1.The concept of vascular blockage disease
Vascular occlusive diseases include: thrombosis of arteries on the basis of sclerosis, arterial embolism after the dislodgement of cardiac thrombus, venous thrombosis, obstruction of blood return after varicose veins, etc.; their clinical manifestations of diseases mainly include: ischemic lesions of the fundus: (ischemic optic papilledema, retinal atherosclerosis, diabetic retinopathy, hypertensive retinopathy, etc.); insufficient blood supply to the brain, cerebral infarction. Coronary heart disease (angina pectoris, heart attack, ischemic myocardial atrophy, etc.); diabetic foot, lower extremity atherosclerosis occlusive disease; lower extremity deep vein thrombosis and its dislodgement causing pulmonary artery infarction, atrial fibrillation wall thrombus dislodgement causing (brain, intestine, limb, etc.) arterial embolism, femoral head necrosis, etc.; all of the above diseases are vascular occlusive diseases.
2.Pathogenic factors and treatment status of vascular blockage diseases
There are four common pathogenic factors of vascular blockage diseases: hardening of blood vessel wall, vascular spasm, increased blood viscosity, and platelet aggregation (hardened plaque shedding, hardened subintimal bleeding, and non-thrombotic embolism are idiopathic and rare causes, so they are not discussed here). In terms of treatment, the common methods are: (1) for vascular wall sclerosis – stent intervention, vascular bypass (no effective drugs in both Chinese and Western medicine at present); (2) for vascular spasm – there are effective drugs in both Chinese and Western medicine (such as nitrates, calcium ion blockers and traditional Chinese medicine such as Musk Heart Pill and Quick-acting Heart Pill; (3) for the treatment of elevated blood viscosity – anticoagulants warfarin, low molecular heparin and lipid-lowering drugs, traditional Chinese medicine to activate blood circulation, increase water intake, and treatment of the primary cause of increased cell (white blood cells, platelets, red blood cells) count; (4) for platelet aggregation – aspirin, hydroclopidogrel and herbal medicines to activate blood circulation and remove blood stasis, etc. However, the above anticoagulant and anti-platelet aggregation drugs are all used for prevention, but for the treatment of thrombus formed by platelet aggregation and blood clotting, only fibrinolytic western drugs such as “urokinase” can dissolve them, but the shortcoming is that their “effective time window” is too short (only 3-4 days). But the shortcoming is that its “effective time window” is too short (only 3~4 hours), thus seriously limiting its effective clinical use.
3.The current R&D status of thrombolytic drugs in the international arena
Thrombolytic drugs are divided into three generations.
The first generation: urokinase (UK), which exists in normal blood and is extracted from human urine, can dissolve thrombus, but it is easy to cause ectopic bleeding, and the systemic fibrinogen consumption is obvious, with a vascular opening rate of 53% in 90 minutes and a complete reperfusion rate (TIMI3 level) of 28%, with an effective time window of 3 hours.
Second generation: alteplase (rt-PA): a tissue-type fibrinolytic enzyme, from human tissue, does not cause ectopic bleeding when dissolving thrombus, mild systemic fibrinogen depletion, 90-minute vascular opening rate greater than 80%, complete reperfusion rate of blood flow (TIMI3 grade) 54%, effective time window in 3-4.5 hours.
Third generation: ralteplase (r-PA) and tenecteplase (TNK-tPA): they are genetically recombinant tissue-type fibrinolytic enzymes that do not cause ectopic bleeding when lysing thrombi. In the case of ralteplase, for example, the systemic fibrinogen consumption is moderate, the 90-minute vascular opening rate is greater than 80%, the complete reperfusion rate (TIMI3 level) is 60%, and the effective time window is still 3 to 4.5 hours.
In response to the above situation, the Chinese medical profession has designed many Chinese medicine prescriptions in an attempt to solve this problem, but the pharmacological effects of most of the listed Chinese patent medicines are mainly anticoagulant, and the more influential drugs such as “pulse luo ning injection (granules), tong hui ling tablet, brain heart capsule, blood circulation and pulse tablet, blood plug tablet, tong xin luo capsule, thrombus heart pulse ning tablet “However, for coronary artery disease with severe arterial stenosis, recurrent cerebral infarction, severe diabetic foot and varicose veins of lower limbs with severe ulcers, they all seem to have “limited efficacy”.
In summary, the current thrombolytic western drugs, only strong thrombolytic power, but its “effective time window” is too short, seriously restricting its clinical use, there are proprietary Chinese drugs and shows “insufficient power”. Because of this, 99.8% of patients with ischemic stroke nationwide do not receive “thrombolytic therapy” (see “Reference Materials”). Therefore, it is of great clinical value to study the effectiveness of a Chinese herbal medicine compound in the treatment of “severe and complicated vascular blockage diseases”.
4.The purpose and significance of researching the Chinese herbal medicine compound for the treatment of vascular blockage diseases
Blocked blood vessel disease is a serious threat to people’s health. However, in the treatment of these diseases, except for stent intervention and vascular bypass, western drugs are limited by the “effective time window”, and the currently listed Chinese patent medicines are “not powerful enough”. The effectiveness of these diseases is seriously limited. This project aims to effectively solve the serious ischemic diseases of the fundus, heart, brain and lower limbs, which is of great social benefits to protect eyesight, save lives and protect productivity; it is also of great significance to reduce the number of disabled people in society, lower the cost of treatment and reduce the burden of medical insurance, as well as to improve the status of Chinese herbal medicine in the treatment of vascular blockage diseases, enhance the viability of proprietary Chinese medicine enterprises and improve the competitiveness of the national pharmaceutical industry. The competitiveness of the national pharmaceutical industry is also of great significance.
5, the classification of drugs related to blood vessel blockage
At present, in the treatment of vascular blockage diseases: drug treatment (non-drug treatment is mainly stent intervention and vascular bypass) is divided into Western medicine and Chinese medicine.
(1) Western drugs: their pharmacological effects are mainly divided into
I. Drugs for vasospasm.
① vasodilators: nitrates (isosorbide mononitrate – mainly for prevention, nitroglycerin – mainly for emergency treatment).
② calcium blocking agents – nifedipine, amlodipine, etc.
II. Drugs for thrombosis.
① anti-platelet aggregation drugs: aspirin, clopidogrel, etc.
② anticoagulants – warfarin, low molecular heparin, etc.
Ⅲ, for thrombolytic drugs
①Urokinase: can dissolve thrombus, effective time window within 3 hours.
(ii) Alteplase: dissolves thrombus without causing ectopic bleeding, with an effective time window of 3 to 4.5 hours.
(2) The situation of proprietary Chinese medicines: dozens of proprietary medicines have been marketed to improve blood supply, such as pulse luo ning injection (granules), Tongxinling tablets, cerebral heart tong capsule, blood activation and blood circulation tablets, blood plugging tablets, Tongxinluo capsules, thrombotic heart pulse ning tablets, etc..
The content of this project is a combination of Chinese and Western medicine pathology, combined with the pharmacology of Chinese medicine, from the treasury of Chinese medicine, from the medicine of tonifying qi, promoting qi, activating blood circulation, resolving blood stasis, softening hardness and dispersing knots. There is no duplication and compatibility with the above existing drugs and patents.
6.Comparison of the efficacy of this Chinese medicine compound with the existing domestic and foreign drugs.
At present, the main products in the international market are “fibrinolytic” drugs, which have been developed to the third generation, while the first generation (urokinase) and the second generation (alteplase) are mainly used in clinical practice; the existing Chinese patent medicines listed in China that have the ability to improve blood supply are not significant or satisfactory in terms of their effectiveness in reopening blood vessels. This formula is compared with it as follows
(1) Compare with the “effective time window”: the “effective time window” of the existing “fibrinolytic” western drugs, both the first generation (urokinase) and the second generation (alteplase), is less than 4.5 hours, but this compound formula far exceeds this time range, and has reached “months and years”.
(2) The opening time of blood vessels: Although it takes 90 minutes for the opening rate of western medicine of fibrinolytic class to reach 50% to 80%, and the symptoms improve significantly (about 50% opening) in 5 to 20 days after the use of this formula, however, according to the biological characteristics of heart and brain cells tolerating ischemia and hypoxia for 30 minutes and 6 minutes respectively, the reperfusion time of blood flow is greater than 30 minutes no matter using western medicine or Chinese medicine. On the contrary, it is of great clinical significance to rescue ischemic marginal zone tissues and promote their cellular resurrection for the herbal compound formula with longer effective time window. Its competitive ability is much higher than that of western drugs with fibrinolytic effect.
(3) Compare with similar Chinese medicine compound formula: Although the existing Chinese medicine compound formula that has been marketed can improve the blood supply of blocked blood vessels, most of them seem to be “powerless” for serious ischemic vascular disease, and so far there is little information about using Chinese medicine alone orally to heal diabetic foot with Wagner grade IV or above, to make the left and right coronary arteries, anterior descending branches and second bridge of the heart There are few reports of patients with 95% to 100% stenosis of the left and right coronary arteries, anterior descending branch, left rotating branch and two bridge vessels of the heart recovering and living normally for several years, and patients with severe blockage of blood vessels in five parts of the brain living normally. (See examples for details)
7.The current indications of the formula and the use of the effect of the introduction
(1) Ophthalmologic diseases: ischemic fundus diseases (diabetic retinopathy, hypertensive retinopathy, ischemic optic papillopathy, etc.) can be significantly improved with this formula, and in some patients, the vision is completely restored to normal.
(2) Neurological diseases: it can control recurrent cerebral infarction; it can also enable some patients who have been paralyzed for more than one year during the rehabilitation period to walk again, or patients with poor walking ability to substantially improve their walking ability.
(3) Cardiology diseases: after coronary artery “stent intervention” or “bypass surgery”, the blood vessels are severely blocked again and cannot be re-treated with non-pharmacological treatment, so that the blood supply can be improved and the heart function can be restored; it can also enable patients who have reached the standard of stent intervention and Patients with typical and severe angina pectoris can achieve the disappearance of symptoms and be able to participate in normal indoor and outdoor activities through the use of Chinese herbal medicine alone without stenting.
(4) Peripheral vascular disease: When diabetic patients have had obvious blood supply disorders in the lower limbs for several years, with ulceration and necrosis for months to years, or even serious infections requiring amputation, blood flow can be recirculated, inflammation subsided, ulcers repaired, and normal life can be achieved through the simple oral use of Chinese herbal medicine of this formula. If varicose veins of lower limbs have swelling, itching, twitching, ulceration and even long-standing ulcers, the symptoms can be relieved in about 1 month and the ulcers can be healed in about 3 months after using this formula. It can significantly improve the symptoms of deep vein thrombosis, lower limb artery embolism and femoral head necrosis.
Since the clinical practice proves the unique effect of this formula, it is titled as “Powerful Blood Stasis Removal and Blood Circulation Formula” or “Powerful Blood Activation and Blood Circulation Formula”.
8. Examples of clinical efficacy of this herbal formula
(1) Cerebral ischemic vascular disease
Xia××: male, 67 years old at the time of consultation, from Dazhong Town, Dafeng City, Jiangsu Province.
On 2011-7-23, the patient suddenly fainted while working in the field, and then relieved himself automatically. He was diagnosed as “cerebral infarction” by a local county hospital and was hospitalized for two times, but the treatment was not effective. In the imaging examination, MRI alone showed five stenoses or occlusions. Specifically, (1) ultrasound: low flow in both vertebral arteries; (2) cranial CT: paraventricular lumen infarction on both sides; (3) cranial MRI: occlusion of the proximal lumen of the right anterior middle cerebral artery, stenosis of the lumen of the right common carotid artery near the bifurcation, thinning of the left vertebral artery with segmental lumen, stenosis of the lumen of the distal right vertebral artery and the proximal basilar artery, and local basic occlusion. The patient had “a history of hypertension for 7 years and diabetes mellitus for 6 years” in the past. During his hospitalization, he was treated with various western drugs and blood-stasis activating Chinese medicine intravenously, and was discharged with aspirin, nifedipine, clopidogrel sulfate (Bolivar) and other drugs, but his condition was not significantly reduced but worsened. After three months of treatment, all symptoms disappeared. So far, no recurrence of the disease has been observed.
(2) Cardiac ischemic vascular disease
Xu××: male, a construction company worker in Dafeng, Jiangsu Province, 69 years old at the time of consultation.
He had a history of hypertension for more than 20 years and underwent stent placement in a provincial people’s hospital in 1999 due to coronary artery stenosis and coronary artery bypass surgery in 2000. (1) 95% stenosis at the end of the main trunk; (2) total closure of the anterior descending branch with visible proximal stent shadow; (3) total closure of the gyral branch; (4) about 60% stenosis at the proximal end of the right coronary artery and 95% stenosis in front of the posterior trigeminal; (5) bridge angiography: (1) SVG-RCA: 90% stenosis at the proximal segment and 95% stenosis at the anastomosis; (2) SVG-LCX. proximal segment 40% stenosis, anastomosis 90% stenosis; (3) LIM-LAD: approximately normal; collateral circulation: none. Due to the systemic condition, he could not be reoperated, so he was treated with “isosorbide mononitrate” and “thiodiazepine” to improve the coronary blood supply; “atorvastatin” to regulate lipids. “Clopidogrel” and “aspirin” are used for anti-platelet aggregation; “metoprolol” is used for heart rate control; “cloxacin “Clopidogrel” and “Aspirin” for antiplatelet aggregation; “Metoprolol” for heart rate control; “Clorazepam” for blood pressure control; “Lexapro” and “Novalis” for hypoglycemic treatment. However, angina pectoris still occurred frequently. At the end of August 2011, he took this formula of traditional Chinese medicine, and his condition was stabilized in one month after treatment. In the past two years, he has maintained treatment without recurrence, and he can live normally, travel, ride an electric bicycle with people, and participate in general social activities.
(3) Lower limb ischemic vascular disease
4. Guo××, male, 51 years old at the time of consultation, worker, from Dafeng, Jiangsu Province
He has been suffering from diabetes mellitus for more than 10 years and has had diabetic foot for more than three years. The small mother toe of the left foot had been necrotic amputation, due to the right foot toe ulcerated water in a local county hospital for nearly three months, after a variety of blood revitalizing Chinese and Western drugs and antibiotics treatment is ineffective, the right foot toe has been necrotic fall off, the middle toe toe has become black and withered, the whole foot surface serious infection, with edema, erosion, pus. The patient was transferred from the endocrinology department to the orthopedic department to prepare for amputation, and because the patient refused, the necrotic tissue was scraped off the right foot sole ulcer, leaving a deep groove that was infected with ooze, and the whole foot was necrotic and smelly, with a foul odor. The right lower limb was severely edematous, unstable and unable to walk. On 2011-7-9, he came to our clinic. After taking this formula for ten days, the edema subsided by nearly half, and the ulcer at the bottom of the foot healed after one month of taking the medicine, and the swelling was only in the front third of the face of the foot, and the inflammation disappeared after two months of taking the medicine, and he was able to walk and ride a bicycle normally and take care of himself.
(All the above cases were treated on an outpatient basis, using this formula alone, without the addition of any western medicine or other proprietary Chinese medicine, and without the use of topical medication. (For more details, please refer to the relevant case description).