Synergistic fat-reducing composition based on supramolecular technology and application thereof

Abstract

The invention relates to the technical field of functional food, and particularly discloses a synergistic fat-reducing composition based on a supramolecular inclusion technology and application thereof.The composition comprises four active extracts including rhizoma polygonati polysaccharide (larger than or equal to 50%), momordica saponin (larger than or equal to 30%), chlorogenic acid (larger than or equal to 40%) and nuciferine (larger than or equal to 20%). The composition is prepared from the following active ingredients in parts by mass: 1-10 parts of rhizoma polygonati, 1-8 parts of bitter gourd, 0.5-5 parts of coffee and 0.5-5 parts of lotus leaves (optimally 5: 4: 2: 2) through molecular inclusion with hydroxypropyl-beta-cyclodextrin or sulfobutyl ether-beta-cyclodextrin. The inclusion ratio is (1: 0.5)-(1: 10), and the composition comprises the following active ingredients in parts by mass: 1-10 parts of rhizoma polygonati, 1-8 parts of bitter gourd, 0.5-5 parts of coffee and 0.5-5 parts of lotus leaves. The problem of multi-component phase separation is solved through supramolecular inclusion, the bioavailability is improved, and triple synergistic fat reduction of inhibiting fat synthesis (FAS), activating decomposition (ATGL) and improving adiponectin is realized. The composition can be used for preparing fat-reducing functional food or health-care products, and the effect of the composition is obviously superior to that of single-component or physical mixed products.

Description

Technical Field

[0001] The present invention relates to the field of functional food technology, and specifically to a plant active ingredient composition based on supramolecular inclusion technology and its application in fat-reducing functional foods or health products, especially to a supramolecular complex of four active ingredients, polygonatum polysaccharide, momordica charantia saponins, coffee chlorogenic acid, and nuciferine, and a cyclodextrin carrier, which achieves synergistic fat-reducing and efficacy-enhancing by improving the solubility and bioavailability of multiple components. Background Art

[0002] As global obesity rates continue to rise, according to data from the World Health Organization in 2024, the proportion of overweight adults has reached 39%. Safe and effective fat reduction methods have become a research focus in the field of public health. Currently, mainstream fat reduction methods can be divided into three categories: 1. Current Status and Limitations of Commonly Used Fat Reduction Methods Lifestyle intervention, including dietary control (such as a low-calorie diet or a ketogenic diet) and regular exercise, is a fundamental approach to obesity prevention and treatment. However, this approach requires long-term adherence, patient compliance is generally low, and its effectiveness is limited in people with moderate to severe obesity.

[0003] Drug treatment: Commonly used drugs in clinical practice include orlistat (lipase inhibitor) and liraglutide (GLP-1 receptor agonist). Although they can quickly reduce body fat percentage, they have side effects such as gastrointestinal reactions (for example, orlistat causes a steatorrhea incidence of about 25%) and cardiovascular risks (some drugs are restricted for use by the FDA), and their long-term safety is questionable.

[0004] Functional foods / health supplements: Due to their safety and availability, they are becoming increasingly popular among those seeking weight loss. Currently, most commercially available products are based on ingredients such as dietary fiber (such as inulin), conjugated linoleic acid (CLA), and L-carnitine. While these can help regulate metabolism, their mechanisms of action are limited (for example, L-carnitine only promotes fatty acid transport) and their efficacy is limited, making them unable to meet consumers' dual demands for "efficacy and safety."

[0005] 2. Research progress of plant active ingredients in the field of fat loss In recent years, natural plant active ingredients have become a research hotspot for fat-reducing functional foods due to their multi-target effects and low toxicity and side effects. The following is the current status of research on several key ingredients: Polygonatum sibiricum active ingredients: Polygonatum sibiricum is a traditional medicinal and edible plant. Its main active ingredient is Polygonatum sibiricum polysaccharide (PSP). Studies have shown that PSP can inhibit the expression of lipase (FAS) by activating the AMPK signaling pathway while promoting the activity of lipase (ATGL).

[0006] Active ingredients of bitter melon: Momordica charantia saponins (MC-S) have been shown to upregulate the expression of fatty acid β-oxidation-related genes (such as CPT1A) by activating PPARα transcription factors.

[0007] Active ingredients of coffee: Chlorogenic acid (CGA) in coffee is a polyphenol compound, and its fat-reducing mechanism includes: ① inhibiting α-glucosidase to delay sugar absorption; ② promoting the secretion of adiponectin by adipose tissue.

[0008] Active ingredients of lotus leaf: Nuciferine in lotus leaf (Nelumbo nucifera) is an aporphine alkaloid that can inhibit the activity of phosphodiesterase (PDE), increase the intracellular cAMP level, and thus activate the protein kinase A (PKA)-mediated lipolysis pathway.

[0009] The above ingredients all show clear fat-reducing potential when used alone, but are limited by the following technical bottlenecks, and their actual application effects are significantly different from theoretical expectations.

[0010] 3. Core Issues of Existing Technologies 1. Multi-component synergistic barriers: The physicochemical properties of plant active ingredients vary significantly (e.g., Polygonatum sibiricum polysaccharide is a high-polarity macromolecule, while nuciferine is a low-polarity small molecule). Phase separation is likely to occur when they are directly physically mixed, resulting in asynchronous release in the body and difficulty in achieving multi-pathway synergistic enhancement.

[0011] 2. Low bioavailability: Momordica charantia saponins, nuciferine and other ingredients have poor water solubility (momordica charantia saponins solubility <0.1 mg / mL). After oral administration, they are easily degraded by gastric acid or excreted by intestinal efflux pumps (such as P-gp). The actual absorption rate is less than 20%.

[0012] 3. Insufficient adaptability of carrier technology: Existing cyclodextrin inclusion technology is mainly targeted at single components (such as β-cyclodextrin inclusion of nuciferine), but has poor compatibility for complex multi-component systems: Natural cyclodextrins (α / β / γ types) have a fixed cavity size (the inner diameter of the β-cyclodextrin cavity is approximately 0.78 nm), and cannot simultaneously accommodate active ingredients of different sizes, such as polygonatum polysaccharide (molecular weight approximately 10 kDa) and chlorogenic acid (molecular weight 354.3 Da). The inclusion rate of unmodified cyclodextrin for highly polar components (such as Polygonatum sibiricum polysaccharide) is low (<15%), and the inclusion complex has poor stability (easily dissociated in the presence of gastric acid).

[0013] In summary, developing a fat-reducing composition that can simultaneously solve the problems of multi-component synergy, bioavailability enhancement, and stable co-delivery is a technical problem that needs to be urgently solved in the current field of functional foods containing plant active ingredients. Summary of the Invention

[0014] In response to the core problems of existing plant active ingredient fat-reducing compositions pointed out in the background technology, such as multi-component synergistic barriers, low bioavailability and insufficient carrier compatibility, the purpose of the present invention is to provide a synergistic fat-reducing composition based on supramolecular inclusion technology, which achieves high efficiency and stabilization of multi-pathway synergistic fat reduction through multi-component co-inclusion at the molecular level, carrier structure optimization and ratio control.

[0015] To achieve the above object, the present invention adopts the following technical solutions: 1. Composition of the synergistic fat-reducing composition The composition comprises an active extract of polygonatum, an active extract of bitter melon, an active extract of coffee, an active extract of lotus leaf, and a cyclodextrin-based supramolecular carrier; the four active extracts and the cyclodextrin-based carrier form a supramolecular complex through molecular inclusion complexation, and the inclusion ratio is the total mass of the active extract: the mass of the cyclodextrin = 1:0.5 to 1:10.

[0016] 2. Specific definition of active extracts To ensure efficacy stability, each active extract must meet the following purity requirements: The active extract of Polygonatum sibiricum is Polygonatum sibiricum polysaccharide (content ≥50%): obtained through a water extraction, alcohol precipitation and macroporous resin purification process, the high-purity polysaccharide can specifically activate the AMPK pathway and inhibit fat synthesis; The active extract of bitter melon is bitter melon saponin (content ≥30%): it is purified by acid hydrolysis-silica gel column chromatography. The high-purity saponin can effectively activate PPARα and promote fatty acid oxidation; The active extract of coffee is chlorogenic acid (content ≥40%): After 70% ethanol extraction and polyamide column enrichment, high-purity chlorogenic acid can significantly increase serum adiponectin levels; The active extract of lotus leaf is nuciferine (content ≥20%): purified by pH gradient extraction-recrystallization, high-purity nuciferine can effectively inhibit phosphodiesterase (PDE) activity.

[0017] 3. Selection of cyclodextrin carriers To address the compatibility issues of multiple components, the cyclodextrin carrier is at least one of hydroxypropyl-β-cyclodextrin (HP-β-CD) or sulfobutyl ether-β-cyclodextrin (SBE-β-CD). This type of modified cyclodextrin enhances the inclusion effect through the following mechanisms: The hydroxypropyl / sulfobutyl substituents increase the hydrophilicity of cyclodextrin and improve its inclusion affinity with Polygonatum sibiricum polysaccharide (high polarity); The cavity size is adjustable (the inner diameter of the HP-β-CD cavity is approximately 0.8-1.0 nm), adapting to active substances of different molecular weights (the molecular weight of Polygonatum sibiricum polysaccharide is approximately 10 kDa, and the molecular weight of chlorogenic acid is 354.3 Da); The steric hindrance of the substituent enhances the stability of the inclusion complex (dissociation rate ≤15% in artificial gastric fluid at pH 1.2, compared with the dissociation rate of natural β-cyclodextrin ≥40%).

[0018] 4. Mass fraction of active ingredient To achieve optimal synergistic effect, the mass proportions of each active extract are: 1-10 parts of polygonatum active extract, 1-8 parts of momordica charantia active extract, 0.5-5 parts of coffee active extract, and 0.5-5 parts of lotus leaf active extract; the optimal ratio is 5 parts of polygonatum, 4 parts of momordica charantia, 2 parts of coffee, and 2 parts of lotus leaf (at this ratio, the comprehensive scores of FAS inhibition rate, ATGL activation rate and adiponectin enhancement rate are the highest).

[0019] 5. Preparation Method The preparation method of the composition comprises the following steps: (a) Extraction and purification: Polygonatum sibiricum, bitter melon, coffee, and lotus leaf were subjected to water extraction and alcohol precipitation (Polygonatum sibiricum), acid hydrolysis (bitter melon), 70% ethanol extraction (coffee), and pH gradient extraction (lotus leaf), respectively. The active extracts were then purified using a macroporous resin / silica gel column / polyamide column. (b) Supramolecular inclusion: The four active extracts were mixed in appropriate proportions and stirred with a cyclodextrin carrier in an aqueous solution at 30-60°C for 2-4 hours (stirring rate 200-400 rpm) to form an inclusion complex through intermolecular hydrogen bonding and van der Waals forces; (c) Drying and molding: The inclusion solution is freeze-dried (-50°C, 10Pa) to obtain a solid complex to avoid high temperature destruction of the active ingredients.

[0020] 6. Application The composition can be used to prepare food or health products with fat-reducing function, and its fat-reducing mechanism is manifested as a triple synergistic effect: inhibiting the activity of lipase (FAS), activating lipase (ATGL) and increasing serum adiponectin levels.

[0021] The present invention solves the core problems of the prior art through the above technical solution, and its beneficial effects are as follows: 1. Multi-ingredient synergistic effect: The supramolecular inclusion structure enables the four active ingredients to coexist in a molecularly dispersed state, avoiding phase separation caused by physical mixing. In vitro release experiments showed that the time difference between the peak release of Polygonatum sibiricum polysaccharide and Nuciferine in the inclusion complex was shortened from 3 hours in the physical mixing group to 0.5 hours, improving the synergistic efficiency by approximately 70%.

[0022] 2. Bioavailability is significantly improved: The hydrophilic substituents of the hydroxypropyl / sulfobutyl modified cyclodextrin improve the water solubility of momordica charantia saponins and nuciferine, and the inclusion complex structure resists dissociation by gastric acid. Pharmacokinetic studies in rats showed that the bioavailability of chlorogenic acid in the inclusion complex group was 2.3 times higher than that in the physical mixture group, and the absorption rate of nuciferine increased from 18% to 45%.

[0023] 3. Strengthening of triple fat-reducing mechanism: The inclusion complex with the optimal ratio showed significant synergy in the high-fat model rat experiment: The FAS enzyme activity inhibition rate reached 62% (compared to 35% in the Polygonatum sibiricum single group); ATGL enzyme activity increased 4.1 times (compared to 2.3 times in the bitter melon alone group); Serum adiponectin levels increased by 35% (compared to 18% in the coffee-only group); Under the combined effects, the body fat percentage of rats was reduced by 28% compared with the model group, and the effect was significantly better than commercially available single ingredient or physical mixed products. DETAILED DESCRIPTION

[0024] The technical solutions of the present invention will be clearly and completely described below in conjunction with specific embodiments of the present invention. Obviously, the embodiments described are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention. The embodiments are only used to explain the present invention and do not constitute a limitation on the scope of protection of the present invention.

[0025] Example 1 A synergistic fat-reducing composition based on supramolecular technology is prepared by the following steps: 1. Extraction and purification of active extracts: Polygonatum sibiricum polysaccharide (content 52%): Take 1 kg of dried Polygonatum sibiricum rhizome, grind it and add 10 times the amount of deionized water, extract it under reflux at 90°C twice (2 hours each time), and combine the extracts; centrifuge it at 4000 rpm for 10 minutes, take the supernatant and add 3 times the volume of 95% ethanol for precipitation for 12 hours, and filter to obtain crude polysaccharide; the crude polysaccharide is purified by D101 macroporous resin column (eluent: water) and freeze-dried to obtain Polygonatum sibiricum polysaccharide.

[0026] Momordica charantia saponins (content 32%): Take 500 g of dried momordica charantia fruit, grind it, add 5 times the amount of 0.1 mol / L hydrochloric acid solution, and hydrolyze it at 80°C for 3 hours; adjust the pH of the hydrolyzate to neutral, extract it with ethyl acetate three times, and combine the organic phases; purify the extract by silica gel column chromatography (eluent: chloroform-methanol = 9:1), and concentrate under reduced pressure to obtain momordica charantia saponins.

[0027] Chlorogenic acid (content 43%): Take 300g of roasted coffee powder, add 5 times the amount of 70% ethanol, and extract twice at 50℃ (1 hour each time). The extracts are combined; the extracts are enriched by polyamide column (eluent: 50% ethanol), concentrated under reduced pressure, and freeze-dried to obtain chlorogenic acid.

[0028] Nuciferine (content 21%): Take 500g of dried lotus leaves, grind them, add 10 times the amount of 0.1mol / L hydrochloric acid solution, soak for 2 hours, adjust the pH to 10, extract with dichloromethane three times, combine the organic phases; dry the extract with anhydrous sodium sulfate, and obtain nuciferine after recrystallization.

[0029] 2. Supramolecular inclusion: Polygonatum sibiricum polysaccharide (5 g), momordica charantia saponins (4 g), chlorogenic acid (2 g), and nuciferine (2 g) were mixed evenly, and 20 g of hydroxypropyl-β-cyclodextrin (HP-β-CD) (inclusion ratio = 1:1.5) was added, placed in 500 mL of deionized water, and stirred at 40 °C and 300 rpm for 3 hours to form a uniform inclusion solution.

[0030] 3. Drying and molding: The inclusion solution was freeze-dried (-50°C, 10 Pa) for 24 hours to obtain a white solid complex.

[0031] Example 2 A synergistic fat-reducing composition based on supramolecular technology is prepared by the following steps: The extraction and purification of the active extract was the same as in Example 1; Supramolecular inclusion: Polygonatum sibiricum polysaccharide (1 g), momordica charantia saponins (1 g), chlorogenic acid (0.5 g), and nuciferine (0.5 g) were mixed, and 5 g of sulfobutyl ether-β-cyclodextrin (SBE-β-CD) was added (inclusion ratio = 1:2.5), and stirred at 40°C and 300 rpm for 3 h; The drying and molding were the same as in Example 1 to obtain the sample of Example 2.

[0032] Example 3 A synergistic fat-reducing composition based on supramolecular technology is prepared by the following steps: The extraction and purification of the active extract was the same as in Example 1; Supramolecular inclusion: Polygonatum sibiricum polysaccharide (10 g), momordica charantia saponins (8 g), chlorogenic acid (5 g), and nuciferine (5 g) were mixed, and 50 g of HP-β-CD was added (inclusion ratio = 1:2). The mixture was stirred at 50°C and 250 rpm for 4 h. The drying and molding were the same as in Example 1 to obtain the sample of Example 3.

[0033] Comparative Example 1 Preparation steps: The extraction, purification and component ratio of the active extract were the same as in Example 1; Supramolecular inclusion: The mixed active substance (13 g) and natural β-cyclodextrin (20 g) were added to deionized water and stirred at 40 °C and 300 rpm for 3 h; The drying and molding were the same as in Example 1 to obtain the sample of Comparative Example 1 (the carrier was unmodified cyclodextrin).

[0034] Comparative Example 2 Preparation steps: The extraction, purification and component ratio of the active extract were the same as in Example 1; Polygonatum sibiricum polysaccharide (5 g), momordica charantia saponins (4 g), chlorogenic acid (2 g), and nuciferine (2 g) were directly mixed evenly without performing the inclusion and drying steps to obtain the sample of Comparative Example 2 (physical mixture).

[0035] Comparative Example 3 Preparation steps: Only Polygonatum sibiricum polysaccharide (5 g) was taken, and 5 g of HP-β-CD was added (inclusion ratio = 1:1). The mixture was stirred at 40°C and 300 rpm for 3 hours, and freeze-dried to obtain the sample of Comparative Example 3 (single component inclusion compound).

[0036] Effect verification experiment Sixty SPF male SD rats (weighing 200±20g) were selected and randomly divided into six groups (10 rats in each group): a blank control group (normal diet), a model group (high-fat diet), Example 1 group, Example 2 group, Example 3 group, Comparative Example 1 group, Comparative Example 2 group, and Comparative Example 3 group (Note: In actual experiments, the grouping needs to be adjusted according to the number of animals; this is a simplified description). Except for the blank control group, the remaining groups were fed a high-fat diet (45% fat content) to establish an obesity model. After four consecutive weeks, each experimental group was gavaged with the corresponding sample at a dose of 100 mg / kg, while the blank and model groups were gavaged with an equal volume of normal saline. After four consecutive weeks of intervention, the following indicators were measured (see Table 1): Table 1

[0037] Experimental Conclusion Examples 1-3: The body fat percentage was reduced by 24-28% compared with the model group, and the FAS inhibition rate, ATGL activation rate and adiponectin level were significantly better than those of the control group, demonstrating that the composition of the present invention can achieve a synergistic fat-reducing effect within the component range, and Example 1 has the best effect.

[0038] Comparative Example 1 (natural cyclodextrin): The body fat percentage was reduced by only 16%, and the chlorogenic acid AUC and nuciferine absorption rate were significantly lower than those in the example, indicating that the inclusion effect of the unmodified cyclodextrin was insufficient, verifying the necessity of modified cyclodextrin.

[0039] Comparative Example 2 (physical mixing): The body fat percentage was only reduced by 10%, and the FAS inhibition rate and ATGL activation rate were close to those of the model group, proving that the synergistic effect of multiple components requires the inclusion structure to achieve synchronous release.

[0040] Comparative Example 3 (single ingredient): The body fat percentage was only reduced by 15%, and the adiponectin level was limitedly improved, which verified the necessity of multi-ingredient synergy.

[0041] The above experimental data show that the present invention effectively solves the problems of multi-component synergy barriers, low bioavailability and insufficient carrier adaptability in the prior art through supramolecular inclusion technology, modified cyclodextrin carriers and optimized component ratios, and has significant technological advancement and application value.

Claims

1. A synergistic fat-reducing composition based on supramolecular technology, characterized by: Contains active extracts of Polygonatum sibiricum, bitter melon, coffee, lotus leaf, and cyclodextrin-based supramolecular carriers; The four active extracts and the cyclodextrin supramolecular carrier form a complex through molecular inclusion reaction, and the inclusion ratio is 1:0.5-1:

10.

2. The composition according to claim 1, wherein: The active extract of Polygonatum sibiricum is Polygonatum sibiricum polysaccharide, with a content of ≥50%; The active extract of bitter melon is bitter melon saponin, with a content of ≥30%; The active extract of coffee is chlorogenic acid, with a content of ≥40%; The active extract of lotus leaf is nuciferine, with a content of ≥20%.

3. The composition according to claim 1 or 2, characterized in that: The cyclodextrin supramolecular carrier is at least one of hydroxypropyl-β-cyclodextrin and sulfobutyl ether-β-cyclodextrin.

4. The composition according to claim 1, characterized in that The mass fractions of each active extract are: 1-10 parts of Polygonatum sibiricum active extract; 1-8 parts of bitter melon active extract; 0.5-5 parts of coffee active extract; 0.5-5 parts of lotus leaf active extract.

5. The composition according to claim 4, characterized in that The optimal mass fraction is: 5 parts of Polygonatum sibiricum active extract; 4 parts of bitter melon active extract; 2 parts of coffee active extract; 2 parts of lotus leaf active extract.

6. A method for preparing the composition according to any one of claims 1 to 5, characterized in that: include: (a) Polygonatum sibiricum, bitter melon, coffee, and lotus leaf were subjected to water extraction, alcohol precipitation, and macroporous resin purification to obtain active extracts; (b) The four active extracts were mixed in proportion and then included with a cyclodextrin-based supramolecular carrier in an aqueous solution at 30-60°C for 2-4 hours with stirring; (c) The inclusion solution was freeze-dried to obtain a solid supramolecular complex.

7. Use of the composition according to any one of claims 1 to 5 in the preparation of food or health products with fat-reducing function.

8. The use according to claim 7, characterized in that: The fat-reducing function is manifested in the simultaneous inhibition of lipase (FAS) activity, activation of lipase (ATGL) and increase in serum adiponectin levels.

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