A sodium alginate / calcium beta-hydroxy-beta-methylbutyrate instant gelation powder with dual functions of fat reduction and muscle gain and application thereof

Abstract

This invention discloses an instant gelling powder of sodium alginate / calcium β-hydroxy-β-methylbutyrate with dual functions of fat reduction and muscle gain, and its application, belonging to the field of functional food or pharmaceutical preparation technology. The powder of this invention is prepared by dry mixing sodium alginate and CaHMB at a weight ratio of 5~10:1~5, preferably 7:3, wherein the guluronic acid content of sodium alginate is ≥50%. In use, 1g of powder is added to 20~40mL of water at 60~100°C, and stirred to form a hydrogel. After oral administration, the powder rapidly forms a gel in the stomach, producing a feeling of fullness, and simultaneously achieves fat reduction, muscle gain, and metabolic regulation functions by regulating myostatin expression. This invention overcomes the limitation of existing weight management products with only one function, innovatively integrating the three major effects of instant satiety, fat reduction, and muscle gain. The preparation process is simple and environmentally friendly, requiring no added chemical excipients, and has significant technological advancement and market application value.

Description

Technical Field

[0001] This invention belongs to the field of functional food or pharmaceutical preparation technology, specifically relating to an instant gelling powder of sodium alginate / calcium β-hydroxy-β-methylbutyrate with dual functions of fat reduction and muscle gain, and its application. Background Technology

[0002] With the increasing severity of obesity in modern society, people have widely recognized the significant health risks it poses. Dietary control is the most commonly used intervention in weight management. However, current research indicates a key flaw in traditional weight loss methods: improvements in body composition are more important than simple weight loss. Numerous clinical observations have confirmed that unscientific weight management methods lead to significant skeletal muscle loss without effectively reducing body fat percentage. This weight loss model, primarily focused on muscle tissue depletion, is not only detrimental to health but also makes it difficult to maintain weight loss, resulting in significant weight rebound.

[0003] Currently, satiety products on the market are mainly divided into three types: glucomannan-based, protein-based, and bulking agent-based. Although these products can produce a feeling of fullness to some extent, they generally suffer from the following technical drawbacks: short duration of action, requirement for large doses, slow onset of action, unstable effects, and potential safety hazards such as intestinal obstruction. In contrast, hydrogel products, as an emerging biodegradable weight management solution, exhibit unique technological advantages: they quickly produce a feeling of fullness by stimulating the gastrointestinal tract and slowing gastric emptying through physical and mechanical action; they promote the secretion of satiety-related hormones to prolong the duration of satiety; and they improve the balance of intestinal flora and metabolic dysfunction through the intestinal barrier function.

[0004] Among natural polysaccharide materials, sodium alginate has been widely used in the food and pharmaceutical fields due to its excellent gelling properties and biocompatibility. Sodium alginate-based hydrogels require the addition of exogenous calcium salts to trigger gelation. This not only reduces energy intake through physical occupancy in the stomach but also regulates the secretion of appetite-related peptides (such as GLP-1 and PYY), inhibits lipid digestive enzyme activity, and promotes the proliferation of beneficial gut microbiota, thus participating in metabolic regulation and weight management at multiple levels. However, current technologies often employ a composite system of sodium alginate and acid-soluble calcium salts (CaCO3) to enhance the gel formation rate of sodium alginate in the acidic environment of the stomach. However, due to significant individual differences in gastric acid secretion, the gel formation rate and stability are difficult to precisely control; some gels are easily destroyed by peristalsis in the stomach, weakening their physical barrier function; long-term use may reduce fat but may also lead to safety hazards such as calcium deposition in the gastric mucosa and electrolyte imbalance, along with the risk of muscle loss. Meanwhile, calcium β-hydroxy-β-methylbutyrate (CaHMB), as a safe and effective functional food ingredient, has gained global recognition in the field of sports nutrition. CaHMB has multiple benefits, including promoting protein synthesis, inhibiting protein breakdown, and regulating muscle energy metabolism; however, current technologies are mainly limited to its compound application with amino acids. Furthermore, existing CaHMB formulations generally suffer from technical bottlenecks such as complex processes (requiring nano-encapsulation or enzymatic hydrolysis), high production costs, and difficulty in large-scale production.

[0005] Based on the above analysis of the current state of technology, there is an urgent need in this field to develop an innovative weight management product that should simultaneously meet the following key requirements: (1) it can quickly generate a lasting and stable feeling of fullness; (2) it can synergistically promote fat metabolism and muscle synthesis; and (3) it has a simplified production process and good industrialization feasibility. Summary of the Invention

[0006] This invention addresses the technical shortcomings of existing weight management products, such as short duration of satiety and lack of synergistic effects in fat loss and muscle gain. It provides an instant-gelling oral powder based on sodium alginate / calcium β-hydroxy-β-methylbutyrate (CaHMB), its preparation method, and its application. Through precise design of the sodium alginate-CaHMB ratio and the application of instant-gelling technology, this invention successfully solves the following two key technical challenges: (1) achieving rapid generation and long-lasting maintenance of satiety; and (2) simultaneously achieving synergistic effects of fat loss and muscle gain. Compared with existing products, this invention simplifies the production process while achieving significant technological breakthroughs, forming a clear competitive advantage in the market.

[0007] This invention provides an instant gelling oral powder composed of sodium alginate and calcium β-hydroxy-β-methylbutyrate, wherein: The sodium alginate contains ≥50% guluronic acid, preferably 50-80%; The weight ratio of sodium alginate to calcium β-hydroxy-β-methylbutyrate is (5~10):(1~5), preferably 7:3; The powder forms a hydrogel within 5 minutes at 60-100°C after contact with water.

[0008] The present invention also provides a method for preparing the powder described above, comprising the following steps: 1) Mix sodium alginate with a guluronic acid content ≥50% with calcium β-hydroxy-β-methylbutyrate in a certain proportion; 2) Use a dry mixing process and mix for 1-5 minutes at room temperature; 3) Pass through an 80-200 mesh sieve to obtain a uniform powder.

[0009] This invention provides the application of the above-mentioned powder in the preparation of formulations that enhance satiety.

[0010] This invention provides the application of the above-mentioned powder in the preparation of fat-reducing and muscle-building preparations.

[0011] The beneficial effects of this invention include: (1) This invention controls the content of guluronic acid (G units), as it directly determines the stability and density of the "egg-box" cross-linked structure formed by sodium alginate and CaHMB. The higher the G unit content, the stronger and more ordered the resulting gel network structure, which allows the hydrogel to remain intact in the mechanical environment of the stomach and fully exert its physical satiety function of water retention and expansion. There is also a hydrogen bond between the anionic part of calcium β-hydroxy-β-methylbutyrate and sodium alginate. The hydrogen bonds generated have both competitive and secondary stabilizing effects, which allows the gel to better adapt to the dynamic digestive tract environment in vivo. However, more precise control of the M / G ratio of sodium alginate is required to manage the competition between hydrogen bonds and ionic bonds. This precise "structure-function" regulation is the key foundation for achieving the simultaneous effect of "immediate satiety" and "long-term metabolic regulation" to obtain synergistic fat reduction and muscle gain effects. Without control of the G unit content, it is impossible to construct a functionalized gel system with the required mechanical properties and sustained-release characteristics. (2) This invention creatively selects calcium β-hydroxy-β-methylbutyrate as the sole calcium source, giving it the dual functions of a cross-linking agent and a metabolically active ingredient. The hydrogel constructed in this way is no longer just a physical carrier, but an integrated active intervention system that can achieve "physical satiety in the stomach" and "slow release in the intestines to regulate metabolism for muscle gain and fat loss" in a time-controlled manner. This results in a fundamental innovation and improvement in both the application purpose (from material preparation to health intervention) and the final effect (from texture improvement to physiological metabolic regulation).

[0012] (3) The powder of the present invention has high resistance to deformation after gelation and can withstand shear force with strain of 67~262%; the powder of the present invention can quickly form hydrogel for rapid and long-lasting satiety regulation, significantly reducing food intake within 4 hours, inhibiting up to 27%, and without affecting total energy balance; when used for weight management, it can reduce body fat by more than 46.7%; when used for muscle growth, it can increase muscle mass by more than 49.5%; (4) The instant gelling oral powder of the present invention is more effective in regulating myostatin expression, reducing myostatin expression, improving muscle morphology, and alleviating muscle fiber atrophy and structural disorder. (5) The preparation process of the present invention is simple and does not require complex additives; and it is applicable to the fields of functional foods and sports nutrition. Attached Figure Description

[0013] Figure 1 The images show the appearance and microstructure of the sodium alginate / β-hydroxy-β-methylbutyrate powder in Example 1 after instant gelation.

[0014] Figure 2 Strain scans of sodium alginate / calcium β-hydroxy-β-methylbutyrate hydrogels with different mannulic acid / guluronic acid ratios.

[0015] Figure 3 Fourier transform rheological analysis of sodium alginate / calcium β-hydroxy-β-methylbutyrate hydrogels with different mannulic acid / guluronic acid ratios.

[0016] Figure 4 The effect of sodium alginate / calcium β-hydroxy-β-methylbutyrate hydrogel on food intake during the fasting / refeeding test is shown. A, B, and C represent the food intake of mice at 2 h, 4 h, and 10 h after gavage, respectively.

[0017] Figure 5 This study aims to improve the effects of sodium alginate / calcium β-hydroxy-β-methylbutyrate hydrogel on fat accumulation and muscle atrophy caused by obesity. A represents the body fat percentage of mice in different treatment groups at the end of the experiment, B represents the weight of epididymal white adipose tissue, C represents the weight of gastrocnemius muscle, and D and E represent the morphological changes of epididymal white adipose tissue and gastrocnemius muscle tissue as assessed by H&E staining (scale bar: 20 μm).

[0018] Figure 6 Immunohistochemical expression analysis of myostatin in mouse gastrocnemius muscle (scale bar: 50 μm). Detailed Implementation

[0019] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0020] The sodium alginate used in Examples 1-2 and Comparative Example 1 of this invention was purchased from Shanghai Maclean Biochemical Technology Co., Ltd., with mannuronic acid / guluronic acid content ratios of 1:2, 1:1, and 2:1, respectively, and a purity ≥90%. The sodium alginate used in Examples 3-4 via gavage was the same sodium alginate used in Example 1, i.e., the mannuronic acid / guluronic acid content ratio was 1:2. Calcium β-hydroxy-β-methylbutyrate was purchased from Shanghai Maclean Biochemical Technology Co., Ltd., with a purity ≥97%.

[0021] Example 1 1. First, prepare an instant gelling oral powder. The weight ratio of sodium alginate (mannuronic acid / guluronic acid content ratio is 1:2) to calcium β-hydroxy-β-methylbutyrate is 7:3. Use a dry mixing process, mix for 1-2 minutes at room temperature, and pass through a 200-mesh sieve to obtain a uniform powder. 2. Add 1g of instant gelling oral powder to 28.6 mL of water at 80 °C, and stir for 5 minutes to form a hydrogel. Figure 1 ).

[0022] The deformation resistance of the gel of the present invention was tested using the following method: The gel samples were directly loaded onto the rheometer stage using a 40 mm diameter plate. The temperature was 25 °C, and the measurement interval was 1000 μm. Strain scanning tests were performed at a fixed frequency of 1 Hz, covering a strain range from 0.1% to 1000%. Simultaneously, data acquisition and analysis were performed using the Fourier transform rheology module of the upgraded TRIOS software. Results are attached. Figure 2 and attached Figure 3 The results show that when the ratio of mannuronic acid to guluronic acid is 1:2, the sodium alginate / calcium β-hydroxy-β-methylbutyrate hydrogel exhibits weak strain overtuning behavior. The storage modulus (G') decreases monotonically and the loss modulus (G") initially increases and then decreases. This indicates that the hydrogel system undergoes an energy dissipation and reconstruction process under continuously increasing shear strain. At the same time, the gel can withstand a shear force of 262% of the strain.

[0023] Example 2 1. First, prepare an instant gelling oral powder. The weight ratio of sodium alginate (mannuronic acid / guluronic acid content ratio of 1:1) to calcium β-hydroxy-β-methylbutyrate is 7:3. Use a dry mixing process to mix for 1-2 minutes at room temperature and pass through a 200-mesh sieve to obtain a uniform powder. 2. The instant gelling oral powder forms a hydrogel within 5 minutes at 80 °C after contact with water.

[0024] The deformation resistance of the gel in this embodiment was tested using the method described in Example 1, and the results are shown in the appendix. Figure 2 and attached Figure 3 The results show that when the ratio of mannuronic acid to guluronic acid is 1:2, the hydrogel exhibits weak strain overtuning behavior, the storage modulus (G') decreases monotonically and the loss modulus (G") shows an initial increase followed by a decrease, indicating that the sodium alginate / β-hydroxy-β-methylbutyrate calcium hydrogel system has an energy dissipation and reconstruction process under continuously increasing shear strain. At the same time, the gel can withstand a shear force of 67% of the strain.

[0025] Comparative Example 1 1. First, prepare sodium alginate (mannuronic acid / guluronic acid content ratio of 2:1) and calcium β-hydroxy-β-methylbutyrate powder with a weight ratio of 7:3. Use a dry mixing process to mix for 1-2 minutes at room temperature and pass through a 200-mesh sieve to obtain a uniform powder. 2. The powder did not form a hydrogel at 80 °C after contact with water.

[0026] Example 3 The short-term satiety ability of Example 1 in this invention was tested using the following method: BALB / c male mice (5 weeks old) were acclimatized for one week before a fasting / refeeding experiment was conducted. Mice were randomly divided into four groups of 15 mice each: the control group (CON) was administered drinking water by gavage; the CaHMB group was administered CaHMB solution (10 mg / mL) by gavage; group A was administered sodium alginate solution (25 mg / mL) by gavage; and groups AC were administered the hydrogel from Example 1 by gavage. Mice were fasted for 13 hours before the experiment but had free access to water. At the start of refeeding, mice were initially administered 0.1 mL / 10 g body weight by gavage, followed by resuming feeding. For the next 11 hours, mice had free access to standard feed and water, and their food intake was recorded at 2, 4, and 10 hours after refeeding.

[0027] The results are attached. Figure 4The results show that the sodium alginate / β-hydroxy-β-methylbutyrate calcium hydrogel has a longer-lasting satiating effect than sodium alginate alone, and has the potential to be a short-term satiating agent. At the same time, the hydrogel significantly reduces food intake within 2-4 hours after gavage, and can inhibit food intake by up to 27%, but the effect disappears over time and does not affect the total energy balance.

[0028] Example 4 The long-term fat loss and muscle gain capabilities of Example 1 in this invention were tested using the following method: Five-week-old male BALB / c mice were randomly divided into five groups: (1) con group (n=6): conventional diet; (2) HFD group (n=6): high-fat diet (HFD); (3) CaHMB group (n=6): each mouse was administered CaHMB solution (10 mg / mL) by gavage; (4) A group (n=6): each mouse was administered sodium alginate solution (25 mg / mL) by gavage; (5) AC group (n=6): each mouse was given hydrogel from Example 1. Simultaneously, mice were administered the hydrogel by gavage daily at a volume of 0.1 mL / 10 g body weight. After a one-week acclimatization period, mice in the con group continued to be fed a conventional diet, while mice in the HFD, CaHMB, A, and AC groups were fed a high-fat diet (D12492) with 60% energy content, intended to rapidly increase body weight and induce obesity. The mice were fed this diet continuously for 6 weeks, with free access to food. Compare the body fat percentage, epididymal fat weight, gastrocnemius muscle weight, and epididymal fat and gastrocnemius muscle tissue sections of each group.

[0029] The results are attached. Figure 5 The results showed that, compared with the body fat percentage of obese mice induced by a high-fat diet, long-term intervention with sodium alginate / calcium β-hydroxy-β-methylbutyrate hydrogel significantly reduced body fat by 46.7%, significantly decreased epididymal fat mass, and resulted in denser fat cell arrangement and reduced diameter. Simultaneously, it increased muscle mass by 49.5%, significantly improving muscle atrophy, and significantly increased gastrocnemius muscle mass, further demonstrating that the hydrogel intervention in Example 1 significantly reduced adipose tissue mass and effectively maintained muscle mass during weight loss.

[0030] The ability of Example 1 of this invention to regulate muscle metabolism was tested using the following method: Gastrocnemius muscle tissue from each group of mice was collected and fixed with 4% paraformaldehyde, followed by dehydration and paraffin embedding. Sections were prepared to a thickness of 4–6 μm. Endogenous catalase activity was blocked by 3% hydrogen peroxide solution and incubated at room temperature in the dark for 25 min. 3% BSA was added to the histochemistry zone to evenly cover the tissue, and the tissue was blocked at room temperature for 30 min. Myostatin primary antibody was added, and the tissue was incubated overnight at 4 °C. Slides were washed three times in PBS (pH 7.4) on a destaining shaker for 5 min each time. After slightly drying the sections, secondary antibody (HRP-labeled) of the corresponding species was added to the zone to cover the tissue, and the tissue was incubated at room temperature for 50 min. DAB staining was used to generate a brown precipitate, indicating the distribution of myostatin. After staining, the tissue was dehydrated with a gradient of alcohols and cleared with xylene, and finally mounted with resin. The samples were observed under a microscope to analyze the distribution and expression of myostatin in the gastrocnemius muscle.

[0031] The results are attached. Figure 6 The results show that obesity caused by a high-fat diet has a significant negative impact on muscle morphology. The intervention of hydrogel in Example 1 is more effective in regulating myostatin expression, improving muscle morphology, and reducing muscle fiber atrophy and structural disorder.

[0032] The embodiments provided above are not intended to limit the scope of the invention, nor are the described steps intended to limit the order of execution. Any obvious modifications made to the invention by those skilled in the art based on existing common knowledge also fall within the scope of protection defined by the claims.

Claims

1. An instant gelling oral powder based on sodium alginate / calcium β-hydroxy-β-methylbutyrate, characterized in that, It is composed of sodium alginate and calcium β-hydroxy-β-methylbutyrate; the powder self-assembles into a hydrogel after contact with water, and slowly creates a feeling of fullness after oral administration; it achieves fat reduction, muscle gain and metabolic regulation functions by regulating myostatin expression.

2. The powder according to claim 1, characterized in that, The weight ratio of sodium alginate to calcium β-hydroxy-β-methylbutyrate is 5~10:1~5.

3. The powder according to claim 1, characterized in that, The weight ratio of sodium alginate to calcium β-hydroxy-β-methylbutyrate is 7:

3.

4. The powder according to claim 1, characterized in that, The sodium alginate has a guluronic acid content of ≥50%.

5. The powder according to claim 1, characterized in that, The sodium alginate has a guluronic acid content of 50-80%.

6. The powder according to claim 1, characterized in that, The powder forms a hydrogel within 5 minutes at 60-100 °C after contact with water.

7. The method for preparing the powder according to any one of claims 1 to 6, characterized in that, Sodium alginate and calcium β-hydroxy-β-methylbutyrate were mixed in a certain proportion and then dry-mixed to form a powder.

8. The use of the powder according to any one of claims 1 to 6 in the preparation of a satiety-enhancing formulation.

9. The use of the powder according to any one of claims 1 to 6 in the preparation of a fat-reducing formulation.

10. The use of the powder according to any one of claims 1 to 6 in the preparation of a muscle-building formulation.

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