Use of carrageenan in pediatric medications or medical food vehicles

Abstract

The present application provides the application of carrageenan with a particle size of 40-60 mu m in children's medicine or special medical food carriers. The present application also provides a preparation process of carrageenan with a particle size of 40-60 mu m, and the present application further provides a children's medicine or special medical food gel. The present application uses carrageenan with a particle size of 40-60 mu m to prepare special medical food, which can meet the requirements of the international dysphagia food framework IDDSI classification standard for the sixth level, and can also be used to prepare children's medicine gel. Not only can the deficiency of the gel performance of carrageenan particles be solved, and the complex process research required by chemical modification or compounding and other methods be reduced, but also the application potential of carrageenan as a food matrix can be developed, and the application range of carrageenan in the fields of food and biological medicine can be widened.

Description

TECHNICAL FIELD

[0001] The present application relates to the application of carrageenan in pediatric drugs or special medical food carriers, and belongs to the field of food and drugs. BACKGROUND

[0002] Carrageenan (Car), also known as carrageenan, kelp gum, etc., is a high molecular weight anionic sulfate linear polysaccharide composed of galactose-3,6 endosulfuric galactose disaccharide units. It is a hydrophilic colloid extracted from red algae such as eucheuma, kelp, etc. The combination form of sulfate ester in carrageenan is diverse, and it is divided into κ-, ι-, λ-, ν-, μ-, ζ-, θ-, and ω-carrageenan according to the different combination modes. Among them, κ-, ι-, and λ-types are the main types used in industrial production. Carrageenan has solubility, gelling, thickening, rheological, stability, synergy, and other physicochemical properties, and also has immunomodulatory, anticoagulant, antioxidant, and anticancer biological activities, and is widely used in food, medicine, chemical industry, energy and environmental protection, etc. In recent years, carrageenan has become a research hotspot in the fields of food and medicine due to its biocompatibility, biodegradability, gel properties, and other multifunctional properties, as well as its biological properties such as antiviral, antibacterial, antihyperlipidemia, anticoagulation, antitumor, and immunomodulation, and has great application potential and development prospects.

[0003] κ-carrageenan and ι-carrageenan can be cross-linked with K + and Ca 2+ ions to form brittle gels, and the gel formation mechanism is to form a three-dimensional double helix network through cross-linking of adjacent sulfate groups (Zheng, R. F., Wang, X. J., Wu, Q. Y., et al. Carrageenan gel water retention mechanism and its application research [J]. Food Safety Guide, 2022, (08): 186-188. DOI: 10.16043 / j.cnki.cfs.2022.08.066.). However, the special composition of carrageenan leads to the formation of hard and brittle gels by carrageenan alone, which is easy to release water during storage, which not only reduces its acceptance, but also affects its quality. In addition, the high hardness of the carrageenan gel alone makes it not friendly to consumers such as children, the elderly, and patients with difficulty swallowing, thereby limiting or reducing its application range. At present, modification or compounding methods are often used to improve the gel properties of carrageenan. However, the modification or compounding method is relatively complex, and different process researches are usually needed for different products or needs, which is time-consuming and laborious, and the research results are not universal.

[0004] In recent years, interdisciplinary research has focused more on particle size, which helps to explore the relationship between the micro and macro properties of various materials. The size of the particle size will affect the characteristics of its polymer material, including texture, taste, overall appearance and function. For example, both micron and nano starch can improve the breaking force, elasticity and water holding capacity of fish myofibrillar protein, and the effect of nano is more significant than that of micron (Effect of micro-and nano-starch on the gel properties, microstructure and water mobility of myofibrillar protein from grass carp), and the difference is due to the nanoscale effect and different microstructure of the gel. However, the current research on carrageenan modification is mainly focused on chemical modification and surface modification, and there is no research on the particle size of carrageenan. SUMMARY

[0005] The present application is based on the study of the particle size of carrageenan, and it is found that the change of the particle size of carrageenan will affect the performance and microstructure of the prepared gel. The present application provides a new use of carrageenan with a specific particle size, specifically, the application in children's medicine or special medical food carrier, and the present application also provides a preparation process of carrageenan with a specific particle size, and a children's medicine gel or special medical food containing carrageenan.

[0006] The present application provides the application of carrageenan with a particle size of 40-60 μm in children's medicine or special medical food carrier.

[0007] Among them, the particle size of the carrageenan is 50 μm ± 3 μm; the carrageenan includes but is not limited to the following types: kappa-, iota-, lambda-, nu-, mu-, zeta-, theta-, and omega-carrageenan.

[0008] Among them, the special medical food refers to a swallowing disorder functional food, which is classified as the 6th level according to the international swallowing disorder food framework IDDSI classification standard.

[0009] The present application also provides a preparation process of carrageenan with a particle size of 40-60 μm, which comprises the following steps: placing 600 g of carrageenan and 15% of silicon dioxide in a vibrating mill hopper, and crushing for 60 min by a vibrating mill to obtain micronized carrageenan with a particle size of 40-60 μm.

[0010] In the process of pulverizing carrageenan, it is found that the particle size of carrageenan powder is easily pulverized in the first 30 minutes of pulverizing time, and the d(0.9) particle size is halved every 10 minutes of prolonging the pulverizing time. However, if the pulverizing time is continuously prolonged, the d(0.9) of the powder changes little, and the d(0.9) particle size is reduced in the range of 2-8 μm every 10 minutes of prolonging the pulverizing time in the last 30 minutes. In addition, if grinding aids such as silicon dioxide are added during the pulverizing process, the particle size expected by the present application can be achieved.

[0011] The present application provides a kind of children's medicine or special medical food gel, which is prepared from CaCl2 or KCl, carrageenan with particle size of 40-60 μm, water, and then adding food or drug raw materials, wherein the amount of CaCl2 in 100 ml water is 0.05-0.1 g, and the amount of carrageenan with particle size of 40-60 μm is 0.5-1 g.

[0012] Further preferably, the amount of CaCl2 in 100 ml water is 0.1 g, and the amount of carrageenan with particle size of 40-60 μm is 1.0 g.

[0013] Preferably, the particle size of the carrageenan is 50 μm±3 μm.

[0014] Preferably, the food includes milk powder, starch and other protein-containing foods; and the drug includes notoginseng total saponins and rhizoma coptidis and other cation-containing drugs.

[0015] The present application also provides a preparation method of the children's medicine or special medical food gel, which comprises the following steps:

[0016] a. dissolving CaCl2 in water to prepare a CaCl2-containing solution;

[0017] b. adding carrageenan with particle size of 40-60 μm, stirring at 80°C until dissolved, then adding the raw materials of food or drug, stirring and dissolving until uniform, and cooling to room temperature to obtain the gel.

[0018] The dysphagia functional food should have the following texture characteristics: ① it should have certain cohesiveness (the ability of food crumbs to combine with each other and form a food mass that is easy to swallow after being crushed), and food with poor cohesiveness is not conducive to forming, is easy to disperse, and is prone to residual in the pharynx, thus increasing the risk of aspiration; ② it should have appropriate adhesiveness. When the adhesiveness of food is too high, the risk of pharyngeal residue is also increased; ③ it should have certain hardness and deformation ability. The food mass formed after chewing should be easy to deform (smoothly pass through the oral cavity and pharynx); and ④ the solid food should have uniform density. The food state and nutrition required by patients with different severity are quite different.

[0019] The present application adopts carrageenan with a particle size of 40-60 μm to prepare a special medical food, which can meet the requirements of the international dysphagia food framework IDDSI guide classification standard of the sixth level, and can also be applied to prepare a drug gel for children. Not only can the deficiency of the gel performance of the carrageenan particles be solved, and the complex process research required by chemical modification or compounding and other methods be reduced, but also the application potential of the carrageenan particles as a food matrix can be developed, and the application range of the carrageenan particles in the fields of food and biological medicine can be widened. Compared with the original powder carrageenan, the hardness of the carrageenan gel with a particle size of 40-60 μm is significantly reduced, and is reduced by 72.52% at a dosage of 1%. The water holding capacity of the carrageenan gel with a particle size of 40-60 μm under low temperature and long-term storage conditions is improved, and the swallowing performance and bitterness inhibition effect are obviously improved. BRIEF DESCRIPTION OF DRAWINGS

[0020] Figure 1 Particle size distribution diagrams (A and B), SEM diagrams (C: A1-A2: C, B1-B2: 20, C1-C2: 40, D1-D2: 60), FTIR diagrams (D), specific surface area and isotherm diagrams (E and F) of carrageenan powders with different grinding times;

[0021] Figure 2 TSI (A and B) of four particle size carrageenan powders, transmission light curve and sample display diagram (C-F: C, 20, 40 and 60);

[0022] Figure 3 Frequency scanning of blank gels of four particle size carrageenans: storage modulus (G') (A) and loss modulus (G") (B), steady-state viscosity curve (C), and temperature scanning test: storage modulus (G') (D and F) and loss modulus (G") (E and G);

[0023] Figure 4 WHC of blank gels, milk gels and total saponins of notoginseng gels of four particle size carrageenans (A, C, E are low temperature conditions; B, D, F are high temperature conditions), and T2 relaxation time distribution diagram (G) of blank gels of four particle size carrageenans;

[0024] Figure 5 SEM diagrams of blank gels (A-D), milk gels (E-H) and total saponins of notoginseng gels (I-L) of blank gels, milk gels and total saponins of notoginseng gels of four particle size carrageenans;

[0025] Figure 6 Taste and bitterness score results of milk gels (A) and total saponins of notoginseng gels (B) of four particle size carrageenans;

[0026] Figure 7 IDDSI test and classification results of blank gels of four particle size carrageenan gels;

[0027] Figure 8 IDDSI test and classification results of 4 particle size carrageenan milk gels;

[0028] Figure 9 IDDSI test and classification results of 4 particle size carrageenan panax notoginseng total saponin gels. DETAILED DESCRIPTION

[0029] Example 1 Preparation process of 40-60 μm carrageenan of the present application

[0030] 600 g of carrageenan was added to the vibration mill hopper and ground for 10 min, then 10% silica 60 g was added and ground for another 30 min, then 30 g of silica was added and ground for 20 min, finally obtaining micronized carrageenan with a particle size of 40-60 μm.

[0031] Comparative example: 600 g of carrageenan and 3% ethanol 18 g were added to the vibration mill hopper and ground for 20 min, then ground for another 15 min, then 2% ethanol 12 g was added and ground for 15 min, finally 2% silica 12 g was added and ground for 3 min, obtaining carrageenan with different particle sizes.

[0032] Example 2 Preparation of carrageenan gel of the present application

[0033] a. Dissolve CaCl2 in water to prepare a solution containing CaCl2;

[0034] b. Add carrageenan with a particle size of 40-60 μm to the solution at 80°C, stir well until dissolved, then add the raw material of food or medicine, stir and dissolve until mixed evenly, cool to room temperature to obtain the gel.

[0035] Example 3 Parameter optimization experiment of carrageenan gel of the present application

[0036] Gels were prepared with 0.05% and 0.1% CaCl2 solution and 0.5% and 1% carrageenan respectively and their texture properties were investigated to optimize the parameters of the carrageenan gel.

[0037] The results show that the gels prepared from 0.05% CaCl2 and 0.5% or 1% carrageenan have poor formability, small hardness and adhesiveness and are easy to break, have large elasticity and poor chewiness, and release a large amount of water after being stored for 1 day. The gels prepared from 0.1% CaCl2 and 0.5% carrageenan have formability and hardness between those of the gels prepared from 0.05% CaCl2 and 0.5% or 1% carrageenan, have small elasticity and chewiness, and are also easy to release water after being stored for 1 day. The gels prepared from 0.1% CaCl2 and 1% carrageenan have good formability, large hardness, small elasticity, and chewiness and adhesiveness equivalent to those of the gels prepared from 0.5% carrageenan. Thus, it is proved that the textural properties of the gels prepared from carrageenan vary with the amount of carrageenan, and the application preferably uses 0.1% CaCl2 and 1% carrageenan to prepare the gels.

[0038] Example 3 Particle size screening test of carrageenan in the application

[0039] 1 Materials

[0040] Carrageenan powder (C) was purchased from Henan Mingxuan Food Co., Ltd., and samples 10, 20, 30, 40, 50 and 60 were obtained by grinding the carrageenan powder for different times. CaCl2 and panax notoginseng total saponins (PNS) were purchased from Xi'an Shennong Biological Technology Co., Ltd., and milk powder (Milk) was purchased from Nestle Co., Ltd.

[0041] 2 Determination of physical indexes of carrageenan powder

[0042] 2.1 Particle size

[0043] The particle sizes corresponding to 10%, 50% and 90% of the cumulative particle size distribution of the seven carrageenan samples were determined by using a Mastersizer 2000 laser particle size analyzer (Malvern Instruments Ltd., UK) under dry testing conditions, namely d (0.1) , d (0.5) and d (0.9) , and each sample was tested in triplicate. The particle size testing parameters were as follows: sample air pressure, 322.5 kPa; sample speed, 80%; obscuration range, 0.5%-6%; sample measurement time, 10 s; and background correction time, 10 s.

[0044] 2.2 SEM

[0045] The microstructure of the samples was observed by using an Inspect F50 field emission scanning electron microscope (FEI Company, Shanghai, China). The powders of C (original powder), 20, 40 and 60 samples were fixed to the sample stage by using double-sided conductive glue, were vacuum-gold-plated by using an ion sputtering instrument, and were then placed under a scanning electron microscope (SEM) for observation and photography.

[0046] 2.3 Fourier Near Infrared Spectroscopy

[0047] A certain amount of C, 20, 40 and 60 samples were taken, ground with KBr and pressed into thin slices. The samples were analyzed using a Nicolet IS10 (Thermo Fisher Scientific, USA) FTIR spectrometer. The scanning range was between 400-4000 cm -1 -1, and the resolution was 0.4 cm -1 .

[0048] 2.4 Specific Surface Area and Porosity

[0049] A certain amount of C, 20, 40 and 60 carrageenan powders were taken into sample tubes, heated and blown to constant weight with nitrogen, and then transferred to an ASAP 2460 full-automatic specific surface area and porosity analyzer (Micromeritics Instrument Co., Ltd., Shanghai, China) for determination.

[0050] 2.5 Water Absorption Swelling Rate of Powder

[0051] 0.1 g of C, 20, 40 and 60 carrageenan powders were taken into 20 ml of water, respectively, and after they were settled at the bottom of a cylindrical transparent glass bottle, the Turbiscan Lab stability analyzer (Formulaction, France) was used to start scanning. Then, scanning was performed every 10 min, and the transmittance (T) and stability parameter (Turbiscan stability index, TSI) of the powder in the solution were recorded within 3 h, so as to track the change of the water absorption swelling time and height of the powder, and thus compare the water absorption swelling rates of the four particle sizes of carrageenan. The TSI value can reflect the change of the transmittance intensity of the sample within the measurement time before each measurement intersects with the previous measurement. The greater the TSI value, the more unstable the system, and the greater the change of the sample.

[0052] 3 Preparation and Characterization of Gel Samples

[0053] 3.1 Preparation of Gels

[0054] Deionized water (100 ml) containing 0.1% CaCl2 was added with C, 20, 40 and 60 carrageenan (1.0%) samples, respectively, and stirred at 80°C until dissolved to prepare C, 20, 40 and 60 carrageenan blank gels. After the samples were cooled to room temperature, they were stored at 4°C overnight for subsequent analysis.

[0055] In 100 ml of deionized water containing 0.1% CaCl2, C, 20, 40 and 60 carrageenan (1.0%) samples were added respectively, stirred at 80°C until dissolved, then milk (17.3%) and total sanchi ginseng saponins (3.2%) were added respectively and stirred until dissolved and mixed uniformly, thus milk carrageenan gels (M-C, M-20, M-40, M-60) and total sanchi ginseng saponins carrageenan gels (PNS-C, PNS-20, PNS-40, PNS-60) were prepared. After the samples were cooled to room temperature, they were stored at 4°C overnight for subsequent analysis.

[0056] 3.2 Rheological measurements

[0057] A HAAKE MARS 40 rheometer (Thermo Fisher Scientific, USA) was used to evaluate the rheological properties of different carrageenan gels. The method was improved based on the description of Wang et al. (Gel properties and network structure of the hydrogel constructed by iota-carrageenan and Ala-Lys dipeptide

[0058] Rheology, Texture and Swallowing Characteristics of a Texture-Modified Dysphagia Food Prepared Using Common Supplementary Materials). The parallel plate geometry with a diameter of 40 mm was used. The rheological characterization was performed by the following sequence: frequency sweep, temperature sweep and steady shear viscosity test. The frequency sweep test was performed at a constant strain of 1 Pa and 25°C, with a frequency range of 0.1-10 Hz. The temperature sweep method was performed at 1 Hz and a strain of 1 Pa, with a temperature range of 20-80°C and 80-20°C, and a heating and cooling rate of 5°C / min. The flow sweep was used to measure the viscosity of the samples at a shear rate of 1-100 s -1 The sample was covered with a volatile-proof lid during the test to prevent solvent evaporation. All measurements were repeated 3 times.

[0059] 3.3 Texture properties

[0060] The textural properties of different gel samples were analyzed using a TA-XT plus texture analyzer (Rapid TA+, Shanghai Tensile Instrument Co. Ltd, China) according to the description of Li et al. (Effect of micro- and nano-starch on the gel properties, microstructure and water mobility of myofibrillar protein from grass carp). The gels were kept at room temperature for 2 h before testing and then cut into cylinders of 20 mm in length. The hardness, adhesiveness, springiness, cohesiveness, and chewiness of the samples were tested with a compression distance of 10 mm, a pre-test and test speed of 1 mm / s, and a post-test speed of 5 mm / s. Each sample was tested in triplicate.

[0061] 3.4 Water holding capacity

[0062] The water holding capacity (WHC) of carrageenan gels was determined by centrifugation. The gels were fixed on a weighed centrifuge tube (W0). The tube with the gel was weighed (W1) and centrifuged at 10,000 r / min at 4°C for 10 min. The supernatant was discarded and the tube with the pellet was inverted for 10 min to drain the supernatant. After 10 min, the remaining water on the surface of the gel was absorbed using filter paper and weighed (W2), and the WHC (%) was calculated by the following equation:

[0063] WHC (%) = (W2 - W0) / (W1 - W0) x 100%

[0064] 3.5 Low-field nuclear magnetic resonance

[0065] The transverse spin-spin relaxation time (T2) of the samples was measured using a MesoMR23-060-I nuclear magnetic resonance analyzer (Niumag Co. Ltd, Suzhou, Jiangsu, China). Briefly, after a cylindrical glass tube containing the gel (~2 g) was inserted into the nuclear magnetic resonance probe, T2 was measured at 21 MHz and 32°C using a 90°-180° pulse sequence. The relevant parameters were: SF = 21 MHz, O1 = 232246 Hz, RFA90° = 2.6, RFA180° = 3.9, TR = 300 ms, TE = 20 ms, Slice width (mm) = 3, Slices = 1, Average = 4, Read Size = 256, Phase Size = 256.

[0066] 3.6 Scanning electron microscopy

[0067] The microstructure of the samples was observed using an Axio Imagerm2 EVO10 field emission scanning electron microscope (Carl Zeiss IMT Co., Ltd., Shanghai, China). Briefly, each freeze-dried sample was taken on double-sided conductive glue, and gold was sprayed for 30 s under high vacuum. The magnification was selected according to the size of the sample and adjusted to the clear image, and the microstructure of the sample was observed and photographed.

[0068] 3.7 IDDSI Test

[0069] The gels were classified according to the IDDSI guidelines. The IDDSI framework defines texture-modified foods and dysphagia thickened liquids into 8 grades, grades 0 to 4 describe the thickness level of liquids, and grades 3 to 7 describe the texture of food. According to the preliminary test, the carrageenan gel samples belong to grade 6. Grade 6 dysphagia food must pass the fork pressure test and spoon pressure test. The characteristics of grade 6 food are: the sample can be eaten with a fork or spoon, can be broken down under the pressure of a fork or spoon, and is soft, tender, moist throughout, but without separate thin liquid, needs to be chewed before swallowing, and the "bite-sized" pieces are suitable in size and oral handling skills (International Dysphagia Diet Standardization Initiative, 2019).

[0070] The present application cut the gels into 1.5 cm x 1.5 cm small pieces according to the IDDSI test method. The fork pressure test and spoon pressure test are to press the gel sample with a fork / spoon with the thumb and fingers until the thumb nail turns white (the pressure is about 17 kpa). This pressure is consistent with the force of the tongue when swallowing. The deformation performance and behavior of the sample were compared with the IDDSI description to evaluate the grade of the gel. The measurement was carried out at room temperature (25°C), the samples were stored at room temperature or in a 4°C refrigerator, and were collected immediately before each test according to their storage temperature. Each sample was tested three times in repetition.

[0071] 3.8 Taste and Bitterness Evaluation

[0072] Sensory evaluation complied with the ethical and testing requirements of the national standard (GB / T 10220-2012) issued by the National Standardization Administration of China (The National Standardization Administration of China. Sensory evaluation GB / T 10220-2012. In National Standards of the People's Republic of China; Standards Press of China: Beijing, China, 2012.). Ten healthy volunteers were invited to evaluate the masking effect. They were aged 22-28 years and had no history of severe allergies, family history, cholecystitis, bad habits, or recent medical history. Before the sensory tests, the participants were trained on dysphagia, dysphagia-prone foods, and the scoring criteria for each indicator to ensure the completeness of the evaluation results. Evaluation process: A 1.5cm × 1.5cm gel sample was taken and chewed and tasted by the volunteers. The texture, taste, adhesion, and swallowability of four types of carrageenan milk gel and Panax notoginseng total saponins gel were evaluated, with a scoring system of 0-10. In addition, the bitterness level of the Panax notoginseng total saponins gel needs to be scored. Water should be provided for rinsing after each sample test to avoid bias.

[0073] 4. Statistical Analysis

[0074] Data are expressed as mean ± standard deviation, with at least three repeated measurements. Statistical analysis was performed using IBM SPSS Statistics (version 21.0, Chicago, IL, USA) software. One-way ANOVA was used for intergroup analysis, and *p < 0.05 was considered statistically significant.

[0075] 5. Discussion of Results

[0076] 5.1 Physical properties of carrageenan powder

[0077] The particle size distribution results of Car raw powder and samples with different grinding times are shown in the figure. Figure 1 (AandB) As the grinding time increases, the particle size of Car powder gradually decreases. The d of the original Car powder... (0.9) The particle size was 244.146 μm. After pulverization for different times, the d of Car... (0.9)142.837, 125.238, 68.477, 60.372, 52.399 and 50.459 μm, respectively, decreased by 41.50%, 48.70%, 71.95%, 75.27%, 78.54% and 79.33%, respectively. It can be seen that the particle size of Car is halved after 20 min of crushing, and the particle size of Car is halved again after 40 min of crushing. The particle size of Car decreases unobviously with the continuous crushing, and the particle size of Car is reduced to about 50 μm at 60 min. However, the particle size difference between the samples crushed for 10 min and 20 min, 30 min and 40 min, and 50 min and 60 min is small, so the present application selects the Car samples of the original powder and crushed for 20 min, 40 min and 60 min for subsequent experiments.

[0078] Table 1. Particle size distribution results of carrageenan with different particle sizes (n = 3, )

[0079]

[0080] The SEM results of the four Car powders are shown in Figure 1 C. It can be seen that the carrageenan C powder is in the shape of a cuboid, a block or a rod, the surface is connected into a sheet, and the length is about 200 μm. After crushing, the particle size of the carrageenan powder decreases to different degrees, which is consistent with the above particle size distribution detection results. The crushed carrageenan powder is in the shape of an irregular block, which is formed by particle agglomeration or extrusion, and the particle size is significantly reduced compared with the original powder. In addition, it can be seen from Figure C that the particle size of part of the small particles in the powder 60 can reach submicron or even nanometer level, and the particles have obvious agglomeration phenomenon. Combined with the analysis of the particle size distribution results, the specific surface area of Car increases after the particle size is reduced, and the small particles are re-agglomerated by the electrostatic adsorption force or are extruded to form new particles during the crushing process.

[0081] The FTIR spectra of the four Car powders are shown in Figure 1 D. It can be seen that the reduction of particle size does not affect the functional groups and molecular skeleton of carrageenan. The characteristic peaks of the Car samples all exist: 847 cm -1 -1 shows a characteristic absorption peak related to the sulfate group on β-D-galactose C4, 930 cm -1 -1 shows a characteristic absorption peak related to -3, 6-endo ether galactose, 1068 cm -1 -1 shows a characteristic peak caused by C-O stretching of 3, 6 galactose (Levy-Ontman O, Abu-Galiyun E, Huleihel M. Studying the Relationship between the Antiviral Activity and the Structure of -Carrageenan Using Ultrasonication. Int J Mol Sci. 2023 Sep 17;24(18): 14200.

[0082] doi:10.3390 / ijms241814200. PMID: 37762503; PMCID: PMC10531741.), 1263 cm -1 -1 is the characteristic absorption peak of total sulfate group SO4. After the particle size of carrageenan is reduced, the peak intensity of its characteristic peak at 1263 cm -1 -1 gradually decreases, indicating that the total sulfate content changes. In addition, 1641 cm -1 -1 in the spectrum is caused by the stretching vibration of bound water, and 3441 cm -1 -1 is caused by the stretching vibration of O-H. After the particle size is reduced, the peak of Car at 3441 cm -1 -1 shifts to low wavenumber direction (Eco-Friendly Extraction, Structure, and Gel Properties of ι-Carrageenan Extracted Using Ca(OH)2), indicating that more hydrogen bonds or hydrogen bond interactions are produced in the system, which is conducive to the ordered arrangement between carrageenan molecular chains.

[0083] The specific surface area and porosity detection results of the four carrageenans are shown in Figure 1 E, and the nitrogen adsorption-desorption isotherms are shown in Figure 1 F. From Figure 1 F, it can be seen that the isotherms of the four powders are characterized by convexity to the relative pressure axis, belonging to the IUPAC-defined type III isotherm. At the same time, all four powders have adsorption hysteresis loops, and with the decrease of particle size, the hysteresis loop becomes more and more obvious. In this area, the adsorption amount when desorbed at the same pressure is always greater than that when adsorbed. According to the relationship between the hysteresis loop and the pore shape, it is speculated that the pore shape of carrageenan powder is crack-like, which is similar to the SEM result, and the slit may be formed by the extrusion and aggregation of small particles. From Figure 1 E, it can be seen that with the decrease of particle size of carrageenan, the S BET and V total of the powder show an increasing trend. Especially for powder 60, the S BET and V total significantly increase, which are 15.2142 m 2 / g and 0.0516 cm 3 / g, respectively, while those of powder C are 1.6389 m 2 / g and 0.0024 cm 3 / g, the specific surface area increased by 9 times, and the pore volume increased by nearly 25 times. Compared with the pore size of C, the pore size of carrageenan powder also increased by 2.5 times after the particle size was reduced, but it was not a gradual increase trend, and all of them belonged to mesopores (2-50nm, IUPAC classification).

[0084] Carrageenan is insoluble in cold water but can absorb water and swell to form a gel. This invention compares the changes in water absorption and swelling of carrageenan powders of four different particle sizes at room temperature to examine their gelation rate. Figure 2 The TSI values ​​of four types of carrageenan powder are shown in the curves of the change in the intensity of the projected light (T), and the comparison graphs of the corresponding samples before and after water absorption and swelling within 3 hours. Figure 2 As can be seen from A, the TSI value of carrageenan increases continuously with decreasing particle size, indicating that the system becomes more unstable, i.e., the swelling and water absorption of the powder are more pronounced, especially for powder 60. Within the first hour ( Figure 2 B) The TSI curves of powders C, 20, and 40 showed similar changes, while the TSI curve of powder 60 had the steepest slope, indicating that its water absorption and swelling rate was the fastest. After 1 hour, the TSI of powders C, 20, and 40 tended to level off, while the TSI of powder 60 showed an upward trend and was significantly higher than the other three, indicating that powder 60 was still in the continuous water absorption and swelling stage. From Figure 2 The CF analysis shows that as the particle size decreases, the temperature (T) change of carrageenan becomes increasingly significant, and the area of ​​change shifts upwards from the bottom of the bottle with increasing time. The T value of powder C showed no significant change within 3 hours, with the decrease mainly occurring at the point where the powder aggregated after water absorption (3-10 mm). The T value changes of powders 20 and 40 primarily occurred in the 3-15 mm range, showing some variation compared to powder C. The T value change of powder 60 occurred in the 3-25 mm range, indicating that the powder expanded upwards after absorbing water and swelling. Most importantly, compared to powders C, 20, and 40, the T value of powder 60 decreased from 60% to 40% and then to 20%, indicating that the powder swelled and formed a gel after absorbing water, thus lowering the T value. This is similar to the findings of Huynh et al. In conclusion, reducing the particle size of carrageenan significantly increases its water absorption swelling rate and degree of swelling, which can be attributed to the increase in the specific surface area and porosity of the powder. This not only allows carrageenan to swell into a gel more quickly under the same conditions, but also reduces the amount of carrageenan needed.

[0085] 5.2 Rheological properties

[0086] The rheological properties of four blank carrageenan gels at a 1% dosage were investigated separately, and the results are as follows: Figure 3 As shown. From the frequency scan results ( Figure 3As shown in A and B), with the decrease in carrageenan particle size, both the storage modulus (G') and loss modulus (G”) of the samples increase, indicating that the decrease in particle size increases the crosslinking density within the carrageenan gel. At 0.1 Hz, the G' value of sample C is lower than that of samples 20, 40, and 60, at 4.4, 35.5, 6.6, and 13.4, respectively, indicating that the decrease in particle size can improve the gel properties of carrageenan. A higher G' value usually indicates a stronger network structure, so the decrease in particle size improves the structural strength of the carrageenan gel to some extent. With the increase in scanning frequency, G' and G” show a slow upward trend, indicating that the physical crosslinking network of the gel is frequency-dependent and has good gel stability. The G' of sample 20 is greater than G”, indicating that the gel is more like an elastic solid, while the G” of the other samples is greater than G', indicating that although the samples appear as solids, they are more like viscoelastic liquids. The reason for this is likely that the gel sample deformed and flowed under external stress. Greater stress increased the relative displacement and friction between gel molecules, thus increasing G”, which is greater than G’. This also indicates that carrageenan gel is suitable as a food matrix for patients with dysphagia, not only reducing the difficulty of swallowing but also decreasing the risk of choking.

[0087] Figure 3 C represents the four types of carrageenan gels in the range of 1–100 s. -1 The steady-state viscosity within the shear rate range was determined. It can be seen that, except for sample 40 which showed no significant change, the viscosity of all samples decreased with increasing shear rate, exhibiting shear-thinning behavior and classifying them as pseudoplastic fluids (non-Newtonian fluids). This is because as the shear rate increases, the internal structure of the gel is gradually disrupted, leading to a decrease in viscosity. This can reduce the difficulty of swallowing to some extent, making it suitable for patients with dysphagia. Compared to sample C, the viscosity of sample 20 decreased, while the viscosities of samples 40 and 60 increased, indicating that reducing particle size can increase the viscosity of carrageenan gel to some extent. A certain viscosity can cause food to clump together, preventing it from crumbling after chewing, thereby reducing the frequency of swallowing and improving the swallowing performance of food. Furthermore, this invention also measured the changes in G' and G” of four carrageenan gels with temperature (Figure DG). As can be seen from the figure, the G' values ​​of the four gels were greater during cooling than during heating, indicating that they enhance the three-dimensional network structure of the gel through hydrogen bonding. During heating, the G' and G” values ​​of the four gels decreased significantly, while they increased during cooling, which is consistent with the finding that carrageenan gels are thermally reversible gels. This phenomenon can be attributed to the weakening of hydrogen bonding with increasing temperature and the strengthening with decreasing temperature.

[0088] 5.3 Texture properties

[0089] As one of the sensory attributes, texture is very important for the evaluation of food palatability and swallowing characteristics. The texture properties of the four blank carrageenan gels during mastication were determined by TPA test simulating the mastication behavior, and the results are shown in Table 2. Hardness is an important parameter that directly reflects the mouthfeel of food, and has a great influence on gumminess and cohesiveness in the texture attributes. Gumminess represents the energy required to break down a semi-solid food into a stable state during mastication. Both hardness and gumminess indicate the mastication force required during oral processing of food. As can be seen from Table 1, with the decrease of the particle size of carrageenan, the hardness and gumminess of the blank gels decrease significantly, and compared with sample C, there are significant differences (p<0.05), and the decrease of sample 60 is the most significant, with a decrease of 72.5% in hardness and 39.8% in gumminess. The decrease of gel hardness and gumminess can be attributed to the weakening of gel strength caused by irregular gel network. This also proves that the decrease of the particle size of carrageenan can reduce the ability of the formed food pellets by its gel to be suitable for swallowing.

[0090] Adhesiveness refers to the adhesion between the probe and the gel sample, which can be explained as the degree of adhesion between food and the oral cavity. Food with high adhesiveness is not suitable for people with swallowing difficulties, because it increases the risk of pharyngeal residue, thereby causing aspiration after swallowing. As shown in Table 1, the decrease of the particle size of carrageenan increases the adhesiveness of the blank gels (except sample 20), which is similar to the results of steady shear viscosity in the rheological properties described above. The difference in adhesiveness of the gels mainly depends on the different network structures, indicating that the gel network structure of carrageenan changes after the particle size decreases. However, overall, the adhesiveness values of the four carrageenan gels are at a relatively low level, indicating that they are not easy to adhere to the teeth or palate, and have good swallowing properties. Cohesiveness is also one of the secondary factors for evaluating the diet of swallowing difficulties, reflecting the internal bonding and structural integrity of the gel network. As shown in Table 1, after the particle size decreases, the cohesiveness of the carrageenan gels increases slightly, but compared with sample C, only sample 20 has a significant difference (p<0.05). This indicates that the carrageenan gels with reduced particle size still have good structural integrity, which can prevent the food mass from being broken down into small particles in the oral cavity, and also helps to reduce the frequency of mastication and swallowing, which is crucial for safe swallowing.

[0091] Table 2. Texture properties of 4 kinds of carrageenan blank gels, milk gels and panax notoginseng total saponins gels under 1% dosage (n=3, )

[0092]

[0093] In addition, the textural properties of milk and panax notoginseng total saponins gels at 1% were also determined (Table 1). It can be seen that the hardness and gumminess of milk and panax notoginseng total saponins gels decreased with the decrease of carrageenan particle size, and there were significant differences (p<0.05) compared with C. In particular, samples Milk-60 and PNS-60 were most significant, the hardness of which decreased by 49.3% and 81.4%, respectively, and the gumminess of which decreased by 59.6% and 83.5%, respectively. Compared with C, the adhesiveness of milk and panax notoginseng total saponins gels increased, which had the same trend as the blank carrageenan gel. However, the cohesiveness of milk and panax notoginseng total saponins gels decreased, which had the opposite trend as the blank carrageenan gel. This may be because the combination of carrageenan with other metal ions in milk and panax notoginseng total saponins, or other ingredients in milk and panax notoginseng total saponins, affected the cohesiveness of the gel. In summary, the decrease of carrageenan powder particle size can significantly reduce the strength and gumminess of its gel, and increase the adhesiveness.

[0094] 5.4 Water holding capacity

[0095] WHC is one of the key parameters for evaluating the water retention performance of soft gels, and gels usually require high WHC values. Studies have shown that the water retention of carrageenan gels is poor, and water will be separated out during long-term storage. The WHC of carrageenan with different particle sizes was investigated, as well as its water retention during storage at low temperature (-4°C) and high temperature (40°C) for one month. As shown in Table 1, the WHC values of the four blank carrageenan gels on the first day were not significantly different, with WHC values between 96.9% and 97.6%, and the WHC value of sample 60 was the best. It is reported that patients with dysphagia often suffer from dehydration and dry mouth (xerostomia). Therefore, it is recommended that individuals with dysphagia consume foods with high initial water content. During low-temperature storage, the water retention of the blank gels decreased to some extent as the number of days increased. After 28 days, the WHC values of samples C and 20 decreased by 8% and 7.5%, respectively, and the WHC values were lower than 90%; the WHC values of samples 40 and 60 remained above 90%, and decreased by 6.4% and 6.8%, respectively (Table 1). Figure 4 A). In addition, at the same time point during low-temperature storage, the WHC values of samples C and 20 were lower than those of samples 40 and 60. This indicates that the decrease of particle size can improve the water retention of carrageenan gels under low-temperature conditions and reduce the separation of water during storage. After one day of high-temperature storage, the WHC values of samples C and 20 were significantly lower than those of samples 40 and 60, which were 91.55%, 92.04%, 94.96% and 96.66%, respectively (Table 1). Figure 4 A). In addition, at the same time point during low-temperature storage, the WHC values of samples C and 20 were lower than those of samples 40 and 60. This indicates that the decrease of particle size can improve the water retention of carrageenan gels under low-temperature conditions and reduce the separation of water during storage. After one day of high-temperature storage, the WHC values of samples C and 20 were significantly lower than those of samples 40 and 60, which were 91.55%, 92.04%, 94.96% and 96.66%, respectively (Table 1). Figure 4B). The WHC value trend of the 7th day of storage was similar to the 1st day, indicating that the decrease of particle size could improve the water holding capacity of carrageenan gel at high temperature. Although the WHC increased with the decrease of particle size at the same time point, the WHC value of the blank gel decreased and was lower than that during the low temperature storage within one month of storage time. It is worth noting that the WHC value of sample 60 decreased more (decreased by 8.99%) than sample C (decreased by 6.33%), and samples 20 and 40 decreased by 5.62% and 7.89%, respectively. This proves that although the decrease of particle size can improve the water holding capacity of carrageenan gel, long-term high-temperature storage will significantly reduce its water holding capacity, so if long-term storage is required, it is recommended to be placed in low-temperature conditions.

[0096] The water holding performance of milk gel and total sanchi ginseng saponin gel under low and high temperature conditions is shown in Figs. Figure 4 C, D, E and F. Like the blank carrageenan gel, the WHC value of milk gel and total sanchi ginseng saponin gel decreased with the extension of storage time under two conditions, especially under high temperature conditions. Accordingly, at each time point, the WHC value of the gel increased with the decrease of particle size, and the water holding performance of sample 60 was significantly better than that of C. This also proves again that the decrease of particle size of carrageenan powder can improve the water holding performance of the gel.

[0097] 5.5 Low-field nuclear magnetic resonance

[0098] Low-field nuclear magnetic resonance is a non-invasive and non-destructive method for obtaining information about mobile protons in samples. The spin-spin relaxation time T2 can further provide information about hydrogen molecule relaxation and migration, and is generally considered an important indicator for evaluating the mobility of water molecules in different parts of the gel system. LF-NMR was used to study the T2 relaxation behavior of the four carrageenan gels to determine the changes in WHC of the gels. In general, the T2 relaxation time can reflect the binding strength of water and its surrounding chemicals, and the shorter the T2 relaxation time, the stronger the interaction between different components. As shown in Fig. Figure 4 G, the tested samples showed two obvious peaks in the range of 0.09-5.25 ms and 460.59-3783.46 ms, respectively. The first peak (T 21 ) can be considered as bound water in the gel network, which is tightly bound to macromolecules through molecular forces; the second peak (T 23 ) can be classified as immobilized water, representing the main water part (more than 90% of the total signal) trapped in the internal structure of the gel network. The peaks of the four carrageenan gels shifted to the low relaxation time direction, indicating that the T2, T 21 , and T 23Compared with the original powder carrageenan, the T2 value of sample 60 decreased significantly, indicating that the smaller particle size enhanced the ability to limit the free movement of water molecules. Sample C had no T 21 peak, and the T 21 peak of samples 20, 40 and 60 had a left shift tendency of 0.77, 0.831 and 0.09 ms, respectively, indicating that the smaller particle size enhanced the binding ability of carrageenan gel to bound water. After the particle size of carrageenan was reduced, the T 23 peak of carrageenan gel decreased significantly and showed a downward trend with the decrease of particle size. Compared with the T 23 peak (1122.67 ms) of sample C, the T 23 peak of samples 20, 40 and 60 decreased to 811.98, 690.55 and 460.59 ms, respectively, and all had a left shift tendency. The decrease of T 23 reflects the lower water activity and mobility of immobilized water in the sample, and indicates the increase of the binding force and interaction between water and polymer in the gel system. Thus, it is proved that the smaller particle size enhances the binding ability of carrageenan gel to immobilized water, thereby improving the water holding capacity of carrageenan gel. The above results prove that there are significant differences in water distribution among carrageenan gels with different particle sizes, and the difference in the distribution of bound water and immobilized water in the gel network explains the change of WHC in carrageenan gels with different grinding times.

[0099] 5.6 SEM

[0100] The SEM results of the blank gels of 4 kinds of carrageenan (A-D), milk gels (E-H) and total saponins of Panax notoginseng gels (I-L) at a dosage of 1% are shown in Figure 5 Figure 6. Figure 5 Figure 5 Figure 5 ​​As shown, all are porous networks. Overall, as the particle size of carrageenan decreases, the microporous structure of the gel changes from loose to compact, and the pore size gradually decreases. The structures of the blank gel and the total saponins of Panax notoginseng gel are quite similar. After the particle size decreases, the microporous structure relatively decreases, but it presents an irregular network shape (Figures D1 and L1). In the blank gel, the pore walls of sample C are hollow and have a certain degree of brittleness (Figure A2); after the particle size decreases, the pore walls of the blank gel are solid and have a certain degree of support (Figure D2). The structure of milk gel is more intuitive. The structures of Milk-C, Milk-20, and Milk-40 are composed of macropores containing micropores. The thickness of the macropore walls gradually decreases with the decrease of particle size, the pore size of the micropores decreases with the decrease of particle size, and the number of pores gradually increases. The structure of sample Milk-60 is entirely composed of micropores. The pore size is small and evenly distributed, resembling a "honeycomb" shape, and the pore walls have a certain thickness and are uniform. Generally, a complete and compact structure is beneficial to improving the water-holding capacity of the gel, binding water within the gel network. This also corroborates the above-mentioned research results on water-holding performance, confirming that reducing the particle size of carrageenan powder can improve the integrity of its gel structure and its water-holding performance.

[0101] The microporous structure of gels can further explain their textural properties. For example, in the blank gel and the total saponins of Panax notoginseng gel, the pore size decreases and the number of pores increases with decreasing particle size, but the structure still exhibits an irregular network pattern. This can, to some extent, explain the gradual decrease in gel hardness and adhesiveness, while a certain degree of cohesion remains. In the milk gel, the micropore distribution becomes increasingly uniform with decreasing particle size, giving it better hardness, adhesiveness, and cohesion among the three gels. However, the pore wall thickness of the macropores gradually thins and eventually disappears, causing a downward trend in hardness and adhesiveness. This also indicates that the macropore size and pore wall thickness of carrageenan gel play a major role in its hardness and adhesiveness.

[0102] 5.7 IDSSI Test

[0103] Based on the internationally standardized terminology and definitions provided by the IDDSI framework, recommended tests using a fork and spoon were conducted to evaluate carrageenan gels of different particle sizes and the feasibility of preparing them as milk carrageenan and Panax notoginseng total saponin carrageenan for use in diets for dysphagia. Fork and spoon pressure tests were performed using gel samples of 1.5cm × 1.5cm, a size close to an adult thumbnail, which helps reduce the risk of choking during swallowing. Figures 7-9 As shown, the blank gels of the four carrageenan samples were easily crushed or broken by the tines of a fork and the bottom of a spoon under pressure that caused the thumbnail to turn white (approximate to the force of the tongue during swallowing), and their shape did not return to its original form after the pressure was removed. This indicates that at a 1% dosage, the blank gels of the four carrageenan samples can be classified as Level 6 (soft and bite-sized) in the IDDSI framework, where chewing and tongue force, rather than biting, break down food into appropriate sizes, thereby reducing the risk of choking.

[0104] Similarly, C, 20, and 40 in the four milk gels and the Panax notoginseng total saponins gel were easily crushed or broken under pressure that caused the thumbnail to turn white, and their shape did not return to its original state after the pressure was removed. Therefore, they can all be classified as IDDSI Level 6 (soft and bite-sized). PNS-60, on the other hand, passed the IDDSI recommended fork crushing test, fork dripping test, and spoon tilting test, meaning the gel could be easily crushed to an appropriate size (≤4 mm) without requiring pressure that caused the thumbnail to turn white. Samples of PNS-60 could accumulate on a fork without falling off the fork twig. Furthermore, it maintained its shape on a spoon with sufficient cohesion and easily detached when the spoon was tilted, leaving no sample on the spoon. This indicates that PNS-60 can be classified as IDDSI Level 5 (crumbly and moist), indicating that minimal chewing or tongue force alone is sufficient to move a food bolus of this texture. This result is consistent with the above textural properties test results, namely that PNS-60 has the lowest hardness and adhesiveness among all samples, and its viscosity will not cause it to adhere to teeth, palate or pharynx, while also having a certain degree of cohesion.

[0105] In summary, all four particle sizes of carrageenan gels have the potential to be suitable texture-modified foods for individuals with dysphagia. Furthermore, smaller particle sizes can reduce the degree of dysphagia associated with carrageenan gel diets, making them more suitable for patients with lower swallowing abilities compared to carrageenan C. Therefore, carrageenan gels of different particle sizes can be designed to provide energy or therapeutic benefits to patients with various dysphagia. The IDDSI framework is a relatively simple and effective testing method for differentiating texture-modified foods for individuals with dysphagia, but its subjective evaluation method based on visual inspection has certain limitations. Therefore, future research requires further investigation and studies to provide more reliable, quantifiable parameters or instrumental methods, thereby contributing to the development and evaluation of gel-based dysphagia-oriented foods.

[0106] 5.8 Taste and Bitterness Evaluation

[0107] The taste evaluation results of four types of carrageenan milk gel and Panax notoginseng total saponin gel are as follows: Figure 6 As shown. With decreasing carrageenan particle size, milk gel ( Figure 6The texture and mouthfeel of milk gel A gradually improved, and swallowability and adhesion (residue) improved, but did not show an increasing trend. Compared with Milk-C, Milk-40 and Milk-60 showed significant improvements in all aspects, while Milk-20 showed no significant difference. This is consistent with the textural properties and SEM results of the milk gels mentioned above, as texture and mouthfeel mainly depend on the microstructure of the gel. The decrease in hardness and adhesiveness of the milk gel, the gradual thinning and disappearance of the pore wall thickness of macropores, and the gradual reduction in the pore size of micropores can all explain the improvement in gel texture, mouthfeel, and swallowing performance. The moderate adhesiveness and cohesiveness of the gel can explain the adhesion (residue) results. All of this demonstrates that as the particle size of carrageenan decreases, the swallowing performance of the gel is significantly improved, thus benefiting patients with dysphagia.

[0108] The evaluation results of the taste and bitterness of Panax notoginseng total saponins gel are as follows: Figure 6 As shown in B, reducing particle size improves the texture and bitterness of Panax notoginseng total saponins gel, while showing no significant difference in taste, swallowing ability, and adhesion. Although the hardness and adhesiveness of Panax notoginseng total saponins gel decrease with decreasing particle size and the micropore size relatively decreases, it still exhibits an irregular network structure, with the pore walls changing from hollow to solid. This may explain why there are no significant differences in taste, swallowing ability, and adhesion among the four types of carrageenan Panax notoginseng total saponins gel. Notably, compared to the Panax notoginseng total saponins solution (score), the bitterness score of the gel gradually increases with decreasing particle size, especially with significant differences between PNS-40 (score) and PNS-60 (score) (p < 0.01), indicating that reducing particle size can significantly improve the bitterness-suppressing effect of carrageenan. Studies have shown that carrageenan has three mechanisms for suppressing bitterness and masking taste: first, it reduces the release of bitter substances by binding with sulfate groups; second, it reduces the perceived bitterness by increasing the viscosity of the solution; and third, it strengthens the liposome membrane by forming more hydrogen bonds with liposomes through high charge, preventing or reducing the leakage of bitter substances. Based on these findings, as the particle size of carrageenan decreases, the micropore walls of the gel change from hollow to solid, the pore size decreases, the number of pores increases, and the viscosity also increases. This indicates that, compared to PNS-C, the bitter total saponins of Panax notoginseng can not only be encapsulated in the relatively dense PNS-60 gel, which slows down its release rate and amount, but also reduce the perceived bitterness by increasing gel viscosity. Therefore, the total saponins of Panax notoginseng gel is not only easier for people with swallowing difficulties to take, but also improves patient compliance, making it suitable for patients with therapeutic needs (especially elderly patients).

Claims

1. A pediatric medicine or special medical food gel, characterized in that: It is prepared from CaCl2 or KCl, carrageenan with a particle size of 40-60μm, water, and food or pharmaceutical raw materials. The amount of CaCl2 used per 100ml of water is 0.05-0.1g, and the amount of carrageenan with a particle size of 40-60μm is 0.5-1g.

2. The pediatric medicine or special medical food gel according to claim 1, characterized in that: The dosage of CaCl2 is 0.1g per 100ml of water, and the dosage of carrageenan with a particle size of 40-60μm is 1.0g.

3. The pediatric medicine or special medical food gel according to claim 1 or 2, characterized in that: The particle size of the carrageenan is 50 μm ± 3 μm.

4. The pediatric medicine or special medical food gel according to claim 1 or 2, characterized in that: The food products mentioned include protein-containing foods or starches; the pharmaceutical products mentioned include drugs containing cationic substances.

5. The pediatric medicine or special medical food gel according to claim 4, characterized in that: The protein-containing foods include milk powder; the cationic drugs include total saponins of Panax notoginseng or Coptis chinensis.

6. A method for preparing a pediatric medicine or special medical food gel according to any one of claims 1-5, characterized in that: Includes the following steps: a. Dissolve CaCl2 in water to prepare a solution containing CaCl2; b. Add carrageenan with a particle size of 40-60μm to a CaCl2-containing solution at 80℃, stir thoroughly until dissolved, then add food or pharmaceutical raw materials, stir until dissolved and mixed evenly, and cool to room temperature to obtain gel.

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