CN106562931A - Preparation method of short-chain fatty acid vesicles - Google Patents
Preparation method of short-chain fatty acid vesicles Download PDFInfo
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- CN106562931A CN106562931A CN201610994882.7A CN201610994882A CN106562931A CN 106562931 A CN106562931 A CN 106562931A CN 201610994882 A CN201610994882 A CN 201610994882A CN 106562931 A CN106562931 A CN 106562931A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1277—Processes for preparing; Proliposomes
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- 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
- 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
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
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- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
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Abstract
The invention discloses a preparation method of short-chain fatty acid vesicles, and belongs to the technical field of preparation of vesicles. With short-chain fatty acid that a carbon chain less than 8 as a raw material, pH titration is conducted under the action of amine or amino acid protonation, and the short-chain fatty acid vesicles are formed when pH of a solution is equal to pka. According to the preparation method provided by the invention, the short-chain fatty acids are self-assembled in a water system, so that the vesicles are formed; and the vesicles, which are prepared by self-assembling main fatty acids in an organism, are good in compatibility and are conducive to cooperative delivery, therefore, a novel enforceable effective approach is provided for the development of an O/W delivery system.
Description
Technical field
The invention belongs to vesicle preparing technical field, and in particular to a kind of preparation method of short-chain fatty acid vesicle.
Background technology
Fatty acid（Fatty Acid）, it is the aliphatic hydrocarbon chain containing carboxyl, its general structure is CH3[CH2]nCOOH。
Fatty acid is closely related with people, and more common satisfied fatty acid has octanoic acid, capric acid, lauric acid, myristic acid, soft in daily life
Fat acid, stearic acid, arachidic acid etc..Short-chain fatty acid（By the product of stodgy saccharide zymolysis in colon）Account in human body
According to consequence, such as acetic acid, propanoic acid and butanoic acid.Mclaughlin have studied fatty acid adjust cholecystokinin chain length according to
Bad mechanism, it is found that different carbon chain fatty acid can promote the release concentration of cholecystokinin.Nanji is rich by zoopery, finding
Meals containing satisfied fatty acid can repair alcoholic liver injury.Fu Hong by with people's differentiated colon cancer Caco-2 as model,
It was found that short-chain fatty acid has obvious inhibition to Proliferation of Human Colon, differentiation and transfer；Tan Li is by setting up rat
Blind loop syndrome model, studies the change of rat plasma D-L lactic acid and short-chain fat acid metabolic, it is found that short-chain fatty acid also has
There is regulating intestinal canal flora and improve function of intestinal canal.
Vesicle (vesicle), as a kind of important self-assembled nano structures, is spontaneously formed by particular molecule, in order row
The double-deck or multilayer film of row forms a kind of nano hollow structure, the features such as with delivery, solubilising, slow release, be widely used in medicine,
The industries such as food.In the food industry, the main application in food of vesicle includes improving the quality structure of food composition, food enclosed in sealed
Raw material or additive, the release for controlling flavor substance and the utilization rate for improving nutrient substance.Such as protease is encapsulated in into phospholipid
It is enough to keep good activity in cheese condenses in vesicle, the loss of milk surum nitrogen, control are reduced in cheese maturation process
The generation of bitterness；Nisin is embedded in vesicle, targeted release where putrefactive microorganisms is realized, suppresses cheese
It is corrupt.Vesicle is also widely used in functional food additives：By additive package in phospholipid capsule bubble, this is effectively reduced
Loss of a little materials in processing is preserved, improves fat-soluble solubility of additive, strengthens its absorbance, and additive is with this side
After formula is entered in vivo, can with its from internal Digestive system destruction, and the effect with directional controlled release；Vitamin C and
Vitamin E is embedded in phospholipid capsule bubble, and to strengthen oral result, in being added to nutriment, biological activity has obtained preferable guarantor
Shield.
When vesicle is used as the carrier of antitumor drug, the toxicity of embedding medicinal can be reduced, overcome drug resistance, improve treatment
Effect.Kakinuma utilizes thermal sensitivity liposome, by heating to rat brain, increased medicine in the poly- of brain tumor position
Collection, improves curative effect.Kubo treats tumor in the bone of hamster using magnetic liposome, it is found that its targeted therapy effect is obvious；Vesicle is also
The carrier of antibacterials and hormonal medicaments is can serve as, and with good effect.
The content of the invention
For the problem that prior art is present, it is an object of the invention to design provide a kind of system of short-chain fatty acid vesicle
The technical scheme of Preparation Method.The method adopts the short-chain fatty acid of biocompatibility for raw material, and good biocompatibility can be applicable to
The fields such as food, health product, cosmetics, medicine, biochemical industry, especially fit bio-pharmaceutical carrier systems, with raising biofacies
The advantages such as capacitive, pH responses.
The preparation method of described a kind of short-chain fatty acid vesicle, it is characterised in that with short-chain fatty acid of the carbochain less than 8
For raw material, under amine or aminoacid protonation, titrated by pH, short-chain fatty acid capsule is formed in pH value of solution=pka
Bubble.
The preparation method of described a kind of short-chain fatty acid vesicle, it is characterised in that short-chain fatty acid is soluble in the aqueous phase molten
Liquid, adds amine or aminoacid protonation.
A kind of preparation method of described short-chain fatty acid vesicle, it is characterised in that short-chain fatty acid 1-5 in molar ratio:
0.5 ratio is mixed homogeneously with amine or aminoacid.
A kind of preparation method of described short-chain fatty acid vesicle, it is characterised in that the carbochain of short-chain fatty acid more than 4 and
Less than 8.
The preparation method of described a kind of short-chain fatty acid vesicle, it is characterised in that adjust pH value=6.5-9.5.
The preparation method of described a kind of short-chain fatty acid vesicle, it is characterised in that short-chain fatty acid vesicle particle size range is
60-180nm。
The preparation method of described a kind of short-chain fatty acid vesicle, it is characterised in that aqueous phase solution is that deionized water or pH exist
The buffer solution of 6-8.
A kind of preparation method of above-mentioned short-chain fatty acid vesicle is reasonable in design, compared with prior art with following beneficial
Effect：
1st, the invention provides one kind is self-assembly of vesicle method with common short-chain fatty acid in human body in aqueous systems, can use
In water-soluble solvent environment, aqueous systems delivery valid density is improved.Using the fatty acid carrier systems biocompatibility of the present invention
It is good, with effective solubilization, and bioavailability can be increased substantially, meet the demand of Drug delivery system.
2nd, short-chain fatty acid of the present invention is self-assembly of vesicle as a kind of new water phase low toxicity carrier in aqueous systems,
Particle size range 60-400nm, meets research data, and particle diameter is more easy to be phagocytized by cells in hundreds of ran, is conducive to being supported into
Divide and reach targeting target.Meanwhile, there is certain slow releasing function to loading composition.
3rd, short-chain fatty acid of the present invention is self-assembly of vesicle in aqueous systems, is from group with biological main fatty acid in vivo
Dress, the compatibility is good, is conducive to collaboration delivery, and for the exploitation of O/W carrier systems a new enforceable effective way is provided.
Description of the drawings
Fig. 1 is transmission electron microscope（TEM）Image, is enanthic acid (100mM) and ethamine in figure（100mM）Under different pH
Microstructure image；
Fig. 2 is low-temperature transmission ultramicroscope（cyro-TEM）Image, is respectively butanoic acid, valeric acid, acid, enanthic acid is in pH=in figure
The 7.4 vesicle cyro-TEM images for being formed；
Fig. 3 is the control of FT-IR spectrograms, and a length of 4 to the 8 short-chain fatty acid FT-IR spectrogram of chain is respectively in figure.
Specific embodiment
With reference to embodiments further illustrating the present invention.
Embodiment 1
A kind of preparation method of short-chain fatty acid vesicle, by butanoic acid, valeric acid, acid or enanthic acid and ethamine press 5mmol/L and
0.5mmol/L is dissolved in deionized water and mixes, and stirs 5-10min, balances 10-60min, adjusts pH=6.5-9.5, you can system
Obtain self assembly vesicle solution.
Characterized by dynamic light scattering and low-temperature transmission electron microscopic respectively：Fig. 2 is fatty acid and ethamine self assembly shape
The low-temperature transmission electron microscope image of vesicle is responded into pH, shows the fatty acid vesicle to form stable homogeneous, vesicle particle diameter model
Enclose for 60-180nm.
Embodiment 2
Short-chain fatty acid vesicle pH response experimental verifications：Enanthic acid and ethamine are dissolved in into deionization by 1mmol/L and 1mmol/L
Then water or pH adjust pH=3-10 to mix in the buffer solution of 6-8 and uniformly.
Morphology characterization is carried out by dynamic light scattering and transmission electron microscopy in different pH scopes：Fig. 1 is enanthic acid and ethamine
The transmission electron microscope image that pH responds vesicle is self-assembly of, shows that in pH=6.5-9.5 vesicle can be formed, work as pH>9.5
The complete depolymerization of vesicle forms micellar structure.
Embodiment 3
Different chain length fatty acid forms vesicle experiment：By butanoic acid, or valeric acid, or acid, or enanthic acid, or octanoic acid and ethamine are pressed
5mmol/L and 0.5mmol/L are dissolved in the water and uniformly mix, and adjust pH=6.5-9.5.
Sampling carries out that Fourier is infrared to carry out 400-4000cm-1Scanning：It is enanthic acid that Fig. 3 is a length of 4 to 8 short-chain fatty acid of chain
The FT-IR spectrograms for being self-assembly of pH response vesicles with ethamine change, in 1560cm-1With 1645 cm-1Go out peak shift and split peak
Show that the carbonyl in fatty acid forms hydrogen bond, further prove that short-chain fatty acid is self-assembly of vesicle.
Embodiment 4
Vesicle experiment is formed to fatty acid in different chain length amine：By enanthic acid and ethamine, or propylamine, or butylamine, amylamine, or amine,
Or heptyl amice is dissolved in the water by 0.2mmol/L and 0.1mmol/L and uniformly mixes, pH=6.5-9.5 is adjusted.Sampling is by dynamic
Light scattering and transmission electron microscopy carry out morphology characterization and can form vesicle.
Embodiment 5
Vesicle experiment is formed to fatty acid in different chain length amine：By enanthic acid and ethamine, or propylamine, or butylamine, amylamine, or amine,
Or heptyl amice is dissolved in deionized water by 0.2mmol/L and 0.2mmol/L and is uniformly mixed, take different pH scopes and characterized.
Equally can obtain, sample has phase in version process by dynamic light scattering and transmission electron microscopy in pH6.5 and pH9.5.
Embodiment 6
Basic amino acid forms vesicle experiment with short-chain fatty acid：By enanthic acid and histidine, or Phenylalanine, or lysine is pressed
0.2mmol/L and 0.2mmol/L are dissolved in deionized water and uniformly mix, and adjust pH value=6.5-9.5, you can be obtained from group
Dress vesicle solution.Sampling carries out morphology characterization by dynamic light scattering and transmission electron microscopy can form vesicle.
Claims (7)
1. a kind of preparation method of short-chain fatty acid vesicle, it is characterised in that the short-chain fatty acid with carbochain less than 8 as raw material,
Under amine or aminoacid protonation, titrated by pH, short-chain fatty acid vesicle is formed in pH value of solution=pka.
2. a kind of preparation method of short-chain fatty acid vesicle as claimed in claim 1, it is characterised in that short-chain fatty acid is molten
In aqueous phase solution, amine or aminoacid protonation are added.
3. a kind of preparation method of short-chain fatty acid vesicle as claimed in claim 1 or 2, it is characterised in that short-chain fatty acid is pressed
Mol ratio 0.5-5:0.5 ratio is mixed homogeneously with amine or aminoacid.
4. a kind of preparation method of short-chain fatty acid vesicle as claimed in claim 1, it is characterised in that the carbon of short-chain fatty acid
Chain is more than 4 and less than 8.
5. a kind of preparation method of short-chain fatty acid vesicle as claimed in claim 1, it is characterised in that adjust pH value=6.5-
9.5。
6. a kind of preparation method of short-chain fatty acid vesicle as claimed in claim 1, it is characterised in that short-chain fatty acid vesicle
Particle size range is 60-180nm.
7. a kind of preparation method of short-chain fatty acid vesicle as claimed in claim 2, it is characterised in that aqueous phase solution for go from
The buffer solution of sub- water or pH in 6-8.
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| CN201610994882.7A CN106562931B (en) | 2016-11-11 | 2016-11-11 | A kind of preparation method of short chain fatty acids vesica |
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| CN201610994882.7A CN106562931B (en) | 2016-11-11 | 2016-11-11 | A kind of preparation method of short chain fatty acids vesica |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108558638A (en) * | 2018-03-30 | 2018-09-21 | 中国科学院过程工程研究所 | A kind of preparation method and application of the fluorescence probe based on self-assembly vesicle |
| CN109550054A (en) * | 2018-11-08 | 2019-04-02 | 浙江工商大学 | A kind of preparation method of short-chain alkyl phosphonic acids vesica |
| CN109810287A (en) * | 2019-01-28 | 2019-05-28 | 扬州大学 | A kind of preparation method of chitosan quaternary ammonium salt-fatty acid vesica |
-
2016
- 2016-11-11 CN CN201610994882.7A patent/CN106562931B/en active Active
Non-Patent Citations (3)
| Title |
|---|
| CAO CAO等: "Chain-Length-Dependent Autocatalytic Hydrolysis of Fatty Acid Anhydrides in Polyethylene Glycol", 《THE JOURNAL OF PHYSICAL CHEMISTRY》 * |
| LI-HUI SUN等: "Controllable Self-Assembly of Sodium Caseinate with a Zwitterionic Vitamin-Derived Bolaamphiphile", 《JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY》 * |
| ZHONG-XIU CHEN等: "Molecular Recognition of Melamine by Vesicles Spontaneously Formed from Orotic Acid Derived Bolaamphiphiles", 《THE JOURNAL OF PHYSICAL CHEMISTRY》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108558638A (en) * | 2018-03-30 | 2018-09-21 | 中国科学院过程工程研究所 | A kind of preparation method and application of the fluorescence probe based on self-assembly vesicle |
| CN108558638B (en) * | 2018-03-30 | 2021-01-15 | 中国科学院过程工程研究所 | Preparation method and application of fluorescent probe based on self-assembled vesicle |
| CN109550054A (en) * | 2018-11-08 | 2019-04-02 | 浙江工商大学 | A kind of preparation method of short-chain alkyl phosphonic acids vesica |
| CN109810287A (en) * | 2019-01-28 | 2019-05-28 | 扬州大学 | A kind of preparation method of chitosan quaternary ammonium salt-fatty acid vesica |
| CN109810287B (en) * | 2019-01-28 | 2020-12-25 | 扬州大学 | Preparation method of chitosan quaternary ammonium salt-fatty acid vesicles |
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Effective date of registration: 20190725 Address after: Hangzhou City, Zhejiang province 310018 Xiasha Higher Education Park is 18 street. Applicant after: Zhejiang Gongshang University Address before: 310023 Xihu District, Zhejiang Province, and the left road, No. 318, Applicant before: Zhejiang University of Science and Technology |
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