CN114053252A - Nano lipid transport carrier of retinol or derivatives thereof and preparation method thereof - Google Patents

Nano lipid transport carrier of retinol or derivatives thereof and preparation method thereof Download PDF

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CN114053252A
CN114053252A CN202111416188.4A CN202111416188A CN114053252A CN 114053252 A CN114053252 A CN 114053252A CN 202111416188 A CN202111416188 A CN 202111416188A CN 114053252 A CN114053252 A CN 114053252A
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retinol
lipid
nano
derivatives
transport carrier
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马守伟
张晨琦
唐毓萍
夷磊
赵毅
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Bloomage Biotech Co Ltd
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Bloomage Biotech Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/07—Retinol compounds, e.g. vitamin A
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
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    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/14—Liposomes; Vesicles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/37—Esters of carboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67—Vitamins
    • A61K8/671—Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
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    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/18—Antioxidants, e.g. antiradicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations

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Abstract

The invention provides a nano lipid transport carrier of retinol or derivatives thereof, which is characterized by comprising 0.05-0.5% of retinol or derivatives thereof, 0.01-5% of liquid lipid, 0.016-10% of solid lipid and 0.02-20% of emulsifier in mass. According to the invention, through adjusting the composition of the nano lipid carrier, the stability of retinol and the derivatives thereof can be obviously improved under the condition of not adding an additional stabilizer, and meanwhile, through the selection and the proportion of the grease and the emulsifier, the use of phospholipid and inorganic salt can be avoided in the preparation process of the nano lipid carrier. The retinol and the nanometer lipid carrier of the retinol derivative are stored for 3 months at 45 ℃ under the condition of no light shielding, and the content of the retinol and the nanometer lipid carrier of the retinol derivative is not less than 55 percent of the initial content.

Description

Nano lipid transport carrier of retinol or derivatives thereof and preparation method thereof
Technical Field
The invention belongs to the field of biological medicines, and particularly relates to a nano lipid transport carrier for retinol or derivatives thereof.
Background
Due to the characteristics of safety and effectiveness, the retinol and the derivatives thereof are widely applied to cosmetics, particularly anti-aging skin care products, and are accepted by most consumers. However, in the practical application process, the retinol and the derivatives thereof are very sensitive to various factors such as light, temperature, water, oxygen, etc., so that the retinol and the derivatives thereof are mostly degraded during the storage, production, shelf life and use processes, thereby failing to really exert the efficacy.
The industry has developed a variety of stabilization techniques for retinol and its derivatives, and the real results are often not ideal. The document US20030232091a1 provides a process in which retinol is encapsulated in a core of hydrophobic material, the retinol content of which is reduced from 100% to 50% after 4 weeks at 50 c, and which is achieved in the presence of antioxidant BHT, while numerous literature and industry experience has shown that BHT is able to stabilize retinol. Even so, this technology still cannot meet the market demand in practical application.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides a nano lipid transport carrier of retinol or derivatives thereof and a preparation method thereof.
Specifically, the present invention relates to the following aspects:
1. the nano lipid transportation carrier of retinol or the derivatives thereof is characterized by comprising 0.05-0.5% of retinol or the derivatives thereof, 0.01-5% of liquid lipid, 0.016-10% of solid lipid and 0.02-20% of emulsifier.
2. The nano lipid transport carrier according to item 1, wherein the ratio of retinol or its derivatives is 0.05-0.3% by mass, the ratio of liquid lipid is 0.5-3% by mass, preferably 0.7-2% by mass, the ratio of solid lipid is 1-6% by mass, preferably 1.5-4% by mass, and the ratio of emulsifier is 0.1-10% by mass, preferably 0.1-5% by mass.
3. The nano lipid transport carrier according to claim 1, wherein the retinol or the derivative thereof is one or more selected from the group consisting of retinol, retinal, retinoic acid, retinol acetate, retinol palmitate, retinol propionate, and hydroxyppinacol retinoic acid ester.
4. The nano lipid transport carrier according to the item 1, wherein the liquid lipid is selected from one or more of triglycerides, carbonates, long-chain linear alkanes and isosorbide ether, preferably from one or two of triglycerides and carbonates;
preferably, the triglyceride is selected from caprylic/capric triglyceride, the carbonate is selected from dioctyl carbonate, the long-chain linear alkane is selected from squalane, and the isosorbide anhydride ether is selected from dimethyl isosorbide anhydride.
5. The nano lipid transport carrier according to the item 1, wherein the solid lipid is selected from one or more of fatty alcohol ester and vegetable wax, and is preferably fatty alcohol ester;
preferably, the fatty alcohol ester is selected from one or two of jojoba esters and cetyl palmitate, and the vegetable wax is selected from one or more of cocoa seed fat, carnauba wax and candelilla wax.
6. The nanolipid transport carrier according to item 1, wherein the emulsifier is selected from one or two of ppg polyethers, polyglyceryl fatty acid esters, preferably ppg polyethers;
preferably, the ppg polyethers are selected from ppg-6-decyltetradecanol polyether-20, and the polyglycerol fatty acid esters are selected from one or more of PEG-4 polyglycerol-2 stearate and polyglycerol-3 methyl glucose distearate.
7. The nano lipid transport carrier according to item 1, wherein the mass ratio of the liquid lipid to the solid lipid is 0.1-0.6:1, preferably 0.2-0.6: 1.
8. The nano lipid transport carrier according to item 1, wherein the mass ratio of the emulsifier to the sum of the liquid lipid and the solid lipid is 0.4-3.5:1, preferably 0.9-1.6: 1.
9. The nano lipid transport carrier according to item 1, wherein the nano lipid transport carrier further comprises one or more than two of a thickener, a preservative, a perfume and a colorant.
10. The method for preparing a nano lipid transport carrier according to any one of items 1 to 9, wherein the method comprises the following steps:
heating and melting the solid lipid, the liquid lipid and the emulsifier at 50-95 ℃;
adding the retinol or its derivatives;
adding water with the same temperature, completely performing phase inversion emulsification, and cooling to room temperature to obtain the nano lipid transport carrier.
According to the invention, through adjusting the composition of the nano lipid carrier, the stability of retinol and the derivatives thereof can be obviously improved under the condition of not adding an additional stabilizer, and meanwhile, through the selection and the proportion of the grease and the emulsifier, the use of phospholipid and inorganic salt can be avoided in the preparation process of the nano lipid carrier. The retinol and the nanometer lipid carrier of the retinol derivative are stored for 3 months at 45 ℃ under the condition of no light shielding, and the content of the retinol and the nanometer lipid carrier of the retinol derivative is not less than 55 percent of the initial content.
Detailed Description
The present invention is further illustrated by the following examples, which are intended to be purely exemplary of the invention and are not intended to be limiting.
Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. Although methods and materials similar or equivalent to those described herein can be used in experimental or practical applications, the materials and methods are described below. In case of conflict, the present specification, including definitions, will control, and the materials, methods, and examples are illustrative only and not intended to be limiting. The present invention is further illustrated by the following examples, which are not intended to limit the scope of the invention.
Vitamin A is a fat-soluble vitamin, organic compound, and has chemical formula of C20H30O, and is stable to heat, acid and alkali, and easy to oxidize, and ultraviolet ray can promote its oxidative damage. Vitamin a includes a1 and a2, a1 being retinol. Retinol and its derivatives have been widely used in cosmetics, especially anti-aging skin care products. Aiming at the problem of instability of retinol and derivatives thereof in the practical application process, the invention provides a nano lipid transport carrier of retinol or derivatives thereof, which is characterized in that the nano lipid transport carrier comprises retinol or derivatives thereof, liquid lipid, solid lipid and an emulsifier. Wherein, in the nano lipid transport carrier, the weight ratio of the retinol or the derivatives thereof is 0.05-0.5%, preferably 0.05-0.3%, for example, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%. The liquid lipid may be present in an amount of 0.01% to 5%, preferably 0.5% to 3%, more preferably 0.7% to 2%, for example, 0.01%, 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5% by mass. The solid lipid may be contained in an amount of 0.016% to 10%, preferably 1 to 6%, more preferably 1.5 to 4%, for example, 0.016%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%. The emulsifier is 0.02 to 20% by mass, preferably 0.1 to 10% by mass, more preferably 0.1 to 5% by mass, and may be, for example, 0.02%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20% by mass.
Wherein the retinol or the derivatives thereof are selected from one or more of retinol, retinal, retinoic acid, retinol acetate, retinol palmitate, retinol propionate and hydroxy pinacol retinoic acid ester.
The liquid lipid is a lipid which is liquid at normal temperature and is selected from one or more of triglycerides, carbonates, long-chain linear alkanes and isosorbide anhydride ethers, and preferably from one or two of the triglycerides and the carbonates; preferably, the triglyceride is selected from caprylic/capric triglyceride, the carbonate is selected from dioctyl carbonate, the long-chain linear alkane is selected from squalane, and the isosorbide anhydride ether is selected from dimethyl isosorbide anhydride.
The solid lipid is a lipid which is solid at normal temperature and is selected from one or more of fatty alcohol ester and vegetable wax, and preferably the fatty alcohol ester; preferably, the fatty alcohol ester is selected from one or two of jojoba esters and cetyl palmitate, and the vegetable wax is selected from one or more of cocoa seed fat, carnauba wax and candelilla wax.
Furthermore, the retinol nano lipid transport carrier does not need to use phospholipid which is a common emulsifier but is expensive, the capability of emulsifying grease is low, and other types of emulsifiers with low cost and high emulsifying power are selected, so that the production and manufacturing cost can be greatly reduced.
The emulsifier of the invention can meet the above conditions, and is selected from one or two of ppg polyethers and polyglycerol fatty acid esters, preferably ppg polyethers; preferably, the ppg polyethers are selected from ppg-6-decyltetradecanol polyether-20, and the polyglycerol fatty acid esters are selected from one or more of PEG-4 polyglycerol-2 stearate and polyglycerol-3 methyl glucose distearate.
In a specific embodiment, the mass ratio of the liquid lipid to the solid lipid is 0.1-0.6:1, preferably 0.2-0.6:1, and may be, for example, 0.1:1, 0.15:1, 0.2:1, 0.25:1, 0.3:1, 0.35:1, 0.4:1, 0.45:1, 0.5:1, 0.6: 1.
In a particular embodiment, the mass ratio of the emulsifier to the sum of the liquid lipid and the solid lipid is 0.4-3.5:1, preferably 0.9-1.6:1, and may be, for example, 0.4:1, 0.9:1, 1:1, 1.5:1, 2:1, 2.5:1, 3: 1.
Further, the nano lipid transport carrier can also comprise one or more than two of thickening agent, preservative, essence and colorant according to the actual application requirement.
The thickening agent is selected from one or more of hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer (SEPINOV EMT 10, EMT-10), xanthan gum, cellulose and derivatives thereof, carbomer, acrylate copolymer and copolymers of acrylate derivatives.
The preservative is selected from one or more of parabens, benzoic acid, sorbic acid, caprylyl hydroximic acid, formaldehyde releaser and polyhydric alcohol.
The essence is selected from (daily) essence or other essential oils.
The colorant is one or more selected from acid red, acid blue, purple pigment, black pigment and brown pigment.
Further, the retinol nano lipid transport vehicle does not require the use of inorganic salts. In practical application, many emulsification systems are not tolerant to salt, and are prone to adverse effects such as system demulsification, polymer disintegration, active salting-out, and increased system irritation.
In a specific embodiment, the nano lipid transport vehicle consists of retinol or its derivatives, liquid lipid, solid lipid, emulsifier and water.
In a specific embodiment, the nano lipid transport vehicle consists of retinol or its derivatives, liquid lipid, solid lipid, emulsifier, thickener and water.
In a specific embodiment, the nano lipid transport vehicle consists of retinol or its derivatives, liquid lipid, solid lipid, emulsifier, thickener, preservative, perfume, colorant and water.
In a specific embodiment, the nano lipid transport carrier consists of retinol or derivatives thereof, caprylic/capric triglyceride, cetyl palmitate, ppg-6-decyltetradecylpolyether-20, a thickening agent and water.
In a specific embodiment, the nano lipid transport vehicle consists of retinol or its derivatives, dicapryl carbonate, jojoba esters, carnauba wax, ppg-6-decyltetradecanol polyether-20, a thickening agent, and water.
The invention also provides a preparation method of the nano lipid transport carrier, which comprises the following steps:
heating and melting the solid lipid, the liquid lipid and the emulsifier at 50-95 ℃;
adding the retinol or its derivatives;
adding water with the same temperature, completely performing phase inversion emulsification, and cooling to room temperature to obtain the nano lipid transport carrier.
The phase inversion emulsification of the invention refers to that a system is converted from a water-in-oil state with more oil and less water into an oil-in-water state with less oil and more water along with the continuous addition of water. The method can also further comprise the step of adding the thickening agent, the preservative, the essence and the coloring agent after the phase inversion emulsification is completed and the cooling is carried out to the room temperature.
Example 1
Mixing 1.5g of cetyl palmitate, 0.9g of caprylic/capric triglyceride and 4g of ppg-6-decyltetradecyltetradecylpolyether-20, heating to 75-85 ℃ for melting, adding 0.1g of hydroxy pinacol retinoic acid ester (HPR) and 0.2g of retinol propionate for dissolving and uniformly stirring, slowly adding deionized water at 75-85 ℃ (the system completes phase inversion in the adding process), ensuring that the weight of the reaction system is 99g, and rapidly cooling to room temperature. Adding 1g of thickener hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer (SEPINOV EMT 10), swelling and stirring uniformly to obtain the nano lipid transport carrier.
Example 2
Mixing 1.5g of cetyl palmitate, 0.9g of caprylic/capric triglyceride and 4g of PEG-4 polyglycerol-2 stearate, heating to 75-85 ℃ for melting, adding 0.1g of hydroxy pinacol retinoic acid ester (HPR) and 0.2g of retinol propionate for dissolving and uniformly stirring, slowly adding deionized water at 75-85 ℃ to enable the weight of a reaction system to be 99g, and rapidly cooling to room temperature. Adding 1g of thickener hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer (SEPINOV EMT 10), swelling and stirring uniformly to obtain the nano lipid transport carrier.
Example 3
Mixing 1.5g of cetyl palmitate, 0.9g of caprylic/capric triglyceride and 4g of polyglycerol-3-methylglucose distearate, heating to 75-85 ℃ for melting, adding 0.1g of hydroxy pinacol retinoic acid ester (HPR) and 0.2g of retinol propionate for dissolving and uniformly stirring, slowly adding deionized water at 75-85 ℃ to enable the weight of a reaction system to be 99g, and rapidly cooling to room temperature. Adding 1g of thickener hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer (SEPINOV EMT 10), swelling and stirring uniformly to obtain the nano lipid transport carrier.
Example 4
Mixing 1.5g of cetyl palmitate, 0.9g of caprylic/capric triglyceride and 4g of polyglycerol-10 stearate, heating to 75-85 ℃ for melting, adding 0.1g of hydroxy pinacol retinoic acid ester (HPR) and 0.2g of retinol propionate for dissolving and uniformly stirring, slowly adding deionized water at 75-85 ℃ to enable the weight of a reaction system to be 99g, and rapidly cooling to room temperature. Adding 1g of thickener hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer (SEPINOV EMT 10), swelling and stirring uniformly to obtain the nano lipid transport carrier.
Example 5
Mixing 1.5g of cetyl palmitate, 0.9g of caprylic/capric triglyceride and 1.1g of ppg-6-decyltetradecylpentadecanol polyether-20, heating to 75-85 ℃ for melting, adding 0.1g of hydroxy pinacol retinoic acid ester (HPR) and 0.2g of retinol propionate for dissolving and uniformly stirring, slowly adding deionized water at 75-85 ℃ to ensure that the weight of the reaction system is 99g, and rapidly cooling to room temperature. Adding 1g of thickener hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer (SEPINOV EMT 10), swelling and stirring uniformly to obtain the nano lipid transport carrier.
Example 6
Mixing 1.5g of cetyl palmitate, 0.9g of caprylic/capric triglyceride and 8g of ppg-6-decyltetradecylpentath-20, heating to 75-85 ℃ for melting, adding 0.1g of hydroxy pinacol retinoic acid ester (HPR) and 0.2g of retinol propionate for dissolving and uniformly stirring, slowly adding deionized water at 75-85 ℃ to enable the weight of a reaction system to be 99g, and rapidly cooling to room temperature. Adding 1g of thickener hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer (SEPINOV EMT 10), swelling and stirring uniformly to obtain the nano lipid transport carrier.
Example 7
Mixing 7.5g of cetyl palmitate, 4.5g of caprylic/capric triglyceride and 20g of ppg-6-decyltetradecylpentadecanol polyether-20, heating to 75-85 ℃ for melting, adding 0.1g of hydroxy pinacol retinoic acid ester (HPR) and 0.2g of retinol propionate for dissolving and uniformly stirring, slowly adding deionized water at 75-85 ℃ to enable the weight of a reaction system to be 99g, and rapidly cooling to room temperature. Adding 1g of thickener hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer (SEPINOV EMT 10), swelling and stirring uniformly to obtain the nano lipid transport carrier.
Example 8
2.5g of jojoba esters, 1g of carnauba wax, 0.9g of caprylic/capric triglyceride and 4g of ppg-6-decyltetradecanol polyether-20 are mixed and heated to 85-95 ℃ for melting, 0.1g of hydroxy pinacol retinoic acid ester (HPR) and 0.2g of retinol propionate are added for dissolving and stirring uniformly, then deionized water with 85-95 ℃ is slowly added to ensure that the weight of the reaction system is 99g, and the reaction system is rapidly cooled to room temperature. Adding 1g of thickener hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer (SEPINOV EMT 10), swelling and stirring uniformly to obtain the nano lipid transport carrier.
Example 9
2.5g of jojoba esters, 1g of carnauba wax, 0.9g of dioctyl carbonate and 4g of ppg-6-decyltetradecanol polyether-20 are mixed and heated to 85-95 ℃ for melting, 0.1g of hydroxy pinacol retinoic acid ester (HPR) and 0.2g of retinol propionate are added for dissolving and stirring uniformly, then deionized water with 85-95 ℃ is slowly added to ensure that the weight of the reaction system is 99g, and the reaction system is rapidly cooled to room temperature. Adding 1g of thickener hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer (SEPINOV EMT 10), swelling and stirring uniformly to obtain the nano lipid transport carrier.
Example 10
2.5g of jojoba esters, 1g of carnauba wax, 0.9g of squalane and 4g of ppg-6-decyltetradecyl alcohol polyether-20 are mixed and heated to 85-95 ℃ for melting, 0.1g of hydroxy pinacol retinoic acid ester (HPR) and 0.2g of retinol propionate are added for dissolving and stirring uniformly, then deionized water with 85-95 ℃ is slowly added to ensure that the weight of the reaction system is 99g, and the reaction system is rapidly cooled to room temperature. Adding 1g of thickener hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer (SEPINOV EMT 10), swelling and stirring uniformly to obtain the nano lipid transport carrier.
Example 11
2.5g of jojoba esters, 1g of cocoa seed fat, 0.9g of squalane and 4g of ppg-6-decyltetradecanol polyether-20 are mixed and heated to 75-85 ℃ for melting, 0.1g of hydroxy pinacol retinoic acid ester (HPR) and 0.2g of retinol propionate are added for dissolving and stirring uniformly, then deionized water at 75-85 ℃ is slowly added to ensure that the weight of the reaction system is 99g, and the reaction system is rapidly cooled to room temperature. Adding 1g of thickener hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer (SEPINOV EMT 10), swelling and stirring uniformly to obtain the nano lipid transport carrier.
Example 12
2.5g of jojoba esters, 1g of carnauba wax, 0.9g of caprylic/capric triglyceride and 4g of ppg-6-decyltetradecanol polyether-20 are mixed and heated to 85-95 ℃ for melting, 0.3g of retinol palmitate is added for dissolving and stirring uniformly, then deionized water with the temperature of 85-95 ℃ is slowly added to ensure that the weight of the reaction system is 99g, and the reaction system is rapidly cooled to room temperature. Adding 1g of thickener hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer (SEPINOV EMT 10), swelling and stirring uniformly to obtain the nano lipid transport carrier.
Example 13
2.5g of jojoba esters, 1g of carnauba wax, 0.9g of caprylic/capric triglyceride and 4g of ppg-6-decyltetradecanol polyether-20 are mixed and heated to 85-95 ℃ for melting, 0.3g of retinol is added for dissolving and stirring uniformly, then deionized water with the temperature of 85-95 ℃ is slowly added to ensure that the weight of the reaction system is 99g, and the reaction system is rapidly cooled to room temperature. Adding 1g of thickener hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer (SEPINOV EMT 10), swelling and stirring uniformly to obtain the nano lipid transport carrier.
Example 14
Mixing and heating 2.3g of cetyl palmitate, 0.1g of caprylic/capric triglyceride and 4g of ppg-6-decyltetradecylpentath-20 until the mixture is melted, adding 0.1g of hydroxy pinacol retinoic acid ester (HPR) and 0.2g of retinol propionate, dissolving and uniformly stirring, slowly adding deionized water at 75-85 ℃ to ensure that the weight of the reaction system is 99g, and rapidly cooling to room temperature. Adding 1g of thickener hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer (SEPINOV EMT 10), swelling and stirring uniformly to obtain the nano lipid transport carrier.
Example 15
2.5g of jojoba esters, 1g of carnauba wax, 0.9g of caprylic/capric triglyceride and 1g of ppg-6-decyltetradecanol polyether-20 are mixed and heated to 85-95 ℃ for melting, 0.1g of hydroxy pinacol retinoic acid ester (HPR) and 0.2g of retinol propionate are added for dissolving and stirring uniformly, then deionized water with 85-95 ℃ is slowly added to ensure that the weight of the reaction system is 99g, and the reaction system is rapidly cooled to room temperature. Adding 1g of thickener hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer (SEPINOV EMT 10), swelling and stirring uniformly. The results show that no nanolipid transport vehicle was obtained.
Comparative example 1
Mixing 2.4g of caprylic/capric triglyceride and 4g of ppg-6-decyltetradecanol polyether-20, heating to 75-85 ℃ for melting, adding 0.1g of hydroxy pinacol retinoic acid ester (HPR) and 0.2g of retinol propionate for dissolving and stirring uniformly, slowly adding deionized water at 75-85 ℃ to ensure that the weight of the reaction system is 99g, and rapidly cooling to room temperature. Adding 1g of thickener hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer (SEPINOV EMT 10), swelling and stirring uniformly to obtain the nano lipid transport carrier.
Comparative example 2
Mixing and heating 2.4g of cetyl palmitate and 4g of ppg-6-decyltetradecanol polyether-20 to 75-85 ℃ for melting, adding 0.1g of hydroxy pinacol retinoic acid ester (HPR) and 0.2g of retinol propionate for dissolving and stirring uniformly, slowly adding deionized water at 75-85 ℃ to ensure that the weight of the reaction system is 99g, and rapidly cooling to room temperature. Adding 1g of thickener hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer (SEPINOV EMT 10), swelling and stirring uniformly to obtain the nano lipid transport carrier.
Comparative example 3
Mixing 1.5g of cetyl palmitate, 0.9g of caprylic/capric triglyceride and 4g of steareth-21, heating to 75-85 ℃ for melting, adding 0.1g of hydroxy pinacol retinoic acid ester (HPR) and 0.2g of retinyl propionate, dissolving and stirring uniformly, slowly adding deionized water at 75-85 ℃ to enable the weight of the reaction system to be 99g, and rapidly cooling to room temperature. Adding 1g of thickener hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer (SEPINOV EMT 10), swelling and stirring uniformly. The results show that no nanolipid transport vehicle was obtained.
Comparative example 4
Mixing 15g of cetyl palmitate, 9g of caprylic/capric triglyceride and 40g of ppg-6-decyltetradecyltetradecylpolyether-20, heating to 75-85 ℃ for melting, adding 0.1g of hydroxy pinacol retinoic acid ester (HPR) and 0.2g of retinol propionate, dissolving and uniformly stirring, slowly adding deionized water at 75-85 ℃ (the system completes phase inversion in the adding process), ensuring that the weight of the reaction system is 99g, and rapidly cooling to room temperature. Adding 1g of thickener hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer (SEPINOV EMT 10), swelling and stirring uniformly. The results show that no nanolipid transport vehicle was obtained.
Specific conditions of the above examples and comparative examples are shown in table 1.
TABLE 1
Figure BDA0003375372390000101
Figure BDA0003375372390000111
Test examples
Stability test
The contents (m) of the initial hydroxy pinacol retinoic acid ester (HPR), retinol propionate, retinol palmitate in the nano lipid transport vehicles prepared in examples 1-15 and comparative examples 1-4 were measured by HPLC methodInitial) Then, the nano lipid transport carrier is placed at 45 degrees for 3 months, and then the contents (m) of hydroxy pinacol retinoic acid ester (HPR), retinol propionate, retinol and retinol palmitate in the nano lipid transport carrier are determined3 months old) And calculating the residual quantity of the nano lipid transport carrier after being placed at 45 degrees for 3 months, and the results are shown in table 3.
Residual amount%3 months old/mInitial*100％
Wherein, the HPR (hydroxy pinacolone retinoic acid ester) content detection method comprises the following steps:
sample pretreatment: accurately weighing 0.5g (accurate to 0.0001g) of sample, adding into 25mL colorimetric tube with plug, adding acetonitrile to constant volume to scale, mixing with vortex mixer, and performing ultrasonic extraction for 20 min. Taking a certain amount of solution, placing in a 10ml centrifuge tube, centrifuging for 10min under 10000r/min, filtering the centrifuged supernatant with a 0.22 μm organic phase filter membrane, and testing the filtrate.
Chromatographic conditions are as follows:
mobile phase: phase A: acetonitrile; phase B: 0.1% aqueous formic acid: weighing 1g (accurate to 0.0001g), dissolving with water and metering to 1000ml, filtering with 0.45 μm water phase microporous membrane, and ultrasonic degassing for 20 min.
The instrument comprises the following steps: high performance liquid chromatograph, diode array detector (Agilent HPLC 1260)
A chromatographic column: ZORBAX Eclipse Plus C18(4.6 × 250mm × 5 μm);
detection wavelength: 380 nm;
mobile phase ratio: and A, B is 95: 5(V/V) isocratic elution;
flow rate: 1 mL/min;
column temperature: 35 ℃;
sample introduction amount: 5 μ L.
The method for detecting the content of the retinol propionate/retinol palmitate/retinol comprises the following steps:
sample pretreatment: accurately weighing 1g (accurate to 0.0001g) of sample, adding an isopropanol solution into a 10mL colorimetric tube with a plug, mixing by vortex, and fixing the volume to the scale by using the isopropanol solution. Performing ultrasonic extraction for 20min, mixing, centrifuging 5mL of the solution in a 10mL centrifuge tube at 10000r/min for 10min, filtering the supernatant with a 0.22 μm filter membrane, and measuring the filtrate.
Chromatographic conditions are as follows:
the instrument comprises the following steps: high performance liquid chromatograph, diode array detector (Agilent HPLC 1260)
A chromatographic column: ZORBAX Eclipse Plus C18(4.6 × 250mm × 5 μm);
mobile phase: methanol;
detection wavelength: 325 nm;
flow rate: 1 mL/min;
column temperature: 35 ℃;
sample introduction amount: 5 μ L.
TABLE 3
Figure BDA0003375372390000131
Note: "-" represents no result detected
The retinol and the derivative thereof nano lipid carrier prepared in the embodiment of the invention have good stability, especially in the embodiments 1-13, the content of the retinol and the derivative thereof nano lipid carrier is not less than 55% of the initial content after being stored for 3 months at 45 ℃ without light.
The stability of the retinol and the derivatives thereof can be obviously improved by the prepared nano lipid carrier, and the use of phospholipid and inorganic salt can be avoided in the preparation process of the nano lipid carrier, so that the instability or demulsification problem caused by the existence of phospholipid and inorganic salt can be reduced.

Claims (10)

1. The nano lipid transportation carrier of retinol or the derivatives thereof is characterized by comprising 0.05-0.5% of retinol or the derivatives thereof, 0.01-5% of liquid lipid, 0.016-10% of solid lipid and 0.02-20% of emulsifier.
2. The nano lipid transport carrier according to claim 1, wherein the weight ratio of retinol or the derivative thereof is 0.05-0.3%, the weight ratio of liquid lipid is 0.5-3%, preferably 0.7-2%, the weight ratio of solid lipid is 1-6%, preferably 1.5-4%, and the weight ratio of emulsifier is 0.1-10%, preferably 0.1-5%.
3. The nano lipid transport carrier of claim 1, wherein the retinol or the derivative thereof is selected from one or more of retinol, retinal, retinoic acid, retinol acetate, retinol palmitate, retinol propionate, and hydroxyppinacol retinoic acid ester.
4. The nano lipid transport carrier according to claim 1, wherein the liquid lipid is selected from one or more of triglycerides, carbonates, long-chain linear alkanes and isosorbide ethers, preferably from one or two of triglycerides and carbonates;
preferably, the triglyceride is selected from caprylic/capric triglyceride, the carbonate is selected from dioctyl carbonate, the long-chain linear alkane is selected from squalane, and the isosorbide anhydride ether is selected from dimethyl isosorbide anhydride.
5. The nano lipid transport carrier according to claim 1, wherein the solid lipid is selected from one or more of fatty alcohol ester and vegetable wax, preferably fatty alcohol ester;
preferably, the fatty alcohol ester is selected from one or two of jojoba esters and cetyl palmitate, and the vegetable wax is selected from one or more of cocoa seed fat, carnauba wax and candelilla wax.
6. The nano lipid transport carrier according to claim 1, wherein the emulsifier is selected from one or two of ppg polyethers, polyglyceryl fatty acid esters, preferably ppg polyethers;
preferably, the ppg polyethers are selected from ppg-6-decyltetradecanol polyether-20, and the polyglycerol fatty acid esters are selected from one or more of PEG-4 polyglycerol-2 stearate and polyglycerol-3 methyl glucose distearate.
7. The nano lipid transport vehicle according to claim 1, wherein the mass ratio of the liquid lipid to the solid lipid is 0.1-0.6:1, preferably 0.2-0.6: 1.
8. The nano lipid transport vehicle according to claim 1, wherein the mass ratio of the emulsifier to the sum of the liquid lipid and the solid lipid is 0.4-3.5:1, preferably 0.9-1.6: 1.
9. The nano lipid transport vehicle according to claim 1, further comprising one or more of a thickener, a preservative, a perfume, and a colorant.
10. The method for preparing a nano lipid transport vehicle according to any one of claims 1 to 9, wherein the preparation method comprises the following steps:
heating and melting the solid lipid, the liquid lipid and the emulsifier at 50-95 ℃;
adding the retinol or its derivatives;
adding water with the same temperature, completely performing phase inversion emulsification, and cooling to room temperature to obtain the nano lipid transport carrier.
CN202111416188.4A 2021-11-25 2021-11-25 Nano lipid transport carrier of retinol or derivatives thereof and preparation method thereof Pending CN114053252A (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6068847A (en) * 1996-10-03 2000-05-30 Johnson & Johnson Consumer Products, Inc. Cosmetic compositions
KR20200051997A (en) * 2018-11-06 2020-05-14 주식회사 코리아나화장품 Cosmetic Composition For Improving Wrinkle Containing Retinol, Glutathione Or Tocopherol Stabilized By Nano-Structured Lipid Carrier
KR20200067768A (en) * 2018-12-04 2020-06-12 주식회사 엘지생활건강 High-content and sustained-release retinoid capsule and composition for improving wrinkles comprising the same

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6068847A (en) * 1996-10-03 2000-05-30 Johnson & Johnson Consumer Products, Inc. Cosmetic compositions
KR20200051997A (en) * 2018-11-06 2020-05-14 주식회사 코리아나화장품 Cosmetic Composition For Improving Wrinkle Containing Retinol, Glutathione Or Tocopherol Stabilized By Nano-Structured Lipid Carrier
KR20200067768A (en) * 2018-12-04 2020-06-12 주식회사 엘지생활건강 High-content and sustained-release retinoid capsule and composition for improving wrinkles comprising the same

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
无: "bio-meso肌活美白淡斑精华液", 《国产特殊化妆品注册信息基本信息》 *

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