Pharmaceutical composition for treating superficial vein thrombosis and preparation method thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and relates to a pharmaceutical composition for treating superficial vein thrombosis and application thereof. The traditional Chinese medicine composition contains oriental wormwood, phaseolus calcaratus, honeysuckle, herba violae, radix achyranthis bidentatae, lumbricus, rhizoma atractylodis, cortex phellodendri, radix paeoniae rubra and leech. The traditional Chinese medicine composition can effectively improve the formation of superficial vein thrombosis of lower limbs.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicines and relates to a pharmaceutical composition for treating superficial vein thrombosis and a preparation method thereof. Background Art

[0002] Acute superficial thrombophlebitis (STP) is one of the venous system diseases in peripheral vascular diseases. The clinical manifestations are the appearance of cords and nodules along the superficial veins of the veins and their branches, red skin with burning sensation, local pain that refuses to be pressed, and hardness to the touch. Some patients may have inflammatory reactions such as surrounding flaky flushing and skin fever. The subjective symptoms are pain and swelling in the lower limbs. If the symptoms are severe, they will be accompanied by systemic symptoms such as fever and headache, which seriously affect work and life.

[0003] This disease often occurs after childbirth, trauma, and surgery. The incidence of postoperative deep vein thrombosis is higher in Europe and the United States, and the incidence in my country has been increasing in recent years. According to literature reports, the incidence of thrombosis and pulmonary infarction above the gastrocnemius venous plexus is as high as 50%, of which 1 / 4 can be fatal. Deep vein thrombosis mostly occurs during various surgeries and in the early postoperative period, and 10% of patients develop the disease 5-9 days after surgery. How to take effective preventive measures in the perioperative period, especially for high-risk patients, is an issue that must be taken seriously. Summary of the invention

[0004] The main purpose of the present invention is to provide a new Chinese medicine composition, specifically a medicine composition for treating superficial vein thrombosis, which can promote blood circulation and dissipate blood stasis, clear away heat and detoxify, promote dampness and reduce swelling, can effectively treat the acute and chronic stages of superficial vein thrombosis of the lower limbs, can quickly improve symptoms such as swelling and pain in the affected limbs, and has a high clinical effectiveness rate.

[0005] Specifically, the present invention adopts the following technical solutions to achieve the above objectives:

[0006] A Chinese medicine composition for treating superficial vein thrombosis, comprising the following components in parts by weight:

[0007] 15-30 parts of Artemisia capillaris, 6-15 parts of Viola yedoensis, 12-30 parts of Adzuki Bean, 15-30 parts of Honeysuckle, 1-6 parts of Leech, 6-12 parts of Pheretima, 6-12 parts of Atractylodes, 6-12 parts of Phellodendron, 9-15 parts of Achyranthes bidentata, 6-12 parts of Red Peony Root, 3-6 parts of Carthamus tinctorius, 15-30 parts of Coix seeds, and 10-30 parts of Astragalus.

[0008] Further, in a preferred embodiment of the present invention, the Chinese medicine composition contains the following components in parts by weight: 30 parts of Artemisia Capillaris, 15 parts of Viola Yedong, 30 parts of Adzuki Bean, 30 parts of Honeysuckle, 6 parts of Leech, 12 parts of Pheretima, 12 parts of Atractylodes, 12 parts of Phellodendron, 15 parts of Achyranthes Bidentata, 12 parts of Red Peony Root, 6 parts of Carthamus Tinctorius, 30 parts of Coix Seed, and 30 parts of Astragalus.

[0009] Further, in a preferred embodiment of the present invention, the composition is composed of the following components in parts by weight: 15 parts of Artemisia Capillaris, 6 parts of Viola Yedong, 12 parts of Adzuki Bean, 15 parts of Honeysuckle, 1 part of Leech, 6 parts of Pheretima, 6 parts of Atractylodes, 6 parts of Phellodendron, 9 parts of Achyranthes Bidentata, 6 parts of Red Peony Root, 3 parts of Carthamus Tinctorius, 15 parts of Coix Seed, and 10 parts of Astragalus.

[0010] Further, in a preferred embodiment of the present invention, the composition is composed of the following components in parts by weight: 23 parts of Artemisia Capillaris, 10 parts of Viola Yedong, 16 parts of Adzuki Bean, 22 parts of Honeysuckle, 3.5 parts of Leech, 9 parts of Pheretima, 9 parts of Atractylodes, 9 parts of Phellodendron, 12 parts of Achyranthes Bidentata, 10 parts of Red Peony Root, 4.5 parts of Carthamus Tinctorius, 23 parts of Coix Seed, and 20 parts of Astragalus.

[0011] Furthermore, the Chinese medicine composition of the present invention can be prepared into any one of decoctions, pills, oral liquid preparations, and granules.

[0012] Furthermore, the preparation of the present invention may also contain excipients, which are one or more of fillers, disintegrants, binders, flavoring agents, preservatives, and colorants.

[0013] The filler is selected from one or more of lactose, microcrystalline cellulose, starch, dextrin, mannitol, glucose and sorbitol.

[0014] The disintegrant is selected from one or more of hydroxypropyl cellulose, cross-linked polyvinyl pyrrolidone, cross-linked sodium carboxymethyl cellulose, cellulose acetate phthalate, and sodium carboxymethyl starch.

[0015] The adhesive is selected from one or more of 3% hydroxypropyl methylcellulose 50% ethanol solution, 10% povidone K30 aqueous solution, 30% starch slurry and 10% carboxymethyl cellulose aqueous solution, preferably 3% hydroxypropyl methylcellulose 50% ethanol solution.

[0016] Further, the granules include the following method:

[0017] 1) Take Artemisia capillaris, Viola yedoensis, Flos Lonicerae, Atractylodes macrocephalae, Achyranthes bidentatae, Paeonia lactiflora and Adzuki bean and perform steam distillation in a multi-functional extraction tank, collect the initial distillation and the re-distillation, store them in a sealed container, and use the distilled medicinal liquid and medicinal residue for later use;

[0018] 2) taking Astragalus, safflower, coix seed, Phellodendron, 1 / 2 amount of leech, earthworm and distilled drug residue, adding water and boiling twice for 1-1.5 hours, combining the two decoctions, filtering and obtaining a filtrate;

[0019] 3) the filtrate of step 2) is combined with the distilled liquid of step 1), concentrated to a relative density of 1.02-1.05 at 80-90° C., cooled to room temperature, and 75-85% ethanol is added to an alcohol content of 40%-60%, and the supernatant is reserved for later use;

[0020] 4) filtering the supernatant of step 3), recovering ethanol, concentrating under reduced pressure at 40-50° C. to a relative density of 1.08-1.12, vacuum drying to a dry extract, and pulverizing into a dry extract powder;

[0021] 5) Crush the remaining 1 / 2 amount of leeches and earthworms into fine powder, mix the fine powder, dry paste powder and pharmaceutical excipients, add a binder to make a soft material, sieve, dry and make granules.

[0022] The pharmaceutical excipients are selected from sucrose and dextrin, and the binder is selected from 3% hydroxypropyl methylcellulose in 50% ethanol solution; the weight ratio of the total weight of the fine powder and dry paste powder to the pharmaceutical excipients is 1:7-9. More specifically, the weight ratio of the total weight of the fine powder and dry paste powder to the pharmaceutical excipients is 1:8. Furthermore, the pharmaceutical excipients are preferably sucrose and dextrin, and the weight ratio of sucrose to dextrin is 2:0.5-1.

[0023] Furthermore, the Chinese medicine composition or the prepared preparation is used in the preparation of drugs for treating superficial vein thrombosis.

[0024] The prescription of the present invention is clear and has definite drug effects. The herb Artemisia capillaris clears away heat and dampness, the herb Di Ding clears away heat and toxic substances, cools blood and reduces swelling, and they are all monarch drugs; the red bean removes dampness and reduces swelling, the honeysuckle clears away heat and toxic substances, the leech and the earthworm promote blood circulation and dredge collaterals, and they are all minister drugs; the phellodendron clears away heat and dampness, the atractylodes lancea removes dampness and strengthens the spleen, the coix seed strengthens the spleen and penetrates dampness, the red peony root clears heat and cools blood, the safflower promotes blood circulation and dredges collaterals, and the astragalus root invigorates qi and reduces swelling, and they are all adjuvant drugs; the herb Achyranthes bidentata guides the downward movement of the drug, and is the guiding drug. All the drugs are used together to play the functions of promoting blood circulation and dispersing blood stasis, clearing away heat and toxic substances, and removing dampness and reducing swelling. The composition of the present invention has the functions of clearing away heat and toxic substances, removing blood stasis and dredge collaterals, and promoting diuresis and reducing swelling, and has good curative effect in clinical treatment of superficial phlebitis. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 : TNF-α content in plasma of rats in each group in the efficacy test after treatment in each example.

[0026] Figure 2 : The IL-β content in the plasma of each group of rats in the efficacy test of each example.

[0027] Figure 3: IL-6 content in plasma of rats in each group in the efficacy test of each example.

[0028] Figure 4 : CRP content in plasma of rats in each group in the efficacy test of each embodiment.

[0029] Figure 5 : DD (μg / ml) content in each group of rats in the efficacy test of each example.

[0030] Figure 6 : Symptom index scores of the observation group and the control group before and after treatment (points).

[0031] Figure 7 : Physical sign index scores of the observation group and the control group before and after treatment (points).

[0032] Figure 8 : Color Doppler ultrasound examination scores of the observation group and the control group before and after treatment (points).

[0033] Fig. 9 : Comparison of treatment effects before and after between the observation group and the control group (people).

[0034] Fig.10 : The anterior-posterior venous recanalization scores (points) of the observation group and the control group.

[0035] Fig.11 : Plasma D-dimer (μg / ml) before and after treatment in the observation group and the control group.

[0036] Fig.12 : FIB (g / L) before and after in the observation group and the control group.

[0037] Fig.13 : Platelet counts before and after the observation group and the control group (×10 9 / L).

[0038] Fig.14 : White blood cell counts before and after the observation group and the control group (×10 9 / L).

[0039] Fig.15 :Neutrophil counts before and after the observation group and the control group (×10 9 / L).

[0040] Fig.16 : Comparison of NLR before and after between the observation group and the control group. DETAILED DESCRIPTION

[0041] The present invention is further described below by way of examples. It should be correctly understood that the examples of the present invention are only some representative formulations, and their purpose is only to illustrate the present invention, rather than to limit the present invention. Therefore, simple improvements to the present invention under the premise of the method of the present invention all belong to the scope of protection claimed in the present invention.

[0042] Example 1: A granule for treating superficial vein thrombosis, the ingredients and dosage are as follows:

[0043] Artemisia capillaris 15g, red bean 12g, honeysuckle 15g, Viola yedoensis 6g, Achyranthes bidentata 9g, Pheretima lumbinis 6g, Atractylodes lancea 6g, Phellodendron chinense 6g, Paeonia lactiflora 6g, Leech 1g, Safflower 3g, Coix seed 15g, Astragalus 10g.

[0044] The granules include the following methods:

[0045] 1) Take Artemisia capillaris, Viola yedoensis, Flos Lonicerae, Atractylodes macrocephalae, Achyranthes bidentatae, Paeonia lactiflora and Adzuki bean and perform steam distillation in a multi-functional extraction tank, collect the initial distillation and the re-distillation, store them in a sealed container, and use the distilled medicinal liquid and medicinal residue for later use;

[0046] 2) taking Astragalus, safflower, coix seed, Phellodendron, 1 / 2 amount of leech, earthworm and distilled drug residue, adding water and boiling twice for 1-1.5 hours, combining the two decoctions, filtering and obtaining a filtrate;

[0047] 3) The filtrate of step 2) is combined with the distilled liquid of step 1), concentrated to a relative density of 1.02-1.05 at 80-90° C., cooled to room temperature, and 75-85% ethanol is added to an alcohol content of 40%-60%, and allowed to stand for 24 hours, and the supernatant is reserved for later use;

[0048] 4) filtering the supernatant of step 3), recovering ethanol, concentrating under reduced pressure at 40-50° C. to a relative density of 1.08-1.12, vacuum drying to a dry extract, and pulverizing into a dry extract powder;

[0049] 5) Crush the remaining 1 / 2 amount of leeches and earthworms into fine powder, mix the fine powder, dry paste powder and pharmaceutical excipients, add a binder to make a soft material, sieve, dry and make granules.

[0050] The pharmaceutical excipients are selected from sucrose and dextrin, and the binder is selected from 3% hydroxypropyl methylcellulose in 50% ethanol solution; the weight ratio of the total weight of the fine powder and dry paste powder to the pharmaceutical excipients is 1:7-9. More specifically, the weight ratio of the total weight of the fine powder and dry paste powder to the pharmaceutical excipients is 1:8. Furthermore, the pharmaceutical excipients are preferably sucrose and dextrin, and the weight ratio of sucrose to dextrin is 2:0.5-1.

[0051] Example 2: A pharmaceutical composition for treating superficial vein thrombosis, the ingredients and dosages are as follows:

[0052] Artemisia capillaris 30g, red bean 30g, honeysuckle 30g, Viola yedoensis 15g, Achyranthes bidentata 15g, Pheretima lumbini 12g, Atractylodes lancea 12g, Phellodendron chinense 12g, Paeonia lactiflora 12g, Leech 6g, Safflower 6g, Coix seed 30g, Astragalus 30g.

[0053] The decoction is prepared according to conventional techniques.

[0054] Example 3: A pharmaceutical composition for treating superficial vein thrombosis, the ingredients and dosages are as follows:

[0055] Artemisia capillaris 23g, Viola yedoensis 10g, Red bean 16g, Honeysuckle 22g, Leech 3.5g, Earthworm 9g, Atractylodes lancea 9g, Phellodendron chinense 9g, Achyranthes bidentata 12g, Red peony root 10g, Safflower 4.5g, Coix seed 23g, Astragalus 20g

[0056] The decoction is prepared according to conventional techniques.

[0057] Example 4: A pharmaceutical composition for treating superficial vein thrombosis, the ingredients and dosages are as follows:

[0058] Artemisia capillaris 30g, red bean 30g, honeysuckle 30g, Viola yedoensis 15g, Achyranthes bidentata 15g, Pheretima lumbini 12g, Atractylodes lancea 12g, Phellodendron chinense 12g, Paeonia lactiflora 12g, Leech 6g, Safflower 6g, Coix seed 30g, Astragalus 30g.

[0059] The granules were prepared according to conventional techniques.

[0060] Example 5: A pharmaceutical composition for treating superficial vein thrombosis, the ingredients and dosages are as follows:

[0061] Artemisia capillaris 30g, red bean 30g, honeysuckle 30g, Viola yedoensis 15g, Achyranthes bidentata 15g, Pheretima lumbini 12g, Atractylodes lancea 12g, Phellodendron chinense 12g, Paeonia lactiflora 12g, Leech 6g, Safflower 6g, Coix seed 30g, Astragalus 30g.

[0062] The oral solution is prepared according to conventional technology.

[0063] Comparative Example 1: A pharmaceutical composition for treating superficial vein thrombosis, the ingredients and dosages are as follows:

[0064] Viola yedoensis 10g, adzuki bean 16g, honeysuckle 22g, leech 3.5g, earthworm 9g, atractylodes 9g, phellodendron 9g, Achyranthes bidentata 12g, red peony root 10g, safflower 4.5g, coix seed 23g, astragalus 20g.

[0065] The decoction is prepared according to conventional techniques.

[0066] Comparative Example 2: A pharmaceutical composition for treating superficial vein thrombosis, the ingredients and dosages are as follows:

[0067] Scutellaria baicalensis 23g, Isatis root 10g, Adzuki bean 16g, Honeysuckle 22g, Leech 3.5g, Pheretima 9g, Atractylodes 9g, Phellodendron 9g, Achyranthes bidentata 12g, Red Peony Root 10g, Safflower 4.5g, Coix seed 23g, Astragalus 20g.

[0068] The decoction is prepared according to conventional techniques.

[0069] Comparative Example 3: A pharmaceutical composition for treating superficial vein thrombosis, the ingredients and dosages are as follows:

[0070] Artemisia capillaris 23g, Viola yedoensis 10g, Taraxacum mongolicum 16g, Isatis root 22g, Scorpio 3.5g, Scolopendra subspinipes 9g, Atractylodes macrocephala 9g, Phellodendron chinense 9g, Achyranthes bidentata 12g, Paeonia lactiflora 10g, Safflower 4.5g, Coix seed 23g, Astragalus membranaceus 20g.

[0071] The decoction is prepared according to conventional techniques.

[0072] Comparative Example 4: A pharmaceutical composition for treating superficial vein thrombosis, the ingredients and dosages are as follows:

[0073] Artemisia capillaris 35g, Viola yedoensis 5g, Adzuki bean 140g, Honeysuckle 30g, Leech 2g, Pheretima 2g, Atractylodes 15g, Phellodendron chinense 17g, Achyranthes bidentata 5g, Red Peony Root 3g, Safflower 2g, Coix seed 10g, Astragalus 5g.

[0074] The decoction is prepared according to conventional techniques.

[0075] Pharmacodynamics experiments

[0076] In order to further prove the efficacy of the Chinese medicine composition of the present invention in treating peripheral vascular disease, especially thromboangiitis obliterans, the inventors commissioned a third-party testing institution with relevant qualifications to carry out relevant pharmacodynamics experiments based on clinical use. The animal model used in the following pharmacodynamics experiments was prepared based on the technology of existing literature.

[0077] 1. Animals, modeling, and grouping

[0078] 1.1 Animals:

[0079] Wistar rats, SPF grade, 180-220 g, experimental animal license number: SYXK(Lu)20230031, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, were adaptively raised for one week before the experiment.

[0080] 1.2 Animal grouping and model preparation

[0081] SD rats were randomly divided into 8 groups, namely, normal control group sham operation group, model group, embodiment 1 group, embodiment 2 group, embodiment 3 group, comparative example 1 group, comparative example 2 group, comparative example 3 group, comparative example 4 group, 8 rats in each group. Each group fasted for 12 hours before surgery, and after isoflurane anesthesia, the hair was removed in the supine position, and the abdomen was disinfected. The model group and the drug-treated group were longitudinally cut along the midline of the abdomen for 2 to 3 cm, and the inferior vena cava and abdominal aorta were separated 2 mm below the left renal vein, and ligated together with a glass tube with a diameter of 0.3 mm, and then slowly withdrawn; finally, the branch veins between the renal vein and the iliac vein were ligated, and the abdomen was sutured with 3-0 sutures and disinfected; after surgery, a warm pad was used to keep the rats warm until they were awake; the sham operation group only separated the inferior vena cava and abdominal aorta without ligation. In Example 1-3 and Comparative Example 1-4, the decoction was administered by gavage (the dosage for human was calculated based on 70 kg, and the dosage for rats was 1.09 g / kg). On the first day after surgery, each administration group was gavaged for 1 week, once a day; the normal control group, sham operation group and model group were gavaged with an equal amount of physiological saline solvent. After the modeling was completed and the administration was performed for 1 week, various indicators were detected.

[0082] 2. Drug reagents

[0083] The decoctions obtained in Examples 1, 2, 3 and Comparative Examples 1-4 of the present invention. IL-1β, IL-6, TNF-α enzyme-linked immunosorbent assay kits were purchased from Nanjing Jiancheng Bioengineering Research Institute, with the item numbers H033-2-7, H019-2-7, and H059-1-5, respectively; PLG kit (Shanghai ELISA Biotechnology Co., Ltd., with the item numbers YJ201055 and YJ401223, respectively);

[0084] 3. Detection indicators

[0085] 3.1 Determination of FDP and DD content in rats

[0086] After anesthesia, blood was collected from the abdominal aorta of rats and placed in sodium citrate anticoagulant tubes. The contents of FDP and DD in the sodium citrate anticoagulant tubes were detected using a fully automatic coagulation analyzer.

[0087] 3.2 Determination of IL-1β, IL-6 and TNF-α contents in rats

[0088] To detect the levels of inflammatory factors, the plasma was separated and the contents of IL-1β, IL-6 and TNF-α were determined according to the ELISA instructions.

[0089] 4. Statistical analysis

[0090] GraphPad Prism software was used to analyze the data. P<0.05 was considered statistically significant.

[0091] 5 Results Analysis

[0092] 5.1 Biochemical indicators of IL-1β, IL-6 and TNF-α in rats

[0093] There was no significant difference between the sham operation group and the blank group, but compared with the model group, the levels of TNF-α, IL-1β, and IL-6 in the plasma of the rats in the model group were significantly increased (P<0.01); compared with the control group, the levels of TNF-α, IL-1β, and IL-6 in the plasma of the rats in each administration group of Examples 1-3 were reduced, with significant differences (P<0.01). Figure 1-3 .

[0094] 5.3 Determination of FDP and DD content in rats of each group

[0095] FDP is a product produced after the degradation of fibrin. When thrombosis occurs in the body, fibrin participates in the formation of thrombus. As the thrombus dissolves, fibrin is broken down and FDP is produced. Therefore, an increase in the level of FDP usually indicates that the process of thrombus formation and dissolution is ongoing. The higher the content in the blood, the better the thrombolytic effect.

[0096] Elevated levels of D-dimer in rats usually indicate some form of coagulation or thrombosis in the body. D-dimer is a fibrin degradation product. When a thrombus forms in the blood, fibrin is broken down to produce D-dimer. The lower the level in the blood, the less likely it is to form a thrombus.

[0097] There was no significant difference between the sham operation group and the blank group, but there were statistical differences in FDP and DD between the model group and the sham operation group and the blank group (P<0.01). Figure 4-5 It can be seen that there are significant differences between Examples 1-3 and Comparative Examples 1-4.

[0098] Clinical Trials

[0099] 1. Research subjects

[0100] 1. Source of cases

[0101] All cases were selected from patients with DVT of damp-heat type who were hospitalized and treated in the Department of Peripheral Vascular Diseases of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 2023 to December 2023. This study has been approved by the Ethics Committee of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine [Approval No.: (2023) Lun Shen No. (004)-YJS].

[0102] 2. Diagnostic criteria

[0103] 1. Western medicine diagnostic criteria for DVT

[0104] Refer to the "Guidelines for the Diagnosis and Treatment of Superficial Vein Thrombosis (Third Edition)" developed by the Vascular Surgery Group of the Surgery Branch of the Chinese Medical Association in 2017.

[0105] (1) Sudden swelling and pain in the affected limb; tenderness in the posterior calf, inner thigh, femoral triangle, and iliac fossa on the affected side.

[0106] (2) The affected limb shows pitting edema, increased soft tissue tension, and increased skin temperature.

[0107] (3) Homans sign and Neuhof sign are positive.

[0108] (4) Most patients have a history of surgery, trauma, fracture, long-term bed rest, and previous risk factors such as pregnancy and tumors.

[0109] (5) Plasma D-dimer is higher than normal.

[0110] (6) Color Doppler ultrasound, magnetic resonance venography, venography, etc. can confirm the diagnosis.

[0111] 2. TCM Syndrome Differentiation Standards for DVT

[0112] Refer to the National TCM Higher Education "14th Five-Year Plan" textbook "Chinese Medicine Surgery" [9] .

[0113] (1) Damp-heat type

[0114] Symptoms: The onset is relatively acute, with swelling, fever, redness, pain and limited movement of the affected limb; the tongue is red, the tongue coating is yellow and greasy, and the pulse is stringy and slippery.

[0115] (2) Blood stasis type

[0116] Symptoms: Swelling of the affected limb, dark purple skin, fixed tenderness, and bulging veins in the limbs; dark tongue or with ecchymosis, white tongue coating, and stringy pulse.

[0117] (3) Qi deficiency and dampness obstruction type

[0118] Symptoms: Swelling of the affected limb for a long time, which is lighter in the morning and heavier in the evening, aggravated by activities and relieved by resting and raising the lower limb, with tortuous blue veins, or accompanied by calf pigmentation, congestive dermatitis, eczema, or ulcers; fatigue; pale tongue with teeth marks on the edges, thin white tongue coating, and deep pulse.

[0119] 3. DVT classification criteria

[0120] Refer to the "Diagnosis and Efficacy Criteria for Lower Limb Superficial Venous Thrombosis (2015 Revised Draft)" of the Peripheral Vascular Disease Professional Committee of the Chinese Association of Integrated Traditional Chinese and Western Medicine.

[0121] (1) Peripheral type: including calf muscle venous plexus thrombosis and calf superficial vein thrombosis. The onset is insidious, with calf pain and positive Homans sign.

[0122] (2) Central type (iliac-femoral vein thrombosis): The onset is acute, with pain and distension in the groin area first, followed by widespread swelling and pain in the lower limbs, tenderness in the femoral triangle, and negative Homans sign.

[0123] (3) Mixed type (superficial vein thrombosis of all lower extremities): The skin of the affected limb is dark red, with widespread swelling and pain, tenderness in the femoral triangle, and positive Homans sign.

[0124] (III) Case selection criteria

[0125] 1. Case inclusion criteria

[0126] (1) Meet the diagnostic criteria for DVT.

[0127] (2) The TCM syndrome type is damp-heat descending.

[0128] (3) Aged ≥18 and ≤70 years old, regardless of gender.

[0129] (4) No contraindications to thrombolysis or anticoagulation.

[0130] (5) Patient informed consent.

[0131] 2. Case Exclusion Criteria

[0132] (1) Patients with severe hypertension, cardiovascular, liver, kidney and other diseases.

[0133] (2) Patients with combined blood system diseases.

[0134] (3) Pregnant and lactating women.

[0135] (4) Those with a history of severe allergies.

[0136] (5) Those who have mental illness or are unable to cooperate.

[0137] (6) Participating in other clinical trial researchers.

[0138] 3. Case exclusion criteria

[0139] (1) Those who have serious adverse reactions (bleeding, allergies, etc.) during the trial and are not suitable to continue the current treatment.

[0140] (2) Those who have poor compliance during the trial and are unable to complete the corresponding treatment as ordered by the doctor.

[0141] (3) Subjects decide to discontinue treatment.

[0142] The exclusion rate should be less than 5% of the total included cases.

[0143] 4. Case dropout criteria

[0144] (1) Withdrawal or inability to complete the trial for any reason.

[0145] (2) Serious adverse events occur.

[0146] The reasons for case dropout were recorded, and the dropout rate should not exceed 10% of the total number of included cases.

[0147] 2. Research Methods

[0148] 1. Case grouping

[0149] According to the "inclusion criteria and exclusion criteria", 64 patients with damp-heat type DVT who were hospitalized and treated in the outpatient department of peripheral vascular disease, Affiliated Hospital of Shandong University of Traditional Chinese Medicine were selected and divided into two groups using the random number table method, 32 cases in the observation group and 32 cases in the control group.

[0150] (II) Observation plan

[0151] 1. Preparation of Huoxue Jiedu Decoction

[0152] Huoxue Jiedu Decoction (the decoction prepared in Example 2) was decocted in water and taken once in the morning and evening. Chinese herbal medicine pieces were purchased from the Affiliated Hospital of Shandong University of Traditional Chinese Medicine.

[0153] 2. Treatment Methods

[0154] (1) General treatment

[0155] ① Rest in bed, elevate the affected limb, and strictly avoid hammering or pressing to keep bowel movements smooth.

[0156] ② If the condition warrants, inferior vena cava filter implantation should be performed.

[0157] ③Based on the patient's condition, select a thrombolytic regimen that is appropriate for the patient's condition.

[0158] (2) Control group

[0159] After a bleeding risk assessment, the patient was given oral rivaroxaban at a dose of 15 mg BID for 14 days and a maintenance dose of 20 mg QD.

[0160] (3) Observation group

[0161] On the basis of the control group, patients were given oral Huoxue Jiedu Decoction, taken once in the morning and evening, 200 ml each time, for 14 days.

[0162] 3. Treatment course: After inclusion, patients in the observation group and the control group took the medicine for 14 days.

[0163] (III) Observation indicators

[0164] 2. Efficacy indicators

[0165] (1) TCM syndrome score.

[0166] ①Symptom index score.

[0167] ②Physical sign index scoring.

[0168] ③Color Doppler ultrasound examination scoring.

[0169] ④Determination of clinical efficacy.

[0170] (2) Venous recanalization score. (See Appendix 2)

[0171] (3) Plasma D-dimer (DD).

[0172] (4) Plasma fibrinogen (Fib).

[0173] (5) Neutrophil count.

[0174] (6) Lymphocyte count.

[0175] (7) Platelet count.

[0176] (8) Neutrophil-Lymphocyte ratio (NLR).

[0177] (9) Platelet-lymphocyte ratio (PLR).

[0178] (10) White blood cells.

[0179] (11)Monocytes.

[0180] 3. Safety indicators

[0181] (1) Routine blood test, routine urine test, routine stool test + occult blood test.

[0182] (2) Liver function and kidney function.

[0183] (3) Electrocardiogram.

[0184] (IV) Detection methods

[0185] 1. Draw 2 mL of peripheral venous blood and send the collected blood sample to the laboratory of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine for testing using a fully automatic blood cell analyzer (XE-2100Sysmexo Kobe, Japan). Record the white blood cell count, neutrophil count, monocyte count, lymphocyte count, platelet count, and calculate the PLR ​​and NLR values.

[0186] 2. Draw 2 mL of peripheral venous blood, store it in sodium citrate coagulation test tubes, and transfer it to the laboratory of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine for testing of plasma D-dimer and plasma fibrinogen using an automatic coagulation analyzer (STA-R Evolution, No.: DMZ-019).

[0187] 3. The color Doppler ultrasound examination is performed by professionals using the GE LOGIQ E9 color Doppler ultrasound diagnostic instrument.

[0188] 5. Methods for determining efficacy

[0189] 1. Refer to Table 1-4 for TCM syndrome scoring.

[0190] Table 1 Symptom index scoring criteria

[0191]

[0192] Table 2 Scoring criteria for physical signs

[0193]

[0194] Table 3 Scoring criteria for color Doppler ultrasound examination

[0195]

[0196] Table 4 Clinical efficacy evaluation

[0197]

[0198] According to the nimodipine method, [(total score before treatment - total score after treatment) / total score before treatment] × 100%

[0199] 2. The venous recanalization score is shown in Table 5.

[0200] Table 5 Venous recanalization scores

[0201]

[0202] Figure 5 Symptom index scores of the observation group and the control group before and after treatment.

[0203] 6. Statistical methods

[0204] SPSS 26.0 statistical software was used for data processing. Normality test was performed for measurement data, and normal distribution data were expressed as mean ± standard deviation. Non-normal distribution data are expressed as median [M(P 25 , P 75 )] indicated. The t-test was used to analyze the data between groups when they were normal and had equal variances, and the rank sum test was used for non-normal distribution data. The chi-square test was used for count data. 2 P < 0.05 indicated a significant difference, and P < 0.01 indicated a very significant difference.

[0205] (VII) Results

[0206] The observation group and the control group each collected 32 cases. One patient in the observation group and the control group was excluded because they did not complete the corresponding treatment according to the doctor's advice; one patient in each group dropped out due to loss of follow-up, and finally 30 cases were collected in the observation group and the control group.

[0207] 7.1 General Data Analysis

[0208] Before the clinical trial began, the gender, age, course of disease and site of infection of the observation group and the control group were statistically analyzed. There was no statistical difference (P>0.05), so the trial could be carried out.

[0209] 7.2. TCM Syndrome Score

[0210] (1) Symptom index score

[0211] There was no significant difference in the TCM symptom index scores between the two groups of patients before treatment (P>0.05). On the 14th day of treatment, the TCM symptom index scores of the observation group were lower than those of the control group, and the difference was statistically significant (P<0.01). The TCM symptom index scores of the two groups of patients on the 14th day of treatment were significantly lower than those before treatment, and the difference was statistically significant (P<0.01). See Table 6, Figure 6 .

[0212] Table 6 Comparison of clinical symptom index scores (points) between the observation group and the control group

[0213]

[0214] (2) Physical sign index scoring

[0215] There was no significant difference in the TCM sign index scores between the two groups of patients before treatment (P>0.05). On the 14th day of treatment, the TCM sign index scores of the observation group were lower than those of the control group, and the difference was statistically significant (P<0.01). The TCM sign index scores of the two groups of patients on the 14th day of treatment were significantly lower than those before treatment, and the difference was statistically significant (P<0.01). See Table 7, Figure 7 .

[0216] Table 7 Comparison of clinical sign index scores (points) between the observation group and the control group

[0217]

[0218] (3) Color Doppler ultrasound examination score

[0219] There was no significant difference in the color Doppler ultrasound examination scores between the two groups before treatment (P>0.05). On the 14th day of treatment, the color Doppler ultrasound examination scores of the observation group were lower than those of the control group, and the difference was statistically significant (P<0.01). The color Doppler ultrasound examination scores of the two groups of patients on the 14th day of treatment were significantly lower than those before treatment, and the difference was statistically significant (P<0.01). See Table 8, Figure 8 .

[0220] Table 8 Comparison of color Doppler ultrasound examination scores (points) between the observation group and the control group

[0221]

[0222] (4) Clinical efficacy assessment

[0223] Among the patients in the observation group, 3 cases were cured, 14 cases were markedly effective, 13 cases were effective, and 0 cases were ineffective, with a total effective rate of 100%. Among the patients in the control group, 0 cases were cured, 1 case was markedly effective, 28 cases were effective, and 1 case was ineffective, with a total effective rate of 96.67%. The total effective rate of the observation group was higher than that of the control group, and the difference was statistically significant (P < 0.01). See Table 9, Fig. 9 .

[0224] Table 9 Comparison of clinical efficacy (%) between the observation group and the control group

[0225]

[0226] Total effective rate = (number of clinically cured cases + number of markedly effective cases + number of effective cases) / total number of cases × 100%

[0227] 2. Venous recanalization score

[0228] There was no significant difference in the venous recanalization scores between the two groups before treatment (P>0.05). On the 14th day of treatment, the venous recanalization scores of the observation group were lower than those of the control group, and the difference was statistically significant (P<0.01). The venous recanalization scores of the two groups on the 14th day of treatment were significantly lower than those before treatment, and the difference was statistically significant (P<0.01). See Table 10, Fig.10 .

[0229] Table 10 Comparison of venous recanalization scores (points) between the observation group and the control group

[0230]

[0231]

[0232] 3. Plasma D-dimer

[0233] The plasma D-dimer levels of the two groups of patients before and after treatment did not conform to the normal distribution. There was no statistically significant difference in the plasma D-dimer levels of the two groups of patients before treatment (P>0.05). On the 14th day of treatment, the plasma D-dimer level of the observation group was lower than that of the control group, and the difference was statistically significant (P<0.05). The plasma D-dimer levels of the two groups of patients on the 14th day of treatment were significantly lower than those before treatment, and the difference was statistically significant (P<0.01). See Table 11, Fig.11 .

[0234] Table 11 Comparison of plasma D-dimer (μg / mL) levels between the observation group and the control group

[0235]

[0236] 4. Plasma fibrinogen

[0237] The plasma fibrinogen levels and differences of the two groups of patients before and after treatment were in accordance with normal distribution. There was no significant difference in the plasma fibrinogen levels between the two groups of patients on the 0th day and the 14th day of treatment (P>0.05). The fibrinogen level of the observation group patients on the 14th day of treatment was significantly reduced, and the difference was statistically significant (P<0.05). The fibrinogen level of the control group patients on the 14th day of treatment decreased, but the difference was not statistically significant (P>0.05). See Table 12, Fig.12 .

[0238] Table 12 Plasma fibrinogen (g / L, ) Level comparison

[0239]

[0240] 5. Platelet count

[0241] The platelet counts of the two groups of patients before and after treatment did not conform to the normal distribution. On the 0th day of treatment, there was no statistically significant difference in the platelet counts of the two groups of patients (P>0.05). On the 14th day of treatment, there was no statistically significant difference in the platelet counts of the two groups of patients (P>0.05). There was no statistically significant difference in the platelet counts of the two groups of patients on the 14th day of treatment compared with before treatment (P>0.05). See Table 13, Fig.13 .

[0242] Table 13 Platelet count (×109 / L)Count comparison

[0243]

[0244] 6. White blood cell count

[0245] The white blood cell counts of the two groups of patients before and after treatment did not conform to the normal distribution. There was no statistically significant difference in the white blood cell counts of the two groups of patients before treatment (P>0.05). On the 14th day of treatment, the white blood cell counts of the observation group were lower than those of the control group, and the difference was statistically significant (P<0.05). The white blood cell counts of the two groups of patients on the 14th day of treatment were significantly lower than those before treatment, and the difference was statistically significant (P<0.01). See Table 14, Fig.14 .

[0246] Table 14 Leukocytes (×10 9 / L)Count comparison

[0247]

[0248] 7. Neutrophil count

[0249] The neutrophil counts of the two groups of patients before and after treatment did not conform to the normal distribution. There was no statistically significant difference in the neutrophil counts of the two groups of patients before treatment (P>0.05). On the 14th day of treatment, the neutrophil count of the observation group was lower than that of the control group, and the difference was statistically significant (P<0.05). The neutrophil counts of the two groups of patients on the 14th day of treatment were significantly lower than those before treatment, and the difference was statistically significant (P<0.01). See Table 15, Fig.14 .

[0250] Table 15 Neutrophils (×10 9 / L)Count comparison

[0251]

[0252] 8.Mononuclear cell count

[0253] The monocyte counts of the two groups of patients before and after treatment did not conform to the normal distribution. There was no statistically significant difference in the monocyte counts of the two groups of patients before treatment (P>0.05). On the 14th day of treatment, the monocyte counts of the observation group were lower than those of the control group, and the difference was statistically significant (P<0.05). The monocyte counts of the two groups of patients on the 14th day of treatment were significantly lower than those before treatment, and the difference was statistically significant (P<0.01). See Table 16, Fig.16 .

[0254] Table 16 Monocytes (×109 / L)Count comparison

[0255]

[0256] 10. Neutrophil-to-lymphocyte ratio (NLR)

[0257] The NLR of the two groups of patients before and after treatment did not conform to the normal distribution. There was no statistically significant difference in NLR between the two groups before and after treatment (P>0.05). The NLR of the two groups of patients on the 14th day of treatment was significantly lower than that before treatment, and the difference was statistically significant (P<0.01).

[0258] Table 18 Comparison of NLR between the observation group and the control group

[0259]

[0260]

[0261] 15. Safety indicators

[0262] During the treatment, no obvious liver and kidney damage was found in the 60 patients in the observation group and the control group, and no adverse reactions such as bleeding and drug allergy occurred.

Claims

1. A Chinese medicine composition for treating superficial vein thrombosis, characterized in that: It is composed of the following components in parts by weight: 15-30 parts of Artemisia capillaris, 6-15 parts of Viola yedoensis, 12-30 parts of Adzuki Bean, 15-30 parts of Honeysuckle, 1-6 parts of Leech, 6-12 parts of Pheretima, 6-12 parts of Atractylodes, 6-12 parts of Phellodendron, 9-15 parts of Achyranthes bidentata, 6-12 parts of Red Peony Root, 3-6 parts of Carthamus tinctorius, 15-30 parts of Coix seeds, and 10-30 parts of Astragalus.

2. The Chinese medicine composition according to claim 1, characterized in that The invention comprises the following components by weight: 30 parts of Artemisia capillaris, 15 parts of Viola yedoensis, 30 parts of Adzuki bean, 30 parts of Honeysuckle, 6 parts of Leech, 12 parts of Pheretima, 12 parts of Atractylodes, 12 parts of Phellodendron, 15 parts of Achyranthes bidentata, 12 parts of Paeonia lactiflora, 6 parts of Carthamus tinctorius, 30 parts of Coix seeds and 30 parts of Astragalus.

3. The Chinese medicine composition according to claim 1, characterized in that: In parts by weight, it is composed of the following components in parts by weight: 15 parts of Artemisia Capillaris, 6 parts of Viola yedoensis, 12 parts of Adzuki Beans, 15 parts of Flos Lonicerae, 1 part of Hirudo, 6 parts of Pheretima, 6 parts of Atractylodes, 6 parts of Phellodendron, 9 parts of Achyranthes Bidentatae, 6 parts of Red Peony Roots, 3 parts of Carthamus, 15 parts of Semen Coicis, and 10 parts of Radix Astragali.

4. The Chinese medicine composition according to claim 1, characterized in that: In parts by weight, it is composed of the following components in parts by weight: 23 parts of Artemisia Capillaris, 10 parts of Viola yedoensis, 16 parts of Adzuki Beans, 22 parts of Flos Lonicerae, 3.5 parts of Hirudo, 9 parts of Pheretima, 9 parts of Atractylodes, 9 parts of Cortex Phellodendri, 12 parts of Achyranthes Bidentatae, 10 parts of Red Peony Roots, 4.5 parts of Carthamus tinctorius, 23 parts of Semen Coicis, and 20 parts of Radix Astragali.

5. A Chinese medicine composition according to any one of claims 1 to 4, characterized in that: The Chinese medicine composition can be prepared into any one of decoctions, pills, oral liquid preparations and granules.

6. The Chinese medicine composition according to claim 6, characterized in that: Excipients are added to the formulation.

7. The drug according to claim 6, characterized in that The excipient is one or more of a filler, a disintegrant, a binder, a flavoring agent, a preservative, and a colorant.

8. A method for preparing the Chinese medicine composition according to any one of claims 1 to 4, characterized in that: The granules include the following methods: 1) Take Artemisia capillaris, Viola yedoensis, Flos Lonicerae, Atractylodes macrocephalae, Achyranthes bidentatae, Paeonia lactiflora and Adzuki bean and perform steam distillation in a multi-functional extraction tank, collect the initial distillation and the re-distillation, store them in a sealed container, and use the distilled medicinal liquid and medicinal residue for later use; 2) taking Astragalus, safflower, coix seed, Phellodendron, 1 / 2 amount of leech, earthworm and distilled drug residue, adding water and boiling twice for 1-1.5 hours, combining the two decoctions, filtering and obtaining a filtrate; 3) the filtrate of step 2) is combined with the distilled liquid of step 1), concentrated to a relative density of 1.02-1.05 at 80-90° C., cooled to room temperature, and 75-85% ethanol is added to an alcohol content of 40%-60%, and the supernatant is reserved for later use; 4) filtering the supernatant of step 3), recovering ethanol, concentrating under reduced pressure at 40-50° C. to a relative density of 1.08-1.12, vacuum drying to a dry extract, and pulverizing into a dry extract powder; 5) Crush the remaining 1 / 2 amount of leeches and earthworms into fine powder, mix the fine powder, dry paste powder and pharmaceutical excipients, add a binder to make a soft material, sieve, dry and make granules.

9. Use of the traditional Chinese medicine composition according to any one of claims 1 to 4 in preparing a drug for treating superficial vein thrombosis.

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