Application of beta-1, 3 / alpha-1, 3-glucan in preparation of medicine with uric acid reducing effect

Abstract

The invention provides an application of beta-1, 3 / alpha-1, 3-glucan in preparation of a medicament with a uric acid reducing effect, and belongs to the field of medicaments. The food-grade beta-1, 3 / alpha-1, 3-glucan aims at solving the problems that in the prior art, uric acid lowering drugs are large in side effect and unstable in effect in an auxiliary mode, the food-grade beta-1, 3 / alpha-1, 3-glucan is provided, hypeluricemia is prevented or intervened, and the food-grade beta-1, 3 / alpha-1, 3-glucan is high in safety and wide in applicability.

Description

Technical Field

[0001] This invention relates to a novel use of β-1,3 / α-1,3-glucan, specifically its use in the preparation of drugs with uric acid-lowering effects, belonging to the pharmaceutical field. Background Technology

[0002] During the body's metabolism, when the level of uric acid in the body is abnormally high for a sustained period, it may not only trigger gouty arthritis, which is characterized by severe pain, but also damage important organ systems such as the kidneys and cardiovascular system. This can increase the risk of health problems such as type 2 diabetes, hypertension, and chronic kidney disease, and seriously affect the body's normal quality of life and long-term health prognosis.

[0003] Currently, clinically used drugs for lowering uric acid are mainly divided into two categories: those that inhibit uric acid production and those that promote uric acid excretion. Drugs that inhibit uric acid production, such as allopurinol and febuxostat, can effectively reduce uric acid synthesis, but they have side effects such as allergic reactions and liver and kidney toxicity. Allopurinol, in particular, has adverse reactions that are correlated with the positivity rate of specific genes, limiting its use in some populations. Drugs that promote uric acid excretion, such as benzbromarone, may cause problems such as urinary tract stones, and long-term use can also affect liver and kidney function. These limitations make finding safe and effective uric acid-lowering products a top priority.

[0004] In terms of non-pharmacological treatment, dietary regulation is an important means of controlling uric acid levels. However, because patients with hyperuricemia often find it difficult to adhere to strict dietary control in the long term, its effectiveness is significantly limited. Therefore, finding natural products and safe foods that can prevent and control elevated uric acid levels has become a research hotspot in recent years.

[0005] β-glucan, as a class of functional polysaccharides, is widely used in the health food field due to its various activities. However, the structural diversity of β-glucan determines its functional specificity; β-glucans from different glycosidic bond linkages and sources exhibit significant differences in biological activity. Among them, β-1,3 / α-1,3-glucan is a novel type of glucan, formed by β-1,3 bonds linked to α-1,3 bonds, creating a chain-like structure of repeating units without side chains. This structure is fundamentally different from traditional β-glucans (such as yeast β-1,3 / 1,6-glucan and oat β-1,3 / 1,4-glucan). This novel glucan is derived from the fermentation product of *Rhizobium pusa*, with a purity ≥90%. It has passed the safety assessment by the National Health Commission (Announcement No. 5 of 2021), and its naturalness and safety have been authoritatively certified. β-1,3 / α-1,3-glucan is composed of glucose molecules linked by alternating β-1,3 and α-1,3 glycosidic bonds, with a clearly defined unit structure and the molecular formula: (C6H... 10O5)n, n≥615. This structure gives it unique biological activity and physical properties.

[0006] Application No. 202211124741.1, entitled "Application of β-glucan or its extract in the preparation of a medicament for improving hyperuricemia," discloses the application of β-glucan or its extract in the preparation of a medicament for improving hyperuricemia. The β-glucan in this invention has a molecular weight of 15.0-17.0 kDa, a β-glucan mass content of 30-90%, and is derived from oats.

[0007] There are currently no research reports on the use of β-1,3 / α-1,3-glucan to lower uric acid. Summary of the Invention

[0008] This invention provides new uses for β-1,3 / α-1,3-glucan.

[0009] This invention provides the use of β-1,3 / α-1,3-glucan in the preparation of drugs with uric acid-lowering effects.

[0010] The aforementioned drugs are those used to prevent or / and intervene in hyperuricemia.

[0011] The aforementioned medication is for the prevention and / or intervention of gout.

[0012] The drug is prepared into a commonly used pharmaceutical formulation by adding pharmaceutically acceptable excipients or auxiliary ingredients, with β-1,3 / α-1,3-glucan as the active ingredient.

[0013] The preparation described is an oral preparation.

[0014] Compared with the β-glucan disclosed in application number 202211124741.1, the β-1,3 / α-1,3-glucan of this invention is a "β / α alternating bond polysaccharide produced by microbial fermentation", while oat β-(1→3,1→4)-glucan is a "natural linear polysaccharide with β-1,4 as the main component and β-1,3 as the discontinuous component in plant cell walls". The two are completely different in terms of bond type, configuration, source and molecular weight range.

[0015] The beneficial effects of this invention are:

[0016] This invention aims to help solve the problems of large side effects and unstable efficacy of existing uric acid-lowering drugs, and provides a food-grade β-1,3 / α-1,3-glucan to prevent or intervene in hyperuricemia, with high safety and wide applicability. Detailed Implementation

[0017] Experimental Example 1: Clinical Trial of the β-1,3 / α-1,3-glucan of the present invention for lowering uric acid The human trials of the β-1,3 / α-1,3-glucan described in this invention are summarized as follows: 1. Target audience selection This study included 71 participants, who were divided into 4 groups according to gender and serum uric acid level: Male hyperuricemia group (12 cases): males, serum uric acid > 428 μmol / L; Male non-hyperuric acid group (11 cases): male, serum uric acid ≤ 428 μmol / L, no history of hyperuricemia; Female hyperuricemia group (12 cases): female, serum uric acid >357μmol / L; Female non-hyperuric acid group (36 cases): female, serum uric acid ≤ 357 μmol / L, with no history of hyperuricemia.

[0018] 2. Diagnostic criteria People with high uric acid: men with serum uric acid > 428 μmol / L, and women with serum uric acid > 357 μmol / L; For individuals without high uric acid: 208 μmol / L ≤ male serum uric acid ≤ 428 μmol / L, 155 μmol / L ≤ female serum uric acid ≤ 357 μmol / L, and no history of gout, urinary tract stones, etc. (This standard references the reference ranges for serum uric acid levels in clinical testing centers of public tertiary hospitals and reference values ​​in literature studies. Normal uric acid range for men: 208-428 μmol / L; normal uric acid range for women: 155-357 μmol / L).

[0019] 3. Inclusion criteria (1) A randomized population with uric acid levels of 150-700 μmol / L; (2) Age 18-65 years old, gender not limited; (3) No medications, including uric acid-lowering drugs, have been taken in the past month; (4) Voluntarily participate in this trial and sign an informed consent form; (5) Able to cooperate in completing follow-up visits and various examinations.

[0020] 4. Exclusion Criteria (1) Patients with secondary hyperuricemia (such as those with renal insufficiency, blood diseases, tumors, etc.); (2) Patients with acute gouty arthritis, urinary tract stones, or renal failure; (3) Those with serious organic diseases of the heart, liver, lungs, brain, etc., or autoimmune diseases or malignant tumors; (4) Individuals allergic to β-1,3 / α-1,3-glucan; (5) Pregnant or breastfeeding women or those planning to conceive; (6) Those currently participating in other clinical trials; (7) Individuals with mental illness or cognitive impairment who are unable to cooperate with the research; (8) Recent surgery or receiving immunotherapy / biologics.

[0021] 5. Observation Indicators 5.1 Efficacy evaluation indicators Main indicators: Serum uric acid levels (μmol / L) before and after β-1,3 / α-1,3-glucan intervention, detected by uricase method; 5.2 Safety Indicators General examination: body temperature, blood pressure, heart rate, etc.; Laboratory tests: complete blood count, urinalysis, liver function tests (ALT, AST, etc.), kidney function tests (creatinine, blood urea nitrogen, etc.); Adverse reaction record: Observe for any discomfort symptoms (such as gastrointestinal reactions, allergies, etc.) that occur during medication, and record the time of occurrence and severity.

[0022] 6. Product usage instructions and precautions Experimental group: The β-1,3 / α-1,3-glucan of this invention was taken at a dose of 350 mg twice a day, dissolved in warm water on an empty stomach before meals, for 4 consecutive weeks.

[0023] Precautions: During the intervention, other uric acid-lowering drugs or foods that affect uric acid metabolism are prohibited. Regular follow-up is necessary to record changes in symptoms and adverse reactions. If serious adverse reactions occur, medication should be discontinued immediately and symptomatic treatment should be administered.

[0024] 7. Statistical Analysis SPSS statistical software was used for data analysis.

[0025] Quantitative data are expressed as mean ± standard deviation (x ± s). Paired t-tests were used to compare data before and after intervention within the group. A p-value < 0.05 was considered statistically significant.

[0026] 8. Results 8.1 Comparison of serum uric acid levels before and after intervention in the population The specific results are shown in Table 1: Table 1. Serum uric acid levels before and after taking β-1,3 / α-1,3-glucan.

[0027] Note: * indicates a significant difference between post-intervention uric acid levels and pre-intervention uric acid levels within the same group (***, p<0.001; **, p<0.01; *, p<0.05). In the male hyperuricemia group: serum uric acid levels decreased significantly after intervention (P<0.01), and in particular, 2 cases dropped to the normal range; In the male non-hyperuric acid group: after intervention, serum uric acid levels remained within the normal range and were significantly reduced (P<0.01), with uric acid levels further decreasing; In the female hyperuricemia group: serum uric acid levels decreased significantly after intervention (P<0.05), and in particular, 3 cases returned to the normal range; In the female non-hyperuric acid group: after intervention, serum uric acid levels remained within the normal range and were significantly reduced (P<0.001), with uric acid levels further decreasing.

[0028] The above results indicate that β-1,3 / α-1,3-glucan has a significant effect on improving uric acid levels in people of different genders and with different uric acid levels, and has good safety.

[0029] The β-1,3 / α-1,3-glucan in this invention exhibits a clear effect in improving uric acid levels in individuals with hyperuricemia. In the experimental group of 24 individuals with hyperuricemia, the vast majority showed varying degrees of reduction in uric acid levels after intervention. Notably, 5 of these individuals achieved uric acid levels within the normal range, confirming its significant improvement effect on hyperuricemia. Furthermore, this glucan demonstrates good safety, with no serious adverse reactions observed during the trial, making it a potentially effective intervention for individuals with hyperuricemia.

[0030] In non-hyperuricemia individuals, the uric acid levels in the experimental group remained within the normal range after intervention, and the uric acid values ​​showed a downward trend. Considering the characteristic that "the higher the uric acid level, the greater the risk of developing the disease" in hyperuricemia individuals, this dextran can reduce the risk of hyperuricemia by lowering uric acid levels in normal individuals, thus demonstrating a preventive effect.

[0031] Example 2: Typical case of β-1,3 / α-1,3-glucan lowering uric acid in this invention. To illustrate the improvement in uric acid levels in more detail, the following are typical case examples: Case 1: Mr. Xie, male, 38 years old. Before taking β-1,3 / α-1,3-glucan, his serum uric acid level was 460 μmol / L, classifying him as a person with hyperuricemia. After taking β-1,3 / α-1,3-glucan continuously for 4 weeks, his serum uric acid level decreased to 352 μmol / L, returning to the normal range, representing a reduction of 23.48%.

[0032] Case 2: Ms. Chen, female, 27 years old. Before taking β-1,3 / α-1,3-glucan, her serum uric acid level was 428 μmol / L, classifying her as a hyperuricemic individual. After taking β-1,3 / α-1,3-glucan continuously for 4 weeks, her serum uric acid level decreased to 334 μmol / L, returning to the normal range, representing a reduction of 21.96%.

[0033] This invention is the first to discover the function of β-1,3 / α-1,3-glucan in improving high uric acid levels, filling the gap in the application of this novel glucan in the field of uric acid regulation and clarifying its core position as an active ingredient for lowering uric acid. Dual function covering the entire population: This glucan can be used in both "improvement of high uric acid levels" and "prevention of high uric acid levels" and covers both male and female populations.

Claims

1. Use of β-1,3 / α-1,3-glucan in the preparation of drugs with uric acid-lowering effects.

2. The use according to claim 1, characterized in that: The medication described is for the prevention and / or intervention of hyperuricemia.

3. The use according to claim 1, characterized in that: The medication described is for the prevention and / or intervention of gout.

4. The use according to any one of claims 1-3, characterized in that: The drug is prepared into a commonly used pharmaceutical formulation by adding pharmaceutically acceptable excipients or auxiliary ingredients, with β-1,3 / α-1,3-glucan as the active ingredient.

5. The use according to claim 4, characterized in that: The preparation described is an oral preparation.

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