesterol and neutral lipid are dissolved in organic solvent, as organic phase；

3）The Freamine Ⅲ of 1 ~ 100mmol/L of configuration, by niacinamide, 30 ~ 60% Freamine Ⅲ, 30 ~ 60% osmotic pressure Conditioning agent and the mixing of 30 ~ 60% deionized water, as interior water phase；

4）By step 3）Water is added in organic phase in middle gained, with homogeneous speed 7200～30000rpm homogeneous organic phase groups Point, while interior water phase components are added thereto, 1～15min of homogeneous, w/o type colostric fluid is obtained；

5）By hydrophilic emulsifier, the Freamine Ⅲ of remaining content, the osmotic pressure regulator of remaining content and remaining content The mixing of deionized water, as outer water phase；

6）With the outer water phase components of homogeneous 7200～30000rpm of speed homogeneous, while by step（3）Obtained w/o type colostric fluid group Point be added thereto, after 1～15min of homogeneous, select ultrasonic power 20%～30%, ultrasound to stop 5 seconds in 5 seconds, to emulsion ultrasound 1～ 20min, stirs to system that in the lump natural cooling is down to room temperature, makes W/O/W type multiple emulsions；

7）Configuration with step 3) in concentration identical Freamine Ⅲ, the multiple emulsion for obtaining is scattered in Freamine Ⅲ, Wherein multiple emulsion and the volume ratio of Freamine Ⅲ are 5:1～1:5, the organic solvent that nitrogen is removed in multiple emulsion is passed through, Many vesicles suspension of cladding niacinamide are obtained.