Traditional Chinese medicine composition for treating heart-kidney yang deficiency syndrome of diabetic nephropathy as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention provides a traditional Chinese medicine composition for treating heart-kidney yang deficiency syndrome of diabetic nephropathy and a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicine. The traditional Chinese medicine composition comprises astragalus membranaceus, prepared rehmannia root, radix pseudostellariae, rheum officinale, rhizoma smilacis glabrae, morinda officinalis, semen cuscutae, creeping rostellularia herb, rhizoma anemarrhenae, leech, stiff silkworm and radix scrophulariae. The traditional Chinese medicine composition disclosed by the invention has the effects of warming and tonifying yang qi, detoxifying and dissolving turbidity, and promoting blood circulation to remove meridian obstruction, and can restore the gasification function of the kidney by tonifying fire and supporting yang, relieve edema and relieve the glomerular hyperfiltration state; the traditional Chinese medicine also has the effects of clearing heat and drying dampness, purging turbidity and detoxifying, reducing toxin accumulation and improving kidney microcirculation so as to delay the development of diabetic nephropathy. The invention further provides a preparation method of the traditional Chinese medicine composition and a medicine for treating heart-kidney yang deficiency of diabetic nephropathy.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a traditional Chinese medicine composition for treating diabetic nephropathy with deficiency of heart and kidney yang, its preparation method, and its application. Background Technology

[0002] Diabetic kidney disease (DKD) is chronic damage to the blood vessels and glomeruli of the kidneys caused by long-term hyperglycemia. It is one of the most common microvascular complications of diabetes and a major cause of chronic kidney disease and end-stage renal disease (kidney failure). Clinically, it often presents with symptoms such as massive proteinuria, hypertension, and edema. Kidney function tests often show decreased urinary albumin and glomerular filtration rate (GFR). Some patients may experience anemia and often have other microvascular complications, such as diabetic retinopathy. Early symptoms are insidious, and later stages may lead to kidney failure, requiring dialysis or kidney transplantation. The "Guidelines for the Diagnosis and Treatment of Diabetic Kidney Disease with Integrated Traditional Chinese and Western Medicine" points out that the main syndrome differentiation of DKD includes liver and kidney yin deficiency syndrome, spleen and kidney qi deficiency syndrome, qi stagnation and blood stasis syndrome, phlegm-dampness retention syndrome, damp-heat retention syndrome, qi and yin deficiency syndrome, spleen and kidney yang deficiency syndrome, phlegm and blood stasis syndrome, yin and yang deficiency syndrome, and heart and kidney yang deficiency syndrome. Among them, heart and kidney yang deficiency syndrome, as a late-stage DKD, often leads to the aggravation of disease complications and has a poor prognosis.

[0003] Modern medicine primarily treats disseminated intravascular coagulation (DKD) by controlling blood pressure (ACEIs / ARBs), blood sugar (oral hypoglycemic agents and insulin injections), and blood lipids (statins and fibrates). However, these treatments have limited ability to slow DKD progression and have certain side effects. The role of Traditional Chinese Medicine (TCM) in disease prevention and / or treatment is receiving increasing attention. Its multi-component and multi-target characteristics give it unique potential in the treatment and recovery of many diseases. Currently, many TCM formulas have been reported to play a synergistic role in the treatment of serious diseases and a core role in disease rehabilitation. Therefore, finding effective drugs for treating DKD from the perspective of TCM holds great promise. Summary of the Invention

[0004] In order to solve the problems existing in the prior art, the first objective of the present invention is to provide a traditional Chinese medicine composition for treating diabetic nephropathy with deficiency of heart and kidney yang and its preparation method, which has the effects of warming and tonifying yang, detoxifying and clearing turbidity, and promoting blood circulation and unblocking collaterals.

[0005] The second objective of this invention is to provide the application of the above-mentioned traditional Chinese medicine composition in the preparation of a medicine for treating diabetic nephropathy with deficiency of heart and kidney yang.

[0006] The third objective of this invention is to provide a drug for treating diabetic nephropathy with deficiency of heart and kidney yang.

[0007] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0008] This invention provides a traditional Chinese medicine composition for treating diabetic nephropathy with deficiency of heart and kidney yang, comprising the following components by mass: Astragalus membranaceus 10-30 parts, Rehmannia glutinosa 10-30 parts, Codonopsis pilosula 10-30 parts, Rheum palmatum 3-12 parts, Smilax glabra 40-60 parts, Morinda officinalis 10-15 parts, Cuscuta chinensis 10-15 parts, Justicia procumbens 40-60 parts, Anemarrhena asphodeloides 6-12 parts, Hirudo medicinalis 3-6 parts, Bombyx mori 3-9 parts, and Scrophularia ningpoensis 10-15 parts.

[0009] Preferably, by weight, it includes the following components: 30 parts Astragalus membranaceus, 30 parts Rehmannia glutinosa, 20 parts Codonopsis pilosula, 6 parts Rheum palmatum, 50 parts Smilax glabra, 10 parts Morinda officinalis, 10 parts Cuscuta chinensis, 50 parts Justicia procumbens, 9 parts Anemarrhena asphodeloides, 3 parts Hirudo medicinalis, 6 parts Bombyx mori, and 15 parts Scrophularia ningpoensis.

[0010] The present invention also provides a method for preparing the above-mentioned traditional Chinese medicine composition, comprising the following steps: mixing the components, adding water and decocting, and filtering the decoction; wherein the amount of water added is 6 to 8 times the total mass of the mixed components.

[0011] Preferably, the method further includes the following steps: filtering the decoction, concentrating the filtrate, and drying it.

[0012] Preferably, the decoction is performed 2 to 3 times, each time for 1 to 3 hours.

[0013] Preferably, the concentrate is an extract with a relative density of 1.20 to 1.25 when concentrated to 60°C.

[0014] Preferably, the drying method includes vacuum drying.

[0015] This invention also provides the application of the above-mentioned traditional Chinese medicine composition in the preparation of a medicine for treating diabetic nephropathy with deficiency of heart and kidney yang.

[0016] The present invention also provides a medicine for treating diabetic nephropathy with deficiency of heart and kidney yang, the medicine comprising the above-mentioned traditional Chinese medicine composition and pharmaceutically acceptable excipients.

[0017] Preferably, the dosage form of the drug includes tablets, decoctions, capsules, granules, pills, suspensions, dispersants, or syrups.

[0018] Compared with the prior art, the beneficial effects of the technical solution of the present invention are as follows:

[0019] This invention is guided by traditional Chinese medicine theory, based on solid clinical practice, and employs modern scientific research methods. It utilizes the principles of warming yang, detoxifying, and unblocking the meridians to treat diabetic nephropathy (heart and kidney yang deficiency syndrome). Compared with similar drugs, the formulation of this invention has sufficient theoretical basis in traditional Chinese medicine, mild medicinal properties, rigorous compatibility, clear pharmacodynamic substances, and significant clinical efficacy, achieving good results within three months.

[0020] This invention utilizes the principles of "warming Yang, detoxifying, and unblocking the meridians" to directly target the key aspects of the pathogenesis of diabetic kidney disease (DKD). Its advantages are: warming and tonifying the spleen and kidney Yang, strengthening the foundation and nourishing the source, resolving the root cause of Yang deficiency in DKD, restoring the kidney's Qi transformation function, improving fluid metabolism disorders, and reducing edema; detoxifying and clearing turbidity, removing pathological products, and reducing toxin accumulation; promoting blood circulation and unblocking the meridians, breaking through "kidney meridian obstruction," improving renal microcirculation, alleviating glomerular hyperfiltration, and combating fibrosis to delay the progression of diabetic nephropathy. This invention complements Western medicine treatments; in addition to lowering blood pressure and blood sugar, traditional Chinese medicine can reduce the side effects of hormones and immunosuppressants and slow the progression of renal interstitial fibrosis. Detailed Implementation

[0021] This invention provides a traditional Chinese medicine composition for treating diabetic nephropathy with deficiency of heart and kidney yang. By weight, it comprises the following components: Astragalus membranaceus 10-30 parts, Rehmannia glutinosa 10-30 parts, Pseudostellaria heterophylla 10-30 parts, Rheum palmatum 3-12 parts, Smilax glabra 40-60 parts, Morinda officinalis 10-15 parts, Cuscuta chinensis 10-15 parts, Justicia procumbens 40-60 parts, Anemarrhena asphodeloides 6-12 parts, Hirudo medicinalis 3-6 parts, Bombyx mori 3-9 parts, and Scrophularia ningpoensis 10-15 parts. Preferably, by weight, it comprises the following components: Astragalus membranaceus 30 parts, Rehmannia glutinosa 30 parts, Pseudostellaria heterophylla 20 parts, Rheum palmatum 6 parts, Smilax glabra 50 parts, Morinda officinalis 10 parts, Cuscuta chinensis 10 parts, Justicia procumbens 50 parts, Anemarrhena asphodeloides 9 parts, Hirudo medicinalis 3 parts, Bombyx mori 6 parts, and Scrophularia ningpoensis 15 parts.

[0022] Astragalus root, derived from the roots of *Astragalus membranaceus* Bge. var. *mongholicus* (Bge.) Hsiao and *A. membranaceus* (Fisch.) Bge. (Fabaceae family), is slightly warm in nature and sweet in taste. It enters the spleen and lung meridians. It belongs to the qi-tonifying category of tonifying herbs. Its functions include tonifying qi and raising yang, consolidating the exterior and stopping sweating, promoting diuresis and reducing edema, generating fluids and nourishing blood, promoting circulation and relieving pain, promoting pus drainage and detoxification, and promoting tissue regeneration and wound healing. It is commonly used to treat shortness of breath, palpitations, fatigue, collapse, spontaneous sweating, night sweats, edema due to weakness, chronic nephritis, chronic diarrhea, rectal prolapse, uterine prolapse, carbuncles that are difficult to ulcerate, slow-healing sores, childhood bronchial asthma, chronic hepatitis B, chronic nephritis, and viral myocarditis.

[0023] Prepared Rehmannia root, the fresh tuberous root of *Rehmannia glutinosa* Libosch. (family Scrophulariaceae), is processed by steaming and drying. It is slightly warm in nature and sweet in taste. It enters the liver and kidney meridians. It belongs to the blood-tonifying category of tonifying herbs. It has the effects of nourishing blood and yin, replenishing essence and marrow. It is used for blood deficiency and chlorosis, palpitations, irregular menstruation, metrorrhagia, liver and kidney yin deficiency, soreness and weakness of the lower back and knees, bone steaming fever, night sweats, seminal emission, internal heat and thirst, dizziness, tinnitus, and premature graying of hair.

[0024] *Pseudostellaria heterophylla* (Miq.) Pax ex Pax et Hoffm., a plant in the Caryophyllaceae family, is a tuberous root. It is neutral in nature, sweet and slightly bitter in taste. It enters the spleen and lung meridians. It belongs to the qi-tonifying category of tonifying herbs. It has the effects of invigorating qi and strengthening the spleen, promoting body fluid production and moistening the lungs. It is used to treat spleen deficiency with fatigue, loss of appetite, post-illness weakness, qi and yin deficiency, spontaneous sweating and thirst, and dry cough due to lung dryness.

[0025] Rhubarb is the dried root and rhizome of *Rheum palmatum*, L., *Rheum tanguticum* Maxim. ex Balf., or *Rheum oj-flcinale* Baill., belonging to the Polygonaceae family. It is cold in nature and bitter in taste. It enters the spleen, stomach, large intestine, liver, and pericardium meridians. It belongs to the purgative category of purgative drugs. It has the effects of purging heat and promoting bowel movement, cooling blood and detoxifying, and removing blood stasis and promoting menstruation. It is commonly used to treat constipation due to excess heat, abdominal pain due to stagnation, incomplete diarrhea, jaundice due to damp-heat, hematemesis due to blood heat, red eyes, swollen throat, intestinal abscesses and boils, amenorrhea due to blood stasis, and traumatic injuries.

[0026] Smilax glabra Roxb., a plant in the Liliaceae family, is a rhizome of this plant. It is neutral in nature and sweet and bland in taste. It enters the Stomach and Liver meridians. It belongs to the category of heat-clearing and dampness-drying herbs under the classification of heat-clearing herbs. It has the effects of detoxifying, eliminating dampness, and promoting joint mobility. It is used to treat damp-heat strangury, leukorrhea, carbuncles, scrofula, scabies, syphilis, and limb contractures and muscle and bone pain caused by mercury poisoning.

[0027] Morinda officinalis root, the dried root of Morinda officinalis How, a plant in the Rubiaceae family, has a sweet and pungent taste and is slightly warm in nature. It enters the kidney and liver meridians. It tonifies kidney yang, strengthens tendons and bones, and dispels wind and dampness. It is used for impotence, seminal emission, infertility due to cold uterus, irregular menstruation, lower abdominal pain due to cold, rheumatic pain, and weakness of tendons and bones.

[0028] Cuscuta chinensis Lam., a plant in the Convolvulaceae family, is a mature seed. It is neutral in nature and has a pungent and sweet taste. It enters the liver, kidney, and spleen meridians. It belongs to the yang-tonifying category of tonifying herbs. It has the effects of tonifying the kidneys and replenishing essence, nourishing the liver and improving eyesight. It is used for kidney deficiency causing lower back pain, impotence, premature ejaculation, cloudy urine, leukorrhea, frequent urination; threatened abortion; and liver and kidney deficiency causing blurred vision and decreased eyesight.

[0029] Rostellularia procumbens (L.) Nees [Justicia procumbens L.], a plant belonging to the genus Rostellularia in the family Acanthaceae. It has a bitter, salty, and pungent taste, and is cold in nature; it enters the lung, liver, and bladder meridians. It has the effects of clearing heat and detoxifying, promoting diuresis and eliminating stagnation, and activating blood circulation and relieving pain. It is mainly used to treat colds with fever, cough, sore throat, red and swollen eyes, malnutrition, damp-heat diarrhea, malaria, jaundice, edema, urinary tract infections, muscle and bone pain, traumatic injuries, carbuncles, boils, and eczema.

[0030] Anemarrhena asphodeloides Bge., a plant in the Liliaceae family, is a rhizome of this herb. It is cold in nature and has a bitter and sweet taste. It enters the Lung, Stomach, and Kidney meridians. It belongs to the category of heat-clearing and fire-purging herbs under the classification of heat-clearing herbs. It has the effects of clearing heat and purging fire, generating fluids and moistening dryness. It is commonly used to treat exogenous febrile diseases, high fever with thirst, dry cough due to lung heat, tidal fever due to bone steaming, internal heat with thirst, and constipation due to intestinal dryness.

[0031] Leeches refer to the entire body of several species of leeches, including *Hirudo niponica* and *Whitman*, belonging to the Hirudinidae family. They are neutral in nature, salty and bitter in taste, and slightly toxic. They enter the liver meridian. They belong to the category of blood-activating and menstruation-regulating drugs under the subclass of blood-activating and stasis-removing drugs. They have the effects of breaking up blood stasis, removing blood stasis, and promoting menstruation. They are used to treat abdominal masses, amenorrhea due to blood stasis, and traumatic injuries.

[0032] *Bombyx mori* L., a moth belonging to the Bombyx mori family, is the dried body of a silkworm larva that dies from infection with *Beauveria bassiana* (Bals.) Vaillant. It is neutral in nature and has a salty and pungent taste. It enters the liver, lung, and stomach meridians. It belongs to the category of wind-dispelling and spasm-relieving drugs under the subclass of liver-calming and wind-extinguishing drugs. It has the effects of dispelling wind and calming convulsions, resolving phlegm and dissipating nodules. It is used to treat infantile convulsions, sore throat, itchy skin, submandibular lymphadenitis, and facial nerve paralysis.

[0033] Scrophularia, the dried root of *Scrophu lenii* ningpoensis Hemsl. or *Scrophularia buergeriana* Miq. (S. oldhami Oliv.), belonging to the Scrophulariaceae family. It is slightly cold in nature and has a sweet, bitter, and salty taste. It enters the Lung, Stomach, and Kidney meridians. It belongs to the category of heat-clearing and blood-cooling herbs under the classification of heat-clearing herbs. It has the effects of cooling the blood and nourishing yin, purging fire and detoxifying. It is used to treat yin deficiency due to febrile diseases, red tongue with thirst, febrile rashes, constipation due to fluid depletion, steaming cough, red eyes, sore throat, scrofula, diphtheria, carbuncles and boils, and hypertension.

[0034] In this invention, Astragalus membranaceus and Rehmannia glutinosa, which are sweet and warm in nature, are the principal herbs, invigorating Yang and Qi, promoting diuresis and reducing swelling, nourishing Yin and tonifying the kidneys, and replenishing essence and marrow. Morinda officinalis warms and tonifies kidney Yang, strengthens tendons and bones, dispels wind and dampness, and assists the principal herbs in warming and tonifying kidney Yang; Rheum palmatum clears the bowels, eliminates turbidity and detoxifies; Hirudo medicinalis breaks up blood stasis and removes blood stasis, and unblocks the meridians and collaterals; Smilax glabra works synergistically with Rheum palmatum to eliminate turbidity and detoxify, and together they are the assistant herbs. Codonopsis pilosula assists Astragalus membranaceus in tonifying Qi and also generates body fluids, preventing the warm herbs from damaging Yin; Cuscuta chinensis tonifies Yin and Yang, benefits essence and astringes, assists Morinda officinalis in warming Yang, and reduces proteinuria; Justicia procumbens clears heat and detoxifies, promotes diuresis and reduces swelling, and assists Morinda officinalis in reducing its warming and drying properties; Anemarrhena asphodeloides clears heat and nourishes Yin, preventing Rheum palmatum and Justicia procumbens from damaging Yin due to their bitter and cold nature, and also restrains the warming properties of Morinda officinalis; Bombyx batryticatus resolves phlegm and dissipates nodules, dispels wind and unblocks the meridians, assists Hirudo medicinalis in removing blood stasis and unblocking the meridians, and also treats pruritus. The above herbs assist the principal and assistant herbs, and treat concurrent symptoms. The guiding herb, Scrophularia, is sweet, bitter, salty, and cold in nature. It nourishes Yin, reduces fire, detoxifies, and disperses nodules, guiding all the herbs into the kidney meridian and harmonizing the entire formula. This formula, through three-dimensional intervention of warming Yang, detoxifying, and unblocking the meridians, targets the pathogenesis of diabetic nephropathy characterized by "deficiency of the root and excess of the branch." The roles of the principal, assistant, and adjuvant herbs are clearly defined, making it suitable for the treatment of diabetic nephropathy (heart and kidney Yang deficiency syndrome). The characteristics of the composition of this invention are: sufficient theoretical basis for formulation, clear pharmacodynamic substances, and significant clinical efficacy.

[0035] The traditional Chinese medicine composition described in this invention can restore the kidney's qi transformation function by tonifying yang, reducing edema, and alleviating glomerular hyperfiltration. It also clears heat and dries dampness, eliminates turbidity and detoxifies, reducing toxin accumulation. It improves renal microcirculation to delay the progression of diabetic nephropathy. Efficacy: Warming and tonifying yang, detoxifying and eliminating turbidity, promoting blood circulation and unblocking collaterals. Indications: Suitable for chest tightness or chest pain, palpitations, aversion to cold and cold limbs, coldness in the lower back and knees, edema, purplish-dark tongue, white coating, deep, thready, weak or intermittent pulse, etc., caused by deficiency of heart and kidney yang; and diabetic nephropathy with the above symptoms.

[0036] This invention also provides a method for preparing the above-mentioned traditional Chinese medicine composition, comprising the following steps: mixing the components, adding water and decocting, and filtering the decoction; the amount of water added is 6 to 8 times the total mass of the mixed components, preferably 7 times. After adding water to the component mixture, the decoction is decocted under natural pressure to obtain a decoction; the number of decoctions is preferably 2 to 3 times, each time for 1 to 3 hours, preferably 2 hours each time. As an optional embodiment, after adding water and decocting, the decoction is filtered, the filtrate is collected, 6 to 8 times the amount of water is added to the residue for a second decoction, after which the decoction is filtered, the filtrate is collected, 6 to 8 times the amount of water is added to the residue for a third decoction, after which the decoction is filtered, the filtrate is collected, and the three filtrates are combined. As another optional embodiment, after adding water and decocting, the decoction is filtered, the filtrate is collected, 6 to 8 times the amount of water is added to the residue for a second decoction, after which the decoction is filtered, the filtrate is collected, and the two filtrates are combined.

[0037] The present invention further includes the following steps: filtering the decoction, concentrating the filtrate, and drying. After adding water to the component mixture described in the present invention, it is decocted under natural pressure. The number of decoctions is 2-3 times, each time for 1-3 hours, preferably 2 hours each time. As an optional embodiment, after adding water and decocting, the decoction is filtered, the filtrate is collected, 6-8 times the amount of water is added to the filter residue for a second decoction, after which the decoction is filtered, the filtrate is collected, 6-8 times the amount of water is added to the filter residue for a third decoction, after which the decoction is filtered, the filtrate is collected, and the three filtrates are combined. As another optional embodiment, after adding water and decocting, the decoction is filtered, the filtrate is collected, 6-8 times the amount of water is added to the filter residue for a second decoction, after which the decoction is filtered, the filtrate is collected, and the two filtrates are combined.

[0038] The concentrate described in this invention is an extract with a relative density of 1.20–1.25, concentrated to 60°C. The concentration method described in this invention can be water bath concentration. The drying method described in this invention includes vacuum drying. After drying, the product is pulverized into a fine powder for use in the preparation of corresponding dosage forms.

[0039] This invention also provides the application of the above-mentioned traditional Chinese medicine composition in the preparation of a medicine for treating diabetic nephropathy with deficiency of heart and kidney yang.

[0040] This invention also provides a medicament for treating diabetic nephropathy with deficiency of heart and kidney yang, the medicament comprising the above-mentioned traditional Chinese medicine composition and pharmaceutically acceptable excipients. This invention uses the above-mentioned traditional Chinese medicine composition as the active pharmaceutical ingredient, and the excipients are used to ensure the convenient preparation and clinical application of the prepared medicament for treating diabetic nephropathy with deficiency of heart and kidney yang. More preferably, the excipients of this invention include, but are not limited to, at least one of diluents, wetting agents, binders, lubricants, colorants, and coating agents.

[0041] Preferably, the dosage form of the drug for treating diabetic nephropathy with deficiency of heart and kidney yang according to the present invention includes tablets, decoctions, capsules, granules, pills, suspensions, dispersants, or syrups. The dosage form of the drug according to the present invention is not limited to these; other achievable dosage forms are within the scope of protection of the present invention.

[0042] The technical solutions of this invention will be clearly and completely described below with reference to the embodiments thereof. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0043] Unless otherwise specified, the following embodiments are all conventional methods.

[0044] Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

[0045] Example 1

[0046] A traditional Chinese medicine composition for treating diabetic nephropathy with deficiency of heart and kidney yang: Astragalus membranaceus 10g, Rehmannia glutinosa 10g, Codonopsis pilosula 10g, Rheum palmatum 3g, Smilax glabra 40g, Morinda officinalis 10g, Cuscuta chinensis 10g, Justicia procumbens 40g, Anemarrhena asphodeloides 6g, Hirudo medicinalis 3g, Bombyx mori 3g, and Scrophularia ningpoensis 10g.

[0047] Preparation method: Mix the components in proportion, add 6 times the total mass of water, and decoct under natural pressure for 1 hour. Filter the decoction, collect the filtrate, add 6 times the amount of water to the residue, and decoct a second time for 1 hour. Filter the decoction again, collect the filtrate, add 6 times the amount of water to the residue, and decoct a third time for 1 hour. Filter the decoction again, collect the filtrate, and combine the three filtrates. Concentrate the filtrate in a water bath to a relative density of 1.20 (60℃) to obtain an extract, dry under reduced pressure, and then pulverize into a fine powder.

[0048] Example 2

[0049] A traditional Chinese medicine composition for treating diabetic nephropathy with deficiency of heart and kidney yang: Astragalus membranaceus 30g, Rehmannia glutinosa 30g, Codonopsis pilosula 30g, Rheum palmatum 12g, Smilax glabra 60g, Morinda officinalis 15g, Cuscuta chinensis 15g, Justicia procumbens 60g, Anemarrhena asphodeloides 12g, Hirudo medicinalis 6g, Bombyx mori 9g, and Scrophularia ningpoensis 15g.

[0050] Preparation method: Mix the components in proportion, add 7 times the total mass of water, and decoct for 3 hours under natural pressure. Filter the decoction, collect the filtrate, add 7 times the amount of water to the residue, and decoct a second time for 3 hours. Filter the decoction again, collect the filtrate, add 7 times the amount of water to the residue, and decoct a third time for 3 hours. Filter the decoction again, collect the filtrate, and combine the three filtrates. Concentrate the filtrate in a water bath to a relative density of 1.25 (60℃) to obtain an extract, dry under reduced pressure, and then pulverize into a fine powder.

[0051] Example 3

[0052] A traditional Chinese medicine composition for treating diabetic nephropathy with deficiency of heart and kidney yang: Astragalus membranaceus 30g, Rehmannia glutinosa 30g, Codonopsis pilosula 20g, Rheum palmatum 6g, Smilax glabra 50g, Morinda officinalis 10g, Cuscuta chinensis 10g, Justicia procumbens 50g, Anemarrhena asphodeloides 9g, Hirudo medicinalis 3g, Bombyx mori 6g, and Scrophularia ningpoensis 15g.

[0053] Preparation method: Mix the components in proportion, add 8 times the total mass of water, and decoct under natural pressure for 2 hours. Filter the decoction, collect the filtrate, add 8 times the amount of water to the residue, and decoct a second time for 2 hours. Filter the decoction again, collect the filtrate, add 8 times the amount of water to the residue, and decoct a third time for 2 hours. Filter the decoction again, collect the filtrate, and combine the three filtrates. Concentrate the filtrate in a water bath to a relative density of 1.25 (60℃) to obtain an extract, dry under reduced pressure, and then pulverize into a fine powder.

[0054] Example 4

[0055] A traditional Chinese medicine composition for treating diabetic nephropathy with deficiency of heart and kidney yang: Astragalus membranaceus 30g, Rehmannia glutinosa 30g, Codonopsis pilosula 20g, Rheum palmatum 6g, Smilax glabra 50g, Morinda officinalis 10g, Cuscuta chinensis 10g, Justicia procumbens 50g, Anemarrhena asphodeloides 9g, Hirudo medicinalis 3g, Bombyx mori 6g, and Scrophularia ningpoensis 15g.

[0056] Preparation method: Mix the components in proportion, add 8 times the total mass of water, and decoct for 2 hours under natural pressure. Filter the decoction and collect the filtrate. Add 8 times the amount of water to the residue and decoct a second time for 2 hours. Filter the decoction and collect the filtrate. Combine the two filtrates.

[0057] Example 5

[0058] A traditional Chinese medicine composition for treating diabetic nephropathy with deficiency of heart and kidney yang: Astragalus membranaceus 30g, Rehmannia glutinosa 30g, Codonopsis pilosula 20g, Rheum palmatum 6g, Smilax glabra 50g, Morinda officinalis 10g, Cuscuta chinensis 10g, Justicia procumbens 50g, Anemarrhena asphodeloides 9g, Hirudo medicinalis 3g, Bombyx mori 6g, and Scrophularia ningpoensis 15g.

[0059] Preparation method: Mix the components in proportion, add 7 times the total mass of water, and decoct for 3 hours under natural pressure. Filter the decoction and collect the filtrate. Add 7 times the amount of water to the residue and decoct a second time. After decoction for 2 hours, filter the decoction and collect the filtrate. Add 8 times the amount of water to the residue and decoct a third time. After decoction for 1 hour, filter the decoction and collect the filtrate. Combine the three filtrates.

[0060] Test case

[0061] 1. Disease diagnosis:

[0062] 1.1. Referring to the "Chinese Guidelines for Clinical Diagnosis and Treatment of Diabetic Kidney Disease": Patients meeting the ADA 2020 diagnostic criteria for diabetes mellitus (DM), with a clear history of DM, a causal relationship between DM and changes in urine protein and renal function, and after excluding other primary and secondary glomerular diseases and systemic diseases, and meeting one of the following criteria, can be diagnosed with DKD: 1. Random urine albumin / creatinine ratio >30 mg / g or urine albumin excretion rate >30 mg / 24h, and repeated UACR or UAER tests within 3–6 months, with 2 out of 3 tests reaching or exceeding the cutoff value; excluding other confounding factors such as infection. Estimated glomerular filtration rate <60 ml / min. -1 (1.73m 2 1) More than 13 months. 3. Kidney biopsy consistent with DKD pathological changes.

[0063] 1.2. Diagnostic criteria for TCM syndromes: (Refer to the <Guidelines for the Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment of Diabetic Kidney Disease>).

[0064] Main symptoms: ① Chest tightness or chest pain; ② Palpitation; ③ Cold limbs; ④ Coldness in the lower back and knees; ⑤ Edema.

[0065] Secondary symptoms: ① Dark purple tongue with white coating; ② Deep, thready, weak, or intermittent pulse.

[0066] A diagnosis can be made if the main symptom is present in one of ① or ② and one of ③, ④ or ⑤, and one of the secondary symptoms is also present.

[0067] 2. Research Methods

[0068] 2.1 Inclusion criteria:

[0069] (1) Meets the diagnostic criteria for diabetic nephropathy and the TCM diagnostic criteria for heart and kidney yang deficiency syndrome;

[0070] (2) The patient's basic information, present medical history, four diagnostic methods, and prescription medication were collected in a standardized manner and met the criteria for heart and kidney yang deficiency syndrome;

[0071] (3) Regular oral administration of traditional Chinese medicine for at least 4 weeks.

[0072] (4) Voluntarily participate in this study and sign the informed consent form.

[0073] 2.2 Exclusion Criteria:

[0074] (1) Patients with diabetic nephropathy who also have other types of kidney disease;

[0075] (2) Patients with a history of critical illnesses such as malignant hypertension, myocardial infarction, cerebrovascular accident, or diabetic ketoacidosis;

[0076] (3) Individuals who are known to be allergic to any of the ingredients in the study drug, or who have an allergic constitution;

[0077] (4) When the clinical researcher believes that the subjects participating in the clinical study cannot cooperate with the observation.

[0078] 2.3 Research Methods:

[0079] Patients were enrolled according to inclusion and exclusion criteria and randomly divided into a traditional Chinese medicine (TCM) group and a control group using a random number table. Both groups received basic treatment. Basic treatment included dietary management: high-quality protein intake of 0.8 g / kg / day and salt intake of <5 g / day. Patients also used ACEI / ARB, SGLT2 inhibitors, and statins to control blood pressure, blood sugar, and blood lipids. In addition to basic treatment, the TCM group received the TCM composition of this invention (prepared in Example 5). Efficacy evaluation indicators included a TCM syndrome scoring scale, and renal function, 24-hour urine protein quantification, urinalysis, and urine albumin / creatinine ratio were examined. Glomerular filtration rate was estimated and statistically analyzed. Safety evaluation indicators included blood routine, liver function, renal function, and urine albumin / creatinine ratio, and statistically analyzed.

[0080] 3. Efficacy criteria

[0081] This was formulated with reference to the relevant schemes of the "Traditional Chinese Medicine Clinical Pathway for Early and Mid-Stage Diabetes and Nephropathy" and the "Traditional Chinese Medicine Clinical Pathway for Late-Stage Diabetes and Nephropathy" proposed by the Department of Medical Administration of the State Administration of Traditional Chinese Medicine in 2011, which covered 22 specialties and 95 diseases.

[0082] 3.1 Traditional Chinese Medicine Syndrome Therapy Standards:

[0083] 3.1.1 Criteria for evaluating the efficacy of treatment for early diabetic nephropathy syndromes:

[0084] (1) Significant effect: The score of the main clinical symptoms decreased by ≥50%.

[0085] (2) Effective: The score of the main clinical symptoms decreased by ≥30% but <50%.

[0086] (3) Invalid: Those that do not meet the above valid standards.

[0087] 3.1.2. Criteria for evaluating the efficacy of treatment for mid-stage diabetic nephropathy syndromes:

[0088] (1) Significant effect: The score of the main clinical symptoms decreased by ≥50%.

[0089] (2) Effective: The score of the main clinical symptoms decreased by ≥30% but <50%.

[0090] (3) Invalid: Those that do not meet the above valid standards.

[0091] 3.1.3 Criteria for Evaluating the Treatment Efficacy of End-Stage Diabetic Nephropathy Syndromes:

[0092] (1) Significant effect: Clinical symptom score reduced by ≥30%.

[0093] (2) Effective: Clinical symptom score reduced by ≥15%, but <30%.

[0094] (3) Invalid: Those that do not meet the above valid standards.

[0095] 3.2 Evaluation criteria for comprehensive treatment efficacy:

[0096] 3.2.1 Criteria for early-stage diabetic nephropathy:

[0097] (1) Significant effect: The main clinical symptom score is reduced by ≥50%, the UACR is reduced by ≥50%, or it returns to normal.

[0098] (2) Effective: The main clinical symptom score decreased by ≥30% but <50%, and the UACR decreased by ≥30% but <50%.

[0099] (3) Invalid: Those that do not meet the above valid standards.

[0100] 3.2.2 Criteria for Evaluating the Treatment Efficacy of Mid-Stage Diabetic Nephropathy:

[0101] (1) Significant effect: The main clinical symptom score is reduced by ≥50%, the urinary protein quantification is reduced by ≥50%, or returns to normal.

[0102] (2) Effective: The main clinical symptom score decreased by ≥30% but <50%, and the quantitative urine protein decreased by ≥30% but <50%.

[0103] (3) Invalid: Those that do not meet the above valid standards.

[0104] 3.2.3 Criteria for evaluating the efficacy of treatment in advanced diabetic nephropathy:

[0105] (1) Significant effect: Clinical symptom score decreased by ≥30%, eGFR increased by ≥10% within 3 months, or serum creatinine decreased by ≥10%.

[0106] (2) Effective: Clinical symptom score decreased by ≥15% but <30%, eGFR stabilized within 3 months, or increased by <10%, or serum creatinine stabilized, or decreased by <10%.

[0107] (3) Invalid: Those that do not meet the above valid standards.

[0108] 3.3 Criteria for Determining Disease-Related Indicators:

[0109] 3.3.1 Criteria for determining early diabetic nephropathy-related indicators:

[0110] (1) Significant effect: UACR decreases by ≥50%, or returns to normal.

[0111] (2) Effective: UACR ≥ 30%, but < 50%.

[0112] (3) Invalid: Those that do not meet the above valid standards.

[0113] 3.3.2. Criteria for determining relevant indicators of mid-stage diabetic nephropathy:

[0114] (1) Significant effect: Quantitative reduction of urinary protein ≥50%.

[0115] (2) Effective: Quantitative urine protein ≥30%, but <50%.

[0116] (3) Invalid: Those that do not meet the above valid standards.

[0117] 3.3.3 Assessment criteria for relevant indicators of advanced diabetic nephropathy:

[0118] (1) Significant effect: eGFR increases by ≥10% or serum creatinine decreases by ≥10% within 3 months.

[0119] (2) Effective: eGFR is stable or increases by <10% within 3 months, or serum creatinine is stable or decreases by <10%.

[0120] (3) Invalid: Those that do not meet the above valid standards.

[0121] 3.4 Observation Indicators:

[0122] (1) Therapeutic indicators:

[0123] UMA, 24-hour urine protein quantification, eGFR, and renal function; information from the four diagnostic methods of Traditional Chinese Medicine (TCM syndrome scale as shown in Table 1). Observations and records were made before and at the end of treatment.

[0124] Table 1 Traditional Chinese Medicine Syndrome Scale

[0125]

[0126]

[0127] (2) Other observation indicators:

[0128] ① Demographic information: gender, age, long-term living region, diet, personal history, history of IgA nephropathy, etc.

[0129] ② Physical examination information: height, weight, blood pressure, etc.

[0130] (3) Safety indicators: Observe blood routine, liver function, electrocardiogram, etc. before and after treatment, ask the patient if there are any obvious discomfort symptoms after taking the medicine and record them in time.

[0131] 4. Experimental Results and Analysis:

[0132] Table 2 Comparison of efficacy and total effective rate between the two groups of patients with diabetic nephropathy

[0133] Group Number of examples Significant effect (number of cases) Valid (number of cases) Invalid (number of cases) Overall effectiveness (%) Traditional Chinese Medicine Group 41 20 16 5 <![CDATA[87.8 # ]]> control group 43 21 12 10 76.7

[0134] Note: Compared with the control group, #P<0.05.

[0135] As shown in Table 2, compared with the control group, the total effective rate of the traditional Chinese medicine group was significantly higher, which was statistically significant (P<0.05).

[0136] Table 3 Comparison of symptom quantification scores between the two groups of diabetic nephropathy patients (x±s)

[0137]

[0138] Note: Compared with the control group, #P<0.05.

[0139] As shown in Table 3, the scores of both primary and secondary symptoms decreased after treatment in both groups. Compared with the control group, the scores of primary and secondary symptoms in the traditional Chinese medicine group decreased significantly after treatment, which was statistically significant (P < 0.05).

[0140] Table 4 Comparison of 24-hour urinary protein quantification and UMA between the two groups of diabetic nephropathy patients

[0141]

[0142] Note: # indicates the comparison with before treatment, ▲ indicates the comparison between the control group and the traditional Chinese medicine group, #P<0.05, ▲P<0.05.

[0143] As shown in Table 4, compared with before treatment, the 24-hour urinary protein quantification and UMA decreased in both groups after treatment, which was statistically significant (P<0.05). After treatment, compared with the control group, the 24-hour urinary protein quantification and UMA decreased significantly in the traditional Chinese medicine group, which was statistically significant (P<0.05).

[0144] Table 5 Comparison of renal function between the two groups of diabetic nephropathy patients

[0145]

[0146] Note: Compared with before treatment, #P<0.05.

[0147] Table 6 Comparison of glomerular filtration rate between the two groups of diabetic nephropathy patients

[0148]

[0149] Note: Compared with before treatment, #P<0.05.

[0150] As shown in Tables 5 and 6, compared with before treatment, renal function and glomerular filtration rate were significantly improved in both the control group and the traditional Chinese medicine group after treatment, with statistical significance (P<0.05). After treatment, there was no significant difference in renal function and glomerular filtration rate between the traditional Chinese medicine group and the control group.

[0151] Typical Cases

[0152] Mr. Li, male, 51 years old, first visit on July 29, 2024. Chief complaint: Intermittent bilateral lower extremity edema for 4 months. Present illness: 4 months ago, he developed bilateral lower extremity edema without obvious cause, along with nausea, poor appetite, fatigue, tinnitus, cold intolerance, nocturia (twice), constipation, and nocturnal chest tightness and shortness of breath. Physical examination: Pale tongue, white coating, thready pulse. Auxiliary examinations: Urinalysis: proteinuria +3, occult blood 1+. 24-hour urine protein quantification: 1.31g / 24h; Renal function tests: blood urea nitrogen 7.33mmol / L, serum creatinine 229.6umol / L. Renal biopsy results: Moderate to severe mesangial proliferative diabetic nephropathy (IIb).

[0153] Traditional Chinese Medicine Diagnosis: Diabetes mellitus (Heart and Kidney Yang Deficiency Syndrome).

[0154] Western medical diagnosis: Diabetic nephropathy.

[0155] Treatment principle: Warm the Yang and benefit the kidneys, detoxify and unblock the meridians.

[0156] Usage: Take 450ml of the decoction prepared in Example 5, 150ml each time, orally twice a day.

[0157] Second visit findings: Improved bilateral lower extremity edema, nausea, and poor appetite, but still fatigued. Physical examination: Pale tongue with white coating, thready and wiry pulse. Auxiliary examinations: Urinalysis: proteinuria +3, occult blood -; 24-hour urine protein quantification: 1.17g / 24h; renal function: blood urea nitrogen 6.27mmol / L, serum creatinine 187.4μmol / L.

[0158] The third examination revealed: no obvious edema, improved fatigue, but persistent tinnitus. Physical examination: pale red tongue with a thin white coating, and thready pulse. Auxiliary examinations: urinalysis: proteinuria +2, occult blood -; 24-hour urine protein quantification: 0.95g / 24h; renal function tests: blood urea nitrogen 6.12mmol / L, serum creatinine 172.7μmol / L.

[0159] Six months later, a follow-up urinalysis showed: urine protein +1, occult blood -; 24-hour urine protein quantification: 0.83g / 24h; renal function: blood urea nitrogen 5.96mmol / L, serum creatinine 168.4μmol / L.

[0160] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine composition for treating diabetic nephropathy with deficiency of heart and kidney yang, characterized in that, By weight, it includes the following components: Astragalus membranaceus 10-30 parts, Rehmannia glutinosa 10-30 parts, Codonopsis pilosula 10-30 parts, Rheum palmatum 3-12 parts, Smilax glabra 40-60 parts, Morinda officinalis 10-15 parts, Cuscuta chinensis 10-15 parts, Justicia procumbens 40-60 parts, Anemarrhena asphodeloides 6-12 parts, Hirudo medicinalis 3-6 parts, Bombyx mori 3-9 parts, and Scrophularia ningpoensis 10-15 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The product comprises the following components by weight: 30 parts Astragalus membranaceus, 30 parts Rehmannia glutinosa, 20 parts Codonopsis pilosula, 6 parts Rheum palmatum, 50 parts Smilax glabra, 10 parts Morinda officinalis, 10 parts Cuscuta chinensis, 50 parts Justicia procumbens, 9 parts Anemarrhena asphodeloides, 3 parts Hirudo medicinalis, 6 parts Bombyx mori, and 15 parts Scrophularia ningpoensis.

3. The preparation method of the traditional Chinese medicine composition according to any one of claims 1-2, characterized in that, Includes the following steps: The components are mixed, water is added and decocted, and the decoction is filtered; the amount of water added is 6 to 8 times the total mass of the mixed components.

4. The production method according to claim 3, characterized by, It also includes the following steps: The decoction is filtered, and the filtrate is concentrated and dried.

5. The preparation method according to claim 4, characterized in that, The decoction is prepared 2 to 3 times, each time for 1 to 3 hours.

6. The preparation method according to claim 4, characterized in that, The concentrate is an extract with a relative density of 1.20 to 1.25 when concentrated to 60°C.

7. The preparation method according to claim 4, characterized in that, The drying method includes vacuum drying.

8. The use of the traditional Chinese medicine composition according to any one of claims 1 to 2 in the preparation of a medicament for treating diabetic nephropathy with deficiency of heart and kidney yang.

9. A medicine for treating diabetic nephropathy with heart-kidney yang deficiency syndrome, characterized in that, The drug comprises the traditional Chinese medicine composition according to any one of claims 1 to 2 and pharmaceutically acceptable excipients.

10. The medicament according to claim 9, characterized in that, The dosage forms of the drug include tablets, decoctions, capsules, granules, pills, suspensions, dispersants, or syrups.

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