CN102688152A - Composite anti-screening agent nanostructured lipid carrier and preparation method thereof - Google Patents

Abstract

The invention discloses a nanostructured lipid carrier for a composite sunscreen agent, the carrier is loaded with active ingredients of a full-band sunscreen agent, and is characterized in that the components in the nanostructured lipid carrier are calculated by weight percentage as: composite sunscreen agent 3-40%; emulsifier 2-15%; complex lipid material 2-20%; the rest is water; the UVA sunscreen is avobenzone, and the UVB sunscreen is at least one compound selected from the following: octocrylene , Octyl p-methoxycinnamate. The composite lipid material is a mixture of solid lipid material and liquid lipid material, and the lipid material is selected from at least one of the following compounds: glycerol triacetate, acetylated monoglyceride, diethyl sebacate, caprylic acid Glyceryl Caprate, Diisopropyl Adipate, Diisopropyl Sebacate, Glyceryl Monostearate, Carnauba Wax, Behenate. The nanostructured lipid carrier has good stability and water solubility, the preparation method is simple and controllable, and has good repeatability, and can be applied to the preparation of sunscreen cosmetics.

Description

Composite sunscreen agent nanostructure lipid carrier and preparation method thereof

technical field

The invention belongs to the technical field of carrier systems in cosmetics and food preparation technology, and relates to a nano-scale carrier and a preparation method thereof, in particular to a nano-structured lipid carrier with a composite sunscreen as an active ingredient and a preparation method thereof.

Background technique

Nowadays, due to environmental pollution, the atmosphere has been damaged to varying degrees, and the impact of ultraviolet rays on the skin is becoming more and more serious. Skin can be damaged when it is exposed to the sun for a long time without taking any protective measures. The ultraviolet rays contained in sunlight are divided into long-wave ultraviolet rays (UVA) of 320nm to 400nm by the skin science community, medium-wavelength ultraviolet rays (UVB) of 280nm to 320nm, and short-wave ultraviolet rays (UVC) of 200nm to 280nm. Ultraviolet rays below 280nm are absorbed by the ozone layer and cannot reach the ground. The ultraviolet rays reaching the ground will have various effects on people's skin. Among them, UVB can cause erythema or blisters on the skin, promote the formation of melanin, cause skin pigmentation, and cause brown spots Formation. It was previously thought that UVA would not have a great impact on the skin, but it has been proved by electron microscopy or histochemical methods that excessive UVA irradiation will have a certain impact on the skin. UVA segment ultraviolet light is different from UVB, and its energy can be Reaching the dermis of the skin, it brings slow changes to the elastic fibers in the vessel wall or combined tissues. Thereby causing the browning of the skin, reducing the elasticity of the skin, promoting the occurrence of wrinkles and aging people rapidly, and also promoting erythema reactions and even triggering phototoxicity or photosensitivity reactions. Continuous UVB and UVA radiation on sensitive skin can damage DNA, reduce immunity, and even induce skin cancer. Therefore, it is increasingly important to defend against excessive UVA and UVB radiation to protect the human body from damage and delay aging.

Sunscreen cosmetics are a hot spot in the development of the global cosmetics industry in recent years. With the improvement of people's living standards, the requirements for the design of sunscreen products have also developed from UVB protection to organic molecule protection that takes into account UVA. Octyl Methoxycinnamate (OMC for short) is a UVB sunscreen agent with good formula applicability, high safety and large UV absorption coefficient, and it is cheap. A survey shows that OMC is One of the most frequently used sunscreen cosmetics. Octocrylene, a UVB absorber, is photostable and can be used to stabilize avobenzone. There are very few chemical sunscreens that block UVA, especially in the UVAI (340–400nm) region. 4-tert-butyl-4'-methoxydibenzoylmethane (trade name Avobenzone, Parsol1789, Eusolex9020, etc., abbreviated as AVO) is one of the UVA filters widely approved by various countries. AVO exists in two forms: enol (CE) and ketone (K). In AVO, these two forms are in balance, and the enol form is dominant. The enol form has a strong absorption band in the UVA region with a wavelength of 357nm. The ketone formula has a strong absorption capacity in the 260nm wavelength region, so it has no absorption effect on UVA or UVB. However, due to the photoinstability of AVO, the proportion of ketones will increase after long-term exposure to light, so sunscreen products containing this filter cannot effectively protect against light.

In order to increase the SPF value of sunscreen products and improve the photostability of UVA filters, many new methods have emerged one after another. Merck has recently launched organic sunscreen UV-Pearls encapsulated by Sol-Gel process, this Eusolex UVPearls promotes SPF value and improves the stability of AVO. With the addition of antioxidants, Wondrak has identified quenchers of photoactive state ingredients to facilitate the harmless dissipation of photoexcitation energy by inhibiting ROS in the formulation. The emergence and application of triplet quenchers, such as octocrylene, have opened up a new way for the photostability application of AVO.

Carrier technology can improve the compatibility and stability of sunscreens, and can also reduce all damage to the skin and the chance of pathogenic mutations. Researchers at home and abroad have turned their attention to the carrier technology and developed such sunscreen carrier delivery systems as microcapsules, porous polymer microspheres, liposomes, and gels. Solid lipid nanoparticles (SLN) have the advantages of controlled release, improved bioavailability, protection of chemically unstable molecules, short peptides from degradation, and improved drug entrapment. However, there are also shortcomings, such as low loading capacity and drug leakage during storage. Based on this, nanostructured lipid carriers (NLC) have been developed, which can improve the shortcomings of SLN. The NLC carrier itself has UV absorption capacity. When the carrier is loaded with sunscreens, NLC can cooperate with chemical sunscreens, showing higher UV absorption performance than emulsions.

Because the compound sunscreen is mainly a fat-soluble substance, it is extremely insoluble in water. Moreover, the UVA sunscreen agent avobenzone is easy to degrade and change color under light. These problems lead to greatly reduced bioavailability of sunscreen products in the prior art. The present invention comes to this end.

Contents of the invention

The purpose of the present invention is to provide a water-soluble composite sunscreen nano-structured lipid carrier with high stability, good compatibility and all bands, which solves the problems of easy degradation and discoloration of sunscreen avobenzone in the prior art.

In order to solve these problems in the prior art, the technical solution provided by the invention is:

A composite sunscreen nanostructured lipid carrier, characterized in that the components in the nanostructured lipid carrier are calculated by weight percentage:

The composite lipid material is a solid-liquid lipid material mixture, wherein the liquid lipid material is selected from triacetin, diethyl sebacate, diisopropyl adipate, diisopropyl sebacate, octanoic acid Glyceryl caprate; solid lipid material selected from glyceryl monostearate, acetylated monoglyceride, carnauba wax, behenate.

Preferably, the emulsifier is selected from at least one of the following compounds: cetyl alcohol, glyceryl stearate, steareth-20, PEG-75 stearate, PEG-100 stearate, Cetearyl Olive Oil Ester, Sorbitan Olive Oil Ester.

Another object of the present invention is to provide a kind of method for preparing described composite sunscreen agent nanostructure lipid carrier, it is characterized in that described method comprises the following steps:

(1) Weigh the emulsifier material and water according to the formula ratio, mix the emulsifier and water, heat and stir to obtain the water phase;

(2) Weigh octocrylene or octyl p-methoxycinnamate and compound lipid material according to the formula ratio, heat and mix to obtain a liquid oil phase;

(3) Weighing an appropriate amount of avobenzone, adding it to the liquid oil phase in step (2), heating and dissolving completely to obtain an oil phase in which avobenzone is dissolved;

(4) Add the oil phase in which avobenzone is dissolved into the water phase in step (1), mix evenly, and then add a high-pressure homogenizer preheated to 65-80°C and a pressure of 60MPa to rotate and homogenize for 3 to 5 times , to obtain nanoemulsion;

(5) cooling the nanoemulsion to room temperature to obtain the nanostructured lipid carrier of the composite sunscreen agent according to claim 1 .

Preferably, the heating temperature in step (1) of the method is controlled within the range of 65-80°C.

Preferably, the heating temperature in step (2) of the method is controlled within the range of 65-80°C.

Preferably, in step (4) of the method, the temperature of the oil phase in which avobenzone is dissolved is controlled within the range of 65-80°C, and the temperature of the water phase is controlled within the range of 65-80°C.

The composite sunscreen nanostructure lipid carrier obtained in the present invention is loaded with active pharmaceutical ingredients: full-band composite sunscreen, the full-band composite sunscreen includes UVA sunscreen and UVB sunscreen, wherein the UVA sunscreen is selected from avobenzone , and must contain, the UVB sunscreen agent is selected from at least one of the following compounds: octocrylene, octyl p-methoxycinnamate. The nanostructured lipid carrier has good stability and water solubility, the preparation method is simple and controllable, and has good repeatability, and can be applied to the preparation of sunscreen cosmetics.

In the present invention, the preferred components of the nanostructured lipid carrier are calculated by weight percentage:

Another object of the present invention is to provide an application of a composite sunscreen nanostructured lipid carrier in the preparation of skin care cosmetics.

The invention applies nanotechnology to the field of cosmetics. The defects of traditional crafts have been well improved. The present invention obtains a nanostructured lipid carrier for a composite sunscreen agent. The advantage of nanostructured lipid carriers (NLC) is that the lipid component can disturb the structure of the stratum corneum, solubilize the drug, and hydrate the drug to slow down the aging process. Release, controlled release, improve drug stability, etc. NLC crystal defects are increased, stability is improved, loading capacity is increased, drug leakage is reduced, and the particles become smaller, the closing effect on the skin is strengthened, and the viscosity is reduced. These advantages lead to a significant increase in the effectiveness of the active ingredients on the skin.

NLC is used to wrap avobenzone to improve its water solubility and light stability. And the present invention does not contain organic solvent, avoiding the stimulation to skin.

Compared with the scheme in the prior art, the advantages of the present invention are:

The preparation of the composite sunscreen nanostructure lipid carrier of the invention is controllable. The composite sunscreen nanostructured lipid carrier with a content of 3%-40% can be prepared by adjusting the formula of the composite sunscreen nanostructured lipid carrier, the number of high-pressure homogenization cycles and other conditions.

The NLC carrier technology in the present invention improves the stability of the active substance avobenzone (AVO) (as shown in Figure 2), and promotes the long-term absorption of the active substance AVO, OCT, OMC on the skin surface to ultraviolet rays, which is conducive to giving full play to the active substance Protects the skin from UV damage. The composite sunscreen-NLC prepared by the invention has better stability and good water solubility, which makes the preparation of the cosmetics containing the composite sunscreen-NLC convenient and simple.

The fat and emulsifier of the composite sunscreen agent-NLC prepared by the invention has good compatibility with skin, and is easy to give full play to the efficacy of the sunscreen agent.

The preparation method of the invention is simple and has good repeatability. It can be added to cosmetic preparations, or used directly. The formula of the invention breaks through the existing application technology of composite sunscreen, and the prepared carrier itself has a shielding effect on ultraviolet rays.

The special structure of the composite sunscreen nanostructured lipid carrier (NLC) obtained by the invention can improve the compatibility and release properties of the three sunscreens. NLC uses a certain proportion of liquid oil or other different lipids and solid lipids as a mixed lipid matrix, which not only increases the drug loading, but also controls drug release. Compared with a single solid lipid matrix, the formation of a complete lattice of lipids can be avoided, and the drug can be expelled, thereby improving drug entrapment.

Description of drawings

The present invention will be further described below in conjunction with accompanying drawing and embodiment:

Fig. 1 is the preparation method flowchart of composite sunscreen agent nanostructure lipid carrier of the present invention;

Fig. 2 is the change result of the retention rate of avobenzone in the nanostructured lipid carrier of the composite sunscreen obtained in the present invention under light.

Detailed ways

The above solution will be further described below in conjunction with specific embodiments. These examples are for illustrating the present invention and are not intended to limit the scope of the present invention. The implementation conditions used in the examples can be further adjusted according to the conditions of specific manufacturers, and the implementation conditions not indicated are usually the conditions in routine experiments.

The preparation of embodiment 1 composite sunscreen agent nanostructure lipid carrier

Composition formula

As shown in Figure 1, the preparation steps of this embodiment are as follows:

1. Weigh 2.0 grams of cetyl alcohol, 2.0 grams of PEG-75 stearate, 3.5 grams of steareth-20, 2.5 grams of glyceryl stearate, and 58.0 grams of deionized water into a beaker, and carry out 70 ℃ Heated in a water bath, and stirred evenly, as the water phase.

2. Weigh 5.0 grams of diethyl sebacate, 2.0 grams of glyceryl monostearate, and 15.0 grams of octocrylene, and heat them in a water bath at 70°C.

3. After the lipid in the beaker is completely melted, add 10.0 grams of avobenzone, heat and dissolve until completely, as the oil phase.

4. Add the oil phase to the water phase and stir evenly. At the same time, turn on the high-pressure homogenizer and preheat it with 75°C deionized water;

5. Inject the uniformly stirred high-temperature emulsion system into a high-pressure homogenizer, adjust the homogenization pressure to 60MPa, and circulate the homogenization 3 times under this pressure;

6. Cool to room temperature to obtain the aqueous dispersion of the composite sunscreen agent-NLC. The particle size of the dispersion measured by a laser particle size analyzer (LD) is d(10)=0.263 μm, d(50)=0.470 μm, d (90)=1.046 μm.

Preparation of Example 2 Composite Sunscreen Nanostructured Lipid Carrier

Composition formula

Preparation steps:

1. Weigh 4.0 grams of glyceryl stearate, 6.0 grams of PEG-100 stearate, and 57.0 grams of deionized water into a beaker, heat in a water bath at 75°C, and stir evenly to serve as the water phase.

2. Weigh 3.0 grams of carnauba wax, 5.0 grams of diisopropyl adipate, and 15.0 grams of octyl p-methoxycinnamate, and heat them in a water bath at 75°C.

3. After the lipid in the beaker is completely melted, add 10.0 g of avobenzone, heat and dissolve until completely, as the oil phase.

4. Add the oil phase to the water phase and stir evenly. At the same time, turn on the high-pressure homogenizer and preheat it with 80°C deionized water;

5. Pour the uniformly stirred high-temperature emulsion system into a high-pressure homogenizer, adjust the homogenization pressure to 60MPa, and cycle the homogenization twice under this pressure;

6. Cool to room temperature to obtain an aqueous dispersion of the composite sunscreen-NLC, and the particle size of the dispersion measured by photon correlation spectroscopy (PCS) is 270 nm.

Preparation of Example 3 Composite Sunscreen Nanostructured Lipid Carrier

Composition formula

Preparation steps:

1. Weigh 1.0 grams of cetyl alcohol, 1.0 grams of PEG-75 stearate, 2.0 grams of steareth-20, 4.5 grams of glyceryl stearate, 2.0 grams of PEG-100 stearate, 61.5 grams Deionized water was put into a beaker, heated in a water bath at 75°C, and stirred evenly to serve as the water phase.

2. Weigh 3.0 grams of caprylic capric glycerides, 3.0 grams of carnauba wax, 3.0 grams of glyceryl monostearate, 5.0 grams of octocrylene, and 9.0 grams of octyl methoxycinnamate and heat them in a water bath at 75°C.

3. After the lipid in the beaker is completely melted, add 5.0 grams of avobenzone, heat and dissolve until completely, as the oil phase.

4. Add the oil phase to the water phase and stir evenly. At the same time, turn on the high-pressure homogenizer and preheat it with 80°C deionized water;

5. Put the uniformly stirred high-temperature emulsion system into the high-pressure homogenizer, adjust the homogenization pressure to 60MPa, and circulate the homogenization 4 times under this pressure;

6. Cool to room temperature to obtain an aqueous dispersion of the composite sunscreen-NLC, and the particle size of the dispersion measured by photon correlation spectroscopy (PCS) is 315 nm.

Preparation of Example 4 Composite Sunscreen Nanostructured Lipid Carrier

Composition formula

Preparation steps:

1. Weigh 3.5 grams of cetearyl olive oil ester, 2.5 grams of sorbitan olive oil ester, and 72.0 grams of deionized water into a beaker, heat in a water bath at 75°C, and stir evenly to form the water phase.

2. Weigh 5.0 grams of glyceryl caprylate, 5.0 grams of glyceryl monostearate, 2.0 grams of octyl p-methoxycinnamate, and 2.0 grams of octocrylene and heat them in a water bath at 75°C.

3. After the lipid in the beaker is completely melted, add 8.0 grams of avobenzone, heat and dissolve until completely, as the oil phase.

4. Add the oil phase to the water phase and stir evenly. At the same time, turn on the high-pressure homogenizer and preheat it with 80°C deionized water;

5. Put the uniformly stirred high-temperature emulsion system into the high-pressure homogenizer, adjust the homogenization pressure to 60MPa, and circulate the homogenization for 5 times under this pressure;

6. Cool to room temperature to obtain an aqueous dispersion of the composite sunscreen-NLC, and the particle size of the dispersion measured by photon correlation spectroscopy (PCS) is 293 nm.

The above examples are only to illustrate the technical conception and characteristics of the present invention, and its purpose is to allow people familiar with this technology to understand the content of the present invention and implement it accordingly, and cannot limit the protection scope of the present invention. All equivalent changes or modifications made according to the spirit of the present invention shall fall within the protection scope of the present invention.

Claims (7)

1. compound sunscreen nano structured lipid carrier is characterized in that composition is counted by its percentage by weight in the said nano structured lipid carrier:

Said complex lipid material is a solid-liquid matrix material mixture, and wherein liquid lipoid material is selected from glyceryl triacetate, ethyl sebacate, adipic acid diisopropyl ester, Dermol DIPS, sad caprin; The solid lipid material is selected from glyceryl monostearate, acetylation monoglyceride, Brazil wax, behenate.

2. compound sunscreen nano structured lipid carrier according to claim 1 is characterized in that said emulsifying agent is selected from least a following chemical compound: spermol, glyceryl stearate, stearyl alcohol polyethers-20, PEG-75 stearate, PEG-100 stearate, cetearyl Fructus Canarii albi grease, sorbitol Fructus Canarii albi grease.

3. method for preparing the described compound sunscreen nano structured lipid carrier of claim 1 is characterized in that said method comprising the steps of:

(1) presses formula proportion weighing emulsifying agent material and water, with emulsifying agent and water mixing post-heating and stir and obtain water;

(2) press formula proportion weighing octocrilene or p-methoxycinnamic acid monooctyl ester and complex lipid material, the heating mixing obtains liquid oil phase;

(3) an amount of avobenzone of weighing joins in the liquid oil phase of step (2), and the oil phase that has obtained dissolving avobenzone is dissolved in heating fully;

The oil phase that (4) will dissolve avobenzone adds the water of step (1), and mix homogeneously adds and is preheated to the high pressure homogenizer rotation homogenizing 3～5 times that 65-80 ℃, pressure are 60MPa, obtains nanoemulsions;

(5) the nanoemulsions cool to room temperature is promptly got the described compound sunscreen nano structured lipid carrier of claim 1.

4. according to the method for claim 3, it is characterized in that step in the said method (1) heating and temperature control is in 65-80 ℃ of scope.

5. according to the method for claim 3, it is characterized in that step in the said method (2) heating and temperature control is in 65-80 ℃ of scope.

6. according to the method for claim 3, it is characterized in that the temperature of having dissolved the oil phase of avobenzone in the step in the said method (4) is controlled in the 65-80 ℃ of scope, the temperature of water is controlled in the 65-80 ℃ of scope.

7. one kind prepares the application of the described compound sunscreen nano structured lipid carrier of claim 1 aspect the preparation skin protection cosmetics.

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