CN112641667B

CN112641667B - High-stability transparent ceramide nanoemulsion gel and preparation and application thereof

Info

Publication number: CN112641667B
Application number: CN202011604982.7A
Authority: CN
Inventors: 骆晔媛; 梁蓉; 杜养标
Original assignee: Jiangsu Ruiting Biotechnology Co ltd
Current assignee: Jiangsu Ruiting Biotechnology Co ltd
Priority date: 2020-12-29
Filing date: 2020-12-29
Publication date: 2022-03-25
Anticipated expiration: 2040-12-29
Also published as: CN112641667A

Abstract

The invention discloses a high-stability transparent ceramide nanoemulsion gel and a preparation method and application thereof, wherein the ceramide nanoemulsion gel comprises ceramide, a solvent, a cosolvent, an emulsifier and water; according to the total mass percentage of the raw materials, the ceramide is 0.1-5%, the solvent is 1-10%, the cosolvent is 50-90%, the emulsifier is 0.5-10%, and the balance is water to 100%. The high-stability transparent ceramide nanoemulsion gel prepared by the invention is transparent viscous liquid to transparent gelatinous solid, and has no obvious change in particle size after being placed at minus 20 ℃ and 50 ℃ for 6 months. The invention provides a preparation method of a high-stability transparent ceramide nanoemulsion gel and application of the high-stability transparent ceramide nanoemulsion gel in the field of cosmetics.

Description

High-stability transparent ceramide nanoemulsion gel and preparation and application thereof

Technical Field

The invention belongs to the technical field of micro-nano carriers, and particularly relates to a high-stability transparent ceramide nanoemulsion gel and preparation and application thereof.

Background

Ceramide is present in all eukaryotic cells and has important regulation effects on cell differentiation, proliferation, apoptosis, aging and other vital activities. Ceramide is used as a main component of intercellular lipid of stratum corneum of skin, is not only used as a second messenger molecule in a sphingomyelin pathway, but also plays an important role in the formation process of the stratum corneum of the skin, and has the effects of maintaining skin barrier, preserving moisture, resisting aging, whitening, treating diseases and the like.

In view of the special function and curative effect of ceramide on skin, ceramide is also rapidly becoming a novel high-grade cosmetic bioactive additive for skin care, hair care and the like in recent years. However, because of the problems of poor solubility and recrystallization of ceramide, it is difficult to add ceramide at high concentration to the dosage form, so that only a very small amount of ceramide has been used in the products so far, and the use level thereof is limited to the conceptual level of raw materials.

In order to solve the above problems, in the market, a transport vehicle for ceramide is often prepared by adding a high content of components such as an emulsifier, a polyol, and cholesterol. However, most of the carriers have the defects of high content of the emulsifier, poor stability and uncertain efficacy.

In addition, the currently marketed ceramide carrier systems are mostly milky white liquid or cream, are mostly white liquid after being diluted by water, have low transparency, are mostly used in emulsion and cream formulas, and have limited application in toning lotion, facial mask liquid and essence due to low transparency.

Disclosure of Invention

This section is for the purpose of summarizing some aspects of embodiments of the invention and to briefly introduce some preferred embodiments. In this section, as well as in the abstract and the title of the invention of this application, simplifications or omissions may be made to avoid obscuring the purpose of the section, the abstract and the title, and such simplifications or omissions are not intended to limit the scope of the invention.

The present invention has been made keeping in mind the above and/or other problems occurring in the prior art.

Therefore, the present invention aims to overcome the defects in the prior art and provide a high-stability transparent ceramide nanoemulsion gel.

In order to solve the technical problems, the invention provides the following technical scheme: a high-stability transparent ceramide nanoemulsion gel comprises ceramide, a solvent, a cosolvent, an emulsifier and water; according to the total mass percentage of the raw materials, the ceramide is 0.1-5%, the solvent is 1-10%, the cosolvent is 50-90%, the emulsifier is 0.5-10%, and the balance is water to 100%.

As a preferable embodiment of the high-stability transparent ceramide nanoemulsion gel of the present invention, wherein: the nano emulsion gel is transparent viscous liquid to transparent gel solid, the particle size is 10-50 nm, and the particle size is not obviously changed after the nano emulsion gel is placed at minus 20 ℃ and 50 ℃ for 6 months.

As a preferable embodiment of the high-stability transparent ceramide nanoemulsion gel of the present invention, wherein: the ceramide comprises one or more of ceramide 2, ceramide 3 and ceramide 6.

As a preferable embodiment of the high-stability transparent ceramide nanoemulsion gel of the present invention, wherein: the solvent is one or more of octyl glyceryl ether, isostearyl glyceryl ether, oleyl glyceryl ether, PEG/PPG-dimethyl ether, n-octyl ether, perfluorobutyl methyl ether, ethyl perfluorobutyl ether, methyl perfluoroisobutyl ether and hexyl decanol myristoyl methylamino propionate.

As a preferable embodiment of the high-stability transparent ceramide nanoemulsion gel of the present invention, wherein: the cosolvent is one or more of glycerol, polyethylene glycol, polypropylene glycol and sorbitol.

As a preferable embodiment of the high-stability transparent ceramide nanoemulsion gel of the present invention, wherein: the emulsifier is one or more of polysorbate, polyoxyethylene sorbitan fatty acid ester, polyglycerol-10 lauric glyceride, polyglycerol-10 myristic glyceride, cetearyl glucoside, sucrose stearate, PEG-60 hydrogenated castor oil, cholesterol polyether-24, di (octyl dodecanol polyether) lauroyl glutamate, behenyl alcohol polyether and straight-chain fatty alcohol polyoxyethylene ether.

It is still another object of the present invention to overcome the disadvantages of the prior art and to provide a method for preparing a transparent ceramide nanoemulsion gel with high stability.

In order to solve the technical problems, the invention provides the following technical scheme: a method for preparing high-stability transparent ceramide nanoemulsion gel comprises the following steps,

mixing and dissolving ceramide and a solvent, and heating to 70-90 ℃ to obtain a phase A;

mixing and dissolving a cosolvent, an emulsifier and water, and heating to 70-90 ℃ to obtain a phase B;

and adding the phase A into the phase B system, uniformly dispersing and mixing at a high speed, and obtaining the high-stability transparent ceramide nanoemulsion gel by adopting a high-pressure microchannel multiphase flow technology.

As a preferred scheme of the preparation method of the high-stability transparent ceramide nanoemulsion gel, the preparation method comprises the following steps: the high-pressure microchannel multiphase flow technology has the pressure of 30-50 MPa and the homogenization times of 2-4.

Another object of the present invention is to overcome the disadvantages of the prior art and provide a method for preparing a high-stability transparent ceramide nano-emulsion gel, which is applied to cosmetics selected from one or more of facial cleanser, facial mask, lotion or emulsion, cream and essence.

The invention has the beneficial effects that:

(1) the high-stability transparent ceramide nanoemulsion gel prepared by the invention is transparent viscous liquid to transparent gelatinous solid, and has no obvious change in particle size after being placed at minus 20 ℃ and 50 ℃ for 6 months. The invention provides a preparation method of a high-stability transparent ceramide nanoemulsion gel and application of the high-stability transparent ceramide nanoemulsion gel in the field of cosmetics.

(2) The high-stability transparent ceramide nano-emulsion gel prepared by the invention can be applied to facial cleanser, facial mask, cosmetic water or emulsion, cream and essence, especially transparent cosmetic water, facial mask and essence, and the product is transparent and uniform and can be kept stable in shelf life. The invention adopts a high-pressure microchannel multiphase flow technology, expands the application of the technology in the preparation of the micro-nano emulsion for cosmetics, saves energy, has low consumption and can realize continuous production.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without inventive exercise. Wherein:

FIG. 1 is a particle size distribution diagram of the nano emulsion prepared in example 1 of the present invention.

FIG. 2 is an appearance diagram of a product (transparent liquid-transparent semi-gel-transparent gel) obtained in example of the present invention.

Detailed Description

In order to make the aforementioned objects, features and advantages of the present invention more comprehensible, specific embodiments thereof are described in detail below with reference to examples of the specification.

In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, but the present invention may be practiced in other ways than those specifically described and will be readily apparent to those of ordinary skill in the art without departing from the spirit of the present invention, and therefore the present invention is not limited to the specific embodiments disclosed below.

Furthermore, reference herein to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one implementation of the invention. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments.

Example 1

Preparing samples according to the raw material proportion in the table 1, mixing ceramide and a solvent to obtain an oil phase, and magnetically stirring the oil phase in a water bath kettle at the temperature of 85 ℃ until the ceramide and the solvent are completely dissolved;

mixing emulsifier and cosolvent to obtain water phase, and heating in 85 deg.C water bath to dissolve completely;

adding the oil phase into the water phase, dispersing at 16000rpm for 3min, and circulating for 3 times at 35MPa by high-pressure microchannel multiphase flow technology to obtain the final product.

TABLE 1 raw material proportioning Table (unit:%)

Note: ●: an opaque gel; very good: a translucent gel; o: transparent gel

Example 2

Ceramide 2:0.2g

Ceramide 3: 0.6g

Ceramide 6: 0.2g

Hexyldecanol myristoyl methylamino propionate: 5g

C11-14 straight-chain fatty alcohol-polyoxyethylene ether: 2g

Cholesterol polyether-24: 2g

Sorbitol: 50g

Water: the balance, total 100g

Mixing ceramide and hexyldecanol myristoyl methylamino propionate to obtain an oil phase, and magnetically stirring in a water bath kettle at 85 ℃ until the ceramide and the myristoyl methylamino propionate are completely dissolved; mixing C11-14 straight-chain fatty alcohol-polyoxyethylene ether, cholesterol polyether-24 and glycerol to obtain a water phase, and heating in a water bath kettle at 85 ℃ until the water phase is completely dissolved; adding the oil phase into the water phase, dispersing at 18000rpm for 3min to obtain primary emulsion. The primary emulsion is divided into 5 parts:

(1) sampling is carried out after 2 times (sample 1), 3 times (sample 2), 4 times (sample 3), 5 times (sample 4) and 6 times (sample 5) of circulation respectively by adopting a high-pressure microchannel multiphase flow technology at 40 MPa.

(2) Sampling was performed after 4 cycles (sample 6) using a high pressure microchannel multiphase flow technique at 20 MPa.

(3) Sampling was performed after 4 cycles (sample 7) using a high pressure microchannel multiphase flow technique at 30 MPa.

(4) Sampling was performed after 4 cycles (sample 8) using a high pressure microchannel multiphase flow technique at 50 MPa.

(5) The sample is sampled after 4 cycles (sample 9) by adopting a high-pressure microchannel multiphase flow technology under 60 MPa.

The particle size and stability results at different temperatures for each sample are shown in table 2 below:

TABLE 2

From the results of the above table, it can be seen that: the particle size of the system is gradually reduced along with the increase of pressure, and when the pressure reaches 40MPa, the particle size changes basically and stably; the particle size gradually decreased with increasing cycle number, and the particle size varied substantially smoothly when 4 times were reached.

Based on a large amount of experimental data, the preferred process: by adopting a high-pressure micro-channel multiphase flow technology, when the pressure is 30-50 MPa and the cycle time is 2-4 times, the ceramide nanoemulsion gel with the particle size range of 10-50 nm and capable of being placed for a long time at the temperature of-20 ℃ and 50 ℃ can be obtained under the conditions.

Example 3

Ceramide 2:0.5g

Ceramide 3: 1.5g

Ceramide 6: 0.5g

PEG/PPG-dimethyl ether: 3g

Methyl perfluoroisobutyl ether: : 3g

Polyglycerol-10 lauric acid glycerol ester: 1g

Cholesterol polyether-24: 3g

Polyethylene glycol: 50g

Water: the balance, total 100g

Mixing ceramide, PEG/PPG-dimethyl ether and methyl perfluoro isobutyl ether to obtain oil phase, and magnetically stirring in 85 deg.C water bath until completely dissolved; mixing cholesterol polyether-24, polyglycerol-10 lauric glyceride and polyethylene glycol-400 to obtain water phase, and heating in 85 deg.C water bath to dissolve completely; adding the oil phase into the water phase, dispersing at 16000rpm for 3min to obtain primary emulsion. The primary emulsion is divided into two parts:

(1) the transparent ceramide nanoemulsion gel is prepared by adopting a high-pressure microchannel multiphase flow technology and circulating for 4 times (sample 1) under 40 MPa.

(2) And circulating for 7 times (sample 2) by adopting a high-pressure homogenizer under 90MPa to prepare the obtained transparent ceramide nanoemulsion gel.

The particle size and stability results at different temperatures for each sample are shown in table 3, below:

TABLE 3

From the results of the above table, it can be seen that: compared with a high-pressure homogenizer, the system has the advantages that the high-pressure microchannel multiphase flow technology is more effective and energy-saving, and the ceramide nanoemulsion gel with smaller and more stable particle size can be obtained under lower pressure and cycle frequency.

Example 4

Ceramide 2:0.5g

Ceramide 3: 1.5g

Ceramide 6: 0.5g

Hexyldecanol myristoyl methylamino propionate: 5g

Cholesterol polyether-24: 2g

PEG-60 hydrogenated castor oil: 1g

Polyethylene glycol-400: 40g of

Water: the balance, total 100g

Mixing ceramide and hexyldecanol myristoyl methylamino propionate to obtain an oil phase, and magnetically stirring in a water bath kettle at 85 ℃ until the ceramide and the myristoyl methylamino propionate are completely dissolved; mixing cholesterol polyether-24, PEG-60 hydrogenated castor oil, and polyethylene glycol-400 to obtain water phase, and heating in water bath at 85 deg.C to dissolve completely; adding the oil phase into the water phase, dispersing at 18000rpm for 3min, and then circulating for 2 times at 40MPa by adopting a high-pressure microchannel multiphase flow technology to prepare the transparent ceramide nanoemulsion gel.

The obtained nano emulsion is transparent gel, and the particle size is measured to be 30nm by adopting a Zeta potential and nano particle size analyzer.

Example 5

Ceramide 2:1g

Ceramide 3: 3g

Ceramide 6: 1g

N-octyl ether: 10g

Polysorbate-60: 2g

Di (octyldodecanol polyether) lauroyl glutamate: 2g

C11-14 straight-chain fatty alcohol-polyoxyethylene ether: 1g

Sorbitol: 50g

Water: the balance, total 100g

Mixing ceramide and n-octyl ether to obtain oil phase, and magnetically stirring in a water bath kettle at 85 ℃ until the ceramide and the n-octyl ether are completely dissolved; mixing polysorbate-60, di (octyl dodecyl polyether) lauroyl glutamate, C11-14 linear fatty alcohol polyoxyethylene ether, and sorbitol to obtain water phase, and heating in 85 deg.C water bath to dissolve completely; adding the oil phase into the water phase, dispersing at 16000rpm for 3min, and circulating for 3 times at 45MPa by high-pressure microchannel multiphase flow technology to obtain the transparent ceramide nanoemulsion gel.

The obtained nano emulsion is transparent gel, and the particle size is measured to be 28nm by adopting a Zeta potential and nano particle size analyzer.

Example 6

The samples of examples 4 and 5 were placed at 50 ℃, 25 ℃ and-20 ℃ respectively, and the particle size stability was measured, and the results are shown in Table 4.

TABLE 4 particle size storage stability

Example 7

Example 4 was added to the mask solution and the stability of the mask solution was tested. The mask formulation is shown in table 5.

TABLE 5 facial mask formula

Name of raw materials	Addition amount (%)
		Water (W)	87.20
Ceramide nanoemulsion gels	2.00
		Butanediol	3.00
1, 3-propanediol	3.00
		Hydroxy phenyl methyl ester	0.10
EDTA disodium salt	0.10
		Carbomer	0.20
Polydimethylsiloxane	3
		Tocopherol acetate	0.1
Glycerol stearate citrate	0.8
		Phenoxyethanol, ethylhexyl glycerol	0.5

Example 8

Example 5 was added to the serum and the stability of the serum was tested. The essence formula is shown in table 6.

TABLE 6 essence formula

Name of raw materials	Addition amount (%)
		Water (W)	89.68
Ceramide nanoemulsion gels	3.00
		Acrylamide dimethyl ammonium taurate/VP copolymer	0.30
Glycerol	3.00
		Butanediol	3.00
Hyaluronic acid sodium salt	0.02
		Trehalose	0.50
Phenoxyethanol, ethylhexyl glycerol	0.50

Example 9

The facial mask and the essence are respectively divided into a normal-temperature sample, a heat-resistant sample, a cold-resistant sample and an illumination sample, the normal-temperature sample is placed in a dark place, the heat-resistant sample is placed in a constant-temperature oven at 50 +/-1 ℃, the cold-resistant sample is placed in a refrigerator at-20 ℃, and the illumination sample is placed in an artificial intelligence climate box. After 3 months, the appearance, color and smell of the sample were observed, and no oil-water separation phenomenon occurred, and the results were as shown in table 7.

Table 7 formulation stability testing

Experimental results show that after the high-stability transparent ceramide nanoemulsion gel is compounded with a matrix, the phenomenon of obvious color change and layering does not occur after the compound is placed for 3 months at normal temperature, high temperature, low temperature and illumination, and the practical application requirements can be met.

Aiming at the problems of poor stability and low transparency of the ceramide transport carrier at present, the nano-emulsion and the gel system are organically combined, and the system is converted into the nano-emulsion gel by forming a space network structure at room temperature through compatibility among a selected special solvent, a cosolvent and a surfactant while the nano-particle size of the carrier particles is ensured. The nano-emulsion gel integrates the dual characteristics of nano-emulsion and gel, not only improves the stability of a nano-emulsion mixing system, but also improves the dispersibility of the gel, and the unique structure and functional characteristics of the nano-emulsion gel endow the nano-emulsion gel with application prospects in the field of cosmetics.

The invention also solubilizes ceramide by using series ether solvents, reduces the grain diameter of the system, keeps the transparency of the diluted system and is beneficial to adding in a transparent cosmetic system.

The high-pressure microchannel multiphase flow technology of the invention is that materials pass through a combined microchannel which can generate turbulent flow, laminar flow and opposite impact cavitation jet under specific pressure, and the materials realize high-efficiency ultramicro crushing, homogenizing and emulsifying under the triple actions of high-speed shearing effect, high-pressure jet opposite impact energy and cavitation effect generated by instantaneous pressure drop of a flow channel, and the emulsified particle size can reach nanometer level. The invention combines the high-pressure micro-channel multiphase flow technology, utilizes the selection of special ether solvents and the compatibility of the emulsifying agent and the cosolvent to prepare the high-stability transparent ceramide nano-emulsion gel which can be used for a transparent cosmetic product system.

It should be noted that the above-mentioned embodiments are only for illustrating the technical solutions of the present invention and not for limiting, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, which should be covered by the claims of the present invention.

Claims

1. A high-stability transparent ceramide nanoemulsion gel is characterized in that: comprises ceramide, solvent, cosolvent, emulsifier and water;

according to the total mass percentage of the raw materials, the ceramide is 0.1-5%, the solvent is 1-10%, the cosolvent is 50-90%, the emulsifier is 0.5-10%, and the balance is water to 100%; wherein the content of the first and second substances,

the solvent is one or more of octyl glyceryl ether, isostearyl glyceryl ether, oleyl glyceryl ether, PEG/PPG-dimethyl ether, n-octyl ether, perfluorobutyl methyl ether, ethyl perfluorobutyl ether, methyl perfluoroisobutyl ether and hexyl decanol myristoyl methylamino propionate;

the cosolvent is one or more of glycerol, polyethylene glycol, polypropylene glycol and sorbitol;

the emulsifier is one or more of polysorbate, polyglycerol-10 lauric glyceride, polyglycerol-10 myristic acid glyceride, PEG-60 hydrogenated castor oil, cholesterol polyether-24, di (octyl dodecanol polyether) lauroyl glutamate and straight-chain fatty alcohol polyoxyethylene ether;

the preparation method of the high-stability transparent ceramide nanoemulsion gel comprises the steps of mixing and dissolving ceramide and a solvent, and heating to 70-90 ℃ to obtain a phase A; mixing and dissolving a cosolvent, an emulsifier and water, and heating to 70-90 ℃ to obtain a phase B; and adding the phase A into the phase B system, uniformly dispersing and mixing at a high speed, and obtaining the high-stability transparent ceramide nanoemulsion gel by adopting a high-pressure microchannel multiphase flow technology.

2. The high stability transparent ceramide nanoemulsion gel of claim 1, wherein: the nano emulsion gel is transparent viscous liquid to transparent gel solid, the particle size is 10-50 nm, and the particle size is not obviously changed after the nano emulsion gel is placed at minus 20 ℃ and 50 ℃ for 6 months.

3. The high stability transparent ceramide nanoemulsion gel of claim 1, wherein: the ceramide comprises one or more of ceramide 2, ceramide 3 and ceramide 6.

4. The method for preparing the high-stability transparent ceramide nanoemulsion gel as claimed in any one of claims 1 to 3, which is characterized in that: comprises the steps of (a) preparing a mixture of a plurality of raw materials,

5. The method of preparing the high stability transparent ceramide nanoemulsion gel of claim 4, wherein: the high-pressure microchannel multiphase flow technology has the pressure of 30-50 MPa and the homogenization times of 2-4.

6. Use of the high stability transparent ceramide nanoemulsion gel according to any one of claims 1 to 3 for the preparation of cosmetics.

7. Use according to claim 6, characterized in that: the cosmetic is selected from one or more of facial cleanser, facial mask, cosmetic water or lotion, cream and essence.