A traditional Chinese medicine composition for nourishing blood and regulating marrow and application thereof

Abstract

The application discloses a traditional Chinese medicine composition for nourishing blood and regulating marrow and application thereof, and belongs to the technical field of traditional Chinese medicine compositions. In view of the defects of hemophilia arthritis treatment in western medicine, such as inhibitor production, frequent injection, high cost and unknown safety of gene therapy, the application provides a traditional Chinese medicine composition for nourishing blood and regulating marrow. Through the synergistic effect of eight Chinese herbal medicine materials, namely, herba agrimoniae, panax notoginseng, poria cocos, bletilla striata, cornus officinalis, angelica sinensis, radix clematidis and radix paeoniae alba, the traditional Chinese medicine composition can achieve the effects of kidney-tonifying, marrow-regulating and yin-yang balancing, can promote the generation of bone marrow hematopoietic materials, and can improve joint microcirculation through blood-nourishing and blood-stasis-removing, so as to repair hemophilia joint damage. The traditional Chinese medicine composition integrates three links of kidney-tonifying, blood-nourishing and meridian-dredging, is suitable for the pathogenesis of marrow deficiency and blood stasis of hemophilia arthritis, provides a new treatment scheme for the treatment of hemophilia arthritis, and the treatment effect of the traditional Chinese medicine composition on hemophilia arthritis is proved through clinical experiments.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine composition technology, and in particular to a traditional Chinese medicine composition for nourishing blood and regulating bone marrow and its application. Background Technology

[0002] Hemophilia is a rare, lifelong, hereditary, bleeding disorder. With the advent of cryoprecipitate and plasma coagulation factor VIII (FVIII) preparations, hemophilic arthropathy has transformed from a life-threatening condition into a lifelong illness. If treatment is not timely or appropriate, it can lead to disability, severely impacting work and life, and placing a heavy burden on families and society.

[0003] Hemophilia is characterized by recurrent abnormal bleeding, with joint bleeding being the most common, accounting for approximately 80% of cases. Joint bleeding is a major cause of synovial hyperplasia, cartilage, and bone damage. Repeated bleeding in the joints of hemophilic patients damages the joints, eventually leading to hemophilic arthritis. When joint bleeding occurs, patients experience significant joint pain, swelling, increased local temperature, and limited joint mobility. Once the bleeding is controlled, the pain lessens, the swelling stops worsening, and the local temperature decreases.

[0004] Reducing bleeding is key to hemophilia treatment, but simply stopping the bleeding is only a temporary measure, not the best approach. Currently, Western medicine treatments for hemophilia include replacement therapy, gene therapy (in clinical practice), and novel dual-antibody therapy, but these have drawbacks such as the production of inhibitors, frequent injections, high costs, and unknown safety profiles of gene therapy. Traditional Chinese medicine believes that the kidneys are the foundation of innate essence, governing bone marrow production. Bone marrow is directly related to hematopoiesis, and since it is stored in the bones and governed by the kidneys, the strength of kidney function directly affects bone marrow spermatogenesis and hematopoiesis. Therefore, methods that nourish the kidneys and replenish marrow can address bone marrow hematopoiesis from the perspective of producing and supplying hematopoietic raw materials. Thus, in the treatment of hemophilia, tonifying the kidneys, nourishing blood, and regulating marrow, and adjusting the yin-yang balance of the kidneys, is a fundamental principle of treating this disease. Summary of the Invention

[0005] To address the aforementioned problems, this invention aims to provide a traditional Chinese medicine composition for nourishing blood and regulating bone marrow, and its application. Through the synergistic effect of eight herbal ingredients—Agrimonia pilosa, Panax notoginseng, Poria cocos, Bletilla striata, Cornus officinalis, Angelica sinensis, Clematis chinensis, and Paeonia lactiflora—it achieves the effects of tonifying the kidneys and regulating bone marrow, balancing Yin and Yang. It not only promotes the production of hematopoietic raw materials in the bone marrow but also improves joint microcirculation by nourishing blood and removing blood stasis, thus addressing both the symptoms and the root cause of hemophilic joint damage. This traditional Chinese medicine composition integrates the three stages of "tonifying the kidneys, nourishing blood, and unblocking the meridians," perfectly aligning with the pathogenesis of bone marrow deficiency and blood stasis in hemophilic arthritis.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0007] This invention provides a traditional Chinese medicine composition for nourishing blood and regulating marrow, comprising eight herbal raw materials: Agrimonia pilosa, Panax notoginseng, Poria cocos, Bletilla striata, Cornus officinalis, Angelica sinensis, Clematis chinensis, and Paeonia lactiflora.

[0008] The weight proportions of different Chinese herbal raw materials are as follows: Agrimonia pilosa 28-32 parts, Panax notoginseng 4-8 parts, Poria cocos 13-17 parts, Bletilla striata 10-14 parts, Cornus officinalis 7-11 parts, Angelica sinensis 10-14 parts, Clematis chinensis 7-11 parts, and Paeonia lactiflora 10-14 parts.

[0009] The preferred weight proportions of different Chinese herbal medicine ingredients are: Agrimonia pilosa 30 parts, Panax notoginseng 6 parts, Poria cocos 15 parts, Bletilla striata 12 parts, Cornus officinalis 9 parts, Angelica sinensis 12 parts, Clematis chinensis 9 parts, and Paeonia lactiflora 12 parts.

[0010] In this traditional Chinese medicine composition, the pharmacological properties of different herbal raw materials are as follows:

[0011] Agrimony: Bitter, astringent, neutral; Functions and indications: Astringent and nourishing to the blood, antimalarial, antidysentery, detoxifying, and tonifying. Used for hemoptysis, hematemesis, metrorrhagia, malaria, bloody dysentery, exhaustion, carbuncles and boils, vulvar itching and leukorrhea.

[0012] Panax notoginseng: sweet, slightly bitter, warm; functions and indications: dispels blood stasis, nourishes blood, reduces swelling and relieves pain. Used for hemoptysis, hematemesis, epistaxis, hematochezia, metrorrhagia, traumatic bleeding, chest and abdominal pain, and swelling and pain from falls.

[0013] Poria cocos: sweet, bland, neutral; functions and indications: promotes diuresis and eliminates dampness, strengthens the spleen, and calms the mind. Used for edema with scanty urine, phlegm retention with dizziness and palpitations, spleen deficiency with poor appetite, loose stools and diarrhea, restlessness, palpitations and insomnia.

[0014] Bletilla striata: bitter, sweet, astringent, cold; functions and indications: astringent and nourishing blood, reducing swelling and promoting tissue regeneration. Used for hemoptysis, hematemesis, traumatic bleeding, carbuncles and boils, and chapped skin.

[0015] Cornus officinalis: Sour, astringent, slightly warm; Functions and indications: Tonifies the liver and kidneys, astringes and consolidates the body. Used for dizziness and tinnitus, soreness and weakness of the lower back and knees, impotence and seminal emission, enuresis and frequent urination, metrorrhagia and leukorrhea, profuse sweating and collapse, internal heat and thirst.

[0016] Angelica sinensis: sweet, pungent, warm; functions and indications: nourishes blood and regulates menstruation, invigorates blood and relieves pain, moistens the intestines and promotes bowel movement. Used for blood deficiency and chlorosis, dizziness and palpitations, irregular menstruation, amenorrhea and dysmenorrhea, abdominal pain due to deficiency and cold, rheumatic arthralgia, traumatic injuries, carbuncles and sores, and constipation due to intestinal dryness.

[0017] Clematis chinensis: pungent, salty, warm; functions and indications: dispels wind and dampness, unblocks meridians and relieves pain. Used for rheumatic pain, numbness of limbs, muscle contracture, difficulty in flexion and extension, and bone stuck in the throat.

[0018] White peony root: bitter, sour, slightly cold; functions and indications: nourishes blood and regulates menstruation, astringes yin and stops sweating, softens the liver and relieves pain, and calms liver yang. Used for blood deficiency and chlorosis, irregular menstruation, spontaneous sweating, night sweats, hypochondriac pain, abdominal pain, limb spasms, headache and dizziness.

[0019] This traditional Chinese medicine composition primarily uses herbs that cool the blood, nourish the blood, remove blood stasis, and regulate the marrow. In this formula, Panax notoginseng invigorates blood circulation, removes blood stasis, reduces swelling, and relieves pain; Agrimonia pilosa astringes and nourishes the blood, invigorates qi, and replenishes deficiency; these two herbs together serve as the principal herbs. Paeonia lactiflora nourishes the blood, softens the liver, and relieves spasms and pain; Angelica sinensis replenishes and invigorates the blood, regulates menstruation, and relieves pain; Cornus officinalis replenishes the blood, strengthens essence, and tonifies the liver and kidneys; these three herbs together serve as the assistant herbs. Bletilla striata astringes and nourishes the blood, reduces swelling, and promotes tissue regeneration; Clematis chinensis dispels wind and dampness, unblocks meridians, and has a good therapeutic effect on rheumatic pain; Poria cocos promotes diuresis and eliminates dampness, relieving pain caused by dampness obstruction; this is the adjuvant herb of the formula. Based on the principle of tonifying the kidneys and replenishing the marrow, Agrimonia pilosa and Panax notoginseng nourish and invigorate the blood; Cornus officinalis and Angelica sinensis tonify the kidneys and nourish the blood; Paeonia lactiflora softens the liver and regulates the marrow; Poria cocos strengthens the spleen and eliminates dampness; Bletilla striata protects the membranes and strengthens the collaterals; and Clematis chinensis promotes joint mobility. The combined effects of these herbs tonify the kidneys and regulate the marrow, balancing Yin and Yang. They promote the production of hematopoietic raw materials in the bone marrow and improve joint microcirculation by nourishing blood and removing blood stasis, thus addressing both the symptoms and the root cause of hemophilic joint damage.

[0020] On the other hand, the present invention provides the application of a traditional Chinese medicine composition for nourishing blood and regulating marrow as described above in the preparation of a drug for treating hemophilic arthritis.

[0021] The beneficial effects of this invention are:

[0022] 1. This invention provides a traditional Chinese medicine composition for nourishing blood and regulating bone marrow, comprising eight herbal ingredients: Agrimonia pilosa, Panax notoginseng, Poria cocos, Bletilla striata, Cornus officinalis, Angelica sinensis, Clematis chinensis, and Paeonia lactiflora. This composition integrates three aspects: "tonifying the kidney, nourishing blood, and unblocking the meridians," achieving the effects of tonifying the kidney, regulating bone marrow, and balancing Yin and Yang. It promotes the production of hematopoietic raw materials in the bone marrow and improves joint microcirculation by nourishing blood and removing blood stasis, addressing both the symptoms and root cause of hemophilic joint damage, thus aligning with the pathogenesis of bone marrow deficiency and blood stasis in hemophilic arthritis. Through network pharmacology studies and drug component mass spectrometry analysis, this traditional Chinese medicine composition has potential therapeutic effects on hemophilic arthritis.

[0023] 2. The traditional Chinese medicine composition in this invention has been clinically proven to be effective in treating hemophilic arthritis. The product is low in cost, easy to use, and of high production quality. The eight herbs used together cool the blood without causing blood stasis, treat blood stasis and regulate bone marrow, and work together to cool and nourish the blood, promote blood circulation and remove blood stasis, tonify the liver and kidneys, regulate bone marrow and strengthen bones. It not only has a good therapeutic effect on the bleeding phase of hemophilic arthritis, but also has a preventive effect on the degenerative phase. Moreover, it also has a good anti-inflammatory and blood-nourishing effect and prevents repeated bleeding in the joint cavity for patients with hemophilia A, B and C. Attached Figure Description

[0024] Figure 1 This is the result of obtaining the common target of the active ingredient and the disease in this invention.

[0025] Figure 2 This is a schematic diagram of the PPI network in this invention.

[0026] Figure 3 The results show the target effects of the traditional Chinese medicine composition in this invention on HA disease.

[0027] Figure 4 This is a schematic diagram of the active ingredient-disease common target-disease network in this invention.

[0028] Figure 5 This is the result of GO analysis in this invention.

[0029] Figure 6 This is the result of KEGG analysis in this invention.

[0030] Figure 7 This is a pathway map of the active ingredient, disease common target, and pathway in this invention.

[0031] Figure 8 The results are from mass spectrometry analysis of the drug components in the traditional Chinese medicine composition of this invention.

[0032] Figure 9 This is a total ion chromatogram of the serum containing the traditional Chinese medicine composition of the present invention. Detailed Implementation

[0033] To enable those skilled in the art to better understand the technical solutions of the present invention, the technical solutions of the present invention will be further described below in conjunction with the accompanying drawings and embodiments.

[0034] Example 1:

[0035] Example 1 provides a traditional Chinese medicine composition for nourishing blood and regulating marrow, comprising eight herbal raw materials: Agrimonia pilosa, Panax notoginseng, Poria cocos, Bletilla striata, Cornus officinalis, Angelica sinensis, Clematis chinensis, and Paeonia lactiflora. The effective range of the weight parts of different herbal raw materials is as follows: Agrimonia pilosa 28-32 parts, Panax notoginseng 4-8 parts, Poria cocos 13-17 parts, Bletilla striata 10-14 parts, Cornus officinalis 7-11 parts, Angelica sinensis 10-14 parts, Clematis chinensis 7-11 parts, and Paeonia lactiflora 10-14 parts.

[0036] In this embodiment, the specific weight proportions of different Chinese herbal medicine raw materials are as follows: Agrimonia pilosa 30 parts, Panax notoginseng 6 parts, Poria cocos 15 parts, Bletilla striata 12 parts, Cornus officinalis 9 parts, Angelica sinensis 12 parts, Clematis chinensis 9 parts, and Paeonia lactiflora 12 parts.

[0037] Furthermore, the preparation method of the traditional Chinese medicine composition in this invention is as follows: weigh different traditional Chinese herbal raw materials according to the weight proportions, soak them in water for half an hour, bring to a boil over high heat, then simmer over low heat for 30 minutes, filter the residue and take the juice, and decoct two to three times depending on the condition, combine the decoctions and take them in divided doses.

[0038] This traditional Chinese medicine composition primarily uses herbs that cool the blood, nourish the blood, remove blood stasis, and regulate the marrow. In this formula, Panax notoginseng invigorates blood circulation, removes blood stasis, reduces swelling, and relieves pain; Agrimonia pilosa astringes and nourishes the blood, invigorates qi, and replenishes deficiency; these two herbs together serve as the principal herbs. Paeonia lactiflora nourishes the blood, softens the liver, and relieves spasms and pain; Angelica sinensis replenishes and invigorates the blood, regulates menstruation, and relieves pain; Cornus officinalis replenishes the blood, strengthens essence, and tonifies the liver and kidneys; these three herbs together serve as the assistant herbs. Bletilla striata astringes and nourishes the blood, reduces swelling, and promotes tissue regeneration; Clematis chinensis dispels wind and dampness, unblocks meridians, and has a good therapeutic effect on rheumatic pain; Poria cocos promotes diuresis and eliminates dampness, relieving pain caused by dampness obstruction; this is the adjuvant herb of the formula. Based on the principle of tonifying the kidneys and replenishing the marrow, Agrimonia pilosa and Panax notoginseng nourish and invigorate the blood; Cornus officinalis and Angelica sinensis tonify the kidneys and nourish the blood; Paeonia lactiflora softens the liver and regulates the marrow; Poria cocos strengthens the spleen and eliminates dampness; Bletilla striata protects the membranes and strengthens the collaterals; and Clematis chinensis promotes joint mobility. The combined effects of these herbs tonify the kidneys and regulate the marrow, balancing Yin and Yang. This promotes the production of hematopoietic raw materials in the bone marrow and improves joint microcirculation by nourishing blood and removing blood stasis, addressing both the symptoms and the root cause of hemophilic joint damage. This method integrates the three stages of "tonifying the kidneys, nourishing blood, and unblocking the meridians," which aligns with the pathogenesis of bone marrow deficiency and blood stasis in hemophilic arthritis.

[0039] Example 2:

[0040] Example 2 involves performing network pharmacology prediction analysis on the traditional Chinese medicine composition from Example 1. The specific steps of the network pharmacology prediction analysis include the following:

[0041] (1) Screening of active ingredients in traditional Chinese medicine compositions and prediction of corresponding targets:

[0042] Based on the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP, https: / / old.tcmsp-e.com / tcmsp.php), chemical components were retrieved using Agrimonia pilosa, Panax notoginseng, Poria cocos, Bletilla striata, Cornus officinalis, Angelica sinensis, Clematis chinensis, and Paeonia lactiflora as keywords. Following the ADME process, active ingredients were screened from the chemical components of the above eight herbal raw materials. A comprehensive evaluation model was established with parameters of oral bioavailability (OB) ≥ 30% and drug-likeness (DL) ≥ 0.18, and chemical components meeting the standards were collected as active ingredients. Simultaneously, active ingredients were supplemented through literature review, constructing an active ingredient database for this traditional Chinese medicine composition.

[0043] The two-dimensional structure of the active ingredient was downloaded from the PubChem database (https: / / pubchem.ncbi.nlm.nih.gov / ), imported into the SwissTargetPrediction database (http: / / www.swisstargetprediction.ch / ), the species was set to "Homo sapiens", and the "Predict Targets" function was used to predict potential target proteins. After removing potential target proteins with a probability value of zero, the data was integrated and deduplicated to finally obtain the potential target proteins corresponding to the active ingredient.

[0044] (2) Construction of a target database for hemophilic arthritis (HA):

[0045] Using "hemophilic arthritis" as the keyword, we searched the GEO (http: / / www.ncbi.nlm.nih.gov / geo / ) database to obtain HA disease targets. After data merging and deduplication, we established an HA disease target database.

[0046] (3) Screening of common targets of active ingredients and diseases:

[0047] Using the Uniprot database (https: / / www.uniprot.org / ) to limit the species to humans, the intersection of the potential target proteins corresponding to the active ingredients of the traditional Chinese medicine composition in this invention with the HA disease targets was obtained by using the Venny2.1 online tool.

[0048] (4) Construction of protein-protein interaction (PPI) network:

[0049] To elucidate the association between the potential target proteins of the active ingredients in this traditional Chinese medicine composition and the targets of HA disease, the common targets of the active ingredients and the disease were imported into the String database (https: / / string-db.org / ), the biological species was set as "Homo sapiens", and the confidence threshold was set to the highest confidence level (0.9) to construct a PPI network model. The PPI network model was imported into Cytoscape 3.9.1 software for visualization analysis. The node size and color depth reflected the degree value, and the edge width reflected the binding rate score, ultimately forming a PPI network map.

[0050] (5) Construction of a network of active ingredients, common disease targets, and diseases:

[0051] Based on the results of (3) and (4), an intersection Venn diagram was generated using the Venny2.1 platform, and an interactive network of "active ingredient-disease common target-disease network" was constructed using Cytoscape 3.9.1 software, and network topology analysis was performed.

[0052] (6) GO function and KEGG pathway enrichment analysis:

[0053] The active ingredient-disease common target was input into the Metascape database (http: / / metascape.org / ), with the species designated as "Homo sapiens" and a significance threshold of P<0.01. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. A multidimensional network map of "active ingredient-disease common target-pathway" was constructed using Cytoscape 3.9.1 to systematically analyze the main biological processes and signaling pathway mechanisms of the traditional Chinese medicine composition in Example 1 in the treatment of HA disease.

[0054] By combining analyses of the TCMSP and SwissTargetPrediction databases, a total of 470 potential target proteins corresponding to active ingredients were identified. Based on the search results for relevant disease targets in the GEO database, and through merging and deduplication, a total of 1127 HA disease targets were obtained. Subsequently, the potential target proteins corresponding to the selected active ingredients and the HA disease targets were input into Venny2.1 for intersection analysis, yielding 51 intersection targets, as shown in the attached figure. Figure 1 As shown, these overlapping targets were used as common targets for active ingredients and diseases.

[0055] The 51 common targets of active ingredients and diseases were imported into the String database. The interaction score was set to the highest value of 0.9, and HA disease targets that did not participate in protein-protein interactions were excluded, thus obtaining a PPI network model. The PPI network model was then imported into Cytoscape 3.9.1 software for further processing and analysis, resulting in the attached PPI network map. Figure 2 As shown. In the appendix Figure 2 In the diagram, the potential target proteins corresponding to the active ingredients and the targets of HA disease are represented by nodes, and their interactions are represented by edges. PPI network analysis shows that among the 51 common targets of active ingredients and diseases, the targets of the traditional Chinese medicine composition in this invention for the action of HA disease include PARP1, CCNE1, PTGS2, CCNB1, PLK1, CCNA2, NRAS, TOP2A, LGALS3, SELP, SERPINE1, and SYK, as shown in the appendix. Figure 3 As shown.

[0056] Fifty-one common targets of active ingredients and diseases were imported into Cytoscape 3.9.1 software to construct an active ingredient-disease common target-disease network. The results are attached. Figure 4 As shown, in the appendix Figure 4In the diagram, potential target proteins of the active ingredient, HA disease targets, and diseases are represented by nodes, and the relationships between them are represented by edges. Topological analysis shows that the degree value reflects the importance of a node. The higher the degree value, the more important the node is in the network. Results show that the traditional Chinese medicine composition in this invention has a good correlation with hemophilic arthritis.

[0057] The GO analysis results are attached. Figure 5 As shown in the attached figure, the KEGG analysis results are as follows. Figure 6 As shown in the figure. KEGG analysis indicates that the traditional Chinese medicine composition of this invention is related to cell division, inflammatory response, lipopolysaccharide response, and angiogenesis. The pathogenesis of hemophilic arthritis is closely related to the inflammatory response, and the treatment of this disease is related to cell division and inhibition of pathological angiogenesis. KEGG analysis shows that the traditional Chinese medicine composition of this invention is related to the Rap1, MAPK, Fc epsilon RI, NF-κB, HIF-1, and GnRH signaling pathways, among which the role of the GnRH signaling pathway in hemophilic arthritis is not yet clear. The Rap1, MAPK, Fc epsilon RI, NF-κB, and HIF-1 signaling pathways may play a certain role in the pathological process of hemophilic arthritis, and these signaling pathways may affect the development of hemophilic arthritis by regulating processes such as inflammation, angiogenesis, and apoptosis.

[0058] Based on KEGG pathway enrichment analysis, the active ingredient-disease common target-pathway of the traditional Chinese medicine composition in this invention was further constructed, as shown in the appendix. Figure 7 As shown, the node size reflects not only the degree value but also the relationship between the active ingredient and the common target of the active ingredient-disease, as well as the relationship between the common target of the active ingredient-disease and the pathway. The larger the node, the higher the correlation. To investigate the mechanism of this traditional Chinese medicine composition in treating HA, KEGG enrichment analysis was performed on the first five pathways (Rap1, MAPK, Fc epsilonRI, HIF-1, ErbB) to analyze the active ingredients at the BP level. Subsequently, target genes were constructed to build an active ingredient-target pathway network diagram. This pathway network provides potential evidence that the traditional Chinese medicine composition of this invention is an effective treatment for HA. The results show that the traditional Chinese medicine composition of this invention has many overlapping targets with these five pathways, so the traditional Chinese medicine composition of this invention has certain therapeutic potential for treating HA.

[0059] Example 3:

[0060] Example 3 describes the mass spectrometry analysis of the traditional Chinese medicine composition from Example 1. The analysis was performed using a high-resolution liquid chromatography-mass spectrometry (HPLC-MS) system (Thermo Q Exactive), employing a C18 column (2.1 × 100 mm, 1.7 μm), with a mobile phase of 0.1% formic acid-water-acetonitrile gradient elution. Mass spectrometry parameters were set as follows: electrospray ionization source (ESI±), full scan resolution 120,000, scan range m / z 100-1500. The traditional Chinese medicine composition sample was extracted with methanol, centrifuged, and purified before analysis. Peak extraction and compound identification were performed using Compound Discoverer 3.3 software, with matching to the HMDB and METLIN databases (mass error ≤ 5 ppm).

[0061] The results of the mass spectrometry analysis of the drug components are attached. Figure 8-9 As shown. Among them, the appendix Figure 8 The total ion chromatogram of this traditional Chinese medicine composition is shown in black (negative ion mode) and red (positive ion mode). (See attached image.) Figure 9 The table shows the total ion chromatogram of the serum containing the herbal composition. Black represents the total ion chromatogram in negative ion mode, and red represents the total ion chromatogram in positive ion mode. The monomeric drugs screened after mass spectrometry analysis of the herbal composition are shown in Table 1 below.

[0062] Table 1. Monomeric drugs screened by mass spectrometry analysis of the traditional Chinese medicine composition in this invention:

[0063]

[0064] From the appendix Figure 8 -Appendix Figure 9As shown in Table 1 above, the main active ingredients of the traditional Chinese medicine composition in this invention include gastrodin, oleanolic acid, salicylic acid, ferulic acid, caffeic acid, paeoniflorin, quinic acid, and ligustrazine H. Gastrodin has the effects of improving microcirculation, anti-inflammation, and neuroprotection. Hemophilic arthritis is often accompanied by joint inflammation and local blood circulation disorders. Gastrodin can play an auxiliary role by reducing inflammation and improving microcirculation around the joints. Oleanolic acid is a pentacyclic triterpenoid compound with anti-inflammatory, antioxidant, and immunomodulatory effects. Studies have shown that it can reduce the release of inflammatory factors (such as TNF-α and IL-6) by inhibiting the NF-κB pathway. This mechanism may be beneficial for the control of inflammation in arthritis. Ferulic acid has anti-inflammatory, antioxidant, and antithrombotic effects. It can reduce joint inflammation by inhibiting inflammatory mediators (such as PGE2) and regulating immune responses, and has a high safety profile, making it suitable for adjunctive treatment of hemophilic arthritis. Paeoniflorin is the main active ingredient of peony, possessing anti-inflammatory, analgesic, and immunomodulatory effects. Its mechanism of action includes inhibiting the COX-2 and NF-κB pathways, reducing synovial inflammation. It has shown promising results in studies of rheumatoid arthritis and also has potential therapeutic effects on hemophilic arthritis. In summary, the oleanolic acid and paeoniflorin in the traditional Chinese medicine composition of this invention may alleviate synovitis, cartilage destruction, and bone erosion in hemophilic arthritis by reducing the release of pro-inflammatory factors, regulating immune cell activity, and protecting the joint matrix through the NF-κB pathway.

[0065] Example 4:

[0066] Example 4 involves a clinical trial of the traditional Chinese medicine composition from Example 1. The specific contents of the clinical trial include:

[0067] In this clinical trial, all patients were hemophilic arthritis patients hospitalized in the Department of Orthopedics and Traumatology of Zhejiang Provincial Hospital of Traditional Chinese Medicine. The conventional treatment group received only routine inpatient treatment, with regular coagulation function checks and coagulation factor replacement therapy during hospitalization, and joint replacement if necessary. In addition to the above treatment, the experimental group took the traditional Chinese medicine composition of this invention twice a day, morning and evening, during hospitalization.

[0068] In the clinical trial, five patients with hemophilic arthritis who took the traditional Chinese medicine composition of this invention were assigned to the experimental group, and five patients who did not take the traditional Chinese medicine composition of this invention were assigned to the conventional treatment group. The coagulation function test results of the experimental group before and after hospitalization are summarized in Table 2 below, and the coagulation function test results of the conventional treatment group before and after hospitalization are summarized in Table 3 below. The average clinical data of the experimental group and the conventional treatment group were then compared, and the results are shown in Table 4 below.

[0069] Table 2. Results of coagulation function tests before and after hospitalization in the experimental group:

[0070] ;

[0071] Table 3. Results of coagulation function tests before and after hospitalization for patients in the routine treatment group:

[0072] ;

[0073] Table 4. Mean values ​​of coagulation function tests before and after hospitalization for patients in the experimental group and the conventional treatment group:

[0074] ;

[0075] The above clinical data show that after taking the traditional Chinese medicine composition of this invention, patients in the experimental group showed significantly better improvement in coagulation function than those in the conventional treatment group. After taking the traditional Chinese medicine composition, fibrinogen (FIB) levels in the experimental group steadily increased to 4.634 g / L (compared to a surge to 6.112 g / L in the conventional treatment group), APTT (amplitude of contraction of thrombus) improved from 78.44 s to 37.22 s (compared to a decrease from 56.52 s to 34.48 s in the conventional treatment group), and joint range of motion remained at 79.44% (compared to a decrease of 10.76 percentage points in the conventional treatment group). Particularly in terms of coagulation balance regulation, the D-dimer level in the experimental group increased by 280% (compared to 571% in the conventional treatment group), indicating that the traditional Chinese medicine composition of this invention can effectively inhibit abnormal thrombus formation and has an effective therapeutic effect on hemophilic arthritis.

[0076] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed. The scope of protection of this invention is defined by the appended claims and their equivalents.

Claims

1. A traditional Chinese medicine composition for nourishing blood and regulating marrow, characterized in that: The traditional Chinese medicine composition is used to treat hemophilic arthritis caused by bone marrow deficiency and blood stasis. The traditional Chinese medicine composition includes eight Chinese herbal raw materials: Agrimonia pilosa, Panax notoginseng, Poria cocos, Bletilla striata, Cornus officinalis, Angelica sinensis, Clematis chinensis, and Paeonia lactiflora. The weight proportions of different Chinese herbal raw materials are as follows: Agrimonia pilosa 28-32 parts, Panax notoginseng 4-8 parts, Poria cocos 13-17 parts, Bletilla striata 10-14 parts, Cornus officinalis 7-11 parts, Angelica sinensis 10-14 parts, Clematis chinensis 7-11 parts, and Paeonia lactiflora 10-14 parts.

2. The traditional Chinese medicine composition for nourishing blood and regulating marrow according to claim 1, characterized in that: The weight proportions of different Chinese herbal raw materials are as follows: Agrimonia pilosa 30 parts, Panax notoginseng 6 parts, Poria cocos 15 parts, Bletilla striata 12 parts, Cornus officinalis 9 parts, Angelica sinensis 12 parts, Clematis chinensis 9 parts, and Paeonia lactiflora 12 parts.

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