CN108451787B

CN108451787B - Vitamin A alcohol-embedded nano lipid carrier and preparation method thereof

Info

Publication number: CN108451787B
Application number: CN201810504590.XA
Authority: CN
Inventors: 陈宝祺; 庞振宜; 潘颀钧; 管岚
Original assignee: SHANGHAI GELAN COSMETICS CO Ltd
Current assignee: SHANGHAI GELAN COSMETICS CO Ltd
Priority date: 2018-05-23
Filing date: 2018-05-23
Publication date: 2020-01-07
Anticipated expiration: 2038-05-23
Also published as: CN108451787A

Abstract

The invention discloses a vitamin A alcohol-embedded nano lipid carrier and a preparation method thereof, relates to the field of skin care products, and solves the problems of high irritation and poor stability when vitamin A alcohol is directly applied to skin care products, wherein the vitamin A alcohol-embedded nano lipid carrier comprises the following components, by weight, 8 ~% of Hawaii bean oil, 8 ~% of palm wax, 1 ~% of vitamin A alcohol, 8 ~% of a non-ionic surfactant, 1 ~% of an alcohol solvent, 0.1 ~% of phospholipid and the balance of water.

Description

Vitamin A alcohol-embedded nano lipid carrier and preparation method thereof

Technical Field

The invention relates to the field of skin care products, in particular to a vitamin A alcohol-embedded nano lipid carrier and a preparation method thereof.

Background

The vitamin A is A acid, A ester and A alcohol respectively, and has the main effects of removing wrinkles, resisting aging, improving rough skin, smoothing skin, enhancing the metabolic function of skin, promoting cuticle exfoliation and resisting aging. Because A acid can irritate skin when directly used, if vitamin A is used for skin care, A alcohol and A ester are used as main components, once the alcohol or ester is absorbed by skin, the vitamin A can be converted into A acid to achieve the effect of skin care, because the vitamin A can absorb light, the vitamin A is easy to deteriorate due to light irradiation and also deteriorate due to oxidation, the vitamin A needs to be protected, and if the vitamin A is used for skin protection, carrier embedding is a good choice, wherein a lipid carrier is the most excellent.

In chinese patent publication No. CN101884416A, a method for embedding vitamin a acetate is disclosed, in which milk fat globule membrane phospholipid, cholesterol, vitamin E and vitamin a acetate are mixed and then added with absolute ethanol, and then treated with a rotary evaporator, a high-speed shear and a high-pressure homogenizer respectively to obtain vitamin a acetate liposome.

The above patent, while capable of entrapping vitamin a, is used to provide different nutrition to consumers and cannot be used in skin care products. At present, the research of embedding vitamin A alcohol by adopting a nano lipid carrier and applying the vitamin A alcohol to skin care products is not reported.

Disclosure of Invention

Aiming at the defects in the prior art, the invention aims to provide a vitamin A alcohol-embedded nano lipid carrier, which is used for embedding vitamin A alcohol by matching Hawaii soybean oil, palm wax and a surfactant, and has the advantages of high embedding rate, good stability and low irritation.

In order to achieve the first purpose, the invention provides the following technical scheme:

a nanometer lipid carrier for embedding vitamin A alcohol comprises the following components in percentage by weight:

8-12% of Hawaii bean oil;

8-12% of palm wax;

1-5% of vitamin A alcohol;

8-12% of a nonionic surfactant;

1-3% of an alcohol solvent;

0.1-1% of phospholipid;

the balance being water.

By adopting the technical scheme, the components of the vitamin A alcohol embedded in the nano lipid carrier mainly comprise oil, wax, surfactant, water and the like, and the currently common oil comprises natural and synthetic oil, wherein the natural oil comprises black currant oil, echium oil, mineral oil, wheat germ oil and the like, and the common solid wax comprises solid oil palm wax, ATO888, honey wax and the like. Although common natural oils such as blackcurrant oil and echium oil have a skin-protecting effect, they contain unsaturated fatty acids, and therefore, if they are stored improperly, they are easily oxidized, which affects the application of skin care products, and at the same time, the prices of blackcurrant oil and echium oil are high, which is not suitable for commercialization.

Hawaii bean oil contains mineral, protein, unit and polyunsaturated fatty acid, and mainly contains oleic acid, palmitoleic acid, linoleic acid, linolenic acid and triglyceride. Wherein, oleic acid has the effects of moisturizing and resisting aging, and palmitoleic acid is an essential fatty acid, has the functions of skin-friendly and skin-moistening, and is an indispensable component for delaying skin and cell aging.

The macadamia oil has similar components to the oil secreted by sebaceous glands in vivo, and the main fatty acid contained in the macadamia oil has the characteristic of protecting the skin. On the other hand, the palm wax can adjust the consistency of oily products, can increase the skin luster and has a moistening effect on the skin. The main functions of the phospholipid are to increase the stability and the permeability of the vitamin A alcohol, promote the recovery of cells and effectively improve the capability of repairing skin. The compounding of the nonionic surfactant and the phospholipid can fully emulsify the water phase and the oil phase and avoid the agglomeration of particles.

Through a large number of experiments, the inventor selects the components to be matched with the embedded vitamin A alcohol, the embedding rate is close to 100%, the stability is good, and the irritation is low.

More preferably, the nonionic surfactant is any one selected from decyl glucoside, polysorbate-80, and poloxamer 188.

By adopting the technical scheme, poloxamer 188 can form a stereoscopic effect, so that particle agglomeration is avoided; decyl glucoside is a mild nonionic surfactant, can not cause dry and astringent feeling on skin, and has the characteristics of easy biodegradation, extreme mildness, no irritation, low toxicity and the like.

More preferably, the alcohol solvent is any one selected from propylene glycol, butylene glycol and pentylene glycol.

More preferably, the phospholipid is selected from any one of egg yolk lecithin, soybean lecithin and hydrogenated lecithin.

By adopting the technical scheme, the lecithin is one of the components forming the cell membrane, the three phospholipids can increase the stability and the permeability of the vitamin A alcohol, and the yolk lecithin has the best effect. The lecithin-coated product can also obviously reduce the water loss capacity of the skin after long-term use, thereby achieving the effects of water locking and moisture retention.

The second purpose of the invention is to provide a preparation method of the vitamin A alcohol-embedded nano lipid carrier, and the nano lipid carrier prepared by the method has the advantages of high embedding rate, good stability and low irritation.

In order to achieve the second purpose, the invention provides the following technical scheme:

a preparation method of a vitamin A alcohol-embedded nano lipid carrier comprises the following steps:

step one, mixing Hawaii bean oil and palm wax, heating to 85-90 ℃ at constant temperature, adding vitamin A alcohol, and uniformly mixing to form an oil phase;

step two, heating water, an alcohol solvent, a non-ionic surfactant and phospholipid to 85-90 ℃ at constant temperature to form a water phase;

adding the oil phase into the water phase, uniformly mixing, and keeping the temperature to 85-90 ℃ to form a mixed phase;

pre-emulsifying the mixed phase by using a homogenizer at the rotation speed of 8000rpm to form mixed phase emulsion;

and step five, feeding the mixed phase emulsion into a high-pressure homogenizer, pressurizing to 600bar in the high-pressure homogenizer, and circulating for 3 times to obtain the vitamin A alcohol-embedded nano lipid carrier.

By adopting the technical scheme, in order to reduce the irritation of the vitamin A alcohol and avoid oxidation, the nano lipid carrier embedded vitamin A alcohol is prepared by adopting a thermal emulsification high-pressure homogenization method, so that the embedding rate and stability can be improved, and the situation that the lipid forms complete lattices and extrudes the medicament is avoided. The periphery of the vitamin A alcohol is coated by wax, so that the medicine can be effectively released, the medicine leakage is reduced, and the irritation to the skin is reduced.

More preferably, the particle size of the vitamin A alcohol-embedded nano lipid carrier is 200-400 nm.

By adopting the technical scheme, the nano lipid carrier prepared by the invention has small particle size, increases the contact area between skin and skin care products, and has the effect of preventing moisture from losing from the skin, and the lipophilic coating outer membrane adopted by the nano lipid carrier can effectively isolate active ingredients from external unstable factors, strengthens skin-friendly property, enables the active ingredients to accurately reach the bottom layer of the skin, continuously releases the active ingredients and provides the most complete nutrients for the skin. The nano lipid carrier has a shielding effect, and for lipid carriers with the particle size of 200nm and 2 μm, the water is easy to evaporate because the holes among large particles are relatively large and the shielding rate is only 20%, while the holes among small particles are relatively small and the shielding rate can reach 60%, so the water is not easy to evaporate, and the smaller the particles are, the stronger the adhesive force is, and the better the shielding effect is.

More preferably, the embedding rate of the vitamin A alcohol-embedded nano lipid carrier is more than 86%.

By adopting the technical scheme, the proportion of the wax in the invention is 8-12%, and the vitamin A alcohol is far higher than 3%, and the vitamin A alcohol is fat-soluble, so the vitamin A alcohol can be effectively dissolved in the mixed emulsion of the oil and the wax, and has higher embedding rate.

More preferably, the interfacial potential of the vitamin A alcohol-embedded nano lipid carrier is-33 to-49 mV.

By adopting the technical scheme, the physical stability can be evaluated by measuring the interface potential, and generally when the interface potential is more than |30| mV, the system belongs to a stable state, the aggregation of the particles is low, and the main reason is that electrostatic repulsion exists between the particles. When the interface potential is between |15| - |30| mV, it indicates that the system has the possibility of agglomeration, when the interface potential is higher than |60| mV, the system has extremely high stability, and when the interface potential is lower than |5| mV, it indicates that the system has the possibility of serious agglomeration. The interfacial potential value of the nano lipid carrier prepared by the invention is-33 mV to-49 mV, which shows that the nano lipid carrier has good stability and dispersibility.

The addition amount of the skin care product is 5-10%.

In summary, compared with the prior art, the invention has the following beneficial effects:

(1) according to the invention, raw materials such as Hawaii bean oil, palm wax and surfactant are mutually matched to embed vitamin A alcohol, and the vitamin A alcohol-embedded nano lipid carrier is applied to skin care products, so that the skin care products have the advantages of low irritation, good drug release and the like, and the oxidation of the vitamin A alcohol is avoided;

(2) the embedding system can well embed vitamin A alcohol, and the embedding rate is close to 100%;

(3) the interface potential value of the nano lipid carrier prepared by the invention is-33 mV to-49 mV, and the nano lipid carrier has good stability and dispersibility.

Drawings

FIG. 1 is a flow chart of the preparation of the present invention.

Detailed Description

The invention is described in detail below with reference to the figures and examples.

Example 1: the vitamin A alcohol-embedded nano lipid carrier comprises the components and the corresponding weight percentage shown in the table 1, and the preparation flow refers to the figure 1 and is prepared by the following steps:

step one, mixing Hawaii bean oil and palm wax, heating to 85 ℃ at constant temperature, adding vitamin A alcohol, and uniformly mixing to form an oil phase;

step two, heating water, an alcohol solvent, a non-ionic surfactant and phospholipid to 85 ℃ at constant temperature to form a water phase;

adding the oil phase into the water phase, uniformly mixing, and keeping the temperature to 85 ℃ to form a mixed phase;

pre-emulsifying the mixed phase by using a homogenizer at the rotation speed of 8000rpm for 30min to form mixed phase emulsion;

Examples 2 to 9: a vitamin a alcohol-embedded nano lipid carrier, which is different from example 1 in that each component and the corresponding weight percentage thereof are shown in table 1.

TABLE 1 Components and weight percentages of examples 1-9

Examples 10 to 19: a vitamin a alcohol-embedded nano lipid carrier, which is different from example 1 in that each component and the corresponding weight percentage thereof are shown in table 2.

TABLE 2 Components and weight percentages of examples 10-19

Example 20: a vitamin a alcohol-embedded nano lipid carrier, which is different from example 1 in that the preparation method comprises the following steps:

step one, mixing Hawaii soybean oil and palm wax, heating to88 ℃ at constant temperature, adding vitamin A alcohol, and uniformly mixing to form an oil phase;

step two, heating water, an alcohol solvent, a non-ionic surfactant and phospholipid to88 ℃ at constant temperature to form a water phase;

adding the oil phase into the water phase, uniformly mixing, and keeping the temperature to88 ℃ to form a mixed phase;

pre-emulsifying the mixed phase by using a homogenizer at the rotation speed of 8000rpm for 35min to form mixed phase emulsion;

Example 21: a vitamin a alcohol-embedded nano lipid carrier, which is different from example 1 in that the preparation method comprises the following steps:

step one, mixing Hawaii soybean oil and palm wax, heating to 90 ℃ at constant temperature, adding vitamin A alcohol, and uniformly mixing to form an oil phase;

step two, heating water, an alcohol solvent, a non-ionic surfactant and phospholipid to 90 ℃ at constant temperature to form a water phase;

adding the oil phase into the water phase, uniformly mixing, and keeping the temperature to 90 ℃ to form a mixed phase;

pre-emulsifying the mixed phase by using a homogenizer at the rotation speed of 8000rpm for 40min to form mixed phase emulsion;

Comparative example 1: a nano lipid carrier for embedding vitamin a alcohol, which is different from the nano lipid carrier in example 1 in that macadamia oil is replaced by wheat germ oil with equal weight percentage.

Comparative example 2: a vitamin a alcohol-embedded nano lipid carrier, which is different from example 1 in that palm wax is replaced with castor wax in an equal weight percentage.

Comparative example 3: a vitamin a alcohol-embedded nano lipid carrier, which is different from that of example 1 in that decyl glucoside is replaced by sodium dodecyl sulfate in equal weight percentage.

In order to determine the oil concentration, wax concentration and surfactant most suitable for preparing the retinol-embedded nano lipid carrier, the inventors set the oil concentration, wax concentration, surfactant type and surfactant concentration as the condition factors of the experiment and collated them as listed in table 3.

TABLE 3 Condition factor leveling Table

Condition factor	1	2	3
				(A) Oil concentration	8	10	12
(B) Wax concentration	12	10	8
				(C) Surfactant species	Decyl glucoside	Polysorbate-80	Poloxamer 188
(D) Surfactant concentration	8％	10％	12％

According to the condition factors in table 3, 9 samples of the vitamin a alcohol-embedded nano lipid carrier were obtained by combining different conditions using the kou method, and the 9 samples were arranged in table 4.

Table 4 experimental design orthogonal meter

Since the particle size and the polydispersity index (PDI) affect the physical stability, drug release, and chemical stability of a sample, they can be important indicators of stability. Table 5 shows the particle size variation of the retinol-embedded nano-lipid carrier measured and recorded at different times, with a measurement temperature of 5 ℃.

The particle size of the sample prepared in the first day is about 200-400 nm, the particle size changes stably after thirty days due to different operating conditions.

The PDI value can be known to the distribution situation of the particle size, when the PDI is less than 0.05, the particle size is in a single distribution, when the PDI is less than 0.08, the particle size is in a nearly single distribution, when the PDI is between 0.08 and 0.7, the particle size is in a moderate dispersion system, and when the PDI is more than 0.7, the particle size is in a multi-distribution system. Table 6 shows the PDI change data at different times and the test temperature is 5 ℃. The PDI value of the sample obtained by the method is about 0.3-0.80 in the first day, so that the nano lipid carrier prepared by the method is a moderate dispersion system, and the PDI of most samples is maintained between 0.3-0.6 after thirty days of storage, so that the particle sizes of the samples are quite consistent.

TABLE 5 mean particle size measurement data of retinol-embedded nano-lipid carrier at different storage time

TABLE 6 polydispersity index (PDI) assay data for retinol-embedded nanoliposome carriers at different storage times

Table 7 shows the interfacial potentials measured at different times in the respective sets of experiments, at a test temperature of 5 ℃ and from the results measured on the first day, the distribution of the interfacial potentials was-33 mV to-49 mV, indicating that the interfacial potentials had an effect on the interfacial potentials under different conditions, and the interfacial potentials were mostly-30 mV or more except No.4 for 30 days of storage, so that the absolute values were all larger than 30mV, indicating that the dispersibility of the nano-lipid carrier prepared thereby was good. The interface potential values of the prepared samples are about-30 mV to-50 mV, which belong to a particle dispersion state with good stability, and the samples prepared by the method have good dispersibility and belong to a stable colloid distribution state.

TABLE 7 interfacial potential detection data of vitamin A alcohol-embedded nano lipid carrier at different storage times

Corresponding embodiment	Group of	Day 1 (mV)	Day 10 (mV)	Day 20 (mV)	Day 30 (mV)
						1	NO.1	-49.1±0.85	-48.4±0.41	-45.6±0.814	-44.2±0.723
2	NO.2	-34.3±0.45	-43.2±0.81	-29.1±0.912	-29.9±1.55
						3	NO.3	-33.7±1.22	-29.5±1.18	-34.7±2.08	-30.1±0.931
4	NO.4	-33.8±0.34	-32.5±1.01	-35.2±1.31	-30.5±0.922
						5	NO.5	-35.1±0.31	-31.9±0.62	-36.2±0.801	-17.6±1.55
6	NO.6	-35.5±1.71	-34.8±0.35	-28.5±1.14	-29.4±0.48
						7	NO.7	-33.7±0.86	-28.1±0.39	-29.3±1.61	-34.1±2.53
8	NO.8	-36.0±0.81	-33.1±1.15	-37.3±1.45	-34.3±1.56
						9	NO.9	-37.6±0.77	-38.5±1.40	-36.1±0.82	-41.6±1.53

The material structure is changed along with the change of the temperature, and the nano-lipid changes the crystal structure when the nano-lipid carrier is prepared by using a hot high-pressure homogenization method. The crystallinity analysis was performed on the 9 samples using differential scanning calorimetry, and the relevant analytical data were collated as table 8. As can be seen from table 8, the crystallinity was reduced when macadamia oil was added, since the crystal arrangement was incomplete due to the addition of macadamia oil, and the smaller the crystallinity, the larger the space of the crystal lattice for coating vitamin a alcohol.

TABLE 8 crystallinity of retinol-embedded nanolipid carrier samples

To find out how the embedding effect is, table 9 shows the data of the embedding rate of the vitamin a alcohol-embedded nano lipid carrier. As can be seen from table 9, the results showed that the entrapment rate was close to 100%, indicating that the lipid carrier had an excellent entrapment effect for retinol. One is that the crystallinity is less than 20%, and the nano-lipid carrier structure has a large embedding space; secondly, the proportion of the wax in the invention is 8-12%, which is much higher than 3% of vitamin A alcohol, and because the vitamin A alcohol is fat-soluble, the vitamin A alcohol can be effectively dissolved in the mixed emulsion of oil and wax, thereby having higher embedding rate.

TABLE 9 detection data of embedding rate of vitamin A alcohol-embedded nano lipid carrier

The samples obtained from examples 1-21 and comparative examples 1-3 were tested for skin irritation according to the test method in chapter 4, section sixth of the technical specifications for cosmetic safety 2015 edition. The results of the skin irritation test are shown in Table 10. from Table 10, it can be seen that, although examples 8, 18 and 19 are slightly irritating, the examples are non-irritating, and comparative examples 1 to 3 are moderately irritating, which indicates that the embedding system of the present invention can embed retinol well, and the components have good compatibility with each other, and can reduce irritation.

Table 10 skin irritation test results

The above description is only a preferred embodiment of the present invention, and the protection scope of the present invention is not limited to the above embodiments, and all technical solutions belonging to the idea of the present invention belong to the protection scope of the present invention. It should be noted that modifications and embellishments within the scope of the invention may occur to those skilled in the art without departing from the principle of the invention, and are considered to be within the scope of the invention.

Claims

1. The vitamin A alcohol-embedded nano lipid carrier is characterized by comprising the following components in percentage by weight:

hawaii soybean oil 8 ~ 12%;

8% of palm wax, 8 ~ 12%;

vitamin a alcohol 1 ~ 5%;

8% of nonionic surfactant 8 ~ 12%;

alcohol solvent 1 ~ 3%;

0.1 ~ 1% of phospholipid;

the balance of water;

the nonionic surfactant is any one of decyl glucoside, polysorbate-80 and poloxamer 188;

the phospholipid is selected from any one of egg yolk lecithin, soybean lecithin and hydrogenated lecithin;

the preparation method of the vitamin A alcohol-embedded nano lipid carrier comprises the following steps:

step one, mixing Hawaii soybean oil and palm wax, heating to 85 ~ 90 ℃ at constant temperature, adding vitamin A alcohol, and mixing uniformly to form an oil phase;

step two, heating water, alcohol solvent, nonionic surfactant and phospholipid to 85 ~ 90 ℃ at constant temperature to form a water phase;

adding the oil phase into the water phase, uniformly mixing, and keeping the temperature to 85 ~ 90 ℃ to form a mixed phase;

2. The vitamin A alcohol-embedded nano lipid carrier as claimed in claim 1, wherein the alcohol solvent is selected from any one of propylene glycol, butylene glycol and pentylene glycol.

3. The vitamin A alcohol embedded nano lipid carrier as claimed in claim 1, wherein the particle size of the vitamin A alcohol embedded nano lipid carrier is 200 ~ 400 nm.

4. The vitamin A alcohol-embedded nano lipid carrier according to claim 1, wherein the embedding rate of the vitamin A alcohol-embedded nano lipid carrier is more than 86%.

5. The vitamin A alcohol-embedded nano lipid carrier according to claim 1, wherein the interface potential of the vitamin A alcohol-embedded nano lipid carrier is-33 ~ -49 mV.