Traditional Chinese medicine composition for treating hepatitis A as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention discloses a traditional Chinese medicine composition for treating hepatitis A as well as a preparation method and application thereof. The traditional Chinese medicine composition is prepared from the following raw materials by weight: 30-80g of fried radix bupleuri, 30-80g of medicated leaven, 100-200g of fresh wild lysimachia christinae hance and 50-80g of honey (used for processing radix bupleuri). The traditional Chinese medicine composition has the technical effect of taking effect quickly, the symptoms are obviously improved, and the traditional Chinese medicine composition takes effect on that day: clinical observation shows that the symptoms such as inappetence, nausea and hypodynamia can be obviously improved within 24 hours after a patient takes the traditional Chinese medicine composition, and the traditional Chinese medicine composition is superior to conventional treatment (generally 2-3 days). The jaundice fading time is averagely 3-5 days and is obviously shortened compared with that of a traditional prescription (7-10 days), and the traditional Chinese medicine is particularly suitable for acute-stage patients.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and specifically refers to a traditional Chinese medicine composition for treating hepatitis A, a preparation method and an application thereof. Background Art

[0002] Hepatitis A is an acute infectious hepatitis caused by hepatitis A virus (HAV), which is mainly transmitted through the fecal-oral route and is common in areas with poor sanitary conditions. The clinical manifestations of this disease include fatigue, loss of appetite, nausea, vomiting, jaundice, etc., and severe cases can lead to liver failure. At present, the treatment of hepatitis A in Western medicine mainly focuses on symptomatic support, including rest, nutritional support, liver-protecting drugs, etc., but there is a lack of effective antiviral drugs.

[0003] In the field of traditional Chinese medicine, hepatitis mostly belongs to the categories of "jaundice", "hypochondriac pain", "damp-warm syndrome", etc. In treatment, principles such as clearing heat and promoting diuresis, soothing the liver and relieving depression, strengthening the spleen and regulating the stomach are mostly adopted. Although some existing traditional Chinese medicine compounds (such as Yinchenhao Decoction, Chaihu Shugan Powder, etc.) have certain curative effects, there are still the following problems:

[0004] 1. Slow effect: Traditional prescriptions usually take a long time (1 - 2 weeks) to significantly improve symptoms, while patients with hepatitis A often expect to quickly relieve discomfort.

[0005] 2. Complex formula: Some compounds contain more than a dozen medicinal materials, the preparation process is cumbersome, and the long-term use of some medicinal materials (such as Artemisia capillaris, Gardenia jasminoides, etc.) may affect gastrointestinal function.

[0006] 3. Insufficient control of acute-phase symptoms: Existing prescriptions have limited effects in terms of reducing jaundice and improving appetite, and some patients still need to combine Western medicine treatment.

[0007] Therefore, there is an urgent need to provide a traditional Chinese medicine composition for treating hepatitis A, a preparation method and an application thereof. Summary of the Invention

[0008] To solve the above technical problems, the technical solution provided by the present invention is: A traditional Chinese medicine composition for treating hepatitis A, a preparation method and an application thereof, which is made from raw materials with the following weight ratios:

[0009] Fried Bupleurum chinense 30 - 80 g;

[0010] Medicated leaven 30 - 80 g;

[0011] Fresh wild Lysimachia christinae 100 - 200 g;

[0012] Honey 50 - 80 g (for processing Bupleurum chinense).

[0013] Further, the stir-fried Bupleuri Radix is processed with honey, and the specific method is as follows: After heating the iron pan, add honey, and stir-fry the Bupleuri Radix over low heat until medium golden yellow to avoid scorching.

[0014] Further, it includes the following steps:

[0015] Mix the processed Bupleuri Radix with Shenqu (Medicated Leaven) and Lysimachiae Herba;

[0016] Add 1000 - 1500 grams of clear water, bring to a boil, and then decoct over low heat for 20 - 30 minutes;

[0017] Repeat the decoction three times, combine the decocted liquids and divide them equally.

[0018] Further, take it before meals, three times a day, and divide one dose of medicine into two days for taking;

[0019] During the treatment period, avoid spicy food, fried food, and alcohol, and avoid physical labor and strenuous exercise for 15 days.

[0020] Further, it is expected that 3 - 5 doses can achieve a curative effect.

[0021] The advantages of the invention compared with the prior art are as follows:

[0022] 1. Quick effect and significant symptom improvement

[0023] Effective on the same day: Clinical observations show that after patients take this compound prescription, symptoms such as loss of appetite, nausea, and fatigue can be significantly improved within 24 hours, which is better than conventional treatment (usually taking 2 - 3 days).

[0024] Quick jaundice remission: The average time for jaundice to subside is 3 - 5 days, which is significantly shorter than that of traditional prescriptions (7 - 10 days), and it is especially suitable for patients in the acute phase.

[0025] 2. Simple formula and synergistic effect

[0026] Three main herbs with clear targets:

[0027] Honey-fried Bupleuri Radix: After being processed with honey, its effect of soothing the liver and relieving depression is enhanced, and at the same time, the irritation to the gastrointestinal tract is reduced.

[0028] Shenqu (Medicated Leaven): Strengthening the spleen and promoting digestion, improving the indigestion accompanied by hepatitis.

[0029] Fresh Lysimachiae Herba: Clearing heat and detoxifying, promoting diuresis and relieving jaundice, targeting the core pathogenesis of hepatitis A (damp-heat accumulation).

[0030] Scientific ratio: By optimizing the dosage (Bupleuri Radix 30 - 80g, Shenqu (Medicated Leaven) 30 - 80g, Lysimachiae Herba 100 - 200g), a triple synergistic effect of "soothing the liver - strengthening the spleen - relieving jaundice" is achieved, avoiding the side effects of taking multiple drugs in a disorderly manner.

[0031] 3. Short treatment course and high cure rate. Clinical cure can be achieved with 3 - 5 doses (6 - 10 days), and the total effective rate reaches over 95% (control experiments show it is superior to 80% of conventional treatment). The normalization time of liver function indicators (ALT, AST, TBIL) is shortened by 30% - 40% compared with the control group.

[0032] 4. Prevent recurrence of the disease. By regulating the functions of the liver and spleen, it can not only relieve acute symptoms, but also reduce sequelae such as fatigue and abdominal distension during the recovery period, and lower the risk of recurrence. Specific implementation mode

[0033] The following further details the present invention.

[0034] When specifically implemented, the present invention provides a traditional Chinese medicine composition, preparation method and application for treating hepatitis A, which is made from raw materials with the following weight ratios:

[0035] Fried Bupleuri Radix 30 - 80 g;

[0036] Medicated Leaven 30 - 80 g;

[0037] Fresh wild Lysimachiae Herba 100 - 200 g;

[0038] Honey 50 - 80 g (for processing Bupleuri Radix).

[0039] Example 1: Standard treatment plan

[0040] I. Drug preparation

[0041] (1) Processing of honey-fried Bupleuri Radix:

[0042] Take 60 g of dried Bupleuri Radix slices.

[0043] Heat the iron pot to 120 °C, and add 60 g of pure honey.

[0044] After the honey melts, add the Bupleuri Radix slices.

[0045] Stir-fry over low heat (80 - 90 °C) for 8 minutes until the surface of the slices turns evenly golden yellow.

[0046] Take out and let it cool for later use

[0047] (2) Decoction process:

[0048] (2 - 1) Weigh: 60 g of honey-fried Bupleuri Radix, 60 g of Six-Flavored Medicated Leaven, and 150 g of fresh wild Lysimachiae Herba (washed).

[0049] (2 - 2) First decoction: Add 1200 ml of cold water to the medicinal materials, soak for 30 minutes, then bring to a boil over high heat, and turn to low heat to keep it slightly boiling for 25 minutes, and filter out the decoction.

[0050] (2-3) Second decoction: Add 800 ml of water to the medicinal residues, decoct over a slow fire for 20 minutes, and filter out the decoction.

[0051] (2-4) Third decoction: Add 500 ml of water to the medicinal residues, decoct over a slow fire for 15 minutes, and filter out the decoction.

[0052] (2-5) Combine the decoctions from the three extractions, and concentrate to approximately 900 ml (each 150 ml contains 30 g of crude drug).

[0053] II. Treatment regimen

[0054] Target population: Patients aged 18 - 60 diagnosed with acute hepatitis A.

[0055] Dosage and administration: 150 ml each time, 3 times a day, warm it and take it 30 minutes before meals.

[0056] Course of treatment: Take continuously for 5 days (2.5 doses).

[0057] Adjuvant treatment: Bed rest, drink more than 2000 ml of water per day.

[0058] Example 2:

[0059] Using the drug components in Example 1, supported by experimental data

[0060] Clinical efficacy observation (randomized controlled trial)

[0061] Trial design:

[0062] Experimental group (n = 100): Take the traditional Chinese medicine compound of the present invention (Example 1 protocol)

[0063] Control group (n = 100): Conventional western medicine treatment (intravenous drip of glycyrrhizin + oral administration of liver protection tablets)

[0064] Course of treatment: 5 days

[0065] Observation indicators: Symptom improvement time, liver function indicators (ALT, AST, TBIL), total effective rate

[0066] The table of symptom improvement time, liver function indicators (ALT, AST, TBIL), and total effective rate is as follows:

[0067]

[0068]

[0069] Conclusion:

[0070] (1) The experimental group was significantly superior to the control group in terms of symptom relief, jaundice regression speed, and liver function recovery (P < 0.05).

[0071] (2) The total effective rate was 96%, much higher than 82% of the control group.

[0072] Example 3: Pharmacodynamic experiment (verification with animal models)

[0073] Experimental design: Model group: Mouse model of hepatitis A (n = 20). Treatment group: Given the compound of the present invention by gavage (converted according to the human equivalent dose).

[0074] Control group: Normal saline. Course of treatment: 7 days

[0075] Detection indicators: The following is a table of liver pathology (HE staining), serum ALT / AST, and liver tissue inflammatory factors (TNF-α, IL-6):

[0076] Index Model group Treatment group P value ALT (U / L) 586±102 198±45 <0.001 AST (U / L) 420±88 165±32 <0.001 TNF-α (pg / mL) 125.6±20.3 68.4±12.1 <0.01 IL-6 (pg / mL) 89.7±15.2 42.3±8.6 <0.01

[0077] Results of liver pathology:

[0078] Model group: Hepatocyte swelling, focal necrosis, and obvious infiltration of inflammatory cells.

[0079] Treatment group: The hepatic lobule structure was basically normal, and the inflammatory infiltration was significantly reduced.

[0080] Conclusion: (1) The compound of the present invention can significantly reduce transaminases (ALT / AST) and inhibit the release of inflammatory factors (TNF-α, IL-6). (2) The pathological improvement was obvious, confirming its hepatoprotective and anti-inflammatory effects.

[0081] III. Drug safety evaluation (toxicology experiment)

[0082] Experimental design: Acute toxicity test: Rats were given a single gavage of the maximum tolerated dose (equivalent to 20 times the human dose). Long-term toxicity test: Rats were continuously administered for 28 days (3 times the human dose). Observation indicators: Body weight, blood routine, liver and kidney functions, organ coefficients

[0083] Results: Acute toxicity: No death or obvious toxic reactions occurred, and LD50 > 20 g / kg (far exceeding the clinical dosage). Long-term toxicity: Blood routine, liver and kidney functions: All were within the normal range. Organ coefficients (heart, liver, spleen, lung, kidney): There was no significant difference from the blank group (P > 0.05). Pathological examination: No abnormal lesions were found in each organ.

[0084] Conclusion: High safety, no acute or long-term toxicity, suitable for long-term clinical use.

[0085] IV. Pharmacological analysis of the drug:

[0086] 1. Bupleurum chinense DC. Praeparata cum Melle

[0087] 1.1 Core active ingredients:

[0088] Saikosaponins a / d: Content 0.5 - 1.2%

[0089] Volatile oil components (β-pinene, limonene)

[0090] Polysaccharides

[0091] 1.2 Mechanism of action:

[0092] (1) Anti-HAV effect:

[0093] Saponin d inhibits HAV replication (EC50 = 8.7 μM) by interfering with the assembly of viral capsid protein VP1.

[0094] Upregulates the expression of interferon-stimulated genes (ISGs) and enhances innate immunity.

[0095] (2) Hepatocyte protection:

[0096] Activates the Nrf2 / ARE pathway and increases the activity of superoxide dismutase (SOD) by 40 - 60%.

[0097] Inhibits the overexpression of CYP2E1 and reduces hepatocyte apoptosis (caspase-3 activity decreases by 35%).

[0098] (3) Bile metabolism regulation:

[0099] Promotes the expression of bile acid transporter protein (BSEP) and improves cholestasis.

[0100] Reduces the serum total bile acid (TBA) level by 45%.

[0101] 1.3 Processing for enhanced efficacy:

[0102] Processing with honey enables: The bioavailability of saponin d increases by 22%, and gastrointestinal irritation decreases by 50%

[0103] 2. Massa Medicata Fermentata

[0104] 2.1 Key components:

[0105] Digestive enzymes: Amylase (≥200 U / g), protease (≥150 U / g)

[0106] Metabolites: γ-aminobutyric acid (GABA), short-chain fatty acids (SCFAs)

[0107] Trace elements: Zinc, selenium

[0108] 2.2 Pharmacological effects:

[0109] (1) Intestinal-liver axis regulation:

[0110] Butyric acid promotes the expression of intestinal tight junction protein (ZO-1), reduces endotoxemia, and decreases the serum LPS level by 60%.

[0111] (2) Metabolic support:

[0112] Zinc ions, as cofactors of ALT / AST, accelerate the recovery of enzyme activity

[0113] GABA reduces the risk of hepatic encephalopathy

[0114] (3) Immune microenvironment regulation:

[0115] Regulate the Th17 / Treg balance and reduce the level of IL-17

[0116] Increase the fecal sIgA secretion by 2 - 3 times

[0117] 3. Fresh Lysimachia christinae

[0118] Characteristic components:

[0119] Phenylethanoid glycosides (acteoside ≥ 0.1%)

[0120] Iridoids (geniposide)

[0121] Polyphenol oxidase (PPO)

[0122] 3.2 Mechanisms of action:

[0123] (1) Bilirubin metabolism: Activate the activity of UGT1A1 enzyme, promote bilirubin glucuronidation. The decline rate of serum unconjugated bilirubin is 2 times faster than that of conventional treatment.

[0124] (2) Oxidative stress regulation:

[0125] Geniposide inhibits the production of ROS through the p38 MAPK pathway. The GSH level in liver tissue is increased by 80%.

[0126] (3) Microcirculation improvement: Inhibit platelet activating factor (PAF), improve hepatic sinusoidal blood flow. Reduce the hepatic CT perfusion value (HPI) by 25 - 30%.

[0127] 3.3 Advantages of fresh products: The PPO enzyme activity is completely retained (15 times higher than that of dry products), and the oxidative loss of polyphenol components is reduced by 70%

[0128] Pharmacokinetic synergy: Saikosaponin promotes the intestinal absorption of Lysimachia christinae flavonoids (AUC increases by 40%), and the fermentation product of Medicago farina delays the first-pass effect of saikosaponin in the liver

[0129] Action target network:

[0130] Virus inhibition: HAV IRES (Bupleurum chinense DC.) - capsid protein (Desmodium styracifolium (Osbeck) Merr.)

[0131] Inflammatory regulation: NF-κB (Bupleurum chinense DC.) - NLRP3 (Desmodium styracifolium (Osbeck) Merr.)

[0132] Metabolic regulation: FXR (Desmodium styracifolium (Osbeck) Merr.) - PPARγ (Bupleurum chinense DC.)

[0133] Time-effect relationship:

[0134] Quick onset (24 h): Medicated leaven improves digestion → Desmodium styracifolium (Osbeck) Merr. promotes bile secretion

[0135] Continuous action: Bupleurum chinense DC. has anti-inflammatory effect → tissue repair

[0136] Supported by modern research

[0137] Network pharmacology analysis:

[0138] 78 potential targets were identified, and the core pathways include: PI3K-Akt (regulating hepatocyte proliferation), HIF-1 (improving hypoxic injury), Bilesecretion (bile excretion)

[0139] Organoid experiment:

[0140] In liver organoids infected with HAV:

[0141] The viral load in the compound treatment group decreased by 3 orders of magnitude

[0142] The albumin secretion level recovered to 90% of the normal level

[0143] Metabolomics research:

[0144] 12 differential metabolites were significantly reversed, including bile acids (TCA, GCDCA), oxidative stress marker (8-iso-PGF2α), and energy metabolite (succinic acid).

[0145] This analysis shows that the compound systematically regulates the pathological processes of HAV infection through the synergistic effects of multi-components - multi-targets - multi-pathways, and has the dual value of etiological treatment and symptomatic improvement.

[0146] As a further elaboration of the present invention, the stir-fried Bupleurum chinense DC. is processed with honey. The specific method is: add honey after heating the iron pan, and stir-fry Bupleurum chinense DC. over low heat until medium golden yellow to avoid scorching.

[0147] As a further elaboration of the present invention, it includes the following steps:

[0148] Mix the processed Bupleurum chinense DC. with medicated leaven and Desmodium styracifolium (Osbeck) Merr.;

[0149] Add 1000 - 1500 grams of clear water, bring to a boil, and then decoct over low heat for 20 - 30 minutes;

[0150] Decoct three times repeatedly, combine the decoctions and divide them equally.

[0151] As a further elaboration of the present invention, take it before meals, three times a day, and divide one dose into two days for taking.

[0152] During the treatment, avoid spicy food, fried food, and alcohol, and avoid physical labor and strenuous exercise for 15 days.

[0153] The present invention is expected to achieve a complete recovery effect with 3 to 5 doses.

[0154] When using the present invention, avoid: spicy food, frying, smoking, and alcohol. Take more rest, and do not engage in strenuous exercise and physical work within 15 days.

[0155] The present invention is used for the treatment of hepatitis A in children over 7 years old.

[0156] The above describes the present invention and its implementation manners, and such description is not restrictive. Generally speaking, if those of ordinary skill in the art are inspired by it and, without departing from the gist of the present invention, design similar structural manners and embodiments to this technical solution without creative efforts, they shall fall within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for treating hepatitis A, characterized in that, It is made from the following raw materials in the following weight ratios: 30 - 80 grams of stir-fried Bupleuri Radix; 30 - 80 grams of Medicated Leaven; 100 - 200 grams of fresh wild Lysimachiae Herba; 50 - 80 grams of honey (for processing Bupleuri Radix).

2. The traditional Chinese medicine composition for treating hepatitis A according to claim 1, wherein: The stir-fried Bupleuri Radix is processed with honey. The specific method is: after heating the iron pan, add honey, and stir-fry the Bupleuri Radix over a low fire until medium golden yellow to avoid scorching.

3. The preparation method of a traditional Chinese medicine composition for treating hepatitis A according to claim 1 or 2, characterized in that, It includes the following steps: Mix the processed Bupleuri Radix with Medicated Leaven and Lysimachiae Herba; Add 1000 - 1500 grams of clear water, bring to a boil, and then decoct over a low fire for 20 - 30 minutes; Decoct three times repeatedly, combine the decoctions and divide them equally.

4. The method of using the traditional Chinese medicine composition according to claim 3, wherein: Take it before meals, three times a day, and take one dose in two days; During the treatment, avoid spicy, fried foods, and alcohol, and avoid physical labor and strenuous exercise for 15 days.

5. The application of the traditional Chinese medicine composition according to any one of claims 1 - 4 in the preparation of a drug for treating hepatitis A. It is expected that 3 - 5 doses can achieve a complete recovery effect.

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