CN108272652A - A kind of ceramide liposome and its preparation method and application - Google Patents
A kind of ceramide liposome and its preparation method and application Download PDFInfo
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- CN108272652A CN108272652A CN201810215403.6A CN201810215403A CN108272652A CN 108272652 A CN108272652 A CN 108272652A CN 201810215403 A CN201810215403 A CN 201810215403A CN 108272652 A CN108272652 A CN 108272652A
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- 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
- A61K8/68—Sphingolipids, e.g. ceramides, cerebrosides, gangliosides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/14—Liposomes; Vesicles
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- 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
- A61K8/34—Alcohols
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- 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
- A61K8/34—Alcohols
- A61K8/345—Alcohols containing more than one hydroxy group
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- 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
- A61K8/35—Ketones, e.g. benzophenone
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- 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
- A61K8/678—Tocopherol, i.e. vitamin E
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
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Abstract
The invention discloses a kind of ceramide liposomes and its preparation method and application.The ceramide liposome includes following component：Glycerine 5~50%, ethoxydiglycol 1~20%, ceramide 0.1~10% and phosphatidase 0 .5~30%, 100% is complemented to water；The wherein described phosphatide is lecithin and/or hydrolecithin, and the ceramide liposome does not include cholesterol；The percentage is the mass percent for accounting for ceramide liposome.Ceramide liposome stability prepared by the present invention is high, and good dispersion in water, grain size reaches 50~500nm of nanoscale；And production is convenient, using common homogeneous blender T25 Digital Package 1 (IKA).
Description
Technical field
The present invention relates to chemical fields, and in particular to a kind of ceramide liposome and its preparation method and application.
Background technology
Ceramide (Ceramride) is also known as sphingolipid (Sphingolipid), is to be present in a kind of fat in skin
Matter plays an important role in epidermal keratinocytes layer formation process.Research in recent years shows drying, furfur, cracking occur when skin
Phenomenon, when barrier function is substantially reduced, skin supplement ceramide can restore rapidly moisturizing and barrier function.It is right in view of its
Skin specific function and curative effect, in recent years, ceramide also rapidly become domestic and international cosmetics company develop it is a kind of novel
Superior cosmetics object active additive.
But ceramide is as dystectic oil soluble material, and the addition in cosmetics is in use, relatively difficult, especially
In aqua product, it is difficult to using.Ceramide is made liposomal form, is on the one hand convenient for ceramide in cosmetic formulations
Use, on the other hand can also improve the compatibility of ceramide and horn cell, provide ceramide with moisturizing, antiallergic and
Maintenance and other effects.But poor dispersion in the stability and water of the ceramide liposome prepared at present, while needing using spy
Different production equipment, being unfavorable for industrialized production, (Qin Dean, what learns the preparation method of people's ceramide liposome emulsions:CN：
98110614.5；Zhang Wanping, Tian Yonghong, Guo Yiguang wait a kind of Ceramide nanoemulsions of and preparation method thereof:,
CN104739658A[P].2015；Xia Qiang thanks to a kind of Ceramide nanoemulsions of strong and preparation method thereof:,CN
103690391B[P].2016)。
There is an urgent need for the ceramide liposomes of good dispersion in a kind of stability height, water to make up the deficiencies in the prior art.
Invention content
The technical problem to be solved by the present invention is to overcome, stability existing for existing ceramide liposome is poor, in water
Dispersed bad, industrialized production there are the defect of limitation, provide a kind of ceramide liposome and preparation method thereof and
Using.Ceramide liposome stability provided by the invention is high, good dispersion in water, and preparation method is convenient, has good
Industrial prospect.
There are certain technology barriers for the preparation of ceramide liposome in the prior art, such as：Liposome is micro-
Grain, it is as high-pressure homogeneous in not having to, it is extremely difficult to Nano grade.The presence of the technology barrier not only increases ceramide liposome work
The cost of industry metaplasia production, also prevents in the field and ceramide liposome is conducted further research and applied.The present invention
Ethoxydiglycol is creatively applied to the preparation of ceramide liposome by people, instead of cholesterol customary in the art,
The replacement of the raw material to prepare during ceramide liposome without using high pressure homogenizer, you can obtains Nano grade
Liposome particle.
The present invention is to solve above-mentioned technical problem by following technical solution：
One of technical scheme of the present invention is：A kind of ceramide liposome comprising following component：Glycerine 5~50%,
Ethoxydiglycol 1~20%, ceramide 0.1~10% and phosphatidase 0 .5~30%, 100% is complemented to water；Wherein institute
It is lecithin and/or hydrolecithin to state phosphatide；The percentage is the mass percent for accounting for ceramide liposome.
Preferably, the ceramide liposome includes following component：Glycerine 10~30%, ethoxydiglycol 1~
10%, ceramide 0.5~10% and phosphatidase 5~10% complement to 100% with water；The percentage is to account for ceramide
The mass percent of liposome.
Lecithin isoreactivity ingredient is aoxidized in order to prevent, and the ceramide liposome further includes preferably anti-oxidant
The content of agent, the antioxidant is preferably 0.1~1%, and the percentage is the mass percent for accounting for ceramide liposome；
Wherein, the antioxidant can be the antioxidant of this field routine, preferably be selected from tocopherol (vitamin E), Vitamin C
It is one or more in acid and its derivative；The derivative is selected from tocopherol acetate, ascorbic acid glucoside, Vitamin C
It is one or more in sour palmitate and 3-O- ethylascorbyls.
The ceramide liposome further includes preferably antiseptic, and the content of the antiseptic is preferably 0.04~
0.7%, more preferably 0.5%, the percentage are the mass percent for accounting for ceramide liposome.Wherein, the antiseptic
It can be the antiseptic of this field routine, preferably be selected from parahydroxyacet-ophenone, hexylene glycol, hydroximic acid, pentanediol, Chlorphenesin
With it is one or more in methyl hydroxybenzoate；More preferably, the ceramide liposome include parahydroxyacet-ophenone 0.5% and oneself two
Alcohol 0.5% or decoyl hydroximic acid 0.05%, the percentage are the mass percent for accounting for ceramide liposome.
In order to enhance liposome moistening effect, the stability of liposome is improved, the ceramide liposome is preferably gone back
Including helping moisturizer, described to help the content of moisturizer be preferably 5~8%, and further preferably 8%；The percentage is to account for god
Mass percent through amide lipid body.Wherein, described to help moisturizer conventional for this field, preferably it is selected from mannose
Alcohol, sorbierite, 1, it is one or more in 3 butanediols, propylene glycol and dipropyl glycol.
In order to improve the stability of liposome, the ceramide liposome further includes preferably assistant for emulsifying agent, described to help
The content of emulsifier is preferably 0.5~2%, and more preferably 1%；The percentage is the quality percentage for accounting for ceramide liposome
Than.Wherein, the assistant for emulsifying agent can be that this field is conventional, be preferably selected from sugar ester, sucrose fatty ester, alkyl glycosides, spit
It is one or more in temperature 80 and polysorbas20.
Technical scheme of the present invention second is that：A kind of preparation method of above-mentioned ceramide liposome comprising following step
Suddenly：
(1) glycerine, ethoxydiglycol, phosphatide and ceramide are taken, selectively add antioxidant, assistant for emulsifying agent and
Moisturizer, Hybrid Heating is helped to obtain glycerite；
(2) the glycerite mixing obtained by step (1) is added in water intaking heating, and homogeneous is cooling, obtains first product；Selectively also
Including：
(3) antiseptic is selectively added into the first product obtained by step (2), is uniformly mixed, you can.
Wherein, the temperature heated described in step (1) is preferably 80~100 DEG C, is more preferably 85 DEG C.
The temperature heated described in step (2) is preferably 80~100 DEG C, is more preferably 85 DEG C.
The speed of homogeneous described in step (2) is preferably 500~5000rpm, is more preferably 2500~4000rpm, into
One step is more preferably 3500rpm.
The speed stirred when homogeneous described in step (2) is preferably 50~300rpm, is more preferably 150rpm.
The time of homogeneous described in step (2) is preferably 3~15min, is more preferably 10min；
The equipment of homogeneous described in step (2) can be common homogeneous blender；
Cooling temperature described in step (2) is preferably 40~60 DEG C, is more preferably 50 DEG C.
The three of technical scheme of the present invention are：A kind of application of above-mentioned ceramide liposome in cosmetics, wherein institute
Ceramide liposome is stated preferably as cosmetic additive agent.
The ceramide liposome is when as cosmetic additive agent, ceramide therein and horn cell compatibility
It is greatly improved, has effects that good moisturizing, antiallergic and repairs.
On the basis of common knowledge of the art, above-mentioned each optimum condition can be combined arbitrarily to get each preferable reality of the present invention
Example.
The reagents and materials used in the present invention are commercially available.
The positive effect of the present invention is that：Ceramide liposome stability prepared by the present invention is high, disperses in water
Property it is good, grain size reach 50~500nm of nanoscale；And production is convenient, using common homogeneous blender T25Digital Package 1
(IKA).
Description of the drawings
Fig. 1 is liposomal particle size distribution map.
Fig. 2 is variation tendency of the patient using skin TEWL values after liposome；The competing product are patent application
Ceramide nanoemulsion in CN201310732992.2；The non-liposomal control refers to that ceramide is directly dissolved
It is obtained in grease (caprylic/capric triglyceride).
Specific implementation mode
It is further illustrated the present invention below by the mode of embodiment, but does not therefore limit the present invention to the reality
It applies among a range.In the following examples, the experimental methods for specific conditions are not specified, according to conventional methods and conditions, or according to quotient
Product specification selects.
" granularmetric analysis test " is used to the granularmetric analysis of liposome obtained by embodiment, which passes through Malvern laser grain
It spends analyzer and tests liposomal particle size size.
The model T25Digital Package 1 (IKA) of homogenizer used in following embodiments.
Embodiment 1
Glycerine 5g, lecithin 1g, ceramide 0.2g, tocopherol acetate 0.1g and ethoxydiglycol 3g are weighed,
85 DEG C are heated to, is stirred to transparent and homogeneous glycerite；In container, water 89.7g is added, is heated to 85 DEG C, opens homogeneous
Machine rate 1000rpm, stir speed (S.S.) 50rpm are slowly added into glycerite, and homogeneous 3min stops homogeneous, and stirring is cooled to 50
DEG C, parahydroxyacet-ophenone 0.5g, hexylene glycol 0.5g is added, is stirred to being completely dissolved.Liposomal particle size is distributed：
82.3% grain size is 164.2 nanometers, and 17.7% is 22.08 nanometers (Fig. 1)；Illustrate that liposome has sufficiently achieved nano particle
Size, and particle diameter distribution is uniform.
Embodiment 2
Glycerine 10g, lecithin 5g, Cer NS g, tocopherol acetate 0.3g and ethoxydiglycol 10g are weighed,
85 DEG C are heated to, is stirred to transparent and homogeneous glycerite；In container, water 71.7g is added, is heated to 85 DEG C, opens homogeneous
Machine rate 1500rpm, stir speed (S.S.) 80rpm are slowly added into glycerite, and homogeneous 4min stops homogeneous, and stirring is cooled to 50
DEG C, parahydroxyacet-ophenone 0.5g, hexylene glycol 0.5g is added, is stirred to being completely dissolved.Liposomal particle size is distributed：
85.6% grain size is 202 nanometers；14.4% is 85 nanometers.
Embodiment 3
Weigh glycerine 20g, lecithin 5g, hydrolecithin 1g, ceramide 0.5g, tocopherol acetate 0.3g, sweet dew
Sugar alcohol 5g and ethoxydiglycol 10g, is heated to 85 DEG C, is stirred to transparent and homogeneous glycerite；In container, it is added
Water 57.2g is heated to 80 DEG C, opens homogenizer rate 1500rpm, stir speed (S.S.) 80rpm and is slowly added into glycerite, homogeneous
5min stops homogeneous, and stirring is cooled to 50 DEG C, and parahydroxyacet-ophenone 0.5g, hexylene glycol 0.5g is added, and is stirred to completely molten
Solution.Liposomal particle size is distributed：91% grain size is 187 nanometers；9% is 275 nanometers.
Embodiment 4
Glycerine 30g, lecithin 30g, hydrolecithin 1g, Cer EOS 0g and ethoxydiglycol 20g are weighed, is added
Heat is stirred to 85 DEG C to transparent and homogeneous glycerite；In container, water 8g is added, is heated to 85 DEG C, opens homogenizer rate
1500rpm, stir speed (S.S.) 80rpm are slowly added into glycerite, and homogeneous 3min stops homogeneous, and stirring is cooled to 50 DEG C, is added
Parahydroxyacet-ophenone 0.5g, hexylene glycol 0.5g are stirred to being completely dissolved.Liposomal particle size is distributed：87.2% grain
Diameter is 243 nanometers；13.8% is 168 nanometers.
Embodiment 5
Glycerine 50g, lecithin 0.5g, Tween-80 1g, ceramide 0.1g and ethoxydiglycol 1g are weighed, is added
Heat is stirred to 85 DEG C to transparent and homogeneous glycerite；In container, water 46.4g is added, is heated to 85 DEG C, opens homogenizer
Rate 1500rpm, stir speed (S.S.) 80rpm are slowly added into glycerite, and homogeneous 5min stops homogeneous, and stirring is cooled to 60 DEG C,
Parahydroxyacet-ophenone 0.5g, hexylene glycol 0.5g is added, is stirred to being completely dissolved.Liposomal particle size is distributed：86.3%
Grain size be 287 nanometers；13.7% is 143 nanometers.
Embodiment 6
Weigh glycerine 30g, lecithin 10g, Cer NP g, ethoxydiglycol 10g, mannitol 3g and 1,3- fourth
Glycol 5g is heated to 85 DEG C, is stirred to transparent and homogeneous glycerite；In container, water 38g is added, is heated to 85 DEG C, opens
Homogenizer rate 1500rpm, stir speed (S.S.) 80rpm are slowly added into glycerite, and homogeneous 4min stops homogeneous, and stirring is cooled to
40 DEG C, parahydroxyacet-ophenone 0.5g, hexylene glycol 0.5g is added, is stirred to being completely dissolved.Liposomal particle size is distributed：
91% grain size is 128 nanometers；9% is 247 nanometers.
Effect example 1
The particle diameter distribution for the ceramide liposome that Examples 1 to 6 is prepared is uniform, is now prepared into using embodiment 3
To liposome carry out water in dispersibility and stability experiment.According to experimental result (table 1) as it can be seen that the ceramide fat detected
The stability of plastid is high, good dispersion in water.
Dispersibility and stability test data in the water for the ceramide liposome that 1 embodiment 3 of table is prepared
Effect example 2
Clinical trial：
According to 5% and 10%, (percentage is weight to the ceramide liposome that embodiment 3 is prepared respectively
Percentage) additive amount be distributed in aqua spraying, ask patient's (red swelling of the skin, itch pain) of slight hormone dependant history of venereal disease, it is early
Evening is each primary using spraying；Wherein, TEWL (transepidermal waterloss) refers to percutaneous loss of moist, is evaluation
One of index of skin barrier function.When barrier function damage, TEWL values increase；On the contrary, when TEWL values reduce, prompting screen
Barrier is repaired.As can be known from Fig. 2：The aqua spraying for being added with 5% and 10% ceramide liposome respectively can be obviously
Improve the skin of patient, it was demonstrated that the reparation of liposome of the invention effect of releiving meets expection.
Claims (10)
1. a kind of ceramide liposome, which is characterized in that it includes following component：Glycerine 5~50%, ethoxydiglycol 1
~20%, ceramide 0.1~10% and phosphatidase 0 .5~30%, 100% is complemented to water；The wherein described phosphatide is lecithin
Fat and/or hydrolecithin, the ceramide liposome do not include cholesterol；The percentage is to account for ceramide liposome
Mass percent.
2. ceramide liposome as described in claim 1, which is characterized in that it includes following component：Glycerine 10~30%,
Ethoxydiglycol 1~10%, ceramide 0.5~10% and phosphatidase 5~10%, 100% is complemented to water；The percentage
Than to account for the mass percent of ceramide liposome.
3. ceramide liposome as claimed in claim 1 or 2, which is characterized in that it further includes antioxidant 0.1~1%；
Preferably, the antioxidant is one kind in tocopherol (vitamin E), ascorbic acid (vitamin C) and its derivative
Or it is a variety of；The derivative is selected from tocopherol acetate, ascorbic acid glucoside, ascorbyl palmitate and 3-O- ethyls
One or more in ascorbic acid, the percentage is the mass percent for accounting for ceramide liposome.
4. ceramide liposome as claimed in claim 1 or 2, which is characterized in that it further includes antiseptic, the antiseptic
Content be preferably 0.04~0.7%, more preferably 0.5%；Preferably, the antiseptic be selected from parahydroxyacet-ophenone, oneself
It is one or more in glycol, hydroximic acid, pentanediol, Chlorphenesin and methyl hydroxybenzoate；More preferably, the ceramide liposome
Including parahydroxyacet-ophenone 0.5% and hexylene glycol 0.5% or decoyl hydroximic acid 0.05%, the percentage is to account for ceramide
The mass percent of liposome.
5. ceramide liposome as claimed in claim 1 or 2, which is characterized in that it further includes assistant for emulsifying agent, described to help breast
The content of agent is preferably 0.5~2%；More preferably 1%；
Preferably, the assistant for emulsifying agent is one in sugar ester, sucrose fatty ester, alkyl glycosides, Tween 80 and polysorbas20
Kind is a variety of；More preferably, the ceramide liposome includes Tween 80 1%；The percentage is to account for ceramide liposome
Mass percent.
6. ceramide liposome as claimed in claim 1 or 2, which is characterized in that the ceramide liposome further includes
Help moisturizer, described to help the content of moisturizer be preferably 5~8%, and the percentage is the quality hundred for accounting for ceramide liposome
Divide ratio.
7. ceramide liposome as claimed in claim 6, which is characterized in that the moisturizer that helps is selected from mannose
Alcohol, sorbierite, 1, it is one or more in 3 butanediols, propylene glycol and dipropyl glycol.
8. a kind of preparation method of such as claim 1~7 any one of them ceramide liposome, which is characterized in that it is wrapped
Include following steps：
(1) glycerine, ethoxydiglycol, phosphatide and ceramide are taken, antioxidant, assistant for emulsifying agent are selectively added and helps guarantor
Humectant, Hybrid Heating obtain glycerite；
(2) the glycerite mixing obtained by step (1) is added in water intaking heating, and homogeneous is cooling, obtains first product；Selectively also wrap
It includes：
(3) antiseptic is selectively added into the first product obtained by step (2), is uniformly mixed, you can.
9. preparation method as claimed in claim 8, which is characterized in that the temperature heated described in step (1) is 80~100
DEG C, preferably 85 DEG C；
The temperature heated described in step (2) is 80~100 DEG C, preferably 85 DEG C；
The speed of homogeneous described in step (2) is 1000~1500rpm；
The speed stirred when homogeneous described in step (2) is 50~100rpm, preferably 80rpm；
The time of homogeneous described in step (2) is 3~5min；
The equipment of homogeneous described in step (2) is common homogeneous blender；
And/or cooling temperature described in step (2) is 40~60 DEG C, preferably 50 DEG C.
10. such as application of the claim 1~7 any one of them ceramide liposome in cosmetics, wherein the nerve
Amide lipid body is preferably as cosmetic additive agent.
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| CN110101591A (en) * | 2019-05-23 | 2019-08-09 | 广州科斯曼生物科技有限公司 | A kind of long-acting moisture-keeping composition and its preparation method and application |
| CN110339085A (en) * | 2019-02-20 | 2019-10-18 | 广东芭薇生物科技股份有限公司 | A kind of composition and its application containing ceramide liposome |
| CN110420127A (en) * | 2019-08-22 | 2019-11-08 | 陕西慧康生物科技有限责任公司 | A kind of essence and preparation method thereof with pearlescent appearance |
| CN110974750A (en) * | 2019-12-30 | 2020-04-10 | 杭州暮色化妆品有限公司 | Repairing and moisturizing composition and preparation method thereof |
| CN111743807A (en) * | 2020-08-03 | 2020-10-09 | 上海奥利实业有限公司 | Water-oil insoluble transparent ceramide aqueous solution and preparation method thereof |
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| CN114028261A (en) * | 2021-11-26 | 2022-02-11 | 浙江宜格企业管理集团有限公司 | Flexible liposome with high ceramide load capacity and preparation method thereof |
| CN114224841A (en) * | 2022-01-21 | 2022-03-25 | 上海彤颜实业有限公司 | WGX-50 liposome, preparation method and application |
| CN115252502A (en) * | 2022-08-26 | 2022-11-01 | 嘉文丽（福建）化妆品有限公司 | Preparation method of hibiscus mutabilis extract liposome and liposome thereof |
| CN115381731A (en) * | 2021-11-02 | 2022-11-25 | 广州雅纯化妆品制造有限公司 | Plant-derived ceramide nano liposome composition and preparation method thereof |
| CN115737453A (en) * | 2022-12-20 | 2023-03-07 | 广州旭帆生物科技有限公司 | Nano-efficacy substance inclusion soluble in transparent aqueous solution and preparation method thereof |
| CN116139036A (en) * | 2022-12-17 | 2023-05-23 | 上海优康化妆品有限公司 | Vitamin C-containing coated particles, preparation method thereof and vitamin C-containing essence |
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