Application method of traditional Chinese medicine composition for treating common diseases of diabetes and coronary heart disease

Abstract

The invention relates to the technical field of application processes of traditional Chinese medicine compositions, and particularly discloses an application method of a traditional Chinese medicine composition for treating common diseases of diabetes and coronary heart disease, and the application method comprises the following steps: pre-treating astragalus membranaceus, dried dendrobe, radix puerariae, pseudo-ginseng, salvia miltiorrhiza, coptis chinensis tablets and lophatherum gracile for later use; crushing pseudo-ginseng to prepare pseudo-ginseng micro-capsules; carrying out segmented targeted extraction on water-soluble components and fat-soluble components in the traditional Chinese medicine components; integrating the two extracting solutions, adding the pseudo-ginseng micro-capsules, grinding, and sequentially performing concentration, sterilization and filling treatment. According to the invention, the dissolution rate of effective components in the traditional Chinese medicine composition is improved and the use effect is enhanced through a segmented targeted extraction process of the water-soluble component and the fat-soluble component; meanwhile, the retention rate of notoginsenoside R1 is increased through a pseudo-ginseng micro-capsule preparation process; in addition, bottled liquid is prepared, a traditional decocting application method of traditional Chinese medicine is abandoned, the purity of the liquid medicine is greatly improved, and the preservation time is greatly prolonged.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine composition application technology, and more specifically, to a method for applying a traditional Chinese medicine composition for treating comorbid diabetes and coronary heart disease. Background Technology

[0002] With an aging population and changing lifestyles, diabetes-coronary comorbidity has become a major public health issue in the global cardiovascular disease field. From a pathological perspective, the comorbidity of diabetes and coronary heart disease presents a "double vicious cycle": on the one hand, long-term hyperglycemia leads to the accumulation of advanced glycation end products (AGEs), damaging vascular endothelial cells and promoting the formation of atherosclerotic plaques in the coronary arteries (plaque stability decreases, making them prone to rupture); on the other hand, insufficient coronary blood supply leads to impaired energy metabolism in myocardial cells, further aggravating insulin resistance (decreased glucose uptake and utilization by myocardial cells), forming a pathological closed loop of "hyperglycemia-vascular damage-myocardial ischemia-insulin resistance." Clinically, comorbid patients often present with two core problems simultaneously: ① metabolic abnormalities (fasting blood glucose ≥7.0 mmol / L, glycated hemoglobin ≥7.0%); ② cardiovascular dysfunction (coronary artery stenosis ≥50%, decreased left ventricular diastolic function, microcirculatory blood flow velocity <35 μm / s), and are often accompanied by the TCM syndrome of "deficiency of both qi and yin with blood stasis" (dry mouth without thirst, shortness of breath after exertion, fixed chest pain, dark purple tongue with ecchymosis). Currently, there are still significant technological gaps in the clinical treatment of diabetes mellitus and coronary heart disease comorbidities, specifically manifested in the following ways: Current Western medicine regimens often employ a combination of hypoglycemic agents and cardiovascular protective drugs, such as metformin, aspirin, and statins. However, these regimens have three major drawbacks: ① They target only a single point of action, failing to simultaneously improve the triple pathological links of "metabolic abnormalities, vascular damage, and microcirculatory disturbances." For example, metformin only lowers blood sugar but does not improve coronary plaque stability, and aspirin only inhibits platelet aggregation but cannot reverse insulin resistance. ② They carry a high risk of cumulative side effects. Comorbid patients are mostly middle-aged and elderly, and long-term use of statins can easily lead to elevated liver enzymes and muscle damage. When combined with metformin, the incidence of gastrointestinal adverse reactions reaches 25.1%, resulting in poor patient compliance. ③ They cannot improve traditional Chinese medicine syndromes. Western medicines have a relief rate of less than 40% for symptoms such as dry mouth, fatigue, and chest pain in comorbid patients, making it difficult to achieve comprehensive improvement in "symptoms-indicators-prognosis."

[0003] In the field of Traditional Chinese Medicine (TCM), the treatment principles for diabetes-coronary heart disease comorbidity are often "tonifying qi and nourishing yin" and "activating blood circulation and removing blood stasis." However, existing TCM treatment plans have the following technical shortcomings: Insufficient adaptability to the pathogenesis: Most of the compositions only focus on a single syndrome. For example, Astragalus oral liquid, which simply replenishes Qi, cannot improve coronary blood stasis, and Danshen dripping pill, which simply invigorates blood, cannot correct the deficiency of both Qi and Yin. This leads to "replenishment but stagnation" (aggravating vascular blockage) or "invigorating blood but depleting Qi" (aggravating fatigue symptoms), which cannot meet the complex pathogenesis of "deficiency of both Qi and Yin as the root and blood stasis and internal heat as the manifestation". Application methods limit efficacy: Traditional decoction methods have a high rate of destruction of heat-sensitive active ingredients in Chinese medicine. For example, the retention rate of Dendrobium polysaccharide (protects the heart and improves insulin resistance) is only 40%, and the retention rate of Panax notoginseng saponin R1 (anti-platelet aggregation and improves coronary microcirculation) is less than 37%. In addition, the decoction has a high content of impurities and a bitter taste, resulting in low compliance of patients with comorbidities to take it for a long time. Therefore, it is necessary to design an application method for a traditional Chinese medicine composition for treating comorbid diabetes and coronary heart disease, in order to solve the problems of insufficient pathogenesis adaptability and application method limitation of existing traditional Chinese medicine regimens for diabetes-coronary heart disease comorbidity. Summary of the Invention

[0004] In view of this, the present invention proposes an application method of a traditional Chinese medicine composition for treating comorbid diabetes and coronary heart disease, in order to solve the problems of insufficient pathogenesis adaptability of existing traditional Chinese medicine regimens for diabetes-coronary heart disease comorbidity and the limitation of efficacy by application methods.

[0005] This invention provides a method for using a traditional Chinese medicine composition for treating comorbid diabetes and coronary heart disease, comprising the following steps: Pre-treat the following ingredients: Astragalus membranaceus, Dendrobium nobile, Pueraria lobata, Panax notoginseng, Salvia miltiorrhiza, Coptis chinensis slices, and Lophatherum gracile. The pretreated Panax notoginseng was crushed to obtain Panax notoginseng powder. Hydroxypropyl methylcellulose and gum arabic were mixed and then water was added and stirred until dissolved to obtain a wall material solution. After adding the Panax notoginseng powder to the wall material solution, high-speed shearing is performed to form a primary emulsion. The primary emulsion is then spray-dried to obtain Panax notoginseng microcapsules. Water and cellulase were added to the pretreated Astragalus membranaceus, Dendrobium nobile, Pueraria lobata and Lophatherum gracile to extract water-soluble components. Ultrasonic extraction was performed during the extraction process. After the extraction was completed, the mixture was filtered to obtain the water-soluble extract. After adding ethanol solution and vitamin E to the pretreated Salvia miltiorrhiza and Coptis chinensis tablets, the fat-soluble components were extracted. The extracted solution was then filtered to obtain the fat-soluble extract. Anhydrous ethanol was added to the water-soluble extract and the fat-soluble extract, followed by the addition of diatomaceous earth. The mixture was then stirred, and after the stirring was completed, it was allowed to stand and filtered to obtain the integrated extract. The Panax notoginseng microcapsules were added to the integrated extract and ground. After grinding, the pH of the system was adjusted to 6.0 to obtain the initial drug solution. The initial medicinal solution is sequentially concentrated, sterilized, and filled to obtain a traditional Chinese medicine composition filling solution for treating comorbid diabetes and coronary heart disease.

[0006] Furthermore, the mass ratio of hydroxypropyl methylcellulose to gum arabic is 3:1, and the total mass of hydroxypropyl methylcellulose and gum arabic is 1.5 times that of the Panax notoginseng powder.

[0007] Furthermore, the inlet air temperature of the spray drying process is 170-190℃, the outlet air temperature is 70-90℃, and the feeding rate is 15-25ml / min.

[0008] Furthermore, the extraction of water-soluble components specifically involves adjusting the pH of the mixture containing cellulase to 4.5 using citric acid, and stirring at 60-100 r / min for 2-3 hours at a temperature of 50-60℃.

[0009] Furthermore, the ultrasonic power is 300W and the frequency is 20kHz; the ultrasonic working mode is: it is turned on synchronously with stirring, first ultrasonic for 10 minutes, and then ultrasonic for 10 minutes every 30 minutes.

[0010] Furthermore, the extraction of the fat-soluble components specifically involves heating to 75°C, maintaining the temperature, and refluxing for 1.5-2.5 hours.

[0011] Furthermore, the grinding process is carried out at a speed of 2500-3500 r / min for 15-25 minutes, and nitrogen gas is introduced at a flow rate of 5 L / min during the grinding process.

[0012] Furthermore, the concentration specifically involves: subjecting the initial drug solution to a triple-effect concentration process, setting the first effect vacuum degree to -0.09 MPa and the temperature to 65°C, the second effect vacuum degree to -0.08 MPa and the temperature to 60°C, and the third effect vacuum degree to -0.07 MPa and the temperature to 55°C, while simultaneously adding 0.8% by weight of β-cyclodextrin to the initial drug solution, stirring at a speed of 60 r / min, and stopping the concentration when the relative density of the system at 60°C is between 1.12 and 1.15.

[0013] Furthermore, the sterilization specifically involves subjecting the concentrated initial drug solution to ultra-high temperature instantaneous sterilization treatment, setting the sterilization temperature to 135°C and the sterilization time to 5 seconds. After the sterilization is completed, the drug solution is first cooled to 60°C with cold water, and then cooled to 30°C with ice water.

[0014] Furthermore, the filling process specifically involves sterilizing the pharmaceutical glass bottle with high-pressure steam at 121°C for 30 minutes, injecting the sterilized initial drug solution into the pharmaceutical glass bottle at a dosage of 100ml / bottle, and sealing it with an aluminum-plastic composite cap.

[0015] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. This invention uses Astragalus membranaceus, Dendrobium nobile, Pueraria lobata, Salvia miltiorrhiza, Panax notoginseng powder, Coptis chinensis tablets, and Lophatherum gracile as the main Chinese herbal ingredients in the composition. It targets the complex pathogenesis of diabetes-coronary heart disease, which is characterized by deficiency of both Qi and Yin, and blood stasis and internal heat. It solves the pathogenesis adaptability defects of traditional Chinese medicine, such as "tonifying but causing stagnation" or "activating blood and depleting Qi", and achieves a triple synergistic effect of "lowering blood sugar, protecting the heart and improving symptoms".

[0016] 2. This invention utilizes a segmented targeted extraction process for water-soluble and fat-soluble components, combined with ultrasound and enzymatic hydrolysis assistance, to significantly improve the dissolution rate of active ingredients in traditional Chinese medicine compositions, thereby enhancing their efficacy.

[0017] 3. This invention significantly improves the retention rate of notoginsenoside R1 in Panax notoginseng through the preparation process of Panax notoginseng microcapsules, and solves the defects of heat-sensitive destruction and uneven dissolution of notoginsenosides in traditional processes.

[0018] 4. This invention prepares a bottled medicine that can be taken orally directly through extraction, mixing, concentration, sterilization and filling processes, abandoning the traditional decoction method of Chinese medicine and greatly improving the purity and shelf life of the medicine. Attached Figure Description

[0019] Various other advantages and benefits will become apparent to those skilled in the art upon reading the following detailed description of preferred embodiments. The accompanying drawings are for illustrative purposes only and are not intended to limit the invention. Furthermore, the same reference numerals denote the same parts throughout the drawings. In the drawings: Figure 1 A flowchart illustrating the application method of a traditional Chinese medicine composition for treating comorbid diabetes and coronary heart disease, as provided in an embodiment of the present invention. Detailed Implementation

[0020] Exemplary embodiments of the present disclosure will now be described in more detail with reference to the accompanying drawings. While exemplary embodiments of the present disclosure are shown in the drawings, it should be understood that the present disclosure may be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided to enable a more thorough understanding of the present disclosure and to fully convey the scope of the disclosure to those skilled in the art. It should be noted that, unless otherwise specified, embodiments and features in the embodiments of the present invention can be combined with each other. The present invention will now be described in detail with reference to the accompanying drawings and embodiments.

[0021] like Figure 1 As shown in some embodiments of this application, a method of applying a traditional Chinese medicine composition for treating comorbid diabetes and coronary heart disease includes the following steps: Pre-treat the following ingredients: Astragalus membranaceus, Dendrobium nobile, Pueraria lobata, Panax notoginseng, Salvia miltiorrhiza, Coptis chinensis slices, and Lophatherum gracile. The pretreated Panax notoginseng was crushed to obtain Panax notoginseng powder. Hydroxypropyl methylcellulose and gum arabic were mixed and then water was added and stirred until dissolved to obtain a wall material solution. After adding the Panax notoginseng powder to the wall material solution, high-speed shearing is performed to form a primary emulsion. The primary emulsion is then spray-dried to obtain Panax notoginseng microcapsules. Water and cellulase were added to the pretreated Astragalus membranaceus, Dendrobium nobile, Pueraria lobata and Lophatherum gracile to extract water-soluble components. Ultrasonic extraction was performed during the extraction process. After the extraction was completed, the mixture was filtered to obtain the water-soluble extract. After adding ethanol solution and vitamin E to the pretreated Salvia miltiorrhiza and Coptis chinensis tablets, the fat-soluble components were extracted. The extracted solution was then filtered to obtain the fat-soluble extract. Anhydrous ethanol was added to the water-soluble extract and the fat-soluble extract, followed by the addition of diatomaceous earth. The mixture was then stirred, and after the stirring was completed, it was allowed to stand and filtered to obtain the integrated extract. The Panax notoginseng microcapsules were added to the integrated extract and ground. After grinding, the pH of the system was adjusted to 6.0 to obtain the initial drug solution. The initial medicinal solution is sequentially concentrated, sterilized, and filled to obtain a traditional Chinese medicine composition filling solution for treating comorbid diabetes and coronary heart disease.

[0022] The pretreatment process specifically includes: Pretreatment process for water-soluble components (Astragalus membranaceus, Dendrobium nobile, Pueraria lobata, Lophatherum gracile): Remove the fibrous roots and rhizome of Astragalus membranaceus, remove residual roots and impurities from Dendrobium nobile, remove the outer skin and insect-infested parts from Pueraria lobata, and remove weeds and yellow leaves from Lophatherum gracile. Wash all ingredients thoroughly. Soak Astragalus membranaceus in 1.2 times its weight of purified water for 4 hours (at 25℃), slice it to a thickness of 2-3 mm, and dry it in a forced-air dryer at 60℃ until the moisture content is 8%-10%. Cut Dendrobium nobile into sections to a length of 3-5 cm, bake it at a low temperature of 50℃ for 2 hours, then soften it again with purified water until the moisture content is 15%-20%. Slice Pueraria lobata into sections to a thickness of 3-4 mm, steam it at 100℃ under normal pressure for 30 minutes, and then sun-dry it until the moisture content is ≤10%. Cut Lophatherum gracile into sections to a length of 2-3 cm, steam it at 120℃ for 30 seconds, and then dry it in a forced-air dryer at 55℃ until the moisture content is ≤12%. Grind the ingredients into 20-40 mesh particles.

[0023] Pretreatment process for fat-soluble components (Salvia miltiorrhiza and Coptis chinensis slices): Remove the fibrous roots and impurities from Salvia miltiorrhiza and Coptis chinensis slices; mix 10 kg of rice wine with every 100 kg of Salvia miltiorrhiza and let it soak for 2 hours, then stir-fry at 120℃ until the surface is slightly charred; slice Coptis chinensis slices to a thickness of 1-2 mm, mix 15 kg of rice vinegar with every 100 kg of Coptis chinensis and let it soak for 1 hour, then stir-fry at 110℃ until the surface is glossy; pulverize the processed Salvia miltiorrhiza and Coptis chinensis into 40-60 mesh particles; Pretreatment process for Panax notoginseng: Remove fibrous roots and impurities, and vacuum dry at 45℃ until the moisture content is ≤8%.

[0024] Specifically, the amounts (by weight) of the pretreated Astragalus membranaceus, Dendrobium nobile, Pueraria lobata, Panax notoginseng, Salvia miltiorrhiza, Coptis chinensis slices, and Lophatherum gracile in the process are as follows: 30 parts Astragalus membranaceus, 30 parts Dendrobium nobile, 30 parts Pueraria lobata, 3 parts Panax notoginseng, 30 parts Salvia miltiorrhiza, 6 parts Coptis chinensis slices, and 15 parts Lophatherum gracile.

[0025] Specifically, Panax notoginseng was pre-treated by ultra-fine grinding using an air jet mill (feeding speed 10 kg / h, grinding pressure 0.8 MPa) to a particle size ≤ 10 μm, and then passed through a 1000-mesh sieve to obtain Panax notoginseng powder. Hydroxypropyl methylcellulose and gum arabic were mixed and then added to purified water at 40℃ to a concentration of 10%, and stirred at 60 r / min until dissolved to obtain a wall material solution. The Panax notoginseng powder was added to the wall material solution and sheared at a speed of 12000 r / min in a high-speed shearing machine to form a primary emulsion. The primary emulsion was then spray-dried to obtain Panax notoginseng microcapsules. The pretreated Astragalus membranaceus, Dendrobium nobile, Pueraria lobata, and Lophatherum gracile were added to an extraction tank. Purified water at 10 times the total mass of the Astragalus membranaceus, Dendrobium nobile, Pueraria lobata, and Lophatherum gracile, along with 0.3% of the total mass of cellulase, were added for water-soluble component extraction. Ultrasonic-assisted extraction was performed during the extraction process. After extraction, the mixture was first filtered through a 100-mesh filter cloth to remove coarse residue, and then filtered again using a plate and frame filter press (0.22 μm filter cloth pore size, 0.3 MPa filtration pressure, 40℃). The filtrate was collected to obtain the water-soluble extract. The pretreated Salvia miltiorrhiza and Coptis chinensis slices were placed into an extraction tank with a jacket and heating. Eight times the total mass of 70% ethanol solution and 0.02% total mass of vitamin E were added to extract the fat-soluble components. After extraction, the crude residue was first removed by filtration through a 100-mesh filter cloth, and then filtered through a plate and frame filter press (filter cloth pore size 0.22μm, filtration pressure 0.3MPa, temperature 40℃). The filtrate was collected to obtain the fat-soluble extract. The water-soluble extract and the fat-soluble extract were added to a mixing tank, and anhydrous ethanol was added to adjust the ethanol concentration of the mixture to 30%. Then, 0.5% by mass of diatomaceous earth was added to the mixture. The mixture was then stirred at 60 r / min for 20 minutes. After stirring, the mixture was allowed to stand for 10 minutes and then filtered again using a plate and frame filter press (filter cloth pore size 0.22 μm, filtration pressure 0.3 MPa, temperature 40 °C). The filtrate was collected to obtain the integrated extract. The integrated extract was added to a colloid mill jar, cooled to 45°C, and then the Panax notoginseng microcapsules were added for grinding. After the grinding was completed, the pH of the system was adjusted to 6.0 to obtain the initial drug solution. The initial medicinal solution is sequentially concentrated, sterilized, and filled to obtain a traditional Chinese medicine composition filling solution for treating comorbid diabetes and coronary heart disease.

[0026] It is understandable that this invention uses Astragalus membranaceus, Dendrobium nobile, Pueraria lobata, Salvia miltiorrhiza, Panax notoginseng powder, Coptis chinensis tablets, and Lophatherum gracile as the main Chinese herbal ingredients in the composition. It targets the complex pathogenesis of diabetes-coronary heart disease, which is characterized by deficiency of both Qi and Yin, and blood stasis and internal heat. It solves the pathogenesis adaptability defects of traditional Chinese medicine, such as "tonifying but causing stagnation" or "activating blood and depleting Qi", and achieves a triple synergistic effect of "lowering blood sugar, protecting the heart and improving symptoms".

[0027] It is understood that the present invention, through segmented targeted extraction of water-soluble and fat-soluble components, combined with ultrasound and enzymatic hydrolysis, greatly improves the dissolution rate of active ingredients in traditional Chinese medicine compositions, thereby enhancing their efficacy.

[0028] It is understandable that the present invention, through the preparation process of Panax notoginseng microcapsules, greatly improves the retention rate of Panax notoginseng saponin R1, and solves the defects of heat-sensitive destruction and uneven dissolution of Panax notoginseng saponins in the traditional process.

[0029] It is understood that this invention prepares a bottled medicinal liquid that can be directly taken orally through extraction, mixing, concentration, sterilization and filling processes, abandoning the traditional decoction method of Chinese medicine and greatly improving the purity and shelf life of the medicinal liquid.

[0030] In some embodiments of this application, the mass ratio of hydroxypropyl methylcellulose to gum arabic is 3:1, and the total mass of hydroxypropyl methylcellulose and gum arabic is 1.5 times that of the Panax notoginseng powder.

[0031] Specifically, the hydroxypropyl methylcellulose (HPMCK15M, viscosity 15000 cP) is mentioned. In some embodiments of this application, the inlet air temperature of the spray drying process is 170-190℃, the outlet air temperature is 70-90℃, and the feeding rate is 15-25ml / min; the inlet air temperature of the spray drying process is preferably 180℃, the outlet air temperature is preferably 80℃, and the feeding rate is preferably 20ml / min.

[0032] In some embodiments of this application, the extraction of water-soluble components specifically involves: adjusting the pH of the mixture containing cellulase to 4.5 using citric acid, and stirring at 60-100 r / min for 2-3 hours at a temperature of 50-60°C; the preferred temperature is 40°C, the preferred rotation speed is 80 r / min, and the preferred stirring time is 2.5 hours.

[0033] Specifically, the cellulase activity is 5000 U / g.

[0034] In some embodiments of this application, the ultrasonic power is 300W and the frequency is 20kHz; the ultrasonic working mode is: it is turned on synchronously with stirring, first ultrasonic for 10 minutes, and then ultrasonic for 10 minutes every 30 minutes.

[0035] In some embodiments of this application, the extraction of the lipid-soluble components specifically involves heating to 75°C, maintaining the temperature, and refluxing for 1.5-2.5 hours.

[0036] Specifically, the condensate temperature is controlled at 15°C during reflux to ensure an ethanol recovery rate of ≥90%.

[0037] In some embodiments of this application, the grinding speed of the grinding process is 2500-3500 r / min, and the grinding time is 15-25 minutes. Nitrogen gas is introduced at a flow rate of 5 L / min during the grinding process; the preferred grinding speed of the grinding process is 2500-3500 r / min.

[0038] Understandably, introducing nitrogen gas at a flow rate of 5 L / min can prevent the oxidation of Panax notoginseng saponins.

[0039] In some embodiments of this application, the concentration specifically involves: subjecting the initial drug solution to a triple-effect concentration process, setting the first effect vacuum degree to -0.09 MPa and the temperature to 65°C, the second effect vacuum degree to -0.08 MPa and the temperature to 60°C, and the third effect vacuum degree to -0.07 MPa and the temperature to 55°C, while simultaneously adding 0.8% by weight of β-cyclodextrin to the initial drug solution, stirring at a speed of 60 r / min, and stopping the concentration when the relative density of the system at 60°C is between 1.12 and 1.15.

[0040] In some embodiments of this application, the sterilization specifically involves subjecting the concentrated initial drug solution to ultra-high temperature instantaneous sterilization treatment, setting the sterilization temperature to 135°C and the sterilization time to 5 seconds, and then cooling the drug solution to 60°C with cold water and then cooling it to 30°C with ice water.

[0041] Specifically, the temperature of the cold water is 4°C.

[0042] In some embodiments of this application, the filling process specifically involves: sterilizing the pharmaceutical glass bottle with high-pressure steam at 121°C for 30 minutes, injecting the sterilized initial drug solution into the pharmaceutical glass bottle at a dosage of 100 ml / bottle, and sealing it with an aluminum-plastic composite cap.

[0043] Example 1 S1. Astragalus membranaceus, dried dendrobium, kudzu root, Panax notoginseng, salvia miltiorrhiza, coptis chinensis slices, and lophatherum gracile are processed according to the pretreatment process described above and set aside for later use. S2. The pre-treated Panax notoginseng was pulverized to a particle size ≤10μm using an air jet mill (feeding speed 10kg / h, pulverizing pressure 0.8MPa). It was then passed through a 1000-mesh sieve to obtain Panax notoginseng powder. Hydroxypropyl methylcellulose and gum arabic were mixed and then purified water at 40℃ was added to a concentration of 10%. The mixture was stirred at 60r / min until dissolved to obtain a wall material solution. S3. Take 4.5g of the wall material solution, add 3g of the Panax notoginseng powder and mix. Place the mixture in a high-speed shearing machine and shear at a speed of 12000r / min to form a primary emulsion. Transfer the primary emulsion to a spray dryer and set the inlet air temperature to 170℃, the outlet air temperature to 70℃ and the feed rate to 15mL / min. After drying, Panax notoginseng microcapsules are obtained. S4. Take 30g of pretreated Astragalus membranaceus, 30g of dried Dendrobium nobile, 30g of Pueraria lobata, and 15g of Lophatherum gracile and add them to the extraction tank. Add 1050g of purified water and 0.3% (w / w) of cellulase. Adjust the pH of the system to 4.5 with citric acid. Turn on the stirring in the extraction tank (60r / min), raise the temperature to 50℃, and keep it at that temperature for 2h. At the same time, turn on the ultrasonic auxiliary device (300W power, 20kHz frequency). First, sonicate for 10min, and then sonicate for 10min every 30min. After the extraction, first filter with a 100-mesh filter cloth to remove coarse residue, and then filter with a plate and frame filter (0.22μm filter cloth pore size, 0.3MPa filtration pressure, 40℃ temperature). Collect the filtrate to obtain the water-soluble extract. S5. Take 30g of pretreated Salvia miltiorrhiza and 6g of Coptis chinensis slices and put them into an extraction tank with a jacket heating. Add 288g of 70% ethanol solution and 0.02% vitamin E by mass, then turn on the jacket heating and heat to 75℃. Maintain reflux extraction for 1.5h, and control the temperature of the condensate at 15℃ during the process. After the extraction, first filter with a 100-mesh filter cloth to remove coarse residue, and then filter with a plate and frame filter press (filter cloth pore size 0.22μm, filtration pressure 0.3MPa, temperature 40℃). Collect the filtrate to obtain the fat-soluble extract. S6. Add the water-soluble extract and the fat-soluble extract to a mixing tank, add anhydrous ethanol to adjust the ethanol concentration of the mixture to 30%, then add 0.5% by mass of diatomaceous earth to the mixture, and stir at 60 r / min for 20 minutes. After stirring, let it stand for 10 minutes, and then filter it again using a plate and frame filter press (filter cloth pore size 0.22 μm, filtration pressure 0.3 MPa, temperature 40℃). Collect the filtrate to obtain the integrated extract. S7. The integrated extract is added to a colloid mill jar, cooled to 45°C, and the Panax notoginseng microcapsules are added. The mixture is then ground at 2500 r / min for 15 minutes. After the grinding is completed, the pH of the system is adjusted to 6.0 with 0.1 mol / L sodium hydroxide solution to obtain the initial drug solution. S8. Transfer the initial drug solution into a triple-effect concentrator, set the first effect vacuum degree to -0.09MPa and temperature to 65℃, the second effect vacuum degree to -0.08MPa and temperature to 60℃, and the third effect vacuum degree to -0.07MPa and temperature to 55℃; turn on the concentrator, and simultaneously add 0.8% by weight of β-cyclodextrin to the initial drug solution, and stir at a speed of 60r / min. Stop the concentration when the relative density of the system at 60℃ is between 1.12 and 1.15, and obtain the concentrated solution. S9. Transfer the concentrated liquid into an ultra-high temperature instantaneous sterilizer, set the sterilization temperature to 135℃ and the sterilization time to 5s. After sterilization, first cool it to 60℃ with cold water, then cool it to 30℃ with ice water. Collect the sterilized liquid. Sterilize the pharmaceutical glass bottle with high-pressure steam at 121℃ for 30 minutes. Inject the sterilized initial liquid into the pharmaceutical glass bottle at a dosage of 100ml / bottle. Seal it with an aluminum-plastic combination cap to obtain a traditional Chinese medicine composition filling liquid for treating diabetes and coronary heart disease comorbidities.

[0044] Example 2 S1. Astragalus membranaceus, dried dendrobium, kudzu root, Panax notoginseng, salvia miltiorrhiza, coptis chinensis slices, and lophatherum gracile are processed according to the pretreatment process described above and set aside for later use. S2. The pre-treated Panax notoginseng was pulverized to a particle size ≤10μm using an air jet mill (feeding speed 10kg / h, pulverizing pressure 0.8MPa). It was then passed through a 1000-mesh sieve to obtain Panax notoginseng powder. Hydroxypropyl methylcellulose and gum arabic were mixed and then purified water at 40℃ was added to a concentration of 10%. The mixture was stirred at 60r / min until dissolved to obtain a wall material solution. S3. Take 4.5g of the wall material solution, add 3g of the Panax notoginseng powder and mix. Place the mixture in a high-speed shearing machine and shear at a speed of 12000r / min to form a primary emulsion. Transfer the primary emulsion to a spray dryer and set the inlet air temperature to 180℃, the outlet air temperature to 80℃ and the feed rate to 20mL / min. After drying, Panax notoginseng microcapsules are obtained. S4. Take 30g of pretreated Astragalus membranaceus, 30g of dried Dendrobium nobile, 30g of Pueraria lobata, and 15g of Lophatherum gracile and add them to the extraction tank. Add 1050g of purified water and 0.3% (w / w) of cellulase. Adjust the pH of the system to 4.5 with citric acid. Turn on the stirring in the extraction tank (80r / min), raise the temperature to 55℃, and keep it warm for 2.5h. At the same time, turn on the ultrasonic auxiliary device (300W power, 20kHz frequency). First, sonicate for 10min, and then sonicate for 10min every 30min. After the extraction, first filter with a 100-mesh filter cloth to remove coarse residue, and then filter with a plate and frame filter (0.22μm filter cloth pore size, 0.3MPa filtration pressure, 40℃ temperature). Collect the filtrate to obtain the water-soluble extract. S5. Take 30g of pretreated Salvia miltiorrhiza and 6g of Coptis chinensis slices and put them into an extraction tank with a jacket heating. Add 288g of 70% ethanol solution and 0.02% vitamin E by mass, then turn on the jacket heating and heat to 75℃. Maintain reflux extraction for 2 hours, and control the temperature of the condensate at 15℃ during the process. After the extraction, first filter with a 100-mesh filter cloth to remove coarse residue, and then filter with a plate and frame filter press (filter cloth pore size 0.22μm, filtration pressure 0.3MPa, temperature 40℃). Collect the filtrate to obtain the fat-soluble extract. S6. Add the water-soluble extract and the fat-soluble extract to a mixing tank, add anhydrous ethanol to adjust the ethanol concentration of the mixture to 30%, then add 0.5% by mass of diatomaceous earth to the mixture, and stir at 60 r / min for 20 minutes. After stirring, let it stand for 10 minutes, and then filter it again using a plate and frame filter press (filter cloth pore size 0.22 μm, filtration pressure 0.3 MPa, temperature 40℃). Collect the filtrate to obtain the integrated extract. S7. The integrated extract is added to a colloid mill jar, cooled to 45°C, and the Panax notoginseng microcapsules are added. The mixture is then ground at 3000 r / min for 20 minutes. After the grinding is completed, the pH of the system is adjusted to 6.0 with 0.1 mol / L sodium hydroxide solution to obtain the initial drug solution. S8. Transfer the initial drug solution into a triple-effect concentrator, set the first effect vacuum degree to -0.09MPa and temperature to 65℃, the second effect vacuum degree to -0.08MPa and temperature to 60℃, and the third effect vacuum degree to -0.07MPa and temperature to 55℃; turn on the concentrator, and simultaneously add 0.8% by weight of β-cyclodextrin to the initial drug solution, and stir at a speed of 60r / min. Stop the concentration when the relative density of the system at 60℃ is between 1.12 and 1.15, and obtain the concentrated solution. S9. Transfer the concentrated liquid into an ultra-high temperature instantaneous sterilizer, set the sterilization temperature to 135℃ and the sterilization time to 5s. After sterilization, first cool it to 60℃ with cold water, then cool it to 30℃ with ice water. Collect the sterilized liquid. Sterilize the pharmaceutical glass bottle with high-pressure steam at 121℃ for 30 minutes. Inject the sterilized initial liquid into the pharmaceutical glass bottle at a dosage of 100ml / bottle. Seal it with an aluminum-plastic combination cap to obtain a traditional Chinese medicine composition filling liquid for treating diabetes and coronary heart disease comorbidities.

[0045] Example 3 S1. Astragalus membranaceus, dried dendrobium, kudzu root, Panax notoginseng, salvia miltiorrhiza, coptis chinensis slices, and lophatherum gracile are processed according to the pretreatment process described above and set aside for later use. S2. The pre-treated Panax notoginseng was pulverized to a particle size ≤10μm using an air jet mill (feeding speed 10kg / h, pulverizing pressure 0.8MPa). It was then passed through a 1000-mesh sieve to obtain Panax notoginseng powder. Hydroxypropyl methylcellulose and gum arabic were mixed and then purified water at 40℃ was added to a concentration of 10%. The mixture was stirred at 60r / min until dissolved to obtain a wall material solution. S3. Take 4.5g of the wall material solution, add 3g of the Panax notoginseng powder and mix. Place the mixture in a high-speed shearing machine and shear at a speed of 12000r / min to form a primary emulsion. Transfer the primary emulsion to a spray dryer and set the inlet air temperature to 190℃, the outlet air temperature to 90℃ and the feed rate to 25mL / min. After drying, Panax notoginseng microcapsules are obtained. S4. Take 30g of pretreated Astragalus membranaceus, 30g of dried Dendrobium nobile, 30g of Pueraria lobata, and 15g of Lophatherum gracile and add them to the extraction tank. Add 1050g of purified water and 0.3% (w / w) of cellulase. Adjust the pH of the system to 4.5 with citric acid. Turn on the stirring in the extraction tank (100r / min). Heat to 60℃ and keep warm for 3h. At the same time, turn on the ultrasonic auxiliary device (300W power, 20kHz frequency). First, sonicate for 10min, and then sonicate for 10min every 30min. After the extraction, first filter with a 100-mesh filter cloth to remove coarse residue, and then filter with a plate and frame filter (0.22μm filter cloth pore size, 0.3MPa filtration pressure, 40℃ temperature). Collect the filtrate to obtain the water-soluble extract. S5. Take 30g of pretreated Salvia miltiorrhiza and 6g of Coptis chinensis slices and put them into an extraction tank with a jacketed heating. Add 288g of 70% ethanol solution and 0.02% vitamin E by mass, then turn on the jacket heating and heat to 75℃. Maintain reflux extraction for 2.5h, and control the temperature of the condensate at 15℃ during the process. After the extraction, first filter with a 100-mesh filter cloth to remove coarse residue, and then filter with a plate and frame filter press (filter cloth pore size 0.22μm, filtration pressure 0.3MPa, temperature 40℃). Collect the filtrate to obtain the fat-soluble extract. S6. Add the water-soluble extract and the fat-soluble extract to a mixing tank, add anhydrous ethanol to adjust the ethanol concentration of the mixture to 30%, then add 0.5% by mass of diatomaceous earth to the mixture, and stir at 60 r / min for 20 minutes. After stirring, let it stand for 10 minutes, and then filter it again using a plate and frame filter press (filter cloth pore size 0.22 μm, filtration pressure 0.3 MPa, temperature 40℃). Collect the filtrate to obtain the integrated extract. S7. The integrated extract is added to a colloid mill jar, cooled to 45°C, and the Panax notoginseng microcapsules are added. The mixture is then ground at 3500 r / min for 25 minutes. After the grinding is completed, the pH of the system is adjusted to 6.0 with 0.1 mol / L sodium hydroxide solution to obtain the initial drug solution. S8. Transfer the initial drug solution into a triple-effect concentrator, set the first effect vacuum degree to -0.09MPa and temperature to 65℃, the second effect vacuum degree to -0.08MPa and temperature to 60℃, and the third effect vacuum degree to -0.07MPa and temperature to 55℃; turn on the concentrator, and simultaneously add 0.8% by weight of β-cyclodextrin to the initial drug solution, and stir at a speed of 60r / min. Stop the concentration when the relative density of the system at 60℃ is between 1.12 and 1.15, and obtain the concentrated solution. S9. Transfer the concentrated liquid into an ultra-high temperature instantaneous sterilizer, set the sterilization temperature to 135℃ and the sterilization time to 5s. After sterilization, first cool it to 60℃ with cold water, then cool it to 30℃ with ice water. Collect the sterilized liquid. Sterilize the pharmaceutical glass bottle with high-pressure steam at 121℃ for 30 minutes. Inject the sterilized initial liquid into the pharmaceutical glass bottle at a dosage of 100ml / bottle. Seal it with an aluminum-plastic combination cap to obtain a traditional Chinese medicine composition filling liquid for treating diabetes and coronary heart disease comorbidities.

[0046] Comparative Example 1 S1. Astragalus membranaceus, dried dendrobium, kudzu root, Panax notoginseng, salvia miltiorrhiza, coptis chinensis slices, and lophatherum gracile are processed according to the pretreatment process described above and set aside for later use. S2. Take 30g of pretreated Astragalus membranaceus, 30g of dried Dendrobium nobile, 30g of Pueraria lobata, 3g of Panax notoginseng, 30g of Salvia miltiorrhiza, 6g of Coptis chinensis slices, and 15g of Lophatherum gracile. Mix them evenly and add them to a decoction pot. Add purified water at a material-to-liquid ratio of 1:12 (g / mL). Heat the pot to 100℃ and bring it to a boil. Then reduce the heat and simmer for 2 hours. After the decoction is finished, collect the filtrate. Add the same volume of purified water to the residue and repeat the above decoction steps. Collect the filtrate. S3. Combine the two filtrates and transfer the combined decoction filtrate into a triple-effect concentrator. Set the first effect vacuum to -0.09 MPa and temperature to 65°C, the second effect vacuum to -0.08 MPa and temperature to 60°C, and the third effect vacuum to -0.07 MPa and temperature to 55°C. Turn on the concentrator and simultaneously add 0.8% of the initial drug solution weight of β-cyclodextrin. Stir at 60 r / min and concentrate until the relative density of the system at 60°C is between 1.12 and 1.15. Stop the concentration to obtain the decoction concentrate.

[0047] Effect test: The concentrated solution prepared in Example 2 and the concentrated solution prepared by the water decoction method in Comparative Example 1 were analyzed by HPLC, and the results are shown in Table 1 below: Table 1. HPLC Detection Results

[0048] As can be seen, the contents of all five components in Example 2 are higher than those in Comparative Example 1, with the differences being most prominent in Panax notoginsenoside R1 (2.47 times) and Tanshinone IIA (2.04 times), confirming the protective effect of "ethanol targeted extraction + microencapsulation" on lipid-soluble / heat-sensitive components.

[0049] Clinical efficacy verification 150 patients were selected (stratified by disease severity: 45 mild cases, 60 moderate cases, and 45 severe cases). All patients took the traditional Chinese medicine composition solution prepared in Example 2 of this invention for treating comorbid diabetes and coronary heart disease (100ml / vial; moderate patients twice daily, mild cases once daily, severe cases 50mL / time, twice daily for the first week, increasing to 100mL / time, twice daily after one week). They were followed up continuously for 18 months, and metabolic indicators, cardiovascular function, TCM syndromes, and safety indicators were regularly monitored. Specific data are shown in Table 2 below.

[0050] As can be seen, the 18-month follow-up showed that fasting blood glucose and glycated hemoglobin in patients with different disease severity could be kept stable within the clinical target range (fasting blood glucose <7.0mmol / L, HbA1c <7.0%), and the reduction at 12 months was 2.8-3.2 times that of the conventional Chinese medicine liquid control group. This proves that the combination of "qi and yin tonification + heat clearing and blood activating" of the present invention can continuously improve insulin resistance and promote glucose metabolism, avoiding the defects of conventional Chinese medicine of "short-term effectiveness and long-term rebound". In moderate patients, coronary flow reserve (CFR) increased by 22.7% over 12 months (compared to only 4.5% in the control group), and in severe patients, left ventricular ejection fraction (LVEF) increased by 11.3% (compared to only 2.9% in the control group). This indicates that the present invention can improve coronary microcirculation and myocardial blood supply through the synergistic effect of tanshinone IIA and notoginsenoside R1 in promoting dissolution and inhibiting aggregation. In contrast, conventional Chinese medicine solutions can only slightly improve microcirculation and cannot reverse early decline in cardiac function. At 12 months, the TCM syndrome score decreased by 50.7%-59.9% (compared to only 17.5%-23.6% in the control group), and the disappearance rate of core symptoms such as dry mouth, fatigue, and chest pain reached 78.3% (compared to only 35.2% in the control group). This confirms the precise suitability of the formula of this invention for the syndrome of "deficiency of both Qi and Yin with blood stasis", and solves the problem of conventional Chinese medicine "improving indicators but not symptoms". During the 18-month follow-up, only 2 patients (1.3%) experienced mild gastrointestinal discomfort (abdominal distension), which was relieved after adjusting the administration time (1 hour after meals). No patients showed abnormal liver or kidney function (ALT, AST, and Scr were all within the normal range) or bleeding tendency (prothrombin time and platelet count were normal), indicating a significant improvement in safety.

[0051] 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 method of applying a traditional Chinese medicine composition for treating comorbid diabetes and coronary heart disease, characterized in that, Includes the following steps: Pre-treat the following ingredients: Astragalus membranaceus, Dendrobium nobile, Pueraria lobata, Panax notoginseng, Salvia miltiorrhiza, Coptis chinensis slices, and Lophatherum gracile. The pretreated Panax notoginseng was crushed to obtain Panax notoginseng powder. Hydroxypropyl methylcellulose and gum arabic were mixed and then water was added and stirred until dissolved to obtain a wall material solution. After adding the Panax notoginseng powder to the wall material solution, high-speed shearing is performed to form a primary emulsion. The primary emulsion is then spray-dried to obtain Panax notoginseng microcapsules. Water and cellulase were added to the pretreated Astragalus membranaceus, Dendrobium nobile, Pueraria lobata and Lophatherum gracile to extract water-soluble components. Ultrasonic extraction was performed during the extraction process. After the extraction was completed, the mixture was filtered to obtain the water-soluble extract. After adding ethanol solution and vitamin E to the pretreated Salvia miltiorrhiza and Coptis chinensis tablets, the fat-soluble components were extracted, and the fat-soluble extract was obtained by filtration. Anhydrous ethanol was added to the water-soluble extract and the fat-soluble extract, followed by the addition of diatomaceous earth. The mixture was then stirred, and after the stirring was completed, it was allowed to stand and filtered to obtain the integrated extract. The Panax notoginseng microcapsules were added to the integrated extract and ground. After grinding, the pH of the system was adjusted to 6.0 to obtain the initial drug solution. The initial medicinal solution is sequentially concentrated, sterilized, and filled to obtain a traditional Chinese medicine composition filling solution for treating comorbid diabetes and coronary heart disease.

2. The method of applying the traditional Chinese medicine composition for treating comorbid diabetes and coronary heart disease according to claim 1, characterized in that, The mass ratio of hydroxypropyl methylcellulose to gum arabic is 3:1, and the total mass of hydroxypropyl methylcellulose and gum arabic is 1.5 times that of the Panax notoginseng powder.

3. The method of applying the traditional Chinese medicine composition for treating comorbid diabetes and coronary heart disease according to claim 2, characterized in that, The inlet air temperature of the spray drying process is 170-190℃, the outlet air temperature is 70-90℃, and the feeding rate is 15-25ml / min.

4. The method of applying the traditional Chinese medicine composition for treating comorbid diabetes and coronary heart disease according to claim 3, characterized in that, The extraction of water-soluble components is specifically carried out by adjusting the pH of the mixture containing cellulase to 4.5 with citric acid, and stirring at 60-100 r / min for 2-3 hours at a temperature of 50-60℃.

5. The method of applying the traditional Chinese medicine composition for treating comorbid diabetes and coronary heart disease according to claim 4, characterized in that, The ultrasonic power is 300W and the frequency is 20kHz. The ultrasonic working mode is: it is turned on synchronously with stirring, first ultrasonic for 10 minutes, and then ultrasonic for 10 minutes every 30 minutes.

6. The method of applying the traditional Chinese medicine composition for treating comorbid diabetes and coronary heart disease according to claim 5, characterized in that, The extraction of the fat-soluble components specifically involves heating to 75°C, maintaining the temperature, and refluxing for 1.5-2.5 hours.

7. The method of applying the traditional Chinese medicine composition for treating comorbid diabetes and coronary heart disease according to claim 6, characterized in that, The grinding process is carried out at a speed of 2500-3500 r / min for 15-25 minutes, during which nitrogen gas is introduced at a flow rate of 5 L / min.

8. The method of applying the traditional Chinese medicine composition for treating comorbid diabetes and coronary heart disease according to claim 7, characterized in that, The concentration process specifically involves: subjecting the initial drug solution to a triple-effect concentration treatment, setting the first effect vacuum degree to -0.09 MPa and the temperature to 65°C, the second effect vacuum degree to -0.08 MPa and the temperature to 60°C, and the third effect vacuum degree to -0.07 MPa and the temperature to 55°C, while simultaneously adding 0.8% by weight of β-cyclodextrin to the initial drug solution, stirring at a speed of 60 r / min, and stopping the concentration when the relative density of the system at 60°C is between 1.12 and 1.

15.

9. The method of applying the traditional Chinese medicine composition for treating comorbid diabetes and coronary heart disease according to claim 7, characterized in that, The sterilization process specifically involves subjecting the concentrated initial drug solution to ultra-high temperature instantaneous sterilization, setting the sterilization temperature to 135°C and the sterilization time to 5 seconds. After the sterilization is completed, the drug solution is first cooled to 60°C with cold water, and then cooled to 30°C with ice water.

10. The method of applying the traditional Chinese medicine composition for treating comorbid diabetes and coronary heart disease according to claim 7, characterized in that, The filling process specifically involves sterilizing the pharmaceutical glass bottle with high-pressure steam at 121°C for 30 minutes, injecting the sterilized initial drug solution into the pharmaceutical glass bottle at a dosage of 100ml / bottle, and sealing it with an aluminum-plastic combination cap.

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