Traditional Chinese medicine composition for treating cerebral hemorrhage and application thereof

Abstract

The invention belongs to the field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating cerebral hemorrhage and application thereof. The traditional Chinese medicine composition comprises the following main active components in parts by mass: 10-30 parts of red ginseng, 10-20 parts of rheum officinale, 0.5-1 part of processed semen strychni, 1-10 parts of leech and 10-30 parts of pseudo-ginseng. Clinical tests show that 24 hours after cerebral hemorrhage attacks, the traditional Chinese medicine composition can obviously improve uw-mRS and mRS of cerebral hemorrhage patients for 90 days, obviously improve the poor prognosis of the cerebral hemorrhage patients and improve the independent living ability. Meanwhile, compared with a placebo group, the traditional Chinese medicine compound group for treating related adverse events has no significant difference (Pgt; 0.05), which indicates that the traditional Chinese medicine composition disclosed by the invention is good in safety. The results show that the traditional Chinese medicine composition can effectively treat cerebral hemorrhage and is good in safety.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine, specifically relating to a traditional Chinese medicine composition for treating cerebral hemorrhage and its application. Background Technology

[0002] Intracerebral hemorrhage (ICH) refers to non-traumatic intracerebral hemorrhage, a common and frequently occurring clinical disease characterized by its rapid onset, varied progression, and rapid changes. Acute ICH seriously endangers human health, exhibiting high mortality and disability rates. However, currently, there are no effective treatments, whether medical or surgical: the FAST study on coagulation factors, the INTERACT-II study on intensive blood pressure reduction, and clinical studies on neurotrophic agents have all been ineffective. The STICH international surgical study on intracerebral hemorrhage has only demonstrated effectiveness for superficial hemorrhages; even with thorough hematoma removal, deep hemorrhages show no significant improvement in long-term mortality or severe disability.

[0003] Traditional Chinese medicine (TCM) has unique advantages in improving function and clinical prognosis due to its multi-target efficacy and fewer side effects. However, previous clinical studies have suggested that using blood-activating and stasis-removing methods to treat patients with hyperacute cerebral hemorrhage within 0-6 hours of onset may increase the risk of rebleeding. Therefore, the selection of TCM for patients with acute cerebral hemorrhage should be more cautious, and appropriate time windows should be chosen for TCM intervention. Currently, there is still a lack of effective TCM compositions for treating acute cerebral hemorrhage in clinical practice, thus it is necessary to develop such a composition. Summary of the Invention

[0004] The first objective of this invention is to provide a traditional Chinese medicine composition for treating cerebral hemorrhage, and the second objective of this invention is to provide the application of this traditional Chinese medicine composition.

[0005] According to a first aspect of the present invention, a traditional Chinese medicine composition for treating cerebral hemorrhage is provided, the main active ingredients comprising, by weight: 10-30 parts of red ginseng, 10-20 parts of rhubarb, 0.5-1 part of processed nux vomica, 1-10 parts of leech, and 10-30 parts of Panax notoginseng.

[0006] This invention posits that "internal wind" is the core pathogenesis of hemorrhagic stroke. Therefore, it focuses on dispelling wind and unblocking the meridians while invigorating qi and promoting blood circulation.

[0007] In this formula, red ginseng, which greatly replenishes vital energy, serves as the principal ingredient; rhubarb, which clears heat and detoxifies, and notoginseng, which invigorates blood and removes blood stasis, serve as the assistant ingredients; processed strychnos nux-vomica and leeches, which dispel wind and unblock the meridians, serve as adjuvant ingredients; and rhubarb, which circulates through all twelve meridians, serves as the guiding ingredient. The entire formula works synergistically to invigorate qi and blood, dispel wind, unblock the meridians, and detoxify.

[0008] The raw materials for this formula come from the following sources: Red ginseng: The dried roots and rhizomes of Panax ginseng CAMey., a plant of the Araliaceae family, after steaming.

[0009] Rhubarb: The dried roots and rhizomes of Rheum palmatum L., Rheum offcinale Baill., and Rheum tanguticum Maxim. ex Balf.

[0010] Processed Strychnos nux-vomica seeds: These are processed products of the traditional Chinese medicine Strychnos nux-vomica, specifically the dried, mature seeds of the plant Strychnos nux-vomica L. (family Loganiaceae), which are cleaned and stir-fried with sand. Because acute cerebral hemorrhage is a critical and severe condition, using a slightly larger dose of Strychnos nux-vomica can enhance the therapeutic effect on serious illnesses. Therefore, the amount of processed Strychnos nux-vomica in the herbal composition of this invention is 0.5-1 part. Furthermore, clinical experience shows that the overall formulation of the herbal composition of this invention has a mild laxative effect, which can reduce the toxicity of Strychnos nux-vomica.

[0011] Leeches: The dried whole body of the leeches *Whitmania Pigra Whitman*, *Whitmania acranutata Whitman*, or *Hirudo nipponica Whitman*.

[0012] Panax notoginseng (Burk.) FH Chen, a plant belonging to the Araliaceae family.

[0013] In some embodiments, the main active ingredients, by weight, include: 30 parts red ginseng, 15 parts rhubarb, 0.8 parts processed nux vomica, 5 parts leech, and 30 parts Panax notoginseng.

[0014] In some embodiments, pharmaceutically acceptable excipients may also be added. Specifically, the excipients used are carriers or excipients commonly used in the art, including but not limited to starch, lactose, glucose, sodium carboxymethyl cellulose, ethyl cellulose and methyl cellulose, malt, gelatin, polyols (such as propylene glycol, glycerol, mannitol), tablets, etc., to help improve the stability or activity of the drug, or to produce an acceptable taste or odor when taken orally.

[0015] In some embodiments, the dosage form of the traditional Chinese medicine composition is a decoction, oral liquid, granules, powder, tablets, pills, or capsules. This facilitates clinical administration.

[0016] According to a second aspect of the present invention, the use of the above-described traditional Chinese medicine composition in the preparation of a medicament for treating cerebral hemorrhage is provided. Specifically, the cerebral hemorrhage is acute cerebral hemorrhage.

[0017] The beneficial effects of this invention include: Clinical trials have shown that taking the traditional Chinese medicine composition of this invention 24 hours after the onset of cerebral hemorrhage significantly improves the 90-day uw-mRS and mRS in patients with cerebral hemorrhage, significantly improves the poor prognosis of patients with cerebral hemorrhage, and enhances their ability to live independently. Meanwhile, there was no significant difference in treatment-related adverse events between the traditional Chinese medicine compound group and the placebo group (P>0.05), indicating that the traditional Chinese medicine composition of this invention has good safety. These results demonstrate that the traditional Chinese medicine composition of this invention can effectively treat cerebral hemorrhage and has good safety. Detailed Implementation

[0018] The present invention will be further described in detail below with reference to specific embodiments. Unless otherwise specified, all raw materials used in the present invention are commercially available. Methods not specifically described employ conventional methods known in the art.

[0019] Example 1 The traditional Chinese medicine decoction for treating cerebral hemorrhage in this embodiment is prepared from the following components: 30g red ginseng, 15g rhubarb, 0.8g processed nux vomica, 5g leech, and 30g Panax notoginseng.

[0020] Take the above components and prepare a traditional Chinese medicine decoction according to the existing methods for preparing traditional Chinese medicine decoctions. The ratio is the dosage for one dose, which is about 300 mL.

[0021] For example, the preparation method of traditional Chinese medicine decoction is as follows: the above-mentioned Chinese medicinal materials are mixed according to the ratio to obtain a mixture, and then soaked in water at a ratio of 1:10 for 0.5 hours and decocted for 0.5 hours. The mixture is filtered to obtain a first filtrate and a residue. The residue is decocted once, and the resulting filtrate is combined with the first filtrate and sterilized. After cooling to room temperature, it is packaged.

[0022] Example 2 The oral liquid of traditional Chinese medicine for treating cerebral hemorrhage in this embodiment is made from the following raw materials: 30g red ginseng, 15g rhubarb, 0.8g processed nux vomica, 5g leech, and 30g Panax notoginseng.

[0023] Take the above components and prepare the traditional Chinese medicine oral liquid according to the existing preparation method of traditional Chinese medicine oral liquid.

[0024] For example, the preparation method of the oral liquid of traditional Chinese medicine is as follows: the above-mentioned Chinese medicinal materials are mixed according to the ratio to obtain a mixture, and then the mixture is added to water at a ratio of 1:15 and soaked for 20 minutes and then decocted for 1 hour. The mixture is filtered to obtain the first filtrate and the residue. The residue is decocted once, and the filtrate obtained is combined with the first filtrate. The mixture is then concentrated to 66 mL, sterilized, cooled to room temperature, and then divided into two bottles, each containing 33 mL.

[0025] Example 3 The traditional Chinese medicine granules for treating cerebral hemorrhage in this embodiment are prepared from the following raw materials: 30g red ginseng, 15g rhubarb, 0.8g processed strychnos nux-vomica, 5g leech, and 30g Panax notoginseng.

[0026] Take the above components, add a carrier or excipient, and prepare traditional Chinese medicine granules according to existing methods for preparing traditional Chinese medicine granules.

[0027] For example, traditional Chinese medicine granules can be prepared by the following methods: The filtrate was obtained according to the method for preparing the decoction in Example 1. The filtrate was concentrated under reduced pressure to obtain a clear extract. Maltodextrin was added to the clear extract, and then spray-dried to obtain a dry extract powder. Next, maltodextrin was added to the dry extract powder to obtain a mixed powder. Then, a 90% (v / v) ethanol-water solution was added to the mixed powder to prepare a soft mass. The soft mass was sieved to obtain wet granules. Finally, the wet granules were dried to obtain the final product. The obtained granules were packaged into packets of approximately 10g each for convenient clinical use and administration.

[0028] Example 4 The traditional Chinese medicine powder for treating cerebral hemorrhage in this embodiment is prepared from the following raw materials: 30g red ginseng, 15g rhubarb, 0.8g processed nux vomica, 5g leech, and 30g Panax notoginseng.

[0029] Take the above components, pulverize and mix them evenly with a suitable carrier or excipient to make a dry powder, forming a powder, which can be taken with water.

[0030] Example 5 The traditional Chinese medicine tablets for treating cerebral hemorrhage in this embodiment are made from the following raw materials: 30g red ginseng, 15g rhubarb, 0.8g processed nux vomica, 5g leech, and 30g Panax notoginseng.

[0031] Take the above components and prepare wet granules according to the method of Example 3. Then compress and dry the wet granules to obtain tablets.

[0032] Example 6 The traditional Chinese medicine capsule for treating cerebral hemorrhage in this embodiment is made from the following raw materials: 30g red ginseng, 15g rhubarb, 0.8g processed nux vomica, 5g leech, and 30g Panax notoginseng.

[0033] Take the above components, pulverize and mix them evenly with a suitable carrier or excipient to make a dry powder, granulate it, and then fill it into capsules to make a capsule preparation.

[0034] To investigate the therapeutic effect of the traditional Chinese medicine composition of the present invention on acute cerebral hemorrhage, the oral liquid of traditional Chinese medicine prepared in Example 2 was used for the following clinical trials.

[0035] I. Relevant Standards 1. TCM syndrome diagnosis: Refer to the TCM syndrome scale for stroke. The TCM syndrome scale for stroke is based on the "Standards for TCM Diagnosis and Efficacy Evaluation of Stroke".

[0036] 2. Inclusion criteria (1) Age ≥ 18 years; (2) Patients with acute cerebral hemorrhage admitted to the hospital within 72 hours of onset; (3) Meets the Western medicine diagnostic criteria and TCM syndrome diagnosis for intracerebral hemorrhage (ICH); (4) Sign the informed consent form.

[0037] 3. Exclusion criteria (1) Having diseases such as pulmonary tuberculosis, pulmonary edema, pulmonary embolism, non-infectious interstitial lung disease, and respiratory and circulatory failure; (2) A clear history of gastrointestinal diseases such as gastrointestinal tumors, inflammatory bowel disease, or active gastrointestinal bleeding within the past 3 months; (3) Patients with immune-related diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjögren's syndrome, or those who are receiving immunotherapy for other diseases, as well as patients who have received any antibiotic treatment within four weeks prior to inclusion in the study.

[0038] 4. Elimination criteria Patients who were mistakenly included after entering clinical trials and were found to be ineligible for inclusion, and patients who met the inclusion criteria but did not take the medication after inclusion, can be considered excluded patients.

[0039] 5. Criteria for determining dropout or loss to follow-up (1) Those lost to follow-up during the treatment period; (2) Those who voluntarily withdraw during the treatment period; (3) Failure to take the research drug as required, or taking less than 2 / 3 of the required dosage; (4) Failure to complete the inspection and assessment within the required timeframe; (5) Patients who meet the inclusion criteria as specified in the clinical trial protocol but fail to complete the trial for some reason.

[0040] All of the above can be considered dropouts or lost-to-follow-up patients. This includes patients who dropped out voluntarily and those whom doctors determined had dropped out. 6. Termination Criteria (1) Those who experience severe adverse reactions during treatment; (2) Those who develop other serious illnesses or die during treatment.

[0041] II. Grouping and Sample Size Subjects who met the inclusion criteria but not the exclusion criteria were randomly assigned in a ratio of approximately 1:1 to either the traditional Chinese medicine compound group or the placebo group using a randomized block design. The traditional Chinese medicine compound group consisted of 329 patients, and the placebo group consisted of 324 patients.

[0042] III. Experimental Drugs and Treatment Methods Both groups of subjects received basic treatment for acute intracerebral hemorrhage according to the AHA guidelines, such as neurocritical care, dehydration to reduce intracranial pressure, blood pressure control, and nutritional support.

[0043] Traditional Chinese medicine compound group: basic treatment + oral liquid of traditional Chinese medicine prepared in Example 2 (33 ml each time, orally, once every 8 hours).

[0044] Placebo group: Basic treatment + placebo (33 ml each time, orally, every 8 hours. The placebo consists of food additives such as dextrin, coloring, and bittering agents, and water (all food grade). Its appearance, taste, and weight are consistent with the above-mentioned oral Chinese medicine liquid).

[0045] Both groups of subjects were treated for 14 days and followed up for 90 days.

[0046] IV. Efficacy Evaluation Indicators According to the international gold standard: 90-day UW-MRS, mRS, mortality rate, disability rate (mRS 3-5 percentage), etc., and a safety evaluation was conducted.

[0047] 1. Primary Outcome Scale 90-day uw-mRS.

[0048] 2. Secondary outcome indicators mRS, death or disability, Barthel Index, EQ-5D-5L utility score, pneumonia, discharge within 28 days, safety.

[0049] V. Statistical Methods Baseline count data were compared between groups using the χ² test; continuous data were compared between groups using the t-test (with the t' test used for unequal variances); ordinal data were compared between groups using the rank-sum test, α = 0.05. The primary outcome measure was modeled using a general linear model, while secondary outcome measures were analyzed according to their distribution. All data analyses were performed using the SAS 9.4 statistical software package.

[0050] VI. Experimental Results 1. Patient baseline comparison The baseline comparison results of the two groups of patients are shown in Table 1: Table 1. Baseline comparison results between the two groups of patients

[0051] As shown in Table 1, apart from the median time from symptom onset to medical attention, there were no statistically significant differences in baseline indicators between the two groups before treatment (P>0.05), indicating comparability.

[0052] 2. Primary and secondary outcome indicators Table 2 shows a comparison of the primary and secondary outcome measures between the two groups of patients after treatment: Table 2. Comparison of primary and secondary outcome measures between the two groups after treatment.

[0053] Note: (1) In the table, MD means mean difference and OR means risk ratio.

[0054] (2) The adjusted model is based on factors such as center, baseline NIHSS, and pre-onset mRS to correct the model results.

[0055] (3) The ordered mRS for poor prognosis is analyzed as an ordered variable with 6 levels. In the ordered mRS test method, there is no mean, only OR and 95% CI. Therefore, there is no mean data for the two groups under the ordered mRS index for poor prognosis.

[0056] (4) Since the number of patients in each group under each indicator in Table 2 has been adjusted, the number of patients in the traditional Chinese medicine compound group under each indicator in Table 2 is less than 329, and the number of patients in the placebo group is less than 324.

[0057] (5) Adverse events include serious adverse events and adverse events of particular concern (AESI).

[0058] As shown in Table 2, the primary outcome measure (90-day unw-mRS) in the traditional Chinese medicine compound group was significantly higher than that in the placebo group, with a statistically significant difference (P=0.03); the important secondary outcome measure (ordinal mRS for poor prognosis) also showed a statistically significant difference compared to the placebo group (P=0.04). This indicates that taking the traditional Chinese medicine composition of this invention 24 hours after the onset of cerebral hemorrhage can significantly improve the 90-day unw-mRS and mRS in patients with cerebral hemorrhage, significantly improve the poor prognosis of patients with cerebral hemorrhage, and improve their ability to live independently. Meanwhile, there was no significant difference in treatment-related adverse events between the traditional Chinese medicine compound group and the placebo group (P>0.05), indicating that the traditional Chinese medicine composition of this invention has good safety. The above results demonstrate that the traditional Chinese medicine composition of this invention can effectively treat cerebral hemorrhage and has good safety.

Claims

1. A traditional Chinese medicine composition for treating cerebral hemorrhage, characterized in that, Its main active ingredients, by weight, include: 10-30 parts red ginseng, 10-20 parts rhubarb, 0.5-1 part processed nux vomica, 1-10 parts leech, and 10-30 parts Panax notoginseng.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, Its main active ingredients, by weight, include: 30 parts red ginseng, 15 parts rhubarb, 0.8 parts processed nux vomica, 5 parts leech, and 30 parts Panax notoginseng.

3. The traditional Chinese medicine composition according to claim 1 or 2, characterized in that, Pharmaceutically acceptable excipients can also be added.

4. The traditional Chinese medicine composition according to claim 1 or 2, characterized in that, The dosage form of the traditional Chinese medicine composition is decoction, oral liquid, granules, powder, tablets, pills or capsules.

5. The use of the traditional Chinese medicine composition according to any one of claims 1 to 4 in the preparation of a medicament for treating cerebral hemorrhage.

6. The application according to claim 5, characterized in that, The cerebral hemorrhage mentioned is an acute cerebral hemorrhage.

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