Imidazole dipeptide composition with improved sleep effect and application thereof

Abstract

The present application belongs to the technical field of biological medicine and functional food, and particularly relates to a compound composition for improving sleep and application thereof in related products. The imidazole dipeptide composition comprises the following components: imidazole dipeptide and taurine. The imidazole dipeptide is extracted from raw materials such as chicken breast by a specific process, and the process is stable, and the active ingredient is clear. Experiments show that the composition compounded by imidazole dipeptide and taurine in a scientific ratio has a significant synergistic effect on improving sleep, can promote the occurrence of sleep, and help improve sleep quality and maintain sufficient sleep. The composition has clear components, is safe and reliable, is suitable for developing various ordinary foods, health foods and medicines with sleep-improving function, and can be made into various dosage forms such as liquid, solid and semi-solid according to actual needs, and has good technical feasibility and broad market application prospect.

Description

Technical Field

[0001] This invention belongs to the fields of biomedicine and functional food technology, specifically relating to an imidazole dipeptide composition with sleep-improving effects and its applications. Background Technology

[0002] Insomnia is the most common sleep disorder in clinical practice, referring to a disruption of sleep continuity related to daytime complaints. It is characterized by the experience of insufficient sleep duration and / or poor sleep quality despite having sufficient sleep opportunities, negatively impacting daytime function. The three main symptoms are excessively short sleep duration, early awakening, and difficulty falling asleep. With the rapid economic development and increasingly fast pace of life in my country, people are experiencing significantly increased life and work pressures, leading to a rising incidence of sleep-related infectious diseases.

[0003] Insomnia is prevalent worldwide. On the one hand, long-term insomnia affects individuals' normal life and work, increasing the risk of various health problems such as chronic fatigue, memory loss, weakened immunity, cardiovascular damage, and metabolic disorders. Severe sleep deprivation can reduce patients' work efficiency and alertness, and may even lead to serious accidents causing huge losses. On the other hand, it creates a huge socioeconomic burden. With its increasingly chronic course, the number of insomnia patients and the incidence of insomnia are showing a year-on-year increasing trend, suggesting that clinicians should pay attention to the health, social, and economic problems caused by insomnia.

[0004] Currently, the main chemical drugs used in clinical treatment of sleep disorders include barbiturates, benzodiazepines, and non-benzodiazepines. These drugs have a rapid onset of action and a clear mechanism of action, but they are prone to causing a series of problems such as dependence and side effects.

[0005] Imidazole dipeptides, also known as histidine dipeptides, are endogenous dipeptides widely found in the skeletal muscle and brain tissue of various vertebrates. They mainly include anserine, carnosine, cetaneosine, and homocarnosine. Imidazole dipeptides possess a variety of physiological functions, primarily involving antioxidation, anti-aging, neuroprotection, diabetes treatment, liver protection, and uric acid reduction.

[0006] Taurine is a sulfur-containing semi-essential amino acid produced in the liver and kidneys of mammals. It is found in various organs, including the retina, brain, heart, and placenta. Taurine has a variety of physiological functions, such as anti-fatigue, anti-aging, memory improvement, and sleep enhancement. In recent years, it has been found that taurine has a bidirectional regulatory effect on sleep, and increased taurine levels have been observed in individuals with sleep disorders. Summary of the Invention

[0007] The purpose of this invention is to overcome the shortcomings of the prior art and provide an imidazole dipeptide composition with sleep-improving effects and its applications. In particular, this invention unexpectedly discovered that by combining imidazole dipeptide and taurine, a synergistic effect is achieved, which can promote sleep, improve sleep quality, and maintain sufficient sleep.

[0008] To achieve the above objectives, the technical solution adopted by the present invention is as follows: In a first aspect, the present invention provides an imidazole dipeptide composition having a sleep-improving effect, the imidazole dipeptide composition comprising, by weight, the following components: 100-400 parts imidazole dipeptide and 125-500 parts taurine.

[0009] Alternatively, in the above-mentioned imidazole dipeptide composition with sleep-improving effects, the imidazole dipeptide composition comprises the following components by weight: 150-250 parts imidazole dipeptide and 200-300 parts taurine.

[0010] Alternatively, in the above-mentioned imidazole dipeptide composition with sleep-improving effect, the imidazole dipeptide composition comprises the following components by weight: 200 parts imidazole dipeptide and 250 parts taurine.

[0011] Alternatively, in the above-mentioned imidazole dipeptide composition with sleep-improving effects, the preparation method of the imidazole dipeptide includes the following steps: S1. Mince the chicken breast; S2. Add an appropriate amount of water to the minced chicken breast, heat at 60-100℃ to extract, so that the solid and liquid are separated, and filtrate 1 is obtained. S3. Add activated carbon to filtrate 1, adsorb at 50-80℃, filter to remove activated carbon, and obtain filtrate 2. S4. Concentrate the filtrate 2 to obtain a concentrated solution. After sterilization and drying, the concentrated solution is obtained.

[0012] Alternatively, in the above-mentioned imidazole dipeptide composition with sleep-improving effects, the preparation method of the imidazole dipeptide includes the following steps: S1. Mince the chicken breast to 2-8mm; S2. Add 2-5 times the amount of water to the minced chicken breast, heat at 60-100℃ for 1-2 hours, filter to remove the residue, and obtain filtrate 1. S3. Add 1-2% activated carbon to filtrate 1, adsorb at 50-60℃ for 0.5-2h, filter to remove activated carbon, and obtain filtrate 2. S4. The filtrate 2 is concentrated under reduced pressure at 65-80℃ to obtain a concentrated solution. After sterilization and drying, the concentrated solution yields the imidazole dipeptide containing the imidazole dipeptide composition.

[0013] As a preferred technical solution of the present invention, the chicken breast meat in step S1 is sourced from white-feathered chickens, yellow-feathered chickens, and black-boned chickens aged 40-60 days.

[0014] As a preferred embodiment of the present invention, the amount of water in step S2 is 5 times.

[0015] As a preferred embodiment of the present invention, the temperature in step S2 is 85°C.

[0016] As a preferred embodiment of the present invention, the extraction time in step S2 is 1 hour.

[0017] As a preferred embodiment of the present invention, the amount of activated carbon used in step S3 is 2%.

[0018] As a preferred embodiment of the present invention, the temperature in step S3 is 55°C.

[0019] As a preferred embodiment of the present invention, the adsorption time in step S3 is 1 hour.

[0020] Alternatively, in the above-mentioned imidazole dipeptide composition with sleep-improving effects, the sum of the contents of anserine and carnosine in the imidazole dipeptide is 5%-20% by mass percentage.

[0021] Alternatively, in the above-mentioned imidazole dipeptide composition with sleep-improving effects, the mass ratio of anserine and carnosine in the imidazole dipeptide is (1.5-4):1.

[0022] Alternatively, in the above-mentioned imidazole dipeptide composition with sleep-improving effects, the taurine raw material can be commercially available, and can be high-purity taurine or food-grade raw material rich in taurine.

[0023] In a second aspect, the present invention provides the use of the imidazole dipeptide composition described in the first aspect above in the preparation of products having sleep-improving functions.

[0024] Alternatively, in the above applications, the product may include general food, health food, pharmaceuticals, cosmetics, or medical devices.

[0025] Alternatively, in the above applications, the product dosage form can be any one of liquid dosage form, gas dosage form, solid dosage form, or semi-solid dosage form.

[0026] The beneficial effects of the present invention are that it provides an imidazole dipeptide composition with sleep-improving effects, the composition comprising imidazole dipeptide and taurine, wherein the imidazole dipeptide and taurine have a synergistic effect, which can promote the occurrence of sleep, and also help improve sleep quality and maintain sufficient sleep, and can be used in the preparation of products with sleep-improving functions. Attached Figure Description

[0027] Figure 1 Experimental procedure for improving sleep efficacy.

[0028] Figure 2 Synergistic effect analysis of imidazole dipeptide and taurine using SynergyFinder 3.0. Detailed Implementation

[0029] To better illustrate the purpose, technical solution, and advantages of this invention, the invention will be further described below with reference to specific embodiments and comparative examples. The purpose of this description is to provide a detailed understanding of the invention, not to limit its scope. All other embodiments obtained by those skilled in the art without inventive effort are within the protection scope of this invention. Unless otherwise specified, the experimental reagents, raw materials, and instruments designed in the embodiments and comparative examples of this invention are all commonly used reagents, raw materials, and instruments.

[0030] Example 1: Preparation of imidazole dipeptide The preparation method of the imidazole dipeptide includes the following steps: S1. Mince chicken breast from 42-day-old white-feathered chickens to 2-8mm. S2. Add 5 times the amount of water to the minced chicken breast, heat at 85°C for 1 hour, filter to remove the residue, and obtain filtrate 1. S3. Add 2% activated carbon to filtrate 1, adsorb at 55℃ for 1 hour, filter to remove activated carbon, and obtain filtrate 2. S4. The filtrate 2 is concentrated under reduced pressure at 70°C to obtain a concentrated solution. After sterilization and drying, the concentrated solution yields the imidazole dipeptide.

[0031] The imidazole dipeptide contains 5%-20% anserine and carnosine by mass percentage, and the mass ratio of anserine to carnosine is (1.5-4):1.

[0032] Example 2: Experiment on the effect of improving sleep To evaluate the synergistic effect of the combination of imidazole dipeptide and taurine, a sleep-improving efficacy experiment was conducted on the combination of the two.

[0033] The imidazole dipeptide described in this embodiment was prepared according to Example 1, and the taurine was commercially available.

[0034] Zebrafish share up to 87% genetic similarity with humans, and many genes related to human sleep regulation function similarly in zebrafish. Their nervous system and physiological functions are, to some extent, similar to humans, exhibiting sleep-wake cycles similar to mammals, including similar stages of rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep. This makes zebrafish an effective model for studying human sleep. Zebrafish are small and live in water, facilitating large-scale behavioral observation and experimental manipulation. Video tracking systems can precisely record zebrafish activity over a specific period, such as swimming speed, distance, and activity frequency, to determine their sleep state. Generally, when zebrafish activity significantly decreases and their responses to stimuli weaken, they are considered to be in a sleep state.

[0035] Wild-type AB strain zebrafish (6 dpf) were randomly selected and placed in 12-well plates (3 replicates), with 10 fish per well and 3 mL of fluid per well. Three groups were established: a normal control group, a model group, and a sample group (concentrations shown in Table 1). Drug administration began at 22:00 and continued until 22:00 the following evening. Except for the normal control group, which underwent normal light-rhythm culture, all other experimental groups were subjected to 24 hours of light deprivation to establish a zebrafish insomnia model. After drug administration, each group was washed twice with embryo culture medium, and the zebrafish were transferred one per well to 48-well plates. 1 mL of embryo culture medium was added to each well, and all groups continued to be cultured under normal light-rhythm for another 24 hours. The sleep time of zebrafish over 10 hours was measured using an automated zebrafish behavior analysis system (ZebraLab 3.3, Viewpoint, France). The sleep improvement effect was calculated using the formula [Sleep improvement effect (%) = (Sleep time of model group - Sleep time of sample group) / (Sleep time of model group - Sleep time of normal group) × 100%]. The statistical analysis results of the above indicators were used to evaluate the sleep improvement efficacy of the samples. The experimental procedure is as follows: Figure 1 As shown.

[0036] Statistical results are expressed as mean ± SD. Statistical analysis was performed using GraphPad Prism 10.1.2 software, and p < 0.05 was considered statistically significant. The experimental results are shown in Table 1.

[0037] SynergyFinder, a standalone web application proposed in 2017, is used for interactive analysis and visualization of multidose combination response data (two or more drugs) and has been widely used to discover novel synergistic drug combinations. This invention uses the online website SynergyFinder 3.0 (https: / / synergyfinder.fimm.fi), selects the HSA model to calculate the synergy index, and assesses whether there is a synergistic effect when imidazole dipeptide and taurine are used together. A synergy index greater than 10 indicates a synergistic effect between the two drugs; a synergy index between -10 and 10 indicates an additive effect; and a synergy index less than -10 indicates an antagonistic effect. The analysis results are as follows: Figure 2 As shown.

[0038] Table 1. Experimental results evaluating the sleep-improving efficacy of the samples (n=5) Note: In the table above, compared with the control group, #### P <0.0001. Compared with the model group, P <0.05, P <0.01, P <0.001, P <0.0001.

[0039] As shown in Table 1, compared with the model group, taurine could prolong the sleep time of zebrafish with light-induced sleep deprivation, but the difference was not significant; imidazole dipeptide could significantly prolong the sleep time of zebrafish with light-induced sleep deprivation. P <0.05); while the combination of imidazole dipeptide and taurine can significantly prolong the sleep time of zebrafish with light-induced sleep deprivation. P <0.05).

[0040] like Figure 2As shown, the synergy index calculated using the online website SynergyFinder 3.0 (https: / / synergyfinder.fimm.fi) is 22.429, which is greater than 10. This indicates that the combination of imidazole dipeptide and taurine has a synergistic effect, which can promote the occurrence of sleep and also help improve sleep quality and maintain sufficient sleep.

[0041] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. An imidazole dipeptide composition having a sleep-improving effect, characterized in that, The imidazole dipeptide composition comprises the following components by weight: 100-400 parts imidazole dipeptide and 125-500 parts taurine.

2. The imidazole dipeptide composition with sleep-improving effects as described in claim 1, characterized in that, The imidazole dipeptide composition comprises the following components by weight: 150-250 parts imidazole dipeptide and 200-300 parts taurine.

3. The imidazole dipeptide composition with sleep-improving effects as described in claim 1, characterized in that, The preparation method of the imidazole dipeptide includes the following steps: S1. Mince the chicken breast; S2. Add an appropriate amount of water to the minced chicken breast, heat at 60-100℃ to extract, so that the solid and liquid are separated, and filtrate 1 is obtained. S3. Add activated carbon to filtrate 1, adsorb at 50-80℃, filter to remove activated carbon, and obtain filtrate 2. S4. Concentrate the filtrate 2 to obtain a concentrated solution. After sterilization and drying, the concentrated solution is obtained.

4. The imidazole dipeptide composition with sleep-improving effect as described in claim 1, characterized in that, The sum of the contents of anserine and carnosine in the imidazole dipeptide is 5%-20% by mass percentage.

5. The imidazole dipeptide composition with sleep-improving effect as described in claim 1, characterized in that, The mass ratio of anserine to carnosine in the imidazole dipeptide is (1.5-4):

1.

6. Use of the imidazole dipeptide composition of any one of claims 1 to 5 in the preparation of a product having sleep-improving function.

7. The application as described in claim 6, characterized in that, The products include general food, health food, pharmaceuticals, cosmetics, or medical devices.

8. The application as described in claim 6, characterized in that, The product dosage form is any one of liquid dosage form, gas dosage form, solid dosage form, and semi-solid dosage form.

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