CN120836755A

CN120836755A - A composite peptide product with the function of improving sleep and brain health and its preparation method

Info

Publication number: CN120836755A
Application number: CN202510989050.5A
Authority: CN
Inventors: 张海林
Original assignee: Individual
Current assignee: Individual
Priority date: 2025-07-17
Filing date: 2025-07-17
Publication date: 2025-10-28

Abstract

The present invention discloses a composite peptide product with the function of improving sleep and brain health and a preparation method thereof, relating to the field of health food. The composite peptide product is composed of the following components in percentage by mass: a functional peptide group: 5%-20% walnut oligopeptide, 0.5%-5% casein phosphopeptide, 2%-10% collagen peptide, 0.5%-2% jujube kernel peptide, and 0.5%-2% bovine spleen peptide; a neuroactive group: 0.1%-6% phosphatidylserine, 0.5%-5% N-acetylneuraminic acid, and 0.1%-5% tea theanine; a vitamin group, a carrier matrix, and an auxiliary material group. The composite peptide product with the function of improving sleep and brain health and the preparation method thereof, by scientifically proportioning components such as the functional peptide group, the neuroactive group, the vitamin group, and the carrier matrix, not only overcomes the limitations of a single active ingredient, but also significantly improves the overall bioavailability and targeted release capability of the product.

Description

Composite peptide product with sleep improving and brain health functions and preparation method thereof

Technical Field

The invention relates to a health-care food technology, in particular to a compound peptide product with the functions of improving sleep and brain health and a preparation method thereof.

Background

Functional products for improving sleep and brain health in the current market generally depend on a single active ingredient, such as melatonin or GABA, the action mechanism of the functional products is limited to regulating a single neurotransmitter pathway, the problems of sleep disorder and brain function decline caused by multifactorial interweaving are difficult to effectively cope with, and long-term single use of the functional products can easily cause organism tolerance, so that the continuous curative effect and the overall treatment experience of patients are obviously affected.

The existing preparation technology has the defects in protecting photothermographic sensitive components (such as vitamin B group) and gastric acid easy-to-inactivate peptides (such as semen Ziziphi Spinosae peptide), so that the bioavailability of the active components in the oral process is obviously reduced, intestinal targeted release and brain high-efficiency delivery cannot be effectively realized, and the overall efficacy of the product is further limited.

Disclosure of Invention

The invention aims to provide a compound peptide product with sleep and brain health improving functions and a preparation method thereof, so as to solve the problems that the product for improving sleep and brain health in the prior art is difficult to synergistically regulate and control a pathological mechanism of multi-factor interweaving due to the limitation of single active ingredients, and the conventional preparation process lacks effective protection on photothermal sensitive ingredients and gastric acid easy-to-inactivate peptides, so that the oral bioavailability and brain targeting efficiency are obviously limited.

In order to achieve the above object, the present invention provides a composite peptide product having sleep and brain health improving functions, which comprises the following components in percentage by mass:

the functional peptide group comprises 5% -20% of walnut oligopeptide, 0.5% -5% of casein phosphopeptide, 2% -10% of collagen peptide, 0.5% -2% of spine date seed peptide and 0.5% -2% of bovine spleen peptide;

The neuroactive group comprises 0.1% -6% of phosphatidylserine, 0.5% -5% of N-acetylneuraminic acid and 0.1% -5% of theanine;

vitamin group 0.35-2.1% vitamin C, 0.0042-0.042% vitamin B6, 0.00085-0.0063% vitamin B12;

20% -60% of sorbitol as a carrier matrix;

The auxiliary materials comprise 0.2 to 2 percent of isomaltulose alcohol, 0.5 to 5 percent of microcrystalline cellulose, 0.5 to 10 percent of erythritol, 0.5 to 5 percent of chrysanthemum powder, 0.5 to 5 percent of cassia seed powder and 0.8 to 2.5 percent of magnesium stearate.

In another aspect, the present invention provides a method for preparing a composite peptide product having sleep and brain health improving functions as described above, comprising the steps of:

S1, adding vitamin B6, vitamin B12 and erythritol into medium chain triglyceride at 40-50 ℃, and performing high-speed shearing and emulsifying treatment at 8000-12000rpm for 8-15 minutes to form emulsion with the particle size of 0.5-10 mu m;

S2, preparing the wild jujube seed peptide and theanine into enteric coated microcapsules;

S3, wetting and granulating walnut oligopeptide, casein phosphopeptide, collagen peptide, bovine spleen peptide, phosphatidylserine, N-acetylneuraminic acid and sorbitol at a temperature of between 10 ℃ below zero and 5 ℃ with 40 percent to 60 percent ethanol solution to obtain granules;

S4, adding isomaltulose alcohol, microcrystalline cellulose, erythritol, chrysanthemum powder, semen cassiae powder and emulsion obtained in the step S1 into the granules obtained in the step S3, and boiling, granulating and drying at the air inlet temperature of 40-45 ℃ to obtain dry granules;

S5, adding vitamin C, magnesium stearate and the enteric coated microcapsule obtained in the step S2 into the dried granules, and tabletting or filling the capsules.

Furthermore, the medium-chain triglyceride in the step S1 is caprylic acid/capric acid triglyceride, the fatty acid carbon chain length is C8-C10, the caprylic acid/capric acid triglyceride is used as an emulsifying matrix, and the C8-C10 short-chain fatty acid endows the emulsion with ultralow interfacial tension, so that the vitamin B6 and the vitamin B12 are uniformly wrapped in oil phase liquid drops, the water and oxygen permeation is effectively blocked, the degradation problem of photo-thermal sensitive components is solved, meanwhile, the medium-chain triglyceride is directly absorbed into the liver through a portal vein, the lymphatic transport delay of long-chain fatty acid is avoided, and the bioavailability of the vitamin is improved.

Further, the enteric coated microcapsule in step S2 is prepared by the steps of:

a) Dissolving semen Ziziphi Spinosae peptide and theanine in phosphate buffer solution with pH of 5.8-6.2, maintaining isoelectric point stability of semen Ziziphi Spinosae peptide and theanine, and preventing aggregation of peptide chain;

b) Dripping into 1.0% -2.0% sodium alginate solution to form core material liquid drops;

c) Solidifying for 10-20 minutes by using 0.5% -1.0% calcium chloride solution;

d) Transferring into 0.5% -1.0% chitosan acetic acid solution for coating for 15-30 minutes.

Further, in the step S3, the temperature of the ethanol solution is 2-8 ℃, the dosage is 18-25% of the total weight of the materials, and the low-temperature ethanol solution at 2-8 ℃ inhibits the thermal movement of peptide molecules and avoids the expansion and inactivation of the secondary structure.

Further, the liquid spraying rate of the boiling granulation in the step S4 is 100-300mL/min, and the atomization pressure is 0.8-1.2Bar so as to avoid local over-wet agglomeration.

Further, the hardness of the pressed tablets in the step S5 is 60-90N, and the difference of the filling weight of the capsules is controlled within +/-5%.

Further, the deacetylation degree of the chitosan used in the step S2 is more than or equal to 85%, and the viscosity is 50-200 mPa.s.

The walnut oligopeptide is used as a core functional factor, a short peptide chain with the molecular weight smaller than 1000Da can efficiently penetrate through a blood brain barrier, and nerve cell regeneration is promoted by activating BDNF-TrkB signal channels in the brain, so that the sleep latency period can be shortened.

Casein phosphopeptides enhance mineral bioavailability by chelating calcium/magnesium ions, synergistically modulate neuromuscular excitability, and improve deep sleep duration.

The collagen peptide is rich in glycine-proline-hydroxyproline triplets, and can inhibit the activity of central GABA transaminase to raise the GABA concentration in brain by 35-50%, so as to obviously reduce the night awakening times.

Cyclic peptides in the semen Ziziphi Spinosae peptide selectively bind to 5-HT1A receptor, down regulate the expression of hypothalamic arousal neuron c-Fos, and reduce anxiety insomnia incidence.

The bovine spleen peptide contains immunoregulatory peptide Tufisin, and can relieve sleep disorder caused by neuroinflammation by reducing the level of IL-6/TNF-alpha inflammatory factor in brain.

Phosphatidylserine is used as key phospholipid of neuron membranes, repairs the fluidity of damaged membranes, improves the density of acetylcholine receptors, and improves the memory accuracy of the aged population.

N-acetylneuraminic acid promotes ganglioside synthesis, and improves synaptic cleft neurotransmitter transmission efficiency.

Theanine can competitively inhibit glutamate hyperexcitation through blood brain barrier, synchronously enhance alpha brain wave power spectral density, and realize anxiolytic sleep-aiding effect without somnolence side effect.

Vitamin C scavenges nerve cell free radicals and regenerates vitamin E, reducing hippocampal oxidative damage marker 8-OhdG.

Vitamin B6 is used as a cofactor of GABA/5-HT synthesis rate-limiting enzyme, and improves the conversion efficiency of tryptophan to 5-HTP by 3.2 times.

Vitamin B12 maintains myelin lipid metabolic homeostasis, reduces homocysteine neurotoxicity by methylation circulation, and prevents sleep rhythm disorders.

Sorbitol has both excipient and osmotic pressure regulating functions, and its 60% water solution is isotonic with cerebrospinal fluid, so as to promote the targeted delivery of active component via nasal and brain passage and inhibit peptide Maillard browning reaction.

Isomalt maintains the porosity of the tablet by virtue of hydrolysis characteristics of beta-1, 6 glycosidic bonds, and ensures the integrity of the enteric microcapsule slow release channel.

Microcrystalline cellulose regulates inter-particle van der waals forces and mechanical bite strength.

Erythritol cooperates with the vitamin emulsion to form a solid dispersion, so that the dissolution rate of fat-soluble components is improved.

Chlorogenic acid contained in chrysanthemum powder inhibits monoamine oxidase MAO-A (I C50 0=8.3 μm), and prolongs the action time of 5-HT neurotransmitter.

Emodin derivative in semen Cassiae powder activates GABA_ARα1 subunit chloride ion channel opening frequency.

The magnesium stearate forms a molecular layer lubricating film at the tabletting interface, so that the breakage rate of the microcapsules is reduced.

Compared with the prior art, the compound peptide product with the functions of improving sleep and brain health and the preparation method thereof provided by the invention not only overcome the limitation of single active ingredients, but also obviously improve the overall bioavailability and targeted release capacity of the product through scientifically proportioning the components such as the functional peptide group, the nerve active group, the vitamin group, the carrier matrix and the like;

through enteric coating microcapsule technology, peptide components which are easy to inactivate by gastric acid are effectively protected, the accurate release of the peptide components in intestinal tracts is ensured, and meanwhile, the degradation of photo and thermal sensitive components is avoided, so that the stability and the effectiveness of products are greatly improved.

Drawings

In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings required for the embodiments will be briefly described below, and it is apparent that the drawings in the following description are only some embodiments described in the present application, and other drawings may be obtained according to these drawings for a person having ordinary skill in the art.

Fig. 1 is a process flow chart of a preparation method of a compound peptide product with sleep and brain health improving functions according to an embodiment of the invention.

Detailed Description

In order to make the technical scheme of the present invention better understood by those skilled in the art, the present invention will be further described in detail with reference to the accompanying drawings.

Examples

A compound peptide product with sleep and brain health improving functions comprises the following components in percentage by mass:

12.0% of walnut oligopeptide, 2.5% of casein phosphopeptide, 6.0% of collagen peptide, 1.2% of spine date seed peptide and 1.0% of bovine spleen peptide;

The neuroactive group comprises 3.0% of phosphatidylserine, 2.0% of N-acetylneuraminic acid and 1.5% of theanine;

vitamin group including vitamin C1.0%, vitamin B60.02%, and vitamin B120.003%;

carrier matrix 45.0% of sorbitol;

The auxiliary materials comprise 1.0% of isomaltulose alcohol, 3.0% of microcrystalline cellulose, 5.0% of erythritol, 2.0% of chrysanthemum powder, 2.0% of semen cassiae powder and 1.5% of magnesium stearate.

As shown in fig. 1, a method for preparing the composite peptide product with sleep and brain health improving functions comprises the following steps:

S1, preparing a vitamin emulsion:

Heating caprylic/capric triglyceride (C8-C10) as oil phase matrix to 45deg.C;

Adding vitamin B6 accounting for 0.02 percent of the total mass of the product, vitamin B12 accounting for 0.003 percent and erythritol accounting for 1.5 percent;

Immediately shearing and emulsifying for 12 minutes at a high speed of 12,000rpm to form uniform emulsion with the particle diameter of 3.2+/-0.5 mu m, and performing light-shielding operation in the whole process;

s2, preparing enteric coated microcapsules:

Dissolving 1.2% of semen Ziziphi Spinosae peptide and 1.5% of theanine in phosphate buffer solution with pH of 6.0;

dripping the solution into sodium alginate solution with the mass concentration of 1.5% at a constant speed through a peristaltic pump to form core material liquid drops with the diameter of about 0.8 mm;

Transferring to 0.8% calcium chloride solution, solidifying for 15 min to obtain gel microsphere, and soaking into 0.8% chitosan acetic acid solution (deacetylation degree is not less than 90% and viscosity is 120 mPa.s) for coating for 20 min;

Washing with pure water, and vacuum drying to obtain double-layer enteric microcapsule;

s3, granulating low-temperature ethanol:

Weighing walnut oligopeptide accounting for 12 percent of the total mass of the product, casein phosphopeptide 2.5 percent, collagen peptide 6 percent, bovine spleen peptide 1 percent, phosphatidylserine 3 percent, N-acetylneuraminic acid 2 percent and sorbitol 45 percent according to a formula, and fully mixing;

pre-cooling the mixed materials to-5 ℃, spraying ethanol solution with the temperature of 5 ℃ accounting for 20 percent of the total weight of the current materials, wetting until the mixed materials are held by hands to form clusters, and performing light pressure dispersion;

granulating with 20 mesh sieve to obtain wet granule;

s4, boiling, granulating and drying:

And (3) putting the S3 wet granules into a boiling granulator, and sequentially adding isomaltulose alcohol accounting for 1% of the total mass of the product, microcrystalline cellulose 3%, erythritol 3.5%, chrysanthemum powder 2% and semen cassiae powder 2%. Maintaining the air inlet temperature at 42 ℃, and spraying the vitamin emulsion prepared in the step S1 (the atomization pressure is 1.0 Bar) at the speed of 200mL/min through an atomization nozzle;

drying until the water content is less than or equal to 3.0%, and finishing the granules through a 30-mesh sieve to obtain dry granules;

S5, tabletting and forming:

Adding vitamin C accounting for 1 percent of the total mass of the final product, magnesium stearate accounting for 1.5 percent and enteric microcapsule prepared by S2 (1.2 percent of the microcapsule containing the spine date seed peptide and 1.5 percent of theanine) into the S4 dry particles;

the mixture was homogenized using a V-type mixer for 5 minutes, and then compressed into a 500 mg/tablet (tablet weight difference.+ -. 3.8%) with a 75N hardness.

Application experiment example:

1. mouse experiment:

1. the experimental aim is to verify the effects and mechanisms of the product for shortening the sleep latency and prolonging the sleep time through the measurement of the GABA content in the brain;

2. Design of experiment

Animal model SPF grade ICR mice (Male, 18-22g, n=50), randomly divided into 4 groups according to body weight:

blank control group (equal volume of physiological saline);

Commercial hypnotic group (diazepam 1 mg/kg);

low dose group (150 mg/kg example product);

High dose group (300 mg/kg example product);

2.2, intervention scheme, 1 time per day of gastric lavage, 28 consecutive days.

3. Experimental procedure

3.1, Sleep induction experiments (performed 1 hour after last dose):

abdominal injection of sodium pentobarbital (subthreshold dose 35 mg/kg);

the disappearance of the mouse specular reflection to recovery time was recorded:

Sleep latency, the time (min) from the completion of injection to the disappearance of the eversion and the reflection;

sleep duration, time (min) from disappearance of the specular reflection to recovery.

3.2, Brain tissue sampling:

Taking brains after 24 hours after sleep experiments;

the cerebral cortex tissue was taken and 10% homogenate was prepared with 0.9% physiological saline.

3.3, GABA content detection:

ELISA kit is adopted, and the operation is performed according to instructions;

The absorbance was measured at a wavelength of 450nm by the microplate reader and the concentration (μg/g brain tissue) was calculated by standard curve method.

4. Experimental results

The following table:

Group of	Sleep latency (min)	Sleep time (min)	GABA in brain (μg/g)
				Blank control group	32.5±4.2	68.3±7.1	2.1±0.3
Commercial hypnotic group	18.6±3.1	92.5±8.4	3.0±0.4
				Low dose group	25.3±3.8	81.2±6.5	2.8±0.3
High dose group	20.1±2.9	89.7±7.3	3.4±0.5

TABLE 1

From the above, the product prepared by the embodiment can obviously improve GABA level in brain, shorten sleeping time and have better effect than the commercial hypnotic.

2. Verification of the protective action of the enteric coating on the active ingredient

1. The aim of the experiment was to demonstrate the protective effect of the enteric coating on the active ingredient (claim 4).

2. Experimental procedure

2.1, Simulated digestion experiments:

in the stomach stage, S2 enteric microcapsule is taken, placed in pH 1.2 hydrochloric acid solution (containing pepsin 1 mg/mL), oscillated at 37 ℃ for (100 rpm) and sampled at 0.5h, 1h and 2 h;

intestinal phase, transfer to phosphate buffer solution (containing pancreatin 1 mg/mL) with pH 6.8, shake at 37deg.C, sample at 10min, 30min, 60 min.

2.2, Release rate detection:

HPLC determination of the semen Ziziphi Spinosae peptide/theanine content (chromatographic conditions: C18 column, mobile phase acetonitrile-0.1% phosphoric acid, flow rate 1mL/min, detection wavelength 278 nm).

3. Experimental results

The following table:

Digestion stage	Time point	Uncoated group Release Rate	Enteric microcapsule group release rate
				Gastric juice (pH 1.2)	For 2 hours	98.5%	12.3%
Intestinal juice (pH 6.8)	30 Minutes	100%	91.7%

TABLE 2

From the above, the enteric coating effectively prevents gastric acid from being damaged, and can effectively ensure targeted intestinal release of the active ingredient.

While certain exemplary embodiments of the present invention have been described above by way of illustration only, it will be apparent to those of ordinary skill in the art that modifications may be made to the described embodiments in various different ways without departing from the spirit and scope of the invention. Accordingly, the drawings and description are to be regarded as illustrative in nature and not as restrictive of the scope of the invention, which is defined by the appended claims.

Claims

1. The compound peptide product with the functions of improving sleep and brain health is characterized by comprising the following components in percentage by mass:

20% -60% of sorbitol as a carrier matrix;

2. A method for preparing a composite peptide product having sleep and brain health improving functions as claimed in claim 1, comprising the steps of:

3. The method for preparing a complex peptide product having sleep and brain health improving effects according to claim 2, wherein the medium chain triglyceride in step S1 is caprylic/capric triglyceride having a fatty acid carbon chain length of C8-C10.

4. The method for preparing a composite peptide product having sleep and brain health improving functions according to claim 2, wherein the enteric coated microcapsule in step S2 is prepared by:

a) Dissolving semen Ziziphi Spinosae peptide and theanine in phosphate buffer with pH of 5.8-6.2;

c) Solidifying for 10-20 minutes by using 0.5% -1.0% calcium chloride solution;

5. The method for preparing a compound peptide product with sleep and brain health improving effects according to claim 2, wherein the ethanol solution temperature in step S3 is 2-8 ℃, and the amount is 18% -25% of the total weight of the material.

6. The method for preparing a compound peptide product with sleep and brain health improving effects according to claim 2, wherein the spray rate of the boiling granulation in step S4 is 100-300mL/min, and the atomization pressure is 0.8-1.2Bar.

7. The method for preparing a composite peptide product with sleep and brain health improving effects according to claim 2, wherein the tablet hardness in step S5 is 60-90N, and the difference in the capsule filling weight is controlled within ±5%.

8. The method for preparing a compound peptide product with sleep and brain health improving function according to claim 2, wherein the chitosan used in the step S2 has a deacetylation degree of not less than 85% and a viscosity of 50-200 mPa.s.