Synergistic uric acid reducing composition having medicinal and edible composite formula with tuna goose carnosine

Abstract

The invention provides a synergistic uric acid reducing composition having a medicinal and edible composite formula with tuna goose carnosine, and relates to the field of medicinal and edible homology. According to the composition, the tuna goose carnosine, the gardenia extract, the chicoric acid, the celery extract and the like are scientifically proportioned, the tuna goose carnosine is extracted by adopting a three-stage membrane separation technology, and efficient utilization of active ingredients is ensured. The composition reduces the generation of uric acid from the source by inhibiting the activity of xanthine oxidase, and achieves the effect of reducing uric acid. Experiments show that the xanthine oxidase inhibition rate of the composition in an in-vitro experiment reaches up to 85%, the serum uric acid level can be reduced by 20% or above in a hyperuricemia animal model, the composition has good safety to the liver and the kidney, and related indexes are extremely small in fluctuation. The composition can be prepared into a solid dosage form or an oral liquid dosage form, is convenient to use, provides a safe and effective uric acid reducing solution for patients with hyperuricemia, and has a remarkable synergistic uric acid reducing effect and a wide application prospect.

Description

Technical Field

[0001] This invention relates to the field of food and medicine homology technology, specifically to a synergistic uric acid-lowering composition with a food and medicine homology compound formulation of tuna angiospermide. Background Technology

[0002] In the research field of uric acid-lowering compositions, current solutions mainly focus on two pathways: First, reducing uric acid production by inhibiting the activity of xanthine oxidase, such as allopurinol, which binds to xanthine oxidase, reducing the enzyme's catalytic efficiency and thus decreasing uric acid production. Second, promoting uric acid excretion, primarily by promoting uric acid excretion through the kidneys, such as benzbromarone, which increases the rate of uric acid excretion in the kidneys and lowers the concentration of uric acid in the blood. In addition, some studies have attempted to combine traditional Chinese medicine extracts with Western medicines, hoping to combine the pharmacological effects of both, and to combine several traditional Chinese medicine extracts to utilize the multi-target characteristics of traditional Chinese medicine to achieve uric acid-lowering effects.

[0003] These technical solutions have a certain degree of theoretical rationale and have achieved some practical effects in lowering uric acid levels. However, upon closer analysis, it is not difficult to find that there are areas where the existing technologies can be improved and perfected.

[0004] Existing uric acid-lowering technologies are mainly divided into three categories: First, xanthine oxidase inhibitors, represented by allopurinol. Although these drugs can effectively inhibit uric acid production, long-term use may lead to adverse consequences such as liver and kidney damage and allergic reactions. Second, uricosuric agents, represented by benzbromarone, mainly promote the excretion of uric acid through the kidneys, but they pose certain risks to patients with renal insufficiency and may cause side effects such as uric acid kidney stones. Third, uric acid-lowering products derived from both food and medicine. These products are usually based on single Chinese herbal extracts or simple compound formulas. Although they have a certain degree of safety and market potential, their uric acid-lowering effect is relatively weak, and there are shortcomings in terms of ingredient standardization and quality control.

[0005] Further analysis reveals the following common shortcomings in existing technologies: First, single-component or simple compound uric acid-lowering compositions are insufficient to address the complex pathological mechanisms of hyperuricemia. Hyperuricemia involves multiple factors, including excessive uric acid production and insufficient excretion. Single-component or simple compound formulations often only target a specific aspect and cannot comprehensively and effectively lower uric acid levels. Second, while some chemical drugs have significant uric acid-lowering effects, long-term use may place a burden on vital organs such as the liver and kidneys, limiting their widespread and long-term clinical application. Third, existing food-medicine homology products have not fully explored the synergistic potential between food ingredients and medicinal materials, and there is room for improvement in component standardization and quality control. This not only affects the uric acid-lowering efficacy of the products but also limits their market competitiveness and consumer trust. These issues provide directions for improvement and innovation in this invention, prompting the development of a more efficient, safe, and stable uric acid-lowering composition to meet the needs of the market and patients. Summary of the Invention

[0006] (a) Technical problems to be solved To address the shortcomings of existing technologies, this invention provides a synergistic uric acid-lowering composition with a medicinal and edible compound formulation of tuna angiosin, thus solving the problems mentioned in the background art.

[0007] (II) Technical Solution A synergistic uric acid-lowering compound with a medicinal and edible homologous compound formulation of tuna anchovy peptide comprises the following components by weight percentage: 30%-50% tuna anchovy peptide, 10%-25% gardenia extract, 5%-15% chicoric acid, 3%-10% celery extract, with the balance being a pharmaceutically or food-grade acceptable carrier, typically a common excipient such as microcrystalline cellulose, maltodextrin, glycerin, starch, lactose, mannitol, hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG), and water, which can be selected according to the dosage form.

[0008] Step 2: Gardenia, chicory, and celery are extracted separately using a water extraction and alcohol precipitation process to obtain extracts. The water extraction and alcohol precipitation process includes: using water as a solvent, extracting 1-3 times at 80-90℃ for 1-3 hours each time; combining the extracts, concentrating them, adding ethanol to make the alcohol content reach 50%-70%, allowing them to stand and precipitate, taking the supernatant, concentrating and drying to obtain the extract. Preferably, the tuna anchovy is purified using a three-stage membrane separation technique: first, the bonito cooking liquid is initially filtered through a ceramic membrane with a pore size of 0.1-0.5 μm at 0.2-0.8 MPa; then, it is further separated through a spiral wound membrane with a molecular weight cutoff of 500-1500 Da at 1.0-2.5 MPa; finally, the fraction with a molecular weight cutoff of 200-1000 Da is spray-dried to obtain a powder with an anchovy content of ≥10%.

[0009] Preferably, the weight ratio of the tuna goose muscle peptide to the gardenia extract is (1.5-2.5):1.

[0010] Preferably, the gardenia extract contains ≥40% genipin and the celery extract contains ≥15% flavonoids.

[0011] Preferably, the preparation method of the composition includes: preparing standardized extracts by subjecting gardenia, chicory, and celery to 80°C water and 60% ethanol precipitation, and then mixing them with tuna goose muscle peptide in a specified ratio.

[0012] Preferably, the composition exhibits a xanthine oxidase inhibition rate of ≥85% in in vitro experiments; Preferably, the composition reduces serum uric acid levels by ≥20% in animal models of hyperuricemia, and the fluctuations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are ≤5%.

[0013] Preferably, the carrier comprises microcrystalline cellulose, maltodextrin, or glycerol, and is formulated into a solid dosage form or an oral liquid dosage form.

[0014] Preferably, the optimal weight ratio of the tuna goose muscle peptide to the gardenia extract is 2:1.

[0015] Preferably, a method for preparing a synergistic uric acid-lowering composition having a medicinal and edible homologous compound formulation with tuna anserine peptide, applied to the above-mentioned synergistic uric acid-lowering composition having a medicinal and edible homologous compound formulation with tuna anserine peptide, includes the following steps: Step 1: Extract tuna goose muscle peptides using a three-stage membrane separation technique; Step 2: Gardenia, chicory, and celery are extracted separately using a water extraction and alcohol precipitation process to obtain extracts. The water extraction and alcohol precipitation process includes: using water as a solvent, extracting 1-3 times at 80-90℃ for 1-3 hours each time; combining the extracts, concentrating them, adding ethanol to make the alcohol content reach 50%-70%, allowing them to stand and precipitate, taking the supernatant, concentrating and drying to obtain the extract. Step 3: Mix tuna cheesin, gardenia extract, chicoric acid and celery extract according to the specified ratio, add a carrier and prepare a solid or liquid dosage form.

[0016] (III) Beneficial Effects This invention provides a synergistic uric acid-lowering composition with a medicinal and edible compound formulation of tuna angiotensin, which has the following beneficial effects: 1. This composition inhibits xanthine oxidase activity through multi-target synergistic action, reducing uric acid production at its source. In vitro experiments show that the xanthine oxidase inhibition rate is as high as 85% or more. In animal experiments, serum uric acid levels in hyperuricemia models decreased by more than 20%, and urinary uric acid excretion increased to 7.9±0.8 mg / 24h (3.8±0.4 in the model group), an increase of 108%. Combined with a 52.3% downregulation of renal URAT1 mRNA expression, this demonstrates that it can both reduce uric acid production and promote uric acid excretion, thereby reducing uric acid reabsorption.

[0017] 2. The composition exhibited good tolerability in safety tests. In the acute toxicity test, healthy ICR mice were administered a dose of 40g / kg by gavage and observed continuously for 14 days. The survival rate was 100%, and the mice showed normal food intake, water intake, and activity. There was no significant difference in weight gain compared to the control group, and no significant change in organ coefficients, indicating low toxicity to the body and suitability for long-term use. This solves the problem that some chemical drugs in the prior art may cause adverse reactions such as liver and kidney damage with long-term use, providing a safer uric acid-lowering option for patients with hyperuricemia. Attached Figure Description

[0018] Figure 1 This is a schematic diagram of the present invention. 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] Example 1: like Figure 1 As shown, this embodiment of the invention provides a synergistic uric acid-lowering composition with a medicinal and edible compound formula of tuna goose peptide. This uric acid-lowering composition is prepared from the following components: 300g tuna goose peptide extract, 150g gardenia extract, 100g chicoric acid, and 50g celery extract. After pulverizing and mixing all components, add 400g of microcrystalline cellulose and compress into tablets using conventional wet granulation process (each tablet contains 500mg of the composition).

[0021] To verify the uric acid-lowering efficacy of the composition in this embodiment, a comparative experimental study on the composition's ability to reduce hyperuricemia was conducted.

[0022] Male SD rats (200±20g) were divided into: normal control group (administered via gavage with physiological saline); Hyperuricemia model group (intraperitoneal injection of potassium oxonate 300 mg / kg); allopurinol group (40 mg / kg by gavage); combination therapy group (300 mg / kg by gavage, 3 times daily).

[0023] Serum uric acid levels were measured after 7 days of continuous intervention, and the results are shown in Table 1: Table 1: Serum uric acid levels (μmol / L) in rats of each group

[0024] Results and conclusions Uric acid-lowering efficacy: The serum uric acid reduction in the combined treatment group (300mg / kg) reached 69.6% (389.5→118.4μmol / L), which was significantly better than that in the allopurinol group (64.0%, p<0.05), proving that the "2:1" ratio of anserine peptide-gardenia still has a strong effect at high doses; Synergistic mechanism evidence: In vitro supplementation experiments showed that the composition inhibited xanthine oxidase (XOD) by 81.3%, which was higher than 79% of the theoretical sum of 102.9% of the inhibition rate of anserine peptide alone (53.7%) and gardenia alone (49.2%). The synergistic index indicating the synergistic effect = (inhibition rate of anserine peptide alone + inhibition rate of gardenia alone) / measured inhibition rate of the composition = (53.7% + 49.2%) / 81.3% ≈ 1.27 (>1.2, indicating a significant synergistic effect). Dosage form advantages: The tablet process allows for sustained release of the active ingredient, with peak blood concentration reached 3 hours after administration and maintained for more than 8 hours, making it suitable for a three-times-daily dosing regimen.

[0025] Example 2: This invention provides a synergistic uric acid-lowering composition with a medicinal and edible compound formula of tuna anchovy extract and tuna anchovy extract. The uric acid-lowering composition is prepared from the following components: 400g tuna anchovy extract, 200g gardenia extract, 80g chicoric acid, and 70g celery extract. The preparation method is as follows: Tuna goose muscle peptide extraction: Bonito cooking water is filtered through a 0.2μm ceramic membrane (0.6MPa), the filtrate is enriched with 200-1000Da components through an 800Da spiral wound membrane (1.8MPa), and spray dried to obtain powder (goose muscle peptide content 13.5%). Gardenia / Celery Extraction: Gardenia crude powder was extracted twice with water at 80℃ using a 1:10 material-to-liquid ratio. The filtrates were combined and ethanol was added to a concentration of 60% for precipitation. The extract was then freeze-dried to obtain gardenia extract (genipin 43.2%). Celery was extracted using the same method and then purified using macroporous resin (flavonoid content 18.1%). Each component is mixed with 230g of microcrystalline cellulose, granulated in a fluidized bed (inlet air temperature 65℃), and then packaged into capsules.

[0026] The efficacy verification method was the same as in Example 1, but the oral gavage dose of the composition was adjusted to 150 mg / kg·d. The results are shown in Table 2. Table 2: Serum uric acid levels and liver and kidney safety (Day 7)

[0027] ( p<0.05, (p<0.01 vs model group) Results and conclusions High efficacy at low doses: At 150 mg / kg·d (only half the dose in Example 1), the uric acid reduction rate still reached 69.5% (368.9→112.6 μmol / L), confirming the synergistic effect of the 2:1 ratio. Breakthrough in liver and kidney safety: ALT / AST fluctuation ≤5% (model group: 58.3±6.2→56.1±5.9U / L), while the allopurinol group showed significant liver damage (ALT↑53.5%) and renal tubular vacuolar degeneration rate <5% (allopurinol group >30%). Process contribution: Fluidized bed granulation improves the thermal stability of goose muscle peptide (60℃ accelerated test for 7 days, content retention rate 98.2% vs conventional granulation 93.5%), ensuring long-term storage of capsules.

[0028] Example 3: This invention provides a synergistic uric acid-lowering composition with a medicinal and edible compound formula of tuna goose peptide. The uric acid-lowering composition is prepared from the following components: 250g tuna goose peptide extract, 100g gardenia extract, 120g chicoric acid, 80g celery extract, and 50g Poria cocos extract. The preparation method is as follows: (1) The extraction of tuna goose muscle peptides was the same as in Example 2, but the molecular weight cutoff of the spiral wound membrane was adjusted to 500 Da; (2) Poria cocos was extracted by hot water reflux (material-liquid ratio 1:15, 80℃×2h×2 times), concentrated and freeze-dried; (3) Mix each component with 200g of glycerin and 600g of pure water evenly, and bottle it as an oral liquid (each 10mL contains 1g of the composition).

[0029] The efficacy verification method was the same as in Example 1, and the oral dose of the composition was 200 mg / kg·d. The results are shown in Table 3. Table 3: Multiple indicators of uric acid metabolism (Day 7)

[0030] Experimental conclusions Uric acid lowering efficiency: The serum uric acid level in the treatment group of the combination was reduced to 124.7±11.6μmol / L, which was 66.9% lower than that in the model group (376.4±31.8μmol / L) (p<0.01), confirming that the oral liquid formulation containing Poria cocos extract has a significant uric acid lowering effect; Mechanism of excretion promotion: Urinary uric acid excretion increased to 7.9±0.8 mg / 24h (3.8±0.4 in the model group), an increase of 108%, combined with a 52.3% downregulation of renal URAT1 mRNA expression, proving that this composition promotes excretion by inhibiting uric acid reabsorption; Dosage form advantages: Oral liquid dosage forms are comparable to solid dosage forms in lowering uric acid at the same dose (200mg / kg·d), and are more suitable for long-term use.

[0031] Example 4: Safety Test Acute toxicity test: Forty healthy ICR mice (half male and half female) were fasted for 12 hours: Experimental group: 0.5% sodium carboxymethyl cellulose suspension, administered by gavage at a dose of 40 g / kg (twice daily); Control group: Equal volume of solvent.

[0032] After 14 days of continuous observation, the results showed: 100% survival rate: No deaths. Normal behavioral characteristics: no abnormalities in eating, drinking, or activity. Weight gain: experimental group (28.5±2.1) g vs control group (27.8±1.9) g (p>0.05) Organ coefficients: There were no significant differences in the indices of heart, liver, spleen, lung, and kidney compared with the control group (p>0.05). Conclusion: The maximum tolerated dose (MTD) of this composition is >40 g / kg, which is much lower than that of allopurinol. (78mg / kg).

[0033] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A synergistic uric acid-lowering composition with a medicinal and edible compound formula of tuna anserine peptide, characterized in that, It includes the following components by weight percentage: 30%-50% tuna angiotensin, 10%-25% gardenia extract, 5%-15% chicoric acid and 3%-10% celery extract, with the balance being pharmaceutically or food-acceptable carriers. The composition achieves a synergistic effect in lowering uric acid by inhibiting both xanthine oxidase (XOD) activity and renal uric acid reabsorption.

2. The synergistic uric acid-lowering composition according to claim 1, which has a medicinal and edible compound formulation with tuna anserine peptide, is characterized in that: The tuna anchovy is purified using a three-stage membrane separation technique, which includes: primary filtration of the bonito cooking water using a ceramic membrane; secondary separation of the filtrate after primary filtration using a spiral wound membrane; and extraction of the target component with a molecular weight of 200-1000 Da, followed by spray drying to obtain a powder with an anchovy content of ≥10%.

3. The synergistic uric acid-lowering composition according to claim 1, which has a medicinal and edible compound formulation with tuna angiosin, is characterized in that: The weight ratio of the tuna goose muscle peptide to the gardenia extract is (1.5-2.5):1, preferably 2:

1.

4. The synergistic uric acid-lowering composition according to claim 1, which has a medicinal and edible compound formulation with tuna anserine peptide, is characterized in that: The gardenia extract contains ≥40% genipin, and the celery extract contains ≥15% flavonoids.

5. The application of the synergistic uric acid-lowering composition according to any one of claims 1-4, which has a medicinal and edible compound formulation with tuna goose muscle peptide, in the preparation of uric acid-lowering functional foods.

6. The application according to claim 5, characterized in that: The composition can reduce serum uric acid levels by ≥20% in hyperuricemia model animals, with no significant change in ALT / AST levels.

7. A method for preparing a synergistic uric acid-lowering composition having a medicinal and edible homologous compound formulation with tuna anserine peptide, applicable to any one of the synergistic uric acid-lowering compositions having a medicinal and edible homologous compound formulation with tuna anserine peptide as described in claims 1-4, characterized in that, Includes the following steps: Step 1: Extract tuna goose muscle peptides using a three-stage membrane separation technique; Step 2: Gardenia, chicory, and celery are extracted separately using a water extraction and alcohol precipitation process to obtain extracts. The water extraction and alcohol precipitation process includes: using water as a solvent, extracting 1-3 times at 80-90℃, each time for 1-3 hours. Combine the extracts, concentrate them, add ethanol to make the alcohol content reach 50%-70%, let them stand to precipitate, take the supernatant, concentrate and dry to obtain the extract; Step 3: Mix tuna cheesin, gardenia extract, chicoric acid and celery extract according to the specified ratio, add a carrier and prepare a solid or liquid dosage form.

8. The method for preparing a synergistic uric acid-lowering composition with tuna anserine peptide as described in claim 7, characterized in that: The three-stage membrane separation process conditions are as follows: ceramic membrane pore size 0.1-0.5μm and operating pressure 0.2-0.8MPa; spiral wound membrane molecular weight cutoff 500-1500Da and operating pressure 1.0-2.5MPa.

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