CN110156911B

CN110156911B - Hydrophobic polysaccharide and preparation method and application thereof

Info

Publication number: CN110156911B
Application number: CN201910418160.0A
Authority: CN
Inventors: 梁颖; 段贵新; 何正义; 王元元; 杨宇明; 凡波
Original assignee: BENGBU MEDICAL COLLEGE
Current assignee: BENGBU MEDICAL COLLEGE
Priority date: 2019-05-20
Filing date: 2019-05-20
Publication date: 2021-03-02
Anticipated expiration: 2039-05-20
Also published as: CN110156911A

Abstract

The invention provides a hydrophobization polysaccharide and a preparation method and application thereof. The hydrophobized polysaccharide has the following structural general formula: G-P-O; wherein G is polysaccharide or disaccharide, P is amino acid or dipeptide, and O is oleic acid; g and P are connected with hydroxyl on the polysaccharide through ester bonds, and P and O are connected through amide bonds. The hydrophobic polysaccharide provided by the invention has loading performance, and propyl gallate can be loaded and dispersed in a water phase through hydrogen bond and hydrophobic effect to prepare water-soluble propyl gallate drug-loaded particles. The method successfully solves the problem of poor biocompatibility of the propyl gallate, and the hydrophobic polysaccharide and the propyl gallate can play a synergistic pharmacological action.

Description

Hydrophobic polysaccharide and preparation method and application thereof

Technical Field

The invention relates to the technical field of high polymer materials and organic synthesis, in particular to hydrophobization polysaccharide and a preparation method and application thereof.

Background

Propyl gallate is an oil-soluble antioxidant with antibacterial activity, and is widely used in the field of food antioxidation. The application method of the gallic acid propyl ester is generally that the gallic acid propyl ester is dissolved in the vegetable oil and then is added into the food. In some antibacterial and antioxidant fields requiring aqueous emulsion, propyl gallate cannot be applied. For example, propyl gallate is non-toxic and has antibacterial activity, but cannot be used in a mouthwash due to the lack of an emulsion product. But food, feed, medicine and traditional Chinese medicinal materials have the advantages of antibiosis, mould prevention and oxidation resistance, and no nontoxic and convenient product is available.

Indoleacetic acid as a plant hormone is widely applied to the field of agricultural production, but the indoleacetic acid is difficult to dissolve in water, and when the indoleacetic acid is used, the indoleacetic acid needs to be dissolved in a sodium hydroxide aqueous solution to prepare a sodium salt, and then the sodium salt is added with water for dilution. The strong oxidizing property of sodium hydroxide easily makes indoleacetic acid invalid, has the harm of generating waste and polluting soil and water, and urgently needs to solve the problem of poor pesticide dosage.

Disclosure of Invention

The invention aims to provide a novel hydrophobized polysaccharide and a preparation method thereof.

It is another object of the present invention to provide uses of the hydrophobized polysaccharide, including use in combination with indoleacetic acid, and use in combination with propyl gallate.

In order to achieve the object of the present invention, in a first aspect, the present invention provides a hydrophobized polysaccharide having the following general structural formula: G-P-O; wherein G is a polysaccharide or a disaccharide (as a hydrophilic group), P is an amino acid or a dipeptide (as a linker arm), and O is oleic acid (as a hydrophobic group); preferably, G is dextran and P is glycylglycine. G and P are connected with hydroxyl on the polysaccharide through ester bonds, and P and O are connected through amide bonds.

The hydrophobic polysaccharide is a functional polysaccharide which is prepared by condensation reaction of glucan and glycylglycine oleate, wherein glucan is used as a hydrophilic group, oleic acid is used as a hydrophobic group, and glycylglycine is used as a loading group.

In the present invention, the polysaccharide is at least one selected from dextran, algal polysaccharide, starch, amylopectin, amylose, pullulan, hydroxyethyldextran, mannan, levan, inulin, chitin, chitosan, chitin, xyloglucan, water-soluble cellulose and the like.

The disaccharide is sucrose or fructose.

The amino acid or the dipeptide is at least one selected from glycylglycine, glutamic acid, L-lysine, L-cysteine, DL-alanine, DL-methionine, L-ornithine, gamma-aminobutyric acid, L-aspartic acid, L-theanine, L-arginine, beta-alanine, L-citrulline, L-histidine and the like.

Preferably, in the general formula G-P-O, G is glucan, P is glycylglycine, and the structure of the hydrophobic polysaccharide is shown in the formula (I):

wherein R is₁、R₂Or R₃Any two of them are H, the rest are

n is any integer greater than 2.

The hydrophobic polysaccharide is prepared by reacting hydroxyl of glucan with carboxyl of glycylglycine, glycylglycine glucan ester is prepared firstly, and then the glycylglycine glucan ester reacts with oleic acid, so that amino of glycylglycine is esterified with oleic acid to obtain hydrophobic glucan.

In a second aspect, the present invention provides a method for preparing the hydrophobized polysaccharide, comprising the steps of:

1) the hydroxyl of polysaccharide or disaccharide and the carboxyl of amino acid or dipeptide are subjected to esterification reaction to generate amino acid or dipeptide esterified polysaccharide;

2) the amino acid or the dipeptide esterified sugar and oleic acid are subjected to condensation reaction to generate the hydrophobic polysaccharide.

When the structure of the hydrophobic polysaccharide is shown as the formula (I), the preparation method is as follows:

reacting glucan and glycyl glycine protected by amino in an organic solvent, adding a proper amount of catalyst and dehydrating agent, and reacting at the temperature of 0-60 ℃ for 1-96 hours to obtain glycyl glycine glucan ester;

secondly, amino protection and removal of glycyl glycine dextran ester are carried out by the following specific method: adding the glycylglycine dextran ester into a sodium hydroxide aqueous solution, quickly dissociating amino of glycylglycine, drying under reduced pressure to remove water, redissolving in an organic solvent, adding oleic acid, a catalyst and a proper amount of a dehydrating agent, reacting at 0-60 ℃ for 1-96 h, and adding water to stop the reaction;

thirdly, filtering the reaction system obtained in the second step, adding an alcohol solvent into the filtrate, collecting the precipitate, and drying to obtain the hydrophobic polysaccharide.

In the above method, the organic solvent in step (i) is at least one selected from dimethylformamide, dimethylsulfoxide, dichloromethane, and the like.

In the method, the catalysts are DMAP (4-dimethylaminopyridine) and DCC (dicyclohexylcarbodiimide), the dehydrating agent is DCC, and the amount of the dehydrating agent and the DCC is proper. In addition, the catalyst can also be selected from pyridine and concentrated sulfuric acid; the dehydrating agent can be selected from inorganic salts such as molecular sieve, calcium chloride, zinc chloride, magnesium sulfate, etc.

In the method, the alcohol solvent is absolute ethyl alcohol or methanol, and the amount of the alcohol solvent is proper.

In the method, the molar ratio of the glucan, the glycylglycine and the oleic acid is 1:1-2:1-2, wherein the glycylglycine and the oleic acid are mixed in the molar ratio. Preferably 1:1:1 or 1:2: 2.

In the method and the step III, the reaction system is filtered, the filter residue is collected and dried, and the DMAP and the byproduct Dicyclohexylurea (DCU) can be recycled.

In a third aspect, the present invention provides any one of the following uses of the hydrophobised polysaccharide, or hydrophobised polysaccharide prepared according to the above method:

a. as active ingredient carriers;

b. for use in pharmaceuticals or antibacterial agents;

wherein the active ingredients comprise medicines and plant growth hormone.

The hydrophobization polysaccharide carrier drug provided by the invention can be used in combination with other drugs.

In a fourth aspect, the invention provides a medicament or composition comprising the hydrophobised polysaccharide, or a hydrophobised polysaccharide prepared according to the above method, and at least one active ingredient.

Preferably, the active ingredient is gallic acid and derivatives thereof, more preferably propyl gallate.

The weight ratio of the hydrophobized polysaccharide to the propyl gallate is 10:1-10:100, preferably 10:4-10: 50.

More preferably, the medicament or the composition is an aqueous emulsion, and the average particle size is 0-1000 nm, preferably below 500 nm. Preferably, the active ingredient is indoleacetic acid and derivatives thereof, more preferably indoleacetic acid.

The weight ratio of the hydrophobized polysaccharide to the indoleacetic acid is 10:1-10:100, preferably 10:4-10: 50.

More preferably, the pharmaceutical or composition is in the form of an aqueous solution.

In a fifth aspect, the present invention provides a process for the preparation of the medicament or composition, the process comprising: dissolving the hydrophobic polysaccharide in water, adding propyl gallate or indoleacetic acid, and treating with probe emulsifier or ultrasonic wave until forming aqueous emulsion or solution with required particle diameter.

Fig. 1 shows the diameters and distribution states of drug-loaded particles formed in an aqueous solution after loading propyl gallate with hydrophobized glucan. The particles formed in the aqueous solution after the propyl gallate is loaded by the hydrophobized glucan are mostly below 500 nanometers, and have obvious advantages compared with the traditional emulsion with the particle size larger than 1 micrometer.

FIG. 2 shows the particle diameter and distribution of hydrophobized dextran in aqueous solution. The self-assembled hydrophobic glucan particle size is less than 200 nanometers, and the self-assembled hydrophobic glucan particle size is polydisperse and is obviously different from the particle size after drug loading.

In a sixth aspect, the invention provides an application of the aqueous emulsion (propyl gallate emulsion) prepared from the hydrophobic polysaccharide and propyl gallate in the antibacterial and antioxidant fields.

In a seventh aspect, the invention provides the use of the above-mentioned aqueous solution prepared from said hydrophobized polysaccharide and indoleacetic acid for plant growth regulation.

By the technical scheme, the invention at least has the following advantages and beneficial effects:

the hydrophobic polysaccharide provided by the invention has loading performance, and propyl gallate can be loaded and dispersed in a water phase through hydrogen bond and hydrophobic effect to prepare water-soluble propyl gallate drug-loaded particles, so that the problem of poor biocompatibility of propyl gallate can be well solved.

The hydrophobic polysaccharide provided by the invention not only has hydrophilic polysaccharide chain segments and hydrophobic oleic acid groups, but also has a connecting arm of amino acid or dipeptide, and the gallic acid (or indoleacetic acid) and the derivatives thereof not only have the hydrophobic water sample effect, but also have the bonding effect of hydrogen bonds, so that the prepared emulsion (or solution) is stable, and the emulsion is not broken under low concentration.

And thirdly, the raw materials used for synthesizing the hydrophobic polysaccharide are safe and nontoxic, and can be used in the fields of food and medicines. The hydrophobized polysaccharide is nontoxic, can be completely decomposed in nature, and has no acute toxicity or long-term toxicity. The propyl gallate emulsion has antibacterial and antioxidant effects.

Drawings

Fig. 1 shows the diameter and distribution of drug-loaded particles formed in an aqueous solution after loading propyl gallate with hydrophobized glucan of the present invention.

FIG. 2 shows the particle diameter and distribution of the hydrophobized glucan of the present invention in an aqueous solution.

FIG. 3 shows the particle size and distribution of an aqueous solution (2.5mg/ml) of propyl gallate in example 7 of the present invention.

FIG. 4 shows the particle size and distribution of an aqueous solution (1.25mg/ml) of propyl gallate in example 7 of the present invention.

FIG. 5 shows the particle size and distribution of an aqueous solution (0.62mg/ml) of propyl gallate in example 7 of the present invention.

FIG. 6 shows the particle size and distribution of an aqueous solution (0.31mg/ml) of propyl gallate in example 7 of the present invention.

FIG. 7 shows the particle size and distribution of an aqueous solution (0.15mg/ml) of propyl gallate in example 7 of the present invention.

FIG. 8 shows the particle size and distribution of an aqueous solution (0.08mg/ml) of propyl gallate in example 7 of the present invention.

FIG. 9 shows the particle size and distribution of an aqueous solution (0.01mg/ml) of propyl gallate in example 7 of the present invention.

FIG. 10 shows the particle size and distribution of propyl gallate drug-loaded particles (2.5mg/ml) in example 7 of the present invention.

FIG. 11 shows the particle size and distribution of propyl gallate drug-loaded particles (1.25mg/ml) in example 7 of the present invention.

FIG. 12 shows the particle size and distribution of propyl gallate drug-loaded particles (0.62mg/ml) in example 7 of the present invention.

FIG. 13 shows the particle size and distribution of propyl gallate drug-loaded particles (0.31mg/ml) in example 7 of the present invention.

Fig. 14 shows the result of a browning experiment of kohlrabi wire in example 8 of the present invention. Wherein, the two samples are photographs taken at the initial stage of the experiment, a is a sample of the kohlrabi silk sprayed with propyl gallate drug-loaded particles with the concentration of 0.1%, and b is a sample of kohlrabi silk without spraying drugs; the lower two samples are photographs taken in 24h of an experiment, wherein a is a sample of propyl gallate drug-loaded particles with the concentration of 0.1% sprayed on kohlrabi silk, and b is a sample of kohlrabi silk without spraying drugs.

Fig. 15 shows the result of a 24h browning test of kohlrabi silk in example 8 of the invention. Wherein, a is a sample of propyl gallate drug-loaded particles with the concentration of 0.1% sprayed on kohlrabi silk, and b is a sample of kohlrabi silk without spraying drugs.

FIG. 16 shows the particle size and distribution of the indoleacetic acid carrier drug of example 12 of the present invention.

FIG. 17 is a 3-day image of wheat and barley seed in example 12 of the present invention.

FIG. 18 is a 4-day image of wheat and barley seed in example 12 of the present invention.

FIG. 19 is a 5-day image of wheat and barley in example 12 of the present invention.

FIG. 20 is a photograph of a 6 th day wheat seed in example 12 of the present invention.

FIG. 21 is a 7-day image of wheat and barley in example 12 of the present invention.

FIG. 22 is an image of wheat and barley on day 8 in example 12 of the present invention.

FIG. 23 is a 9-day image of wheat and barley in example 12 of the present invention.

FIG. 24 is a 10-day image of wheat and barley in example 12 of the present invention.

Detailed Description

The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention. Unless otherwise specified, the technical means used in the examples are conventional means well known to those skilled in the art, and the raw materials used are commercially available products.

The molecular weight of the dextran used in the following examples was 10000 g/mol.

Example 1 hydrophobized polysaccharide and method for producing the same

The hydrophobized polysaccharide prepared in this example is prepared by reacting glycylglycine with hydroxyl of dextran, and reacting glycylglycine dextran ester with oleic acid to esterify glycylglycine carboxyl with oleic acid to obtain hydrophobized dextran. The preparation method comprises the following steps:

1. dissolving 100g (0.01mol) of glucan in 2L of N, N-Dimethylformamide (DMF), adding 1.6g (0.01mol) of glycylglycine protected by amino, adding 1g of catalyst DMAP and 10g of dehydrating agent DCC, reacting at room temperature for 48h, filtering to remove a byproduct dicyclohexylurea, adding a small amount of water into the filtrate to terminate the reaction, and adding 2L of absolute ethyl alcohol to obtain a white precipitate, namely glycylglycine glucan ester.

2. Adding 100g glycylglycine dextran ester into 1N aqueous solution 1L of NAOH, removing protecting group to free amino group of glycylglycine, and distilling the reaction system under reduced pressure to remove water.

3. Redissolving 100g of the deprotected glycylglycine dextran ester in a proper amount of 2L DMF, adding 2.8g (0.01mol) of oleic acid, adding 1g of catalyst DMAP and 10g of dehydrating agent DCC, reacting at room temperature for 48h, filtering to remove a byproduct dicyclohexylurea, adding a small amount of water into the filtrate to terminate the reaction, and adding 2L of absolute ethyl alcohol to obtain a white precipitate, namely the hydrophobized dextran.

And (3) filtering and collecting filter residues of the reaction system in the

steps

2 and 3 to obtain a byproduct Dicyclohexylurea (DCU), and drying the filter residues for recycling.

Example 2 hydrophobized polysaccharide and method for producing the same

The preparation method comprises the following steps:

1. dissolving 100g (0.01mol) of glucan in 4L of N, N-Dimethylformamide (DMF), adding 3.2g (0.02mol) of glycylglycine protected by amino, adding 2g of catalyst DMAP and 20g of dehydrating agent DCC, reacting at 40 ℃ for 24h, filtering to remove a byproduct dicyclohexylurea, adding a small amount of water into the filtrate to terminate the reaction, and adding 4L of anhydrous methanol to obtain a white precipitate, namely glycylglycine glucan ester.

2. Adding glycylglycine dextran ester 100g into 1N aqueous solution of NAOH 2L, removing protecting group to free amino group of glycylglycine, and distilling the reaction system under reduced pressure to remove water.

3. Re-dissolving 100g of the deprotected glycylglycine dextran ester in 4L of DMF, adding 5.6g (0.02mol) of oleic acid, adding 2g of catalyst DMAP and 20g of dehydrating agent DCC, reacting at 40 ℃ for 24h, filtering to remove a byproduct dicyclohexylurea, adding a small amount of water into the filtrate to terminate the reaction, and adding 4L of anhydrous methanol to obtain a white precipitate, namely the hydrophobized dextran.

Example 3 hydrophobized polysaccharide and method for producing the same

The preparation method comprises the following steps:

1. dissolving 100g (0.01mol) of glucan in 1L of N, N Dimethylformamide (DMF), adding 2.4g (0.015mol) of glycylglycine protected by amino, adding 0.5g of catalyst DMAP and 5g of dehydrating agent DCC, reacting at 50 ℃ for 12h, filtering to remove a byproduct dicyclohexylurea, adding a small amount of water into filtrate to terminate the reaction, and adding 1L of absolute ethyl alcohol to obtain a white precipitate, namely glycylglycine glucan ester.

2. 100g of glycylglycine dextran ester is added into 500ml of 1N aqueous solution of NAOH, the protecting group is removed, the amino group of glycylglycine is dissociated, and the reaction system is decompressed and distilled to remove water.

3. Re-dissolving 100g of the deprotected glycylglycine dextran ester in 1LDMF, adding 4.2g (0.015mol) of oleic acid, adding 0.5g of catalyst DMAP and 5g of dehydrating agent DCC, reacting at 50 ℃ for 12h, filtering to remove a byproduct dicyclohexylurea, adding a small amount of water into the filtrate to terminate the reaction, and adding 1L of absolute ethyl alcohol to obtain a white precipitate, namely the hydrophobized dextran.

Example 4 propyl gallate emulsion and method of making

Dissolving 30g of the hydrophobized polysaccharide prepared in example 1 in 1L of water, then adding 10g of propyl gallate, adding 3L of water at room temperature after completely dissolving, and treating by using a probe emulsifier or ultrasonic waves until polydisperse aqueous emulsion with the average particle size of 615.1nm is formed, namely propyl gallate emulsion.

Example 5 propyl gallate emulsion and method of making

Dissolving 30g of the hydrophobized polysaccharide prepared in the example 2 in 500mL of water, then adding 20g of propyl gallate, adding 500mL of water at room temperature after completely dissolving, and treating by using a probe emulsifier or ultrasonic waves until a polydisperse aqueous emulsion with the particle size less than 1 μm is formed, namely the propyl gallate emulsion.

Example 6 propyl gallate emulsion and method of making

30g of the hydrophobized polysaccharide prepared in example 3 is dissolved in 2L of water, then 5g of propyl gallate is added, after complete dissolution, 2L of water is added at room temperature, a probe emulsifier or ultrasonic treatment is used until the average particle size of 240.1nm (79.3%) and 3.1 nm (20.7%) are formed, and polydisperse aqueous emulsion is the propyl gallate emulsion.

Example 7 stability of propyl gallate emulsion and solubilization of hydrophobized dextran

The stability of the propyl gallate emulsions prepared in examples 4-6 was investigated with respect to solubilization of the hydrophobized dextran.

Gallic acid is trihydroxyphenol having a hydrophobic group (propyl group), and is present in the form of aggregates in an aqueous solution, and therefore is hardly soluble in water. Fig. 3 to 9 show the particle size and distribution of propyl gallate formed in aqueous solutions at different concentrations, and even when diluted to a concentration of 0.01mg/ml, gallic acid is present in the form of micro-and nano-scale polydisperse aggregates, and in aqueous solutions, monomolecular solutions cannot be formed.

Dissolving 10g propyl gallate and 30g hydrophobic dextran in 4L water, emulsifying to obtain water emulsion of drug-loaded particles with propyl gallate concentration of 2.5mg/ml, diluting, and detecting with particle size distribution instrument to obtain particle size and particle size distribution shown in figures 10-13. The particle diameters of the drug-loaded particles with the concentration of the propyl gallate of 2.5mg/ml are all smaller than 700nm, the drug-loaded particles are polydisperse, the drug-loaded particles exist in an aggregate form, and the particle diameters and the distribution are obviously different from those of a propyl gallate aqueous solution. The particle diameters of the drug-loaded particles with the concentration of the propyl gallate of 2.5mg/ml are all less than 500nm, the drug-loaded particles are polydisperse, the drug-loaded particles exist in an aggregate form, and the particle diameters and the distribution are obviously different from those of a propyl gallate aqueous solution. And no particles are detected in the emulsion after the concentration of the propyl gallate drug-loaded particles is less than 0.62 mg/ml. The drug-loaded particles exist in the form of aggregates at high concentration, and the aggregates can be uniformly distributed in the aqueous solution after dilution. After the concentration of the propyl gallate drug-loaded particles is less than 0.62mg/ml, no propyl gallate self-aggregates appear. The solubilization of the hydrophobized glucan carrier is obvious.

EXAMPLE 8 use of propyl gallate emulsion

Specific applications of the propyl gallate emulsions prepared in examples 4-6 are as follows: in order to investigate the antioxidant activity of the propyl gallate emulsion, an experiment for influencing the browning of kohlrabi filaments by propyl gallate drug-loaded particles is carried out. The results are shown in fig. 14 and 15. Fig. 14a shows a sample of kohlrabi silk sprayed with 0.1% propyl gallate drug-loaded particles, and fig. 14b shows a control kohlrabi silk sample. The upper two samples are photographs of the initial start experiment and the lower two samples are photographs of the samples after 24 h. After 24h, the kohlrabi silk in the control group turns brown and starts to rot, and the spraying group is in good condition. Fig. 15 is an enlarged photograph of fig. 14.

Example 9 Indolylacetic acid aqueous solution and Process for preparing the same

30g of the hydrophobized polysaccharide prepared in example 1 was dissolved in 1L of water, then 10g of indoleacetic acid was added, after complete dissolution, 3L of water were added at room temperature, and treated with a probe emulsifier or sonication until an aqueous solution was formed.

Example 10 Indolylacetic acid aqueous solution and Process for preparing the same

30g of the hydrophobized polysaccharide prepared in example 1 was dissolved in 0.5L of water, 20g of indoleacetic acid was added, and after complete dissolution, 0.5L of water was added at room temperature, and treated with a probe emulsifier or with ultrasound until an aqueous solution was formed.

Example 11 aqueous Indolylacetic acid solution and Process for its preparation

30g of the hydrophobized polysaccharide prepared in example 1 was dissolved in 2L of water, then 5g of indoleacetic acid was added, after complete dissolution 3L of water were added at room temperature, and treated with a probe emulsifier or ultrasound until an aqueous solution was formed.

Example 12 drug Loading and drug Release Studies of hydrophobized Glucan

The indole acetic acid/hydrophobized dextran aqueous solutions prepared in examples 9 to 12 were examined for drug loading and drug release properties of the hydrophobized dextran.

In order to examine the drug loading and drug releasing properties of the hydrophobized glucan, 10mg of insoluble indoleacetic acid and 50mg of hydrophobized glucan are dissolved in 2ml of water, and the indoleacetic acid carrier drug is prepared by ultrasonic treatment. Diluting to 0.5mg/ml carrier drug solution, detecting by a particle size distribution instrument, and detecting no particle, which indicates that the indoleacetic acid is uniformly distributed in water. The results are shown in FIG. 16.

The drug release performance of the indoleacetic acid drug-loaded particles is inspected by adopting a wheat seedling raising experiment. And selecting plump wheat seeds, respectively placing the wheat seeds in a groove, adding water for soaking, and intervening with indoleacetic acid medicine-carrying particle liquid medicine. A high concentration drug solution group (indoleacetic acid concentration 16mg/ml), a medium concentration drug solution group (indoleacetic acid concentration 4mg/ml), a low concentration drug solution group (indoleacetic acid concentration 1mg/ml)) and a control group were set. The growth state of wheat is shown in fig. 17-24. The high-concentration liquid medicine group obviously inhibits the growth of wheat, and the low-concentration medicine group is not different from the control group, so that the indolacetic acid medicine-carrying particles can play a medicine effect role.

At present, the problem of insoluble drugs such as propyl gallate and indoleacetic acid is solved by mainly adopting a conventional emulsifier for solubilization and compounding with other drugs. For example, CN201710812180.7 discloses a compound antioxidant, which is prepared from a free radical quencher, a peroxide decomposer, a synergist, an emulsifier, a co-emulsifier and water, and exists in the form of microemulsion. The emulsifier is one or more of span-20, tween-60, tween-80, glycerin fatty acid ester, propylene glycol fatty acid ester, sorbitan fatty acid ester, and sucrose fatty acid ester with limited emulsifying capacity. The auxiliary emulsifier is one or more of ethanol, ethylene glycol, propylene glycol and glycerol. Although the emulsifiers are food and drug emulsifiers, the solubilizing effect is limited and the toxicity is large. In comparison, the hydrophobization polysaccharide has good drug loading, drug releasing and safety and more excellent performance.

Although the invention has been described in detail hereinabove with respect to a general description and specific embodiments thereof, it will be apparent to those skilled in the art that modifications or improvements may be made thereto based on the invention. Accordingly, such modifications and improvements are intended to be within the scope of the invention as claimed.

Claims

1. A hydrophobized polysaccharide, characterized in that the structure of the hydrophobized polysaccharide is according to formula (I):

wherein R is₁、R₂Or R₃Any two of them are H, the rest are

n is any integer greater than 2;

the preparation method of the hydrophobized polysaccharide comprises the following steps: 1) the hydroxyl of the glucan and the carboxyl of glycyl glycine are subjected to esterification reaction to generate glycyl glycine glucan ester; 2) glycylglycine dextran ester and oleic acid are subjected to condensation reaction to generate hydrophobic polysaccharide.

2. The process for preparing a hydrophobized polysaccharide according to claim 1, comprising the steps of:

1) the hydroxyl of the glucan and the carboxyl of glycyl glycine are subjected to esterification reaction to generate glycyl glycine glucan ester;

2) glycylglycine dextran ester and oleic acid are subjected to condensation reaction to generate hydrophobic polysaccharide.

3. The method according to claim 2, characterized in that the preparation method is as follows:

reacting glucan and glycyl glycine protected by amino in an organic solvent, adding a proper amount of catalyst and dehydrating agent, reacting at the temperature of 0-60 ℃ for 1-96 hours to obtain glycyl glycine glucan ester;

4. The method according to claim 3, wherein the organic solvent of step (i) is at least one selected from dimethylformamide, dimethylsulfoxide or dichloromethane; and/or

The catalyst is dimethylamino pyridine, and the dehydrating agent is dicyclohexyl carbodiimide; and/or

The alcohol solvent is absolute ethyl alcohol or methanol; and/or

The molar ratio of the glucan to the glycylglycine to the oleic acid is 1:1-2:1-2, wherein the glycylglycine and the oleic acid are mixed in an equal molar ratio.

5. Use of a hydrophobised polysaccharide according to claim 1, or a hydrophobised polysaccharide prepared according to the process of any of claims 2 to 4, in any of the following applications:

a. for making active ingredient carriers;

b. for use in pharmacy or for the preparation of antibacterial agents;

wherein the active ingredients are propyl gallate and indoleacetic acid.

6. A composition comprising the hydrophobized polysaccharide of claim 1, or the hydrophobized polysaccharide prepared by the process of any of claims 2 to 4, and at least one active ingredient;

wherein the active ingredients are propyl gallate and indoleacetic acid.

7. The composition of claim 6, wherein the weight ratio of hydrophobized polysaccharide to propyl gallate is from 10:1 to 10: 100; the weight ratio of the hydrophobized polysaccharide to the indoleacetic acid is 10:1-10: 100.

8. The composition of claim 7, wherein the weight ratio of hydrophobized polysaccharide to propyl gallate is from 10:4 to 10: 50; the weight ratio of the hydrophobized polysaccharide to the indoleacetic acid is 10:4-10: 50.

9. The composition of claim 8, wherein the composition is in the form of an aqueous emulsion.

10. A method of preparing the composition of claim 9, comprising: dissolving the hydrophobic polysaccharide in water, adding propyl gallate or indoleacetic acid, and treating with probe emulsifier or ultrasonic wave until forming aqueous emulsion or solution with required particle diameter.