Casein peptide-containing composition capable of improving sleep as well as preparation method and application of casein peptide-containing composition

Abstract

The invention discloses a casein peptide-containing composition capable of improving sleep as well as a preparation method and application of the casein peptide-containing composition. The casein peptide-containing composition comprises the following components: casein peptide nanoparticles which are prepared by an ultrasonic nanocrystallization technology; the multi-layer micro-capsule coating comprises a double-layer structure formed by natural polysaccharide and a lipid compound, so that the stability of casein peptide in gastrointestinal tracts is improved; an enzyme inhibitor for temporarily inhibiting the activity of pepsin to enhance the bioavailability of casein peptide; according to the casein peptide sleep-aiding composition, through the comprehensive technical design of multi-layer micro-capsule enveloping, nanocrystallization and enzyme inhibitor sheet layers, the stability, the bioavailability and the sleep-aiding effect of the casein peptide sleep-aiding composition are remarkably improved, and the casein peptide sleep-aiding composition shows superiority in the aspects of user experience and production feasibility.

Description

Technical Field

[0001] The invention belongs to the technical field of bioactive substance application and food health care products, and specifically relates to a composition containing casein peptides and having the function of improving sleep, and a preparation method and application thereof. Background Art

[0002] In recent years, with the accelerated pace of life and increased stress, insomnia and poor sleep quality have become more common, and the market demand for sleep-aid products has gradually increased. Casein peptides, as a bioactive peptide, are an ideal ingredient for improving sleep because of their natural, safe and non-addictive characteristics. Studies have shown that casein peptides can regulate the excitability of the central nervous system by promoting the secretion of neurotransmitters such as γ-aminobutyric acid (GABA) and serotonin, thereby achieving relaxation and sleep-aiding effects. However, the existing sleep-aid compositions containing casein peptides still have some technical difficulties in practical applications, which are mainly manifested in the following aspects:

[0003] Poor stability

[0004] Casein peptides are easily degraded in acidic environments such as gastric acid, making it difficult for them to maintain activity in the gastrointestinal tract. In addition, casein peptides are sensitive to temperature and humidity, and are easily affected by the environment during storage and transportation, and have poor stability. The activity of the active ingredients of traditional sleep-aiding compositions often decreases significantly after long-term storage, making it difficult to ensure the sleep-aiding effect of the product within its validity period.

[0005] Low bioavailability

[0006] Since casein peptide molecules are large and easily decomposed by proteases in the digestive tract, their absorption rate in the small intestine is low and their bioavailability is limited. In the prior art, the lack of absorption efficiency is often compensated by increasing the dosage, but this method will increase costs and may bring unnecessary gastrointestinal burden. Improving the absorption efficiency of casein peptides has always been a technical problem.

[0007] Short duration of action

[0008] Traditional casein peptide compositions are released quickly in the gastrointestinal tract and often fail to achieve a long-lasting sustained-release effect. As a result, the active ingredients that aid sleep are quickly absorbed or decomposed in a short period of time, making it difficult to maintain an effective concentration in the body for a long time, resulting in a short-lasting sleep-aiding effect and the need for frequent replenishment, which affects the user experience.

[0009] Gastrointestinal irritation

[0010] Some casein peptide compositions may cause some discomfort in gastric acid, especially for users with gastrointestinal sensitivity, which may cause mild gastrointestinal irritation. Traditional compositions lack gastrointestinal adaptability, which limits their application in sensitive populations.

[0011] In order to solve the above technical problems, existing studies have attempted to improve through methods such as microencapsulation technology, sustained-release dosage forms and absorption enhancers, but these methods still have certain limitations. For example, the existing single-layer coating technology is difficult to achieve ideal protection and sustained-release effects in the gastrointestinal tract, resulting in unstable release of sleep-aiding ingredients; at the same time, the absorption effect of the sleep-aiding composition is still limited, resulting in the inability to significantly improve bioavailability. Therefore, there is an urgent need for a new technical solution that can significantly improve the stability, bioavailability and sustained-release effect of casein peptides while ensuring their effectiveness, thereby providing a lasting sleep-aiding effect and meeting the market demand for efficient sleep-aiding products. Summary of the invention

[0012] In order to solve the problems raised in the above-mentioned background technology, the present invention provides a composition containing casein peptides that improves sleep, and a preparation method and application thereof. The present invention significantly improves the stability, bioavailability and sleep-aiding effect of the casein peptide sleep-aiding composition through the comprehensive technical design of multi-layer microcapsule coating, nano-sizing and enzyme inhibitor sheet layers, and shows superiority in user experience and production feasibility.

[0013] To achieve the above object, the present invention provides the following technical solutions:

[0014] A composition for improving sleep containing casein peptides, comprising the following ingredients:

[0015] Casein peptide nanoparticles: prepared by ultrasonic nanocrystallization technology;

[0016] Multilayer microcapsule coating: includes a double-layer structure formed by natural polysaccharide and lipid complex to improve the stability of casein peptides in the gastrointestinal tract;

[0017] Enzyme inhibitors: used to temporarily inhibit the activity of pepsin to enhance the bioavailability of casein peptides.

[0018] The inner layer of the multi-layer microcapsule coating contains a complex of chitosan and arabinose, which can be dissolved when the pH value of the intestinal tract is 6.8 or higher.

[0019] The outer layer of the multilayer microcapsule membrane contains a composite lipid of stearic acid glyceryl ester and palmitic acid glyceryl ester, which is used to maintain the stability of the casein peptide under different temperature and humidity conditions.

[0020] The enzyme inhibitor is a component selected from egg white powder or sunflower seed polypeptide, which is used to delay the degradation of casein peptide during digestion.

[0021] Wherein, the particle size range of the casein peptide nanoparticles is 50-200 nanometers.

[0022] The composition is of a sustained-release type and can gradually release casein peptides in the gastrointestinal tract to achieve a sustained sleep-aiding effect.

[0023] A method for preparing a sleep-improving composition containing casein peptides, comprising the following steps:

[0024] a) dissolving casein peptide in deionized water, adding phospholipid or silica nano-adjuvant, and performing ultrasonic treatment to prepare casein peptide nanoparticles;

[0025] b) suspending casein peptide nanoparticles in a complex polysaccharide solution of chitosan and arabinose, and cross-linking with sodium tripolyphosphate after emulsification to form an inner layer microcapsule;

[0026] c) encapsulating the inner layer microcapsules in a lipid layer of stearyl glyceryl and palmitic glyceryl, and forming an outer layer envelope by spray condensation;

[0027] d) suspending the double-layer microcapsules in a solution containing an enzyme inhibitor, and coating the enzyme inhibitor sheet by a roll coating process to obtain a finished product.

[0028] Wherein, the frequency of the ultrasonic treatment is 40kHz, and the treatment time is 10 to 15 minutes.

[0029] The cooling temperature of the spray condensation method is controlled at 10 to 15° C. to ensure the uniformity and stability of the outer coating.

[0030] The invention discloses an application of a sleep-improving composition containing casein peptides. The composition is used for preparing sleep-aiding food, health care products or medicines to improve sleep quality, shorten the time to fall asleep and prolong the time of deep sleep.

[0031] Compared with the prior art, the present invention has the following beneficial effects:

[0032] 1. Significantly improved stability

[0033] Traditional casein peptide sleep-aiding compositions are usually affected by gastric acid and the external environment, resulting in easy degradation of active ingredients and poor storage stability. However, the present invention uses multi-layer microcapsule coating technology (including a chitosan-arabinose composite inner layer and a stearic acid glyceryl-palmitic acid glyceryl composite outer layer) to effectively isolate the invasion of moisture and acidic substances, greatly extending the shelf life of casein peptides. The double-layer coating structure provides physical protection, allowing the product to maintain a high level of activity stability under conditions of high temperature and humidity.

[0034] 2. Bioavailability is significantly improved

[0035] In the prior art, the bioavailability of casein peptides is low, and usually a higher dose is required to achieve the desired effect. The present invention reduces the diameter of casein peptide particles to about 100 nanometers through nano-processing, significantly increasing the specific surface area, thereby promoting rapid absorption in the small intestine. At the same time, the present invention innovatively adds an enzyme inhibitor sheet, which can inhibit protease activity in the stomach, reduce the degradation of casein peptides in the stomach, and increase the proportion of effective ingredients entering the small intestine, thereby improving bioavailability. Compared with traditional compositions, the absorption efficiency of the casein peptides of the present invention is increased by about 1.5 times, so that the same sleep-aiding effect can be achieved at a low dose.

[0036] 3. The sleep-aiding effect is more lasting and significant

[0037] The present invention designs a multi-layer coating sustained-release mechanism, so that the casein peptide is gradually released in the small intestine, thereby maintaining an effective concentration in the body for a long time. This sustained-release design ensures that the casein peptide can play a sleep-aiding role in the body for a long time, not only helping to fall asleep faster, but also prolonging deep sleep time. Compared with the prior art, the sustained-release composition of the present invention has significantly improved effects in shortening the time to fall asleep and prolonging the duration of deep sleep.

[0038] 4. Improvement of gastrointestinal adaptability and user experience

[0039] Traditional casein peptide products may cause discomfort in the gastric acid environment, but the double-layer coating structure and enzyme inhibitor sheet in the present invention can effectively isolate the casein peptide from direct contact with gastric acid, significantly reducing gastrointestinal irritation. This design not only reduces gastrointestinal discomfort after taking, but also avoids the early decomposition of casein peptides in the stomach, making the product more suitable for long-term use and improving the overall user experience.

[0040] 5. The preparation process is highly feasible and has a wide range of applications

[0041] The nano-encapsulation, microencapsulation and roll-coating coating technologies used in the present invention have simple processes and low production costs, and are suitable for industrial large-scale production. In addition, the sustained-release characteristics and stability design of the composition make it suitable for daily sleep-aiding health care products and can also be expanded to the field of medicines that require long-term release. The multi-dosage design of the product meets the needs of different consumers and helps to expand the scope of market application.

[0042] In summary, the present invention significantly improves the stability, bioavailability and sleep-aiding effect of the casein peptide sleep-aiding composition through the comprehensive technical design of multi-layer microcapsule coating, nano-ization and enzyme inhibitor sheet, and shows superiority in user experience and production feasibility. Compared with the prior art, the present invention provides an efficient, stable and user-friendly sleep-aiding composition with significant application value and market potential. DETAILED DESCRIPTION

[0043] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0044] The present invention provides a sleep-improving composition containing casein peptides and a preparation method thereof, which effectively improves the stability and absorption efficiency of casein peptides in vivo by adopting a multi-layer microencapsulation coating and an enzyme inhibitor design, thereby achieving the purpose of improving sleep. The present invention aims to overcome the problems of poor stability and low bioavailability of existing casein peptide sleep-aiding compositions.

[0045] Example 1: Preparation of a composition for improving sleep

[0046] Nano-pretreatment of casein peptides

[0047] Materials: casein peptide, deionized water, phospholipids or silicon dioxide (as nano-additive).

[0048] Steps: Dissolve casein peptide in deionized water to form a 10 mg / mL solution. Subsequently, add 0.5% (w / v) phospholipid or silica as a nano-adjuvant. Use an ultrasonic processor (40kHz, 15 minutes) to nano-treat the solution to reduce the casein peptide particle size to about 100 nanometers. This process helps to increase the specific surface area of ​​the casein peptide, thereby improving its bioavailability.

[0049] The nano-processed casein peptide has a small particle size, which can significantly increase its adhesion and permeability to the small intestinal epithelial cells, thereby improving absorption efficiency. In addition, the smaller particle size allows the casein peptide to be packaged in microcapsules more efficiently, further reducing its contact with air and moisture during processing and storage, and improving stability.

[0050] Nano-processing can effectively increase the specific surface area of ​​casein peptide particles, making them easier to absorb after entering the gastrointestinal tract. The high-frequency vibration generated by ultrasound can break up the agglomeration of particles, making the casein peptide solution more uniform and stable, providing good conditions for subsequent microencapsulation.

[0051] Inner microencapsulation coating

[0052] Materials: chitosan (0.5%, w / v), arabinose (0.5%, w / v), sodium tripolyphosphate (as a cross-linking agent).

[0053] Steps: Chitosan and arabinose are dissolved in deionized water, and the pH of the solution is adjusted to 5.5 to form a stable emulsion. Then, the nanosized casein peptide particles are slowly added to the chitosan-arabinose solution and stirred evenly to form an emulsion. The emulsion is slowly dripped into a crosslinker solution containing sodium tripolyphosphate by titration to form an inner microcapsule structure under crosslinking, and then the inner microcapsule is dried at 40°C.

[0054] After nano-sizing, casein peptides have a smaller particle size. If directly exposed to gastric acid, they are easily decomposed quickly, affecting their sleep-inducing effect. The chitosan-arabinose composite coating can provide effective protection in gastric acid, avoiding the degradation of casein peptides. When the microcapsules enter the small intestine, due to the high pH of the small intestine environment, the inner coating gradually dissolves, thereby releasing the casein peptides and promoting their absorption in the small intestine.

[0055] Chitosan-arabinose complex has good biocompatibility and can dissolve in the alkaline environment of the intestine (pH 6.8 and above), thereby achieving directional release of casein peptides. By using sodium tripolyphosphate as a cross-linking agent, the bonds between chitosan molecules can be stabilized to form a stable inner layer structure, thereby improving the tolerance of casein peptides in gastric acid.

[0056] Outer lipid envelope

[0057] Ingredients: Glyceryl Stearate, Glyceryl Palmitate.

[0058] Steps: Stearic acid glyceryl and palmitic acid glyceryl are mixed in a ratio of 1:0.5 and heated at 70°C until completely melted. The dried inner microcapsules are added to the molten lipid solution for encapsulation. The spray condensation method (cooling temperature is controlled at 10-15°C) is used to quickly encapsulate the lipids on the surface of the microcapsules to form an outer membrane structure.

[0059] The outer lipid coating has good temperature tolerance and moisture isolation, which can further protect casein peptides from moisture and acidic substances in the environment. Especially in the stomach, the outer coating can effectively prevent casein peptides from contacting gastric acid, allowing them to pass through the stomach stably and gradually degrade and release active ingredients when entering the small intestine. This "slow-release" property allows casein peptides to be continuously released in the small intestine for a longer period of time, providing a sleep-aiding effect.

[0060] The outer layer of stearic acid glyceryl and palmitic acid glyceryl composite coating can provide stable protection under different temperature and humidity conditions. The presence of the lipid layer reduces the direct contact between water molecules and casein peptides, further extending the shelf life of the product. The outer coating effectively delays the release of casein peptides by controlling the permeability and moisture content of the environment, ensuring that it remains stable in the stomach and does not degrade prematurely.

[0061] Enzyme inhibitor sheet coating

[0062] Ingredients: Egg white powder or sunflower seed peptide (as enzyme inhibitor).

[0063] Steps: suspend the double-layer microcapsules in a solution containing 0.2% (w / v) egg white powder or sunflower seed polypeptide, stir evenly, then use a roller coating process to evenly wrap the enzyme inhibitor on the surface of the double-layer microcapsules, and dry at 50°C to form an enzyme inhibition sheet.

[0064] The enzyme inhibitor sheet mainly inhibits the activity of pepsin and trypsin, allowing casein peptides to reach the small intestine more intact and be effectively absorbed. Specifically, when the enzyme inhibitor comes into contact with the protease in the stomach, it will bind to its active site, thereby reducing the activity of the protease and reducing the premature decomposition of the casein peptide. At the same time, the presence of the enzyme inhibitor sheet can protect the integrity of the casein peptide throughout the gastrointestinal tract, allowing its concentration in the small intestine to be maintained for a longer time, thereby enhancing the sleep-aiding effect.

[0065] Egg white powder and sunflower seed peptides contain natural protease inhibitors that can temporarily inhibit the activity of pepsin and trypsin, thereby protecting casein peptides from premature decomposition. This inhibitory effect effectively improves the effective absorption of casein peptides in the small intestine and increases bioavailability.

[0066] Example 2: Use of a composition for improving sleep

[0067] The composition is used for preparing sleep-aiding food, health-care products or medicines to improve sleep quality, shorten sleep-onset time and prolong deep sleep time.

[0068] Usage: Users take the composition 30 minutes before going to bed at night. The recommended dosage is 1-2 grams each time.

[0069] Effect verification: After taking it for 2 weeks in a row, it can be observed that the user's sleep time is significantly shortened, the frequency of night awakenings is reduced, and the proportion of deep sleep is increased.

[0070] As a bioactive peptide, casein peptide inhibits the excitability of the central nervous system by binding to GABA receptors, promotes serotonin secretion, and produces a relaxing and hypnotic effect. In addition, the lipid and polysaccharide coating technology in the formula helps the sustained release of casein peptide, making its effect more lasting.

[0071] Example 3: Stability and bioavailability testing

[0072] Stability test: The sleep-improving composition was stored at 37°C (relative humidity 75%) for 30 days to detect the activity changes of casein peptides. The results showed that the double-layer coating structure could maintain more than 90% of the activity of casein peptides, which was significantly better than the control group without coating (the activity retention rate was only 60%).

[0073] Bioavailability experiment: In a rat model, the absorption efficiency of the composition of the present invention and conventional casein peptides was compared. Within 2 hours after taking, the casein peptide concentration of the composition of the present invention in plasma was 1.5 times that of the control group, indicating that the composition effectively improved the bioavailability of casein peptides.

[0074] Experiments have verified that multi-layer microencapsulation and enzyme inhibition sheets can significantly prolong the action time of casein peptides in the body and increase their effective concentration. At the same time, the lipid layer forms a protective layer in gastric acid, avoiding premature degradation of casein peptides and further increasing the absorption in the small intestine.

[0075] Example 4: Comparative experiment on sleep-aiding effect

[0076] A comparative experiment was conducted among 30 volunteers, who continuously took the sleep-improving composition and casein peptide tablets without enzyme inhibitors and microcapsule coating. The results showed that the average time to fall asleep in the experimental group taking the composition of the present invention was shortened by 15 minutes, and the deep sleep increased by more than 20%, while the control group only achieved a slight improvement.

[0077] Result analysis: The combined design of double-layer coating and enzyme inhibitor sheet ensures the slow release of casein peptide in the body and longer sleep-aiding effect, effectively improving the user's sleep quality.

[0078] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A composition for improving sleep containing casein peptide, characterized in that: Includes the following ingredients: Casein peptide nanoparticles: prepared by ultrasonic nanocrystallization technology; Multilayer microcapsule coating: includes a double-layer structure formed by natural polysaccharide and lipid complex to improve the stability of casein peptides in the gastrointestinal tract; Enzyme inhibitors: used to temporarily inhibit the activity of pepsin to enhance the bioavailability of casein peptides.

2. The composition for improving sleep according to claim 1, characterized in that: The inner layer of the multi-layer microcapsule coating comprises a complex of chitosan and arabinose, and can be dissolved when the pH value of the intestinal tract is 6.8 or higher.

3. The composition for improving sleep according to claim 1 or 2, characterized in that: The outer layer of the multi-layer microcapsule coating contains a composite lipid of stearic acid glyceryl ester and palmitic acid glyceryl ester, which is used to maintain the stability of casein peptide under different temperature and humidity conditions.

4. The composition for improving sleep according to claim 3, characterized in that: The enzyme inhibitor is a component selected from egg white powder or sunflower seed polypeptide, and is used to delay the degradation of casein peptide during digestion.

5. The composition for improving sleep according to claim 3, characterized in that: The particle size of the casein peptide nanoparticles ranges from 50 to 200 nanometers.

6. The composition for improving sleep according to claim 3, characterized in that: The composition is of a sustained-release type and can gradually release casein peptides in the gastrointestinal tract to achieve a continuous sleep-aiding effect.

7. A method for preparing a sleep-improving composition containing casein peptides, characterized in that: The following steps are involved: a) dissolving casein peptide in deionized water, adding phospholipid or silica nano-adjuvant, and performing ultrasonic treatment to prepare casein peptide nanoparticles; b) suspending casein peptide nanoparticles in a complex polysaccharide solution of chitosan and arabinose, and cross-linking with sodium tripolyphosphate after emulsification to form an inner layer microcapsule; c) encapsulating the inner layer microcapsules in a lipid layer of stearyl glyceryl and palmitic glyceryl, and forming an outer layer envelope by spray condensation; d) suspending the double-layer microcapsules in a solution containing an enzyme inhibitor, and coating the enzyme inhibitor sheet layer by a roll coating process to obtain a finished product.

8. The preparation method according to claim 7, characterized in that: The frequency of the ultrasonic treatment is 40 kHz, and the treatment time is 10 to 15 minutes.

9. The preparation method according to claim 7, characterized in that: The cooling temperature of the spray condensation method is controlled at 10 to 15° C. to ensure the uniformity and stability of the outer coating.

10. An application of a composition for improving sleep containing casein peptides, characterized in that: The composition is used for preparing sleep-aiding food, health-care products or medicines to improve sleep quality, shorten sleep-onset time and prolong deep sleep time.