A traditional Chinese medicine composition for preventing or treating hyperuricemia and kidney damage and its application

Abstract

The present invention belongs to the technical field of traditional Chinese medicine, and specifically relates to a traditional Chinese medicine composition for preventing or treating hyperuricemia and its kidney damage and its application. The technical problem to be solved by the present invention is to provide a new option for preventing or treating hyperuricemia. The technical solution of the present invention is a traditional Chinese medicine composition for preventing or treating hyperuricemia and its kidney damage, comprising the following ingredients: thistle, lily, lotus seed, kudzu root, peach kernel, angelica and cinnamon. The traditional Chinese medicine composition of the present invention has the effects of inhibiting uric acid synthesis and improving kidney damage, can be used to prevent and treat hyperuricemia, protect the kidneys, and does not cause liver damage, providing a basis for further developing it into a food, health product or medicine for preventing or treating hyperuricemia.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for preventing or treating hyperuricemia and kidney damage and an application thereof. Background Art

[0002] Hyperuricemia (HUA) is a group of metabolic diseases caused by factors such as impaired purine metabolism or decreased uric acid excretion. Long-term, chronic hyperuricemia leads to excessive urate deposition in joints, kidneys, and other areas, potentially leading to persistent gout and chronic kidney damage. In recent years, with improvements in living standards and changes in dietary patterns in my country, the prevalence and mortality of hyperuricemia in adults have been increasing. It has become the fourth most common disease in my country after hyperglycemia, hyperlipidemia, and hypertension, and the second most common metabolic disease after diabetes. Currently, the number of people suffering from HUA in my country has reached 190 million. Uric acid is the end product of purine metabolism in the liver, muscle, and small intestine, typically formed by the breakdown of adenosine and guanine. The purine breakdown product, xanthine, then reacts with hypoxanthine through a series of enzymatic reactions, including xanthine oxidase (XO), to convert it into uric acid. Hyperuricemia is usually related to chronic heart disease, hypertension, etc. Therefore, timely and reasonable use of uric acid-lowering drugs in patients can reduce uric acid deposition in the body, reduce gout attacks, alleviate heart damage, and reduce the occurrence of other complications.

[0003] Currently, clinical drug treatments for hyperuricemia can be divided into three main categories: those that reduce uric acid synthesis, represented by xanthine oxidase (XOD) inhibitors such as allopurinol, febuxostat, and topiroxostat; those that enhance uric acid excretion, represented by urate transporter 1 (URAT1) inhibitors such as benzbromarone and probenecid; and those that regulate uric acid metabolism and hydrolysis (uricase). However, all of these drugs have significant adverse reactions, such as gastrointestinal symptoms, rashes, liver damage, bone marrow suppression, skeletal muscle and connective tissue symptoms, and fatal hypersensitivity reactions. For example, febuxostat and allopurinol have a higher incidence of acute renal failure than other drugs and can cause acute liver damage, making long-term use contraindicated. Benzbromarone and probenecid, both small molecule drugs, should be used with caution in patients with urinary tract stones, hepatic and renal insufficiency, gastrointestinal ulcers, the elderly, and children, resulting in significant clinical conflict. Uricase, on the other hand, has significant drawbacks, such as triggering an immune response and having a short efficacy. Therefore, the search for safe and effective preventive and treatment drugs is urgent.

[0004] Although TCM does not have names for hyperuricemia and gout, acute attacks of gout are primarily classified under the TCM categories of "gout," "heat arthralgia," and "white tiger calendar" based on their clinical manifestations, while intermittent periods of hyperuricemia and gout are primarily classified under the categories of "blood poison" and "turbid poison." Clinically, hyperuricemia is primarily divided into syndromes such as spleen and kidney yang deficiency, damp-heat accumulation, blood stasis, phlegm and turbidity, and liver and kidney yin deficiency. Treatment focuses on clearing heat and dampness, tonifying the kidney and strengthening the spleen, strengthening the spleen and eliminating dampness, and clearing turbidity and removing blood stasis. The pathogenesis of hyperuricemia is relatively complex, and TCM has significant advantages in treating this type of disease, especially Chinese medicines and food-related herbs and their compound prescriptions, which have multiple components, multiple steps, and are highly safe, making them particularly suitable for the prevention and treatment of this type of complex disease closely related to lifestyle. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to provide a new option for preventing or treating hyperuricemia.

[0006] The technical solution of the present invention is a traditional Chinese medicine composition for preventing or treating hyperuricemia and its associated kidney damage, comprising the following ingredients: thistle, lily, lotus seed, kudzu root, peach kernel, angelica root, and cinnamon bark. Thistle cools the blood and stops bleeding, dissipates blood stasis, detoxifies, and eliminates carbuncles; lily and lotus seed nourish the spleen and kidneys, clears the heart and calms the mind; kudzu root promotes fluid production and quenches thirst, promoting blood circulation and activating collaterals; peach kernel, angelica root, and cinnamon bark activate blood circulation, dispel blood stasis, and warm the meridians. The rational combination of ingredients in the entire formula works together to achieve the effects of clearing heat, strengthening the spleen and nourishing the heart, dispelling blood stasis, purging turbidity, and expelling acid.

[0007] Furthermore, the weight proportions of the ingredients are as follows: 3-24 parts of thistle, 3-20 parts of lily, 5-30 parts of lotus seeds, 5-30 parts of kudzu root, 3-20 parts of peach kernel, 3-20 parts of angelica and 2-10 parts of cinnamon.

[0008] Preferably, the weight proportion of the ingredients is as follows: 12 parts of thistle, 10 parts of lily, 15 parts of lotus seeds, 15 parts of kudzu root, 8 parts of peach kernel, 8 parts of angelica and 5 parts of cinnamon.

[0009] The present invention also provides a preparation method of the traditional Chinese medicine composition, comprising the following steps: mixing thistle, lily, lotus seed, kudzu root, peach kernel, angelica and cinnamon, adding water, extracting twice, filtering the extract after each extraction, combining the extracts; concentrating; drying; and crushing to obtain powder.

[0010] Furthermore, during the extraction process, the mass-to-volume ratio of the material to the liquid (g / mL) is 1:3 to 1:20.

[0011] Preferably, during the first extraction, the mass-to-volume ratio of the material to the liquid (g / mL) is 1:10.

[0012] Preferably, during the first extraction, the mass-to-volume ratio of the material to the liquid (g / mL) is 1:8.

[0013] Specifically, each extraction time is 1 to 3 hours.

[0014] Preferably, each extraction time is 1.5 h.

[0015] The present invention also provides a traditional Chinese medicine composition obtained by the above preparation method.

[0016] The present invention also provides use of the above-mentioned traditional Chinese medicine composition in preparing a medicine for treating or preventing hyperuricemia.

[0017] The present invention also provides the use of the above-mentioned traditional Chinese medicine composition in preparing a medicine for treating or preventing hyperuricemia kidney damage.

[0018] Among them, the application is the use of the above-mentioned traditional Chinese medicine composition in the preparation of drugs for inhibiting xanthine oxidase, lowering uric acid levels, improving renal dysfunction caused by hyperuricemia, lowering inflammatory factor levels, reducing renal fibrosis caused by hyperuricemia and / or improving liver function.

[0019] Furthermore, the inflammatory factors are IL-1β, IL-6 and TNF-α.

[0020] The present invention also provides a medicine, food or health product for treating or preventing hyperuricemia, comprising the above-mentioned Chinese medicine composition.

[0021] The present invention also provides a medicine, food or health product for treating or preventing hyperuricemia renal damage, comprising the above-mentioned Chinese medicine composition.

[0022] In particular, the above-mentioned medicine also includes pharmaceutically acceptable adjuvants.

[0023] Further, the auxiliary agent is dextrin, sugar or starch.

[0024] Furthermore, the dosage form of the drug is tablets, injections, capsules, pills or granules.

[0025] Particularly, the food is at least one of fresh food, air-dried food, freeze-dried food, canned food or salted food.

[0026] Beneficial effects of the present invention: The present invention addresses the deficiencies of existing drug treatments and, based on years of clinical practice, has been continuously optimized to form a fixed prescription for the treatment of hyperuricemia. The prescription is composed of seven herbs: thistle, lily, lotus seed, kudzu root, peach kernel, angelica root, and cinnamon bark. It has the effects of clearing heat, strengthening the spleen and nourishing the heart, removing blood stasis, purging turbidity, and excreting acid. It is clinically used for the prevention and treatment of hyperuricemia and its complications, with significant effects and high safety. In order to further explore its effect characteristics, an animal model of hyperuricemia was constructed to study the effects of the compound on uric acid synthesis and uric acid excretion in hyperuricemia mice and its protective effect on kidney damage and liver damage. The results showed that the compound can inhibit liver xanthine oxidase, reduce blood uric acid, blood creatinine, blood urea nitrogen, and urine protein levels, increase urine uric acid levels, reduce serum IL-1β, IL-6, TNF-α levels, and kidney F4 / 80 and FN expressions, and has no effect on liver function indicators AST and ALT. The results indicate that the present invention has the effects of inhibiting uric acid synthesis, improving kidney damage, and can be used to prevent and treat hyperuricemia, protecting the kidneys, and does not cause liver damage, providing a basis for further development into food, health products, or medicines for preventing or treating hyperuricemia. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 .HE staining of kidneys of mice in each group (20×).

[0028] Figure 2 .F4 / 80 staining images of kidneys of mice in each group (20×).

[0029] Figure 3 .Masson staining of kidneys of mice in each group (20×).

[0030] Figure 4 Fibronectin staining of kidneys of mice in each group (20×).

[0031] Figure 5 .α-SMA staining images of kidneys of mice in each group (20×).

[0032] Figure 6 .HE staining of the liver of mice in each group (10×). DETAILED DESCRIPTION

[0033] Sources of reagents and materials used in the following examples:

[0034] KM mice were purchased from Zhuhai Baishitong Laboratory Animal Co., Ltd.; medicinal materials were purchased from Guangdong Medicinal Materials Company; potassium oxonate (CAS No. 2207-75-2), hypoxanthine (CAS No. 68-94-0), and allopurinol (CAS No. 315-30-0) were purchased from Shanghai Yuanye Biotechnology Co., Ltd. Uric acid, XOD enzyme, creatinine, urea nitrogen, urine protein, ALT, and AST detection kits were purchased from Nanjing Jiancheng Bioengineering Research Institute Co., Ltd.; IL-1β, IL-6, and TNF-α detection kits were purchased from Jiangsu Enzyme Immunity Industry Co., Ltd.

[0035] Example 1 Drug Preparation

[0036] Take 72g of thistle, 60g of lily, 90g of lotus seed, 90g of kudzu root, 48g of peach kernel, 48g of angelica, and 30g of cinnamon, add water and heat under reflux to extract twice. The first time, add 10 times the amount of water of the drug mass to extract for 1.5h, and the second time, add 8 times the amount of water to extract for 1 hour. Filter, combine the extracts, concentrate and dry into powder for use. When using, add 0.5% sodium carboxymethyl cellulose to dissolve it into the corresponding concentration of drug solution.

[0037] Example 2 Effect of use of the medicine

[0038] Male KM mice aged 7 to 8 weeks were selected and divided into blank control group (Control), model group (Model), allopurinol group (AP, 10 mg / kg / d), low-dose compound group (FL, 6.4 g / kg / d), and high-dose compound group (FH, 12.8 g / kg / d) according to their body weight using a random number table method, with 6 mice in each group.

[0039] Seven- to eight-week-old male KM mice were fed a standard diet and given normal drinking water. After one week of adaptive feeding, mice in the control group were gavaged with 0.5% CMC-Na (0.1 mL / 10 g) and intraperitoneally injected with PBS (0.1 mL / 10 g) daily. The remaining groups received intraperitoneal injections of potassium oxonate (200 mg / kg / d) and oral hypoxanthine (500 mg / kg / d). The allopurinol group received oral allopurinol (10 mg / kg / d), while mice in the FL and FH groups received 6.4 g / kg / d and 12.8 g / kg / d of the compound extract, respectively, at a dose volume of 0.1 mL / 10 g for 21 days. After 21 days of dosing, the mice were placed in metabolic cages for 24-hour urine collection. All groups were fasted for 24 hours, anesthetized with isoflurane, and blood was collected by enucleation. After blood collection, the mouse heart was perfused with 30 mL of normal saline. After perfusion, the kidneys and liver were removed in sequence.

[0040] Indicator Assays: Serum uric acid and liver XOD enzyme levels were measured according to the instructions of the uric acid and XOD enzyme assay kits. Creatinine, urea nitrogen, and urine protein were measured according to the instructions of the creatinine, urea nitrogen, and urine protein assay kits to assess renal function. The inflammatory cytokines IL-1β, IL-6, and TNF-α were measured according to the instructions of the IL-1β, IL-6, and TNF-α assay kits to assess renal inflammation. ALT and AST were measured according to the instructions of the ALT and AST assay kits to assess liver function. Kidney and liver tissues were collected and fixed in 4% paraformaldehyde for 24 hours. After dehydration, they were embedded in paraffin blocks and cut into 4-μm sections. The sections were oven-dried at 65°C for 1 hour. After gradient dewaxing with organic reagents, they were stained with hematoxylin and eosin, Masson staining, and immunohistochemistry to assess histopathology, inflammatory infiltration, and fibrosis. GraphPad Prism 9.4.1 software was used for data analysis and graphing. Two-group comparisons were performed with the two-tailed unpaired t-test, and multiple groups were compared with one-way analysis of variance (ANOVA) followed by Tukey's multiple comparison test. Data are expressed as mean ± standard error (x ± s). P < 0.05 indicated statistically significant differences.

[0041] Experimental results:

[0042] 1. Inhibit xanthine oxidase and reduce uric acid levels

[0043] Uric acid levels in each group of mice are shown in Table 1. Compared with the blank control group, the model group showed significantly increased levels of XOD in the liver and serum, significantly increased serum uric acid, and significantly decreased urine uric acid levels. The high-dose compound significantly reduced liver XOD enzyme levels and serum uric acid levels. This suggests that the compound can inhibit xanthine oxidase, reduce uric acid synthesis, and improve hyperuricemia.

[0044] Table 1. Statistics of uric acid metabolism indicators in each group

[0045]

[0046] Note: Compared with the blank group: ** P<0.01, *** P<0.001, **** P < 0.0001;

[0047] Compared with the model group: △ P<0.05, △△ P<0.01, △△△ P<0.001, △△△△ P<0.0001.

[0048] 2. Improve renal dysfunction caused by hyperuricemia

[0049] (1) Results of routine biochemical indicators of renal function

[0050] The results of renal function-related index tests are shown in Table 2. The blood urea nitrogen and urine protein levels in the model group were significantly increased, while those in each drug-treated group showed a downward trend. In particular, the urea nitrogen and urine protein levels in the high-dose drug-treated group were significantly lower than those in the model group. Compared with the blank group, the endogenous creatinine clearance rate of mice in the model group was significantly decreased. The compound drug group was able to significantly reverse this change and increase the endogenous creatinine clearance rate, indicating that the drug has a good improvement effect on the renal function abnormalities caused by hyperuricemia in mice.

[0051] Table 2. Statistical table of renal function indicators in each group

[0052]

[0053] Note: Compared with the blank group: *** P<0.001; compared with the model group: △ P<0.05, △△ P<0.01, △△△ P<0.001, △△△△ P<0.0001.

[0054] (2) HE staining results

[0055] HE staining showed that ( Figure 1 ), the normal control group mice had normal renal tubular cell morphology and no obvious infiltration in the kidneys, while the model group mice showed severe renal damage, loose and disordered renal tubular structure, glomerular atrophy and other obvious morphological changes, which were significantly improved after administration of the compound.

[0056] 3. Inflammatory index detection

[0057] (1) Levels of inflammatory factors

[0058] The results of serum inflammatory factor level detection are shown in Table 3. The levels of IL-1β, IL-6 and TNF-α in the model group were significantly higher than those in the blank group. The levels of IL-1β, IL-6 and TNF-α in each drug-treated group were all lower, especially in the high-dose compound group. The inflammatory level decreased significantly, indicating that the compound can significantly improve the inflammatory phenotype of hyperuricemia mice.

[0059] Table 3. Statistical table of serum inflammatory indicators in each group

[0060] Group IL-1β (ng / L) IL-6 (ng / L) TNF-α (ng / L) Blank control group (control) 83.58±2.20 111.20±2.64 740.60±8.96 Model group (model) <![CDATA[104.30±1.96 **** ]]> <![CDATA[134.40±1.44 **** ]]> <![CDATA[987.20±26.07 **** ]]> Compound low-dose group (FL) 97.80±1.37 <![CDATA[122.90±2.38 △ ]]> <![CDATA[860.60±47.40 △ ]]> Compound high-dose group (FH) <![CDATA[94.61±1.92 △ ]]> <![CDATA[117.00±3.50 △△△ ]]> <![CDATA[819.90±14.91 △△ ]]> Allopurinol group (AP) <![CDATA[94.43±3.42 △ ]]> <![CDATA[117.60±2.44 △△△ ]]> <![CDATA[817.90±21.05 △△ ]]>

[0061] Note: Compared with the blank group: ****P<0.0001; compared with the model group: △ P<0.05, △△ P<0.01, △△△ P<0.001.

[0062] (2) Immunohistochemical staining results (F4 / 80)

[0063] like Figure 2 As shown in Table 4, compared with the blank group mice, the expression of F4 / 80 in the kidneys of the model group mice was significantly increased, and the compound significantly reduced the renal macrophage infiltration of hyperuricemia mice in a dose-dependent manner.

[0064] Table 4. Statistics of F4 / 80 positive areas in the kidneys of mice in each group

[0065] Group Positive area (%) Blank control group (control) 0.367±0.158 Model group (model) <![CDATA[6.434±1.298 *** ]]> Compound low-dose group (FL) <![CDATA[1.475±0.303 △△ ]]> Compound high-dose group (FH) <![CDATA[0.590±0.151 △△△ ]]> Allopurinol group (AP) <![CDATA[0.750±0.054 △△△ ]]>

[0066] Note: Compared with the blank group: *** P<0.001; compared with the model group: △△ P<0.001, △△△ P<0.001.

[0067] 4. Reduce renal fibrosis in mice with high uric acid levels

[0068] (1) Masson staining results

[0069] The results are as follows Figure 3 As shown in Table 5, the collagen deposition in the kidneys of the model group mice was significantly higher than that in the blank group, while the collagen deposition in each drug-treated group was significantly reduced, indicating that the compound can significantly reduce renal fibrosis in hyperuricemia mice.

[0070] Table 5. Statistics of positive areas in each group

[0071] Group Positive area (%) Blank control group (control) 2.559±0.361 Model group (model) <![CDATA[22.460±1.176 **** ]]> Compound low-dose group (FL) <![CDATA[4.741±0.272 △△△△ ]]> Compound high-dose group (FH) <![CDATA[4.680±1.047 △△△△ ]]> Allopurinol group (AP) <![CDATA[3.497±0.881 △△△△ ]]>

[0072] Note: Compared with the blank group: **** P<0.0001; compared with the model group: △△△△ P<0.0001.

[0073] (2) Immunohistochemical staining results (Fibronectin)

[0074] like Figure 4 and Figure 6 As shown in the results, compared with the blank group mice, the expression of FN in the kidneys of the model group mice was significantly increased. After administration of the compound prescription, the expression of FN in the kidneys of hyperuricemia mice was significantly reduced in a dose-dependent manner, indicating that the prescription can improve renal fibrosis in hyperuricemia mice.

[0075] Table 6. Statistics of FN-positive areas in the kidneys of mice in each group

[0076] Group Positive area (%) Blank control group (control) 0.151±0.025 Model group (model) <![CDATA[3.221±0.479 **** ]]> Compound low-dose group (FL) <![CDATA[1.228±0.073 △△△ ]]> Compound high-dose group (FH) <![CDATA[0.306±0.058 △△△△ ]]> Allopurinol group (AP) <![CDATA[0.303±0.038 △△△△ ]]>

[0077] Note: Compared with the blank group: **** P<0.0001; compared with the model group: △△△ P<0.001, △△△△ P<0.0001.

[0078] (3) Immunohistochemical staining results (α-SMA)

[0079] like Figure 5 As shown in Table 7, compared with the blank group mice, the expression of α-SMA in the kidneys of the model group mice was significantly increased, and the compound administration significantly reduced the expression of this protein in the kidneys of hyperuricemia mice in a dose-dependent manner, indicating that the compound can improve renal fibrosis in hyperuricemia mice.

[0080] Table 7. Statistical table of α-SMA positive area in the kidneys of mice in each group

[0081] Group Positive area (%) Blank control group (control) 0.196±0.063 Model group (model) <![CDATA[1.896±0.350 *** ]]> Compound low-dose group (FL) <![CDATA[0.951±0.0774 △ ]]> Compound high-dose group (FH) <![CDATA[0.408±0.113 △△△ ]]> Allopurinol group (AP) <![CDATA[0.281±0.051 △△△ ]]>

[0082] Note: Compared with the blank group: *** P<0.001; compared with the model group: △ P<0.05, △△△ P<0.001.

[0083] 5. Liver function test results

[0084] like Figure 6 The results of liver HE staining showed that although there was no obvious liver lesion among the mice in the short-term drug administration groups, the ALT values ​​of the model group and the positive drug group were significantly higher than those of the blank control group, while there was no significant difference between the compound group and the blank group, and there was a downward trend compared with the model and positive drug groups, indicating that the compound did not cause liver damage.

[0085] Table 8. Statistical table of serum liver function indicators of mice in each group

[0086] Group ALT(U / L) AST(U / L) Blank control group (control) 3.15±0.58 10.47±1.33 Model group (model) <![CDATA[6.31±0.65 * ]]> 16.70±1.58 Compound low-dose group (FL) 3.52±1.13 16.60±1.94 Compound high-dose group (FH) 3.72±1.04 13.89±1.63 Allopurinol group (AP) <![CDATA[6.93±0.60 * ]]> <![CDATA[17.57±2.12 * ]]>

[0087] Note: Compared with the blank group: *P<0.05.

Claims

1. A Chinese medicine composition for preventing or treating hyperuricemia and renal damage caused by hyperuricemia, characterized in that: The invention is prepared from the following ingredients in weight proportions: 3-24 parts of thistle, 3-20 parts of lily, 5-30 parts of lotus seeds, 5-30 parts of kudzu root, 3-20 parts of peach kernel, 3-20 parts of angelica and 2-10 parts of cinnamon.

2. The Chinese medicine composition according to claim 1, characterized in that: The invention is prepared from the following ingredients in weight proportions: 12 parts of thistle, 10 parts of lily, 15 parts of lotus seeds, 15 parts of kudzu root, 8 parts of peach kernel, 8 parts of angelica and 5 parts of cinnamon.

3. The method for preparing the Chinese medicine composition according to claim 1 or 2, characterized in that: The method comprises the following steps: mixing thistle, lily, lotus seed, kudzu root, peach kernel, angelica and cinnamon, adding water, extracting twice, filtering the extract after each extraction, combining the extracts; concentrating; drying; and crushing.

4. The preparation method according to claim 3, characterized in that: Have one of the following characteristics: a. During the extraction process, the mass-to-volume ratio of the material to the liquid (g / mL) is 1:3 to 1:20; b. Each extraction time is 1~3h.

5. The preparation method according to claim 4, characterized in that: Have one of the following characteristics: c. During the first extraction, the mass-to-volume ratio of the material to the liquid (g / mL) was 1:10; d. During the second extraction, the mass-to-volume ratio of the material to the liquid (g / mL) was 1:8; e. Each extraction time is 1.5h.

6. Use of the traditional Chinese medicine composition according to claim 1 or 2 or the traditional Chinese medicine composition prepared by the method according to any one of claims 3 to 5 in the preparation of a medicament for treating or preventing hyperuricemia.

7. Use of the traditional Chinese medicine composition according to claim 1 or 2 or the traditional Chinese medicine composition prepared by the method according to any one of claims 3 to 5 in the preparation of a medicament for treating or preventing renal damage caused by hyperuricemia.

8. A drug for treating or preventing hyperuricemia, characterized in that: The effective ingredient is the traditional Chinese medicine composition according to claim 1 or 2 or the traditional Chinese medicine composition prepared by the method according to any one of claims 3 to 5.

9. A drug for treating or preventing renal damage caused by hyperuricemia, characterized in that: The effective ingredient is the traditional Chinese medicine composition according to claim 1 or 2 or the traditional Chinese medicine composition prepared by the method according to any one of claims 3 to 5.

10. The drug according to claim 8 or 9, characterized in that: Have one of the following characteristics: f. The drug further contains a pharmaceutically acceptable adjuvant; g. The dosage form of the drug is tablets, capsules, pills or granules.

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