CN114712261A - Nano-liposome containing ceramide-like extract and preparation method and application thereof - Google Patents

Nano-liposome containing ceramide-like extract and preparation method and application thereof Download PDF

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Publication number
CN114712261A
CN114712261A CN202210339058.3A CN202210339058A CN114712261A CN 114712261 A CN114712261 A CN 114712261A CN 202210339058 A CN202210339058 A CN 202210339058A CN 114712261 A CN114712261 A CN 114712261A
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China
Prior art keywords
ceramide
extract
phospholipid
mixed solution
liposome
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CN202210339058.3A
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Chinese (zh)
Inventor
李吉来
董良春
朱梁希
吴飞飞
曾施敏
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Guangzhou Gialen Cosmetics Co ltd
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Guangzhou Gialen Cosmetics Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/68Sphingolipids, e.g. ceramides, cerebrosides, gangliosides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/02Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/14Liposomes; Vesicles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34Alcohols
    • A61K8/345Alcohols containing more than one hydroxy group
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/55Phosphorus compounds
    • A61K8/553Phospholipids, e.g. lecithin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/63Steroids; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/02Preparations for care of the skin for chemically bleaching or whitening the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/20Chemical, physico-chemical or functional or structural properties of the composition as a whole
    • A61K2800/26Optical properties
    • A61K2800/262Transparent; Translucent
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/41Particular ingredients further characterized by their size
    • A61K2800/413Nanosized, i.e. having sizes below 100 nm
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/56Compounds, absorbed onto or entrapped into a solid carrier, e.g. encapsulated perfumes, inclusion compounds, sustained release forms

Abstract

The invention discloses a nanoliposome containing a ceramide-like extract, and a preparation method and application thereof. The invention prepares the nano-liposome containing the ceramide-like extract by taking the ceramide-like extract, cholesterol, phospholipid, glycerol, polyalcohol and water as raw materials. The nano liposome is semitransparent or transparent, and the average particle size is less than 200 nm; the ceramide-like nano liposome has high stability and good water dispersibility, can be directly used as cosmetics and can be optionally matched with a cosmetic formula, so that the difficult problem that the ceramide-like nano liposome is difficult to directly apply to the cosmetics is solved; the preparation method is simple and controllable, and has good repeatability.

Description

Nano liposome containing ceramide-like extract and preparation method and application thereof
Technical Field
The invention relates to the technical field of carrier systems in the cosmetic preparation technology, in particular to a nanoliposome containing a ceramide-like extract and a preparation method and application thereof.
Background
Ceramide (Ceramide), namely Ceramide N-acyl Sphingosine, is a class of amide compounds formed by condensing Sphingosine (Sphingosine) and long-chain fatty acid, is a class of compounds rather than a compound, and mainly exists in cell membranes and intercellular matrixes of stratum corneum. The structure of the amide is characterized in that the amide also contains two lipophilic long-chain alkyl groups and two hydrophilic hydroxyl groups besides the amide structure. The invention relates to a ceramide-like extract which is a ceramide-like (mannose erythritol esters, Mels) extract applied in the earlier stage of the company (Chinese patent application No. 201910667983.7), is a glycolipid biosurfactant component, and is found to contain a spatial structure similar to ceramide, and two long-chain alkyl groups similar to ceramide and two or more hydrophilic hydroxyl groups. In addition, Mels easily penetrates into the intercellular spaces of the stratum corneum of the skin, forms liquid crystals, maintains skin moisture, has moisturizing, skin moistening and skin barrier repair effects, and has partial effects similar to those of ceramide. Most of the existing ceramides are obtained by separating animals and plants, and the existing ceramides have the disadvantages of low yield, extremely high economic cost and great limitation on application. Therefore, the ceramide in the invention has similar ceramide structure and effect, is safe and nontoxic, can be used as a substitute of ceramide, improves the effect and reduces the cost.
The Liposome (Liposome) has very close structure with the plasma membrane system of the human body, namely the most basic structure and functional unit, namely 'cell', and has very good physiological compatibility with the human body, so that when the Liposome is used as a carrier system, the human body has little rejection reaction to the Liposome; the membrane structure of the liposome mainly comprises phospholipid and cholesterol, the phospholipid is used as the basis of the membrane structure of the liposome, the cholesterol plays a role in stabilizing the liposome structure, and the cholesterol can play a role in enhancing the stability of the liposome structure when environmental conditions are changed (such as temperature, osmotic pressure, pH and the like); the ceramide is a novel bioactive substance, mainly contains three or more Mels active substance components of Mel-A (mannose-1-erythritol-2, 3-dicamba-4, 6-diacetate), Mel-B (mannose-1-erythritol-2, 3-dicamba-6-acetate) and Mel-C (mannose-1-erythritol-2, 3-dicamba-4-acetate), and the content of the three Mels active substance components in the ceramide-like extract is more than 45%; ceramide-like compounds have wide development prospects in skin and hair care applications, and cosmetics containing ceramide-like compounds form a research hotspot. There have been many studies reporting that the prevention of water loss in the skin and the inhibition of melanin brown spots can be achieved by using a product such as an external cream containing a ceramide. However, the currently prepared ceramide-like extract is oily liquid, the stability and the water dispersibility of the ceramide-like extract are poor, and the ceramide-like extract is difficult to be directly applied to cosmetics and the like.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide the nanoliposome containing the ceramide extract, which has high stability and good water dispersibility and can be directly applied to cosmetics.
The invention also aims to provide a preparation method of the nanoliposome containing the ceramide-like extract.
The invention also aims to provide the application of the nano-liposome containing the ceramide-like extract.
In order to achieve the purpose, the invention adopts the following technical scheme:
a nanoliposome containing a ceramide-like extract comprises the following components in percentage by mass: 1-10% of ceramide-like extract, 0.0-3.0% of cholesterol, 3-15% of phospholipid, 25-50% of glycerol, 5-25% of polyalcohol and the balance of water; preferably comprises the following components in percentage by mass: 3-8% of ceramide extract, 0.2-0.5% of cholesterol, 10% of phospholipid, 30-35% of glycerol, 17-18% of polyalcohol and the balance of water.
The ceramide-like extract is an extract containing a novel Mels bioactive substance prepared and extracted by a bio-emulsion fermentation method (refer to patent application CN201910667983.7), mainly contains three or more Mels active substance components of Mel-A, Mel-B, Mel-C, and has the effect similar to ceramide, wherein the content of the three Mels active substance components in the ceramide-like extract is more than 45%.
The phospholipid is at least one of hydrogenated phospholipid, liquid lecithin, soybean phospholipid, egg yolk lecithin and cephalin.
The hydrogenated phospholipid is preferably at least one of hydrogenated lecithin and hydrogenated soybean phospholipid.
The purity of the phospholipids is more than or equal to 70 percent.
The polyalcohol is at least one of butanediol and pentanediol; preferably a combination of butanediol and pentanediol; more preferably butanediol and pentanediol in a mass ratio of 15: 2 to obtain the compound.
The water is preferably at least one of deionized water, purified water and water for injection.
The particle size of the nano liposome containing the ceramide-like extract is 50-700nm, the average particle size is less than 200nm, and the nano liposome is uniformly distributed and is semitransparent or transparent; the preferable particle size is 60-650nm, and the average particle size is 179-197 nm.
The preparation method of the nanoliposome containing the ceramide-like extract comprises the following steps:
(1) heating ceramide-like extract to 70-80 deg.C, adding phospholipid, cholesterol and polyalcohol, and stirring at 70-80 deg.C to obtain uniform mixed solution A;
(2) adding glycerol into the mixed solution A at the temperature of 70-80 ℃, and uniformly stirring to obtain a uniform mixed solution B;
(3) adding water into the mixed solution B at the temperature of 70-80 ℃, and uniformly stirring to obtain a uniform mixed solution C;
(4) and (3) keeping the temperature of the mixed solution C at 70-75 ℃, and homogenizing to obtain the nanoliposome containing the ceramide-like extract.
The heating degree in the step (1) is preferably 75-80 ℃.
The stirring in the step (1) is shear stirring, and the condition of the shear stirring is preferably 120-240 rpm in order to obtain a uniform system with uniform mixing.
The temperature in the step (2) is preferably 70-75 ℃.
The temperature in the step (3) is preferably 70-75 ℃.
The homogenization conditions in step (4) are preferably as follows: homogenizing for 3-10 times at high pressure of 35-40MPa, and homogenizing for the last time at 80 MPa; more preferably: homogenizing for 5-6 times under high pressure of 35-40MPa, and homogenizing for the last time under 80 MPa.
The application of the nano-liposome containing the ceramide-like extract in preparing daily chemical products.
The daily chemical product has at least one of the following effects: moisturizing, caring skin, whitening, and removing speckle.
Compared with the prior art, the invention has the following advantages and effects:
1. according to the invention, the oily ceramide-like extract is prepared into the nano liposome, so that the problems that the ceramide-like extract is poor in water dispersibility and difficult to directly apply to cosmetics are effectively solved, and meanwhile, the ceramide-like extract is substituted for ceramide, so that the application resources of ceramide are expanded;
2. because the liposome membrane structure can play a role in enhancing the stability of the liposome structure, the ceramide-like extract is wrapped in the nano-liposome to be free from or less influenced by the change of environmental conditions, and the stability of the ceramide-like extract is improved.
3. The preparation method of the ceramide-like extract liposome has the advantages of simple process, high stability of the nano liposome, good water dispersibility and good biocompatibility, and can be directly used as cosmetics and optionally matched with a cosmetic formula; the preparation method is controllable and has good repeatability.
Drawings
Fig. 1 is a distribution diagram of the particle size of the nanoliposome containing the ceramide-like extract obtained in example 1.
Fig. 2 is a distribution diagram of the particle size of the nanoliposome containing the ceramide-like extract obtained in example 2.
Fig. 3 is a distribution diagram of the particle size of the nanoliposome containing the ceramide-like extract obtained in example 3.
Detailed Description
The above embodiments are further described with reference to the following detailed description and accompanying drawings. The following description is only for the purpose of illustrating the objects, effects and technical features of the present invention, and does not limit the scope of the present invention.
EXAMPLE 1 preparation of nanoliposomes containing ceramide-like extracts
1. The composition of the liposome system is shown in table 1:
TABLE 1 nanoliposome system components containing ceramide-like extract composition one
Prescription composition Quality (g) Mass percent (%)
Ceramide-like extract 80 8.0
Hydrogenated lecithin 100 10.0
Cholesterol 3 0.3
Glycerol 350 35.0
Butanediol 150 15.0
Pentanediol 20 2.0
Purified water 297 29.7
2. Preparation method
(1) Heating 80g ceramide-like extract (prepared according to example 2 of patent CN201910667983.7, the same below) to 75 deg.C, adding 100g hydrogenated lecithin, 3g cholesterol, 150g butanediol, and 20g pentanediol, stirring at constant temperature of 70-75 deg.C, and optionally shearing and stirring (150rpm) to obtain uniform mixed solution;
(2) adding 350g of glycerol into the mixed solution at the constant temperature of 70-75 ℃, and uniformly stirring to prepare uniform mixed solution;
(3) adding 297g of purified water into the mixed solution at the constant temperature of 70-75 ℃, and uniformly stirring to prepare a mixed solution;
(4) carrying out constant temperature treatment on the mixed solution at 70-75 ℃, and carrying out circulation treatment through a high-pressure homogenizer for 6 times, wherein the former five times of homogenization pressure is 36-38 MPa, and the sixth time of homogenization circulation pressure is 80MPa, and homogenizing to obtain uniform and stable nano-liposome containing ceramide;
the obtained nanometer liposome containing ceramide is transparent, and particle size distribution is determined by particle size analyzer, and the result is shown in FIG. 1, wherein the particle size of liposome of nanometer liposome preparation is 60-420nm, and the average particle size is 179.2 nm; and are uniformly distributed.
Testing of stability: the nanometer liposome containing ceramide is stored in a shade place at room temperature for 24 months, and the appearance and the particle size of the liposome are not obviously changed.
Testing of Water dispersibility: the nano-liposome containing the ceramide is placed in water and stirred, so that the water dispersibility is good.
Example 2 preparation of nanoliposomes containing ceramide-like extracts
1. The composition of the liposome system is shown in table 2:
TABLE 2 nanoliposome system components containing ceramide-like extract
Prescription composition Quality (g) Mass percent (%)
Ceramide-like extract 50 5.0
Hydrogenated lecithin 50 5.0
Soybean lecithin 50 5.0
Cholesterol 2 0.2
Glycerol 300 30.0
Butanediol 130 13.0
Pentanediol 50 5.0
Purified water 368 36.8
2. Preparation method
(1) Heating 50g of ceramide-like extract to 80 ℃, adding 50g of hydrogenated lecithin, 50g of soybean phospholipid, 2g of cholesterol, 130g of butanediol and 50g of pentanediol, keeping the temperature at 70-75 ℃, stirring, and shearing and stirring (180rpm) if necessary to prepare a uniform mixed solution;
(2) adding 300g of glycerol into the mixed solution at the constant temperature of 70-75 ℃, and uniformly stirring to prepare uniform mixed solution;
(3) adding 368g of purified water into the mixed solution at the constant temperature of 70-75 ℃, and uniformly stirring to prepare a mixed solution;
(4) carrying out constant temperature of 70-75 ℃ on the mixed solution, carrying out circulation treatment by a high-pressure homogenizer for 5 times, wherein the homogenization pressure for the first four times is 38-40 MPa, and the homogenization circulation pressure for the 5 th time is 80MPa, and homogenizing to obtain uniform and stable nano-liposome containing the ceramide;
the obtained nanoliposome containing ceramide is semitransparent, and particle size distribution is determined by particle size analyzer, and as shown in FIG. 2, the liposome particle size of the nanoliposome preparation is 60-650nm, and the average particle size is 196.5 nm; and are uniformly distributed.
Testing of stability: the nanometer liposome containing ceramide is stored in a shade place at room temperature for 24 months, and the appearance and the particle size of the liposome are not obviously changed.
Testing of Water dispersibility: the nano-liposome containing the ceramide is placed in water and stirred, so that the water dispersibility is good.
EXAMPLE 3 preparation of nanoliposomes containing ceramide-like substances
1. The composition of the liposome system is shown in table 3:
TABLE 3 ceramide-like nanoliposome system components III
Prescription composition Mass (g) Mass percent (%)
Ceramide-like extract 30 3.0
Hydrogenated lecithin 40 4.0
Liquid lecithin 60 6.0
Cholesterol 5 0.5
Glycerol 350 35.0
Butanediol 140 14.0
Pentanediol 30 3.0
Purified water 345 34.5
2. Preparation method
(1) Heating 30g of ceramide-like extract to 80 ℃, adding 40g of hydrogenated lecithin, 60g of liquid lecithin, 5g of cholesterol, 140g of butanediol and 30g of pentanediol, keeping the temperature at 70-75 ℃, stirring, and shearing and stirring (180rpm) if necessary to prepare a uniform mixed solution;
(2) adding 350g of glycerol into the mixed solution at the constant temperature of 70-75 ℃, and uniformly stirring to prepare uniform mixed solution;
(3) adding 345g of purified water into the mixed solution at the constant temperature of 70-75 ℃, and uniformly stirring to prepare a mixed solution;
(4) carrying out constant temperature treatment on the mixed solution at 70-75 ℃, and carrying out circulation treatment through a high-pressure homogenizer for 6 times, wherein the former five times of homogenization pressure is 36-38 MPa, and the sixth time of homogenization circulation pressure is 80MPa, and homogenizing to obtain uniform and stable nano-liposome containing ceramide;
the obtained ceramide-containing nanoliposome is nearly transparent, and the particle size distribution of the nanoliposome preparation is measured by a particle size analyzer, and the results are shown in fig. 3, wherein the particle size of the liposome of the nanoliposome preparation is measured to be in the range of 60-550nm, and the average particle size is 183.1 nm; and are uniformly distributed.
Testing of stability: the nanometer liposome containing ceramide is stored in a shade place at room temperature for 24 months, and the appearance and the particle size of the liposome are not obviously changed.
Testing of Water dispersibility: the nano-liposome containing the ceramide is placed in water and stirred, so that the water dispersibility is good.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.

Claims (10)

1. A nanoliposome containing a ceramide-like extract is characterized by comprising the following components in percentage by mass: 1-10% of ceramide extract, 0.0-3.0% of cholesterol, 3-15% of phospholipid, 25-50% of glycerol, 5-25% of polyalcohol and the balance of water.
2. The nanoliposome containing a ceramide-like extract as claimed in claim 1, which is characterized by comprising the following components in percentage by mass: 3-8% of ceramide extract, 0.2-0.5% of cholesterol, 10% of phospholipid, 30-35% of glycerol, 17-18% of polyalcohol and the balance of water.
3. The nanoliposome containing a ceramide-like extract as claimed in claim 1 or 2, wherein:
the phospholipid is at least one of hydrogenated phospholipid, liquid lecithin, soybean phospholipid, egg yolk lecithin and cephalin;
the polyalcohol is at least one of butanediol and pentanediol.
4. The nanoliposome containing a ceramide-like extract as claimed in claim 3, wherein:
the hydrogenated phospholipid is at least one of hydrogenated lecithin and hydrogenated soybean phospholipid;
the polyalcohol is a compound of butanediol and pentanediol.
5. The nanoliposome containing a ceramide-like extract as claimed in claim 1 or 2, wherein:
the particle size of the nano-liposome containing the ceramide-like extract is 50-700nm, the average particle size is less than 200nm, and the nano-liposome is uniformly distributed.
6. The method for preparing nanoliposomes containing a ceramide-like extract as claimed in any one of claims 1 to 5, which comprises the steps of:
(1) heating ceramide-like extract to 70-80 deg.C, adding phospholipid, cholesterol and polyalcohol, and stirring at 70-80 deg.C to obtain uniform mixed solution A;
(2) adding glycerol into the mixed solution A at the temperature of 70-80 ℃, and uniformly stirring to obtain a uniform mixed solution B;
(3) adding water into the mixed solution B at the temperature of 70-80 ℃, and uniformly stirring to obtain a uniform mixed solution C;
(4) and (3) keeping the temperature of the mixed solution C at 70-75 ℃, and homogenizing to obtain the nanoliposome containing the ceramide-like extract.
7. The method of claim 6, wherein:
the heating degree in the step (1) is 75-80 ℃;
the temperature in the step (2) is 70-75 ℃;
the temperature in the step (3) is 70-75 ℃.
8. The method of claim 6, wherein:
the homogenization conditions in the step (4) are as follows: homogenizing for 3-10 times at high pressure of 35-40MPa, and homogenizing for the last time at 80 MPa.
9. Use of the nanoliposome containing a ceramide-like extract as claimed in any one of claims 1 to 5 in the preparation of daily chemical products.
10. Use according to claim 9, characterized in that: the daily chemical product has at least one of the following effects: moisturizing, caring skin, whitening, and eliminating speckle.
CN202210339058.3A 2022-04-01 2022-04-01 Nano-liposome containing ceramide-like extract and preparation method and application thereof Pending CN114712261A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115300444A (en) * 2022-08-24 2022-11-08 深圳浦瑞健康科技有限公司 Preparation method and application of propolis liposome

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101214198A (en) * 2007-12-28 2008-07-09 清华大学 Ceramide nano liposome preparations and preparation and application thereof
CN112280806A (en) * 2019-07-23 2021-01-29 广东现代汉方科技有限公司 Method for preparing ceramide by emulsification fermentation and application thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101214198A (en) * 2007-12-28 2008-07-09 清华大学 Ceramide nano liposome preparations and preparation and application thereof
CN112280806A (en) * 2019-07-23 2021-01-29 广东现代汉方科技有限公司 Method for preparing ceramide by emulsification fermentation and application thereof

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115300444A (en) * 2022-08-24 2022-11-08 深圳浦瑞健康科技有限公司 Preparation method and application of propolis liposome
CN115300444B (en) * 2022-08-24 2023-08-04 深圳浦瑞健康科技有限公司 Preparation method and application of propolis liposome

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