CN110721096A

CN110721096A - Method for preparing lecithin nano-emulsion capable of being filtered through sterilization grade and nano-emulsion obtained by method

Info

Publication number: CN110721096A
Application number: CN201910986357.4A
Authority: CN
Inventors: 胡嘉奂; 贺来健
Original assignee: Fritillaria Maternal And Infant Products (shanghai) Co Ltd
Current assignee: Fritillaria Maternal And Infant Products (shanghai) Co Ltd
Priority date: 2019-10-17
Filing date: 2019-10-17
Publication date: 2020-01-24

Abstract

The present invention provides a method for preparing a lecithin nanoemulsion filterable by sterilization grade, wherein the method comprises a step of inserting an auxiliary surfactant into the lecithin nanoemulsion. The invention also provides lecithin nanoemulsion obtained by the method and capable of passing through a sterilization grade filter, wherein the average particle size of the lecithin nanoemulsion is about 100 nanometers, and the lecithin nanoemulsion can pass through a 0.22 micron sterilization grade filter.

Description

Method for preparing lecithin nano-emulsion capable of being filtered through sterilization grade and nano-emulsion obtained by method

Technical Field

The invention provides a method for preparing lecithin nanoemulsion capable of being filtered by a sterilization grade and the lecithin nanoemulsion capable of being filtered by the sterilization grade obtained by the method.

Background

In 1844 Gohley, French, discovered lecithin from egg yolk and was named Lecithos (lecithin) in Greek. Lecithin is a mixture of animal and plant tissues and yolk, and is a yellow brown greasy substance, and its components include phosphoric acid, choline, fatty acid, glycerol, glycolipid, triglyceride and phospholipid.

Lecithin is an important component of cell membranes and has extremely high biocompatibility. Lecithin is broadly defined as a variety of phospholipid products, including Phosphatidylcholine (PC), Phosphatidylethanolamine (PE), Phosphatidic Acid (PA), Phosphatidylinositol (PI), etc., and in the narrow sense, lecithin refers to phosphatidylcholine. The higher the purity of PC, the smaller the odor and the stronger the emulsifying property. The lecithin has a tail with a double-hydrophobic structure, can be directly dispersed in water to form vesicles which are in an ordered phospholipid bilayer structure, so that the lecithin meets the condition of an emulsifier in the surfactant and can serve as the emulsifier to a certain extent.

However, lecithin is difficult to apply in cosmetics. The prior art mainly discloses the use of lecithin for the preparation of liposomes, microemulsions and nanoemulsions, wherein both microemulsion and nanoemulsion technologies require the addition of preservatives or preservative systems to meet the microbiological legislation requirements of existing cosmetics when applied to cosmetics. As the demand and call for preservative-free cosmetics have become higher in recent years, a trend is toward preservative-free microemulsions and nanoemulsions.

The sterilization filtration is a stable and efficient sterilization method, and can avoid the impact of high-temperature sterilization on the stability of the emulsion. Neither the prior lecithin microemulsions or nanoemulsions for cosmetic use have been reported to be filterable by a 0.22 micron sterilization scale.

Therefore, there is an urgent need to develop a method for preparing lecithin nanoemulsion filterable by sterilization grade and lecithin nanoemulsion filterable by sterilization grade obtained by the method.

Disclosure of Invention

The inventor surprisingly finds that a conical auxiliary surfactant can be embedded into the lecithin nanoemulsion through a mixed micelle technology, so that the structure of the lecithin nanoemulsion is more compact and complete, the probability of the lecithin nanoemulsion attached to the surface of a filter membrane is reduced, and the filtering efficiency is improved.

The method for preparing lecithin nanoemulsion capable of being filtered through a sterilization grade can be used for industrial production of cosmetics.

Accordingly, in one aspect, the present invention provides a method for preparing a lecithin nanoemulsion filterable by sterilization grade, wherein the method comprises a step of embedding an auxiliary surfactant into the lecithin nanoemulsion by a mixed micelle technique.

The term "mixed micelle technique" as used according to the present invention has the general meaning known to those skilled in the art, and refers to the intercalation of a co-surfactant into lecithin nanomolecules to form mixed micelles.

According to a preferred embodiment of the present invention, the secondary surfactant is tapered. Generally, the structure of lecithin when forming emulsion droplets is of the reverse cone type. The inventor surprisingly finds that according to the space accumulation parameter theory, the emulsifier with the cone-shaped molecular structure can be well embedded into the surface layer of lecithin emulsion droplets, so that the emulsion droplet structure is more compact. Therefore, the lecithin nanoemulsion with the average particle size of about 100 nanometers can be prepared by embedding the auxiliary surfactant into the lecithin nanoemulsion, and the lecithin nanoemulsion can easily pass through a 0.22-micrometer sterilization grade filter.

According to a preferred embodiment of the present invention, the auxiliary surfactant is selected from one or more of sucrose laurate, decaglycerol laurate and PEG-40 hydrogenated castor oil.

According to a preferred embodiment of the invention, the method comprises the steps of:

1) dispersing lecithin in an oil phase, and then adding a water phase to be homogenized and dispersed completely to obtain lecithin nanoemulsion;

2) and embedding an auxiliary surfactant into the lecithin nanoemulsion, and homogenizing under high pressure to obtain the lecithin nanoemulsion capable of being filtered at a sterilization level.

Another aspect of the present invention provides lecithin nanoemulsion filterable by sterilization grade obtained according to the method, wherein the lecithin nanoemulsion has an average particle size of around 100 nm and can pass through a sterilization grade filter of 0.22 μm.

According to a preferred embodiment of the invention, the lecithin nanoemulsion filterable by aseptic grade comprises: 65-95 wt% of water phase, 1-30 wt% of oil phase, 1-5 wt% of lecithin and 1-5 wt% of auxiliary surfactant.

According to another preferred embodiment of the invention, the lecithin nanoemulsion filterable by aseptic grade comprises: 75-90 wt% of water phase, 5-25 wt% of oil phase, 1-3 wt% of lecithin and 1-3 wt% of auxiliary surfactant.

According to a preferred embodiment of the present invention, the aqueous phase is selected from at least one of water, glycerol and glycol.

According to a preferred embodiment of the present invention, the diol is at least one selected from the group consisting of 1, 3-propanediol, 1, 2-propanediol, 1, 3-butanediol, 1, 2-pentanediol and 1, 2-hexanediol.

According to another preferred embodiment of the invention, the oil phase is selected from squalane or jojoba oil.

According to a particularly preferred embodiment of the invention, the lecithin nanoemulsion filterable by aseptic grade comprises: 30-80 wt% of water, 10-30 wt% of glycerol, 3-20 wt% of squalane or jojoba oil, 1-10 wt% of 1, 3-propylene glycol, 1-5 wt% of lecithin and 1-5 wt% of auxiliary surfactant.

More preferably, the lecithin nanoemulsion filterable by aseptic grade comprises: 50-70 wt% of water, 10-30 wt% of glycerol, 5-10 wt% of squalane or jojoba oil, 1-5 wt% of 1, 3-propylene glycol, 1-3 wt% of lecithin and 1-3 wt% of auxiliary surfactant.

According to a most preferred embodiment of the present invention, the lecithin nanoemulsion filterable by aseptic grade consists of 30-80 wt% of water, 10-30 wt% of glycerol, 3-20 wt% of squalane or jojoba oil, 1-10 wt% of 1, 3-propanediol, 1-5 wt% of lecithin and 1-5 wt% of auxiliary surfactant.

More preferably, the lecithin nanoemulsion filterable by sterilization grade consists of 50-70 wt% of water, 10-30 wt% of glycerol, 5-10 wt% of squalane or jojoba oil, 1-5 wt% of 1, 3-propanediol, 1-3 wt% of lecithin and 1-3 wt% of auxiliary surfactant.

The method for preparing lecithin nanoemulsion capable of being filtered through sterilization grade and the lecithin nanoemulsion capable of being filtered through sterilization grade obtained by the method have the advantages over the lecithin nanoemulsion of the prior art:

1. according to the method for preparing the lecithin nanoemulsion capable of being filtered through the sterilization level, the conical auxiliary surfactant is embedded into the lecithin nanoemulsion through the mixed micelle technology, so that the structure of lecithin nanoemulsion droplets is more tight and complete, the probability of the lecithin nanoemulsion droplets being attached to the surface of a filter membrane is reduced, and the filtering efficiency is improved. The lecithin nanoemulsion prepared by the preparation method can be prepared into lecithin nanoemulsion with the particle size of about 100 nanometers, and can easily pass through a 0.22 micron sterilization-level filter;

2. the lecithin nanoemulsion capable of being filtered through the sterilization grade does not need to be additionally added with a preservative, and can avoid high-temperature sterilization, so that the obtained lecithin nanoemulsion has good stability and can be stored for a long time, and therefore, the lecithin nanoemulsion can be used for industrial production of cosmetics.

Drawings

FIG. 1 is a sterile-filterable lecithin nanoemulsion prepared in example 1.

FIG. 2 shows the particle size distribution as measured by beckman LSI3320 dynamic light scattering particle size distribution meter for lecithin nanoemulsion without embedded tapered auxiliary surfactant prepared in comparative example 1.

FIG. 3 shows the particle size distribution as measured by a beckmann LSI3320 dynamic light scattering particle size distribution meter of sterile-filterable lecithin nanoemulsion prepared according to example 1 of the present invention.

Detailed Description

Example 1: preparation of the degerming filterable lecithin nanoemulsion of the invention

The preparation method comprises the following steps: adding 1.2g lecithin into 5g squalane and 1.8g 1, 3-propylene glycol, stirring for dissolving and dispersing, adding 20g glycerol, homogenizing to obtain multiphase gel, adding 1g decaglycerol laurate and 71g water, and homogenizing under high pressure by SPX-1000 high pressure homogenizer of APV company to obtain the lecithin nanoemulsion capable of sterilizing and filtering.

Example 2: preparation of the degerming filterable lecithin nanoemulsion of the invention

Serial number	Name of Chinese	Content (g)
			1	Water (W)	62
2	Glycerol	30
			3	Squalane	5
4	1, 3-propanediol	1
			5	Lecithin	1
6	Sucrose laurate	1

The preparation method comprises the following steps: adding 1g of lecithin into 5g of squalane and 1g of 1, 3-propylene glycol, stirring, dissolving and dispersing, adding 30g of glycerol, homogenizing to obtain a multiphase gel, adding 1g of sucrose laurate and 62g of water, and homogenizing under high pressure to obtain the lecithin nanoemulsion capable of being sterilized and filtered.

Example 3: preparation of the degerming filterable lecithin nanoemulsion of the invention

Serial number	Name of Chinese	Content (g)
			1	Water (W)	56
2	Glycerol	20
			3	Jojoba oil	10
4	1, 3-propanediol	10
			5	Lecithin	2
6	Sucrose laurate	2

The preparation method comprises the following steps: adding 2g of lecithin into 10g of jojoba oil and 10g of 1, 3-propylene glycol, stirring, dissolving, dispersing, adding 20g of glycerol, homogenizing to obtain multiphase gel, adding 2g of sucrose laurate and 56g of water, and homogenizing under high pressure to obtain the lecithin nanoemulsion capable of being sterilized and filtered.

Example 4: preparation of the degerming filterable lecithin nanoemulsion of the invention

Serial number	Name of Chinese	Content (g)
			1	Water (W)	32
2	Glycerol	30
			3	Squalane	20
4	1, 3-propanediol	10
			5	Lecithin	3
6	PEG-40 hydrogenated Castor oil	5

The preparation method comprises the following steps: adding 3g of lecithin into 20g of squalane and 10g of 1, 3-propylene glycol, stirring, dissolving and dispersing, adding 30g of glycerol, homogenizing to obtain a multiphase gel, adding 5g of PEG-40 hydrogenated castor oil and 32g of water, and homogenizing under high pressure to obtain the lecithin nanoemulsion capable of being sterilized and filtered.

Comparative example 1: preparation of lecithin nanoemulsion without cone-embedded auxiliary surfactant

Serial number	Name of Chinese	Content (g)
			1	Water (W)	63
2	Glycerol	30
			3	Squalane	5
4	1, 3-propanediol	1
			5	Lecithin	1

The preparation method comprises the following steps: adding 1g lecithin into 5g squalane and 1g 1, 3-propylene glycol, stirring for dissolving and dispersing, adding 20g glycerol, homogenizing to obtain multiphase gel, adding 72g water, and homogenizing under high pressure by SPX-1000 high pressure homogenizer of APV company to obtain lecithin nanoemulsion capable of sterilizing and filtering.

Experimental example 1: the filtration membrane passing performance test of 25mm diameter 0.22 μm of the degerming filterable lecithin nanoemulsion prepared in example 1 of the present invention and the lecithin nanoemulsion prepared in comparative example 1 without the insertion of the tapered auxiliary surfactant was compared

First, FIGS. 2 and 3 show the particle size distributions measured by beckman LSI3320 dynamic light scattering particle size distribution meter of the sterile-filterable lecithin nanoemulsion prepared in example 1 of the present invention and the lecithin nanoemulsion prepared in comparative example 1 without the insertion of the tapered auxiliary surfactant. Those skilled in the art will appreciate that particle size distribution testing is performed by diluting the sample 20-50 times with deionized water and adding to a beckman LSI3320 dynamic light scattering particle size distribution meter. As shown in the figure, the particle size of the lecithin nanoemulsion did not change much before and after the conical auxiliary surfactant was embedded. However, when the degerming filterable lecithin nanoemulsion prepared in example 1 of the present invention and the lecithin nanoemulsion prepared in comparative example 1 without the cone-shaped embedded auxiliary surfactant were tested by passing through a 25mm diameter 0.22 μm filtration membrane, it was found that, even if all the particles were below 0.2 μm, only 10ml of the lecithin nanoemulsion could be filtered and clogged when passing through a 25mm diameter 0.22 μm filtration membrane without the cone-shaped embedded auxiliary surfactant. After the conical auxiliary surfactant is embedded, even if the particle size is not obviously changed, 100ml of lecithin nanoemulsion can easily pass through a filter membrane with the diameter of 25mm and the diameter of 0.22 micron, and is not blocked after passing.

Without wishing to be bound by any theory, the applicant has surprisingly found that: from the theory of stacking parameters, the microstructure of the emulsion droplets can be roughly estimated from the molecular structure of the emulsifier (i.e., the auxiliary surfactant of the present invention). The stacking parameter p ═ V/Ao × lc, V and lc are the volume and extended chain length of the emulsifier molecules, and Ao is the projected area of the emulsifier molecules. When the stacking parameter is between 0.5 and 1, the emulsifier molecule is in a truncated cone structure, and emulsion droplets are easy to form a double-layer structure; when the packing constant is less than 0.5, the emulsifier molecules are in a cone-shaped structure, and the emulsion droplets are easy to form a single-layer structure and can be regularly and tightly arranged on the surfaces of the emulsion droplets.

The accumulation parameter of lecithin is more than 0.5, and the lecithin is in a truncated cone structure, so that a double-layer liposome structure is easy to form, gaps are formed after the lecithin is arranged on the surface of the emulsion drop, and the surface of the emulsion drop is rough. The light is difficult to pass through after being refracted for many times, and the formed emulsion is in an opaque state. The accumulation constant of the auxiliary surfactant with the conical molecular structure is less than 0.5, and the auxiliary surfactant can be well embedded into the surface of lecithin emulsion droplets, so that the structure of the emulsion droplets is more compact and complete. After intercalation, the particle size of the emulsion droplets did not change significantly, but the emulsion was translucent due to a smoother surface and less light refraction.

Therefore, when the nano-emulsion passes through the 0.22 micron filtration membrane, the nano-emulsion without the added conical auxiliary surfactant cannot pass through although the particle size is smaller than the pore size of 0.22 micron; and the conical auxiliary surfactant can pass through the filter smoothly after being added. The auxiliary surfactant with the conical molecular structure can be well embedded into the surface layer of lecithin emulsion droplets, so that the structure of the emulsion droplets is more compact and complete, the probability of the emulsion droplets attaching to the surface of a filter membrane is reduced, and the filtration efficiency is improved. Therefore, the lecithin nanoemulsion with the average particle size of about 100 nanometers can be prepared by embedding the auxiliary surfactant into the lecithin nanoemulsion, and the lecithin nanoemulsion can easily pass through a 0.22-micrometer sterilization grade filter.

Experimental example 2: stability evaluation of lecithin nanoemulsion prepared by the present invention

The lecithin nanoemulsion prepared in examples 1-4 of the present invention was placed in a biological incubator at 5 deg.C, 40 deg.C, circulating (-5-40 deg.C, cycle 24h) and room temperature, and observed every other week, and the results are shown in the following table.

The above results show that the lecithin nanoemulsion prepared in the embodiments 1-4 of the present invention can be kept stable for three months at 5 ℃, 40 ℃, circulation (-5-40 ℃, cycle 24h) biological incubator and room temperature, and thus meets the stability requirement.

Claims

1. A method of preparing a lecithin nanoemulsion filterable by aseptic scale, wherein the method comprises the step of embedding a co-surfactant into the lecithin nanoemulsion.

2. The method of claim 1, wherein the co-surfactant is tapered.

3. The method of claim 1, wherein the co-surfactant is selected from at least one of sucrose laurate, decaglycerol laurate, and PEG-40 hydrogenated castor oil.

4. A method according to any one of claims 1-3, wherein the method comprises the steps of:

1) dispersing lecithin in an oil phase, and then adding a water phase to be homogenized and dispersed completely to obtain lecithin nanoemulsion; and

2) and (3) embedding an auxiliary surfactant into the lecithin nanoemulsion to obtain the lecithin nanoemulsion which can be filtered through a sterilization grade.

5. Lecithin nanoemulsion filterable by sterile grade obtained by the process according to any one of claims 1 to 4, wherein the lecithin nanoemulsion has an average particle size of around 100 nm and can pass through a sterile grade filter of 0.22 μm.

6. Lecithin nanoemulsion filterable by aseptic grade according to claim 5, wherein the lecithin nanoemulsion comprises: 65-95 wt% of water phase, 1-30 wt% of oil phase, 1-5 wt% of lecithin and 1-5 wt% of auxiliary surfactant.

7. Lecithin nanoemulsion filterable by aseptic grade according to claim 6, wherein the lecithin nanoemulsion comprises: 75-90 wt% of water phase, 5-25 wt% of oil phase, 1-3 wt% of lecithin and 1-3 wt% of auxiliary surfactant.

8. Lecithin nanoemulsion filterable by sterile grade according to claim 6, wherein the aqueous phase is selected from at least one of water, glycerol and glycols.

9. Lecithin nanoemulsion filterable by sterile grade according to claim 6, wherein the diol is selected from at least one of 1, 3-propanediol, 1, 2-propanediol, 1, 3-butanediol, 1, 2-pentanediol and 1, 2-hexanediol.

10. Lecithin nanoemulsion filterable by sterile grade according to claim 6, wherein the oil phase is selected from squalane or jojoba oil.

11. Lecithin nanoemulsion filterable by sterile grade according to any of claims 5-10, wherein the lecithin nanoemulsion comprises: 30-80 wt% of water, 10-30 wt% of glycerol, 3-20 wt% of squalane or jojoba oil, 1-10 wt% of 1, 3-propylene glycol, 1-5 wt% of lecithin and 1-5 wt% of auxiliary surfactant.

12. Lecithin nanoemulsion filterable by sterile grade according to any of claims 5 to 10, wherein the lecithin nanoemulsion consists of 30 to 80% by weight of water, 10 to 30% by weight of glycerol, 3 to 20% by weight of squalane or jojoba oil, 1 to 10% by weight of 1, 3-propanediol, 1 to 5% by weight of lecithin and 1 to 5% by weight of auxiliary surfactants.