Double gel easy to swallow and capable of loading functional factors and preparation method thereof

Abstract

The invention belongs to the technical field of functional factor carrier preparation, and particularly relates to a double gel easy to swallow and capable of loading functional factors and a preparation method of the double gel. The double gel is composed of oleogel and hydrogel, and the mass ratio of the oleogel to the hydrogel is (3-5): (5-7). The double gel is not easy to soften and disintegrate at high temperature, has good stability, and effectively solves the problems of easy layering and low strength of the traditional gel; the gel is low in swelling rate and can avoid burst release of drugs; the lipid-soluble functional factor carrier has good water binding capacity and balanced oil binding capacity, is suitable for loading lipid-soluble functional factors, and can realize controllable slow release of the functional factors. After texture optimization, the product meets the IDDSI level 4 standard, and is suitable for people with dysphagia. Besides, the preparation process is simple, the prepared double gel can be applied to development of medicines, health care products and foods for special medical purposes for people with dysphagia, the application range is wide, and an efficient, safe and easy-to-industrialize scheme is provided for delivery of functional components.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of functional factor carrier preparation, and particularly relates to a double gel capable of being easily swallowed and loading functional factors and a preparation method thereof. BACKGROUND

[0002] Gel as an important functional material is widely used in drug carriers, nutritional supplements and other aspects. Traditional gels play a key role in many products due to their unique physical and chemical properties such as viscoelasticity and water retention. In the aspect of drug carriers, gels can control the release rate of drugs and improve the bioavailability of drugs. However, there are many problems in the practical application of traditional gels, which seriously restricts their further development and application.

[0003] Traditional gels show weak oil-water interface binding, which is one of the key factors leading to unstable gel performance. In the gel system, the interaction between the oil phase and the water phase is crucial for the overall structure and performance of the gel. When the oil-water interface binding is not firm, the gel layering phenomenon is prone to occur during the preparation, storage and use of the gel. This layering not only destroys the uniformity of the gel, but also destroys the gel structure, thereby reducing the gel strength. The reduction of gel strength will trigger a series of chain reactions, the most obvious of which is the increase of the swelling rate. The increase of the swelling rate will cause the volume of the gel to expand, further affecting the physical properties and chemical stability of the gel, limiting its application in some products with high requirements for structural stability.

[0004] Single gels have obvious deficiencies in thermal stability. Many single gels are prone to softening or even disintegration at high temperatures due to their low melting point or poor crystallinity. In addition, during long-term storage, changes in temperature can also cause changes in the performance of single gels, affecting the quality and stability of the product. For example, during drug storage, if the gel carrier is unstable, it will cause the active ingredients of the drug to lose effectiveness, thereby reducing the efficacy of the drug.

[0005] For some gel products that need to achieve sustained release of active substances, such as drug sustained-release preparations, the stability of the gel during gastrointestinal digestion is crucial. However, gels with low strength often show instability in the gastrointestinal digestion environment. Factors such as digestive enzymes, acid-base environment in the gastrointestinal tract can damage the structure of the gel, leading to premature decomposition of the gel, and thus the sustained release effect of the active substance is not ideal. This not only affects the absorption and utilization of active substances in the body, but also may reduce the efficacy of active substances, and cannot achieve the expected therapeutic or health care effect.

[0006] At present, although some products for dysphagia population have appeared in the market, there are still many problems. On the one hand, although some products have soft texture and are easy to swallow, they lack effective loading and protection of functional factors, and cannot meet the needs of dysphagia population for nutrition, health care and medical treatment. On the other hand, although some products add functional factors, due to the poor stability of the gel system, the functional factors are easily inactivated or released unevenly during storage and digestion, and the expected functional effect cannot be achieved. It is urgent to develop a gel carrier with good stability and loaded with functional factors suitable for dysphagia population. SUMMARY

[0007] The present application aims to provide a double gel with easy chewing and swallowing and loaded with functional factors and a preparation method thereof. Liposoluble functional factors are loaded in monoglyceride and peanut oil, and mixed in a hydrogel containing gelatin to form an oral double gel delivery system. By changing the ratio of oil gel and hydrogel, the microstructure, texture, rheology and release of functional factors in the simulated digestion environment are regulated. The double gel can be applied to the development of oral drugs, health products and functional foods for dysphagia population.

[0008] In one aspect, the present application provides a double gel with easy swallowing and capable of loading functional factors, which is composed of a hydrogel and an oil gel; The hydrogel takes gelatin as the matrix, and the content of the gelatin in the hydrogel is 1% to 5% by mass percentage; The oil gel takes vegetable oil as the matrix and monoglyceride as the gelling agent, and the content of the monoglyceride in the oil gel is 5% to 15% by mass percentage; The mass ratio of the oil gel and the hydrogel is 3 to 5:5 to 7.

[0009] Further, in the double gel, the vegetable oil is peanut oil, olive oil or coconut oil.

[0010] Further, in the double gel, the content of gelatin in the hydrogel is 5% by mass percentage; the vegetable oil in the oil gel is peanut oil, and the content of monoglyceride in the oil gel is 10% by mass percentage.

[0011] Further, in the double gel, the hardness of the double gel is 1878 to 3912 N / m 2 , and the adhesiveness is ≤33 J / m 3 .

[0012] Further, in the double gel, the mass ratio of the oil gel and the hydrogel in the double gel is 5:5.

[0013] Further, the double gel can effectively delay lipid decomposition.

[0014] Further, the functional factor is a fat-soluble functional factor.

[0015] Further, the fat-soluble functional factor is a fat-soluble substance with activity such as galangin, carotenoid, coenzyme Q10, phytosterol, fat-soluble vitamin, etc.

[0016] On the other hand, the present application also provides a preparation method of the double gel, comprising the following steps: S1, preparing a hydrogel: dissolving gelatin in water, heating and stirring until fully mixed, and cooling to 4°C to form a hydrogel; S2, preparing an oil gel: dissolving monoglyceride in vegetable oil, and cooling to room temperature to form an oil gel; S3, mixing the hydrogel and the oil gel in proportion, homogenizing, and cooling to form a double gel.

[0017] In another aspect, the present application also provides the double gel as a carrier for use in the preparation of a drug, health product, nutritional supplement and / or functional food for dysphagia patients.

[0018] Further, in the application, the active ingredient of the drug, health product, nutritional supplement and / or functional food is a fat-soluble ingredient.

[0019] Finally, the present application also provides the double gel as a carrier for use in the preparation of a drug, health product, nutritional supplement and / or functional food for moderate to severe dysphagia patients.

[0020] Compared with the prior art, the technical solution provided by the present application has at least the following beneficial effects or advantages: (1) The double gel system of the present application strengthens the oil-water interface combination, effectively enhances the bonding force between the oil-water interface compared with the single gel system, solves the delamination problem of the traditional gel, and greatly improves the stability of the gel system.

[0021] (2) The swelling rate of the double gel system with a mass ratio of oil phase gel to water phase gel of 5:5 is significantly reduced compared with the single water gel, effectively avoiding the functional factor burst phenomenon caused by excessive swelling, preventing the destruction of the gel structure, and ensuring the stability and effectiveness of the functional factor during delivery.

[0022] (3) The double gel system provided by the present application has excellent water holding capacity, with a water holding capacity of more than 80%. The double gel system with a mass ratio of oil phase gel to water phase gel of 5:5 has more balanced oil holding capacity. This characteristic makes it an ideal carrier for loading fat-soluble functional factors, which can fully meet the loading requirements of different functional factors.

[0023] (4) Through XRD analysis, it is found that the crystallinity of the double gel is significantly improved with the increase of the oil phase content, and it can maintain stable form under high temperature environment, and is not easy to soften and disintegrate, thereby ensuring the stability of the functional factor under high temperature condition. In the in vitro digestion experiment, it is found that the double gel system significantly reduces the release rate of free fatty acid, which realizes the controllable release of the functional factor, prolongs the action time of the functional factor in the body, and improves the bioavailability.

[0024] (5) The double gel system meets the needs of people with difficulty in swallowing, and the hardness range is 1238~3912N / m 2 , the low adhesion is not more than 138J / m 3 , which meets the IDDSI 4 level standard. This texture feature makes the patient easy to swallow without chewing, and there is no risk of sticking to the throat, especially suitable for patients with moderate to severe difficulty in swallowing, which provides a safe and convenient way for the special group to intake functional factors.

[0025] (6) The double gel system provided by the application shows a very high embedding rate for the fat-soluble functional factor, which is much higher than traditional carriers such as emulsion and microcapsule, and better retains the antioxidant activity of the functional factor. This advantage ensures the activity and stability of the functional factor during delivery, and provides high-quality functional ingredients for patients with difficulty in swallowing.

[0026] (7) The preparation method of the application is simple, only needs to homogeneously mix the hydrogel and the oil gel, without complex equipment and tedious process flow, which has high industrial production value.

[0027] (8) The double gel system provided by the application has wide applicability and can be used as a carrier for a variety of functional ingredients. Not only suitable for drugs to realize precise delivery and long-term release of drugs, but also can be used for health products to improve the stability and bioavailability of functional factors; at the same time, it provides safe and effective nutritional support for patients with difficulty in swallowing in the field of special medical use food.

[0028] The application solves the technical problems of traditional gels in stability, slow release, and swallowing applicability by a unique double gel system design. Not only provides an efficient and safe solution for the delivery of functional ingredients, but also has a simple preparation process and wide application prospect, which has high industrial value and is expected to be popularized and applied in the fields of medicine, health products and food. BRIEF DESCRIPTION OF DRAWINGS

[0029] Figure 1 is the apparent graph of different systems loaded with high-geranial.

[0030] Figure 2 is the graph of high-geranial embedding rate determination results of different systems.

[0031] Figure 3 Figure for the results of determination of antioxidant capacity of different systems of galangin.

[0032] Figure 4 Figure for the results of the effect of different oils on the elasticity and hardness of the gel.

[0033] Figure 5 Figure for the results of the effect of different gelling agents on the elasticity and hardness of the gel.

[0034] Figure 6 Figure for the results of the effect of different amounts of monoglycerides on the elasticity and hardness of the gel.

[0035] Figure 7 Figure for the results of the effect of different hydrogel bases on the elasticity and hardness of the gel.

[0036] Figure 8 Figure for the results of the effect of different amounts of gelatin on the elasticity and hardness of the gel.

[0037] Figure 9 Figure for the optical microscope of different double gel gel systems.

[0038] Figure 10 Figure for the T2 spin-lattice relaxation time of different gel systems.

[0039] Figure 11 Figure for the relative area percentage and hydrogen proton density image of different double gel systems.

[0040] Figure 12 Figure for the X-ray diffraction of different gel systems.

[0041] Figure 13 Figure for the Fourier infrared spectrum of different gel systems.

[0042] Figure 14 Figure for the swelling rate curve of different gel systems.

[0043] Figure 15 Figure for the water and oil holding capacity test results of different gel systems.

[0044] Figure 16 Figure for the viscosity curve of different gels.

[0045] Figure 17 Figure for the free fatty acid release curve of different gels in in vitro digestion simulation.

[0046] Figure 18 Figure for the IDDSI test results of different gels.

[0047] Figure 19 Figure for the macrograph of different gels. DETAILED DESCRIPTION

[0048] The technical solutions of the present application will be described below in conjunction with examples, but the present application is not limited to the following examples.

[0049] In order for those skilled in the art to better understand the technical solutions of the present application and to implement them, the present application will be further described below in conjunction with specific examples and drawings, but the examples are not limiting to the present application.

[0050] The experimental methods and detection methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials described are all commercially available unless otherwise specified.

[0051] Gingerol, purity ≥98%.

[0052] Example 1 This example is to screen and obtain a gingerol delivery system.

[0053] By evaluating the loading capacity, encapsulation efficiency and antioxidant performance of gingerol in emulsion, microcapsule and double gel system, an effective gingerol delivery system is screened, and the specific steps are as follows: Emulsion preparation: 5% gelatin, 10% soybean oil, 0.2% gingerol, and the rest water are weighed by mass percentage, 0.2% gingerol in the total mass of the emulsion is dissolved in soybean oil, mixed with gelatin and the remaining raw materials, high-speed shearing 12000 rpm, 3 min to form the initial emulsion, and then ultrasonic treatment to refine the droplets, power 150 W, 5 min, ice bath temperature control, to prepare gingerol emulsion.

[0054] Microcapsule preparation: 5% gelatin, 10% soybean oil, 3% maltodextrin, 0.2% gingerol in the total mass of the capsule, and the rest water are weighed by mass percentage, gingerol is dissolved in soybean oil to prepare a gingerol-oil phase mixture, gelatin and maltodextrin are dissolved in water, and the gingerol-oil phase mixture is added, high-speed shearing (10000 rpm, 2 min) to form an emulsion, and a spray dryer is used to prepare microcapsules to obtain gingerol microcapsules.

[0055] Double gel preparation: gelatin with a mass percentage concentration of 5% is used to prepare a hydrogel, soybean oil is used as a matrix to prepare an oil gel with 5% monoglyceride in the mass of the oil gel, and 0.2% gingerol in the total mass of the double gel, and the rest water, and the double gel is prepared by shearing method, and the specific steps are as follows: S1, preparation of gelatin hydrogel: gelatin is added to deionized water. The mixture is heated to 60℃ and stirred for 2h. After that, the mixture is cooled at 4℃ for 12h to realize gelatin mixing; S2, Preparation of oil gel: monoglyceride was completely dissolved in peanut oil at 85℃ to form oil phase mixture, during the cooling process of the oil phase mixture, gingerol was added and mixed well, the mixture was cooled to room temperature and then stored in the refrigerator for 24h.

[0056] S3, Preparation of double gel: oil gel and water gel were heated and stirred at 90℃ to obtain a dissolved state. At 50℃, cool for 10min, mix the oil gel and water gel in a mass ratio of 3:7 in a homogenizer, high-speed homogenization for 1min, to form different gel samples. Then cooled at 4℃ for 1h to form Bigel structure. That is, gingerol double gel is prepared.

[0057] Take pictures of the above prepared gingerol emulsion, gingerol double gel and gingerol microcapsules, and observe the appearance, the results are shown in Figure 1 Test the embedding rate of gingerol in gingerol emulsion, gingerol double gel and gingerol microcapsules, the test results are shown in Figure 2 The double gel system has a high embedding capacity of gingerol, which may be due to the special structure of the double gel, its unique two-phase environment can better accommodate fat-soluble drugs. The encapsulation structure of the microcapsule may have limitations in space or binding mode. The liquid form of the emulsion, as well as its stability and structural characteristics, makes its embedding capacity for drugs relatively weak. Test the antioxidant performance of gingerol emulsion, gingerol double gel and gingerol microcapsules by DPPH free radical scavenging experiment, the results are shown in Figure 3 The antioxidant property of gingerol double gel system is the strongest, which is also related to the spatial structure of the double gel. The core-shell structure of the surface of the emulsion and microcapsule system makes it difficult for gingerol to directly contact with free radicals, resulting in weaker antioxidant property. Therefore, the double gel is the optimal system for gingerol loading and delivery.

[0058] Example 2 This example is to optimize the component composition of the gingerol double gel loading and delivery system.

[0059] 2.1 Screening of oil gel composition Referring to the double gel preparation method in Example 1, replace the soybean oil in the double gel preparation method in Example 1 with olive oil, peanut oil and coconut oil respectively, and evaluate the gel elasticity and hardness of the prepared gingerol double gel (olive oil), gingerol double gel (peanut oil) and gingerol double gel (coconut oil), the results are shown in Figure 4 The content of saturated fatty acids in coconut oil is high, the molecules are closely arranged, the gel structure formed is stable, the elasticity is high and the hardness is low; the content of unsaturated fatty acids in olive oil is high, the intermolecular force is relatively weak, the elasticity is low and the hardness is high. The composition of peanut oil is between the two, the elasticity is moderate. Peanut oil is selected as the best base material.

[0060] Referring to the preparation method of the double gel in Example 1, the monoglyceride in the preparation method of the double gel in Example 1 is replaced by polyglycerol polyricinoleate, monoglyceride (monoglyceride) and candelilla wax to determine the gel agent of the oil gel base material. The results are shown in Figure 5 The candelilla wax is mainly composed of long-chain fatty acids and alcohols, has a long and regular molecular chain, and has strong intermolecular force, so the double gel prepared therefrom has high hardness and low elasticity. The monoglyceride molecule contains a hydrophilic hydroxyl group and an oleophilic fatty acid chain, and has a relatively simple structure, so the double gel prepared therefrom has moderate hardness and elasticity. The polyglycerol polyricinoleate molecule is large, has multiple glycerol units and ricinoleate groups, and such a complex structure makes the intermolecular interaction not tight, so the double gel prepared therefrom has good elasticity and low hardness. The monoglyceride is selected as the gel agent, and the hardness and elasticity of the galangin double gel prepared by using 5%, 10% and 15% of the monoglyceride by mass percentage in the oil gel are tested, and the results are shown in Figure 6 The network structure formed by the monoglyceride at different concentrations is different in theory. When the monoglyceride concentration is 5% by mass percentage, the network structure is moderate, and the hardness and elasticity are balanced. When the monoglyceride concentration is 10%, the cross-linking degree changes, and the structure formed has a certain stability, which is more conducive to the elasticity. When the monoglyceride concentration is 15%, the molecules are closely aggregated, the hardness increases, but the flexibility of the structure is poor, and the elasticity decreases. The monoglyceride with a mass percentage of 10% is selected as the best addition amount.

[0061] 2.2 Screening of hydrogel composition Referring to the preparation method of the double gel in Example 1, the gelatin in the preparation of the gelatin hydrogel in the preparation method of the double gel in Example 1 is replaced by gelatin, chitosan and carboxymethyl cellulose, and the hardness and elasticity of the double gel formed by different hydrogel base materials are tested to determine the hydrogel base material. The results are shown in Figure 7 The hydrogen bond between the chitosan molecules is relatively weak, the structure formed is relatively tight, the hardness is low, and the elasticity is relatively large. The carboxymethyl cellulose has many polar groups, the intermolecular force is strong, the structure is tight, the hardness is high, and the elasticity is poor. Compared with the others, the gelatin has balanced performance in all aspects, moderate hardness and good elasticity, and the safety and biocompatibility of the gelatin are good. The gelatin is selected as the best hydrogel base material.

[0062] Referring to the preparation method of the double gel in Example 1, the gelatin hydrogel in the preparation of the double gel in Example 1 is replaced by 1%, 3% and 5%, and the elasticity and hardness of the galangin double gel prepared by using 1%, 3% and 5% of the gelatin by mass percentage in the hydrogel are tested to determine the addition concentration of the gelatin, and the results are shown in Figure 8The differences in the intermolecular interactions and network structures of gelatin at different concentrations are shown. When the concentration of gelatin is 3%, there is a moderate cross-linked network structure between the molecules, so that it exhibits lower hardness and higher elasticity. At a high concentration of 5%, the degree of cross-linking between gelatin molecules is significantly enhanced, forming a more compact and stable network structure, which presents higher hardness and lower elasticity. In the case of a low concentration of 1%, the number of gelatin molecules is relatively small, and it is difficult for the molecules to form an effective connection network, thereby resulting in poor hardness and elasticity. The selected amount of gelatin with a mass percentage of 5% is the best addition amount.

[0063] Example 3 This example is to prepare a berberine double gel with a mass ratio of oil gel to hydrogel of 5:5.

[0064] S1, Preparation of gelatin hydrogel: weigh gelatin according to the amount of 5% of the mass percentage of hydrogel, and add gelatin to deionized water. Heat the mixture to 60℃ and stir at 300 rpm for 2h. After that, cool the mixture at 4℃ for 12h to realize gelatin mixing, and prepare the hydrogel.

[0065] S2, Preparation of oil gel: weigh monoglyceride according to the amount of 10% of the mass percentage of oil gel, and completely dissolve monoglyceride into peanut oil at 85℃ to form an oil phase mixture with 10% of the total mass of monoglyceride as oil phase. During the cooling process of the above oil phase mixture, add 0.2% of berberine to the total mass of the double gel, and mix thoroughly. Cool the mixture to room temperature, and then store it in the refrigerator for 24h. Prepare the oil gel.

[0066] S3, Preparation of double gel: heat the oil gel and the hydrogel at 90℃ respectively, and stir at 300 rpm to obtain a dissolved state. Cool at 50℃ for 10min, and add the oil gel and the hydrogel to the homogenizer according to the mass ratio of 5:5, homogenize at 10000 rpm for 1min to form a gel sample. Then cool at 4℃ for 1h to form a Bigel structure, and obtain a berberine double gel with a mass ratio of oil gel to hydrogel of 5:5 (5O:5H).

[0067] Example 4 This example is to prepare a berberine double gel with a mass ratio of oil gel to hydrogel of 3:7.

[0068] The preparation method of this example is the same as that of Example 3, except that the mass ratio of oil gel to hydrogel in the double gel is 3:7. A berberine double gel with a mass ratio of oil gel to hydrogel of 3:7 (3O:7H) is prepared.

[0069] Example 5 This example is to prepare a berberine double gel with a mass ratio of oil gel to hydrogel of 7:3.

[0070] The preparation method of this example is the same as that of Example 3, except that the mass ratio of the oil gel and the hydrogel in the double gel is 7:3, and an oleogel-hydrogel double gel of pungol with a mass ratio of 7:3 is prepared.

[0071] Test Example 1 This test example is to characterize the performance of different samples by taking the pungol double gels prepared in Examples 3-5 (5O:5H, 3O:7H, and 7O:3H) as test samples and taking the oleogel (Oleogel) and the hydrogel (Hydrogel) as controls.

[0072] (1) Morphological analysis and color difference The samples were observed under a 20x objective lens using an optical microscope. The sample differences were analyzed by a color difference meter. The morphological results are shown in Figure 9 , which shows that the 3O:7H double gel system has more water, and as the oil volume fraction increases, the free water content decreases, and aggregation occurs in the middle of the droplets, resulting in coagulation. Therefore, the above ratio range can form a good double gel effect. The color test results of different gel systems are shown in Table 1.

[0073] Table 1 Color characteristics of different gel systems

[0074] As can be seen from Table 1, the brightness and whiteness are the highest when 3O:7H, which may be related to the optimization of light reflection by the microstructure of the mixture (uniform gel network). Higher oleogel ratio (5O:5H, 7O:3H) can lead to densification or phase separation of the structure, reducing the light scattering efficiency.

[0075] (2) Low-field nuclear magnetic water distribution The gel was cut into the same triangular pyramid, and the low-field nuclear magnetic resonance spectrometer was used to measure at room temperature. The T2 spectrum was obtained by MultiExp Inv Analysis software inversion CPMG exponential decay curve, and the percentage content of each group of water was obtained by integrating the peak area in the spectrum. The results are shown in Figure 10 , Figure 11 The low-field nuclear magnetic transverse relaxation time T2 can reflect the freedom of water in the sample. A larger T2 reflects that the water molecules are weakly combined with the solid components, and the water movement is high, and vice versa. As can be seen from Figure 10 , the 3O:7H double gel has a relatively high T 23 , indicating that there is a relatively high free water in the gel at this time; and as the oil phase increases, the T 22The peak gradually increased, indicating that the oil phase gradually covered the surface of the gel, the space network structure gradually tended to be tight, and more water was trapped. The non-flowing water in the double gel was more firmly linked to the network structure. Figure 11 It can be seen that the 3O:7H double gel shows a more red phenomenon, indicating that it contains high-density protons and contains more water; while 7O:3H has lower water content, and the gel structure changes.

[0076] (3) XRD detection The freeze-dried sample was placed on the sample stage for scanning. The parameters were set as follows: tube voltage 40 kV, tube current 40 mA, scanning was performed in the diffraction angle range of 5°-50°, and the scanning rate was 3° / min. The results are shown in Figure 12 . All Bigel samples showed a hump-like signal, indicating that they mainly had an amorphous structure. All ratios had a sharp peak at 19.69°, and the addition of oil made the double gel gradually form crystals, and the relative crystallinity of 3O:7H, 5O:5H and 7O:3H was 13.7, 25.32 and 25.73, respectively. With the increase of oil gel content, the intensity of this peak gradually increased, indicating that the double gel with higher oil gel ratio had a more stable and ordered structure.

[0077] (4) FTIR detection The differences between different samples were compared using a Fourier transform spectrometer. Scanning was performed 16 times at a speed of 2 cm -1 in the wavelength range of 4000-400 cm -1 . The results are shown in Figure 13 . All double gel samples had a wide peak at 3700-3000 cm -1 , corresponding to the O-H stretching vibration of water molecules in the gel hydrogel and fatty acyl molecules in the oil gel. With the increase of oil gel / hydrogel ratio, the intensity of the peak gradually decreased, indicating the decrease of hydrogen bond in the gel. The peaks at about 2900, 2800 and 1460 cm −1 represent C-H or C-H stretching vibration, which is attributed to the saturated and unsaturated fatty acyl chains in the oil phase. The signal of these peaks increased significantly with the increase of oil gel / hydrogel ratio. The absorption signal of C-O stretching vibration in the oil phase at 1740 and 1160 cm −1 also increased. The peak at 1650 cm −1 is caused by the C-O stretching vibration of gelatin. No new peak appeared in this process, indicating that there is no chemical interaction between the gelatin hydrogel and the peanut oil gel.

[0078] (5) Swelling rate determination A 1 g sample was immersed in 10 mL of deionized water and stored at room temperature for 2 h, 4 h, 8 h, 12 h, and 24 h. The gel sample was taken out, the surface water was wiped off, and the sample was weighed to calculate the gel swelling rate. The results are shown in Table 1. Figure 14 As shown in Table 1, all the gels showed a rapid water absorption phenomenon in a short time, except that the oil gel and the 70:30 double gel showed a loose condition in water. Among them, the 30:70 double gel showed a slow swelling speed after 12 h. The swelling curve of the 50:50 double gel was significantly lower than that of the water gel and the 30:70 double gel, which indicated that there was a relationship between the size and depth of the gap in the gel microstructure and the swelling behavior.

[0079] (6) Water and oil retention test A 3 g gel sample was poured into a pre-weighed 50 mL centrifuge tube, and after being placed at room temperature for 2 h, the sample was centrifuged at 8000 g for 15 min. After centrifugation, the sample bottom seepage was water, and the upper layer was oil. The liquid was sucked out with a needle, weighed, and the water and oil retention was calculated. The results are shown in Table 2. Figure 15 As shown in Table 2, the water and oil retention can reflect the stability and strength of the double gel. The water retention of all the double gels was more than 80%, indicating that the gel network structure of the system could effectively block the internal water. And the higher the proportion of oil gel, the higher the water retention of the double gel. The water gel composed of only gelatin had the highest water retention. However, too high oil gel content led to a decrease in oil retention, which might be because the network structure formed by less than 50% oil gel and water gel was more solid, thereby stabilizing the internal space structure, improving the water retention, and stabilizing the oil retention.

[0080] (7) Linear viscoelasticity test The apparent viscosity of the sample was tested by flow scanning. The viscosity of the sample was measured at a shear rate of 0.1 s -1 to 100 s -1 . The temperature and frequency were set to 25°C and 1 Hz, respectively. The test results are shown in Table 3. Figure 16 As shown in Table 3, the apparent viscosity of all the gels decreased with the increase of the shear rate, reflecting the shear thinning behavior. This phenomenon can be attributed to the fact that the originally tightly packed gel structure is broken under shear, thereby leading to a decrease in viscosity. However, the 50:50 double gel system showed better stability than the other two groups, which might be closely related to its network structure and internal support.

[0081] Test Example 2 This test example is an in vitro digestion performance test of different double gel samples.

[0082] Oral cavity: 1 g of the sample was crushed and added to 10 mL of simulated saliva. The mixture was shaken in a water bath at 37°C for 10 min. The completed sample was quickly placed in ice water to terminate the reaction. Then 5 mL of the sample was taken out.

[0083] Stomach: 15 mL of simulated gastric fluid was mixed with the previously digested sample. The mixture was shaken at 37 °C for 2 h, and 2 mL of sample was taken every 30 min. The digestion process was terminated by increasing the pH of the sample to 7.0.

[0084] Small intestine: 45 mL of simulated intestinal fluid was added to the sample after gastric digestion. The mixture was shaken at 37 °C for 2 h. Every 30 min, 2 mL of the digested sample was collected and the digestion reaction was terminated in an ice water bath. During the 2 h of small intestine digestion, 0.2 mol / L NaOH was constantly added to maintain the pH at 7.0, and the volume of consumed NaOH was recorded over time.

[0085] The lipid digestion of the double gels was evaluated by determining the rate of free fatty acid release during in vitro simulated intestinal digestion of the double gel samples. As shown in Figure 17 , the free fatty acid release of all double gel samples showed a rapid release at the beginning of the reaction due to the excess of pancreatic lipase, the oil emulsified to form micelles quickly reacted with the enzyme, showing a rapid release of free fatty acid. As the reaction continued, the enzyme binding sites were gradually saturated and the high levels of galangin in the digestion solution inhibited the activity of the lipase, resulting in a gradual slowing of the rate of free fatty acid release until it reached equilibrium. Among them, the 5O:5H double gel system showed a more stable gel network structure, effectively reducing the oil decomposition rate; the rapid release of free fatty acid in the 3O:7H double gel system was due to its low oil gel content.

[0086] Test Example 3 (1) IDDSI determination According to the IDDSI test, the fork drop, fork pressure and spoon tilt tests were performed on the samples. When testing during fork pressure, the sample was subjected to thumb pressure fork evaluation deformation by a thumb pressure device. The IDDSI test results, including fork drop, fork pressure and spoon tilt tests, are shown in Figure 18 , the flow characteristics were tested by the fork drop method to test the passage of the double gel through the fork tines. It was shown that all gels could be stacked on the fork without persistent dripping, and were classified as level 4. The cross pressure test results showed that, except for the 7O:3H double gel sample, the remaining gel samples could be broken without small particles or flocculation, leaving a clear mark on the sample.

[0087] The spoon tilting experiment results show that the residual amount of gel 3O:7H, 5O:5H is less after tilting. The 7O:3H double gel has high viscosity, and may not slide down when tilted, causing a large amount of food residue, which does not meet the dietary needs of IDDSI dysphagia. High-viscosity food may require more tongue pressure to push the bolus into and through the throat, increasing the risk of obstruction. It is shown that the double gel of the mass ratio of oil gel and water gel between 3O:7H-5O:5H meets the needs of people with dysphagia, and the 5O:5H double gel sample is the best active material-loaded double gel system for people with dysphagia.

[0088] (2) Food simulation experiment for dysphagia According to the F14C03 P / 20 dysphagia food detection method in the texture analyzer. The TPA method was used, the test height was 15 mm, the test speed was 10.0 mm / sec, and the sample was graded according to the standard. As shown in Table 2 and Figure 19 The gelatin hydrogel has the highest hardness, but the adhesion is extremely low, and the coagulation is high. The tongue needs to be crushed, but due to the high coagulation, the bolus may be better, which is suitable for patients with mild dysphagia. The single oil gel has high adhesion, which may cause throat sticking risk. With the increase of the proportion of oil gel, the hardness of the double gel decreases significantly (from 7800→1238 N / m²), which is easier to swallow. At the same time, the 5O:5H water gel has more stable state and lower adhesion, which can effectively ensure the stability of the double gel loaded with active ingredients, and is more suitable for patients with moderate to severe dysphagia.

[0089] Table 2 Simulation test results of different gels for dysphagia

[0090] 5O:5H double gel is the most suitable formula for patients with dysphagia, which has low hardness, low adhesion and high structural stability, meets the IDDSI 4-level standard, is suitable for drug development, realizes precise delivery and long-term release of drugs; can also be used for health products to improve the stability and bioavailability of functional factors; at the same time, in the field of special medical purpose food, it can also provide safe and effective nutritional support for patients with dysphagia.

[0091] As described above, the basic principles, main features and advantages of the present application are better described. The above examples and descriptions only describe the preferred embodiments of the present application, and the present application is not limited by the above examples. Without departing from the spirit and scope of the present application, various changes and improvements to the technical solutions of the present application made by those skilled in the art shall fall within the scope of protection of the present application.

Claims

1. A double gel easy to swallow and capable of loading functional factors, characterized in that, The double gel is composed of a hydrogel and an oil gel; The hydrogel is based on gelatin, and the content of the gelatin in the hydrogel is 1-5% by mass percentage; The oil gel is based on vegetable oil, and the oil gel is based on monoglyceride, and the content of the monoglyceride in the oil gel is 5-15% by mass percentage; The mass ratio of the oil gel to the hydrogel is 3-5:5-7.

2. The double gel according to claim 1, characterized in that, The vegetable oil is peanut oil, olive oil or coconut oil.

3. The double gel of claim 1, wherein, The content of the gelatin in the hydrogel is 5% by mass percentage; the vegetable oil in the oil gel is peanut oil, and the content of the monoglyceride in the oil gel is 10% by mass percentage.

4. The double gel of claim 3, wherein, The double gel has a hardness of 1878 to 3912 N / m 2 adhesion ≤ 33 J / m 3 .

5. The double gel of claim 4, wherein, The mass ratio of the oil gel to the hydrogel in the double gel is 5:

5.

6. The double gel of claim 5, wherein, The double gel can effectively delay lipid decomposition.

7. Process for the preparation of a double gel according to any one of claims 1 to 6, characterized in that, The method comprises the following steps: S1, preparing a hydrogel: dissolving gelatin in water, heating and stirring until fully mixed, and cooling to 4℃ to form a hydrogel; S2, preparing an oil gel: dissolving monoglyceride in vegetable oil, and cooling to room temperature to form an oil gel; S3, mixing the hydrogel and the oil gel in a certain proportion, homogenizing and cooling to form a double gel.

8. Use of the double gel according to any one of claims 3-6 as a carrier for preparing a medicine, health product, nutritional supplement or functional food for people with difficulty in swallowing.

9. Use according to claim 8, characterized in that, The active ingredient of the medicine, health product, nutritional supplement or functional food is a fat-soluble ingredient.

10. Use of the double gel according to claim 5 as a carrier for preparing a medicine, health product, nutritional supplement or functional food for people with moderate to severe difficulty in swallowing.

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