A traditional Chinese medicine composition with multi-target anti-viral and anti-inflammatory activities, and a preparation method and application thereof

Abstract

Abstract: This invention discloses a traditional Chinese medicine composition (Da Zhuque Decoction) with multi-target antiviral and anti-inflammatory activities, its preparation method, and its application. The composition consists of the following raw materials in parts by weight: Alisma plantago-aquatica 2-4 parts, Prunus armeniaca 4-6 parts, Chrysanthemum indicum 4-6 parts, Artemisia annua 5-7 parts, Morus alba leaf 5-7 parts, Gypsum 5-7 parts, Poria cocos 7-9 parts, Scutellaria baicalensis 8-10 parts, Rehmannia glutinosa 8-10 parts, Plantago asiatica 11-13 parts, Taraxacum mongolicum 14-16 parts, and Glycyrrhiza uralensis 3-5 parts. This invention overcomes the limitations of traditional qualitative formulation of traditional Chinese medicines. By limiting the specific synergistic ratio of artemisinin and baicalin (1:2.5~3.0), it achieves highly efficient inhibition of respiratory viruses (IC50=12.5μg / mL) and significant downregulation of inflammatory factors (IL-6, TNF-α). Meanwhile, the preparation process of "plaster decoction first - licorice extraction alone" solves the problem of easy decomposition of heat-sensitive components, increasing the artemisinin retention rate to over 95%. This invention has a clear material basis, controllable quality, and is suitable for preparing drugs or health products for the prevention and treatment of viral pneumonia.

Description

Technical Field Traditional Chinese medicine technology, biomedicine, plant extracts 1. Background Technology Existing antiviral drugs (such as remdesivir and parvovir) generally suffer from problems such as single-target efficacy, easy induction of drug resistance, and significant hepatotoxicity and nephrotoxicity. While traditional Chinese medicine compound formulas can exert effects on multiple targets, they have two major fatal flaws: The material basis is vague: relying solely on qualitative descriptions based on the "principal, assistant, adjuvant, and guide" formulas, and lacking precise quantitative ratios, leads to huge differences in efficacy between different batches of the drug.

[0001] The process is crude: the traditional "one-pot stew" decoction method causes the decomposition of heat-sensitive components (such as artemisinin) and the hydrolysis of acidic components (such as baicalin), making it difficult to maximize the efficacy.

[0002] The present invention aims to solve the above problems and provide a traditional Chinese medicine compound preparation (Da Zhuque Tang) with precise formulation, advanced process and definite curative effect. 2. Summary of the Invention Technical issues

[0004] This invention provides a traditional Chinese medicine composition with a clear material basis, controllable quality, and significant antiviral and anti-inflammatory effects, and clarifies the synergistic ratio of its core active ingredients.

[0005] Technical solution (core formula) This invention provides a traditional Chinese medicine composition, which is composed of the following raw materials in parts by weight: Alisma plantago-aquatica 2-6 parts, apricot kernel 4-8 parts, wild chrysanthemum 4-8 parts, artemisia annua 5-8 parts, mulberry leaf 5-8 parts, gypsum 5-8 parts, poria cocos 6-10 parts, scutellaria baicalensis 8-12 parts, rehmannia glutinosa 8-12 parts, plantain seed 9-12 parts, dandelion 12-18 parts, licorice root 3-6 parts. Beneficial effects

[0006] Synergistic effect: The ratio of artemisinin to baicalin was clearly defined as 1:2.5~3.0. At this ratio, the two have a synergistic effect on inhibiting viral replication (IC50=12.5μg / mL).

[0007] Dual blocking: It can both inhibit viral replication and significantly reduce IL-6 and TNF-α inflammatory factors (by more than 40%), preventing cytokine storm.

[0008] Technological innovation: Through the process of "pre-decoction of gypsum + single extraction of licorice", the retention rate of artemisinin has been increased from the traditional 51.3% to over 95%.

[0009] 3. The specific implementation methods (examples and comparative examples) are as follows: Example 1: Optimal Implementation Formula (Da Zhuque Tang - Standard Type) Raw material ratio (unit: grams) Alisma plantago-aquatica 3g, apricot kernel 5g, wild chrysanthemum 5g, artemisia annua 6g, mulberry leaf 6g, gypsum 6g, poria cocos 8g, scutellaria baicalensis 9g, rehmannia glutinosa 9g, plantain seed 12g, dandelion 15g, licorice root 4g.

[0010] Preparation method First decoction: Place the gypsum in an extraction tank, add 10 times the amount of purified water, and decoct at 100℃ for 30 minutes.

[0011] Extraction of multiple herbs: Add all herbs except raw licorice root, add water to cover the herbs, decoct twice (1 hour each time), and combine the filtrates.

[0012] Single extraction: Add water to raw licorice and extract at 80℃ for 30 minutes, then filter.

[0013] Refining: Combine the filtrates, adjust the pH to 6.5, concentrate under reduced pressure at 60°C to a clear extract with a relative density of 1.10 (60°C), add excipients and granulate.

[0014] Test data • Chemical composition: Each gram of the preparation contains artemisinin ≥ 0.5 mg and baicalin ≥ 8.0 mg.

[0015] • Cellular experiments: The IC50 of viral inhibition rate against Vero E6 cells was 12.5 μg / mL.

[0016] • Anti-inflammatory experiment: IL-6 inhibition rate was 72.1%, and TNF-α inhibition rate was 65.3%.

[0017] Example 2: Verification of Formula Ratio Floating (Da Zhuque Tang - Enhanced Version) (This verifies the reasonableness of the upper limit of claim 1, and applies to severely ill or physically robust patients.) Raw material ratio (unit: grams) Alisma plantago-aquatica 5g (+2), apricot kernel 7g (+2), wild chrysanthemum 7g (+2), artemisia annua 8g (+2), mulberry leaf 8g (+2), gypsum 8g (+2), poria cocos 10g (+2), scutellaria baicalensis 11g (+2), rehmannia glutinosa 11g (+2), plantain seed 14g (+2), dandelion 17g (+2), licorice root 6g (+2).

[0018] Preparation process Same as Example 1.

[0019] Test data • Cytotoxicity: Cell viability >92% within safe concentration range.

[0020] • Efficacy data: The IL-6 inhibition rate increased to 78.2%, and the anti-inflammatory efficacy was enhanced, but the cost increased accordingly.

[0021] Example 3: Verification of the formula ratio (Da Zhuque Tang - Mild type) (Verify the reasonableness of the lower limit of claim 1, applicable to prevention or the frail) Raw material ratio (unit: grams) Alisma plantago-aquatica 1g (-2), apricot kernel 3g (-2), wild chrysanthemum 3g (-2), artemisia annua 4g (-2), mulberry leaf 4g (-2), gypsum 4g (-2), poria cocos 6g (-2), scutellaria baicalensis 7g (-2), rehmannia glutinosa 7g (-2), plantain seed 10g (-2), dandelion 13g (-2), licorice root 2g (-2).

[0022] 4. Preparation process Same as Example 1.

[0023] Test data • Safety: Cell survival rate >99%, extremely high safety.

[0024] • Efficacy data: The IC50 value was 28.7 μg / mL, which was weaker than the standard type, but still significantly better than the blank control group (P<0.05), proving that it was still effective under the experimental verification of dosage increase and decrease.

[0025] 5. Comparative Example 1: Traditional Process vs. Traditional Process Formula and process The formula is the same as in Example 1, but the traditional mixed decoction method is used: all medicinal materials (including gypsum and licorice) are mixed, decocted twice under normal pressure, and then combined and concentrated.

[0026] Data Comparison Detection index: Example 1 of this invention; Comparative Example 1 (conventional method); Variation range Artemisinin retention rate was 95.2% - 51.3%, a significant decrease. The baicalin content decreased by 26% from 8.0 mg / g to 5.9 mg / g. The antiviral IC50 was 12.5 μg / mL, while the efficacy was significantly reduced at 35.8 μg / mL. 6. Conclusion: This invention demonstrates that the process of "pre-decoction of gypsum + extraction of licorice" has an unexpected technical effect on protecting heat-sensitive components.

[0027] An antiviral traditional Chinese medicine composition, characterized in that it comprises the following raw materials in parts by weight: Alisma plantago-aquatica 2-6 parts, apricot kernel 4-8 parts, wild chrysanthemum 4-8 parts, artemisia annua 5-18 parts, mulberry leaf 5-16 parts, gypsum 5-10 parts, poria cocos 6-12 parts, scutellaria baicalensis 8-16 parts, rehmannia glutinosa 8-16 parts, plantain seed 8-20 parts, dandelion 12-26 parts, licorice root 4-8 parts.

[0028] According to claim 1, the traditional Chinese medicine composition is characterized in that the preferred weight proportions of the raw material are: Alisma plantago-aquatica 3 parts, apricot kernel 5 parts, wild chrysanthemum 5 parts, artemisia annua 6 parts, mulberry leaf 6 parts, gypsum 6 parts, poria cocos 8 parts, scutellaria baicalensis 9 parts, rehmannia glutinosa 9 parts, plantain seed 12 parts, dandelion 15 parts, and raw licorice root 4 parts.

[0029] The traditional Chinese medicine composition according to claim 1 is characterized in that the weight ratio of the core active ingredient artemisinin to baicalin in the composition is 1:2.5~3.0.

[0030] A method for preparing a traditional Chinese medicine composition as described in any one of claims 1-3, characterized by comprising the following steps: First, decoct gypsum in water for 20-30 minutes; then add the remaining medicinal materials except for raw licorice root for water extraction; extract raw licorice root separately with water; combine the extracts, adjust the pH to 6.0-7.0, concentrate at low temperature, precipitate with alcohol, and dry to obtain the final product.

[0031] The use of the traditional Chinese medicine composition according to any one of claims 1-3 in the preparation of drugs or health products for the prevention and / or treatment of viral pneumonia.

[0032] 8. Instruction manual diagrams • Figure 1 Content of main chemical components in Da Zhuque Decoction Mixture.

[0033] • Figure 2 HPLC chemical fingerprint of Da Zhuque Decoction (indicating characteristic peaks of artemisinin and baicalin).

[0034] • Figure 3 Cellular experiment verification graph (showing the negative correlation curve between drug concentration and virus inhibition rate).

[0035] • Figure 4 : Bar chart of inflammatory factor inhibition (comparing IL-6 and TNF-α levels in the model group and the drug treatment group).

[0036] • Figure 5 Comparison chart of process stability (comparing the component retention rates of the conventional method and the method of this invention).

Claims

1. An antiviral traditional Chinese medicine composition, characterized in that, Composed of the following parts by weight of active pharmaceutical ingredient: Alisma plantago-aquatica 2-6 parts, apricot kernel 4-8 parts, wild chrysanthemum 4-8 parts, artemisia annua 6-10 parts, mulberry leaf 10-14 parts, gypsum 4-8 parts, poria cocos 6-10 parts, scutellaria baicalensis 7-11 parts, rehmannia glutinosa 7-11 parts, plantain seed 10-14 parts, dandelion 13-17 parts, licorice root 2-6 parts.

2. The traditional Chinese medicine composition according to the above claims, characterized in that, The preferred weight proportions of the active pharmaceutical ingredient are: Alisma plantago-aquatica 4 parts, apricot kernel 6 parts, wild chrysanthemum 6 parts, artemisia annua 8 parts, mulberry leaf 12 parts, gypsum 6 parts, poria cocos 8 parts, scutellaria baicalensis 9 parts, rehmannia glutinosa 9 parts, plantain seed 12 parts, dandelion 15 parts, licorice root 4 parts.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The weight ratio of the core active ingredient artemisinin to baicalin in the composition is 1:2.5~3.

0.

4. A method for preparing the traditional Chinese medicine composition according to any one of claims 1-3, characterized in that, Includes the following steps: First, decoct gypsum in water for 20-30 minutes; then add the remaining medicinal materials except for raw licorice root for water extraction; extract raw licorice root separately with water; combine the extracts, adjust the pH to 6.0-7.0, concentrate at low temperature, precipitate with alcohol, and dry to obtain the final product.

5. The use of the traditional Chinese medicine composition according to any one of claims 1-3 in the preparation of drugs or health products for the prevention and / or treatment of viral pneumonia.

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