CN111820281B - Sustained-release nutritional VC (vitamin C) lutein peptide chewable tablet and preparation method thereof - Google Patents
Sustained-release nutritional VC (vitamin C) lutein peptide chewable tablet and preparation method thereof Download PDFInfo
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Abstract
The invention provides a sustained-release nutritional VC lutein peptide chewable tablet and a preparation method thereof, wherein the chewable tablet comprises the following components: bovine colostrum powder, goat milk powder, concentrated whey protein, marine fish oligopeptide, casein phosphopeptide, soybean peptide, soybean protein powder, sea cucumber peptide, oyster peptide, fruit and vegetable powder, lactose, resistant dextrin, chitosan oligosaccharide, fructo-oligosaccharide, vitamin C, lutein ester, xylo-oligosaccharide, erythritol, sorbitol, citric acid, silicon dioxide, maltodextrin and magnesium stearate; also comprises a targeting slow-release biocompatible microcapsule. The chewable tablets prepared by the preparation method and the components provided by the invention can release marine fish oligopeptide, casein phosphopeptide, sea cucumber peptide, soybean peptide and oyster peptide with nutrition in intestinal tracts, can penetrate through a blood brain barrier to act on eye cells, repair eye fatigue, provide lutein ester and citric acid required by eye work, and provide brain cell work so as to improve brain nutrition.
Description
Technical Field
The invention belongs to the technical field of compound biology, and particularly relates to a sustained-release nutritional VC lutein peptide chewable tablet and a preparation method thereof.
Background
With the continuous and rapid development of economy, the continuous improvement of living standard, the rapid development of Internet and the intelligent degree of mobile phones in China, the mobile phones become part of our lives, the dependence on mobile phones and electronic products in children, teenagers and other groups also leads to the trend and phenomenon of generally declining eyesight, the damage of screen light to the retina is slow and irreversible, the damage to the health of the teenagers in China is huge, and the eye protection for the teenagers is not obvious.
According to the research report issued by the world health organization in 2019, the number of Chinese shortsightedness reaches as many as 6 hundred million, which is almost half of the total population. And teenagers' myopia rates are also the highest rate in all countries around the world. The unhealthy eyesight affects people's daily life, study and work, threatens the health of residents, and increases social burden. The attention of society to eye care and eye care also draws a lot of social capital into the industry, but eye care enterprises generally have the conditions of lack of core competitiveness, single product and service, low personnel quality and the like. The curative effect of part of the medicines is exaggerated, and the health care measures are used for replacing the medical measures, thereby bringing great negative effects to the industry. And the existing medicines lack composition components which can effectively aim at the eyesight protection, slowly release active peptide beneficial to the eyesight protection to nourish the optic nerve, improve the immunity, provide nutrition for brain cells and improve the intelligence, and chewable tablets prepared by the composition components.
Disclosure of Invention
Aiming at the defects, the invention provides the sustained-release nutritional VC lutein peptide chewable tablet which can release marine fish oligopeptide, casein phosphopeptide, sea cucumber peptide, soybean peptide and oyster peptide with nutritional effect in intestinal tracts, can pass through a blood brain barrier to act on eye cells, repairs eye fatigue, provides lutein ester and citric acid required by eye work, assists bovine colostrum powder, goat milk powder, concentrated whey protein and soybean protein powder digested in stomach to further enhance human immunity, and provides brain cell work to further improve brain nutrition, and the preparation method thereof.
The invention provides the following technical scheme: a sustained-release nutritional VC lutein peptide chewable tablet comprises the following components in each 1g of the chewable tablet:
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.
Wherein the fructo-oligosaccharide is extracted from herba Cichorii, and lutein ester is extracted from flos Tagetis Erectae.
Further, each 1g of chewable tablet also comprises 20-30 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.
Further, the poly (2-ethyl-2-oxazoline) grafted glucan nanoparticle comprises the following components in parts 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.
Further, 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 rate of 9-11 mL/h to permeate the polyCarbonate film at 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 lecithin solution impregnation process 5, 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.
Further, various fruit and vegetable powders in the fruit and vegetable powder comprise the following components in parts 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.
Further, 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.
Further, the ultrafiltration membrane adopted in the step 4) has the molecular weight cutoff of 1200-1500 u.
Further, the spray drying of the step 4) is carried out at a temperature of 5 ℃ to 10 ℃.
The invention also provides a preparation method of the sustained-release nutritional VC lutein peptide chewable tablet, which is characterized by comprising the following steps of:
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 sustained-release peptide composition obtained 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, continuously stirring for 10-15 min, and sieving with a 5-10 mesh sieve to obtain wet granules;
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 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 fructo-oligosaccharide of the weight component, the xylo-oligosaccharide of the weight component, the erythritol of the weight component and the vitamin C of the weight componentThe sorbitol of the weight components is dissolved in 100ml to 150ml of distilled water, the mixture is evenly and rotatably sprayed on the wet particles wrapped by the silicon dioxide obtained in the step S5 at the spraying rate of 1.5ml/min to 2.0ml/min and the atomizing pressure of 1.5MPa to 2.0MPa, and after being evenly mixed, the mixture is evenly sprayed by 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.
The invention has the beneficial effects that:
1. the fruit and vegetable powder added in equal proportion can be used for enhancing the peristalsis of gastrointestinal tracts and the fruit taste of the chewable tablets, improving the mouthfeel and avoiding constipation caused by eating the chewable tablets, and the various fruit and vegetable powder contains various celluloses, vitamins and minerals, so that the deficiency of various trace elements or certain nutrient substances which are lacked by diseases of human bodies can be effectively supplemented.
2. During the preparation process of the chewable tablet, micromolecular peptide with peptide activity, such as marine fish oligopeptide, casein phosphopeptide, sea cucumber peptide, oyster peptide and soybean peptide, is directly combined with a glucan skeleton of poly (2-ethyl-2-oxazoline) grafted glucan through a targeted slow release biocompatible microcapsule, can also be wrapped in micelles with glucan hydrophobic cores, then is attached to the surface of a polycarbonate film, an alpha-lactalbumin/amino acid wrapping layer is attached to the outer layer, a kappa-carrageenan-lecithin double-layer film is attached to the outermost layer, the active small peptide can be effectively wrapped by oil through the kappa-carrageenan-lecithin, the chewable tablet has hydrophile lipophilicity, after entering the stomach, the kappa-carrageenan-lecithin double-layer film and bovine colostrum powder, goat milk powder, concentrated whey protein and soybean protein powder are digested by enzymes such as pepsin and the like, the covalent bond between kappa-carrageenan and lecithin is released, the polycarbonate film of poly (2-ethyl-2-oxazoline) grafted glucan nanoparticles with negative charges kappa-carrageenan and alpha-lactalbumin/amino acid coating layers and the primarily decomposed bovine colostrum powder, goat milk powder, concentrated lactalbumin and soybean protein powder are left to enter the intestinal tract, after entering the intestinal tract, the 3-connection-beta-D-galactopyranose and the 4-connection-3, 6-dehydration-alpha-D-galactopyranose units on the surfaces of the kappa-carrageenan enter the neutral pH environment of the intestinal tract from the strongly acidic environment in the stomach, and the poly (2-ethyl-2-oxazoline) grafted glucan nanoparticles with negative charges kappa-carrageenan and alpha-lactalbumin/amino acid coating layers are led to enter the neutral pH environment of the intestinal tract The pH around the ester film is less than the pKa of the ester film, so that the ionic electrostatic repulsion between network structures is reduced, the integral decomposition is caused, and the small peptide of the alpha-lactalbumin/amino acid coating layer is released.
3. The alpha-lactalbumin consists of 123 amino acids, has the molecular weight of about 14kda, comprises a highly structured alpha-helical domain and a beta-sheet domain, has 4 disulfide bonds, NH 2-terminal glutamic acid and COOH-terminal leucine, and can ensure the activity and stability of the active small peptide attached to the poly (2-ethyl-2-oxazoline) grafted glucan nano-particles wrapped inside the alpha-lactalbumin; a part of the alpha-lactalbumin/amino acid can be integrally decomposed in the intestinal tract, and is absorbed by the intestinal tract together with the stomach digests of the bovine colostrum powder, the goat milk powder, the concentrated lactalbumin and the soybean protein powder;
due to the fact that α -lactalbumin, has an isoelectric point between approximately pH4.6-4.9, which makes it negatively charged above this pH range, at neutral pH, the amino acid loses hydrogen molecules, so that a side chain with negative charge is generated, and the other part of alpha-lactalbumin/amino acid can carry marine fish oligopeptide, casein phosphopeptide, sea cucumber peptide, oyster peptide and soybean peptide which are wrapped by poly (2-ethyl-2-oxazoline) grafted glucan nanoparticles to pass through a blood brain barrier, enter into nourishing eye nerve cells and brain nerve cells in the brain, provide energy and required lutein esters for the activity of the eye nerve cells, provide molecular-level nutrition for transmitter transmission between neurites and axons of the brain nerve cells in learning activity, activate nerve activity and ensure brain nerve nutrition in the learning process.
4. The targeting sustained-release biocompatible microcapsule provided by the application adopts 4- (dimethylamino) pyridine and N- (3- (dimethylamino) propyl) -N-ethylcarbodiimide hydrochloride as coupling agents, electrostatic attraction is formed by carboxyl on poly (2-ethyl-2-oxazoline) and hydroxyl on glucan, aminated and carboxylated poly (2-ethyl-2-oxazoline) are grafted to glucan with hydroxyl to form nano-particles with a poly (2-ethyl-2-oxazoline) grafted glucan shell structure, different core filling amounts of the nano-particles can be adjusted by adding 3,3' -dithiopropionic acid, and different drug loading amounts are further ensured, the glucan is a hydrophilic substance, and a mixture of various active peptides can be directly combined with the skeleton of the glucan, it can also be encapsulated in micelles with a hydrophobic core of dextran.
5. The chewable tablet disclosed by the invention has the advantages of natural materials, various components, light concentration and convenience in intake, can meet the requirements of various nutrients of teenagers by taking health as a central thought, is assisted by regulating substances with physiological functions and the regulation and control effect of peptides on cells, breaks through the short plate of the existing product, and provides the chewable tablet which is convenient to use, safe and reliable, can quickly and timely deliver the nutrients to each cell of all tissues of the whole body, can regulate and control the physiological functions of cell growth, replication, multiplication and metabolism, and protects the driving of the growth and development of the teenagers.
Drawings
FIG. 1 is a walking route chart of a normal control group of mice in an open-box experiment in example 1 of the effect of the present invention;
FIG. 2 is a walking route chart of an open-box experiment of mice in a stress group in example 1 of the effect of the present invention;
FIG. 3 is a walking route chart of an open box experiment of mice fed with the chewable tablet water dispersion agent of example 1 in effect example 1 of the present invention;
FIG. 4 is a walking route chart of open box experiment of mice fed with the chewable tablet water dispersion agent of example 2 in effect example 1 of the present invention;
FIG. 5 is a walking route chart of open box experiment of mice fed with the chewable tablet water dispersion agent of example 3 in Effect example 1 of the invention;
Detailed Description
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, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
In the sustained-release nutritional VC leaf yellow protein peptide chewable tablet provided by this embodiment, each 1g of the chewable tablet includes the following components:
6mg of bovine colostrum powder, 100mg of goat milk powder, 10mg of concentrated whey protein, 8mg of marine fish oligopeptide, 5mg of casein phosphopeptide, 6mg of soybean peptide, 5mg of soybean protein powder, 100mg of sea cucumber peptide, 13mg of oyster peptide, 10mg of fruit and vegetable powder, 4mg of lactose, 1mg of resistant dextrin, 1mg of chitosan oligosaccharide, 10mg of fructooligosaccharide, 80mg of vitamin C, 5mg of lutein ester, 1mg of xylooligosaccharide, 0.5mg of erythritol, 15mg of sorbitol, 0.05mg of citric acid, 0.05mg of silicon dioxide, 10mg of maltodextrin and 0.5mg of magnesium stearate; the targeted slow release biocompatible microcapsule is 20 mg.
The targeted sustained-release biocompatible microcapsule comprises the following components in parts by weight: 15 parts of a polycarbonate film with the aperture of 180nm and the thickness of 30 mm; 12 parts of alpha-lactalbumin; 18 parts of amino acid; 8 parts of kappa-carrageenan; 12 parts of lecithin; 25 parts of poly (2-ethyl-2-oxazoline) grafted glucan nanoparticles; 0.05 part of N, N-dimethylformamide.
The poly (2-ethyl-2-oxazoline) grafted glucan nanoparticle comprises the following components in parts by weight:
2.5 parts of poly (2-ethyl-2-oxazoline); 0.2 part of succinic anhydride; 0.5 part of 3,3' -dithiopropionic acid; 1 part of N- (3- (dimethylamino) propyl) -N-ethyl carbodiimide hydrochloride; 2 parts of 4- (dimethylamino) pyridine; and 3 parts of glucan.
The preparation method of the poly (2-ethyl-2-oxazoline) grafted glucan nanoparticle comprises the following steps:
m1: dissolving 2.5 parts of poly (2-ethyl-2-oxazoline) and 0.2 part of succinic anhydride in dichloromethane to form a mixed solution of a poly (2-ethyl-2-oxazoline) organic solution with a concentration of 7mmol/L and a succinic anhydride organic solution with a concentration of 25mmol/L, adding 2 parts of 4- (dimethylamino) pyridine to the mixed solution, and stirring and reacting at the rotation speed of 75rpm and the temperature of 25 ℃ for 12 hours;
m2: mixing the mixture obtained in the M1 step with diethyl ether at a weight-to-volume ratio of 1:8 for reaction for 10min, precipitating in diethyl ether to obtain a crude poly (2-ethyl-2-oxazoline) product with the amino and carboxyl at the tail end, and drying the crude poly (2-ethyl-2-oxazoline) product with the amino and carboxyl at the tail end for 18h under vacuum to obtain crude poly (2-ethyl-2-oxazoline) product powder with the amino and carboxyl at the tail end;
m3: dissolving 3 parts of glucan in dimethyl sulfoxide, dissolving the glucan in microwave for 3 hours under the condition of 10mHz, adding crude poly (2-ethyl-2-oxazoline) powder obtained in the M2 step and 0.5 part of N- (3- (dimethylamino) propyl) -N-ethylcarbodiimide hydrochloride, stirring the mixture at 28 ℃ for 60 minutes, adding 0.5 part of 3,3' -dithiopropionic acid and 0.5 part of N- (3- (dimethylamino) propyl) -N-ethylcarbodiimide hydrochloride, stirring the mixture at 28 ℃ for 60 minutes, dialyzing the obtained mixture under a dialysis membrane with the molecular size of 3200Da for 1 hour, and freeze-drying the dialyzed mixture at-100 ℃ to obtain the poly (2-ethyl-2-oxazoline) grafted glucan nanoparticles.
The preparation method of the targeting sustained-release biocompatible microcapsule comprises the following steps:
a1: dissolving 18 parts of amino acid and 12 parts of alpha-lactalbumin in distilled water, fully stirring and hydrating for 30min at 80rpm, filtering the obtained mixed solution under a 0.40-micron polyvinylidene fluoride filter, and taking the filtered supernatant to obtain amino acid-alpha-lactalbumin mixed supernatant;
a2: dissolving 8 parts of kappa-carrageenan and 12 parts of lecithin in distilled water to form a kappa-carrageenan solution with the concentration of 3mmol/L and a lecithin solution with the concentration of 10 mmol/L;
a3: dissolving 15 parts of polycarbonate film in a phosphate buffer solution containing sodium chloride at a concentration of 0.13M, impregnating 25 parts of poly (2-ethyl-2-oxazoline) grafted glucan nanoparticles through the polycarbonate film at a rate of 9mL/h, and then impregnating the amino acid-. alpha. -lactalbumin mixed supernatant obtained in the step A1 through the polycarbonate film at a rate of 9mL/h at 5cm 2 Standing for 3min under the nitrogen flow with the blowing speed of/L; a is to be2, soaking the kappa-carrageenan solution obtained in the step at the speed of 9mL/h into the polycarbonate film at the depth of 5cm 2 Standing for 3min under nitrogen flow at blowing rate of/L, soaking lecithin solution obtained in the step A2 at a rate of 9mL/h to penetrate through polycarbonate film, continuously dripping 0.05 part of N, N-dimethylformamide during lecithin solution soaking process, and soaking at 5cm after finishing soaking 2 And standing for 3min under the blowing speed of nitrogen gas flow, and drying the product in vacuum for 10min to obtain the targeted slow-release biocompatible microcapsule.
The fruit and vegetable powder comprises the following components in parts by mass: the blueberry fruit and blueberry fruit powder comprises, by weight, 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 blueberry powder.
The preparation method of the marine fish oligopeptide in the chewable tablets comprises the following steps:
1) according to the weight components, 500 parts of deep sea salmon skin is ground, 1L of distilled water is added, a homogenizer is adopted for homogenization, the homogenized mixture is treated at 85 ℃ for 10min, then the temperature is rapidly reduced to 60 ℃, and the pH value is adjusted to 8.5 by adopting HCl solution with the concentration of 1N and NaOH solution with the concentration of 1N;
2) adding 20 parts of papain to the mixture obtained in the step 1), carrying out enzymolysis for 1h, 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 parts of pepsin into the mixture obtained in the step 2), carrying out enzymolysis for 1h, inactivating the enzyme at 150 ℃ for 10min, and cooling at room temperature;
4) centrifuging the mixture obtained in the step 3) for 20min at 12000 Xg, taking supernatant, performing ultrafiltration on the supernatant by using an ultrafiltration membrane with the molecular weight cutoff of 1200u, and performing spray drying on the filtered solution at the temperature of 5 ℃ by using a spray dryer to obtain the marine fish oligopeptide dry powder.
The embodiment also provides a preparation method of the sustained-release nutritional VC lutein peptide chewable tablet, which comprises the following steps:
s1: dissolving 8mg of marine fish oligopeptide, 5mg of casein phosphopeptide, 6mg of soybean peptide, 100mg of sea cucumber peptide and 13mg of oyster peptide in a NaCl solution with the volume ratio of 1:2.5 and the concentration of 0.15M, and stirring at the rotating speed of 80rpm and the temperature of 20 ℃ for 30 min;
s2: adding 20mg of targeted sustained-release biocompatible microcapsule into the mixture obtained in the step S1, stirring at 100rpm and 28 ℃ for 30min, and continuously dropwise adding ethanol solution during stirring to obtain a targeted sustained-release biocompatible microcapsule-encapsulated peptide composition;
s3: vacuum freeze-drying the targeted sustained-release biocompatible microencapsulated peptide composition obtained in the step S2 at a vacuum degree of 0.03MPa and a temperature of-2 ℃ to obtain sustained-release peptide composition freeze-dried powder;
s4: dissolving 6mg of bovine colostrum powder, 100mg of goat milk powder, 10mg of concentrated whey protein, 5mg of soybean protein powder and the freeze-dried powder of the sustained-release peptide composition obtained in the step S3 in glycerol and distilled water in a volume ratio of 2:3, stirring for 15min at a rotating speed of 200rpm, adding the fruit and vegetable powder with weight components, continuously stirring for 10min, and sieving with a 5-mesh sieve to obtain wet particles;
s5: uniformly mixing the wet granules obtained in the step S4 with 0.05mg of silicon dioxide to obtain silicon dioxide-coated wet granules;
s6: dissolving 5mg of lutein ester, 80mg of vitamin C, 0.05mg of citric acid, 4mg of lactose, 1mg of chitosan oligosaccharide, 10mg of fructo-oligosaccharide, 10mg of xylo-oligosaccharide, 0.5mg of erythritol and 15mg of sorbitol in 100ml of distilled water, uniformly and rotatably spraying the wet granules wrapped by silicon dioxide obtained in the step S5 at the spraying speed of 1.5ml/min and the atomizing pressure of 1.5MPa, uniformly mixing, and then uniformly spraying the mixture by 5cm 2 Blowing nitrogen for 10min at a/L speed;
s7: and uniformly stirring 1mg of resistant dextrin, 10mg of maltodextrin and 0.5mg of magnesium stearate with the granules obtained in the step S6, and tabletting to obtain 1g of the sustained-release nutritional VC lutein peptide chewable tablets.
Example 2
In the sustained-release nutritional VC leaf yellow protein peptide chewable tablet provided by this embodiment, each 1g of the chewable tablet includes the following components:
50mg of bovine colostrum powder, 10mg of goat milk powder, 150mg of concentrated whey protein, 1mg of marine fish oligopeptide, 70mg of casein phosphopeptide, 0.5mg of soybean peptide, 0.5mg of soybean protein powder, 13mg of sea cucumber peptide, 100mg of oyster peptide, 100mg of fruit and vegetable powder, 1mg of lactose, 5mg of resistant dextrin, 10mg of chitosan oligosaccharide, 1mg of fructooligosaccharide, 5mg of vitamin C, 100mg of lutein ester, 0.6mg of xylooligosaccharide, 10mg of erythritol, 0.5mg of sorbitol, 1mg of citric acid, 1mg of silicon dioxide, 0.08mg of maltodextrin and 1mg of magnesium stearate; 30mg of targeted sustained-release biocompatible microcapsule;
the targeted sustained-release biocompatible microcapsule comprises the following components in parts by weight: 20 parts of a polycarbonate film with the aperture of 250nm and the thickness of 15 mm; 18 parts of alpha-lactalbumin; 12 parts of amino acid; 12 parts of kappa-carrageenan; 8 parts of lecithin; 35 parts of poly (2-ethyl-2-oxazoline) grafted glucan nanoparticles; 0.1 part of N, N-dimethylformamide.
The poly (2-ethyl-2-oxazoline) grafted glucan nanoparticle comprises the following components in parts by weight:
5 parts of poly (2-ethyl-2-oxazoline); 0.5 part of succinic anhydride; 1 part of 3,3' -dithiopropionic acid; 1.5 parts of N- (3- (dimethylamino) propyl) -N-ethylcarbodiimide hydrochloride; 2.5 parts of 4- (dimethylamino) pyridine; 6 parts of glucan;
the preparation method of the poly (2-ethyl-2-oxazoline) grafted glucan nanoparticle comprises the following steps:
m1: dissolving 5 parts of poly (2-ethyl-2-oxazoline) and 0.5 part of succinic anhydride in dichloromethane to form a mixed solution of a poly (2-ethyl-2-oxazoline) organic solution with a concentration of 15 mmol/L and a succinic anhydride organic solution with a concentration of 45mmol/L, adding 4- (dimethylamino) pyridine in weight percent to the mixed solution, and stirring at a rotation speed of 150rpm and a temperature of 28 ℃ for reaction for 24 hours;
m2: mixing the mixture obtained in the M1 step with diethyl ether at a weight-to-volume ratio of 1:8 for reaction for 15min, precipitating in 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 for 36h to obtain crude poly (2-ethyl-2-oxazoline) product powder with terminal amination and carboxylation;
m3: 6 parts of glucan is dissolved in dimethyl sulfoxide, microwave dissolution is carried out for 4 hours under the condition of 20mHz, then poly (2-ethyl-2-oxazoline) crude product powder obtained in the M2 step and 0.75 part of N- (3- (dimethylamino) propyl) -N-ethyl carbodiimide hydrochloride are added, after stirring for 30 minutes at 32 ℃, 1 part of 3,3' -dithiopropionic acid and 0.75 part of N- (3- (dimethylamino) propyl) -N-ethyl carbodiimide hydrochloride are added, after stirring for 30 minutes at 32 ℃, the obtained mixture is dialyzed for 2 hours under a dialysis membrane with the molecular size of 3800Da, and freeze-drying is carried out at-100 ℃ to obtain the poly (2-ethyl-2-oxazoline) grafted glucan nano-particles.
The preparation method of the targeting sustained-release biocompatible microcapsule comprises the following steps:
a1: dissolving 12 parts of amino acid and alpha-lactalbumin of the weight component in distilled water, fully stirring and hydrating for 20min at 100rpm, filtering the obtained mixed solution under a 0.30-micron polyvinylidene fluoride filter, and taking the filtered supernatant to obtain amino acid-alpha-lactalbumin mixed supernatant;
a2: dissolving 12 parts of kappa-carrageenan and 8 parts of lecithin in distilled water to form a kappa-carrageenan solution with the concentration of 7mmol/L and a lecithin solution with the concentration of 3 mmol/L;
a3: dissolving 20 parts of polycarbonate film in a phosphate buffer solution containing sodium chloride at a concentration of 0.15M, impregnating 35 parts of poly (2-ethyl-2-oxazoline) grafted glucan nanoparticles through the polycarbonate film at a rate of 11mL/h, and then impregnating the amino acid- α -lactalbumin mixed supernatant obtained in the step A1 through the polycarbonate film at a rate of 11mL/h at a concentration of 5cm 2 Standing for 5min under the nitrogen flow with the blowing speed of/L; the kappa-carrageenan solution obtained in step A2 was impregnated through a polycarbonate film at a rate of 11mL/h at 5cm 2 Standing for 5min under nitrogen flow at blowing rate of L, soaking lecithin solution obtained in A2 at 11mL/h rate to penetrate polycarbonate film, dripping 0.1 part of N, N-dimethylformamide during lecithin solution soaking process, and soaking at 5cm after finishing soaking 2 And standing for 5min under the nitrogen flow with the blowing speed of L, and drying the product in vacuum for 15min to obtain the targeted slow-release biocompatible microcapsule.
The chewable tablet comprises the following components in parts by mass: the blueberry fruit and blueberry fruit powder comprises, by weight, 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 balance blueberry powder.
The preparation method of the ocean fish oligopeptide in the chewable tablets comprises the following steps:
1) according to the weight components, 600 parts of deep sea salmon skin is ground, 1.5L of distilled water is added, a homogenizer is adopted for homogenization, the homogenized mixture is treated at 100 ℃ for 10min, then the temperature is rapidly reduced to 60 ℃, and the pH value is adjusted to 8.5 by adopting HCl solution with the concentration of 1N and NaOH solution with the concentration of 1N;
2) adding 30 parts of papain to the mixture obtained in the step 1), carrying out enzymolysis for 2h, 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 40 parts of pepsin into the mixture obtained in the step 2), carrying out enzymolysis for 2h, inactivating the enzyme at 170 ℃ for 15min, and cooling at room temperature;
4) centrifuging the mixture obtained in the step 3) for 10min at 12000 Xg, taking supernatant, performing ultrafiltration on the supernatant by using an ultrafiltration membrane with the molecular weight cutoff of 1500u, and performing spray drying on the filtered solution at 10 ℃ by using a spray dryer to obtain the marine fish oligopeptide dry powder.
The embodiment also provides a preparation method of the sustained-release nutritional VC lutein peptide chewable tablet, which comprises the following steps:
s1: dissolving 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 a NaCl solution with the volume ratio of 3.5:5.5 and the concentration of 0.15M, and stirring for 40min at the rotating speed of 120rpm and the temperature of 15 ℃;
s2: adding 30mg of targeted sustained-release biocompatible microcapsule into the mixture obtained in the step S1, stirring at the rotating speed of 100rpm and the temperature of 26 ℃ for 15min, and continuously dropwise adding an ethanol solution in the stirring process to obtain a targeted sustained-release biocompatible microcapsule-encapsulated peptide composition;
s3: vacuum freeze-drying the targeted sustained-release biocompatible microencapsulated peptide composition obtained in the step S2 at a vacuum degree of 0.06MPa and a temperature of-4 ℃ to obtain sustained-release peptide composition freeze-dried powder;
s4: dissolving 50mg of bovine colostrum powder, 10mg of goat milk powder, 150mg of concentrated whey protein, 0.5mg of soybean protein powder and the sustained-release peptide composition freeze-dried powder obtained in the step S3 in glycerol and distilled water in a volume ratio of 4:5, stirring at 200rpm for 10min, adding the fruit and vegetable powder with weight components, continuously stirring for 15min, and sieving with a 10-mesh sieve to obtain wet granules;
s5: uniformly mixing the wet granules obtained in the step S4 with 1mg of silicon dioxide to obtain wet granules wrapped by the silicon dioxide;
s6: dissolving 100mg of lutein ester, 5mg of vitamin C, 1mg of citric acid, 1mg of lactose, 10mg of chitosan oligosaccharide, 1mg of fructooligosaccharide, 0.6mg of xylooligosaccharide, 10mg of erythritol and 0.5mg of sorbitol in 150ml of distilled water, uniformly and rotatably spraying the wet granules wrapped by silicon dioxide obtained in the step S5 at the spraying rate of 2.0ml/min and the spraying pressure of 2.0MPa, uniformly mixing, and then, uniformly spraying the mixture by 10cm 2 Blowing nitrogen for 10min at a/L speed;
s7: and uniformly stirring 5mg of resistant dextrin, 0.08mg of maltodextrin and 1mg of magnesium stearate with the granules obtained in the step S6, and tabletting to obtain 1g of the sustained-release nutritional VC lutein peptide chewable tablet.
Example 3
In the sustained-release nutritional VC leaf flavoprotein peptide chewable tablet provided in this embodiment, each 1g of the chewable tablet comprises the following ingredients:
28mg of bovine colostrum powder, 55mg of goat milk powder, 80mg of concentrated whey protein, 4.5mg of marine fish oligopeptide, 37.5mg of casein phosphopeptide, 3.25mg of soybean peptide, 5.25mg of soybean protein powder, 56.5mg of sea cucumber peptide, 56.5mg of oyster peptide, 55mg of fruit and vegetable powder, 2.5mg of lactose, 3mg of resistant dextrin, 5.5mg of chitosan oligosaccharide, 5.5mg of fructo-oligosaccharide, 42.5mg of vitamin C, 52.5mg of lutein ester, 0.8mg of xylo-oligosaccharide, 5.25mg of erythritol, 7.5mg of sorbitol, 0.5mg of citric acid, 0.5mg of silicon dioxide, 5mg of maltodextrin and 0.75mg of magnesium stearate; 25mg of targeted sustained-release biocompatible microcapsule;
the targeting sustained-release biocompatible microcapsule comprises the following components in parts by weight: 18 parts of polycarbonate film with the aperture of 200nm and the thickness of 23 mm; 15 parts of alpha-lactalbumin; 15 parts of amino acid; 10 parts of kappa-carrageenan; 10 parts of lecithin; 20 parts of poly (2-ethyl-2-oxazoline) grafted glucan nanoparticles; 0.5 part of N, N-dimethylformamide.
The poly (2-ethyl-2-oxazoline) grafted glucan nanoparticle comprises the following components in parts by weight:
3.75 parts of poly (2-ethyl-2-oxazoline); 0.35 part of succinic anhydride; 0.75 part of 3,3' -dithiopropionic acid; 1.25 parts of N- (3- (dimethylamino) propyl) -N-ethylcarbodiimide hydrochloride; 2.25 parts of 4- (dimethylamino) pyridine; 4.5 parts of glucan;
the preparation method of the poly (2-ethyl-2-oxazoline) grafted glucan nanoparticle comprises the following steps:
m1: dissolving 3.75 parts of poly (2-ethyl-2-oxazoline) and 0.35 part of succinic anhydride in methylene chloride to form a mixed solution of an organic solution of poly (2-ethyl-2-oxazoline) with a concentration of 11 mmol/L and an organic solution of succinic anhydride with a concentration of 35mmol/L, adding 2.25 parts of 4- (dimethylamino) pyridine to the mixed solution, and stirring at a rotation speed of 100rpm and a temperature of 27 ℃ for reaction for 18 hours;
m2: mixing the mixture obtained in the M1 step with diethyl ether at a weight-to-volume ratio of 1:8 for reaction for 12min, precipitating in diethyl ether to obtain a crude poly (2-ethyl-2-oxazoline) product with the amino and carboxyl at the tail end, and drying the crude poly (2-ethyl-2-oxazoline) product with the amino and carboxyl at the tail end for 24h under vacuum to obtain crude poly (2-ethyl-2-oxazoline) product powder with the amino and carboxyl at the tail end;
m3: dissolving 4.5 parts of glucan in dimethyl sulfoxide, performing microwave dissolution for 3.5 hours under the condition of 15mHz, adding crude poly (2-ethyl-2-oxazoline) powder obtained in the M2 step and 0.625 part of N- (3- (dimethylamino) propyl) -N-ethylcarbodiimide hydrochloride, stirring for 45 minutes at 30 ℃, adding 0.75 part of 3,3' -dithiopropionic acid and 0.625 part of N- (3- (dimethylamino) propyl) -N-ethylcarbodiimide hydrochloride, stirring for 45 minutes at 30 ℃, dialyzing the obtained mixture for 1.5 hours under a dialysis membrane with the molecular size of 3600Da, and performing freeze-drying at-100 ℃ to obtain the poly (2-ethyl-2-oxazoline) grafted glucan nanoparticles.
The preparation method of the targeting sustained-release biocompatible microcapsule comprises the following steps:
a1: dissolving 15 parts of amino acid and 15 parts of alpha-lactalbumin in distilled water, fully stirring and hydrating for 25min at 90rpm, filtering the obtained mixed solution under a 0.35-micron polyvinylidene fluoride filter, and taking the filtered supernatant to obtain amino acid-alpha-lactalbumin mixed supernatant;
a2: dissolving 10 parts of kappa-carrageenan and 10 parts of lecithin in distilled water to form a kappa-carrageenan solution with the concentration of 5mmol/L and a lecithin solution with the concentration of 6.5 mmol/L;
a3: dissolving 18 parts of polycarbonate film in a phosphate buffer solution containing sodium chloride at a concentration of 0.14M, impregnating 20 parts of poly (2-ethyl-2-oxazoline) grafted glucan nanoparticles through the polycarbonate film at a rate of 10mL/h, and then impregnating the amino acid-. alpha. -lactalbumin mixed supernatant obtained in the step A1 through the polycarbonate film at a rate of 10mL/h at a concentration of 5cm 2 Standing for 3-5 min under the nitrogen flow with the blowing speed of/L; the kappa-carrageenan solution obtained in step A2 was impregnated at a rate of 10mL/h through a polycarbonate film at 5cm 2 Standing for 4min under nitrogen flow at blowing rate of/L, soaking lecithin solution obtained in step A2 at 10mL/h rate to penetrate polycarbonate film, dripping 0.5 part of N, N-dimethylformamide during lecithin solution soaking process, and soaking at 5cm after finishing soaking 2 Standing for 45min under the blowing speed of nitrogen gas flow, and drying the product in vacuum for 13min to obtain the targeted slow-release biocompatible microcapsule.
The chewable tablet comprises the following components in parts by mass: the blueberry fruit and vegetable powder comprises, by weight, 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 balance blueberry powder.
The preparation method of the ocean fish oligopeptide in the chewable tablets comprises the following steps:
1) according to the weight components, 550 parts of deep sea salmon skin is ground, 1.25L of distilled water is added, a homogenizer is adopted for homogenization, the homogenized mixture is treated for 10min at the temperature of 92 ℃, then the temperature is rapidly reduced to 60 ℃, and the pH value is adjusted to 8.5 by adopting HCl solution with the concentration of 1N and NaOH solution with the concentration of 1N;
2) adding 25 parts of papain to the mixture obtained in the step 1), carrying out enzymolysis for 1.5h, and adjusting the pH to 8.5 by adopting a 1N HCl solution and a 1N NaOH solution;
3) adding 38 parts of pepsin into the mixture obtained in the step 2), carrying out enzymolysis for 1-2 h, inactivating enzyme at 160 ℃ for 12min, and cooling at room temperature;
4) centrifuging the mixture obtained in the step 3) for 15min at 13500 Xg, taking supernatant, performing ultrafiltration on the supernatant by using an ultrafiltration membrane with the molecular weight cutoff of 1350u, and performing spray drying on the filtered solution at the temperature of 8 ℃ by using a spray dryer to obtain the marine fish oligopeptide dry powder.
The embodiment also provides a preparation method of the sustained-release nutritional VC lutein peptide chewable tablet, which comprises the following steps:
s1: dissolving 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 a NaCl solution with the volume ratio of 2:3 and the concentration of 0.15M, and stirring at the rotating speed of 100rpm and the temperature of 18 ℃ for 35 min;
s2: adding 25mg of targeted sustained-release biocompatible microcapsule into the mixture obtained in the step S1, stirring at the rotating speed of 150rpm and the temperature of 27 ℃ for 18min, and continuously dropwise adding an ethanol solution in the stirring process to obtain a targeted sustained-release biocompatible microcapsule-encapsulated peptide composition;
s3: vacuum freeze-drying the targeted sustained-release biocompatible microencapsulated peptide composition obtained in the step S2 at a vacuum degree of 0.045MPa and a temperature of-3 ℃ to obtain sustained-release peptide composition freeze-dried powder;
s4: dissolving 28mg of bovine colostrum powder, 55mg of goat milk powder, 80mg of concentrated whey protein, 5.25mg of soybean protein powder and the slow-release peptide composition freeze-dried powder obtained in the step S3 in glycerol and distilled water with the volume ratio of 3:4, stirring for 12min at the rotating speed of 225rpm, adding the fruit and vegetable powder with the weight components, continuously stirring for 13min, and sieving with an 8-mesh sieve to obtain wet granules;
s5: uniformly mixing the wet granules obtained in the step S4 with 0.5mg of silicon dioxide to obtain wet granules wrapped by the silicon dioxide;
s6: mixing lutein ester 52.5mg, vitamin C42.5 mg, and lemon 0.5mgCitric acid, 2.5mg of lactose, 5.5mg of chitosan oligosaccharide, 5.5mg of fructo-oligosaccharide, 0.8mg of xylo-oligosaccharide, 5.25mg of erythritol and 7.5mg of sorbitol were dissolved in 125ml of distilled water, and the mixture was uniformly rotary-sprayed on the silica-coated wet granules obtained in the step S5 at a spraying rate of 1.8ml/min and an atomizing pressure of 1.8MPa, and after uniformly mixing, the mixture was 8cm 2 Blowing nitrogen for 10min at a/L speed;
s7: and uniformly stirring 3mg of resistant dextrin, 5mg of maltodextrin and 0.75mg of magnesium stearate with the granules obtained in the step S6, and tabletting to obtain 1g of the sustained-release nutritional VC lutein peptide chewable tablet.
Effect example 1
Performing an open-box experiment by using SD rats, and selecting 30 SD rats which are male, 5-6 weeks old and male, wherein the weight of the SD rats is 160-180 g (the weight difference is less than 20%); purchased from shanghai slaike experimental animal technology limited [ production license number: SCXK (Shanghai), 2007 & 0005], SPF class. The animals were kept for 7 days before the experiment, and the animals were allowed to adapt to the breeding environment.
The experimental stress method comprises the following steps: stress stimulation was performed twice daily at irregular times without fixed sequence: clamping tail for 3 min; suspending tail for 15 min; the cage was tilted for 24hr and ultrasonically stimulated for 10 min. Animal body weights were recorded weekly and observed at the cage. The model simulates the phenomenon that the human beings are not fixedly stimulated by the surrounding environment, so that behaviors and reaction retardation are generated, the rat is in a mental stress state every day due to the stimulation, and the rat falls into a stress state similar to the phenomenon that the human beings are subjected to long-term occurrence of bad events, and is easy to cause emotional depression and reaction retardation after going for a long time.
And (3) open box testing: after 100ml of the chewable tablet water dispersion of examples 1-3 was continuously taken for 3 weeks and all animals were 1hr after the last administration, the animals were placed in an open box device and the movement trajectory of the animals was examined within 30 min. And (3) reading data after the detection is finished, and acquiring data such as the total movement distance, the movement speed, the movement distance of the central area and the like within 30min, wherein the data are shown in table 1 and figures 1-5.
Open box and video capture software was purchased from Shanghai Ji Mass software, Inc. The method for detecting the motion trajectory of a white object (rat) in a video area is carried out by adopting a black background with all the periphery and the bottom. And when the rat is placed in the open box, all the rats are placed at corners, the experimenter leaves the open box immediately, after 30min, the animal is moved out after the movement track of the equipment is completely recorded, the open box is cleaned, the smell is covered by alcohol spraying, the inner part and the bottom of the periphery of the open box are cleaned again, and after the alcohol is completely volatilized, the rat in the next batch is replaced, and the detection is continued.
TABLE 1 OFT results after administration of chewable tablet water dispersion to stressed rats
As can be seen from the diagrams 1-5 of the OFT result, the movement tracks of all groups of animals in an open box within 30min are obviously different, the range and the path of the activity of the animals in a stress group are obviously lower than those of other groups, the path of the animals entering a central area is also obviously different between groups, and the walking path of the animals in a blank control group in the central area is obviously higher than those of other groups, so that the exploration consciousness of long-term stress rats to unknown spaces is obviously reduced.
While the invention has been described with reference to a preferred embodiment, various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. It will be readily apparent to those skilled in the art that various modifications to these embodiments may be made, and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present invention is not limited to the above embodiments, and those skilled in the art should make modifications and alterations without departing from the scope of the present invention. It is intended that the invention not be limited to the particular embodiments disclosed, but that the invention will include all embodiments falling within the scope of the appended 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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| CN101991036A (en) * | 2010-09-17 | 2011-03-30 | 吉林大学 | Egg white protein nutritive peptide chewable tablet and preparation method thereof |
| CN105614898A (en) * | 2016-01-28 | 2016-06-01 | 青岛海洋生物医药研究院股份有限公司 | Marine compound protein powder containing oyster peptide and preparation method of marine compound protein powder containing oyster peptide |
| CN106236739A (en) * | 2016-07-27 | 2016-12-21 | 上海宣泰生物科技有限公司 | Compositions containing phylloxanthin/lutein ester and application thereof |
| CN107647385A (en) * | 2017-07-31 | 2018-02-02 | 浦江县泰如食品科技有限公司 | A kind of fishbone dust and the preparation method of protein peptide mixture chewable tablets |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101991036A (en) * | 2010-09-17 | 2011-03-30 | 吉林大学 | Egg white protein nutritive peptide chewable tablet and preparation method thereof |
| CN105614898A (en) * | 2016-01-28 | 2016-06-01 | 青岛海洋生物医药研究院股份有限公司 | Marine compound protein powder containing oyster peptide and preparation method of marine compound protein powder containing oyster peptide |
| CN106236739A (en) * | 2016-07-27 | 2016-12-21 | 上海宣泰生物科技有限公司 | Compositions containing phylloxanthin/lutein ester and application thereof |
| CN107647385A (en) * | 2017-07-31 | 2018-02-02 | 浦江县泰如食品科技有限公司 | A kind of fishbone dust and the preparation method of protein peptide mixture chewable tablets |
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