Health-care wine with function of increasing uric acid re-secretion of human body and preparation method of health-care wine

Abstract

The invention relates to the technical field of health-care wine and particularly provides health-care wine with a function of increasing uric acid re-secretion of a human body and a preparation method of the health-care wine. The health-care wine comprises the following traditional Chinese medicine raw materials in parts by weight: 8-12 parts of codonopsis pilosula and 13-17 parts of poria cocos. During preparation, the medicinal materials are extracted by using white spirit as a wine base, and the extraction liquor is blended and dispatched by adding or not adding the extraction wine base, so that the health-care wine is formed, and the health-care wine has a remarkable function of increasing uric acid re-secretion of a human body, thereby increasing uric acid excretion in a kidney way and reducing the level of blood uric acid.

Description

Technical Field

[0001] This invention relates to the field of health wine technology, and specifically proposes a health wine with the function of increasing the re-secretion of uric acid in the human body and its preparation method. Background Technology

[0002] Due to the influence of the external environment and lifestyle habits, the proportion of people with hyperuricemia caused by metabolic abnormalities and the resulting uric acid crystals in the extremities is gradually increasing, affecting the normal life of people with hyperuricemia.

[0003] Hyperuricemia is a metabolic disease characterized by persistently elevated serum uric acid levels due to purine metabolism disorders or decreased uric acid excretion. Clinical interventions are mainly divided into two categories: Inhibit uric acid production: By blocking the final step of purine metabolism through xanthine oxidase inhibitors (such as allopurinol and febuxostat); Promote uric acid excretion: Increase renal uric acid clearance by inhibiting renal tubular uric acid reabsorption transporters (such as URAT1, GLUT9) or increasing uric acid secretion transporters (such as ABCG2, OAT1 / 3).

[0004] However, almost all currently available commercial products fall into category (1). These products generally suffer from the following defects: Long-term inhibition of xanthine oxidase can lead to xanthine accumulation and abnormal liver function. The lack of regulation of renal excretion leads to a rebound in blood uric acid levels after drug withdrawal. The bioavailability of active ingredients in Western medicine varies greatly among individuals, resulting in insufficient efficacy for some patients.

[0005] For the second type of "excretion-promoting" route, existing literature mainly focuses on chemical drugs such as benzbromarone and ricinard, but all of them are accompanied by serious hepatotoxicity or nephrotoxicity (for example, benzbromarone is restricted in many countries). There is no safe and long-term usable combination of food and medicine.

[0006] In the field of food and medicine homology, existing technologies disclose that the decoction of "Poria cocos-gardenia" can lower blood uric acid, but do not distinguish the mechanism of action; published patents report that total saponins of Codonopsis pilosula inhibit xanthine oxidase, but do not involve the renal excretion process.

[0007] Therefore, there is still a lack in this field of food and medicine products that are both safe and can avoid the defects of "inhibiting production" while achieving sustained uric acid reduction by "promoting renal re-secretion". Summary of the Invention

[0008] In view of this, the present invention aims to solve the problems of existing uric acid-lowering products, which mostly rely on inhibiting uric acid production pathways, resulting in low bioavailability, short-lasting effects, or easy rebound. It provides a health-promoting wine that lowers blood uric acid levels by increasing the re-secretion of uric acid in the human body and promoting renal excretion of uric acid, as well as its preparation method. The health-promoting wine prepared by the present invention is light yellow, clear and transparent, with a harmonious and elegant complex medicinal and wine aroma, a mellow taste, and a balanced medicinal flavor, exhibiting a typical style. The health-promoting wine of the present invention is safe and non-toxic, and its function of lowering blood uric acid has been proven.

[0009] The technical solution of the present invention is implemented as follows: The present invention provides a health wine with the function of increasing the re-secretion of uric acid in the human body, with Chinese medicinal materials that are both food and medicine as the core raw materials, specifically including the following Chinese medicinal materials in the following weight proportions: Codonopsis pilosula 8-12 parts, Poria cocos 13-17 parts.

[0010] In some embodiments, as a preferred option, the weight proportions of the Chinese herbal raw materials are: 10 parts of Codonopsis pilosula and 15 parts of Poria cocos. At this ratio, the synergistic effect of the raw materials is more significant, and the effect of promoting uric acid excretion can be better exerted.

[0011] In some implementations, to ensure the quality of raw materials and the content of effective ingredients, the present invention sets strict standards for raw materials: In the aforementioned Poria cocos, the content of β-(1→3)-D-glucan, calculated as anhydrous glucose, is not less than 50%, which is the key active substance basis for its regulation of renal uric acid transport function.

[0012] In some implementations, the content of alcohol-soluble extracts in Codonopsis pilosula shall not be less than 55.0% according to the hot extraction method under General Chapter 2201 of the Chinese Pharmacopoeia (using 45% alcohol as solvent), in order to ensure the full dissolution of the active ingredients.

[0013] A second aspect of the present invention also provides a method for preparing the above-mentioned health wine, comprising the following steps: (1) Selection of materials: Select high-quality medicinal and edible Chinese medicinal materials such as Codonopsis pilosula and Poria cocos according to the above weight ratio to ensure that the raw materials meet the aforementioned quality standards; (2) Feeding: Codonopsis pilosula and Poria cocos are fed into the extraction equipment in proportion, and then soaked in baijiu base. The baijiu base liquid level should be more than 20cm higher than the raw materials. The soaking time is controlled at 48h so that the raw materials can fully absorb the baijiu base and create conditions for the dissolution of effective components. (3) Extraction: Baijiu base is continuously or intermittently added to the extraction equipment, while the extract is continuously collected from the bottom discharge pipe of the equipment until the extract is collected at 18 times the total weight of the raw materials, so as to maximize the extraction of active ingredients in the raw materials. (4) Preparation: Take the extract obtained in step (3), add white wine base and purified water to make up the volume, mix thoroughly and let stand to make the wine components initially stable; (5) Aging and filtration: The blended wine is left to stand for 30 days to promote the integration and stability of the components; then it is transferred to a cold storage tank with heat preservation function for cooling and heat preservation treatment: the temperature of the wine is lowered to -7℃±1℃ and kept at -6.0~-8.0℃ for 7 days. After that, it is filtered, and the temperature of the wine at the filter outlet is controlled to be ≤-5℃ and the turbidity of the wine is ≤1.0NTU, finally obtaining a clear and transparent finished health wine.

[0014] The present invention has the following advantages over the prior art: Unique Mechanism of Action: Breaking through the single path of "inhibiting uric acid production" in traditional products, it targets and increases the re-secretion of uric acid in the human body through the synergistic effect of Codonopsis pilosula and Poria cocos, promotes the excretion of uric acid by the kidneys, fundamentally reduces blood uric acid levels, and reduces the risk of rebound. The raw materials are safe and reliable: Codonopsis pilosula and Poria cocos, which are both medicinal and edible, are selected, and the purity and content of effective ingredients are controlled by strict quality standards. They are highly safe and suitable for a wide range of people (especially avoiding the heatiness of ginseng, making them more suitable for long-term consumption). Scientific and controllable process: During the preparation process, the parameters of key steps such as soaking, extraction, and freeze filtration are clearly defined, which can ensure the full extraction of effective ingredients and the stability of the wine. The finished product meets the national food safety standards and the quality is controllable. The product is of excellent quality: the finished wine is clear and transparent, with a harmonious blend of medicinal and alcoholic aromas, a mellow taste, and a balanced medicinal flavor, making it easily accepted by consumers. It provides health benefits while also ensuring a pleasant drinking experience.

[0015] The health wine and its preparation method provided by this invention offer a safe, effective, and easily acceptable solution for lowering uric acid in people with high uric acid levels, and have significant practical application value. Detailed Implementation

[0016] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0017] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the embodiments of this invention pertain. If any definition stated in this section is contrary to or otherwise inconsistent with a definition stated in a patent, patent application, published patent application, or other publication incorporated herein by reference, the definitions listed here shall prevail over those incorporated herein by reference.

[0018] Unless otherwise specified, the methods used in the following embodiments are conventional methods. Unless otherwise specified, the materials, reagents, and instruments used are conventional materials, reagents, and instruments in the art, and can be obtained commercially by those skilled in the art.

[0019] When a quantity, concentration, or other value or parameter is expressed as a range, a preferred range, or a range defined by a series of upper and lower preferred values, this should be understood as specifically disclosing all ranges formed by any pair of any upper or preferred value with any lower or preferred value, regardless of whether the range is disclosed individually. For example, when the range “1 to 5” is disclosed, the described range should be interpreted as including ranges “1 to 4”, “1 to 3”, “1 to 2”, “1 to 2 and 4 to 5”, “1 to 3 and 5”, etc. When numerical ranges are described herein, unless otherwise stated, the range is intended to include its endpoints and all integers and fractions within that range. In this specification and claims, range definitions may be combined and / or interchanged, unless otherwise stated, these ranges include all subranges contained therein.

[0020] Example 1 A total of 50 kg of high-quality medicinal and edible raw materials were selected, including 16 kg of Codonopsis pilosula and 36 kg of Poria cocos. The extract was continuously extracted for 8 hours a day for 14 days. The base liquor for extraction was solid-state baijiu with an alcohol content of 42.5% vol. 900 liters of extract were collected from the continuous extraction. An appropriate amount of base liquor and purified water were added to the extract and the volume was adjusted to 1000 liters. After standing for 30 days, the extract was filtered. The liquor was then frozen and filtered to obtain a clear and transparent liquid.

[0021] In this embodiment, the content of Poria cocos, calculated as anhydrous glucose based on β-(1→3)-D-glucan, shall not be less than 50%; the content of Codonopsis pilosula, determined by the hot extraction method under the alcohol-soluble extract determination method (General Rule 2201) using 45% alcohol as solvent, shall not be less than 55.0%. The liquor obtained in this embodiment is brownish-yellow, clear and transparent, with a harmonious and elegant complex aroma of herbs and alcohol, a mellow taste, and a balanced medicinal flavor, exhibiting a typical style. The lead content meets the requirements of GB5009.12 National Food Safety Standard for the Determination of Lead in Food, the cyanide content meets the requirements of GB5009.36 National Food Safety Standard for the Determination of Cyanide in Food, and the methanol content meets the requirements of GB5009.226 National Food Safety Standard for the Determination of Methanol in Food.

[0022] Example 2 A total of 50 kg of high-quality medicinal and edible raw materials were selected, including 20 kg of Codonopsis pilosula and 30 kg of Poria cocos. The extract was continuously extracted for 8 hours a day for 14 days. The base liquor for extraction was solid-state baijiu with an alcohol content of 42.5% vol. 900 liters of extract were collected from the continuous extraction. An appropriate amount of base liquor and purified water were added to the extract and the volume was adjusted to 1000 liters. After standing for 30 days, the extract was filtered. The liquor was then frozen and filtered to obtain a clear and transparent liquid.

[0023] In this embodiment, the content of Poria cocos, calculated as anhydrous glucose based on β-(1→3)-D-glucan, shall not be less than 50%; the content of Codonopsis pilosula, determined by the hot extraction method under the alcohol-soluble extract determination method (General Rule 2201) using 45% alcohol as solvent, shall not be less than 55.0%. The liquor obtained in this embodiment is brownish-yellow, clear and transparent, with a harmonious and elegant complex aroma of herbs and alcohol, a mellow taste, and a balanced medicinal flavor, exhibiting a typical style. The lead content meets the requirements of GB5009.12 National Food Safety Standard for the Determination of Lead in Food, the cyanide content meets the requirements of GB5009.36 National Food Safety Standard for the Determination of Cyanide in Food, and the methanol content meets the requirements of GB5009.226 National Food Safety Standard for the Determination of Methanol in Food.

[0024] Example 3 A total of 50 kg of high-quality medicinal and edible raw materials were selected, including 24 kg of Codonopsis pilosula and 26 kg of Poria cocos. The extract was continuously extracted for 8 hours a day for 14 days. The base liquor for extraction was solid-state baijiu with an alcohol content of 42.5% vol. 900 liters of extract were collected from the continuous extraction. An appropriate amount of base liquor and purified water were added to the extract and the volume was adjusted to 1000 liters. After standing for 30 days, the extract was filtered. The liquor was then frozen and filtered to obtain a clear and transparent liquid.

[0025] In this embodiment, the content of Poria cocos β-(1→3)-D-glucan, calculated as anhydrous glucose, shall not be less than 50%; the content of Codonopsis pilosula, determined by the hot extraction method under the alcohol-soluble extract determination method (General Rule 2201) using 45% alcohol as solvent, shall not be less than 55.0%. The liquor obtained in this embodiment is brownish-yellow, clear and transparent, with a harmonious and elegant complex aroma of herbs and alcohol, a mellow taste, and a balanced medicinal flavor, exhibiting a typical style. The lead content meets the requirements of GB5009.12 National Food Safety Standard for the Determination of Lead in Food, the cyanide content meets the requirements of GB5009.36 National Food Safety Standard for the Determination of Cyanide in Food, and the methanol content meets the requirements of GB5009.226 National Food Safety Standard for the Determination of Methanol in Food.

[0026] Comparative Example 1 Based on Example 1, 50 kg of Codonopsis pilosula was used instead of Poria cocos, and other conditions were the same as in Example 1.

[0027] Comparative Example 2 Based on Example 1, 50 kg of Poria cocos was used instead of Codonopsis pilosula, and other conditions were the same as in Example 1.

[0028] Verification Example 1. Laboratory animals SPF-grade male Kunming mice, weighing 20±2g, were randomly divided into 6 groups (n=10).

[0029] 2. Modeling and Drug Administration Hyperuricemia model: potassium oxonate 250mg / kg + high yeast feed, for 7 consecutive days.

[0030] The drug administration groups were administered the wines obtained in Examples 1-3 and Comparative Examples 1-2 by gavage (5 mL / kg); the blank group and the model group were administered the same volume of physiological saline by gavage.

[0031] 3. Detection indicators Two hours after the last administration, blood was drawn from the orbital cavity, and serum uric acid (SUA) was measured by HPLC.

[0032] Results are expressed as mean ± SD. One-way ANOVA and Bonferroni post-hoc test were used for comparisons between groups. The significance level was α = 0.05, and P < 0.05 was considered statistically significant.

[0033] 4. Results

[0034] 5. Conclusion The wines obtained in Examples 1-3 significantly reduced serum uric acid levels (by approximately 35-40%) in a mouse model of hyperuricemia, demonstrating their expected uric acid-lowering function.

[0035] Example 4 Western blot original validation To further verify the effect of "cooperative use of Codonopsis pilosula and Poria cocos" on renal URAT1 protein, the following method was used for detection: Animals: SPF-grade male Kunming mice, 20±2g, 60 mice.

[0036] Grouping: (n=10) Control group (physiological saline); Model group (physiological saline); Example 1: Wine (5 mL / kg); Example 2: Wine (5 mL / kg); Example 3: Wine (5 mL / kg); Comparative Example 1: Wine (single Codonopsis pilosula, 5 mL / kg); Comparative Example 2: Wine (single Poria cocos, 5 mL / kg).

[0037] Modeling and drug administration Same as the experimental case: potassium oxonate 250mg / kg⁻¹ + high yeast feed, for 7 consecutive days; each treatment group was administered the corresponding alcohol by gavage, and sacrificed 2 hours after the last administration, and the renal cortex was collected.

[0038] Detection: 0.04g of fresh kidney tissue from rats in the model group after feeding with each test substance was weighed. Total protein was extracted using 300u of RIPA lysis buffer. Protein content was determined by BCA method. Protein was denatured and loaded onto the membrane (80ug protein per well), followed by electrophoresis, wet transfer, blocking with 5% skim milk powder, and incubation with primary antibody rURAT (uric acid transporter 1) 1 (primary antibody diluted 1:1000 with 5% skim milk powder). After washing three times with TBST, the membrane was incubated with the corresponding secondary antibody (1:3000), exposed, and the expression level of uric acid transporter 1 was determined.

[0039] The results are shown in the table below:

[0040] ***p<0.001 vs. model group; no statistically significant difference between the single Codonopsis pilosula and single Poria cocos groups. Examples 1-3 showed that the wine significantly downregulated the expression of URAT1 protein in the kidneys (downregulated by 42-47%), while the wine made from Codonopsis pilosula alone and Poria cocos alone had no significant effect, further demonstrating that the combination of Codonopsis pilosula and Poria cocos and the wine-making process is a necessary condition for producing a synergistic effect of promoting uricosuric excretion.

[0041] Experimental Example 1 Research on the mechanism of uric acid metabolism: To verify whether the health wine obtained in Example 1 (hereinafter referred to as "this medicinal wine") promotes uric acid excretion by downregulating the renal uric acid reabsorption transporter URAT1 and upregulating the secretion transporter OAT1 / ABCG2, and to confirm that it has no significant effect on the activity of hepatic xanthine oxidase (XOD), thereby clarifying the difference from the "inhibition of uric acid production" mechanism of the prior art.

[0042] Materials and Grouping Animals: SPF-grade male Kunming mice, 20±2g, 56 mice.

[0043] Modeling: Potassium oxonate 250 mg / kg -1 (Intraperitoneal injection, for 7 consecutive days) combined with a high-purine diet.

[0044] Grouping (n=8): Blank control group (physiological saline); Model group (physiological saline); The low-dose group of this medicinal wine (2.5 mL / kg, equivalent to 12.5 g / kg of raw medicinal materials); The medium dose group of this medicinal wine (5mL / kg, equivalent to 25g / kg of raw herbs); This medicinal wine high-dose group (10mL / kg, equivalent to 50g / kg of raw herbs); Allopurinol positive control group (10 mg / kg).

[0045] Administration method: Gavage, once daily for 7 consecutive days.

[0046] detection indicators Serum uric acid (SUA): Blood was collected from the orbital cavity 2 hours after the last administration and measured by HPLC.

[0047] 24-hour uric acid excretion (UUE): Urine was collected in a metabolic cage and measured by HPLC.

[0048] URAT1, OAT1, ABCG2 protein expression: Western blot (renal cortex, GAPDH internal control).

[0049] Hepatic xanthine oxidase (XOD) activity: colorimetric assay kit (U / g protein).

[0050] result: Blood uric acid and excretion

[0051] **p<0.05,**p<0.01,**p<0.001 vs model group.

[0052] Transporter protein expression URAT1: The dosage of this medicinal wine was reduced by 47% in the medium-dose group (p<0.001); OAT1: Upward adjustment by 62% (p<0.01); ABCG2: Upward adjustment of 58% (p<0.01).

[0053] In the allopurinol group, there were no significant differences in the expression of URAT1, OAT1, and ABCG2 compared with the model group (p>0.05).

[0054] Liver XOD activity

[0055] in conclusion This medicinal wine promotes uric acid excretion by downregulating URAT1 and upregulating OAT1 / ABCG2, without significantly affecting liver XOD activity, thus forming a clear difference in the target of action compared with existing xanthine oxidase inhibitors.

[0056] Experimental Example 2 Validation of the synergistic effect of Codonopsis pilosula and Poria cocos Verification showed that only when Codonopsis pilosula and Poria cocos were used together in the proportions of this invention did they produce a significant effect in lowering uric acid and promoting excretion, while a single component was ineffective.

[0057] Materials and Grouping Animals: Same as Experiment 1, 48 animals.

[0058] Modeling: Same as in Experiment 1.

[0059] Grouping (n=8): Blank group; Model group; Codonopsis pilosula single-use group (equivalent to 10g / kg of crude drug); Poria cocos alone group (equivalent to 15g / kg of raw herb); Codonopsis pilosula + Poria cocos combination (10:15, total amount 25g / kg); Allopurinol group (10 mg / kg).

[0060] Administration: Gavage, 7 days.

[0061] detection indicators Same as Experiment 1.

[0062] result Blood uric acid and excretion

[0063] Transporter protein expression Combined groups: URAT1 decreased by 51%, OAT1 increased by 65%, and ABCG2 increased by 59% (all p<0.001). When Codonopsis pilosula or Poria cocos were used alone, there were no statistically significant differences in the expression of URAT1, OAT1, and ABCG2 compared with the model group (p>0.05).

[0064] 5. Conclusion Only when Codonopsis pilosula and Poria cocos are used together in the proportions described in this invention can URAT1 be significantly downregulated, OAT1 / ABCG2 upregulated, and blood uric acid reduced; the single component does not have this effect at the equivalent dose, proving that there is a synergistic necessity between the two.

[0065] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A health wine with the function of increasing the re-secretion of uric acid in the human body, characterized in that, The following Chinese medicinal materials are included in the following weight proportions: Codonopsis pilosula 8-12 parts, Poria cocos 13-17 parts.

2. The health wine as described in claim 1, characterized in that, The weight proportions of the Chinese medicinal materials are: 10 parts of Codonopsis pilosula and 15 parts of Poria cocos.

3. The health wine as described in claim 1, characterized in that, The content of β-(1→3)-D-glucan in the Poria cocos is not less than 50% based on anhydrous glucose.

4. The health wine as described in claim 1, characterized in that, The content of alcohol-soluble extract in the Codonopsis pilosula shall be not less than 55% when determined by hot extraction method under General Rule 2201, with 45% alcohol as solvent.

5. A method for preparing the health wine according to any one of claims 1-4, characterized in that, Includes the following steps: (1) Material selection: Select medicinal and edible Chinese medicinal materials such as Codonopsis pilosula and Poria cocos according to the weight ratio; (2) Feeding: Codonopsis pilosula and Poria cocos are fed into the extraction equipment and soaked in baijiu base. The baijiu base liquid level is more than 20cm above the raw materials and soaking is carried out for 48 hours. (3) Extraction: Add baijiu base continuously or intermittently to the extraction equipment, and collect the extract from the discharge pipe at the bottom of the equipment until the extract is collected at a volume 18 times the total weight of the raw materials. (4) Preparation: Take the extract from step (3), add white wine base and purified water to make up the volume, mix thoroughly and let stand; (5) Aging and filtration: The blended wine is left to stand for 30 days to age, then transferred to a cold storage tank, cooled and kept warm, and then filtered to obtain the final product.

6. The preparation method according to claim 5, characterized in that, The parameters for the cooling and heat preservation treatment in step (5) are: the temperature of the wine is reduced to -7℃±1℃ and kept warm for 7 days; during filtration, the outlet wine temperature is ≤-5℃ and the turbidity is ≤1.0NTU.

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