CN111346056A - Preparation method of α -glucosyl hesperidin modified lutein liposome - Google Patents
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Abstract
The invention discloses a preparation method of α -glucosyl hesperidin modified lutein liposome, which is obtained by modifying α -glucosyl hesperidin and comprises the following steps of (1) dissolving lutein and lipid to obtain a lutein lipid solution, (2) hydrating the lipid film, and performing ultrasonic treatment to obtain a dispersion liquid, (3) dropwise adding a α -glucosyl hesperidin solution into the dispersion liquid, stirring at room temperature overnight, and (4) extruding the dispersion liquid through a polycarbonate film to obtain the lutein liposome, wherein the lutein liposome modified by α -glucosyl hesperidin has the properties of high stability and long-term circulation, and the absorption of lutein in eyes is remarkably improved.
Description
One, the technical field
The invention belongs to the technical field of functional food processing, and particularly relates to a preparation method of α -glucosyl hesperidin modified lutein liposome.
Second, background Art
Lutein, a natural carotenoid widely found in vegetables, fruits, flowers and certain algae organisms, is not synthesized by the human body itself and must be ingested or supplemented from the diet. Lutein is one of the main components of macular pigment of eyes, has the functions of absorbing blue light and enhancing retina tissues, and has obvious effects on the aspects of protecting vision, preventing cataract and the like. However, the molecular structure of lutein has a long carbon chain and contains a plurality of hydrophobic groups, so that the lutein has poor solubility in water, and the application of lutein in the fields of food, medicines and the like is limited.
The lutein is embedded in the forms of microcapsule technology, nano self-emulsifying carrier, nano-emulsifying composite system, liposome and the like, and is an effective means for improving the solubility, the tolerance to the external environment and the bioavailability. The lutein is embedded in the form of liposome, the preparation process is simple, and the lutein has higher loading capacity and encapsulation efficiency. The liposome is mainly phagocytized by a reticuloendothelial system after being loaded with drugs to activate the autoimmune function of a body, but the liposome is easy to be eliminated by a mononuclear macrophage system and the reticuloendothelial system in the body because the structure of the liposome membrane is similar to a biological membrane. It has been found that the stability of liposomes in blood can be increased by attaching a polyhydroxy group-containing substance to the phospholipid molecule, exposing some hydrophilic polysaccharides or polyhydroxy groups on the liposome surface. When the two factors of steric hindrance and increasing the hydrophilicity of the membrane surface act together, the liposome forms a long-acting liposome. In the existing research, polyethylene glycol (PEG) polymers with hydrophilicity and flexibility are often adopted to modify the surface of liposome, so that the adsorption of plasma components and the surface of the liposome is hindered, and the time of the liposome in systemic circulation is prolonged. For example, chinese patent CN101843584B discloses a compound of all-trans retinoic acid and liposome and its application, and the compound has better stability in serum system. However, after long-term use of the liposome modified by PEG, human bodies can generate anti-PEG IgG, and the immunogenicity of PEG can cause obvious humoral immune reaction, so that the blood half-life of the liposome modified by PEG is obviously shortened. Therefore, a substitute of PEG which can be circulated for a long time and is safe and nontoxic is searched, and the targeting location and the biological value of the liposome are effectively improved.
The invention modifies the lutein liposome with α -glucosyl hesperidin, the α -glucosyl hesperidin is coated on the surface of the lutein liposome through self-assembly, the α -glucosyl hesperidin hydrophobic head is positioned at the head of the liposome, and the hydrophilic end glucoside group is exposed on the surface of the liposome.
Third, the invention
The invention aims to provide a preparation method of α -glucosyl hesperidin modified lutein liposome, and the lutein liposome prepared by the method has good stability, long-acting circulation and high biological safety.
In order to achieve the purpose, the invention adopts the technical scheme that:
(1) dissolving lutein and lipid phase in chloroform-methanol solution at volume ratio of 2: 1 to obtain lutein lipid solution.
(2) Rotary evaporation is carried out to remove the organic solvent, so that the compound forms a uniform film at the bottom of the round-bottom flask, the vacuum degree is increased to 0.1MPa, and continuous pumping is carried out for 30 min.
(3) Adding phosphate solution into the composite film obtained in the step (2) for hydration, wherein the hydration temperature is 40-60 ℃, and the time is 30-120 min;
(5) carrying out ultrasonic treatment under the ice-water bath stirring condition, wherein the ultrasonic power is 800W, the pulse is 5s/5s, the treatment time is 10-30 min, then continuously stirring for 3-6 h at the temperature of 30-40 ℃, and the stirring rotating speed is 800-1200 r/min;
(6) centrifuging the dispersion obtained in the step (5) for 10min at the speed of 10000r/min, and removing the non-embedded lutein;
(7) α -glucosyl hesperidin is dissolved in a phosphate solution to obtain a α -glucosyl hesperidin solution with the mass concentration of 0.5-10%, the α -glucosyl hesperidin solution is dripped into the dispersion liquid obtained in the step (6), and the mixture is stirred at room temperature overnight;
(8) extruding the dispersion liquid obtained in the step (7) for 10-20 times through a 200nm polycarbonate membrane, and removing excess α -glucosyl hesperidin through a G200 sephadex column to obtain the α -glucosyl hesperidin-lutein liposome.
Preferably, in the step (1), the lipid phase consists of cholesterol and dipalmitoylphosphatidylcholine, the mass ratio of the cholesterol to the dipalmitoylphosphatidylcholine is 0.1-0.5, the concentration of lutein in the lutein lipid solution is 0.1-2.0%, and the mass ratio of lutein to the lipid phase is 0.1-0.5 mg/100 mg.
Preferably, the volume ratio of the lutein solution and the α -glucosyl hesperidin solution in the step (7) is 1: 2-1: 10, the dropping speed is 10-30 drops per minute, and the stirring speed is 100-700 r/min.
Compared with the prior art, the invention has the following beneficial effects:
(1) the liposome takes cholesterol and dipalmitoyl phosphatidylcholine as wall materials, is an ideal carrier for embedding lutein, and has high lutein encapsulation rate (more than or equal to 90 percent);
(2) α -glucosyl hesperidin modifies lutein liposome to form a dense protective layer on the surface of the liposome, effectively avoids the shrinkage and aggregation of the liposome through steric hindrance effect, makes the distribution uniformity of the liposome and improves the internal and external stability of the liposome;
(3) α -glucosyl hesperidin is coated on the surface of lutein liposome through self-assembly, the α -glucosyl hesperidin hydrophobic head is positioned at the head of the liposome, and the hydrophilic end glycoside group is exposed on the surface of the liposome, so that the slow release performance of the lutein liposome is improved, the accumulation of lutein in the liver and spleen is reduced, and the absorption of lutein in eyes is obviously improved.
(4) The invention adopts a film dispersion method to prepare the liposome, the probe type intermittent ultrasonic treatment forms small single-chamber liposome, and the lutein liposome is obtained after the extrusion of polycarbonate film, the average grain diameter is less than 200nm, and the storage stability is high.
Drawings
FIG. 1 α -in vitro release curve of glucose hesperidin modified lutein liposome
Detailed Description
The following examples are intended to describe the invention in further detail, but are not intended to limit the invention in any way.
Example 1
Dissolving lutein, cholesterol and dipalmitoyl phosphatidylcholine in chloroform-methanol solution with volume ratio of 2: 1 to obtain 0.1% lutein ester solution, performing rotary evaporation to remove organic solvent, forming a uniform film on the bottom of a round-bottom flask by a compound, increasing the vacuum degree to 0.1MPa, continuously pumping for 30min, adding phosphate solution into the compound film for hydration at the hydration temperature of 60 ℃ for 120min, performing ultrasonic treatment under the condition of ice-water bath stirring with ultrasonic power of 800W and pulse for 5s/5s, continuously stirring for 3h at the temperature of 30 ℃ after the treatment time is 20min, stirring at the rotation speed of 1000r/min, centrifuging for 10min under the speed of 10000r/min of dispersion liquid, removing the lutein which is not embedded, dropwise adding α -glucosyl hesperidin solution into the dispersion liquid (stirring at the room temperature for overnight), extruding the obtained dispersion liquid for 10 times through a polycarbonate film with the wavelength of 200nm, and removing excessive α -glucosyl hesperidin by a G200 sephadex gel column to obtain α -glucosyl glucoside-liposome.
Dissolving lutein, cholesterol and dipalmitoyl phosphatidylcholine in chloroform-methanol solution with volume ratio of 2: 1 to obtain 0.1% lutein ester solution, performing rotary evaporation to remove organic solvent to form a uniform film on the bottom of a round bottom flask, increasing the vacuum degree to 0.1MPa, continuously pumping for 30min, adding phosphate solution into the compound film for hydration at the hydration temperature of 60 ℃ for 120min, performing ultrasonic treatment under the condition of ice-water bath stirring with ultrasonic power of 800W and pulse of 5s/5s for 20min, continuously stirring for 3h at the temperature of 30 ℃ with stirring speed of 1000r/min, centrifuging for 10min under the condition of 10000r/min of dispersion liquid to remove unencapsulated lutein, extruding the obtained dispersion liquid for 10 times through a polycarbonate film with the thickness of 200nm, and removing excess α -glucosyl hesperidin by a G200 dextran gel column to obtain common lutein which is used as a control group.
The control group and the experimental group are subjected to in-vitro simulated gastric and intestinal digestion experiments, and research results show that when the lutein content is 0.1%, the release rate of the lutein in the control group in gastric juice is higher than 30%, and the release rate of the lutein in intestinal juice is higher than 20%. The release rate of lutein in gastric juice is lower than 25% and the release rate in intestinal juice is lower than 15%. The lutein liposome obtained from the control group and the experimental group is respectively subjected to intragastric lavage treatment on C57BL/6 mice. Lutein in eyes, livers and spleens of mice after 10h of gastric lavage treatment is extracted, and high performance liquid chromatography detection shows that the content of lutein in eye plasma of the mice in an experimental group is obviously higher than that of lutein in eye plasma of a control group. The research also finds that the elimination half-life period of the lutein liposome in the experimental group in the mouse body is obviously prolonged compared with that of the lutein liposome in the control group.
Example 2
Dissolving lutein, cholesterol and dipalmitoyl phosphatidylcholine in chloroform-methanol solution with volume ratio of 2: 1 to obtain 2% lutein ester solution, performing rotary evaporation to remove organic solvent, forming a uniform film on the bottom of a round-bottomed flask by a compound, increasing the vacuum degree to 0.1MPa, continuously pumping for 30min, adding phosphate solution into the compound film for hydration at the hydration temperature of 55 ℃ for 100min, performing ultrasonic treatment under the condition of ice-water bath stirring with ultrasonic power of 800W and pulse for 5s/5s, after the treatment time of 30min, continuously stirring for 3h at the temperature of 40 ℃, stirring at the rotating speed of 1000r/min, centrifuging for 10min under the speed of 10000r/min of dispersion liquid, removing the lutein which is not embedded, dropwise adding α -glucosyl hesperidin solution (10%) into the dispersion liquid, stirring overnight at room temperature, extruding the obtained dispersion liquid for 20 times through a polycarbonate film with the wavelength of 200nm, and removing excessive α -glucosyl hesperidin by a G200 sephadex gel column to obtain α -glucosyl hesperidin-liposome-liposome.
Dissolving lutein, cholesterol and dipalmitoyl phosphatidylcholine in chloroform-methanol solution with volume ratio of 2: 1 to obtain 2% lutein ester solution, performing rotary evaporation to remove organic solvent, forming a uniform film on the bottom of the round-bottom flask, increasing vacuum degree to 0.1MPa, continuously pumping for 30min, adding phosphate solution into the compound film for hydration at a hydration temperature of 55 ℃ for 100min, performing ultrasonic treatment under the condition of ice-water bath stirring with ultrasonic power of 800W and pulse for 5s/5s, continuously stirring for 3h at a temperature of 40 ℃ after the treatment time of 30min, stirring at a rotation speed of 1000r/min, centrifuging for 10min at a speed of 10000r/min of dispersion liquid, removing non-embedded lutein, extruding the obtained dispersion liquid for 10 times through a polycarbonate film with the thickness of 200nm, and removing excess α -glucosyl glucoside by using a G200 sephadex column to obtain common lutein liposome serving as a control group orange peel.
The average particle size of the experimental liposome is smaller than that of the control group, and the polydispersity index PDI value of the experimental liposome is smaller than that of the control group, which shows that the dispersibility of the α -glucosyl hesperidin modified lutein liposome is good, the experimental group and the control group are respectively stored for 7 days under the normal temperature condition, and the lutein retention rate of the experimental group is obviously higher than that of the control group.
Claims (3)
1. A preparation method of α -glucosyl hesperidin modified lutein liposome is characterized by comprising the following steps:
(1) dissolving lutein and lipid phase in chloroform-methanol solution at volume ratio of 2: 1 to obtain lutein lipid solution;
(2) rotary evaporating to remove organic solvent, allowing the compound to form a uniform film at the bottom of the round-bottom flask, increasing the vacuum degree to 0.1MPa, and continuously pumping for 30 min;
(3) adding phosphate solution into the composite film obtained in the step (2) for hydration, wherein the hydration temperature is 40-60 ℃, and the time is 30-120 min;
(5) carrying out ultrasonic treatment under the ice-water bath stirring condition, wherein the ultrasonic power is 800W, the pulse is 5s/5s, the treatment time is 10-30 min, then continuously stirring for 3-6 h at the temperature of 30-40 ℃, and the stirring rotating speed is 800-1200 r/min;
(6) centrifuging the dispersion obtained in the step (5) for 10min at the speed of 10000r/min, and removing the non-embedded lutein;
(7) α -glucosyl hesperidin is dissolved in a phosphate solution to obtain a α -glucosyl hesperidin solution with the mass concentration of 0.5-10%, the α -glucosyl hesperidin solution is dripped into the dispersion liquid obtained in the step (6), and the mixture is stirred at room temperature overnight;
(8) extruding the dispersion liquid obtained in the step (7) for 10-20 times through a 200nm polycarbonate membrane, and removing excess α -glucosyl hesperidin through a G200 sephadex column to obtain the α -glucosyl hesperidin-lutein liposome.
2. The preparation method of α -glucosyl hesperidin-modified xanthophyll liposome as claimed in claim 1, wherein the lipid phase in step (1) comprises cholesterol and dipalmitoylphosphatidylcholine, the mass ratio of cholesterol to dipalmitoylphosphatidylcholine is 0.1-0.5, the concentration of xanthophyll in the xanthophyll lipid solution is 0.1-2.0%, and the mass ratio of xanthophyll to lipid phase is 0.1-0.5 mg/100 mg.
3. The preparation method of the hesperidin-modified lutein liposome according to claim 1, characterized in that the volume ratio of the lutein in the step (7) to the α -glucosyl hesperidin is 1: 2-1: 10, the dropping speed is 10-30 drops per minute, and the stirring speed is 100-700 r/min.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114303915A (en) * | 2021-12-28 | 2022-04-12 | 华南理工大学 | Method for promoting carotenoid and lutein accumulation of corn sprout seedling by ultrasonic |
| CN114947126A (en) * | 2020-12-15 | 2022-08-30 | 江苏省农业科学院 | Method for improving bioavailability of beta-carotene by modifying hesperidin |
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| US7446101B1 (en) * | 2003-12-12 | 2008-11-04 | Bioactives, Llc | Bioavailable carotenoid-cyclodextrin formulations for soft-gels and other encapsulation systems |
| WO2016100972A2 (en) * | 2014-12-19 | 2016-06-23 | Kemin Industries, Inc. | Intraocular delivery of bioactive molecules using iontophoresis |
| CN105726482A (en) * | 2016-01-27 | 2016-07-06 | 江苏省农业科学院 | Xanthophyll nano-liposome and preparation method thereof |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7446101B1 (en) * | 2003-12-12 | 2008-11-04 | Bioactives, Llc | Bioavailable carotenoid-cyclodextrin formulations for soft-gels and other encapsulation systems |
| WO2016100972A2 (en) * | 2014-12-19 | 2016-06-23 | Kemin Industries, Inc. | Intraocular delivery of bioactive molecules using iontophoresis |
| CN105726482A (en) * | 2016-01-27 | 2016-07-06 | 江苏省农业科学院 | Xanthophyll nano-liposome and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| MOHAMED A.MORSY等: "Prevention of rat liver fibrosis by selective targeting of hepatic stellate cells using hesperidin carriers", 《INTERNATIONAL JOURNAL OF PHARMACEUTICS》 * |
| YOSHIAKI MIYAKE等: "Isolation of C-Glucosylflavone from Lemon Peel and Antioxidative Activity of Flavonoid Compounds in Lemon Fruit", 《JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114947126A (en) * | 2020-12-15 | 2022-08-30 | 江苏省农业科学院 | Method for improving bioavailability of beta-carotene by modifying hesperidin |
| CN114303915A (en) * | 2021-12-28 | 2022-04-12 | 华南理工大学 | Method for promoting carotenoid and lutein accumulation of corn sprout seedling by ultrasonic |
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