Starch-based gel carrier for collaborative delivery of vitamin D-calcium and preparation method of starch-based gel carrier

Abstract

The invention discloses a starch-based gel carrier for collaborative delivery of vitamin D-calcium and a preparation method thereof. According to the invention, calcium ions and vitamin D nutrients are delivered by preparing a starch-based gel carrier, and the release of the carrier in a simulated in-vitro stomach and intestine digestion stage is determined. The starch-based gel carrier prepared by the invention can realize targeted release of calcium ions and vitamin D in an intestinal digestion stage, and is relatively low in cost and simple in process. By taking common corn starch and sodium laurate as examples, after a starch-sodium laurate compound and a starch-vitamin D compound suspension are added into nano calcium carbonate, formation of gel is induced in situ, and slow release of calcium ions and vitamin D in a gastric digestion stage and rapid release of calcium ions and vitamin D in an intestinal digestion stage are realized. The gel carrier can realize protection of vitamin D in a stomach digestion stage and targeted release of vitamin D in an intestinal digestion part, and can effectively improve absorption of vitamin D by a human body so as to assist absorption of calcium ions by the human body.

Description

Technical Field

[0001] This invention belongs to the fields of food and chemical industry, and specifically relates to a method for preparing a starch-based gel carrier for vitamin D-calcium synergistic delivery. Background Technology

[0002] Osteoporosis is the most common age-related degenerative bone disease, especially in older women. Clinically, it is characterized by low bone mass and damage to the bone microstructure, leading to increased bone fragility and a higher risk of fractures. Treatment options primarily include medication and autologous bone grafting. Frontiers in endocrinology , 2022, 13:989648), but all have certain drawbacks or increase the patient's pain. Therefore, preventing osteoporosis through diet has important social significance. Calcium supplementation can effectively maintain the dynamic balance of bone metabolism, while vitamin D is the main nutrient that regulates calcium absorption and bone metabolism ( , 2022, 13:989648). Physiological reviews , 2016, 96(1): 365-408). The human body mainly synthesizes vitamin D through the skin after exposure to ultraviolet radiation, and obtains very little from the diet (only 10%). Nutrients , 2023, 15(5),1111). Therefore, it is necessary to increase vitamin D intake while supplementing calcium, which is beneficial for preventing and alleviating osteoporosis in the elderly. However, vitamin D is a fat-soluble vitamin and needs a carrier to deliver it in order to achieve the purpose of nutritional supplementation.

[0003] Starch is an abundant natural resource. It possesses functional properties such as biodegradability, good biocompatibility, and renewability. As a green raw material, many researchers have focused on starch, with starch-lipid complexes being extensively studied. These are known as the fifth type of resistant starch, and small amounts of natural starch-lipid complexes have also been found in some grains. This complex can not only achieve the sustained and controlled release of hydrophobic substances (such as volatile antibacterial substances and nutrients), but can also be added to food to prepare functional foods. Compared with the direct loading and delivery of substances by starch-lipid complexes, starch-based gel carriers have greater application potential. Starch and fatty acid salts can form V-shaped complexes, which are negatively charged polyelectrolytes. These substances exhibit good water solubility due to the repulsive force of their own charge. After introducing hydrogen ions or salt ions to neutralize the negative charge, the complex molecules gradually aggregate to form a gel due to the disappearance of electrostatic repulsion, making it a good starch-based gel carrier. Starch-fatty acid complexes and gels have shown application potential in multiple fields due to their unique properties.

[0004] Most existing technologies utilize starch and similar materials as external coatings to form complexes with guest molecules, thereby achieving the protective delivery of the guest substances. For example, starch can effectively load 1.96% vitamin D in the form of a complex. However, the development of its utilization methods needs further improvement. Based on this, starch-fatty acid salt complexes are prepared using starch, a green, renewable, and inexpensive resource, as a raw material. Using this complex as a substrate, gel-type carriers that can synergistically deliver vitamin D and calcium are prepared. This type of gel delivery carrier can enrich the variety of nutritional health foods for the elderly population in China, greatly improve their quality of life, enhance their sense of happiness and fulfillment, promote healthy aging, and has significant economic benefits and social significance. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the present invention aims to provide a safe, green, low-cost, and simple-to-operate vitamin D-calcium co-delivery starch-based gel carrier. This invention can simultaneously supply calcium ions and assist in the delivery of vitamin D, maximizing the absorption of calcium ions by the human body.

[0006] The objective of this invention is achieved through the following technical solution: A method for preparing a starch-based gel carrier for vitamin D-calcium co-delivery includes the following steps: (1) Prepare a starch suspension with a concentration of 0.5-20%, and after gelatinization, add 0.5-20% fatty acid salt or 0.1-5% vitamin D respectively. After precipitation and separation, obtain starch-fatty acid salt complex and starch-vitamin D complex. (2) Disperse the starch-fatty acid salt complex and starch-vitamin D complex obtained in step (1) in water and stir thoroughly to obtain a suspension of 0.5-15%; (3) Add 0.1-10% of nano-calcium carbonate powder to the suspension obtained in step (2) and stir to disperse thoroughly; (4) Add 0.1-5% of a weakly acidic substance to the mixture obtained in step (3); (5) Let the mixture obtained in step (4) stand for 5-30 minutes to obtain a starch-based gel carrier containing calcium ions and vitamin D; Preferably, in step (1), the starch is one of waxy corn starch, ordinary corn starch, high amylose corn starch, or wheat starch.

[0007] Preferably, in step (1), the fatty acid salt is one of lauryl salt, myristate salt, palmitate salt, and stearate salt.

[0008] Preferably, in step (1), vitamin D is one of vitamin D2 and vitamin D3.

[0009] In step (1), precipitation separation is a conventional technique in the field, such as ethanol precipitation, propanol precipitation, butanol precipitation, isopropanol precipitation, and water evaporation precipitation.

[0010] Preferably, the composite in step (2) is in one of the following forms: solid powder, block, or high-concentration liquid.

[0011] In step (3), stirring and dispersing is a conventional technique in the field, and can be one of magnetic stirrers, high-speed shear machines, stirring paddles, or vortex oscillation dispersion.

[0012] Preferably, in step (4), the weak acidic substance is one of gluconolactone, dilute hydrochloric acid, dilute sulfuric acid, dilute hydrochloric acid, acetic acid, gluconic acid, citric acid, phosphoric acid, and sulfurous acid.

[0013] The operating temperatures in steps (1), (2), (3), (4), and (5) are all at room temperature. The vitamin D-calcium synergistic delivery starch-based gel carrier prepared by the above method is...

[0014] This invention utilizes calcium ion-induced starch-fatty acid salt complexes to form a gel, effectively delivering vitamin D and calcium ions, thereby achieving synergistic delivery of vitamin D and calcium ions and providing technical support for improving the efficient absorption of calcium ions. Calcium supplementation effectively maintains the dynamic balance of bone metabolism, while vitamin D is the main nutrient regulating calcium absorption and bone metabolism. The human body mainly synthesizes vitamin D through skin irradiation by ultraviolet radiation, obtaining relatively little from the diet (only 10%). Therefore, it is necessary to supplement calcium supplementation while simultaneously increasing vitamin D intake, which is beneficial for preventing and alleviating osteoporosis in the elderly. In this invention, a calcium ion-induced starch-based gel carrier is prepared to deliver vitamin D, achieving vitamin D delivery while supplementing calcium. Furthermore, the preparation process of this invention is simple, low-cost, and easy to operate.

[0015] Compared with the prior art, the advantages of the present invention are as follows: (1) The method of preparing the gel carrier in this invention is simple. It mainly involves calcium ions inducing starch-based materials to generate a gel carrier in situ. The gel carrier is an aqueous substance, which is more easily accepted by the oral cavity. At the same time, the viscoelasticity of the gel is beneficial for the elderly.

[0016] (2) The present invention mainly delivers starch-vitamin D complex through gel delivery. Compared with traditional delivery methods, this method can further improve the delivery efficiency of vitamin D, is easy to operate, has low cost, and is simple in process, making it more conducive to industrial production and large-scale application. Attached Figure Description

[0017] Figure 1The release curves of calcium ions by the starch-based gel carriers obtained in Comparative Example 1, Comparative Example 2, Example 1, and Example 2 during simulated digestion in vitro are shown.

[0018] Figure 2 The release curves of vitamin D from the starch-based gel carriers obtained in Comparative Example 1, Comparative Example 2, Example 1, and Example 2 are shown in the in vitro simulated digestion process. Detailed Implementation

[0019] To better understand the present invention, the following description, in conjunction with embodiments, further illustrates the present invention. However, the scope of protection claimed by the present invention is not limited to the scope described in the embodiments.

[0020] The following examples illustrate the technical solution of the present invention. The technical solution of the present invention is not limited to these examples; starch-based gel carriers for vitamin D-calcium co-delivery prepared by other methods are also applicable.

[0021] The vitamin D content was determined using the following method: High-performance liquid chromatography (HPLC) was employed. The detection column was HC-C18, the mobile phase was methanol / acetonitrile (20 / 80), the flow rate was 1 mL / min, and vitamin D was detected at 264 nm using a UV detector.

[0022] In this example, calcium ion release was determined as follows: a mixture of 1.7 mmol / L nitric acid and 1.7 mmol / L pyridinedicarboxylic acid was prepared as the mobile phase, with a flow rate of 0.9 mL / min and a column temperature of 30°C. The calcium ion content at each digestion stage was detected using a non-inhibited conductivity detector and a Metrosep C6-150 / 4.0 column.

[0023] Example 1 (1) Prepare a 5% ordinary corn starch suspension, gelatinize it, and then add 10% sodium lauryl nitrate or 0.2% vitamin D3 respectively. After precipitation and separation, obtain starch-sodium lauryl nitrate complex and starch-vitamin D complex. (2) Disperse the starch-sodium lauryl complex and starch-vitamin D complex obtained in step (1) in water and stir thoroughly to obtain a 5% suspension; (3) Add 0.5% of nano-calcium carbonate powder to the suspension obtained in step (2) and stir to disperse thoroughly; (4) Add 0.1% gluconolactone to the mixture obtained in step (3); (5) Let the mixture obtained in step (4) stand for 20 minutes to obtain a starch-based gel carrier containing calcium ions and vitamin D; After testing, such as Figure 1As shown, the obtained starch-based gel carrier can release less calcium ions and vitamin D during the gastric digestion stage, while releasing calcium ions and vitamin D more rapidly during the intestinal digestion stage, thus achieving gastric-protected delivery of vitamin D.

[0024] Figure 1 The release curves of calcium ions by the starch-based gel carriers obtained in Comparative Example 1, Comparative Example 2, Example 1, and Example 2 during simulated digestion in vitro are shown.

[0025] Figure 2 The release curves of vitamin D from the starch-based gel carriers obtained in Comparative Example 1, Comparative Example 2, Example 1, and Example 2 are shown in the in vitro simulated digestion process.

[0026] like Figure 1 As shown in Example 1, the calcium ion release rate of the gel carrier sample was relatively low and the release curve was relatively flat in the stomach stage. However, in the intestinal stage, the calcium ion release rate increased significantly, and the release curve rose significantly. The different trends in the calcium ion release curves in the stomach and intestine stages are mainly due to the difference in pH environment between the stomach and intestine. Figure 2 As shown, the release rate of vitamin D from the gel carrier was very low in all samples during gastric digestion, almost approaching 0%. This is likely because the gel structure remained relatively intact during gastric digestion, with the starch-vitamin D complex tightly encapsulated and not digested, resulting in extremely low vitamin D release. During intestinal digestion, the release rate of all samples increased rapidly, eventually reaching approximately 70%-80%. This is mainly because the intestinal environment disrupted the gel structure, exposing the starch-vitamin D complex within the gel, which was then digested, leading to the release of vitamin D from the complex. These results indicate that this type of gel carrier can achieve the simultaneous release of calcium ions and vitamin D, effectively improving the body's absorption of calcium ions.

[0027] Example 2 (1) Prepare a 5% ordinary corn starch suspension, gelatinize it, and then add 5% sodium lauryl precipitate or 0.2% vitamin D3 respectively. After precipitation and separation, obtain starch-sodium lauryl precipitate complex and starch-vitamin D complex. (2) Disperse the starch-sodium lauryl complex and starch-vitamin D complex obtained in step (1) in water and stir thoroughly to obtain a 5% suspension; (3) Add 0.5% of nano-calcium carbonate powder to the suspension obtained in step (2) and stir to disperse thoroughly; (4) Add 1% gluconolactone to the mixture obtained in step (3); (5) Let the mixture obtained in step (4) stand for 20 minutes to obtain a starch-based gel carrier containing calcium ions and vitamin D; Tests showed that the obtained starch-based gel carrier released low levels of vitamin D and calcium ions during gastric digestion, but released them rapidly during intestinal digestion, which can effectively improve the body's absorption of calcium ions.

[0028] Example 3 (1) Prepare a 0.5% ordinary corn starch suspension, gelatinize it, and then add 0.5% sodium stearate or 0.1% vitamin D2 respectively. After precipitation and separation, obtain starch-sodium stearate complex and starch-vitamin D complex. (2) Disperse the starch-sodium stearate complex and starch-vitamin D complex obtained in step (1) in water and stir thoroughly to obtain a 0.5% suspension; (3) Add 0.1% of nano calcium carbonate powder to the suspension obtained in step (2) and stir thoroughly to disperse; (4) Add 0.1% citric acid to the mixture obtained in step (3); (5) Let the mixture obtained in step (4) stand for 20 minutes to obtain a starch-based gel carrier containing calcium ions and vitamin D; Tests showed that the obtained starch-based gel carrier effectively retains calcium ions and vitamin D during gastric digestion and rapidly releases them during intestinal digestion, which can effectively improve the body's absorption of vitamin D and thus promote the absorption of calcium ions.

[0029] Example 4 (1) Prepare a 20% ordinary corn starch suspension, gelatinize it, and then add 20% sodium palmitate or 5% vitamin D2 respectively. After precipitation and separation, obtain starch-sodium palmitate complex and starch-vitamin D complex. (2) Disperse the starch-sodium palmitate complex and starch-vitamin D complex obtained in step (1) in water and stir thoroughly to obtain a 20% suspension; (3) Add 10% nano calcium carbonate powder to the suspension obtained in step (2) and stir and disperse thoroughly; (4) Add 5% gluconolactone to the mixture obtained in step (3); (5) Let the mixture obtained in step (4) stand for 20 minutes to obtain a starch-based gel carrier containing calcium ions and vitamin D; Tests showed that the obtained starch-based gel carrier effectively retains calcium ions and vitamin D during gastric digestion and rapidly releases them during intestinal digestion, which can effectively improve the body's absorption of vitamin D and thus promote the absorption of calcium ions.

[0030] Comparative Example 1 (1) Prepare a 5% ordinary corn starch suspension, gelatinize it, add 10% sodium laurate, and obtain a starch-sodium laurate complex after precipitation and separation. (2) Disperse the starch-sodium lauryl complex obtained in step (1) in water, add 5 mg of vitamin D3, and stir thoroughly to obtain a 5% suspension; (3) Add 0.5% of nano-calcium carbonate powder to the suspension obtained in step (2) and stir to disperse thoroughly; (4) Add 0.1% gluconolactone to the mixture obtained in step (3); (5) Let the mixture obtained in step (4) stand for 20 minutes to obtain a starch-based gel carrier containing calcium ions and vitamin D.

[0031] After testing, such as Figure 1 , 2 As shown, calcium ions maintain a low release rate during the gastric digestion stage, but vitamin D is released rapidly during the gastric digestion stage, failing to achieve the protective delivery effect of vitamin D.

[0032] Comparative Example 2 (1) Prepare a 5% ordinary corn starch suspension, gelatinize it, add 5% sodium laurate, and obtain a starch-sodium laurate complex after precipitation and separation. (2) Disperse the starch-sodium lauryl complex obtained in step (1) in water, add 2 mg of vitamin D3, and stir thoroughly to obtain a 5% suspension; (3) Add 0.5% of nano-calcium carbonate powder to the suspension obtained in step (2) and stir to disperse thoroughly; (4) Add 0.1% gluconolactone to the mixture obtained in step (3); (5) Let the mixture obtained in step (4) stand for 20 minutes to obtain a starch-based gel carrier containing calcium ions and vitamin D.

[0033] After testing, such as Figure 1 , 2 As shown, vitamin D is released rapidly during the gastric digestion stage, which is not conducive to its stable arrival at the intestinal absorption stage, thus its effect in assisting calcium ion absorption is relatively weak.

[0034] It should be noted that, for those skilled in the art, the implementation of this invention is not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of this invention should be considered equivalent substitutions and are included within the protection scope of this invention.

Claims

1. A starch-based gel carrier for vitamin D-calcium synergistic delivery and its preparation method, characterized in that, Includes the following steps: (1) Prepare a starch suspension with a concentration of 0.5-20%, and after gelatinization, add 0.5-20% fatty acid salt or 0.1-5% vitamin D respectively. After precipitation and separation, obtain starch-fatty acid salt complex and starch-vitamin D complex. (2) Disperse the starch-fatty acid salt complex and starch-vitamin D complex obtained in step (1) in water and stir thoroughly to obtain a suspension of 0.5-15%; (3) Add 0.1-10% of nano-calcium carbonate powder to the suspension obtained in step (2) and stir to disperse thoroughly; (4) Add 0.1-5% of a weakly acidic substance to the mixture obtained in step (3); (5) Let the mixture obtained in step (4) stand for 5-30 minutes to obtain a starch-based gel carrier containing calcium ions and vitamin D.

2. The preparation method according to claim 1, characterized in that, In step (1), the starch is one of waxy corn starch, ordinary corn starch, high amylose corn starch, and wheat starch.

3. The preparation method according to claim 1, characterized in that, In step (1), the fatty acid salt is one of lauryl salt, myristate salt, palmitate salt, and stearate salt.

4. The preparation method according to claim 1, characterized in that, In step (1), the vitamin D is one of vitamin D2 and vitamin D3.

5. The preparation method according to claim 1, characterized in that, The composite described in step (2) is in one of the following forms: solid powder, block, or high-concentration liquid.

6. The preparation method according to claim 1, characterized in that, In step (4), the weak acidic substance is one of gluconolactone, dilute hydrochloric acid, dilute sulfuric acid, dilute hydrochloric acid, acetic acid, gluconic acid, citric acid, phosphoric acid, and sulfurous acid.

7. A starch-based gel carrier for vitamin D-calcium synergistic delivery prepared by the preparation method according to any one of claims 1 to 6.

Images