Pharmaceutical composition for treating lower limb venous insufficiency and limb lymphedema
By using a pharmaceutical composition composed of 12 Chinese medicines such as Yinchen and Cymbidium, the treatment problems of lower limb venous insufficiency and limb lymphedema were solved, significantly reducing FIB content, reducing edema, and improving clinical efficiency.
Patent Information
- Application Number
- CN202411918018.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-25
- Publication Date
- 2025-03-04
AI Technical Summary
The prior art is difficult to effectively treat lower limb venous insufficiency and limb lymphedema, which seriously affects the quality of life of patients.
A pharmaceutical composition is adopted, including 12 Chinese medicines such as Yinchen, Silkworm, Red Bean, Atractylodes, Yellow Cypress, Coix seed, Soap Bean, Achyranthes, Red Peony, Angelica, Astragalus and Murata. Through pharmacological effects such as promoting blood circulation, promoting dampness and unblocking meridians, clearing heat and detoxifying, the symptoms and signs of patients with lymphedema in the lower limbs are improved.
It significantly reduces the content of FIB, reduces the degree of edema with affected limbs, is clinically efficient, can improve the symptoms and signs of patients with lymphedema with lower limbs and improves quality of life.
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Figure CN119548597A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of traditional Chinese medicines and relates to a pharmaceutical composition for treating lower limb venous insufficiency and limb lymphedema. Background Art
[0002] Lymphedema is a progressive disease caused by lymphatic transport dysfunction, which leads to the retention of lymph in the subcutaneous tissue and even causes fibrous tissue hyperplasia. The early clinical manifestations are mainly limb edema, and in the late stage, skin swelling may occur, accompanied by repeated skin infections, lymphangitis, etc., which seriously affect the quality of life of patients. It ranks second in the World Health Organization's ranking of disabling diseases. Lymphedema affects about 200 million people worldwide. The incidence of secondary lymphedema is higher than that of primary lymphedema, and it is more common in women than in men. Lymphedema of the lower limbs is more common than that of the upper limbs, and is usually related to infection, obesity, chronic venous insufficiency and postoperative malignant tumors. Limb lymphedema is a common and difficult clinical disease that has attracted more and more attention from clinicians.
[0003] Limb lymphedema belongs to the category of "big foot wind", "athlete's foot", "elephantiasis", "edema" and "little disease" in traditional Chinese medicine. The formation of this disease is mostly due to damp heat infiltrating the skin and flowing into the limbs, or due to spleen deficiency and water retention, dampness blocking the qi mechanism, meridian obstruction, and qi and blood stasis. In short, the pathological nature of this disease is always due to deficiency of the root and excess of the superficial. In the early stage, it is mostly spleen deficiency, cold and dampness blocking the collaterals, and dampness and heat stagnation; as the course of the disease lasts for a long time, the positive energy is damaged, mostly phlegm and dampness blocking the collaterals, qi deficiency and blood stasis, and blood stasis blocking the collaterals will cause rough and hard skin. Traditional Chinese medicine has a long history of treating edema and has a definite effect. However, there are few studies on the medication rules for limb lymphedema. In order to better inherit the essence, maintain integrity and innovation, and improve the clinical efficacy of traditional Chinese medicine in treating limb lymphedema, with the help of the TCM inheritance auxiliary platform, data mining and collation of relevant literature on TCM treatment of limb lymphedema were carried out. By analyzing and summarizing the prescription and medication rules of TCM treatment of limb lymphedema, new methods and ideas were provided for the clinical treatment of limb lymphedema. Summary of the invention
[0004] The main purpose of the present invention is to provide a new pharmaceutical composition, specifically a pharmaceutical composition for treating lower extremity venous insufficiency and limb lymphedema. The pharmaceutical composition of the present invention has been found in clinical applications to significantly reduce the content of FIB, effectively reduce the degree of edema of the affected limb, and has a high clinical efficacy, which is of positive significance for the treatment of limb lymphedema.
[0005] Specifically, the present invention adopts the following technical solutions to achieve the above objectives:
[0006] A pharmaceutical composition for treating lower limb venous insufficiency and limb lymphedema, comprising the following components in parts by weight: 15-60 parts of Artemisia capillaris, 6-12 parts of Bombyx batryticatus, 12-30 parts of Adzuki bean, 6-15 parts of Atractylodes macrocephala, 6-15 parts of Phellodendron chinense, 15-30 parts of Coix seeds, 3-9 parts of Gleditsia sinensis, 9-15 parts of Achyranthes bidentata, 9-15 parts of Red Peony Root, 9-15 parts of Angelica sinensis, 10-30 parts of Astragalus membranaceus, and 9-15 parts of Morus twig.
[0007] Further, in a preferred embodiment of the present invention, 15 parts of Artemisia capillaris, 6 parts of Bombyx batryticatus, 12 parts of red bean, 6 parts of Atractylodes lancea, 6 parts of Phellodendron chinense, 15 parts of Coix seeds, 3 parts of Gleditsia thorns, 9 parts of Achyranthes bidentata, 9 parts of Red Peony Root, 9 parts of Angelica sinensis, 10 parts of Astragalus, and 9 parts of Morus twig.
[0008] Further, in a preferred embodiment of the present invention, 60 parts of Artemisia capillaris, 12 parts of Bombyx batryticatus, 30 parts of Adzuki bean, 15 parts of Atractylodes lancea, 15 parts of Phellodendron chinense, 30 parts of Coix seeds, 39 parts of Gleditsia chinensis, 15 parts of Achyranthes bidentata, 15 parts of Red Peony Root, 15 parts of Angelica sinensis, 30 parts of Astragalus, and 15 parts of Morus twig.
[0009] Further, in the most preferred embodiment of the present invention, 30 parts of Artemisia capillaris, 9 parts of Bombyx batryticatus, 21 parts of red bean, 10 parts of Atractylodes macrocephala, 10 parts of Phellodendron chinense, 20 parts of Coix seeds, 6 parts of Gleditsia chinensis, 12 parts of Achyranthes bidentata, 12 parts of Red Peony Root, 12 parts of Angelica sinensis, 20 parts of Astragalus, and 12 parts of Morus twig.
[0010] The present invention provides a specific use of the pharmaceutical composition, namely, use of the pharmaceutical composition in preparing a drug for treating lower extremity venous insufficiency, limb lymphedema, and deep vein thrombosis.
[0011] The present invention provides a Chinese medicine preparation prepared from the above-mentioned pharmaceutical composition, a Chinese medicine preparation prepared from the pharmaceutical composition of the present invention. The Chinese medicine preparation is an oral solid preparation and / or an oral liquid preparation. It is further preferred that the oral solid preparation is a decoction.
[0012] Compared with the prior art, the present invention has the following beneficial effects:
[0013] 1) The herb Artemisia capillaris in the prescription is bitter and good at clearing heat and removing dampness. For example, "Ben Cao Zheng Yi" states: "Artemisia capillaris, with a light taste and diuretic effect, is a special medicine for treating damp-heat in the spleen and stomach... It is the quickest to promote diuresis, so it can treat damp-heat itching in the lower part of the body, swelling of the shins and tarsus, and watery sores." Bombyx batryticatus is pungent and salty, and has a neutral nature. "Ben Cao Jing Shu" believes that it "has a light smell and taste, floats and rises, is yang, and enters the foot Jueyin, hand Taiyin, and Shaoyang meridians", and has the effects of dispelling wind and stopping spasms, resolving phlegm and unblocking collaterals. Artemisia capillaris and Bombyx batryticatus are both the main medicines for clearing heat, removing dampness and unblocking collaterals. Red bean removes dampness and promotes blood circulation, Atractylodes lancea strengthens the spleen and dries dampness, Phellodendron chinense clears heat and dries dampness, Coix seed strengthens the spleen and penetrates dampness, and Morus twigs remove rheumatism and benefit joints. They are all assistant medicines, helping Artemisia capillaris and Bombyx batryticatus to clear heat and remove dampness, and activate blood circulation and unblock collaterals. Alisma orientalis promotes diuresis and penetrates dampness, and has the effect of reducing turbidity. Bombyx Batryticatus and Rhizoma Alismatis, one ascending and the other descending, regulate the Qi, make the clear Yang rise and the turbid Yin descend. Astragalus membranaceus replenishes Qi and reduces swelling to strengthen the body, while Angelica sinensis, Paeonia lactiflora, and Gleditsia sinensis activate blood circulation, remove blood stasis and dredge collaterals, and are adjuvants. Achyranthes bidentata activates blood circulation and promotes urination, leading the medicine downward to the lower Jiao, and is the guiding medicine. All the medicines are used together to achieve the functions of removing dampness and reducing swelling, activating blood circulation and dredge collaterals, and ascending the clear and descending the turbid.
[0014] 2) Pharmacological experiments show that the prescription of the present invention contains a new prescription composed of 12 ingredients, which significantly reduces the IL-1
[0015] The contents of IL-β, IL-6, TNF-α, and IL-4 in Examples 1-3 were more significant than those in Comparative Examples 1-4 (P < 0.01). The desired technical effects of the present invention could not be achieved by using different formulations or dosages of the present invention, which further illustrates the creativity of the prescriptions and dosages of the present invention.
[0016] 3) The pharmaceutical composition of the present invention has few but fine medicinal flavors, and the prescription is mostly compatible with drugs for promoting blood circulation and qi, promoting dampness and unblocking collaterals, clearing away heat and detoxifying, etc., reflecting the important role of promoting blood circulation and promoting diuresis in the treatment of this disease, and can improve the symptoms and signs of patients with lower limb lymphedema (damp-heat syndrome), effectively reduce the degree of edema of the affected limbs, and reduce the FIB level. After treatment, the clinical symptom index scores and FIB content of the patients in the observation group were improved (P<0.01), and the effective rate was 100%. BRIEF DESCRIPTION OF THE DRAWINGS
[0017] Figure 1 : The TNF-β1 content in the plasma of each group of mice in the efficacy test after treatment in each example.
[0018] Figure 2 : The IL-1β content in the plasma of each group of mice in the efficacy test of each example.
[0019] Figure 3 : IL-6 content in plasma of each group of mice in the efficacy test of each example.
[0020] Figure 4 : The IL-4 content in the plasma of each group of mice in the efficacy test of each example.
[0021] Figure 5 : Comparison of FIB (g / L) between the observation group and the control group.
[0022] Figure 6 : Comparison of TCM symptom scores between the observation group and the control group.
[0023] Figure 7 : Comparison of treatment status between the observation group and the control group. DETAILED DESCRIPTION
[0024] 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.
[0025] Example 1: A pharmaceutical composition for treating lower limb venous insufficiency and limb lymphedema, the ingredients and dosages of which are as follows: 15 parts of Artemisia capillaris, 6 parts of Bombyx batryticatus, 12 parts of Adzuki bean, 6 parts of Atractylodes macrocephala, 6 parts of Phellodendron chinense, 15 parts of Coix seeds, 3 parts of Gleditsia sinensis, 9 parts of Achyranthes bidentata, 9 parts of Red Peony Root, 9 parts of Angelica sinensis, 10 parts of Astragalus, and 9 parts of Morus twig.
[0026] The decoction is prepared by conventional process.
[0027] Example 2: A pharmaceutical composition for treating lower limb venous insufficiency and limb lymphedema, the ingredients and dosages of which are as follows: 60 parts of Artemisia Capillaris, 12 parts of Bombyx Batryticatus, 30 parts of Adzuki Bean, 15 parts of Atractylodes Macrocephala, 15 parts of Phellodendron Amurense, 30 parts of Coix Seed, 39 parts of Gleditsia Striata, 15 parts of Achyranthes Bidentata, 15 parts of Red Peony Root, 15 parts of Angelica Sinensis, 30 parts of Astragalus, and 15 parts of Morus Ramulus.
[0028] The decoction is prepared by conventional process.
[0029] Example 3: A pharmaceutical composition for treating lower limb venous insufficiency and limb lymphedema, the ingredients and dosages of which are as follows: 30 parts of Artemisia capillaris, 9 parts of Bombyx batryticatus, 21 parts of Adzuki bean, 10 parts of Atractylodes macrocephala, 10 parts of Phellodendron chinense, 20 parts of Coix seeds, 6 parts of Gleditsia sinensis, 12 parts of Achyranthes bidentata, 12 parts of Red Peony Root, 12 parts of Angelica sinensis, 20 parts of Astragalus membranaceus, and 12 parts of Morus twig.
[0030] The decoction is prepared by conventional process.
[0031] Comparative Example 1: A pharmaceutical composition for treating lower limb venous insufficiency and limb lymphedema, the ingredients and dosages are as follows: 30 parts of Artemisia Capillaris, 9 parts of Bombyx Batryticatus, 21 parts of Adzuki Bean, 10 parts of Atractylodes, 10 parts of Phellodendron, 20 parts of Coix Seed, 6 parts of Gleditsia Spinosa, 12 parts of Achyranthes Bidentata, 12 parts of Red Peony Root, 12 parts of Angelica Sinensis, and 20 parts of Astragalus.
[0032] The decoction is prepared by conventional process.
[0033] Comparative Example 2: A pharmaceutical composition for treating lower limb venous insufficiency and limb lymphedema, the ingredients and dosages are as follows: 30 parts of Artemisia Capillaris, 9 parts of Bombyx Batryticatus, 10 parts of Phellodendron Amurense, 20 parts of Coix Seed, 6 parts of Gleditsia Spina, 12 parts of Achyranthes Bidentata, 12 parts of Red Peony Root, 12 parts of Angelica Sinensis, 20 parts of Astragalus, and 12 parts of Morus Ramulus.
[0034] The decoction is prepared by conventional process.
[0035] Comparative Example 3: A pharmaceutical composition for treating lower limb venous insufficiency and limb lymphedema, the ingredients and dosages of which are as follows: 30 parts of Artemisia Capillaris, 20 parts of Bombyx Batryticatus, 15 parts of Adzuki Bean, 20 parts of Atractylodes Macrocephala, 5 parts of Phellodendron Amurense, 16 parts of Coix Seed, 6 parts of Gleditsia Sinensis, 6 parts of Achyranthes Bidentata, 6 parts of Red Peony Root, 20 parts of Angelica Sinensis, 20 parts of Astragalus, and 10 parts of Morus Ramulus.
[0036] The decoction is prepared by conventional process.
[0037] Comparative Example 4: A pharmaceutical composition for treating lower limb venous insufficiency and limb lymphedema, the ingredients and dosages are as follows: 30g of Artemisia capillaris, 30g of red bean, 30g of Coix seed, 12g of stir-fried Atractylodes lancea with bran, 12g of Phellodendron chinense, 15g of Alisma orientalis, 15g of Cyathula capitata, and 12g of stir-fried Bombyx batryticatus, prepared into a decoction using conventional methods.
[0038] Pharmacodynamics experiments
[0039] To further prove the efficacy of the pharmaceutical 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 conduct 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.
[0040] 1. Animals, modeling, and grouping
[0041] 1.1 Animals:
[0042] C57BL / 6J male mice, SPF grade, 6-8 weeks old, 20-25g, 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.
[0043] 1.2 Animal grouping and model preparation
[0044] After several healthy C57BL / 6J male mice were adaptively raised for 1 week, sodium pentobarbital was injected intraperitoneally for anesthesia, and the skin was prepared and disinfected routinely. 0.1% evansblue 0.1ml was injected subcutaneously into the left paw of the mouse to identify the lymph nodes and lymphatic vessels. After 5-10 minutes, the left inguinal skin was cut circumferentially, the inguinal and popliteal lymph nodes were removed, and the deep lymphatic vessels were destroyed. A silicone ring with a width of about 2-3mm was fixed to the edge of the incision skin with a 6-0 suture, leaving a gap to prevent the skin from contracting and healing and blocking the formation of superficial lymphatic vessels. After 5-7 days, obvious edema appeared in the hind limbs of the mice.
[0045] Sham operation group: After 1 week of adaptive feeding, 10 healthy C57BL / 6J male mice were anesthetized by intraperitoneal injection of sodium pentobarbital and routine skin preparation and disinfection. Only the left inguinal skin was circumferentially incised without damaging the lymph nodes and lymphatic vessels. A silicone ring with a width of about 2-3 mm was directly fixed to the skin edge using 6-0 thread. No edema appeared in the hind limbs of the mice.
[0046] Administration: The constructed mouse models were randomly divided into the model group, Example 1 group, Example 2 group, Example 3 group, Comparative Example 1 group, Comparative Example 2 group, Comparative Example 3 group, Comparative Example 4 group, 10 mice in each group, and 10 normal groups were selected.
[0047] Among them, ① sham operation group: gavage with normal saline (equal amount); ② normal group: gavage with normal saline (equal amount); ③ drug administration group: respectively administered with the decoction of the corresponding embodiment of the present invention, gavage, calculated according to the crude drug dose, the administration dose is 22.62g / kg. Drug intervention was given daily starting from the third day after modeling, and continued for 28 days.
[0048] 1.2 Drug reagents
[0049] The decoctions obtained in Examples 1-3 of the present invention and Comparative Examples 1-4.
[0050] IL-1β, IL-6, IL-4, and TNF-α enzyme-linked immunosorbent assay kits were purchased from Nanjing Jiancheng Bioengineering Institute with catalog numbers H034-4-4, H020-1-5, and H066-2-7, respectively.
[0051] PLG kit (Shanghai ELISA Biotechnology Co., Ltd., catalog numbers YJ241057 and YJ601215).
[0052] 3. Statistical analysis
[0053] GraphPad Prism 9.0 software was used for statistical analysis of the data, and the quantitative data were expressed as x±s. P<0.05 was considered statistically significant.
[0054] 4 Results Analysis
[0055] 4.1 Biochemical indicators of IL-1β, IL-6, TNF-α, and IL-4 in mice
[0056] There was no significant difference between the sham operation group and the blank group (P>0.05), indicating that the impact of the surgery was small. Furthermore, compared with the sham operation group and the blank group, the levels of IL-1β, IL-6, TNF-α, and IL-4 in the plasma of mice in the model group were significantly increased (P<0.0001), indicating that the model was successfully established.
[0057] Figure 1 : The TNF-α content in the plasma of mice in the sham operation group, blank group, model group and each group of mice in the efficacy test after treatment in the examples; The TNF-α content in Examples 1-3 was significantly lower than that in Comparative Examples 1-4, and there was a significant difference (P<0.01, P<0.05).
[0058] Figure 2 : The IL-β content in the plasma of each group of mice in the efficacy test of each example.
[0059] The IL-β content in the plasma of mice in the sham operation group, blank group, model group and each group in the efficacy test after treatment in the examples; the IL-β content of Examples 1-3 was significantly lower than that of Comparative Examples 1-4, and there was a significant difference (P<0.01, P<0.05).
[0060] Figure 3 : IL-6 content in plasma of each group of mice in the efficacy test of each example.
[0061] The IL-6 content in the plasma of mice in the sham operation group, blank group, model group and each group in the efficacy test after treatment in the examples; the IL-6 content of Examples 1-3 was significantly lower than that of Comparative Examples 1-4, and there was a significant difference (P<0.01).
[0062] Figure 4 : The IL-4 content in the plasma of each group of mice in the efficacy test of each example.
[0063] The IL-4 content in the plasma of mice in the sham operation group, blank group, model group and each group in the efficacy test after treatment in the examples; the IL-4 content of Examples 1-3 was significantly lower than that of Comparative Examples 1-4, and there was a significant difference (P<0.01).
[0064] Clinical Trials
[0065] 1. Research subjects
[0066] 1. Source of cases
[0067] All cases were selected from 30 patients with lower limb lymphedema (damp-heat syndrome) who visited the Department of Peripheral Vascular Diseases, Affiliated Hospital of Shandong University of Traditional Chinese Medicine from February 2023 to May 2024. The control group was 30 healthy subjects from the Physical Examination Center of Affiliated Hospital of Shandong University of Traditional Chinese Medicine.
[0068] 2. Diagnostic criteria
[0069] 1.2 Diagnostic criteria
[0070] 1.2.1 Western medicine diagnostic criteria
[0071] According to "Vascular Lymphangiology" and "Lymphedema - Diagnosis and Treatment", the diagnosis of lower limb lymphedema is based on medical history and physical signs.
[0072] (1) Clinical features consistent with lower extremity lymphedema:
[0073] ① Slow onset.
[0074] ② In the early stage, it presents as pitting edema.
[0075] ③ Edema originates from the distal extremities: toes, ankles, and dorsum of feet.
[0076] ④ Less pain.
[0077] ⑤Accompanied by a feeling of heaviness in the affected limb.
[0078] ⑥ Skin changes: dryness, roughness, growth of papilloma, etc.
[0079] (2) Exclude lower limb edema caused by other causes such as venous edema, renal edema, and cardiogenic edema.
[0080] (3) Auxiliary examinations, such as color Doppler ultrasonography of the lower limbs showing subcutaneous fibrous tissue hyperplasia and / or subcutaneous effusion, lymphatic angiography, and MRI lymphatic imaging, can help with diagnosis.
[0081] 1.2.2 Clinical staging of limb lymphedema
[0082] According to the consensus on the diagnosis and treatment of lymphedema set by the International Society of Lymphology in 2020, limb lymphedema is divided into 4 stages:
[0083] Latent or sublatent stage (stage 0): There is impaired lymphatic transport function, subtle changes in tissue fluid and changes in subjective symptoms, but the swelling is not yet obvious.
[0084] Mild (Stage 1): Lymphedema limbs show pitting edema, which disappears when the limbs are raised, and no fibrotic skin lesions appear.
[0085] Moderate (stage 2): Tissue fibrosis or skin sclerosis begins to appear in the limbs. Edema is slightly reduced when the limbs are raised. In the later stage, the degree of fibrosis worsens and the limbs are no longer sunken.
[0086] Severe (stage 3): There are leucoderma-like changes, no pitting of the limbs, nutritional skin changes such as acanthosis, rough and dry skin, further fat deposition and fibrosis, and warty overgrowth. Infection or cellulitis may occur.
[0087] Stages 1 and 2 are not accompanied by Stemmer's sign (inability to pinch a wrinkle at the base of the second toe).
[0088] 1.2.3 TCM diagnostic criteria
[0089] With reference to Traditional Chinese Medicine Surgery, the diagnostic criteria for lymphedema with damp-heat syndrome were formulated:
[0090] Main symptoms: ① Swelling and pain in the affected limb; ② Local skin is tense and there is depression when pressed.
[0091] Secondary symptoms: ① Red, tough, and rough skin; ② Feeling of heaviness and soreness in the limbs; ③ Accompanied by chills and fever.
[0092] Tongue and pulse: ① Red tongue with yellow and greasy coating; ② Slippery and rapid pulse.
[0093] The diagnosis can be made by combining two main symptoms, or one main symptom and two secondary symptoms, with medical history, symptoms, tongue and pulse.
[0094] 1.3 Inclusion criteria
[0095] 1.3.1 Inclusion criteria for the observation group
[0096] (1) The patient meets the Western medical diagnostic criteria for lower limb lymphedema and the clinical stage is 1-2.
[0097] (2) Meet the TCM diagnostic criteria for lower limb lymphedema of damp-heat type.
[0098] (3) Aged between 18 and 74 years old.
[0099] (4) Those who voluntarily sign the informed consent form.
[0100] 1.3.2 Inclusion criteria for the control group
[0101] (1) Those who have no history of lower limb swelling or pain, have not been diagnosed with lower limb lymphedema, and do not meet the TCM syndrome of damp-heat descending.
[0102] (2) Aged between 18 and 74 years old.
[0103] (3) Those who voluntarily sign the informed consent form.
[0104] 1.4 Exclusion criteria
[0105] (1) Patients with lymphedema after tumor surgery have shorter survival or whose tumors spread and metastasize.
[0106] (2) Patients with local lymphedema due to ulcers, trauma, surgical incisions, etc.
[0107] (3) Patients with severe cardiovascular, cerebrovascular, liver, kidney and hematopoietic system diseases or a history of mental illness.
[0108] (4) Pregnant and lactating women.
[0109] (5) Patients with combined deep vein thrombosis of the lower limbs.
[0110] 1.5 Elimination criteria
[0111] (1) Those who did not take the medication according to the trial protocol.
[0112] (2) Research subjects have poor treatment compliance or are unwilling to continue participating in the clinical trial.
[0113] (3) Incomplete data may affect the judgment of efficacy and safety.
[0114] 1.6 Shedding Standard
[0115] (1) Severe allergic reactions, progressive edema, or other serious adverse events occur.
[0116] (2) During the study, the subject develops certain comorbidities (such as deep vein thrombosis of the lower limbs), complications (such as erysipelas) or special physiological changes and is no longer suitable for continued participation in the study.
[0117] (3) Those who withdraw from the trial at any time or for any reason and fail to complete clinical observation will be considered dropouts. When a subject drops out, the researcher must fill in the reason for dropout in the case report form.
[0118] 2 Research Methods
[0119] 2.1.1 Treatment plan for the observation group
[0120] The patient orally took the decoction of Example 3 (provided by the Pharmacy Department of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine), twice a day, morning and evening, 200 ml each time, and took it warm 30 minutes after a meal. During the period of taking the Chinese medicine, the patient was forbidden to eat raw, cold, spicy and other irritating foods, and avoid wind and cold. The course of treatment was 14 days.
[0121] 2.1.2 Treatment plan for the control group
[0122] The patient took furosemide tablets 20 mg orally, produced by Hebei Dongfeng Pharmaceutical Co., Ltd., approval number: National Medicine Standard H13021856, drug standard code 86902605000969. The course of treatment was 14 days.
[0123] 2.2 Observation indicators
[0124] 2.2.2.2 Changes in plasma FIB
[0125] Detection method: Take 2 ml of peripheral venous blood and store it in a 3.2% sodium citrate coagulation test tube (batch number: 2010250, manufacturer: Zhejiang Gongdong Medical Instrument Co., Ltd.), centrifuge it at a speed of 3000r / min, take plasma, and detect FIB with a fully automatic coagulometer (fully automatic coagulometer, model: STA-REvolution, number: DMZ-019).
[0126] 2.2.2.3 Changes in TCM Syndrome Score
[0127] Fill in the TCM syndrome score table truthfully before and after treatment. The TCM syndrome score table is formulated with reference to "Chinese Medicine Surgery" and the Guidelines for Diagnosis and Treatment of Common Diseases in Peripheral Vascular Diseases (2015).
[0128] 2.3 Efficacy evaluation
[0129] This study was formulated in accordance with the 2002 "Guidelines for Clinical Research of New Chinese Medicines"
[0130] (1) Basically cured: The patient's clinical symptoms and signs disappear or basically disappear, and the TCM syndrome score decreases by ≥95%.
[0131] (2) Significantly effective: Clinical symptoms and signs are significantly improved compared with before, and the TCM syndrome score is reduced by 70%≤<95%.
[0132] (3) Effective: Clinical symptoms and signs improved, and the TCM syndrome score decreased by 30%≤<70%.
[0133] (4) Ineffective: The patient's clinical symptoms and signs did not improve, or even worsened, and the TCM syndrome score decreased by less than 30%.
[0134] Calculation formula (nimodipine method) = [(score before treatment - score after treatment) / score before treatment] × 100%.
[0135] 2.4 Safety Assessment
[0136] The safety of treatment can be assessed by comparing the changes in blood routine, liver and kidney function before and after treatment. During the medication period, patients should be closely observed for adverse reactions, and any adverse events should be recorded in a timely manner and appropriate treatment measures should be taken promptly.
[0137] 2.5 Statistical methods
[0138] SPSS 22.0 statistical software was used for processing. The measurement data were tested for normality. Normally distributed data were expressed as mean ± standard deviation (X ± s); non-normally distributed data were expressed as median (interquartile range) [M (P25, P75)]. The data that met the normal distribution and variance homogeneity were tested by t-test, the paired sample t-test was used for intra-group comparison, the data that did not meet the normal distribution were tested by non-parametric test, and the count data were tested by chi-square test. P < 0.05 was considered statistically significant.
[0139] 3 Results
[0140] 3.1 Comparability analysis between the observation group and the control group before treatment
[0141] 3.1.1 FIB analysis results of the two groups before treatment
[0142] Fibrinogen (FIB) is a coagulation factor I. Under the action of thrombin, it cross-links into fibrin and participates in blood coagulation. In addition, FIB is also one of the indicators of inflammation. As an acute phase protein, it can increase in a short period of time under many stress conditions, such as infection and severe trauma. FIB exists in plasma and also in lymph. In normal human blood, the concentration of FIB is between 2.0 and 4.0 g / L, accounting for 2% to 3% of the total plasma protein. In lymph, its concentration is about 20% to 40% of that in plasma.
[0143] The FIB of the observation group was (4.44±0.63) g / L, and that of the control group was (3.12±0.47) g / L. The observation group was significantly higher than the control group, P<0.05, and the difference was statistically significant. See Table 1 and Figure 5 .
[0144] Table 1 Comparison of FIB results between the control group and the observation group
[0145]
[0146] 3.2.3 TCM Syndrome Score
[0147] Paired t-test was performed on the TCM syndrome scores before and after treatment. The results showed that the TCM syndrome score after treatment (3.56±2.14) was significantly lower than that before treatment (11.7±1.95), P<0.001, and the difference was statistically significant. See Table 2 and Figure 6 .
[0148] Table 2 Comparison of TCM syndrome scores between the control group and the observation group
[0149]
[0150] 3.3 Analysis of treatment effectiveness
[0151] For patients who completed the treatment, the results of TCM syndrome score before and after treatment were statistically analyzed and the effective rate was analyzed. The results showed that 5 cases were basically cured, 15 cases were significantly effective, 10 cases were effective, and 0 cases were ineffective. The cure rate was 16.67% and the total effective rate was 100%. In the control group, there was 0 case basically cured, 7 cases were significantly effective, 16 cases were effective, and 7 cases were ineffective. The total effective rate was 86.7%, see Table 3 and Figure 7 .
[0152] Table 3 Comparison of treatment effects between the control group and the observation group
[0153]
Claims
1. A pharmaceutical composition, characterized in that The invention is composed of the following components in parts by weight: 15-60 parts of Artemisia capillaris, 6-12 parts of Bombyx batryticatus, 12-30 parts of Adzuki bean, 6-15 parts of Atractylodes lancea, 6-15 parts of Phellodendron amurense, 15-30 parts of Coix seeds, 3-9 parts of Gleditsia sinensis, 9-15 parts of Achyranthes bidentata, 9-15 parts of Red Peony Root, 9-15 parts of Angelica sinensis, 10-30 parts of Astragalus membranaceus and 9-15 parts of Morus twig.
2. The pharmaceutical composition according to claim 1, characterized in that The invention comprises the following components by weight: 15 parts of Artemisia capillaris, 6 parts of Bombyx batryticatus, 12 parts of Adzuki bean, 6 parts of Atractylodes macrocephala, 6 parts of Phellodendron amurense, 15 parts of Coix seeds, 3 parts of Gleditsia chinensis, 9 parts of Achyranthes bidentata, 9 parts of Red Peony Root, 9 parts of Angelica sinensis, 10 parts of Astragalus membranaceus and 9 parts of Morus twig.
3. The pharmaceutical composition according to claim 1, characterized in that The invention comprises the following components in parts by weight: 60 parts of Artemisia capillaris, 12 parts of Bombyx batryticatus, 30 parts of Adzuki bean, 15 parts of Atractylodes macrocephala, 15 parts of Phellodendron amurense, 30 parts of Coix seeds, 39 parts of Gleditsia sinensis, 15 parts of Achyranthes bidentata, 15 parts of Paeonia lactiflora, 15 parts of Angelica sinensis, 30 parts of Astragalus membranaceus and 15 parts of Morus twig.
4. The pharmaceutical composition according to claim 1, characterized in that The invention comprises the following components in parts by weight: 30 parts of Artemisia capillaris, 9 parts of Bombyx batryticatus, 21 parts of Adzuki bean, 10 parts of Atractylodes macrocephala, 10 parts of Phellodendron amurense, 20 parts of Coix seeds, 6 parts of Gleditsia chinensis, 12 parts of Achyranthes bidentata, 12 parts of Paeonia lactiflora, 12 parts of Angelica sinensis, 20 parts of Astragalus membranaceus and 12 parts of Morus twig.
5. Use of the pharmaceutical composition according to any one of claims 1 to 4 in the preparation of a medicament for treating lower extremity venous insufficiency.
6. Use of the pharmaceutical composition according to any one of claims 1 to 4 in the preparation of a drug for treating limb lymphedema.
7. A Chinese medicine preparation, characterized in that: The traditional Chinese medicine preparation is prepared from the pharmaceutical composition described in any one of claims 1 to 4.
8. The Chinese medicine preparation according to claim 7, characterized in that: The traditional Chinese medicine preparation is an oral solid preparation and / or an oral liquid preparation.
9. The Chinese medicine preparation according to claim 8, characterized in that: The oral solid preparation is a decoction.