CN118077890A

CN118077890A - Intestinal canal slow-release vesicle and microcapsule with taste masking function, and preparation methods and applications thereof

Info

Publication number: CN118077890A
Application number: CN202311278018.3A
Authority: CN
Inventors: 邹立强; 马晨露; 刘伟; 叶雄; 马丽; 周莹颖; 徐志强; 谢有发; 黄鑫
Original assignee: Nanchang University
Current assignee: Nanchang University
Priority date: 2023-09-28
Filing date: 2023-09-28
Publication date: 2024-05-28

Abstract

The invention provides an intestinal slow-release vesicle and microcapsule with taste masking function, and a preparation method and application thereof, and relates to the field of foods or health products. The vesicle comprises a vesicle core and a vesicle membrane wrapping the vesicle core, wherein the water phase raw materials for forming the vesicle core comprise: an active ingredient, a saccharide, water and a thickener; the oil phase raw materials for forming the vesicle membrane comprise: phospholipids, oils, oleogels, with or without: an oil-soluble emulsifier. The invention provides the intestinal canal slow-release vesicle with high safety and taste masking function, solves the problem that active ingredients have pungency, bitter and other bad senses, ensures that the active ingredients wrapped by the structure can be safely added into foods and health care products, expands the application scene of the active ingredients with bad flavors, promotes the health effect of the active ingredients, and simultaneously can realize the slow release of the active ingredients in intestinal canal and permanently exert the functional activity of the active ingredients. No organic reagent with high residual risk is added, and the edible safety is higher.

Description

Intestinal canal slow-release vesicle and microcapsule with taste masking function, and preparation methods and applications thereof

Technical Field

The invention relates to the field of foods or health-care products, in particular to an intestinal slow-release vesicle and microcapsule with taste masking function, and a preparation method and application thereof.

Background

At present, many active ingredients beneficial to health influence the edibility of the active ingredients due to pungent and bitter flavors and the like, and further limit the application of the active ingredients in foods or health care products. In particular, many new food sources (such as epigallocatechin gallate, bitter peptides, etc.) that can be added as needed have not been widely used in foods and health products, mainly to avoid that the pungent flavors such as spicy, bitter, etc. affect the sensory experience of the product.

A large amount of essence and sweetener are usually added to foods and health products to mask bad flavors. The addition of sweeteners can also reduce the perception of bitterness and astringency by increasing the threshold of bitterness and astringency and deceiving the brain. For example, patent document CN116420874a can suppress the bitter taste of epigallocatechin gallate and/or caffeine in a composition by adding microcrystalline cellulose and sugar alcohol to the composition; patent document EP2641477A1 uses at least one starch derivative including high amylose starch, dextrin and/or maltodextrin to mask the bitter and astringent tastes of catechins.

The field can also remove parts of the active ingredient structure that cause bitterness, peppery feeling, etc. by using chemical blocking agents to chemically react with the active ingredient. For example, patent document CN113501829a combines EGCG with glucose under heating to perform an addition reaction, and dehydrates, cyclizes, separates and purifies the glucose group attached to EGCG to obtain an EGCG-glucose adduct with reduced bitterness; patent document CN101066120a removes the pungency by using an ethanol or methanol pungency remover.

Although the use of a sweetener can mask bad flavors, each person has different perception and tolerance to taste, and the taste masking effect is inconsistent, the addition of the sweetener can only alleviate the flavors through seasoning, and cannot be completely masked. When using chemical blocking agents to cover bad flavors, chemical reactions are often involved, a plurality of blocking agents cannot be added at will, which is unfavorable for processing and production of foods and health care products, and the treatment cost of the method is high, and the treatment process has the risk of organic hazard residues, so that the method still cannot be widely applied.

The vesicle is an encapsulation structure formed spontaneously by the natural vesicle composition, and can load the active ingredients into the vesicle, so that the contact of the active ingredients with the external environment is effectively blocked, and the bad flavors of the active ingredients are blocked. For example, non-patent literature, "phospholipid nanovesicle construction of epigallocatechin gallate (EGCG) and anti-caries study thereof" discloses a preparation method of EGCG nanovesicles, which comprises the steps of preparing phospholipid complexes from egg yolk lecithin and EGCG, then dripping the phospholipid complexes into an aqueous phase containing tween-80 and ultrapure water by an ethanol injection method to prepare the EGCG nanovesicles, wherein ethanol is used in the preparation process, belongs to an organic reagent, has a residual risk, aims at enhancing the stability of EGCG, and has poor taste masking effect on EGCG, so that the defects cannot be suitable for the requirements of foods or health products on improving the organoleptic aspects of products.

Therefore, how to provide a vesicle with high safety and taste masking function is a technical problem to be solved by those skilled in the art.

Disclosure of Invention

Therefore, the invention aims to provide the intestinal canal slow-release vesicle and the microcapsule which have high safety and taste masking function, as well as the preparation method and the application thereof, and solve the problem that the active ingredients have bad senses such as pungency, bitterness and the like, so that the active ingredients wrapped by the structure can be safely added into foods and health care products, the application scene of the active ingredients with bad flavors is enlarged, the health effect of the active ingredients is promoted to be exerted, and meanwhile, the slow release of the active ingredients in the intestinal canal can be realized, and the functional activity of the active ingredients can be permanently exerted.

In order to achieve the above purpose, the present invention provides the following technical solutions:

in a first aspect, the invention provides an intestinal slow-release vesicle with taste masking function, which comprises a vesicle core and a vesicle membrane wrapping the vesicle core,

The aqueous phase raw materials forming the capsule core comprise: an active ingredient, a saccharide, water and a thickener;

the oil phase raw materials for forming the vesicle membrane comprise: phospholipids, oils and oleogels, with or without: an oil-soluble emulsifier.

Further, the mass ratio of the active ingredient, the carbohydrate, the water and the thickener is 1-30: 1 to 50:19.9 to 97:0.1 to 1; the mass ratio of the phospholipid, the grease, the oil-soluble emulsifier and the oil gel is 5-80: 19.9 to 93:0 to 10:0.1 to 2; the mass ratio of the water phase raw material to the oil phase raw material is 1:2 to 10.

Further, the mass percentage of the active ingredient in the water phase raw material is 1-5%, the mass percentage of the saccharide in the water phase raw material is 5-50%, and the mass percentage of the thickener in the water phase raw material is 0.1-1%;

The mass percentage of the phospholipid in the oil phase raw material is 5% -80%, the mass percentage of the oil-soluble emulsifier in the oil phase raw material is 0% -10%, and the mass percentage of the oil gel in the oil phase raw material is 0.1% -2%;

the mass ratio of the water phase raw material to the oil phase raw material is 1:2 to 10.

Preferably, the mass percentage of the active ingredient in the water phase raw material is 5%, the mass percentage of the saccharide in the water phase raw material is 30% -55%, and the mass percentage of the thickener in the water phase raw material is 0.2% -0.5%.

More preferably, the mass percentages of the active ingredient, the saccharide and the thickener in the water phase raw material are any one of the following combinations: 5%, 30%, 0.5%;5%, 40%, 0.5%;5%, 50%, 0.5%;5%, 40%, 0.2%;5%, 55% and 0.5%.

Most preferably, the mass percentage of the active ingredient in the water phase raw material is 5%, the mass percentage of the saccharide in the water phase raw material is 40%, and the mass percentage of the thickener in the water phase raw material is 0.5%;

Preferably, the mass percentage of the phospholipid in the oil phase raw material is 45% -60%, the mass percentage of the oil-soluble emulsifier in the oil phase raw material is 8% -10%, and the mass percentage of the oil gel in the oil phase raw material is 1% -2%.

More preferably, the mass percentages of the phospholipid, the oil-soluble emulsifier and the oil gel in the oil phase raw material are any one of the following combinations: 55%, 0%, 1%;50%, 0%, 2%;60%, 0%, 2%;45%, 8%, 1.5%;50%, 8%, 2%;45%, 10% and 2%.

Most preferably, the mass percentage of the phospholipid in the oil phase raw material is 55%, the mass percentage of the oil soluble emulsifier in the oil phase raw material is 8%, and the mass percentage of the oil gel in the oil phase raw material is 2%.

Preferably, the mass ratio of the aqueous phase raw material to the oil phase raw material is 1:6.

Further, the active ingredient includes at least one of capsaicin, piperine, ginger extract, gingerol, garlicin, xanthosine, bitter peptides, albumin peptides, blood peptides, tea polyphenols, catechin, EGCG (epigallocatechin gallate), propolis flavone, NMN (nicotinamide mononucleotide), NADH (reduced nicotinamide adenine dinucleotide), glutathione, pagodatree flower bud extract, dihydromyricetin, caffeine, deer blood, yeast extract, pig liver extract, beef liver extract, tortoise plastron peptide, turtle peptides, bird's nest acids, oyster peptides, chondroitin sulfate, gamma-aminobutyric acid, taurine, L-carnitine, corn peptides, balsam pear peptides, ginseng peptides, bovine bone peptides, dendrobium nobile extracts.

Further, the saccharide substance includes at least one of sucrose, lactose, fructose, glucose, polydextrose, trehalose, lactulose, xylose, arabinose, mannooligosaccharide, maltose, oligomaltose, oligoisomaltose, oligoisomaltulose, maltotriose, maltitol, mannitol, sorbitol, xylitol, erythritol, maltodextrin, alpha-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin, hydroxypropyl-beta-cyclodextrin.

Further, the thickener comprises at least one of xanthan gum, pectin, locust bean gum, tamarind gum, carrageenan, sodium alginate, karaya gum, curdlan, psyllium seed gum, papaya seed gum, peach gum, konjac gum, pullulan, acacia, guar gum, gellan gum, gelatin, agar, microcrystalline cellulose, sodium carboxymethyl cellulose, methylcellulose, and hydroxypropyl methylcellulose.

Further, the oil-soluble emulsifier comprises at least one of sorbitan monolaurate, mono-and diglycerides, citric acid fatty acid glyceride, sucrose fatty acid ester, polyglycerol ricinoleate, polyglycerol fatty acid ester, diacetyl tartaric acid mono-and diglycerides, lactic acid fatty acid glyceride, acetylated mono-and diglycerides, and propylene glycol fatty acid ester.

Further, the grease comprises at least one of soybean oil, camellia oil, walnut oil, peanut oil, rapeseed oil, sunflower oil, corn oil, linseed oil, coconut oil, medium chain triglyceride, palm oil, grape seed oil, peony seed oil, olive oil, wheat germ oil, fish oil, algae oil and conjugated linoleic acid.

Further, the oleogel comprises at least one of cholesterol, sitosterol, oryzanol, palmitic acid, beeswax, rice bran wax, sunflower seed wax, ethylcellulose, and glyceryl stearate.

In a second aspect, the present invention provides a method for preparing the intestinal sustained-release vesicle with taste masking function, which is characterized by comprising the following steps: and carrying out high-pressure homogenization treatment on the water phase raw material forming the capsule core and the oil phase raw material forming the vesicle membrane, centrifuging the mixture, and collecting a lower product to obtain the intestinal slow-release vesicle with taste masking function.

Further, the pressure of the high-pressure homogenization is 200-800 bar, and the homogenization times are 1-5 times; the centrifugal force of the centrifugal treatment is 4000-15000 g, and the time is 10-20 min.

Preferably, the pressure of the high-pressure homogenization is 600bar, and the homogenization times are 3 times; the centrifugal force of the centrifugal treatment is 15000g and the time is 15min.

In a third aspect, the present invention provides a microcapsule, the raw materials of which comprise a core material, a wall material and water,

The core material is the intestinal slow-release type vesicle with taste masking function, or the intestinal slow-release type vesicle with taste masking function obtained by the preparation method.

Further, the wall material comprises at least one of sodium caseinate, sodium starch octenyl succinate, whey protein isolate, soy protein isolate, high fructose corn syrup, starch, maltodextrin, acacia, gelatin, pectin, hydroxypropyl methylcellulose, erythritol, xylitol, glucose, sucrose, lactose, alpha-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin, hydroxypropyl-beta-cyclodextrin; the mass ratio of the core material to the wall material to the water is 10:40:50.

Preferably, the wall material is prepared from sodium caseinate and maltodextrin in a mass ratio of 2:1, whey protein isolate and maltodextrin are mixed according to the mass ratio of 1:1, whey protein isolate and maltodextrin according to a mass ratio of 2:1 or gamma-cyclodextrin and acacia in the mass ratio of 2: 1.

In a fourth aspect, the present invention provides a method for preparing the microcapsule, comprising the steps of:

Stirring the core material, the wall material and water in proportion until the core material, the wall material and the water are uniformly dispersed, and homogenizing the mixture under high pressure to obtain microcapsule mother liquor;

and dehydrating and drying the microcapsule mother liquor to obtain the microcapsule.

Further, the pressure of the high-pressure homogenization is 200-800 bar, and the times are 1-5 times.

Preferably, the high pressure homogenization is performed at a pressure of 400bar for a number of 2 times.

In a fifth aspect, the present invention provides the intestinal slow-release vesicle with taste masking function, or the application of the intestinal slow-release vesicle with taste masking function obtained by the preparation method in preparing food or health care products.

The technical scheme of the invention has the following advantages:

The intestinal slow-release vesicle with taste masking function is prepared by mixing water phase raw materials (active ingredients, sugar substances, water and thickening agents) forming a vesicle core and oil phase raw materials (phospholipids, grease, oil gel and oil-soluble emulsifying agents) forming a vesicle membrane, wherein the sugar substances and the thickening agents in the water phase raw materials are matched with the phospholipids, the oil gel and the oil-soluble emulsifying agents in the oil phase raw materials to form a stable support for the vesicle structure, so that the complete vesicle membrane is formed, the problem that the active ingredients cannot be imported due to bad sense such as pungency, bitter and astringent is solved, the active ingredients wrapped by the structure can be safely added into foods and health care products, the application scene of the active ingredients with bad taste is enlarged, the health effect is promoted to be exerted, and meanwhile, the slow release of the active ingredients in the intestinal tract can be realized, and the functional activity of the active ingredients can be permanently exerted. No organic reagent with high residual risk is added, and the edible safety is higher.

Specifically, the carbohydrate in the aqueous phase raw material has the function of improving osmotic pressure, and provides hydrogen bonds to help intermolecular bonding, and certain carbohydrate (such as cyclodextrin) can also increase the solubility of the active substance, and the carbohydrate attracts with the hydrophilic end of phospholipid, assembles at the oil-water interface and forms vesicles. Experiments prove that the carbohydrate in the water phase raw material plays a vital role in forming and stabilizing the vesicle structure, and the vesicle structure formed after the carbohydrate is omitted is unstable, is easy to break, does not have a complete cavity and does not have the capability of loading active ingredients. The thickener in the water phase raw material has the function of improving the stability of the water phase in the vesicle. By properly increasing the viscosity of the aqueous phase, the active ingredient is not easily leaked from the vesicles. The oil-soluble emulsifier and the oil gel in the oil phase raw material play a role in reinforcing the structural stability of the vesicle, so that a firmer vesicle structure is formed, the sample stability is improved, the grease only provides the functions of dispersing the phospholipid and the oil-soluble emulsifier, and the grease can be removed through centrifugation after the vesicle is formed, so that the overall greasy feeling of the vesicle is reduced, and the higher encapsulation rate is realized.

The preparation method of the intestinal slow-release vesicle with taste masking function mainly comprises the steps of high-pressure homogenization and centrifugation, wherein the oil phase raw material forming the vesicle membrane and the water phase raw material forming the vesicle core are fully mixed by utilizing the high-pressure homogenization technology, then the formation of the vesicle structure is promoted by centrifugation, in the centrifugation process, the vesicle layer membrane is obtained at the water-oil interface by water-in-oil droplets, the vesicle wrapping the vesicle core is formed by spontaneous assembly and migration, excessive oil can be removed by centrifugation, and the lower product is collected, namely the intestinal slow-release vesicle with the taste masking function. In summary, loading the active material by this method not only imparts a masking effect to the bad flavor but also removes unnecessary fat by centrifugation, reducing the burden on the body.

Compared with the EGCG nano vesicle in the prior art (the phospholipid nano vesicle construction of epigallocatechin gallate (EGCG) and the caries resistance research thereof), the vesicle provided by the invention has certain advantages: ethanol is used in the preparation process of the EGCG nano vesicle, belongs to an organic reagent, has residual risk, and is not added with any organic reagent with residual risk; the preparation process of the EGCG nano vesicle involves the operation of constant-temperature water bath at 35-40 ℃, and the EGCG is promoted to be degraded by heating; in the preparation process of the EGCG nano vesicle, 4 hours of condensation reflux is needed, the process is complex, the time is long, and the preparation process is very simple and easy to operate; the EGCG nano vesicle aims at improving the stability of EGCG, and although a vesicle encapsulation structure is also formed, the product prepared by the method still has heavy bitter taste and can not realize good taste masking effect through testing, and the vesicle provided by the invention can well encapsulate active ingredients in the vesicle and mask the bad flavor of the active ingredients.

Compared with the water-in-oil emulsion in the prior art, the vesicle provided by the invention has certain advantages: for water-in-oil emulsions, the oil phase is eventually distributed outside the droplets by adding hydrophilic and hydrophobic surfactants to the two immiscible phases, and then homogenizing the resulting water-in-oil droplets, while the aqueous solution is encapsulated inside the droplets. Grease can physically isolate the active from contact with the oral cavity, preventing it from releasing a bad flavor, but it usually requires the addition of more fat, is greasy in taste, is poorly palatable, and can also place additional burden on the body. In addition, the stability of water-in-oil emulsions is relatively poor, and direct disruption after centrifugation is difficult to achieve effective encapsulation of the active ingredient. The vesicle provided by the invention is obtained through centrifugal treatment, the system stability is obviously higher, the encapsulation effect is better, the loading capacity is higher, unnecessary grease is removed through centrifugation, the greasy feeling is reduced, the palatability is good, and the physical burden is smaller.

The invention also provides a microcapsule which is prepared by taking the intestinal slow-release type vesicle with taste masking function as a core material and adding the wall material, and can be directly taken as food or health care products or can be added into the food or health care products as a nutrition enhancer. After the vesicles are made into the microcapsules, the application scene of the product is widened, the product types are enriched, and more choices are provided for consumers.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are needed in the description of the embodiments or the prior art will be briefly described, and it is obvious that the drawings in the description below are some embodiments of the present invention, and other drawings can be obtained according to the drawings without inventive effort for a person skilled in the art.

FIG. 1 is a schematic flow chart of the preparation of vesicles in an embodiment of the invention;

FIG. 2 is a transmission electron micrograph of vesicles prepared according to example 2 of the invention;

FIG. 3 is a schematic flow chart of the preparation of microcapsules in an embodiment of the invention;

FIG. 4 is a comparative view showing the appearance of aqueous phase raw material solutions during vesicle preparation in examples 1 to 4 and comparative example of the present invention;

FIG. 5 is a comparative view showing the appearance after high-pressure homogenization treatment and after centrifugation treatment in the preparation of vesicles according to examples 1 to 4 and comparative example of the present invention;

FIG. 6 is a graph showing comparison of encapsulation efficiency of vesicles prepared in examples 1 to 4 and comparative example of the present invention;

FIG. 7 is a graph showing the microscopic morphology of vesicles prepared in comparative examples and examples 2 and 4;

FIG. 8 is a graph showing comparison of intestinal sustained-release effects of vesicles prepared in examples 1 to 4 and comparative examples of the present invention;

FIG. 9 is a graph showing the comparison of binding strength between aqueous phase raw material solution and mucin during vesicle preparation in comparative example and example 2, example 4, and EGCG;

FIG. 10 is a graph showing the distribution of sensory scores of aqueous phase raw material solutions during the preparation of vesicles according to comparative examples and examples 2 and 4 of the present invention and EGCG and example 2.

Detailed Description

The following examples are provided for a better understanding of the present invention and are not limited to the preferred embodiments described herein, but are not intended to limit the scope of the invention, any product which is the same or similar to the present invention, whether in light of the present teachings or in combination with other prior art features, falls within the scope of the present invention.

The specific experimental procedures or conditions are not noted in the examples and may be followed by the operations or conditions of conventional experimental procedures described in the literature in this field. The materials or instruments used are all conventional products commercially available, including but not limited to those used in the examples of the present invention.

Example 1

The embodiment provides a vesicle, which consists of a vesicle core and a vesicle membrane wrapping the vesicle core,

Aqueous phase raw material forming capsule core: epigallocatechin gallate (EGCG), gamma-cyclodextrin, water and xanthan gum according to the mass ratio of 5:20:74.5:0.5 mixing;

oil phase raw material for forming vesicle membrane: phospholipid, corn oil and beeswax according to the mass ratio of 55:44:1, mixing;

the mass ratio of the water phase raw material to the oil phase raw material is 1:6.

The preparation flow of the vesicle is shown in figure 1, and the specific method is as follows:

mixing water phase raw material forming capsule core and oil phase raw material forming vesicle membrane in proportion, homogenizing at 600bar pressure for 3 times, centrifuging the mixture at 15000g for 15min to remove excessive oil, and collecting lower layer product to obtain vesicle.

Example 2

The present embodiment provides a vesicle, and the raw materials and the preparation method refer to embodiment 1, and the difference is that the mass ratio of EGCG, γ -cyclodextrin, water and xanthan gum is 5:30:64.5:0.5. the vesicle structure obtained in this example was observed by transmission electron microscopy, and as shown in fig. 2, a closed vesicle with clear edges and complete appearance was seen.

Example 3

The present embodiment provides a vesicle, and the raw materials and the preparation method refer to embodiment 1, and the difference is that the mass ratio of EGCG, γ -cyclodextrin, water and xanthan gum is 5:40:54.5:0.5.

Example 4

The present embodiment provides a vesicle, and the raw materials and the preparation method refer to embodiment 1, and the difference is that the mass ratio of EGCG, γ -cyclodextrin, water and xanthan gum is 5:50:44.5:0.5.

Example 5

Aqueous phase raw material forming capsule core: catechin, maltodextrin, water and xanthan gum in a mass ratio of 5:5:89.8:0.2 mixing;

oil phase raw material for forming vesicle membrane: phospholipid, mono-and diglyceride fatty acid ester, conjugated linoleic acid and oryzanol according to the mass ratio of 35:5:59.5:0.5 mixing;

The mass ratio of the water phase raw material to the oil phase raw material is 1:5.

The preparation of vesicles is described in example 1.

Example 6

Aqueous phase raw material forming capsule core: catechin, sucrose, water and carrageenan in a mass ratio of 5:20:74.8:0.2 mixing;

oil phase raw material for forming vesicle membrane: phospholipid, conjugated linoleic acid and sitosterol according to the mass ratio of 40:59:1, mixing;

The preparation of vesicles is described in example 1.

Example 7

Aqueous phase raw material forming capsule core: catechin, maltose, water and locust bean gum according to a mass ratio of 5:30:64.8:0.2 mixing;

Oil phase raw material for forming vesicle membrane: phospholipid, fatty acid ester of mono-glycerol and diglycerol, corn oil and sitosterol according to the mass ratio of 40:5:53.5:1.5, mixing;

The preparation of vesicles is described in example 1.

Example 8

Aqueous phase raw material forming capsule core: catechin, isomaltooligosaccharide, water and sodium alginate in a mass ratio of 5:40:54.8:0.2 mixing;

Oil phase raw material for forming vesicle membrane: the mass ratio of the phospholipid, the linseed oil and the sitosterol is 50:48:2, mixing;

The preparation of vesicles is described in example 1.

Example 9

Aqueous phase raw material forming capsule core: catechin, gamma-cyclodextrin, water and xanthan gum in a mass ratio of 5:50:44.5:0.5 mixing;

oil phase raw material for forming vesicle membrane: phospholipid, sunflower oil and sitosterol according to the mass ratio of 60:38:2, mixing;

The preparation of vesicles is described in example 1.

Example 10

Aqueous phase raw material forming capsule core: bitter peptide, fructose, water and xanthan gum in a mass ratio of 5:20:74.8:0.2 mixing;

Oil phase raw material for forming vesicle membrane: phospholipid, citric acid fatty acid ester, algae oil and rice bran wax according to the mass ratio of 30:5:64.5:0.5 mixing;

The preparation of vesicles is described in example 1.

Example 11

Aqueous phase raw material forming capsule core: bitter peptide, maltose, water and pectin according to the mass ratio of 5:30:64.8:0.2 mixing;

Oil phase raw material for forming vesicle membrane: phospholipid, polyglycerol fatty acid ester, camellia oil and rice bran wax according to the mass ratio of 40:5:54:1, mixing;

The preparation of vesicles is described in example 1.

Example 12

Aqueous phase raw material forming capsule core: bitter peptide, maltose, water and sodium alginate according to the mass ratio of 5:40:54.8:0.2 mixing

Oil phase raw material for forming vesicle membrane: phospholipid, polyglycerol ricinoleate, coconut oil and beeswax according to the mass ratio of 45:8:45.5:1.5, mixing;

The preparation of vesicles is described in example 1.

Example 13

Aqueous phase raw material forming capsule core: bitter peptide, maltose, water and pectin according to the mass ratio of 5:50:44.5:0.5 mixing;

Oil phase raw material for forming vesicle membrane: phospholipid, polyglycerol ricinoleate, coconut oil and beeswax according to the mass ratio of 50:8:40:2, mixing;

The preparation of vesicles is described in example 1.

Example 14

Aqueous phase raw material forming capsule core: piperine, gamma-cyclodextrin, water and gellan gum according to the weight ratio of 5:30:64.8:0.2 mixing;

oil phase raw material for forming vesicle membrane: phospholipid, sucrose fatty acid ester, corn oil and glyceryl stearate according to the mass ratio of 30:10:59.5:0.5 mixing;

The preparation of vesicles is described in example 1.

Example 15

Aqueous phase raw material forming capsule core: piperine, gamma-cyclodextrin, water and agar according to the proportion of 5:40:54.8:0.2 mixing;

Oil phase raw material for forming vesicle membrane: phospholipid, sorbitan monolaurate, corn oil and cholesterol in a mass ratio of 40:10:49:1, mixing;

The preparation of vesicles is described in example 1.

Example 16

Aqueous phase raw material forming capsule core: piperine, gamma-cyclodextrin, water and microcrystalline cellulose according to the proportion of 5:50:44.8:0.2 mixing;

oil phase raw material for forming vesicle membrane: phospholipid, sorbitan monolaurate, medium Chain Triglyceride (MCT) and cholesterol in a mass ratio of 45:10:43.5:1.5, mixing;

The preparation of vesicles is described in example 1.

Example 17

Aqueous phase raw material forming capsule core: piperine, gamma-cyclodextrin, water and carrageenan according to the proportion of 5:55:39.5:0.5 mixing;

oil phase raw material for forming vesicle membrane: phospholipid, sorbitan monolaurate, conjugated linoleic acid and cholesterol in a mass ratio of 45:10:43:2, mixing;

The preparation of vesicles is described in example 1.

Example 18

The embodiment provides a microcapsule, which is prepared from core materials, wall materials and water,

The core material is the vesicle prepared in example 9;

The wall material is sodium caseinate,

The preparation flow of the microcapsule is shown in figure 3, and the specific method is as follows:

Core material, wall material and water are mixed according to the weight ratio of 10:40:50, stirring to a uniform dispersion state, and homogenizing for 2 times under 400bar pressure to obtain microcapsule mother liquor; and (5) dehydrating and drying the microcapsule mother liquor to obtain the microcapsule.

Example 19

The core material is the vesicle prepared in example 9;

the wall material is prepared from sodium caseinate and OSA starch according to a mass ratio of 2: 1a composition of the composite material,

The method of preparing microcapsules is described in example 18.

Example 20

The core material is the vesicle prepared in example 9;

the wall material is prepared from sodium caseinate and maltodextrin in a mass ratio of 2: 1a composition of the composite material,

The method of preparing microcapsules is described in example 18.

Example 21

The core material is the vesicle prepared in example 13;

the wall material is prepared from whey protein isolate and maltodextrin according to a mass ratio of 1: 1a composition of the composite material,

The method of preparing microcapsules is described in example 18.

Example 22

The core material is the vesicle prepared in example 13;

the wall material is prepared from whey protein isolate and maltodextrin according to a mass ratio of 2: 1a composition of the composite material,

The method of preparing microcapsules is described in example 18.

Example 23

The core material is the vesicle prepared in example 17;

The wall material is prepared from gamma-cyclodextrin and acacia in a mass ratio of 2: 1a composition of the composite material,

The method of preparing microcapsules is described in example 18.

Comparative example

This comparative example provides a vesicle, consisting of a vesicle core and a vesicle membrane surrounding the vesicle core,

Aqueous phase raw material forming capsule core: epigallocatechin gallate (EGCG), water and xanthan gum according to the mass ratio of 5:74.5:0.5 mixing;

Oil phase raw material for forming vesicle membrane: phospholipid and corn oil according to the mass ratio of 55:45 mixing;

The preparation of vesicles is described in example 1.

The comparative example also provides a microcapsule, the raw materials consist of core material, wall material and water,

The core material is the vesicle prepared in the comparative example;

The wall material is sodium caseinate,

The method of preparing microcapsules is described in example 18.

Experimental example 1

The following studies were performed using vesicles prepared in examples 1 to 4 and comparative examples as experimental subjects:

1. Appearance change during vesicle preparation

The appearance of the aqueous phase raw material solution during vesicle preparation of examples 1 to 4 and comparative example was photographed as shown in fig. 4. The addition of gamma-cyclodextrin significantly promoted dissolution of EGCG, with increasing concentration of gamma-cyclodextrin, the transparency of the aqueous raw material solution increased, indicating complete dissolution of EGCG. This is because the cavity structure of gamma-cyclodextrin increases the solubility of EGCG in water.

The appearances of examples 1 to 4 and comparative examples after high pressure homogenization treatment and after centrifugation treatment during vesicle preparation were photographed as shown in fig. 5. The coarse emulsion after high-pressure homogenization treatment is milky and fine liquid. As the concentration of γ -cyclodextrin increased, the vesicles prepared in example 2 and example 3 separated from the oil phase, and the vesicles prepared in example 4 disappeared from the oil phase. This is because the addition of an excess of gamma cyclodextrin can enhance the hydrophilicity of the interfacial layer, potentially leading to the emulsion transitioning from a water-in-oil phase to an oil-in-water phase. After centrifugation, the upper layer is the oil phase and the lower layer is the prepared vesicle.

2. Encapsulation efficiency of vesicles

Encapsulation efficiency (EE%) is an important indicator for evaluating the encapsulation effect of the vehicle, which can be used to evaluate the encapsulation effect of vesicles on EGCG. Dialysis is a common method for determining the EE% of water-soluble active ingredient. Since EGCG is easily degraded in neutral and alkaline aqueous solutions, phosphate buffer (ph=5.5, 50 mm) is used as a dialysis solution to ensure stability of EGCG during dialysis. Preliminary experiments have found that 12 hours can result in more than 90% of the non-encapsulated EGCG being released. Thus, a dialysis time point of 12 hours was selected to evaluate the encapsulation efficiency of vesicles, and the results are shown in fig. 6. The encapsulation rate of the vesicles prepared in the embodiment to EGCG reaches more than 70%. With the addition of gamma-cyclodextrin, the encapsulation efficiency of example 2 increased to about 90% with a maximum encapsulation efficiency of 92.11% ± 0.56%. However, further addition of gamma cyclodextrin had a detrimental effect on vesicle encapsulation, and the vesicle encapsulation rates of examples 3 and 4 were slightly reduced.

3. Microcosmic morphology of vesicles

The structural distribution and microstructure of the vesicles were observed using transmission electron microscopy, as shown in fig. 7. The vesicle is about 100-300 nm in size, and the outer surface is of a multi-layer membrane structure. With increasing gamma-cyclodextrin content, vesicle morphology changes. For the comparative example where no gamma-cyclodextrin was added, the vesicle-like structure was visible at 200nm, but the inner aqueous phase was blurred with respect to the vesicle membrane, and no fully closed embedded vesicles were formed, probably due to incomplete dissolution of EGCG without gamma-cyclodextrin. Thus, EGCG tends to bind to the hydrophilic head of phospholipids, forming a mixture with phospholipids, rather than forming an entrapped structure. For example 2, after addition of gamma cyclodextrin, nano-scale vesicles were observed at 1 μm and a multilayer film of the outer surface of circular vesicles was seen at 200 nm. For example 4, with further increase in cyclodextrin content, the round shape of the vesicles changed at 500nm and 200nm, the vesicle-like structure was visible at 200nm, the boundary between the aqueous phase and the vesicle membrane was clear, but the vesicle membrane was irregular and tended to rupture. This may be due to excessive leakage of gamma cyclodextrin from the core, resulting in damage to the vesicle membrane, affecting the encapsulation effect. Several rectangular crystalline materials were also observed at 1 μm, formed by recrystallization of gamma-cyclodextrin leaking from the capsule core.

4. Intestinal slow release properties of vesicles

The study adopts a dialysis method to evaluate the intestinal slow release performance of vesicles on EGCG, and the specific method is as follows:

5g of the aqueous phase stock solution of example 2 and the vesicle samples prepared in example 2, example 4 and comparative example were immersed in 500mL of simulated intestinal fluid in a dialysis bag having a molecular weight of 10kDa, dialyzed at 25℃and 100rpm, and the EGCG content in the buffer outside the dialysis bag was measured by sampling at preset incubation time points (0.5, 1,2,3,4, 6, 8, 12 and 24 h).

The results are shown in FIG. 8. The release rate of the aqueous phase raw material solution was 48.87% ± 0.55% in the first 2 hours, whereas the release rate of EGCG in vesicles was only between 1.86% ± 1.00% (example 4) and 4.08% ± 0.97% (comparative example), with almost no EGCG release. After 12h, the release amount of the aqueous phase raw material solution is 92.14 +/-1.74%, and the release amount of EGCG in the vesicle is only about 10%, which indicates that the vesicle can effectively encapsulate EGCG and has good EGCG slow release capability. The 24 hour release of vesicles indicated that addition of gamma cyclodextrin was effective to reduce the EGCG release from 19.59% + -0.77% (comparative) to 10.31% + -0.35% (example 2) of vesicles, which is related to the ability of gamma cyclodextrin to form stable complexes with EGCG. The addition of too much gamma cyclodextrin resulted in increased release of EGCG, probably due to deformation and rupture of the phospholipid membrane resulting in leakage of EGCG due to excessive addition of gamma cyclodextrin, which is consistent with the TEM results of fig. 7. Nevertheless, vesicles still exhibit excellent EGCG enteric slow release properties.

5. Bitter taste masking effect of vesicles

(1) QCM-D analysis

Mucin is an important substance constituting an oral mucosal barrier in the oral cavity, and the bitter and astringent tastes of EGCG in the oral cavity are mainly derived from the binding of EGCG to mucins in the oral mucosa. Thus, mucin was chosen as a substrate to mimic the interaction of EGCG with oral proteins when consumed on QCM-D. The specific method comprises the following steps:

Before measurement, appropriate amounts of the aqueous phase raw material solution of comparative example, the aqueous phase raw material solution of example 2, and the vesicles prepared in example 2 and example 4 were dispersed in PBS buffer having ph=5.5 and 50mM, to ensure the same EGCG concentration (1% wt). Mucin was dissolved in PBS buffer (ph=6.8, 50 mm) to make oral mucin solution (ph=6.8, 3.2% w/v) and stirred overnight to enhance protein hydration. A measurement baseline was established with PBS buffer (ph=6.8, 50 mm), oral mucus solution was introduced into the module, flowed through a QCM-D instrument equipped SiO ₂ chip (model QSX 301) at 25 ℃ at a rate of 0.6mL/min, allowed sufficient time for the substrate to adsorb onto the chip and settle, and then a mucin-free PBS buffer (ph=6.8, 50 mm) was introduced to remove the weakly adsorbed molecular layer. Once a stable mucin layer was formed, the aqueous phase stock solution of the comparative example was introduced into the module at the same flow rate. The buffer wash step (ph=6.8, 50 mm) was repeated until the exposed EGCG in the aqueous solution formed a rigid structure on the chip. Binding strength analysis of other samples to mucin followed the same procedure. The more EGCG the sample is exposed to, the greater the magnitude of the frequency shift detected in the QCM-D experiment, reflecting the more pronounced the bitter and astringent taste of the sample in the oral cavity.

The frequency shift results for the different samples are shown in fig. 9. EGCG solution (1% wt) shifted maximally (-54.30 Hz.+ -. 0.91 Hz). After EGCG forms a complex with gamma-cyclodextrin (aqueous stock solution of example 2), the binding strength with mucin is slightly reduced to-40.55 Hz.+ -. 0.15Hz. Early studies showed that gamma-cyclodextrin can be used to reduce the bitter taste of drugs but cannot be completely eliminated. The vibration frequency of the EGCG encapsulated by the vesicle is obviously reduced, and particularly, the vibration frequency change of the embodiment 2 is minimal, and the EGCG has stronger resistance to the combination effect of EGCG and mucin, and the frequency change is only-4.59 Hz plus or minus 1.24Hz. In the absence of cyclodextrin, the binding strength of the comparative example to mucin was still great because part of EGCG of the comparative example was still exposed on the vesicle surface and could bind to mucin. The binding strength of example 4 was slightly increased because excessive addition of gamma cyclodextrin in the vesicles caused deformation of the phospholipid membrane, disruption of the phospholipid vesicle structure, and leakage of part of the core inside the vesicles, binding to mucin.

(2) Sensory evaluation

The present study evaluates the bitterness, astringency, bitter aftertaste, astringency, sweetness and greasiness of the samples. 10 evaluators each evaluated EGCG solution (1% wt), EGCG-cyclodextrin complex solution (aqueous stock solution of example 2), vesicles prepared in comparative example, vesicles prepared in example 2, vesicles prepared in example 4, purified water, phospholipids and gamma-cyclodextrin. The levels of bitter, astringent, bitter aftertaste and astringent aftertaste are respectively: pure water 0; EGCG solution 10; the pure gamma-cyclodextrin sweet taste is set to 10; the greasy feel level of the pure phospholipid was set to 10. In the sensory evaluation program, the bitter taste, the astringency, the bitter aftertaste, the astringency, and the sweetness were derived from EGCG, the γ -cyclodextrin, and the greasy feeling was derived from phospholipid. The distribution of these six sensory evaluation scores for the samples is shown in fig. 10. EGCG has the least odor masking effect when the complex is formed with gamma cyclodextrin. The masking effect of EGCG without addition of gamma cyclodextrin was also poor in the comparative example. And the addition of gamma-cyclodextrin in the aqueous phase raw material can obviously improve the flavor masking capability of EGCG. The sample of example 2 had little bitter taste, with only a slight greasy feel and sweetness. The masking effect of the sample of example 4 on bitterness was also well evaluated. Although previous experiments found that the addition of too much gamma cyclodextrin resulted in vesicle rupture and EGCG leakage, the slight rupture was probably not noticeable to the evaluator due to the short residence time of the vesicles in the mouth during sensory evaluation, and thus the sensory evaluation of example 2 and example 4 differed little. This result is consistent with previous analysis, and the addition of gamma-cyclodextrin in appropriate amounts to vesicles can significantly mask the bitter taste of EGCG.

Sensory evaluation each average score is shown in table 1.

Table 1 scoring results of sensory evaluation

6. Summary

The vesicles prepared by the embodiment of the invention reduce the bitter taste of EGCG and delay the release of EGCG in intestinal tracts. This effect is mainly due to the fact that EGCG is located in the inner aqueous phase containing gamma-cyclodextrin. The gamma-cyclodextrin and the phospholipid nano vesicles can block the combination of EGCG and oral mucin and delay the release of EGCG. The amount of gamma-cyclodextrin added affects the ability of the vesicles to mask the bitter taste of EGCG and its sustained release ability: the proper addition of gamma-cyclodextrin can improve the combination of phospholipid and EGCG by increasing the hydrogen bond interaction force between the phospholipid head region and EGCG, but excessive addition of gamma-cyclodextrin can lead to rupture of phospholipid membrane, thereby reducing the encapsulation efficiency and the sustained release effect of EGCG. The oil content in the product can be greatly reduced by centrifugal treatment, and EGCG is more beneficial to playing the roles of reducing lipid and losing weight.

Experimental example 2

This experimental example evaluates the texture, the direct inlet sense of the vesicles prepared in examples 5-17, and the sense after dispersion in water. The results are shown in Table 2.

TABLE 2 evaluation of Effect of examples 5 to 17

Experimental example 3

This experimental example evaluates the appearance, the sensory properties of the inlet, the powder flowability and the rehydration dissolution of the microcapsules prepared in examples 18-23. The results are shown in Table 3.

TABLE 3 evaluation of Effect of examples 18 to 23

As shown in Table 3, the microcapsules prepared in examples 18 to 23 of the present invention were all milky white powder; the vesicle adopted by the core material has no bad flavor, and the microcapsule prepared by the core material has no bad flavor at the same inlet; the powder fluidity and rehydration solubility are related to the materials selected for the wall material, and when the wall material is compatible with maltodextrin and sodium caseinate/whey protein isolate (examples 20-22) or compatible with gamma-cyclodextrin and acacia (example 23), the powder fluidity is good, the microcapsule rehydrates well, and the microcapsule is not easy to agglomerate.

It is apparent that the above examples are given by way of illustration only and are not limiting of the embodiments. Other variations or modifications of the above teachings will be apparent to those of ordinary skill in the art. It is not necessary here nor is it exhaustive of all embodiments. While still being apparent from variations or modifications that may be made by those skilled in the art are within the scope of the invention.

Claims

1. An intestinal slow-release vesicle with taste masking function is characterized by comprising a vesicle core and a vesicle membrane wrapping the vesicle core,

2. The intestinal slow-release vesicle with taste masking function according to claim 1, wherein,

The mass ratio of the active ingredients to the saccharides to the water to the thickener is 1-30: 1 to 50:19.9 to 97:0.1 to 1;

The mass ratio of the phospholipid, the grease, the oil-soluble emulsifier and the oil gel is 5-80: 19.9 to 93:0 to 10:0.1 to 2;

3. The intestinal slow-release vesicle with taste masking function according to claim 1, wherein,

The mass percentage of the active ingredient in the water phase raw material is 1-5%, the mass percentage of the saccharide in the water phase raw material is 5-50%, and the mass percentage of the thickener in the water phase raw material is 0.1-1%;

The mass ratio of the water phase raw material to the oil phase raw material is 1:2 to 10 percent of the total weight of the composite,

Preferably, the mass percentage of the active ingredient in the water phase raw material is 5%, the mass percentage of the saccharide in the water phase raw material is 30% -55%, and the mass percentage of the thickener in the water phase raw material is 0.2% -0.5%;

more preferably, the mass percentage of the active ingredient in the aqueous phase raw material is 5%, the mass percentage of the saccharide in the aqueous phase raw material is 40%, and the mass percentage of the thickener in the aqueous phase raw material is 0.5%;

Preferably, the mass percentage of the phospholipid in the oil phase raw material is 45% -60%, the mass percentage of the oil-soluble emulsifier in the oil phase raw material is 8% -10%, and the mass percentage of the oil gel in the oil phase raw material is 1% -2%;

more preferably, the mass percentage of the phospholipid in the oil phase raw material is 55%, the mass percentage of the oil soluble emulsifier in the oil phase raw material is 8%, and the mass percentage of the oil gel in the oil phase raw material is 2%;

4. The intestinal tract-delayed-release vesicle with taste masking function according to claim 1, wherein the active ingredient comprises at least one of capsaicin, piperine, ginger extract, gingerol, garlicin, xanthosine, bitter peptides, albumin peptides, blood peptides, tea polyphenols, catechin, epigallocatechin gallate, propolis flavones, nicotinamide mononucleotide, reduced nicotinamide adenine dinucleotide, glutathione, pagodatree flower bud extract, dihydromyricetin, caffeine, deer blood, yeast extract, pig liver extract, beef liver extract, tortoise plastin, turtle peptides, bird nest acids, oyster peptides, chondroitin sulfate, gamma-aminobutyric acid, taurine, levocarnitine, corn peptides, balsam pear peptides, ginseng peptides, bovine bone peptides, dendrobium nobile extract;

The saccharide substance comprises at least one of sucrose, lactose, fructose, glucose, polydextrose, trehalose, lactulose, xylose, arabinose, mannooligosaccharide, maltose, oligomaltose, oligoisomaltose, oligoisomaltulose, maltoulose, maltitol, mannitol, sorbitol, xylitol, erythritol, maltodextrin, alpha-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin and hydroxypropyl-beta-cyclodextrin;

The thickener comprises at least one of xanthan gum, pectin, locust bean gum, tamarind gum, carrageenan, sodium alginate, karaya gum, curdlan, psyllium seed gum, papaya seed gum, peach gum, konjac gum, pullulan, acacia, guar gum, gellan gum, gelatin, agar, microcrystalline cellulose, sodium carboxymethylcellulose, methylcellulose, and hydroxypropyl methylcellulose;

The oil-soluble emulsifier comprises at least one of sorbitan monolaurate, mono-and diglyceride fatty acid esters, citric acid fatty acid glyceride, sucrose fatty acid ester, polyglycerol ricinoleate, polyglycerol fatty acid ester, diacetyl tartaric acid mono-and diglyceride, lactic acid fatty acid glyceride, acetylated mono-and diglyceride fatty acid ester, and propylene glycol fatty acid ester;

The grease comprises at least one of soybean oil, camellia oil, walnut oil, peanut oil, rapeseed oil, sunflower oil, corn oil, olive oil, almond oil, sesame oil, linseed oil, coconut oil, medium chain triglyceride, palm oil, grape seed oil, peony seed oil, olive oil, wheat germ oil, fish oil, algae oil and conjugated linoleic acid;

the oil gel comprises at least one of cholesterol, sitosterol, oryzanol, palmitic acid, beeswax, rice bran wax, sunflower seed wax, ethyl cellulose and glyceryl stearate.

5. The method for producing an intestinal tract slow-release vesicle with taste masking function according to any one of claims 1 to 4, comprising the steps of: and carrying out high-pressure homogenization treatment on the water phase raw material forming the capsule core and the oil phase raw material forming the vesicle membrane, centrifuging the mixture, and collecting a lower product to obtain the intestinal slow-release vesicle with taste masking function.

6. The method for producing an intestinal tract slow-release vesicle with taste masking function according to claim 5, wherein,

The pressure of the high-pressure homogenization is 200-800 bar, and the homogenization times are 1-5 times;

the centrifugal force of the centrifugal treatment is 4000-15000 g, the time is 10-20 min,

Preferably, the high-pressure homogenizing pressure is 600bar, and the times are 3 times; the centrifugal force of the centrifugal treatment is 15000g and the time is 15min.

7. A microcapsule is characterized in that the microcapsule comprises a core material, a wall material and water,

The core material is the intestinal slow-release type vesicle with taste masking function according to any one of claims 1 to 4, or the intestinal slow-release type vesicle with taste masking function obtained by the preparation method according to claim 5 or 6.

8. A microcapsule according to claim 7, characterized in that,

The wall material comprises at least one of sodium caseinate, sodium starch octenyl succinate, whey protein isolate, soy protein isolate, high fructose corn syrup, starch, maltodextrin, acacia, gelatin, pectin, hydroxypropyl methylcellulose, erythritol, xylitol, glucose, sucrose, lactose, alpha-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin and hydroxypropyl-beta-cyclodextrin;

the mass ratio of the core material to the wall material to the water is 10:40:50.

9. A method of preparing microcapsules according to claim 7 or 8, comprising the steps of:

Dehydrating and drying the microcapsule mother liquor to obtain the microcapsule,

Preferably, the pressure of the high-pressure homogenization is 200-800 bar, the times are 1-5 times,

More preferably, the high pressure homogenization is performed at a pressure of 400bar for a number of 2 times.

10. The use of the intestinal slow-release vesicle with taste masking function according to any one of claims 1 to 4, or the intestinal slow-release vesicle with taste masking function obtained by the preparation method according to claim 5 or 6, or the microcapsule according to claim 7 or 8, or the microcapsule obtained by the preparation method according to claim 9, in the preparation of food or health-care products.