Use of corn oligopeptide in the preparation of a special medical-purpose formula food or drug for improving sarcopenia

Abstract

The present invention provides the use of corn oligopeptides in the preparation of a special medical-purpose formula food or drug for improving sarcopenia, belonging to the field of medical foods and drugs. The present invention discovers for the first time that corn oligopeptides can effectively improve sarcopenia. The experimental results show that after intervention with corn oligopeptides in an animal model of sarcopenia syndrome, compared with the model group, the grasping force and endurance of rats in the corn oligopeptide group are significantly improved, and the muscle coefficients of the gastrocnemius and plantar muscles of the rats are significantly increased (P<0.05). Corn oligopeptides have broad application prospects in the preparation of special medical-purpose formula foods or drugs for improving sarcopenia.

Description

Technical Field

[0001] The invention belongs to the field of medical food and medicine, and specifically relates to the use of corn oligopeptides in improving muscle attenuation. Background Art

[0002] Sarcopenia (SP) was first proposed by Professor Rosenberg IH of Tufts University in the United States in 1989. It is also known as sarcopenia, skeletal myopenia, and sarcopenia. It is a progressive, systemic, and comprehensive degenerative disease associated with aging, mainly manifested by a decrease in muscle quantity and quality and a decrease in function. According to statistics, 6% to 24% of the elderly aged 60 to 70 suffer from SP, and the prevalence rate of people over 80 years old exceeds 50%. In addition to affecting the structure and function of skeletal muscle, SP can also reduce the quality of life, increase the probability and frequency of hospitalization, increase the burden of care, and even increase the risk of death, seriously endangering the health of the elderly.

[0003] The etiology of SP has not been fully elucidated. It is currently believed to include the following aspects: (1) Aging-related muscle wasting. Aging-related muscle wasting is the most common muscle wasting, and aging can also become a high-risk factor for other causes of SP. Among the elderly, aging is the main basis for the onset of SP; (2) Insufficient exercise-related muscle wasting. Long-term inactivity such as long-term bed rest and long-term sitting can lead to a decrease in muscle mass and strength and even muscle atrophy, while proper exercise can prevent the occurrence of SP to a certain extent; (3) Disease-related muscle wasting, including organ failure such as heart, lung, liver, and kidney, muscle wasting related to inflammatory diseases, malignant tumors or endocrine diseases, and also includes denervation muscle wasting caused by peripheral nerve damage; (4) Nutrition-related muscle wasting. Nutritional absorption disorders caused by malabsorption, gastrointestinal dysfunction or drug-induced anorexia, such as insufficient intake of vitamins and protein, can all cause muscle wasting.

[0004] In addition to medication, nutritional supplementation is one of the main means to improve the nutritional status of the elderly, people who are bedridden for a long time, and people with sarcopenia. At present, both domestic and foreign countries advocate the use of special nutritional foods to improve the muscle attenuation of patients with sarcopenia. my country's "National Food Safety Standard General Rules for Special Medical Purpose Formulated Foods" (GB 29922-2013) stipulates that in order to meet the special needs of people with restricted food intake, digestion and absorption disorders, metabolic disorders or specific disease states for nutrients or diets, specially processed and prepared formula foods, namely special medical purpose formula foods, are divided into complete nutrition formula foods, specific complete nutrition formula foods and non-complete nutrition formula foods. However, complete nutrition formula foods need to be used as a single source of nutrition to meet the needs of the target population, and have strict requirements on the content of each nutrient. The special nutritional foods for sarcopenia that have been reported so far have complex ingredients.

[0005] For example, a Chinese patent application with the publication number CN113367349A discloses a composition for sarcopenia. The composition is composed of 20 - 35% whey protein, 20 - 35% soy protein isolate, 15 - 25% whey protein peptides, and 25 - 40% corn oligopeptides by weight. This composition can effectively treat or assist in treating patients with sarcopenia clinically, especially sarcopenia in the elderly over 60 years old in the central plains region of China. However, the mechanism of action for improving sarcopenia in this composition is not clear, and it has multiple components, high costs, and fixed combinations of multiple components, resulting in low flexibility in use.

[0006] Non - full - nutrition formula foods mainly include nutrient components, electrolyte formulas, thickening components, liquid formulas, and amino acid metabolism disorder formulas, etc. Among them, nutrient components include protein (amino acid) components, fat (fatty acid) components, and carbohydrate components; such foods can be used in combination with other foods under the guidance of a doctor or clinical dietitian according to the special conditions or needs of individual patients. They have simple components and high flexibility; therefore, if a non - full - nutrition formula food that can effectively improve sarcopenia can be explored, and then a doctor or clinical dietitian selects appropriate foods for combined consumption according to the metabolic characteristics and other special nutritional needs of the elderly, long - term bedridden patients, and patients with sarcopenia, it will be more targeted to improve the nutritional status and metabolic status of the elderly, long - term bedridden patients, and patients with sarcopenia, increase their protein synthesis, prevent muscle loss, and thus further prevent the development of chronic diseases, which will have important significance and application value for promotion. Summary of the Invention

[0007] The purpose of the present invention is to provide the use of corn oligopeptides in the preparation of a special medical purpose formula food or drug for improving sarcopenia.

[0008] The present invention provides the use of corn oligopeptides in the preparation of a special medical purpose formula food or drug for improving sarcopenia.

[0009] Furthermore, the special medical purpose formula food or drug can prevent and / or treat sarcopenia.

[0010] Furthermore, the special medical purpose formula food or drug can improve the grip strength of patients.

[0011] Furthermore, the special medical purpose formula food or drug can improve the endurance of patients.

[0012] Furthermore, the special medical purpose formula food or drug can increase the muscle coefficient.

[0013] Furthermore, the food for special medical purposes or the medicine can increase the muscle fiber diameter of muscles.

[0014] Furthermore, the muscle is one or more of gastrocnemius, soleus, tibialis anterior, and plantaris.

[0015] Furthermore, the muscle is one or two of gastrocnemius and plantaris.

[0016] Furthermore, the food for special medical purposes or the medicine is a preparation prepared with corn oligopeptide as the active ingredient and common excipients used in foods for special medical purposes or medicines.

[0017] Furthermore, the preparation is an oral preparation, and the oral preparation is preferably powder, decoction, oral liquid, granule, capsule, powder, pill, or tablet.

[0018] The weight-average molecular weight of the corn oligopeptide (Corn Oligopeptide, COP) is 282.4, and the proportion of the hydrolyzate with a relative molecular weight less than 1000 is 98.66%.

[0019] The corn oligopeptide of the present invention, also known as corn oligopeptide powder, is a powdery product mainly composed of oligopeptides with a relative molecular weight less than 1000, produced by an enzymatic (protease) hydrolysis method using corn protein as the raw material. The corn oligopeptide of the present invention complies with the standard of "corn oligopeptide powder" specified in the standard number QB / T 4707-2014 and the record number 46757-2014.

[0020] The present invention first discovers that corn oligopeptide can effectively improve muscle atrophy. The experimental results show that after the corn oligopeptide intervenes in the animal model of muscle atrophy syndrome, compared with the model group, the grasping force and endurance of the rats in the corn oligopeptide group are significantly improved, and the muscle coefficients of the gastrocnemius and plantaris of the rats are significantly increased (P<0.05). Corn oligopeptide has broad application prospects in the preparation of foods for special medical purposes or medicines for improving muscle atrophy.

[0021] The food for special medical purposes or the medicine for improving muscle atrophy syndrome provided by the present invention uses corn oligopeptide as the active ingredient, has a simple composition and low preparation cost, and is suitable for industrial production.

[0022] Obviously, based on the above content of the present invention, according to the common general technical knowledge and conventional means in the art, without departing from the above basic technical idea of the present invention, various other forms of modification, substitution, or change can also be made.

[0023] The following is a further detailed description of the above content of the present invention in the form of specific embodiments. However, this should not be construed as limiting the scope of the above subject matter of the present invention to the following examples. All technologies implemented based on the above content of the present invention fall within the scope of the present invention. Brief Description of the Drawings

[0024] Figure 1 . Weight change trends of the model control group and the blank control group.

[0025] Figure 2 . Effect of Dex on the grasping force of rats.

[0026] Figure 3 . Effect of Dex on the muscle coefficient of rats.

[0027] Figure 4 . Effect of corn oligopeptide on the weight gain trend of rats.

[0028] Figure 5 . Effect of corn oligopeptide on the grasping force of rats.

[0029] Figure 6 . Effect of corn oligopeptide on the endurance of rats: (A) Distance; (B) Time.

[0030] Figure 7 . Effect of corn oligopeptide on the muscle coefficients of the gastrocnemius and plantaris muscles of rats.

[0031] Figure 8 Effect of corn oligopeptide on muscle fibers of rats. Detailed Description of the Embodiments

[0032] The raw materials and equipment used in the present invention are all known products, obtained by purchasing commercially available products.

[0033] Example 1: Effect of corn oligopeptide on improving muscle atrophy

[0034] 1 Materials and Methods

[0035] 1.1 Test Samples

[0036] Corn oligopeptide: Purchased from Zhejiang Haishi Biotechnology Co., Ltd. The sample is light yellow to brownish yellow; powdery, without caking; has a unique taste and smell, and no foreign visible impurities.

[0037] The molecular weight distribution of the corn oligopeptide was investigated by gel permeation chromatography (GPC), and the results are as follows in the table:

[0038]

[0039]

[0040] It can be seen that the corn oligopeptide used in the present invention has a weight-average molecular weight of 282.4, and the proportion of hydrolysates with a relative molecular weight less than 1000 is 98.66%.

[0041] 1.2 Experimental animals

[0042] One hundred and forty-four 6-week-old SPF male SD rats were used. The distribution of rats in each group is shown in Table 1. They were housed in the SPF animal house of West China School of Public Health, Sichuan University. The animal house was kept quiet, clean, ventilated and with appropriate lighting. The temperature was 23 ± 2 °C, the humidity was 40% - 70%, and the light-dark cycle was 12 h. At the same time, the animals were allowed free access to water and sufficient food. The water and feed were sterilized, and the bedding was changed every 3 days (by high-pressure sterilization). Five animals were housed in each cage during the feeding period.

[0043] 1.3 Experimental methods

[0044] 1.3.1 Model establishment

[0045] After 3 days of adaptive feeding, 40 rats were randomly selected according to their body weights as the blank control group (abbreviated as CON group), and saline (0.5 mg / kg.bw) was injected daily. The remaining animals were intraperitoneally injected with dexamethasone (abbreviated as Dex) injection (1.0 mg / kg.bw) to establish an animal model of sarcopenia. The body weights were measured twice a week. The grasping force of the rats was measured 7 days and 14 days after model establishment. After 14 days, 8 rats from the CON group and the Dex group were collected to measure the muscle coefficient and muscle fiber diameter of the gastrocnemius, soleus, tibialis anterior, and plantaris muscles.

[0046] 1.3.2 Intervention with test substances

[0047] After the model establishment, according to the body weights of the animals, the model control group was randomly divided into 3 groups, namely the self-recovery group, the Dex group, and the Dex + COP dose group (2.0 g / kg.bw), with 32 rats in each group. The specific experimental methods are shown in Table 1.

[0048] Table 1. Experimental methods for intervention with test substances

[0049]

[0050] The body weights were measured twice a week. The grasping force of the rats was measured at 7 days, 14 days, 21 days, 28 days, and 35 days after the start of intervention in each group. The gastrocnemius, soleus, tibialis anterior, and plantaris muscles were collected at 14 days, 21 days, 28 days, and 35 days to measure the muscle coefficient and muscle fiber diameter. To determine whether corn oligopeptide has an improving effect on sarcopenia.

[0051] 2 Observation indexes

[0052] 2.1 Body weight

[0053] Weigh the rats once every two weeks to observe the weight gain trend and food intake of the rats.

[0054] 2.2 Grip strength test of rats

[0055] Measure the grip strength of the rats using a digital grip strength meter on the 7th day, 14th day of modeling, 14th day, 21st day, 28th day, and 35th day of intervention. The specific operation is as follows: After the rats adapt to the environment for 10 minutes, start the grip strength test. Let the rats grasp the metal pull rod of the digital grip meter, hold the rat's tail, and gradually pull backward until the rat releases the metal pull rod. The force at the moment of release is recorded as the maximum tension. Each rat is tested 5 times, and the interval between each test is 40 minutes.

[0056] 2.3 Endurance test of rats

[0057] The rats run on a 6-channel treadmill until exhaustion. The treadmill is set at a certain slope. The criterion for judging exhaustion is that the rats are not afraid of the electric shock at the end of the channel and lie prostrate without moving. The monitoring indicators are the running distance and time.

[0058] 2.3 Muscle wet weight and coefficient

[0059] On the 14th day of modeling, 14th day, 21st day, 28th day, and 35th day of intervention, weigh and record the gastrocnemius muscle, soleus muscle, tibialis anterior muscle, and plantaris muscle, and calculate the ratio of each muscle to the total body weight. Muscle coefficient = muscle wet weight / body weight.

[0060] 2.4 HE staining to measure muscle fiber diameter

[0061] On the 14th day of modeling, 14th day, 21st day, 28th day, and 35th day of intervention, perform HE staining on the muscles. Count the muscle fiber diameters of the gastrocnemius muscle, soleus muscle, tibialis anterior muscle, and plantaris muscle for each sample with 300 - 500 muscle fibers, and take the average value.

[0062] 3 Statistical methods and result determination

[0063] 3.1 Statistical methods

[0064] Use SPSS 20.0 software for data statistical analysis. Body weight, grip strength, muscle mass (gastrocnemius muscle, soleus muscle), muscle coefficient, and muscle fiber diameter are all measurement data, expressed as mean ± standard deviation If the data meet the normal distribution and homogeneity of variance, one-way ANOVA with a completely randomized design is used for statistical analysis. If P < 0.05, further pairwise comparisons between each dose group of the test substance and the model control group are performed using Dunnett-t. If the data do not meet the normal distribution and homogeneity of variance, appropriate variable transformations are carried out. After meeting the requirements of normality or homogeneity of variance, the transformed data are used for statistics; if the purpose of normality or homogeneity of variance is still not achieved after variable transformation, the rank sum test is used for statistics.

[0065] 3.2 Result determination

[0066] During the model establishment stage, if any one of the indicators of the grasping force, muscle coefficient, and muscle fiber diameter of the four muscles of the rats in the model control group decreases compared with those in the blank control group, and it is statistically significant, it is considered that the muscle atrophy syndrome model is successfully established;

[0067] During the intervention stage, if any one of the indicators of the grasping force, muscle coefficient, and muscle fiber diameter of the four muscles in the Dex+COP group increases compared with those in the Dex group, and it is statistically significant, it can be determined that corn oligopeptide has the effect of improving dexamethasone-induced muscle atrophy in rats.

[0068] 4 Experimental results

[0069] 4.1 Effect of Dex on the body weight growth trend of rats

[0070] As Figure 1 shown in and Table 2, intraperitoneal injection of Dex led to a decrease in the body weight of rats. From the 3rd day of model establishment to the end of model establishment, the body weight of the rats in the model control group decreased significantly compared with that in the blank control group (P<0.01).

[0071] Table 2. Comparison of body weight (g) between the model control group and the blank control group

[0072]

[0073] Note: Compared with the blank control group, * P<0.05, ** P<0.01.

[0074] 4.2 Effect of Dex on the grasping force of rats

[0075] As Figure 2 shown in and Table 3, at the beginning of model establishment, there was no difference in the grasping force between the blank control group and the model control group, but after the model establishment, the grasping force of the rats in the model control group decreased significantly compared with that in the blank control group (P<0.01).

[0076] Table 3. Effect of Dex on the grasping force of rats

[0077]

[0078] Note: Compared with the blank control group, ** P<0.01.

[0079] 4.3 Effect of Dex on the muscle coefficient of rats

[0080] As Figure 3As can be seen from Table 4, after the model was established, compared with the blank control group, the muscle fibers of the gastrocnemius, soleus, tibialis anterior, and plantar muscles of the rats in the model control group were all reduced, and the differences were statistically significant (all P < 0.05).

[0081] Table 4. Effects of Dex on the muscle coefficients of rats

[0082]

[0083] Note: Compared with the blank control group, * P < 0.05, ** P < 0.01.

[0084] 4.4 Effects of corn oligopeptides on the weight gain trend of rats

[0085] After 5 weeks of intervention with corn oligopeptides, generally, the body weights of the rats in each group showed an increasing trend. However, there was no significant difference in the body weight of the rats in the corn oligopeptide group compared with the Dex group (P > 0.05), as shown in Figure 4 and Table 5.

[0086] Table 5. Effects of corn oligopeptides on the body weight change (g) of rats

[0087]

[0088]

[0089] 4.5 Effects of corn oligopeptides on the grip strength of rats

[0090] In the third week of intervention with corn oligopeptides, compared with the Dex group, the grip strength of the rats in the corn oligopeptide group increased at 4 and 5 weeks (P < 0.05), Figure 5 , Table 6.

[0091] Table 6. Effects of corn oligopeptides on the grip strength of rats

[0092]

[0093] Note: Compared with the Dex group, * P < 0.05, ** P < 0.01.

[0094] 4.6 Effects of corn oligopeptides on the endurance of rats

[0095] The effects of corn oligopeptides on the endurance of rats were determined by the distance and time that the rats ran on the treadmill. The experimental results showed that after the intervention with corn oligopeptides, compared with the Dex group, the endurance of the rats was significantly improved (P < 0.05), as shown in Figure 6 , Table 7.

[0096] Table 7. Effects of corn oligopeptides on the endurance of rats

[0097]

[0098]

[0099] Note: Compared with the Dex group, * P < 0.05

[0100] 4.7 Effect of corn oligopeptide on muscle index of rats

[0101] As shown in Table 8, Figure 7 after 3 weeks of corn oligopeptide intervention, compared with the Dex group, the muscle indices of the gastrocnemius and plantaris muscles of rats were effectively increased (P < 0.05).

[0102] Table 8. Effect of corn oligopeptide on muscle index of gastrocnemius muscle of rats (%)

[0103]

[0104] Note: Compared with the Dex group, * P < 0.05

[0105] 4.8 Effect of corn oligopeptide on muscle fibers of rats

[0106] As shown in Table 9, Figure 8 after 5 weeks of intervention, under the microscope after HE staining ( Figure 8 A), it can be seen that the muscle fiber structures of the four muscles of the rats in the blank group are intact, and the muscle fiber cells are arranged neatly and closely. After 5 weeks of natural recovery in the self - recovery group of rats, the arrangement of muscle fiber cells in the gastrocnemius muscle is still relatively sparse, and the muscle fiber structures of the other three muscles are relatively intact. In the DEX group of rats, the muscle fibers of the four muscles are significantly thinner, the gap between muscle fibers increases, the arrangement of muscle fiber cells is not neat, and the structure is incomplete. After corn oligopeptide intervention, it can be seen that the muscle fiber structures of the four muscles of the rats are significantly restored, the muscle fiber cells are arranged closely, and the gap between muscle fibers is significantly reduced. As Figure 8 shown in B, compared with the rats in the DEX group, the cross - sectional area of the soleus muscle fibers of the rats in the DEX + corn oligopeptide group is significantly increased, and the difference is statistically significant (P < 0.05). Secondly, as Figure 8 shown in C, by statistically analyzing the distribution of the cross - sectional area (CSA) of the soleus muscle fibers, it is found that compared with the rats in the blank group, the number of thinner muscle fibers (CSA < 1500μm 2 ) in the DEX group of rats increases, and the number of thicker muscle fibers (CSA > 1500μm 2 ) decreases. Compared with the rats in the DEX group, the number of thicker muscle fibers (CSA > 2500μm 2 ) in the DEX + COP group of rats increases, and the number of thinner muscle fibers (CSA < 2500μm 2 ) decreases.

[0107] Table 9. Effects of corn oligopeptides on muscle fibers of soleus muscles in rats (μm 2 , n = 6, )

[0108] muscle blank group self - recovery group DEX group DEX + COP group soleus muscle 2251.40±310.50 1881.65±434.34 1519.70±232.79 <![CDATA[2289.40±466.05 * >

[0109] Note: Compared with the DEX group, * P < 0.05

[0110] The experimental results showed that by observing through HE staining method, it was found that the muscle fibers of rats in the DEX group were significantly thinned, the gap between muscle fibers increased, the arrangement of muscle fiber cells was irregular, and the structure was incomplete. After intervention with corn oligopeptides, it could be seen that the structure of muscle fibers in rats was significantly restored, the muscle fiber cells were arranged closely, and the gap between muscle fibers was significantly reduced. It indicated that the corn oligopeptides of the present invention could significantly improve the condition of muscle attenuation.

[0111] In summary, compared with the blank control group, the body weight of rats in the Dex group decreased significantly with the extension of the modeling time. At the end of modeling, the body weight and grasping force of rats in the Dex group decreased significantly, and the muscle coefficients of gastrocnemius, soleus, tibialis anterior, and plantaris muscles decreased, suggesting that the modeling was successful.

[0112] Corn oligopeptides were intervened for 35 days, and samples were taken at 14 days, 21 days, 28 days, and 35 days to observe the changes of various indicators at each time point. Two behavioral indicators (grasping force experiment, treadmill experiment) showed that compared with the Dex group, the grasping force and endurance of rats in the corn oligopeptide group were effectively improved. In addition, corn oligopeptides reversed the decrease in gastrocnemius muscle coefficient induced by Dex, indicating that both of them may have a certain improvement effect on muscle morphology and size, and it was further confirmed in the muscle pathological sections after 35 days of intervention.

[0113] The above experimental results showed that corn oligopeptides could effectively improve Dex-induced muscle atrophy in rats and could be used to prepare special medical use formula foods or drugs for improving muscle attenuation.

[0114] The present invention provides the use of corn oligopeptides in the preparation of special medical use formula foods or drugs for improving muscle attenuation. The present invention first found that corn oligopeptides could effectively improve muscle attenuation. The experimental results showed that after intervening in the animal model of muscle attenuation syndrome with corn oligopeptides, compared with the model group, the grasping force and endurance of rats in the corn oligopeptide group were significantly improved, the muscle coefficients of gastrocnemius and plantaris muscles of rats were significantly increased (P < 0.05), and it was also observed through HE staining under the microscope that the condition of muscle attenuation was significantly improved. Corn oligopeptides have broad application prospects in the preparation of special medical use formula foods or drugs for improving muscle attenuation.

Claims

1. Use of corn oligopeptide in the preparation of a special medical-purpose formulated food or medicine for improving grip strength, muscle coefficient and fiber diameter of muscle, characterized in that: The weight-average molecular weight of the corn oligopeptide is 282.4, and the proportion of the hydrolyzate with a relative molecular weight less than 1000 is 98.66%.

2. The use according to claim 1, wherein: The muscle is one or more of gastrocnemius, soleus, tibialis anterior, and plantaris.

3. The use according to claim 2, characterized in that: The muscle is one or two of gastrocnemius and plantaris.

4. The use according to any one of claims 1 to 3, characterized in that: The special medical purpose formula food or drug is a preparation prepared with corn oligopeptide as the active ingredient and the excipients commonly used in special medical purpose formula foods or drugs.

5. The use according to claim 4, wherein: The preparation is an oral preparation.

6. The use according to claim 5, wherein: The oral preparation is a decoction, granule, capsule, powder, pill, or tablet.

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