Composition for promoting auditory sense system development and application
By combining IGF-1 with structural triglycerides in a specific ratio, the research gaps in the development of the auditory sensory system of OPO and OPL were addressed, significantly improving the auditory responsiveness and neurotransmitter content in zebrafish and promoting the development of the auditory sensory system.
Patent Information
- Application Number
- CN202511498573.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-10-20
- Publication Date
- 2025-12-26
AI Technical Summary
Existing technologies lack specific research on the role of OPO and OPL in promoting the development of the auditory sensory system in infants and young children, especially their effects on serotonin, acetylcholinesterase levels, and GABA receptor expression, which affect the development of the infant's auditory sensory system.
By combining IGF-1 with structural triglycerides (such as 1,3-dioleoyl-2-palmitoylglycerol and 1-oleoyl-2-palmitoyl-3-linoleoylglycerol) in a specific ratio, a composition is formed to promote the development of the auditory sensory system, increase the content of neurotransmitters, and enhance the survival and differentiation of neurons.
It significantly improved the movement speed and distance of zebrafish after auditory stimulation, increased the content of serotonin and acetylcholinesterase, and promoted the expression of GABA receptors, thereby promoting the development of the auditory sensory system.
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Figure CN121196166A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of food technology, and in particular to a composition and its application that promotes the development of the auditory sensory system. Background Technology
[0002] Insulin-like growth factor-1 (IGF-1) is a basic polypeptide cytokine with neurofunctional properties that plays a crucial role in the development and maturation of the central nervous system in infants and young children. IGF-1 promotes the development of auditory and sensory nerves by activating downstream signaling pathways of the IGF-1 receptor, driving the proliferation, differentiation, and synapse formation of neural progenitor cells.
[0003] 1,3-Dioleoyl-2-palmitoylglycerol (OPO) and 1-oleoyl-2-palmitoyl-3-linoleic acid triglyceride (OPL) in breast milk are two important structural triglycerides. Their molecular characteristics include palmitic acid at the sn-2 position, and unsaturated fatty acids (oleic acid or linoleic acid) distributed at the sn-1 and sn-3 positions. In OPO, the palmitic acid at the sn-2 position reduces the production of insoluble calcium soaps, thereby promoting the absorption of fats and minerals such as calcium and phosphorus in the infant's intestines and reducing constipation. In OPL, the linoleic acid at the sn-3 position participates in the construction and functional regulation of cell membranes during nervous system development. The synergistic effect of OPO and OPL not only provides infants with an efficient energy source but also contributes significantly to the "golden structure" of breast milk fat by improving support for the maturation of key physiological systems. It is worth noting that the OPL content in Chinese breast milk is significantly higher than that in OPO, while the opposite is true for breast milk in Europe and the United States. Therefore, conducting research on the synergistic ratio of OPO and OPL is of great significance for developing infant formula that is more suitable for the physique of Chinese babies.
[0004] Existing research shows that OPO and OPL can effectively improve calcium absorption, promote infant bone development, reduce soapy stools, and enhance infant gut comfort. However, no studies have yet found evidence regarding the effects of OPO or OPL on increasing serotonin (5-HT) and acetylcholinesterase levels, promoting γ-aminobutyric acid (GABA) receptor expression, or promoting the development of the auditory sensory system. Therefore, researching and exploring the specific relationships between them is of great significance. Summary of the Invention
[0005] In view of this, the present invention provides a composition and application for promoting the development of the auditory sensory system, which promotes the development of auditory sensory system by combining a specific amount of IGF-1 (insulin-like growth factor-1) with structural triglycerides.
[0006] To solve the above-mentioned technical problems, the technical solution provided by the present invention is as follows: In a first aspect, the present invention provides a composition for promoting the development of the auditory sensory system, comprising the following components in parts by weight: 0.1 parts of IGF-1 and 1 to 1500 parts of structural triglycerides.
[0007] Compared to existing technologies, the composition for promoting the development of the auditory sensory system provided by this invention improves the sensitivity of response to auditory or sensory stimuli by compounding a specific amount of IGF-1 with structural triglycerides. Furthermore, it supports the survival, differentiation, and synapse formation of auditory sensory neurons through important neurotransmitters in the auditory sensory system (such as serotonin, acetylcholine, and GABA), thereby regulating the excitability of the auditory sensory neural pathway and promoting the development of the auditory sensory system.
[0008] Preferably, the IGF-1 includes bovine milk IGF-1.
[0009] This invention does not impose any special limitations on the preparation method of bovine milk IGF-1; conventional operations in the field can be used.
[0010] Preferably, the structural triglyceride comprises 1,3-dioleoyl-2-palmitoyl triglyceride and 1-oleoyl-2-palmitoyl-3-linoleoyl triglyceride in a mass ratio of 1:(0.4~1.8).
[0011] More preferably, the structural triglyceride comprises 1,3-dioleoyl-2-palmitoyl triglyceride and 1-oleoyl-2-palmitoyl-3-linoleoyl triglyceride in a mass ratio of 1:(0.6~1.5).
[0012] More preferably, the mass ratio of the 1,3-dioleoyl-2-palmitoylglycerol to the 1-oleoyl-2-palmitoyl-3-linoleoylglycerol is 1:(0.8~1.2).
[0013] More preferably, the composition comprises the following components in parts by weight: 0.1 parts of IGF-1, 1 to 800 parts of 1,3-dioleoyl-2-palmitoylglycerol triglyceride, and 1 to 1000 parts of 1-oleoyl-2-palmitoyl-3-linoleoylglycerol triglyceride.
[0014] More preferably, the composition comprises the following components in parts by weight: 0.1 parts of IGF-1, 5 to 700 parts of 1,3-dioleoyl-2-palmitoylglycerol triglyceride, and 5 to 800 parts of 1-oleoyl-2-palmitoyl-3-linoleoylglycerol triglyceride.
[0015] The present invention does not impose any special limitations on the preparation method of the composition for promoting the development of the auditory sensory system; it is sufficient to mix the components evenly.
[0016] Secondly, the present invention provides the application of the composition for promoting the development of the auditory sensory system in the preparation of products that promote the development of the auditory sensory system.
[0017] Preferably, the product promoting the development of the auditory sensory system includes at least one of health food, special medical purpose formula food, infant formula food, or special dietary food.
[0018] More preferably, the product promoting the development of the auditory sensory system includes at least one of infant formula, children's formula, liquid milk, baby food, nutritional supplements, or dietary supplements.
[0019] Thirdly, the present invention provides a product for promoting the development of the auditory sensory system, comprising the aforementioned composition for promoting the development of the auditory sensory system and other substances.
[0020] Preferably, the other substances include at least one of proteins, carbohydrates, vitamins, or human milk oligosaccharides.
[0021] The present invention has the following beneficial effects: This invention provides a composition and its application for promoting the development of the auditory sensory system. The composition comprises bovine milk IGF-1, 1,3-dioleoyl-2-palmitoylglycerol, and 1-oleoyl-2-palmitoyl-3-linoleoylglycerol. Experimental results show that the composition provided by this invention, with its specific ratio, can significantly promote the development of the auditory sensory system in zebrafish through the synergistic effect of its components, increasing the movement speed and average distance traveled by zebrafish after auditory stimulation, increasing the content of serotonin and acetylcholinesterase in the zebrafish supernatant, and promoting the expression of the GABA receptor gene, thereby significantly promoting the development of the auditory sensory system in zebrafish. Attached Figure Description
[0022] Figure 1 This is a comparison chart of the swimming speeds of zebrafish in different groups after being stimulated by auditory stimulation in the efficacy test of this invention; Figure 2 This is a comparison chart of the swimming distances of zebrafish in different groups after being stimulated by auditory stimulation in the efficacy test of this invention; Figure 3 This is a comparison chart of GABA receptor expression levels in zebrafish from different groups during the efficacy test of this invention. Figure 4 This is a comparison chart of the 5-HT content in zebrafish from different groups during the efficacy test of this invention. Figure 5 This is a comparison chart of the acetylcholinesterase content in zebrafish from different groups during the efficacy test of this invention. In the figure, different letters indicate significant differences between the corresponding groups, P < 0.05. Detailed Implementation
[0023] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are for illustrative purposes only and are not intended to limit the invention.
[0024] In the embodiments and comparative examples of this invention, the method for preparing bovine milk IGF-1 includes the following steps: S1. Centrifuge fresh milk (to remove fat), adjust the isoelectric point of the resulting skim milk to 4.2, centrifuge again (to remove casein), and collect the whey; S2. While stirring, add a 35% saturated ammonium sulfate solution to the whey, let it stand at room temperature for 1 hour, then centrifuge (to remove impurities). Dialyze and concentrate the resulting supernatant to obtain IGF-1 containing a small amount of salt (i.e., the bovine milk IGF-1 in the embodiments and comparative examples of this invention).
[0025] Unless otherwise specified, all materials used in the embodiments and comparative examples of this invention are commercially available products.
[0026] To better illustrate the present invention, further examples are provided below.
[0027] Example 1 This embodiment provides a composition for promoting the development of the auditory sensory system, comprising bovine milk IGF-1, OPO, and OPL in a mass ratio of 0.1:2:0.8. The mass ratio of OPO to OPL is 1:0.4.
[0028] Example 2 This embodiment provides a composition for promoting the development of the auditory sensory system, comprising bovine milk IGF-1, OPO, and OPL in a mass ratio of 0.1:60:48. The mass ratio of OPO to OPL is 1:0.8.
[0029] Example 3 This embodiment provides a composition for promoting the development of the auditory sensory system, comprising bovine milk IGF-1, OPO, and OPL in a mass ratio of 0.1:10:10. The mass ratio of OPO to OPL is 1:1.
[0030] Example 4 This embodiment provides a composition for promoting the development of the auditory sensory system, comprising bovine milk IGF-1, OPO, and OPL in a mass ratio of 0.1:500:700. The mass ratio of OPO to OPL is 1:1.4.
[0031] Example 5 This embodiment provides a composition for promoting the development of the auditory sensory system, the components of which include bovine milk IGF-1 and OPO in a mass ratio of 0.1:10.
[0032] Example 6 This embodiment provides a composition for promoting the development of the auditory sensory system, the components of which include bovine milk IGF-1 and OPL in a mass ratio of 0.1:1.
[0033] Comparative Example 1 This comparative example provides a substance that promotes the development of the auditory sensory system, composed of bovine milk IGF-1.
[0034] Comparative Example 2 This comparative example provides a substance that promotes the development of the auditory sensory system, composed of OPO.
[0035] Comparative Example 3 This comparative example provides a substance that promotes the development of the auditory sensory system, composed of OPL.
[0036] Comparative Example 4 This comparative example provides a composition for promoting the development of the auditory sensory system, consisting of OPO and OPL in a mass ratio of 1:1.
[0037] Efficacy test Using zebrafish as the research subject, this study investigated the effects of different compositions / substances on the movement, GABA receptor gene expression, 5-HT content, and acetylcholinesterase content of zebrafish after stimulation.
[0038] Acetylcholine, GABA, and 5-HT are important neurotransmitters in the central nervous system, playing crucial roles in neuronal growth, differentiation, and synapse formation. In auditory perception, acetylcholine is a key excitatory neurotransmitter in the auditory pathway, related to auditory signal gain and auditory attention; GABA modulates the excitability of the auditory pathway, influencing auditory processing and emotional responses; 5-HT is the main inhibitory neurotransmitter in the auditory system, responsible for fine-tuning, frequency selection, and signal filtering, and is essential for auditory development. Zebrafish, with their transparent embryos, in vitro development, short reproductive cycle, and high egg production, offer several advantages for evaluating auditory sensory system development experiments, facilitating large-scale real-time observation and high-throughput screening.
[0039] 1. Animal testing and grouping Wild-type zebrafish (AB strain) were housed in transparent square or round aquariums under standard conditions. A blank control group and experimental groups were established. The zebrafish in the blank control group received no treatment, while the zebrafish in each experimental group received 2 wt% of the composition / substance in their feeding system. Specific grouping details are shown in Table 1. Individual zebrafish were selected for testing to minimize interference from group effects.
[0040] Wild-type AB strain zebrafish, 5 days post-fertilization (5 dpf), were randomly selected and placed in cell culture plates. For the startle response test, one zebrafish was placed in each well; for other tests, 30 zebrafish were placed in each well, with three replicates. An auditory startle response device was used to record the zebrafish's movement after auditory stimulation; movement speed and average distance traveled were used to quantify the startle response. One day after feeding, zebrafish samples were collected from each group. Total RNA was extracted from the zebrafish using a kit, and the expression level of the GABA receptor gene was detected by qPCR. The supernatant from the zebrafish samples was also collected, and the levels of 5-HT and acetylcholinesterase in each group were detected by ELISA. Results are expressed as mean ± standard deviation. Normality was tested using SPSS software. Data conforming to a normal distribution were considered statistically significant (P < 0.05).
[0041] Table 1 Grouping of each experimental group
[0042] 2. Experimental Results 2.1 Movement of Zebrafish The results of swimming speed and distance of each group of zebrafish after auditory stimulation are as follows: Figures 1-2 As shown in Table 2.
[0043] Table 2. Movement patterns of zebrafish in each group.
[0044] Note: In the table, different letters indicate significant differences between the corresponding groups, P < 0.05.
[0045] From Table 2 and Figures 1-2 It can be seen that, compared with the blank control group, experimental groups 1-10 significantly improved the swimming speed and distance of zebrafish after auditory stimulation. Among them, the experimental groups using the combination of milk IGF-1, OPO, and OPL (experimental groups 7-10) showed a significantly higher improvement in zebrafish movement than the other experimental groups (experimental groups 1-6). Experimental groups 9-10 (with a higher ratio of OPL to OPO) showed a more significant effect on improving the movement speed and distance of zebrafish after auditory stimulation, indicating that the IGF-1+OPO+OPL combination has a synergistic effect in promoting the development of the auditory sensory system in zebrafish.
[0046] 2.2 Expression level of GABA receptor gene in zebrafish The results of GABA receptor gene expression levels in each group of zebrafish are as follows: Figure 3 As shown in Table 3.
[0047] Table 3. GABA receptor gene expression levels in zebrafish from each group.
[0048] Note: In the table, different letters indicate significant differences between the corresponding groups, P < 0.05.
[0049] from Figure 3 As shown in Table 3, compared with the blank control group, all experimental groups significantly enhanced the expression of the GABA receptor gene. There were no statistically significant differences between experimental groups 1-3 and experimental groups 4-6. Experimental groups 7-10 (combination of bovine milk IGF-1, OPO, and OPL) were more effective in promoting the expression of the zebrafish GABA receptor gene than the single action of one of bovine milk IGF-1, OPO, and OPL or the combination of two of them (experimental groups 1-6). This indicates that the IGF-1+OPO+OPL composition provided by this invention has a synergistic effect in regulating the excitability of the auditory pathway.
[0050] 2.3 Zebrafish 5-HT content The results of 5-HT content in each group of zebrafish are as follows: Figure 4 As shown in Table 4.
[0051] Table 4. 5-HT content of zebrafish in each group
[0052] Note: In the table, different letters indicate significant differences between the corresponding groups, P < 0.05.
[0053] from Figure 4 As shown in Table 4, compared with the blank control group, all experimental groups significantly increased the 5-HT content of zebrafish. The experimental groups with the combined effects of milk IGF-1, OPO and OPL (experimental groups 7-10) showed better results. Among them, the zebrafish in experimental group 10 had the highest 5-HT content.
[0054] 2.4 Zebrafish acetylcholinesterase content The results of acetylcholinesterase content in each group of zebrafish are as follows: Figure 5 As shown in Table 5.
[0055] Table 5. Acetylcholinesterase content in zebrafish of each group.
[0056] Note: In the table, different letters indicate significant differences between the corresponding groups, P < 0.05.
[0057] from Figure 5As shown in Table 5, compared with the blank control group, all experimental groups significantly increased the acetylcholinesterase content of zebrafish. The experimental groups (experimental groups 7-10) with the combined action of milk IGF-1, OPO and OPL had better effects. Among them, the zebrafish in experimental group 10 had the highest acetylcholinesterase content.
[0058] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions or improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.
Claims
1. A composition for promoting the development of the auditory sensory system, characterized in that, The components include the following parts by weight: 0.1 parts of IGF-1 and 1 to 1500 parts of structured triglycerides.
2. The composition for promoting the development of the auditory sensory system as described in claim 1, characterized in that, The IGF-1 includes bovine milk IGF-1.
3. The composition for promoting the development of the auditory sensory system as described in claim 1, characterized in that, The structural triglycerides comprise 1,3-dioleoyl-2-palmitoyl triglyceride and 1-oleoyl-2-palmitoyl-3-linoleoyl triglyceride in a mass ratio of 1:(0.4~1.8).
4. The composition for promoting the development of the auditory sensory system as described in claim 3, characterized in that, The structural triglycerides comprise 1,3-dioleoyl-2-palmitoyl triglyceride and 1-oleoyl-2-palmitoyl-3-linoleoyl triglyceride in a mass ratio of 1:(0.6~1.5).
5. The composition for promoting the development of the auditory sensory system as described in claim 4, characterized in that, The mass ratio of 1,3-dioleoyl-2-palmitoylglycerol to 1-oleoyl-2-palmitoyl-3-linoleoylglycerol is 1:(0.8~1.2).
6. The composition for promoting the development of the auditory sensory system as described in claim 1 or 3, characterized in that, The composition comprises the following components in parts by weight: 0.1 parts of IGF-1, 1 to 800 parts of 1,3-dioleoyl-2-palmitoyl glycerol and 1 to 1000 parts of 1-oleoyl-2-palmitoyl-3-linoleoyl glycerol.
7. The use of the composition according to any one of claims 1 to 6 for promoting the development of the auditory sensory system in the preparation of products for promoting the development of the auditory sensory system.
8. The use of the composition for promoting the development of the auditory sensory system as described in claim 7 in the preparation of products for promoting the development of the auditory sensory system, characterized in that, The products that promote the development of the auditory sensory system include at least one of the following: health food, special medical purpose formula food, infant formula food, or special dietary food.
9. A product for promoting the development of the auditory sensory system, characterized in that, Includes the composition for promoting the development of the auditory sensory system as described in any one of claims 1 to 6 and other substances.
10. The product for promoting the development of the auditory sensory system as described in claim 9, characterized in that, The other substances include at least one of proteins, carbohydrates, vitamins, or human milk oligosaccharides.