The Theory of Collateral Diseases in Traditional Chinese Medicine
The concepts of meridians, collaterals, collateral vessels, and collateral diseases are all rooted in the Huangdi Neijing (Yellow Emperor’s Inner Canon). Zhang Zhongjing’s formulas such as Xuanfu Hua Decoction, Dahuang Zhechong Pill, and Didao Pill, which utilize insect-based medicines, were recognized until the Qing Dynasty when Ye Tianshi proposed the phrase “chronic illness enters the collaterals, chronic pain enters the collaterals.” These eight words have become a significant pathological concept in TCM.
Collateral disease is not an independent disease category; any condition that fits the characteristics of chronic illness or chronic pain can be termed collateral disease. Cardiovascular diseases, diabetes, malignant tumors, and rheumatic immune diseases can all be explained using the theory of collateral diseases. However, as Ye Tianshi stated: “After reviewing all medical literature, none mention collateral diseases,” and “if physicians do not understand the treatment methods for collaterals, they will find themselves increasingly at a loss.” Collateral diseases present a significant challenge left by history for contemporary practitioners.
Chronic illness and chronic pain are both clinical concepts and theoretical pathologies. Despite advancements in modern medicine, conditions such as cardiovascular diseases, diabetes, and malignant tumors remain unresolved, and ancient practitioners also found these diseases difficult to treat. Chronic illness and pain require the unblocking of collaterals to enhance therapeutic efficacy. Unfortunately, due to historical limitations, the theory of collateral diseases has not formed a systematic framework. Therefore, establishing a national key laboratory to advocate for the integrated development of theory, clinical practice, and new drug research aligns with the developmental principles of TCM.
The formation of the entire academic theoretical system of TCM relies on the combination of philosophy, experimental science, and clinical practice, and the study of collateral diseases is no exception. It is essential to adhere to the guidance of TCM’s holistic system theory while integrating modern experimental techniques, with a focus on clinical applications to address major diseases. This involves combining the overall with the local, qualitative with quantitative assessments. In the diagnosis and treatment of collateral diseases, we advocate for incorporating physical and chemical examinations into TCM diagnostic analysis, which is indispensable for the development of collateral disease theory. Additionally, we must persist in translational medicine. Finally, we need to develop the industry; once industrialized, our effective experiences can circulate more widely, and our clinical experiences and academic achievements can benefit the public on a larger scale.
The focus of collateral disease studies is on the diagnosis and treatment of collateral diseases. We combine classical TCM theories with major clinical diseases to explore new theoretical models for treating significant clinical conditions. The entire research route begins with proposing a “three-dimensional network system” research framework, then delving into the temporal and spatial differences to study the functions of collaterals, the onset of collateral diseases, their pathogenesis, diagnosis, and treatment, thereby preliminarily establishing a “diagnosis and treatment system for collateral diseases.”
The three-dimensional aspect examines collateral diseases from the perspectives of time, space, and functional consistency. Ancient practitioners categorized meridians into bie luo (branch collaterals), xi luo (connecting collaterals), chan luo (intertwined collaterals), and sun luo (grandchildren collaterals), representing a network hierarchy. Zhang Jingyue described yang collaterals as “superficial and external,” while meridians “run deep within the flesh,” and yin collaterals as “deep and internal,” which reflects the concept of spatial positioning. Ye Tianshi stated, “Yin collaterals are the collaterals subordinate to the internal organs,” indicating that yin collaterals are distributed among the internal organs. The introduction of spatial concepts is crucial as it pertains to the exploration of the pathogenesis of diseases in TCM, reflecting the chronic pathological processes of various difficult-to-treat diseases transitioning from meridians to collaterals, from qi to blood, and from functional disorders to organic damage. This is a key focus of collateral disease theory and a weak link that has been overlooked in the history of TCM academic development. Strengthening research on this critical pathological link will help improve the clinical diagnostic and treatment levels for various difficult-to-treat diseases.
The cyclical state and rhythm of qi and blood circulation, including the timing and speed of their flow, are also worthy of study. Zhenjiu Dacheng states: “From the start of the Yin hour, over a day and night, the human nutritive and defensive qi circulates around the body at fifty degrees, with qi traveling 13,500 zhang (0.52 m/s, compared to the modern medical nerve conduction speed of 50 m/s), and blood traveling 810 zhang (0.03 m/s, with microcirculation blood flow speed of 0.03 cm/s) (qi flow/blood flow = 16.7). The circulation of qi and blood, the flow of yin and yang, follows the rhythms of day and night, in harmony with the heavens, and continues in cycles.” Understanding these patterns of qi and blood circulation is significant for further research into their biological mechanisms and has important implications for the treatment of many clinical diseases.
The spatial characteristics of collaterals include: branches diverging and subdividing; the collateral body being narrow and net-like in distribution; collaterals being divided into yin and yang, circulating internally and externally. The speed characteristics include: qi and blood flowing slowly, dispersing superficially; terminal connections allowing for the exchange of fluids and blood; bidirectional flow for functional regulation. Qi and blood run through the meridians, while their functions are realized within the collaterals. “Meridians are responsible for the flow of blood and qi, while nourishing yin and yang is achieved within the collaterals.”
The characteristics of the onset of collateral diseases are summarized as “chronic illness enters the collaterals, chronic pain enters the collaterals, chronic stasis enters the collaterals.” The pathological characteristics can be encapsulated in the twelve words: “easy to stagnate, easy to stasis, easy to accumulate and form.” Eight categories of syndromes have been summarized: “collateral qi stagnation (deficiency), collateral vessel obstruction, collateral vessel constriction, collateral vessel blockage, heat toxin stagnation in collaterals, collateral stasis accumulation, collateral vessel damage, and collateral deficiency leading to lack of nourishment,” which guide clinical medication. The clinical manifestations of these eight categories of collateral disease syndromes include: pain, bi syndrome, numbness, atrophy, paralysis, bleeding, edema, and rashes. The diagnostic methods for collateral diseases include: identifying pathogenic factors, assessing the duration of the disease, distinguishing between qi and blood conditions, analyzing yin and yang, differentiating between cold and heat, deficiency and excess, and evaluating the shape and color of the collaterals, including physical and chemical examinations. The macro TCM diagnostic analysis methods currently include organ differentiation, eight principles differentiation, qi, blood, and body fluid differentiation, and sanjiao differentiation, all based on traditional observation, listening, questioning, and pulse-taking to collect medical history data. With the introduction of experimental techniques into TCM clinical practice, the four diagnostic methods have been extended, necessitating the development of diagnostic analysis theories that align with modern examination methods, thus elevating TCM pathogenesis theories to a new level.
Ancient practitioners summarized the medicinal substances for unblocking collaterals into four categories: pungent substances for unblocking collaterals, insect medicines for unblocking collaterals, vine-based medicines for unblocking collaterals, and tonifying medicines for collateral deficiency. These medicines are more effective than Western calcium channel blockers in alleviating coronary artery spasms. Ye Tianshi’s view on “tonifying collateral deficiency” is, in fact, a representative aspect of collateral disease treatment. For instance, what is the difference between treating collateral qi deficiency and qi deficiency? TCM states, “deficiency should be tonified.” The Si Jun Zi Tang (Four Gentlemen Decoction) is a typical qi tonifying formula. Qi deficiency is treated by tonifying qi, while blood deficiency is treated by tonifying blood; tonification is sufficient. However, collateral deficiency is different; it requires both unblocking and tonifying. Collateral unblocking medicines can be categorized by function into seven types: promoting qi and unblocking collaterals, resolving stasis and unblocking collaterals, dispersing masses and unblocking collaterals, eliminating phlegm and unblocking collaterals, expelling wind and unblocking collaterals, detoxifying and unblocking collaterals, and nourishing collaterals. These medicines are very important in clinical practice. In recent years, there has been a misunderstanding that collateral disease is merely a blood stasis syndrome. The categorization of unblocking medicines into seven types shows that only the resolving stasis and unblocking category overlaps with blood-activating and stasis-resolving, thus expanding the range of clinical formula options. Therefore, collateral disease and blood stasis syndrome are two distinct pathological concepts that overlap in meaning yet remain independent.
Chinese Pharmacopoeia 2020 Edition
Tongxinluo Capsules
Tongxinluo Jiaonang
This product is a capsule made from ginseng, leeches, scorpions, red peony, cicada slough, earthworm, centipede, sandalwood, aromatic myrrh, frankincense (processed), fried sour jujube seed, and borneol.
[Properties] This product is a hard capsule, with contents that are gray-brown to gray-black granules and powder; it has a fragrant aroma, slightly fishy smell, and a slightly salty and bitter taste.
[Functions and Indications] Tonifies qi, activates blood, unblocks collaterals, and alleviates pain. It is used for coronary heart disease with angina pectoris due to heart qi deficiency and blood stasis obstructing the collaterals, with symptoms including chest tightness, stabbing pain, constricting pain that is fixed and unchanging, palpitations with spontaneous sweating, shortness of breath, and fatigue, with a purple or dark tongue or stasis spots, and a thin, choppy, or intermittent pulse. It is also used for stroke due to qi deficiency and blood stasis obstructing the collaterals, with symptoms including hemiplegia or unilateral numbness, facial drooping, and slurred speech.
[Dosage and Administration] Oral administration. Take 2-4 capsules each time, three times a day.
[Precautions] Contraindicated in patients with bleeding disorders, pregnant women, women during menstruation, and those with yin deficiency and excess heat type stroke.
[Specifications] Each capsule contains 0.26g
[Storage] Sealed.
[Formula Analysis]
Tongxinluo Capsules are the first collateral-unblocking formula developed by Academician Wu Yiling based on the theory of collateral diseases in TCM, representing a key medication for “vascular system diseases.” In this formula, ginseng is the monarch herb that greatly tonifies the original qi and benefits qi to assist blood circulation. Leeches, earthworms, red peony, frankincense, and aromatic myrrh are the minister herbs that activate blood, break blood stasis, and unblock collaterals. Scorpions and centipedes are the assistant herbs that unblock collaterals and alleviate pain, while sandalwood regulates qi, relieves chest tightness, and alleviates pain; borneol unblocks orifices and alleviates pain; cicada slough extinguishes wind and alleviates pain; fried sour jujube seed nourishes the heart and calms the spirit, serving as the adjuvant herbs. The combination of these herbs works together to tonify qi, activate blood, promote qi flow, and alleviate pain.
[Clinical Applications]
1. Chest Bi: Caused by insufficient heart qi, blood stasis obstructing the heart vessels, and loss of nourishment to the heart. Symptoms include chest tightness, stabbing pain in the precordial area, palpitations, shortness of breath, fatigue, and spontaneous sweating, with a thin, choppy pulse and a pale purple tongue; this is seen in coronary heart disease with angina pectoris presenting these symptoms.
2. Stroke: Caused by qi deficiency and blood stasis, leading to obstruction of the collaterals. Symptoms include hemiplegia, generalized numbness, facial drooping, and slurred speech; this is seen in ischemic stroke presenting these symptoms.
Additionally, there are reports that this product can also be used to treat hyperlipidemia, vertebrobasilar insufficiency, migraine, non-alcoholic fatty liver disease, and early diabetic nephropathy.
[Pharmacology and Toxicology]
This product has effects of anti-myocardial ischemia, anti-cerebral ischemia, improving hemodynamics, and anti-thrombotic effects.
1. Anti-myocardial ischemia: This product can reduce the degree and extent of myocardial ischemia in dogs with ligated coronary arteries and reduce the area of infarction; it can also alleviate isoproterenol-induced myocardial tissue necrosis in rats and reduce myocardial cell apoptosis; it decreases serum levels of procollagen type I carboxy-terminal peptide (PICP) and type III collagen amino N-terminal peptide (PⅢNP) in rats with left anterior descending coronary artery ligation-induced ventricular remodeling.
2. Hemodynamics: This product, when administered via the duodenum, can increase coronary blood flow and left ventricular function in dogs; it can also increase cerebral blood flow and reduce cerebrovascular resistance in anesthetized dogs.
3. Anti-ischemia-reperfusion injury: This product can reduce the area of myocardial infarction in rats with left coronary artery ligation-induced myocardial ischemia-reperfusion injury, decrease plasma creatine kinase (CK) activity, and reduce the degree of myocardial cell necrosis; it can also reduce apoptosis of myocardial cells after ischemia-reperfusion injury, downregulate Bax protein expression, and upregulate Bcl-2 protein expression; it can also reduce the adhesion and adhesion stress of brain capillary endothelial cells and polymorphonuclear leukocytes in rats with cerebral ischemia-reperfusion injury.
4. Anti-cerebral ischemia: This product can reduce brain tissue damage caused by focal cerebral ischemia in rats, decrease the volume of cerebral infarction, improve neurological symptoms, and reduce whole blood viscosity.
5. Improving microcirculation: This product can increase blood flow velocity, improve blood flow dynamics, and ameliorate microcirculatory disorders in the auricle of mice induced by high molecular dextran; it enhances t-PA activity in blood stasis model rats and reduces PAI activity.
6. Anti-thrombotic: This product has an inhibitory effect on platelet aggregation in rats and can also inhibit thrombus formation in rabbits; it reduces tail thrombus formation in rats induced by carrageenan and increases AT-Ⅲ activity and D-dimer levels.
7. Others: This product can inhibit chloroform-induced ventricular arrhythmias in mice and lower serum TCLDL levels in hyperlipidemic rats.
[Prescription Drug Instructions]
[Drug Name] Generic Name: Tongxinluo Capsules
[Ingredients] Ginseng, leeches, scorpions, red peony, cicada slough, earthworm, centipede, sandalwood, aromatic myrrh, frankincense (processed), fried sour jujube seed, borneol.
[Properties] This product is a hard capsule, with contents that are gray-brown to gray-black granules and powder; it has a fragrant aroma, slightly fishy smell, and a slightly salty and bitter taste.
[Indications] Tonifies qi, activates blood, unblocks collaterals, and alleviates pain. It is used for coronary heart disease with angina pectoris due to heart qi deficiency and blood stasis obstructing the collaterals, with symptoms including chest tightness, stabbing pain, constricting pain that is fixed and unchanging, palpitations with spontaneous sweating, shortness of breath, and fatigue, with a purple or dark tongue or stasis spots, and a thin, choppy, or intermittent pulse. It is also used for stroke due to qi deficiency and blood stasis obstructing the collaterals, with symptoms including hemiplegia or unilateral numbness, facial drooping, and slurred speech.
[Specifications] Each capsule contains 0.26g
[Dosage and Administration] Oral administration. Take 2-4 capsules each time, three times a day.
[Adverse Reactions] Post-marketing surveillance data indicate that this product may cause gastrointestinal adverse reactions such as nausea, vomiting, abdominal pain, bloating, diarrhea, and gastric discomfort, as well as rashes, itching, and dizziness.
[Contraindications] Contraindicated in patients with bleeding disorders, pregnant women, women during menstruation, and those with yin deficiency and excess heat type stroke.
[Precautions] Patients experiencing gastric discomfort after taking the medication should switch to taking it after meals.
[Pharmacology and Toxicology]
Non-clinical pharmacodynamic test results suggest that this product can reduce the degree of myocardial ischemia in dogs and rats with acute myocardial infarction models, decrease the area of myocardial ischemia, improve myocardial blood supply and oxygenation, increase coronary blood flow and left ventricular work; it can reduce the area of myocardial no-reflow in pigs with acute myocardial infarction-reperfusion models, decrease myocardial infarction area; it can inhibit collagen fiber proliferation after myocardial infarction in rats, reduce collagen deposition, lower angiotensin II (Ang II) levels in myocardial tissue, inhibit ventricular remodeling, and improve cardiac function; it can reduce the area of cerebral infarction in rats with focal cerebral ischemia models, decrease cerebrovascular permeability, and alleviate cerebral edema; it can reduce pathological damage such as neuronal degeneration and necrosis, and Nissl body disappearance in mice with global cerebral ischemia models, improve neurological behavior, protect ischemic brain tissue, increase superoxide dismutase (SOD) activity in brain tissue, and lower malondialdehyde (MDA) levels; it can lower serum total cholesterol and low-density lipoprotein levels in hyperlipidemic rats, increase high-density lipoprotein levels, and inhibit thrombus formation and platelet aggregation in rats.
Additionally, exploratory studies on the mechanism of action suggest that this product may lower excitatory amino acids in the brains of rats with middle cerebral artery occlusion models, reduce endothelin (ET) levels, inhibit endothelin gene expression, promote vascular endothelial growth factor expression in rats with cerebral ischemia models, protect brain capillary endothelial cells, and promote capillary neogenesis; it improves endothelial function in rabbit atherosclerosis models, alleviating the damage to endothelium-dependent vasodilation caused by hypercholesterolemia, enhances the expression of endothelial nitric oxide synthase (eNOS) genes in ischemic myocardium, increases eNOS activity, and elevates nitric oxide (NO) levels in plasma and tissues; it inhibits the expression of mitogen-activated protein kinase (MAPK) after rabbit vascular surgery and reduces vascular intimal proliferation, lowers blood TC, LDL-C, ET levels, and increases NO levels; it reduces lipid content in plaques in rabbit vulnerable plaque models, increases plaque fibrous cap thickness, lowers blood lipids and plasma fibrinogen levels, and inhibits inflammatory factor expression, thus stabilizing vulnerable plaques; it inhibits serotonin-induced coronary artery spasms in pigs; through these multiple mechanisms, it exerts cardioprotective and anti-thrombotic effects.
[Storage] Sealed.
[Shelf Life] 36 months.
[Standards] Chinese Pharmacopoeia 2020 Edition
[Approval Number] National Medicine Standard Code Z19980015
[Manufacturer] Company Name: Shijiazhuang Yiling Pharmaceutical Co., Ltd.
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