CN111820281B - Sustained-release nutritional VC (vitamin C) lutein peptide chewable tablet and preparation method thereof - Google Patents

Abstract

The invention provides a slow-release nutritional VC lutein peptide chewable tablet and a preparation method thereof. The chewable tablet includes the following components: bovine colostrum powder, goat milk powder, whey protein concentrate, marine fish oligopeptide, casein Protein phosphopeptide, soybean peptide, soybean protein powder, sea cucumber peptide, oyster peptide, fruit and vegetable powder, lactose, resistant dextrin, chitosan oligosaccharide, fructooligosaccharide, vitamin C, lutein ester, xylo-oligosaccharide, erythromycin Sugar alcohol, sorbitol, citric acid, silicon dioxide, maltodextrin, magnesium stearate; also includes targeted sustained-release biocompatible microcapsules. The chewable tablet prepared by the preparation method and composition provided by the invention can release marine fish oligopeptide, casein phosphopeptide, sea cucumber peptide, soybean peptide and oyster peptide with nutritional effect in the intestinal tract, and can pass through the blood-brain barrier and act on Eye cells, repair eye fatigue and provide lutein ester and citric acid needed for eye work, provide brain cells to work and improve brain nutrition.

Description

Sustained-release nutritional VC lutein peptide chewable tablet and preparation method thereof

technical field

The invention belongs to the technical field of composite biology, in particular to a slow-release nutritional VC lutein peptide chewable tablet and a preparation method thereof.

Background technique

With the continuous rapid development of my country's economy, the continuous improvement of living standards, the rapid development of my country's Internet, the degree of intelligence of mobile phones, mobile phones have become part of our lives, and children, teenagers and other groups rely on mobile phones and electronic products, which also leads to widespread vision. The downward trend and phenomenon, the damage of screen light to the retina is slow and irreversible, which is a huge harm to the health of teenagers in our country, and it is urgent to protect the eyes of teenagers.

According to a research report released by the World Health Organization in 2019, there are as many as 600 million people with myopia in China, almost half of the total population. Teenagers also have the highest rates of myopia of any country in the world. Unhealthy eyesight affects people's daily life, study and work, threatens residents' health, and increases social burden. The society's emphasis on eye care and eye care has also attracted a lot of social capital to enter the industry, but eye care companies generally lack core competitiveness, single products and services, and low quality of personnel. Some medicines exaggerate their efficacy and replace medical measures with health care measures, which has brought great negative effects to the industry. And the existing medicine lacks the active peptides that can effectively protect vision, release the active peptides that are beneficial to vision protection, nourish the ocular nerve, improve immunity, provide nutrition for brain cells, and improve intelligence, and a composition prepared by using the same. Chewable tablets.

SUMMARY OF THE INVENTION

Aiming at the above defects, the present invention provides a marine fish oligopeptide, casein phosphopeptide, sea cucumber peptide, soybean peptide and oyster peptide that can release nutrition in the intestinal tract, and can pass through the blood-brain barrier and act on eye cells , Repair eye fatigue and provide lutein ester and citric acid needed for eye work, and assist in the digestion of bovine colostrum powder, goat milk powder, whey protein concentrate and soy protein powder in the stomach to enhance human immunity, The invention provides a slow-release nutritional VC lutein peptide chewable tablet and a preparation method thereof, which provides the work of brain cells and improves the nutrition of the brain.

The present invention provides the following technical solutions: a sustained-release nutritional VC lutein peptide chewable tablet, each 1 g of the chewable tablet includes the following components:

Colostrum powder 6mg～50mg, goat milk powder 10mg～100mg, whey protein concentrate 10mg～150mg, marine fish oligopeptide 1mg～8mg, casein phosphopeptide 5mg～70mg, soybean peptide 0.5mg～6mg, soybean protein powder 0.5 mg～5mg, sea cucumber peptide 13mg～100mg, oyster peptide 13mg～100mg, fruit and vegetable powder 10mg～100mg, lactose 1mg～4mg, resistant dextrin 1mg～5mg, chitosan oligosaccharide 1mg～10mg, fructooligosaccharide 1mg～10mg, vitamin C 5mg～80mg, lutein ester 5mg～100mg, xylo-oligosaccharide 0.6mg～1mg, erythritol 0.5mg～10mg, sorbitol 0.5mg～15mg, citric acid 0.05mg～1mg, silicon dioxide 0.05 mg～1mg, maltodextrin 0.08mg～10mg, magnesium stearate 0.5mg～1mg.

Among them, oligofructose was extracted from chicory, and lutein ester was extracted from marigold.

Further, each 1 g chewable tablet also includes 20 mg to 30 mg of targeted sustained-release biocompatible microcapsules, and the targeted sustained-release biocompatible microcapsules, in terms of weight components, include the following components: 15-20 parts polycarbonate films with a thickness of 250 nm and a thickness of 15-30 mm; 12-18 parts of α-whey protein; 12-18 parts of amino acids; 8-12 parts of kappa-carrageenan; 8 parts of lecithin ~12 parts; 25 to 35 parts of poly(2-ethyl-2-oxazoline)-grafted dextran nanoparticles; 0.05 to 0.1 part of N,N-dimethylformamide.

Further, the poly(2-ethyl-2-oxazoline)-grafted dextran nanoparticles, in terms of components by weight, include the following components:

2.5 to 5 parts of poly(2-ethyl-2-oxazoline); 0.2 to 0.5 parts of succinic anhydride; 0.5 to 1 part of 3,3'-dithiopropionic acid; N-(3-(dithiopropionic acid) 1 to 1.5 parts of methylamino)propyl)-N-ethylcarbodiimide hydrochloride; 2 to 2.5 parts of 4-(dimethylamino)pyridine; 3 to 6 parts of dextran;

The preparation method of the poly(2-ethyl-2-oxazoline) grafted dextran nanoparticle comprises the following steps:

M1: The poly(2-ethyl-2-oxazoline) of the weight component and the succinic anhydride of the weight component are dissolved in dichloromethane to form a poly(2-ethyl-2-oxazoline) with a concentration of 7mmol/L～15mmol/ - a mixed solution of ethyl-2-oxazoline) organic solution and 25mmol/L～45mmol/L concentration succinic anhydride organic solution, to the mixed solution, add the weight component of 4-(dimethylamino)pyridine , at 75 rpm to 150 rpm and a temperature of 25 ℃ to 28 ℃ for 12 h to 24 h;

M2: mixing the mixture obtained in the step M1 and diethyl ether at a weight-to-volume ratio of 1:8 for 10 to 15 min, and precipitating in the diethyl ether to obtain a terminally aminated and carboxylated poly(2-ethyl-2- oxazoline) crude product, the terminal aminated and carboxylated poly(2-ethyl-2-oxazoline) crude product was dried under vacuum for 18h-36h to obtain the terminal amination and carboxylation The poly(2-ethyl-2-oxazoline) crude product powder;

M3: Dissolve the dextran of the weight component in dimethyl sulfoxide, dissolve it in a microwave for 3h to 4h under the condition of 10mHz to 20mHz, and then add the poly(2-ethyl-2-oxane obtained in the step M2) oxazoline) crude product powder, N-(3-(dimethylamino)propyl)-N-ethylcarbodiimide hydrochloride of 1/2 the weight component, at 28℃～32℃ After stirring for 30min-60min, add the 3,3'-dithiopropionic acid of the weight component and the N-(3-(dimethylamino)propyl)-N of the remaining half of the weight component -Ethylcarbodiimide hydrochloride, after stirring at 28℃～32℃ for 30min～60min, the obtained mixture was dialyzed for 1h～2h under a dialysis membrane with a molecular pore size of 3200Da～3800Da, at -100℃ Lyophilized to obtain poly(2-ethyl-2-oxazoline)-grafted dextran nanoparticles.

Further, the preparation method of the targeted slow-release biocompatible microcapsules comprises the following steps:

A1: Dissolve the amino acid of the weight component and the α-lactalbumin of the weight component in distilled water, fully stir and hydrate at 80 rpm to 100 rpm for 20 min to 30 min, and place the obtained mixed solution at 0.30 μm to 0.40 μm. Filtration under a polyvinylidene fluoride filter, taking the filtered supernatant to obtain the amino acid-α-lactalbumin mixed supernatant;

A2: Dissolve the κ-carrageenan of the weight component and the lecithin of the weight component in distilled water to form a κ-carrageenan solution with a concentration of 3mmol/L～7mmol/L, 3mmol//L～10mmol //L of lecithin solution;

A3: Dissolve the polycarbonate film of the weight component in a phosphate buffer containing a sodium chloride concentration of 0.13M to 0.15M, and dissolve the weight component of the poly(2-ethyl-2-oxo) oxazoline)-grafted glucan nanoparticles were impregnated and penetrated through the polycarbonate film at a rate of 9 mL/h to 11 mL/h, and then the amino acid-α-lactalbumin mixed supernatant obtained in the A1 step was mixed with Dip through the polycarbonate film at a rate of 9mL/h～11mL/h, and let stand for 3min～5min under a nitrogen flow with a blowing speed of 5cm ² /L; put the kappa-carrageenan solution obtained in step A2 into 9mL The polycarbonate film was immersed at a rate of /h～11mL/h and left for 3min～5min under a nitrogen flow with a blowing speed of 5cm ² /L, and the lecithin solution obtained in the step A2 was 9mL/h The rate of ~11mL/h was immersed through the polycarbonate film. During the immersion process of the lecithin solution, the N,N-dimethylformamide of the weight component was continuously added dropwise. After standing for 3 min to 5 min under a nitrogen flow with a blowing rate of ² /L, the product is dried in a vacuum for 10 min to 15 min to obtain the targeted slow-release biocompatible microcapsules.

Further, the various fruit and vegetable powders in the fruit and vegetable powder, in terms of mass fraction, include the following components: 10%-20% of kiwi fruit powder, 5%-15% of tomato powder, 10%-20% of blackberry powder, and 5%-20% of pumpkin powder. 15%, carrot powder 10%-15%, mushroom powder 5%-20%, and the balance is blueberry powder.

Further, the preparation method of described marine fish oligopeptide comprises the following steps:

1) In terms of components by weight, 500 parts to 600 parts of deep-sea salmon skins are minced, 1L to 1.5L of distilled water is added, homogenized by a homogenizer, and the homogenized mixture is processed at 85°C to 100°C 10min, then rapidly cooled to 60°C, using 1N HCl solution and 1N NaOH solution to adjust pH to 8.5;

2) adding 20 to 30 parts of papain to the mixture obtained in the step 1), enzymatic hydrolysis for 1 h to 2 h, and adjusting the pH to 8.5 by using 1N HCl solution and 1N NaOH solution;

3) Add 35 to 40 parts of pepsin to the mixture obtained in the step 2), enzymatically hydrolyze for 1 h to 2 h, inactivate the enzyme at 150 ° C to 170 ° C for 10 min to 15 min, and cool at room temperature;

4) Centrifuge the mixture obtained in the step 3) at 12000×g～15000×g for 10min～20min, take the supernatant, ultrafilter the supernatant with an ultrafiltration membrane, and filter the supernatant after the ultrafiltration The liquid is spray-dried by a spray dryer to obtain the dry powder of the marine fish oligopeptide.

Further, the molecular weight cut-off of the ultrafiltration membrane used in the step 4) is 1200u-1500u.

Further, the spray drying in the step 4) is carried out at a temperature of 5°C to 10°C.

The present invention also provides the preparation method of the above-mentioned sustained-release nutritional VC lutein peptide chewable tablet, which is characterized by comprising the following steps:

S1: combine the marine fish oligopeptide of the weight component, the casein phosphopeptide of the weight component, the soybean peptide of the weight component, the sea cucumber peptide of the weight component, and the The oyster peptide is dissolved in ethanol with a volume ratio of (1:2.5)～(3.5:5.5) and a NaCl solution with a concentration of 0.15M, and stirred for 30min～40min at a rotating speed of 80rpm～120rpm and a temperature of 15℃～20℃;

S2: Add the targeted slow-release biocompatible microcapsules of the weight component into the mixture obtained in the step S1, and stir at a speed of 100 rpm to 200 rpm and a temperature of 26 ° C to 28 ° C for 15 min to 30 min. During the stirring process The ethanol solution is continuously added dropwise to obtain a targeted slow-release biocompatible microcapsule-encapsulated peptide composition;

S3: vacuum freeze-drying the peptide composition encapsulated in the targeted sustained-release biocompatible microcapsules obtained in the step S2 at a vacuum degree of 0.03 MPa to 0.06 MPa and -4 °C to -2 °C to obtain a sustained-release peptide composition lyophilized powder;

S4: combining the colostrum powder of the weight component, the goat milk powder of the weight component, the whey protein concentrate of the weight component, the soybean protein powder of the weight component and the obtained milk powder obtained in the step S3 The freeze-dried powder of the sustained-release peptide composition is dissolved in glycerol and distilled water with a volume ratio of 2:3 to 4:5, and after stirring at a rotational speed of 200 rpm to 250 rpm for 10 to 15 minutes, the fruit and vegetable powder of the weight component is added and the stirring is continued for 10 minutes to 10 minutes. After 15min, after passing through 5-10 mesh sieves, wet granules are obtained;

S5: the wet particles in the step S4 are dry-mixed with the silica of the weight component to obtain the wet particles wrapped in silica;

S6: combine the lutein ester of the weight component, the vitamin C of the weight component, the citric acid of the weight component, the lactose of the weight component, the chitosan oligosaccharide of the weight component, the The fructooligosaccharide of the weight component, the xylo-oligosaccharide of the weight component, the erythritol of the weight component and the sorbitol of the weight component are dissolved in 100ml to 150ml of distilled water, and 1.5ml /min ~ 2.0ml/min spray rate, atomization pressure 1.5MPa ~ 2.0MPa uniform rotary spray on the silica-coated wet particles obtained in the step S5, after mixing uniformly, at 5cm ² /L ~ 10cm ² / Blow nitrogen at L rate for 10min;

S7: after the resistant dextrin of the weight component, the maltodextrin of the weight component, and the magnesium stearate of the weight component are evenly stirred with the particles obtained in the step S6, press into tablets to obtain 1 g of the sustained-release nutritional VC lutein peptide chewable tablet.

The beneficial effects of the present invention are:

1. It can enhance the peristalsis of the gastrointestinal tract and the fruity taste of the chewable tablet by providing the fruit and vegetable powder added in an even proportion of the fruit, improve the taste, and will not cause constipation due to the consumption of the chewable tablet, and various fruit and vegetable powders contain A variety of cellulose, vitamins and minerals can effectively supplement the lack of various trace elements or certain nutrients that the human body lacks due to disease.

2. During the production process of chewable tablets, small molecular peptides with peptide activity—ocean fish oligopeptides, casein phosphopeptides, sea cucumber peptides, oyster peptides and soybean peptides are directly combined with polymer peptides through targeted slow-release biocompatible microcapsules. (2-ethyl-2-oxazoline)-glucan-glucan-glucan skeleton binding, can also be encapsulated in the micelles of the dextran hydrophobic core, and then attached to the surface of the polycarbonate film, The α-lactalbumin/amino acid coating layer is attached to the outer layer, and the κ-carrageenan-lecithin bilayer membrane is attached to the outermost layer, which can effectively encapsulate the active small peptides through κ-carrageenan-lecithin. And it has hydrophilic and lipophilic properties. After entering the stomach, the κ-carrageenan-lecithin bilayer membrane is first digested by pepsin and other enzymes together with bovine colostrum powder, goat milk powder, whey protein concentrate and soybean protein powder. - The covalent bond between carrageenan-lecithin is unwound, leaving the negatively charged κ-carrageenan and α-lactalbumin/amino acid coated poly(2-ethyl-2-oxazole) Polycarbonate film of grafted glucan nanoparticles and preliminarily decomposed colostrum powder, goat milk powder, whey protein concentrate and soy protein powder enter the intestinal tract. 3-Linked-β-D-galactopyranose and 4-Linked-3,6-anhydro-α-D-galactopyranose units move from a strongly acidic environment in the stomach to a neutral pH environment in the gut Inside, make negatively charged κ-carrageenan and α-lactalbumin/amino acid-coated poly(2-ethyl-2-oxazoline)-grafted dextran nanoparticles around a polycarbonate film The pH is lower than its own pKa, which in turn reduces the ionic electrostatic repulsion between its network structures, resulting in its overall decomposition, releasing α-lactalbumin/amino acid-coated small peptides.

3. α-lactalbumin is composed of 123 amino acids, with a molecular weight of about 14kda, and contains a highly structured α-helical domain and β-sheet domain with 4 disulfide bonds, NH2-terminal glutamic acid and COOH-terminal leucine, which can ensure the activity and stability of the small active peptides attached to the poly(2-ethyl-2-oxazoline)-grafted glucan nanoparticles encapsulated inside; α-lactalbumin /A part of amino acids can be broken down in the intestinal tract as a whole and absorbed by the intestinal tract together with the stomach digests of bovine colostrum powder, goat milk powder, whey protein concentrate and soy protein powder;

Due to alpha-lactalbumin, the isoelectric point is approximately between pH 4.6-4.9, which makes it negatively charged above this pH range, and at neutral pH, amino acids lose hydrogen molecules, resulting in negatively charged side chains , another part of α-lactalbumin/amino acids can carry marine fish oligopeptides, casein phosphopeptides, sea cucumber peptides, oysters with poly(2-ethyl-2-oxazoline) grafted glucan nanoparticles Peptides and soybean peptides pass through the blood-brain barrier and enter the brain to nourish ophthalmic nerve cells and brain nerve cells, provide energy and lutein esters for the activities of eye nerve cells, and provide neurites for brain nerve cells in learning activities. , Transmitter transmission between axons provides nutrients at the molecular level, making neural activity active and ensuring brain neurotrophy during learning.

4. The targeted sustained-release biocompatible microcapsules provided in this application use 4-(dimethylamino)pyridine and N-(3-(dimethylamino)propyl)-N-ethylcarbodiimide hydrochloride The salt is used as a coupling agent to form electrostatic attraction between the carboxyl group on poly(2-ethyl-2-oxazoline) and the hydroxyl group on dextran, and the aminated and carboxylated poly(2-ethyl-2 -oxazoline) was grafted onto dextran with hydroxyl groups to form nanoparticles of poly(2-ethyl-2-oxazoline) grafted dextran shell structure, by adding 3,3'-disulfide After replacing propionic acid, the different core filling amounts of nanoparticles can be adjusted to ensure that different drug loadings are in them. Dextran is a hydrophilic substance, and the mixture of various active peptides can be directly combined with the backbone of dextran. , can also be encapsulated in micelles with a hydrophobic core of dextran.

5. The present invention has the chewable tablet of the present invention which is natural in material, diverse in ingredients, light in concentration, convenient in intake, and has macronutrients, macroelements, and trace elements, and takes health as the central idea, and satisfies various nutritional needs of teenagers, Supplemented by regulating substances with physiological functions and the regulating effect of "peptides" on cells, it breaks the shortcomings of existing products and provides a convenient, safe and reliable method that can quickly and timely deliver nutrients to all tissues and cells of the body. It can also regulate the physiological functions of cell growth, replication, reproduction and metabolism, and escort the growth and development of young people.

Description of drawings

Fig. 1 is the mouse open-box experiment walking route map of the normal control group in Effect Example 1 of the present invention;

Fig. 2 is the mouse open-box experiment walking route map of the stress group in Effect Example 1 of the present invention;

Fig. 3 is the experimental walking route diagram of the open box experiment of feeding the mice with the chewable tablet water dispersion of Example 1 in the effect example 1 of the present invention;

Fig. 4 is the experimental walking route diagram of the open box experiment of feeding mice of Example 2 chewable tablet water dispersion in Effect Example 1 of the present invention;

Fig. 5 is the walking route diagram of the open-box experiment of feeding mice of Example 3 chewable tablet aqueous dispersion in Effect Example 1 of the present invention;

Detailed ways

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

Example 1

A slow-release nutritional VC lutein peptide chewable tablet provided in this embodiment, each 1g of the chewable tablet includes the following components:

Colostrum powder 6mg, goat milk powder 100mg, whey protein concentrate 10mg, marine fish oligopeptide 8mg, casein phosphopeptide 5mg, soybean peptide 6mg, soybean protein powder 5mg, sea cucumber peptide 100mg, oyster peptide 13mg, fruit and vegetable powder 10mg, Lactose 4mg, Resistant Dextrin 1mg, Chitooligosaccharide 1mg, Fructooligosaccharide 10mg, Vitamin C 80mg, Lutein Esters 5mg, Xylo-oligosaccharide 1mg, Erythritol 0.5mg, Sorbitol 15mg, Citric Acid 0.05mg , silicon dioxide 0.05mg, maltodextrin 10mg, magnesium stearate 0.5mg; targeted slow-release biocompatible microcapsules 20mg.

Among them, the targeted sustained-release biocompatible microcapsules, in terms of weight components, include the following components: 15 parts of polycarbonate films with a pore size of 180 nm and a thickness of 30 mm; 12 parts of α-lactalbumin; 18 parts of amino acids; κ -8 parts of carrageenan; 12 parts of lecithin; 25 parts of poly(2-ethyl-2-oxazoline) grafted glucan nanoparticles; 0.05 part of N,N-dimethylformamide.

Wherein, the poly(2-ethyl-2-oxazoline)-grafted dextran nanoparticles, in terms of weight components, include the following components:

2.5 parts of poly(2-ethyl-2-oxazoline); 0.2 part of succinic anhydride; 0.5 part of 3,3'-dithiopropionic acid; N-(3-(dimethylamino)propyl)-N- 1 part of ethylcarbodiimide hydrochloride; 2 parts of 4-(dimethylamino)pyridine; 3 parts of dextran.

The preparation method of poly(2-ethyl-2-oxazoline)-grafted dextran nanoparticles, comprising the following steps:

M1: 2.5 parts of poly(2-ethyl-2-oxazoline) and 0.2 parts of succinic anhydride were dissolved in dichloromethane to form 7 mmol/L/concentration poly(2-ethyl-2-oxazole) Lin) organic solution and 25mmol/L concentration of succinic anhydride organic solution mixed solution, add 2 parts of 4-(dimethylamino)pyridine to the mixed solution, stir and react at 75rpm and 25℃ for 12h;

M2: The mixture obtained in step M1 and diethyl ether were mixed and reacted at a weight-to-volume ratio of 1:8 for 10 min, and then precipitated in diethyl ether to obtain a terminal aminated and carboxylated poly(2-ethyl-2-oxazoline) crude product , the terminal aminated and carboxylated poly(2-ethyl-2-oxazoline) crude product was dried under vacuum for 18 h to obtain the terminally aminated and carboxylated poly(2-ethyl-2-oxazole) phenoline) crude product powder;

M3: Dissolve 3 parts of dextran in dimethyl sulfoxide, dissolve it in a microwave at 10mHz for 3h, then add the poly(2-ethyl-2-oxazoline) crude product powder obtained in step M2, 0.5 part of N-(3-(dimethylamino)propyl)-N-ethylcarbodiimide hydrochloride, after stirring at 28°C for 60min, 0.5 part of 3,3'-dithiopropionic acid, 0.5 part of N-(3-(dimethylamino)propyl)-N-ethylcarbodiimide hydrochloride was stirred at 28°C for 60min, and the resulting mixture was placed on a dialysis membrane with a molecular pore size of 3200Da. Dialyzed for 1 h, freeze-dried at -100 °C to obtain poly(2-ethyl-2-oxazoline)-grafted dextran nanoparticles.

The preparation method of targeted sustained-release biocompatible microcapsules comprises the following steps:

A1: Dissolve 18 parts of amino acids and 12 parts of α-lactalbumin in distilled water, fully stir and hydrate at 80 rpm for 30 minutes, filter the obtained mixed solution under a 0.40 μm polyvinylidene fluoride filter, and take the filtered supernatant to obtain amino acid-α-lactalbumin mixed supernatant;

A2: Dissolve 8 parts of κ-carrageenan and 12 parts of lecithin in distilled water to form a κ-carrageenan solution with a concentration of 3 mmol/L and a lecithin solution with a concentration of 10 mmol//L;

A3: Dissolve 15 parts of polycarbonate film in phosphate buffer containing 0.13M sodium chloride, and graft 25 parts of poly(2-ethyl-2-oxazoline) with dextran nanoparticles The particles were impregnated through the polycarbonate film at a rate of 9 mL/h, and then the amino acid-α-lactalbumin mixed supernatant obtained in step A1 was impregnated and penetrated through the polycarbonate film at a rate of ⁹ mL/h. The κ-carrageenan solution obtained in step A2 was immersed and penetrated through the polycarbonate film at a rate of 9 mL/h, and was allowed to stand for 3 min under a nitrogen stream with a blowing speed of 5 cm ² /L. , immerse the lecithin solution obtained in step A2 through the polycarbonate film at a rate of 9 mL/h, and continuously add 0.05 part of N,N-dimethylformamide dropwise during the immersion process of the lecithin solution. After standing for 3 min under a nitrogen flow with a blowing speed of 5 cm ² /L, the product was dried in vacuum for 10 min to obtain targeted slow-release biocompatible microcapsules.

The various fruit and vegetable powders in the fruit and vegetable powder are calculated by mass fraction, including the following ingredients: 10% of kiwi fruit powder, 15% of tomato powder, 10% of blackberry powder, 15% of pumpkin powder, 10% of carrot powder, 20% of mushroom powder, and the balance is blueberry pink.

The preparation method of marine fish oligopeptide in chewable tablet comprises the following steps:

1) In terms of components by weight, 500 parts of deep-sea salmon skins were minced, added with 1 L of distilled water, homogenized by a homogenizer, and the homogenized mixture was treated at 85 ° C for 10 min, and then rapidly cooled to 60 ° C, using a concentration of Adjust pH to 8.5 for 1N HCl solution and 1N NaOH solution;

2) Add 20 parts of papain to the mixture obtained in step 1), enzymolysis for 1 h, and adjust the pH to 8.5 by using 1N HCl solution and 1N NaOH solution;

3) Add 35 parts of pepsin to the mixture obtained in step 2), hydrolyze for 1 hour, inactivate the enzyme at 150° C. for 10 minutes, and cool at room temperature;

4) The mixture obtained in step 3) was centrifuged at 12000 × g for 20 min, the supernatant was taken, the supernatant was ultrafiltered with an ultrafiltration membrane with a molecular weight cut-off of 1200u, and the filtrate after the ultrafiltration was subjected to a spray dryer Spray drying at 5°C to obtain dry powder of marine fish oligopeptide.

The present embodiment also provides a preparation method of the above-mentioned sustained-release nutritional VC lutein peptide chewable tablet, comprising the following steps:

S1: Dissolve 8 mg of marine fish oligopeptide, 5 mg of casein phosphopeptide, 6 mg of soybean peptide, 100 mg of sea cucumber peptide and 13 mg of oyster peptide in ethanol with a volume ratio of 1:2.5 and NaCl solution with a concentration of 0.15M , stirring at 80 rpm for 30 min at a temperature of 20 °C;

S2: Add 20 mg of targeted slow-release biocompatible microcapsules to the mixture obtained in step S1, stir at 100 rpm and 28°C for 30 min, and continuously add ethanol solution dropwise during the stirring process to obtain a targeted slow-release biophase Microencapsulated peptide compositions;

S3: vacuum freeze-drying the peptide composition encapsulated in the targeted sustained-release biocompatible microcapsules obtained in step S2 at a vacuum degree of 0.03 MPa and -2 °C to obtain a freeze-dried powder of the sustained-release peptide composition;

S4: Dissolve 6 mg of bovine colostrum powder, 100 mg of goat milk powder, 10 mg of whey protein concentrate, 5 mg of soybean protein powder and the slow-release peptide composition freeze-dried powder obtained in step S3 in glycerol with a volume ratio of 2:3 After stirring with distilled water at 200rpm for 15min, adding the fruit and vegetable powder of the weight component and continuing to stir for 10min, after passing through a 5-mesh sieve, wet granules were obtained;

S5: dry-mix the wet granules in step S4 with 0.05 mg of silica to obtain silica-coated wet granules;

S6: 5 mg of lutein ester, 80 mg of vitamin C, 0.05 mg of citric acid, 4 mg of lactose, 1 mg of chitooligosaccharide, 10 mg of fructooligosaccharide, 10 mg of xylo-oligosaccharide, 0.5 mg of erythrose Alcohol and 15 mg of sorbitol were dissolved in 100 ml of distilled water, sprayed uniformly on the silica ^- coated wet particles obtained in step S5 at a spray rate of 1.5 ml/min and an atomization pressure of 1.5 MPa. Blow nitrogen at L rate for 10min;

S7: Mix 1 mg of resistant dextrin, 10 mg of maltodextrin and 0.5 mg of magnesium stearate with the granules obtained in step S6, and press into tablets to obtain 1 g of slow-release nutritional VC lutein peptide chewable tablets.

Example 2

A slow-release nutritional VC lutein peptide chewable tablet provided in this embodiment, each 1g of the chewable tablet includes the following components:

Colostrum powder 50mg, goat milk powder 10mg, whey protein concentrate 150mg, marine fish oligopeptide 1mg, casein phosphopeptide 70mg, soybean peptide 0.5mg, soybean protein powder 0.5mg, sea cucumber peptide 13mg, oyster peptide 100mg, fruit and vegetable powder 100mg, lactose 1mg, resistant dextrin 5mg, chitosan oligosaccharide 10mg, fructooligosaccharide 1mg, vitamin C 5mg, lutein ester 100mg, xylo-oligosaccharide 0.6mg, erythritol 10mg, sorbitol 0.5mg, Citric acid 1mg, silicon dioxide 1mg, maltodextrin 0.08mg, magnesium stearate 1mg; targeted slow-release biocompatible microcapsules 30mg;

Targeted sustained-release biocompatible microcapsules, in terms of components by weight, include the following components: 20 parts of polycarbonate films with a pore size of 250 nm and a thickness of 15 mm; 18 parts of α-lactalbumin; 12 parts of amino acids; κ- 12 parts of carrageenan; 8 parts of lecithin; 35 parts of poly(2-ethyl-2-oxazoline) grafted glucan nanoparticles; 0.1 part of N,N-dimethylformamide.

Poly(2-ethyl-2-oxazoline)-grafted dextran nanoparticles, by weight component, include the following components:

5 parts of poly(2-ethyl-2-oxazoline); 0.5 part of succinic anhydride; 1 part of 3,3'-dithiopropionic acid; N-(3-(dimethylamino)propyl)-N- 1.5 parts of ethylcarbodiimide hydrochloride; 2.5 parts of 4-(dimethylamino)pyridine; 6 parts of dextran;

The preparation method of poly(2-ethyl-2-oxazoline)-grafted dextran nanoparticles, comprising the following steps:

M1: 5 parts of poly(2-ethyl-2-oxazoline) and 0.5 parts of succinic anhydride were dissolved in dichloromethane to form 15 mmol/concentration poly(2-ethyl-2-oxazoline) The mixed solution of the organic solution and the organic solution of succinic anhydride with a concentration of 45 mmol/L was added with 4-(dimethylamino)pyridine of the weight component to the mixed solution, and the reaction was stirred at 150 rpm and 28 ° C for 24 h;

M2: The mixture obtained in step M1 and diethyl ether were mixed and reacted at a weight-to-volume ratio of 1:8 for 15 min, and then precipitated in diethyl ether to obtain a terminal aminated and carboxylated poly(2-ethyl-2-oxazoline) crude product , the terminal aminated and carboxylated poly(2-ethyl-2-oxazoline) crude product was dried under vacuum for 36 h to obtain the terminally aminated and carboxylated poly(2-ethyl-2-oxazole) phenoline) crude product powder;

M3: Dissolve 6 parts of dextran in dimethyl sulfoxide, dissolve in a microwave at 20mHz for 4h, then add the crude poly(2-ethyl-2-oxazoline) powder obtained in step M2, 0.75 part 1 part of 3,3'-dithiopropionic acid, 0.75 part of N-(3-(dimethylamino)propyl)-N-ethylcarbodiimide hydrochloride was stirred at 32°C for 30min, and the resulting mixture was placed on a dialysis membrane with a molecular pore size of 3800Da. Dialyzed for 2 h, freeze-dried at -100 °C to obtain poly(2-ethyl-2-oxazoline)-grafted dextran nanoparticles.

The preparation method of targeted sustained-release biocompatible microcapsules comprises the following steps:

A1: Dissolve 12 parts of amino acids and α-lactalbumin by weight in distilled water, fully stir and hydrate at 100 rpm for 20 min, filter the obtained mixed solution under a 0.30 μm polyvinylidene fluoride filter, take the filtered The supernatant was obtained to obtain amino acid-α-lactalbumin mixed supernatant;

A2: Dissolve 12 parts of kappa-carrageenan and 8 parts of lecithin in distilled water to form a solution of kappa-carrageenan with a concentration of 7 mmol/L and a lecithin solution of 3 mmol//L;

A3: Dissolve 20 parts of polycarbonate film in phosphate buffer containing 0.15M sodium chloride, and graft 35 parts of poly(2-ethyl-2-oxazoline) with dextran nanoparticles The particles were impregnated through the polycarbonate film at a rate of 11 mL/h, and then the amino acid-α-lactalbumin mixed supernatant obtained in step A1 was impregnated through the polycarbonate film at a rate of 11 mL/h, at 5 cm ² / The κ-carrageenan solution obtained in step A2 was immersed and permeated through the polycarbonate film at a rate of 11 mL/h, and was allowed to stand for 5 min under a nitrogen stream with a blowing speed of 5 cm ² /L. , the lecithin solution obtained in step A2 was dipped through the polycarbonate film at a rate of 11 mL/h, and 0.1 part of N,N-dimethylformamide was continuously added dropwise during the dipping process of the lecithin solution. After standing for 5 min under a nitrogen flow with a blowing speed of 5 cm ² /L, the product was dried in vacuum for 15 min to obtain targeted slow-release biocompatible microcapsules.

The various fruit and vegetable powders in the fruit and vegetable powder in the chewable tablet are calculated by mass fraction, including the following ingredients: 20% of kiwi fruit powder, 5% of tomato powder, 20% of blackberry powder, 5% of pumpkin powder, 15% of carrot powder, 5% of mushroom powder, and the rest The amount is blueberry powder.

The preparation method of marine fish oligopeptide in chewable tablet comprises the following steps:

1) In terms of weight components, 600 parts of deep-sea salmon skins were minced, added with 1.5 L of distilled water, homogenized by a homogenizer, and the homogenized mixture was treated at 100° C. for 10 minutes, then rapidly cooled to 60° C., using Adjust pH to 8.5 with 1N HCl solution and 1N NaOH solution;

2) To the mixture obtained in step 1), add 30 parts of papain, enzymolysis for 2h, and adjust the pH to 8.5 with 1N HCl solution and 1N NaOH solution;

3) Add 40 parts of pepsin to the mixture obtained in step 2), enzymatically hydrolyze for 2 hours, inactivate the enzyme at 170° C. for 15 minutes, and cool at room temperature;

4) The mixture obtained in step 3) was centrifuged at 12000 × g for 10 min, and the supernatant was taken, and the supernatant was ultrafiltered with an ultrafiltration membrane having a molecular weight cut-off of 1500 u, and the filtrate after the ultrafiltration was sprayed by a spray dryer. Spray drying at a temperature of 10° C. to obtain dry powder of marine fish oligopeptide.

The present embodiment also provides a preparation method of the above-mentioned sustained-release nutritional VC lutein peptide chewable tablet, comprising the following steps:

S1: Dissolve 1mg of marine fish oligopeptide, 70mg of casein phosphopeptide, 0.5mg of soybean peptide, 13mg of sea cucumber peptide and 100mg of oyster peptide in ethanol with a volume ratio of 3.5:5.5 and NaCl with a concentration of 0.15M In the solution, stir at 120rpm and 15℃ for 40min;

S2: Add 30 mg of targeted slow-release biocompatible microcapsules to the mixture obtained in step S1, stir at 100 rpm for 15 minutes at a temperature of 26 °C, and continuously add ethanol solution dropwise during the stirring process to obtain a targeted slow-release biophase Microencapsulated peptide compositions;

S3: vacuum freeze-drying the peptide composition encapsulated in the targeted sustained-release biocompatible microcapsules obtained in step S2 at a vacuum degree of 0.06 MPa and -4 °C to obtain a freeze-dried powder of the sustained-release peptide composition;

S4: Dissolve 50 mg of bovine colostrum powder, 10 mg of goat milk powder, 150 mg of whey protein concentrate, 0.5 mg of soybean protein powder and the slow-release peptide composition freeze-dried powder obtained in step S3 in a volume ratio of 4:5 Glycerol and distilled water were stirred at 200 rpm for 10 minutes, then the fruit and vegetable powder of the weight component was added and stirred for 15 minutes, and after passing through a 10-mesh sieve, wet granules were obtained;

S5: dry-mix the wet granules in step S4 with 1 mg of silica to obtain silica-coated wet granules;

S6: 100 mg of lutein ester, 5 mg of vitamin C, 1 mg of citric acid, 1 mg of lactose, 10 mg of chitooligosaccharide, 1 mg of fructooligosaccharide, 0.6 mg of xylo-oligosaccharide, 10 mg of erythritol and 0.5 mg of sorbitol was dissolved in 150 ml of distilled water, and the wet granules coated with silica obtained in step S5 were uniformly rotated and sprayed at a spray rate of ^2.0 ml/min and an atomization pressure of 2.0 MPa. Blow nitrogen at L rate for 10min;

S7: Mix 5 mg of resistant dextrin, 0.08 mg of maltodextrin and 1 mg of magnesium stearate with the granules obtained in step S6, and press into tablets to obtain 1 g of slow-release nutritional VC lutein peptide chewable tablets.

Example 3

A slow-release nutritional VC lutein peptide chewable tablet provided in this embodiment, each 1g of the chewable tablet includes the following components:

Colostrum powder 28mg, goat milk powder 55mg, whey protein concentrate 80mg, marine fish oligopeptide 4.5mg, casein phosphopeptide 37.5mg, soybean peptide 3.25mg, soybean protein powder 5.25mg, sea cucumber peptide 56.5mg, oyster peptide 56.5 mg, fruit and vegetable powder 55mg, lactose 2.5mg, resistant dextrin 3mg, chitooligosaccharide 5.5mg, fructooligosaccharide 5.5mg, vitamin C 42.5mg, lutein ester 52.5mg, xylo-oligosaccharide 0.8mg, erythrose Alcohol 5.25mg, sorbitol 7.5mg, citric acid 0.5mg, silicon dioxide 0.5mg, maltodextrin 5mg, magnesium stearate 0.75mg; targeted slow-release biocompatible microcapsules 25mg;

Targeted sustained-release biocompatible microcapsules, in terms of components by weight, include the following components: 18 parts of polycarbonate films with a pore size of 200 nm and a thickness of 23 mm; 15 parts of α-lactalbumin; 15 parts of amino acids; κ- 10 parts of carrageenan; 10 parts of lecithin; 20 parts of poly(2-ethyl-2-oxazoline) grafted glucan nanoparticles; 0.5 part of N,N-dimethylformamide.

Poly(2-ethyl-2-oxazoline)-grafted dextran nanoparticles, by weight component, include the following components:

3.75 parts of poly(2-ethyl-2-oxazoline); 0.35 parts of succinic anhydride; 0.75 parts of 3,3'-dithiopropionic acid; N-(3-(dimethylamino)propyl)-N- 1.25 parts of ethylcarbodiimide hydrochloride; 2.25 parts of 4-(dimethylamino)pyridine; 4.5 parts of dextran;

The preparation method of poly(2-ethyl-2-oxazoline)-grafted dextran nanoparticles, comprising the following steps:

M1: 3.75 parts of poly(2-ethyl-2-oxazoline) and 0.35 parts of succinic anhydride were dissolved in dichloromethane to form 11 mmol/concentration poly(2-ethyl-2-oxazoline) organic The mixed solution of the solution and the organic solution of succinic anhydride with a concentration of 35 mmol/L was added to the mixed solution by adding 2.25% of 4-(dimethylamino)pyridine, and the reaction was stirred at 100 rpm and 27 °C for 18 h;

M2: The mixture obtained in step M1 and diethyl ether were mixed and reacted for 12 minutes at a weight-to-volume ratio of 1:8, and then precipitated in diethyl ether to obtain a terminal aminated and carboxylated poly(2-ethyl-2-oxazoline) crude product , the terminal aminated and carboxylated poly(2-ethyl-2-oxazoline) crude product was dried under vacuum for 24h to obtain the terminally aminated and carboxylated poly(2-ethyl-2-oxazole) phenoline) crude product powder;

M3: Dissolve 4.5 parts of dextran in dimethyl sulfoxide, dissolve it in a microwave at 15mHz for 3.5h, then add the poly(2-ethyl-2-oxazoline) crude product powder obtained in step M2, 0.625 parts of N-(3-(dimethylamino)propyl)-N-ethylcarbodiimide hydrochloride, after stirring at 30°C for 45 min, 0.75 parts of 3,3'-dithiopropionic acid was added , 0.625 parts of N-(3-(dimethylamino)propyl)-N-ethylcarbodiimide hydrochloride, after stirring at 30°C for 45min, the resulting mixture was dialyzed with a molecular pore size of 3600Da Dialyzed under the membrane for 1.5 h, and freeze-dried at -100 °C to obtain poly(2-ethyl-2-oxazoline)-grafted dextran nanoparticles.

The preparation method of targeted sustained-release biocompatible microcapsules comprises the following steps:

A1: Dissolve 15 parts of amino acids and 15 parts of α-lactalbumin in distilled water, fully stir and hydrate at 90 rpm for 25 minutes, filter the obtained mixed solution under a 0.35 μm polyvinylidene fluoride filter, and take the filtered supernatant to obtain amino acid-α-lactalbumin mixed supernatant;

A2: Dissolve 10 parts of κ-carrageenan and 10 parts of lecithin in distilled water to form a 5 mmol/L κ-carrageenan solution and a 6.5 mmol//L lecithin solution;

A3: The polycarbonate film of 18 was dissolved in a phosphate buffer containing 0.14M sodium chloride, and 20 parts of poly(2-ethyl-2-oxazoline) were grafted to dextran nanoparticles Dip through the polycarbonate film at a rate of 10mL/h, and then immerse the amino acid-α-lactalbumin mixed supernatant obtained in step A1 through the polycarbonate film at a rate of 10mL/h, at 5cm ² /L Let stand for 3min ~ 5min under a nitrogen stream with a blowing speed; immerse the κ-carrageenan solution obtained in step A2 through the polycarbonate film at a rate of 10mL/h, and stand for 4min under a nitrogen stream with a blowing speed of 5cm ² /L Then, the lecithin solution obtained in step A2 was impregnated through the polycarbonate film at a rate of 10 mL/h, and 0.5 part of N,N-dimethylformamide was continuously added dropwise during the impregnation of the lecithin solution, and the impregnation was completed. After standing for 45 minutes under a nitrogen flow with a blowing speed of 5 cm ² /L, the product was dried in vacuum for 13 minutes to obtain targeted slow-release biocompatible microcapsules.

The various fruit and vegetable powders in the fruit and vegetable powder in the chewable tablet are calculated by mass fraction, including the following ingredients: 15% of kiwi fruit powder, 10% of tomato powder, 15% of blackberry powder, 10% of pumpkin powder, 12.5% of carrot powder, 12.5% of mushroom powder, and the rest The amount is blueberry powder.

The preparation method of marine fish oligopeptide in chewable tablet comprises the following steps:

1) In terms of components by weight, 550 parts of deep-sea salmon skins were minced, 1.25 L of distilled water was added, homogenized by a homogenizer, the homogenized mixture was treated at 92 ° C for 10 min, and then rapidly cooled to 60 ° C, using Adjust pH to 8.5 with 1N HCl solution and 1N NaOH solution;

2) To the mixture obtained in step 1), add 25 parts of papain, enzymolysis for 1.5h, and adjust the pH to 8.5 by using 1N HCl solution and 1N NaOH solution;

3) Add 38 parts of pepsin to the mixture obtained in step 2), enzymatically hydrolyze for 1 h to 2 h, inactivate the enzyme at 160° C. for 12 min, and cool at room temperature;

4) The mixture obtained in step 3) was centrifuged at 13500 × g for 15 min, and the supernatant was taken, and the supernatant was ultrafiltered with an ultrafiltration membrane with a molecular weight cut-off of 1350u. Spray drying at 8°C to obtain dry powder of marine fish oligopeptide.

The present embodiment also provides a preparation method for the sustained-release nutritional VC lutein peptide chewable tablet, comprising the following steps:

S1: Dissolve 4.5mg of marine fish oligopeptide, 37.5mg of casein phosphopeptide, 3.25mg of soybean peptide, 56.5mg of sea cucumber peptide and 56.5mg of oyster peptide in ethanol with a volume ratio of 2:3 and a concentration of In 0.15M NaCl solution, stirring at 100rpm and 18°C for 35min;

S2: Add 25 mg of targeted slow-release biocompatible microcapsules to the mixture obtained in step S1, and stir at 150 rpm and 27°C for 18 minutes. During the stirring process, ethanol solution is continuously added dropwise to obtain targeted slow-release biocompatible Microencapsulated peptide compositions;

S3: vacuum freeze-drying the peptide composition encapsulated in the targeted sustained-release biocompatible microcapsules obtained in step S2 at a vacuum degree of 0.045 MPa and -3 °C to obtain a freeze-dried powder of the sustained-release peptide composition;

S4: Dissolve 28 mg of colostrum powder, 55 mg of goat milk powder, 80 mg of whey protein concentrate, 5.25 mg of soybean protein powder and the slow-release peptide composition freeze-dried powder obtained in step S3 in a volume ratio of 3:4 Glycerol and distilled water were stirred at 225 rpm for 12 minutes, then the fruit and vegetable powder of the weight component was added to continue stirring for 13 minutes, and after passing through an 8-mesh sieve, wet granules were obtained;

S5: dry-mix the wet granules in step S4 with 0.5 mg of silica to obtain silica-coated wet granules;

S6: 52.5mg lutein ester, 42.5mg vitamin C, 0.5mg citric acid, 2.5mg lactose, 5.5mg chitooligosaccharide, 5.5mg fructooligosaccharide, 0.8mg xylo-oligosaccharide, 5.25mg 1 mg of erythritol and 7.5 mg of sorbitol were dissolved in 125 ml of distilled water, sprayed uniformly on the silica-coated wet particles obtained in step S5 at a spray rate of 1.8 ml/min and an atomization pressure of 1.8 MPa, and mixed well After that, nitrogen was blown at a rate of 8 cm ² /L for 10 min;

S7: Mix 3 mg of resistant dextrin, 5 mg of maltodextrin and 0.75 mg of magnesium stearate with the granules obtained in step S6, and press into tablets to obtain 1 g of slow-release nutritional VC lutein peptide chewable tablets.

Effect example 1

SD rats were used for open-box experiment, 30 SD rats were selected, male, 5-6 weeks old, male, body weight 160-180g (body weight difference was less than 20%); purchased from Shanghai Slack Laboratory Animal Technology Co., Ltd. Production license number: SCXK (Shanghai), 2007-0005], SPF grade. The animals were reared for 7 days before the experiment, so that the animals were adapted to the rearing environment.

Stress method in this experiment: stress stimulation was performed twice a day at random times without a fixed sequence: tail clipping for 3 minutes; tail suspension for 15 minutes; cage tilting for 24 hours, and ultrasonic stimulation for 10 minutes. Animal body weights were recorded weekly and cage-side observations were made. This model simulates the unsteady stimuli caused by the surrounding environment, resulting in the phenomenon of unresponsive behavior and slow response. The above stimuli make the rats in a state of mental stress every day, similar to that of humans when bad things happen for a long time, they will fall into stress The state, if it goes on for a long time, can easily lead to emotional depression and unresponsiveness.

Open box test: 100ml of chewable tablet water dispersion in Example 1-3 was taken continuously for 3 weeks, and 1 hr after the last dose of all animals, the animals were put into the open box device, and the animal movement track within 30min was detected. After the detection is completed, read the data, and obtain the data of the total movement distance, movement speed, and movement distance in the central area within 30 minutes, as shown in Table 1 and Figure 1-5.

The open box and video shooting software were purchased from Shanghai Jiliang Software Co., Ltd. All black backgrounds around and at the bottom are used to capture the movement trajectory of white objects (rat) in the video area for detection. When it started to be put into the open box, put it all in the corner, and the experimenter left immediately. After 30 minutes, the equipment completely recorded the movement trajectory and then removed the animal, cleaned the open box, sprayed alcohol to cover up the smell, cleaned the inside and bottom of the open box again, and waited for the alcohol. After complete volatilization, the next batch of rats was replaced to continue the test.

Table 1 OFT results of stressed rats taking chewable tablet water dispersion

From Figures 1 to 5 of the results of this OFT, it can be seen that the movement trajectories of animals in each group within 30 minutes in the open box are significantly different. The range and distance of activities of animals in the stress group are significantly lower than those in other groups. , the distance into the central area also has obvious differences between groups. The walking distance in the central area of the animals in the blank control group is significantly higher than that in the other groups, indicating that the long-term stress rats' awareness of exploring unknown spaces has decreased significantly. The chewable tablets provided in this application can Significantly improves the supply of nutrients to the cranial and ophthalmic nerves, and releases active peptides that are beneficial for vision protection to nourish the ophthalmic nerves, improve immunity, provide nutrition for brain cells, and enhance intelligence.

While the present invention has been described with reference to the preferred embodiments, various modifications may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. The foregoing description of the embodiments is provided to facilitate understanding and use of the present invention by those of ordinary skill in the art. It will be apparent to those skilled in the art that various modifications to these embodiments can be readily made, and the generic principles described herein can be applied to other embodiments without inventive step. Therefore, the present invention is not limited to the above-mentioned embodiments, and improvements and modifications made by those skilled in the art according to the disclosure of the present invention without departing from the scope of the present invention should all fall within the protection scope of the present invention. The present invention is not limited to the specific embodiments disclosed herein, but includes all technical solutions falling within the scope of the claims.

Claims (8)

1. A sustained-release nutritional VC lutein peptide chewable tablet is characterized in that each 1g of the chewable tablet comprises the following components:

6-50 mg of bovine colostrum powder, 10-100 mg of goat milk powder, 10-150 mg of concentrated whey protein, 1-8 mg of marine fish oligopeptide, 5-70 mg of casein phosphopeptide, 0.5-6 mg of soybean peptide, 0.5-5 mg of soybean protein powder, 13-100 mg of sea cucumber peptide, 13-100 mg of oyster peptide, 10-100 mg of fruit and vegetable powder, 1-4 mg of lactose, 1-5 mg of resistant dextrin, 1-10 mg of chitosan oligosaccharide, 1-10 mg of fructo-oligosaccharide, 5-80 mg of vitamin C, 5-100 mg of lutein ester, 0.6-1 mg of xylose oligosaccharide, 0.5-10 mg of erythritol, 0.5-15 mg of sorbitol, 0.05-1 mg of citric acid, 0.05-1 mg of silicon dioxide, 0.08-10 mg of maltodextrin and 0.5-1 mg of magnesium stearate; each 1g of chewable tablet also comprises 20 mg-30 mg of targeted sustained-release biocompatible microcapsule, and the targeted sustained-release biocompatible microcapsule comprises the following components in parts by weight: 15 to 20 parts of polycarbonate film with the aperture of 180 to 250nm and the thickness of 15 to 30 mm; 12-18 parts of alpha-lactalbumin; 12-18 parts of amino acid; 8-12 parts of kappa-carrageenan; 8-12 parts of lecithin; 25-35 parts of poly (2-ethyl-2-oxazoline) grafted glucan nanoparticles; 0.05 to 0.1 portion of N, N-dimethylformamide; the marine fish oligopeptide, the casein phosphopeptide, the sea cucumber peptide, the oyster peptide and the soybean peptide are directly combined with a glucan skeleton of poly (2-ethyl-2-oxazoline) grafted glucan through a targeted slow release biocompatible microcapsule, or are wrapped in micelles of a glucan hydrophobic core, and then are attached to the surface of a polycarbonate film, an alpha-lactalbumin/amino acid wrapping layer is attached to the outer layer, and a kappa-carrageenan-lecithin double-layer film is attached to the outermost layer.

2. The VC xanthophyll peptide chewable tablet of sustained release nutritional type according to claim 1, wherein the poly (2-ethyl-2-oxazoline) grafted glucan nanoparticles comprise the following components by weight:

2.5-5 parts of poly (2-ethyl-2-oxazoline); 0.2 to 0.5 portion of succinic anhydride; 0.5 to 1 portion of 3,3' -dithiopropionic acid; 1-1.5 parts of N- (3- (dimethylamino) propyl) -N-ethyl carbodiimide hydrochloride; 2-2.5 parts of 4- (dimethylamino) pyridine; 3-6 parts of glucan;

the preparation method of the poly (2-ethyl-2-oxazoline) grafted glucan nanoparticle comprises the following steps:

m1: dissolving the weight component of poly (2-ethyl-2-oxazoline) and the weight component of succinic anhydride in dichloromethane to form a mixed solution of a poly (2-ethyl-2-oxazoline) organic solution with the concentration of 7mmol/L to 15 mmol/L and a succinic anhydride organic solution with the concentration of 25mmol/L to 45mmol/L, adding the weight component of 4- (dimethylamino) pyridine into the mixed solution, and stirring and reacting for 12h to 24h at the rotating speed of 75rpm to 150rpm and the temperature of 25 ℃ to 28 ℃;

m2: mixing the mixture obtained in the M1 step with diethyl ether at a weight-to-volume ratio of 1:8 for reaction for 10-15 min, precipitating in the diethyl ether to obtain a crude poly (2-ethyl-2-oxazoline) product with terminal amination and carboxylation, and drying the crude poly (2-ethyl-2-oxazoline) product with terminal amination and carboxylation under vacuum condition for 18-36 h to obtain crude poly (2-ethyl-2-oxazoline) product powder with terminal amination and carboxylation;

m3: dissolving the dextran of the weight component in dimethyl sulfoxide, dissolving the dextran in the dimethyl sulfoxide by microwave for 3 to 4 hours under the condition of 10 to 20mHz, then adding the crude product powder of the poly (2-ethyl-2-oxazoline) obtained in the M2 step and half of the N- (3- (dimethylamino) propyl) -N-ethylcarbodiimide hydrochloride of the weight component, stirring the mixture for 30 to 60 minutes at the temperature of between 28 and 32 ℃, adding the 3,3' -dithiopropionic acid of the weight component and the remaining half of the N- (3- (dimethylamino) propyl) -N-ethylcarbodiimide hydrochloride of the weight component, stirring the mixture for 30 to 60 minutes at the temperature of between 28 and 32 ℃, dialyzing the obtained mixture for 1 to 2 hours under a dialysis membrane with the molecular pore size of between 3200 to 3800Da, and (3) freeze-drying at-100 ℃ to obtain the poly (2-ethyl-2-oxazoline) grafted glucan nano-particles.

3. The VC lutein peptide chewable tablet of sustained release nutrition type according to claim 1, wherein the preparation method of the targeted sustained release biocompatible microcapsule comprises the following steps:

a1: dissolving the amino acid and the alpha-lactalbumin in the weight components in distilled water, fully stirring and hydrating for 20min to 30min at 80rpm to 100rpm, filtering the obtained mixed solution under a polyvinylidene fluoride filter with the particle size of 0.30 mu m to 0.40 mu m, and taking the filtered supernatant to obtain the mixed supernatant of the amino acid and the alpha-lactalbumin;

a2: dissolving the weight component of the kappa-carrageenan and the weight component of lecithin in distilled water to form a kappa-carrageenan solution with the concentration of 3 mmol/L-7 mmol/L and a lecithin solution with the concentration of 3 mmol/L-10 mmol/L;

a3: dissolving the polycarbonate film with the weight component in a phosphate buffer solution with sodium chloride concentration of 0.13-0.15M, impregnating the poly (2-ethyl-2-oxazoline) grafted glucan nano-particles with the weight component through the polycarbonate film at the rate of 9-11 mL/h, and then impregnating the amino acid-alpha-lactalbumin mixed supernatant obtained in the step A1 through the polycarbonate film at the rate of 9-11 mL/h, and impregnating the mixed supernatant at the rate of 5cm ² Standing for 3-5 min under the nitrogen flow with the blowing speed of/L; impregnating the kappa-carrageenan solution obtained in the step A2 at the speed of 9-11 mL/h through the polycarbonate film at the thickness of 5cm ² Standing for 3-5 min under nitrogen gas flow at blow rate of/L, impregnating the lecithin solution obtained in the step A2 at the rate of 9-11 mL/h through the polycarbonate film, continuously dripping N, N-dimethylformamide with the weight component in the impregnation process of the lecithin solution, and after the impregnation is finished, keeping the concentration of N, N-dimethylformamide at 5cm ² Standing for 3-5 min under the nitrogen flow with the blowing speed of L, and drying the product in vacuum for 10-15 min to obtain the targeted sustained-release biocompatible microcapsule.

4. The VC lutein peptide chewable tablet of sustained release nutrition type according to claim 1, characterized in that various fruit and vegetable powders in the fruit and vegetable powder comprise the following components by mass: 10-20% of kiwi fruit powder, 5-15% of tomato powder, 10-20% of blackberry powder, 5-15% of pumpkin powder, 10-15% of carrot powder, 5-20% of mushroom powder and the balance blueberry powder.

5. The VC xanthophyll peptide chewable tablet of sustained release nutritional type according to claim 1, characterized in that the preparation method of the marine fish oligopeptide comprises the following steps:

1) according to the weight components, 500-600 parts of deep sea salmon skin is ground, 1-1.5L of distilled water is added, a homogenizer is adopted for homogenization, the homogenized mixture is treated at 85-100 ℃ for 10min, then the temperature is rapidly reduced to 60 ℃, and the pH value is adjusted to 8.5 by adopting 1N HCl solution and 1N NaOH solution;

2) adding 20-30 parts of papain to the mixture obtained in the step 1), carrying out enzymolysis for 1-2 h, and adjusting the pH to 8.5 by adopting a HCl solution with the concentration of 1N and a NaOH solution with the concentration of 1N;

3) adding 35 to 40 parts of pepsin into the mixture obtained in the step 2), carrying out enzymolysis for 1 to 2 hours, inactivating the enzyme at the temperature of between 150 and 170 ℃ for 10 to 15 minutes, and cooling at room temperature;

4) centrifuging the mixture obtained in the step 3) for 10-20 min at 12000 Xg-15000 Xg, taking supernatant, ultrafiltering the supernatant by using an ultrafiltration membrane, and spray-drying the filtered solution after ultrafiltration by using a spray dryer to obtain the ocean fish oligopeptide dry powder.

6. The VC xanthophyll peptide chewable tablet of sustained release nutritional type according to claim 5, characterized in that the ultrafiltration membrane used in step 4) has a molecular weight cut-off of 1200-1500 u.

7. The VC lutein peptide chewable tablet of sustained release nutritional type according to claim 5, wherein the spray drying of step 4) is performed at a temperature of 5-10 ℃.

8. The preparation method of the sustained-release nutritional VC lutein peptide chewable tablet according to any one of claims 2 to 7, characterized by comprising the following steps:

s1: dissolving the marine fish oligopeptide, the casein phosphopeptide, the soybean peptide, the sea cucumber peptide and the oyster peptide in a volume ratio of (1:2.5) - (3.5:5.5) to 0.15M NaCl solution, and stirring at a rotating speed of 80-120 rpm and a temperature of 15-20 ℃ for 30-40 min;

s2: adding the targeted sustained-release biocompatible microcapsules into the mixture obtained in the step S1, stirring at the rotating speed of 100-200 rpm and the temperature of 26-28 ℃ for 15-30 min, and continuously dropwise adding an ethanol solution during stirring to obtain a targeted sustained-release biocompatible microencapsulated peptide composition;

s3: carrying out vacuum freeze drying on the targeted sustained-release biocompatible microencapsulated peptide composition obtained in the step S2 at a vacuum degree of 0.03-0.06 MPa and-4-2 ℃ to obtain sustained-release peptide composition freeze-dried powder;

s4: dissolving the bovine colostrum powder, the goat milk powder, the concentrated whey protein, the soybean protein powder and the freeze-dried powder of the slow-release peptide composition in the step S3 in glycerol and distilled water in a volume ratio of 2: 3-4: 5, stirring at 200-250 rpm for 10-15 min, adding the fruit and vegetable powder in the weight components, continuously stirring for 10-15 min, and sieving with a 5-10 mesh sieve to obtain wet particles;

s5: uniformly mixing the wet granules obtained in the step S4 with the silica in the weight component to obtain silica-coated wet granules;

s6: mixing said weight component of lutein ester, said weight component of vitamin C, said weight component of citric acid, said weight component of lactose, said weight component of chitosan oligosaccharide, said weight component of fructo-oligosaccharide, said weight component of xylo-oligosaccharide, said weight component of lactoseDissolving erythritol serving as a quantitative component and sorbitol serving as a weight component in 100 ml-150 ml of distilled water, uniformly and rotatably spraying the wet particles coated with silicon dioxide obtained in the step S5 at a spraying rate of 1.5 ml/min-2.0 ml/min and an atomizing pressure of 1.5 MPa-2.0 MPa, uniformly mixing, and then uniformly spraying the mixture at a speed of 5cm ² /L～10cm ² Blowing nitrogen for 10min at a/L speed;

s7: and uniformly stirring the resistant dextrin, the maltodextrin and the magnesium stearate of the weight components with the granules obtained in the step S6, and tabletting to obtain 1g of the sustained-release nutritional VC lutein peptide chewable tablet.

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