Traditional Chinese medicine formula granules for treating gangrene and preparation method thereof

Abstract

The invention relates to traditional Chinese medicine formula granules for treating gangrene and a preparation method thereof, and belongs to the field of traditional Chinese medicine preparations. The traditional Chinese medicine formula granules for treating gangrene are mainly prepared from the following components in parts by weight: 8-15 parts of peach kernels, 5-10 parts of rheum officinale, 5-10 parts of cassia twigs, 5-10 parts of liquorice, 10-20 parts of poria cocos, 8-15 parts of rhizoma alismatis, 10-15 parts of angelica sinensis and 10-20 parts of salvia miltiorrhiza. The traditional Chinese medicine formula granules have the effects of breaking blood, removing blood stasis, promoting blood circulation and dredging collaterals. The traditional Chinese medicine is mainly used for treating damp-heat toxin exuberance syndrome, blood accumulation syndrome and the like of diabetic foot (gangrene) clinically, and has a remarkable effect.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine preparations, and relates to a traditional Chinese medicine formula granule for treating gangrene and its preparation method. Background Technology

[0002] Diabetic foot, known in Traditional Chinese Medicine as "Tuoju," is described in the *Huangdi Neijing* as "occurring on the toes, called Tuoyong. Its symptoms are red, black, and fatal; if it is not red, black, fatal, or declining, it should be cut off immediately, otherwise death will ensue." The pathogenesis of diabetic foot is characterized by deficiency of the root and excess of the branch. The root deficiency lies in the depletion of Qi, Yang, and Yin, while the branch excess manifests as dampness, heat, toxins, Qi stagnation, and blood stasis.

[0003] Currently, the pathogenesis of diabetic foot is generally believed to be related to the interaction of damp-heat, toxins, and blood stasis, namely, "stagnation of qi and blood, obstruction of collaterals, and excessive damp-heat and fire toxins damaging the body's vital energy, leading to putrefaction and damage." Due to prolonged thirst and thirst, diabetic foot leads to deficiency of qi and yin, resulting in an inability to circulate body fluids and blood to the extremities. This results in insufficient qi, blood, essence, and fluids in the extremities, loss of nourishment of the tendons and veins, insufficient blood supply to the wound tissue, and the inability to remove necrotic tissue and regenerate new tissue, ultimately forming a difficult-to-heal ulcer.

[0004] Traditional Chinese medicine has significant therapeutic effects on diabetic foot, and can exert its effects through multiple methods and pathways, giving it unique advantages. Summary of the Invention

[0005] The main objective of this invention is to provide a traditional Chinese medicine formula granule for treating gangrene and its preparation method. The traditional Chinese medicine formula granule described in this invention is mainly used clinically for the treatment of diabetic foot (gangrene) with damp-heat toxicity syndrome, blood stasis syndrome, etc.

[0006] The present invention employs the following technical solutions to achieve the above objectives: A traditional Chinese medicine formula granule for treating gangrene is mainly prepared from the following ingredients: Peach kernel 8-15 parts by weight, rhubarb 5-10 parts by weight, cinnamon twig 5-10 parts by weight, licorice root 5-10 parts by weight, poria cocos 10-20 parts by weight, alisma plantago-aquatica 8-15 parts by weight, angelica sinensis 10-15 parts by weight, salvia miltiorrhiza 10-20 parts by weight.

[0007] The preparation method of the above-mentioned traditional Chinese medicine formula granules mainly includes the following steps: Step 1: Crush Angelica sinensis and Cinnamomum cassia to obtain a mixed fine powder; add water containing L-ascorbic acid palmitate to the mixed fine powder, soak at room temperature for 30-60 minutes, heat for steam distillation, maintain a gentle boil, and collect the distillate; distill until the distillate no longer increases, let stand, and separate the volatile oil using a separatory funnel to obtain a mixed volatile oil for later use; dissolve α-lipoic acid in the mixed volatile oil, then add micronized silica gel and mix evenly to obtain a mixture for later use; dissolve β-cyclodextrin and add it to the mixture, keep warm at 50-60℃ and stir for 1-1.5 hours to obtain inclusion complex I; distilled mixture I is for later use; Step 2: Crush peach kernels to obtain peach kernel powder; add water containing citric acid to the peach kernel powder, heat for steam distillation, maintain a gentle boil, and collect the distillate; distill until the distillate no longer increases, let stand, and separate the volatile oil using a separatory funnel to obtain peach kernel volatile oil for later use; dissolve β-cyclodextrin and NaCl, add the peach kernel volatile oil while stirring, and keep warm at 50-60℃ with stirring for 1-1.5 hours to obtain inclusion complex II; the distilled mixture II is for later use; Step 3: Mix the mixture I after distillation in Step 1 and the mixture II after distillation in Step 2, add licorice, poria cocos, alisma plantago-aquatica and salvia miltiorrhiza, reflux extract, then add rhubarb and water, continue reflux extract, filter, and obtain the extract; Step 4: Concentrate the extract under reduced pressure to obtain a clear paste. Add cross-linked polyvinylpyrrolidone (0.2-0.3% of the weight of the clear paste), mix well, dry, and pulverize to obtain a dry paste powder. Mix the dry paste powder, inclusion compound I from step 1, and inclusion compound II from step 2. Add an appropriate amount of xylitol and 93% ethanol solution to prepare a soft material. Granulate, dry, and package to obtain traditional Chinese medicine formula granules.

[0008] Preferably, the amount of water added in step 1 is 8-10 times the weight of the mixed fine powder.

[0009] Preferably, in step 1, the amount of L-ascorbate palmitate added to the water is 0.2 mg / g.

[0010] Preferably, in step 1, the mass-to-volume ratio of β-cyclodextrin, micronized silica gel, α-lipoic acid, and mixed volatile oil is (4-6):(0.1-0.2):(0.03-0.05):1 (g / g / g / mL).

[0011] Preferably, the amount of water added in step 2 is 8-10 times the weight of the peach kernel powder.

[0012] Preferably, the amount of citric acid added to the water in step 2 is 10 mg / g.

[0013] Preferably, in step 2, the mass-to-volume ratio of β-cyclodextrin, NaCl, and peach kernel volatile oil is (4-6):(0.1-0.2):1.

[0014] Preferably, in step 4, the amount of cross-linked polyvinylpyrrolidone added is 0.2-0.3% of the weight of the extract.

[0015] The present invention has the following beneficial effects: This invention's formula has the effects of breaking up blood stasis, promoting blood circulation, and unblocking collaterals. Clinically, it is mainly used to treat diabetic foot (gangrene) with damp-heat toxicity and blood stasis, with significant effects. To further improve the clinical efficacy of the formula, the applicant optimized the preparation process. Pharmacological tests have confirmed that the volatile oils in peach kernel, cinnamon twig, and angelica can significantly improve the pharmacological activity of the preparation. However, the presence of volatile oils has a significant impact on the preparation of granules and their stability. Based on this, the applicant optimized the granule preparation process, including optimizing the inclusion process of volatile oils, so that the final produced granules meet the standards and are stable, with high pharmacological activity, which can improve the stability and clinical efficacy of the preparation. Detailed Implementation

[0016] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. After reading the present invention, any modifications of the present invention in various equivalent forms by those skilled in the art will fall within the scope of protection of the claims of this application.

[0017] Example 1: Traditional Chinese Medicine Composition Peach kernel 15g, rhubarb 10g, cinnamon twig 10g, licorice root 10g, poria cocos 20g, alisma plantago-aquatica 15g, angelica sinensis 15g, salvia miltiorrhiza 20g.

[0018] Example 2: Traditional Chinese Medicine Composition Peach kernel 8g, rhubarb 5g, cinnamon twig 5g, licorice root 5g, poria cocos 10g, alisma plantago-aquatica 8g, angelica sinensis 10g, salvia miltiorrhiza 10g.

[0019] Example 3: Traditional Chinese Medicine Composition Peach kernel 10g, rhubarb 6g, cinnamon twig 6g, prepared licorice root 6g, poria cocos 15g, alisma plantago-aquatica 10g, angelica sinensis 12g, salvia miltiorrhiza 15g.

[0020] Example 4: Traditional Chinese Medicine Preparation Step 1: Crush 12g of Angelica sinensis and 6g of Cinnamomum cassia to obtain a mixed fine powder; add 180g of deionized water (containing 0.03g of L-ascorbic acid palmitate) to the mixed fine powder, soak at room temperature for 30min, then start heating for steam distillation, maintaining a gentle boil, and collect the distillate; distill until the distillate no longer increases, let stand, and separate the volatile oil using a separatory funnel to obtain a mixed volatile oil for later use; weigh the raw materials according to the ratio of β-cyclodextrin:micronized silica gel:α-lipoic acid:mixed volatile oil = 6:0.2:0.03:1 (g / g / g / mL), first dissolve α-lipoic acid in the mixed volatile oil, then add micronized silica gel and mix evenly to obtain a mixture for later use; dissolve β-cyclodextrin in an appropriate amount of hot water, then add the mixture while stirring, keep warm at 50℃ and stir for 1.5h to obtain inclusion complex I; distilled mixture I is for later use; Step 2: Crush 10g of peach kernels to obtain peach kernel powder; add 100g of deionized water (containing 1g of citric acid) to the peach kernel powder, heat for steam distillation, maintain a gentle boil, and collect the distillate; distill until the distillate no longer increases, let stand, and separate the volatile oil using a separatory funnel to obtain peach kernel volatile oil for later use; weigh the raw materials according to the ratio of β-cyclodextrin:NaCl:peach kernel volatile oil = 6:0.2:1 (g / g / mL), first dissolve β-cyclodextrin and NaCl in an appropriate amount of hot water, then add peach kernel volatile oil while stirring, keep warm at 60℃ and stir for 1 hour to obtain inclusion complex II; the distilled mixture II is for later use; Step 3: Mix the distilled mixture I from Step 1 and the distilled mixture II from Step 2, add 6g of licorice, 15g of poria cocos, 10g of alisma plantago-aquatica and 15g of salvia miltiorrhiza, and reflux extract at 80℃ for 1.5h. Then add 6g of rhubarb and 500g of deionized water, and continue to reflux extract for 0.5h. Filter to obtain the extract. Step 4: Concentrate the extract under reduced pressure to a clear paste with a relative density of 1.30-1.35 (65℃), add 0.3% (by weight of cross-linked polyvinylpyrrolidone) and mix well, then dry and pulverize to obtain a dry paste powder; mix the dry paste powder, inclusion compound I from step 1 and inclusion compound II from step 2, add an appropriate amount of xylitol and 93% ethanol solution to prepare a soft material, granulate, dry, and package (10g per bag) to obtain the traditional Chinese medicine formula granules.

[0021] Example 5 Step 1: Crush 12g of Angelica sinensis and 6g of Cinnamomum cassia to obtain a mixed fine powder; add 150g of deionized water (containing 0.036g of L-ascorbic acid palmitate) to the mixed fine powder, soak at room temperature for 60min, then start heating for steam distillation, maintaining a gentle boil, and collect the distillate; distill until the distillate no longer increases, let stand, and separate the volatile oil using a separatory funnel to obtain a mixed volatile oil for later use; weigh the raw materials according to the ratio of β-cyclodextrin:micronized silica gel:α-lipoic acid:mixed volatile oil = 4:0.1:0.05:1 (g / g / g / mL), first dissolve α-lipoic acid in the mixed volatile oil, then add micronized silica gel and mix evenly to obtain a mixture for later use; dissolve β-cyclodextrin in an appropriate amount of hot water, then add the mixture while stirring, keep at 60℃ and stir for 1h to obtain inclusion complex I; distilled mixture I is for later use; Step 2: Crush 10g of peach kernels to obtain peach kernel powder; add 80g of deionized water (containing 0.8g of citric acid) to the peach kernel powder, heat for steam distillation, maintain a gentle boil, and collect the distillate; distill until the distillate no longer increases, let stand, and separate the volatile oil using a separatory funnel to obtain peach kernel volatile oil for later use; weigh the raw materials according to the ratio of β-cyclodextrin:NaCl:peach kernel volatile oil = 4:0.1:1 (g / g / mL), first dissolve β-cyclodextrin and NaCl in an appropriate amount of hot water, then add peach kernel volatile oil while stirring, keep warm at 50℃ and stir for 1.5h to obtain inclusion complex II; the distilled mixture II is for later use; Step 3: Mix the distilled mixture I from Step 1 and the distilled mixture II from Step 2, add 6g of licorice, 15g of poria cocos, 10g of alisma plantago-aquatica and 15g of salvia miltiorrhiza, and reflux extract at 80℃ for 1.5h. Then add 6g of rhubarb and 300g of deionized water, and continue to reflux extract for 0.5h. Filter to obtain the extract. Step 4: Concentrate the extract under reduced pressure to a clear paste with a relative density of 1.30-1.35 (65℃), add 0.2% (by weight of cross-linked polyvinylpyrrolidone) and mix well, then dry and pulverize to obtain a dry paste powder; mix the dry paste powder, inclusion compound I from step 1 and inclusion compound II from step 2, add an appropriate amount of xylitol and 93% ethanol solution to prepare a soft material, granulate, dry, and package (10g per bag) to obtain the traditional Chinese medicine formula granules.

[0022] Example 6 Step 1: Crush 12g of Angelica sinensis and 6g of Cinnamomum cassia to obtain a mixed fine powder; add 170g of deionized water (containing 0.034g of L-ascorbic acid palmitate) to the mixed fine powder, soak at room temperature for 40min, then start heating for steam distillation, maintaining a gentle boil, and collect the distillate; distill until the distillate no longer increases, let stand, and separate the volatile oil using a separatory funnel to obtain a mixed volatile oil for later use; weigh the raw materials according to the ratio of β-cyclodextrin:micronized silica gel:α-lipoic acid:mixed volatile oil = 5:0.2:0.04:1 (g / g / g / mL), first dissolve α-lipoic acid in the mixed volatile oil, then add micronized silica gel and mix evenly to obtain a mixture for later use; dissolve β-cyclodextrin in an appropriate amount of hot water, then add the mixture while stirring, keep warm at 60℃ and stir for 1h to obtain inclusion complex I; distilled mixture I is for later use; Step 2: Crush 10g of peach kernels to obtain peach kernel powder; add 90g of deionized water (containing 0.9g of citric acid) to the peach kernel powder, heat for steam distillation, maintain a gentle boil, and collect the distillate; distill until the distillate no longer increases, let stand, and separate the volatile oil using a separatory funnel to obtain peach kernel volatile oil for later use; weigh the raw materials according to the ratio of β-cyclodextrin:NaCl:peach kernel volatile oil = 5:0.2:1 (g / g / mL), first dissolve β-cyclodextrin and NaCl in an appropriate amount of hot water, then add peach kernel volatile oil while stirring, keep warm at 60℃ and stir for 1 hour to obtain inclusion complex II; the distilled mixture II is for later use; Step 3: Mix the distilled mixture I from Step 1 and the distilled mixture II from Step 2, add 6g of licorice, 15g of poria cocos, 10g of alisma plantago-aquatica and 15g of salvia miltiorrhiza, and reflux extract at 80℃ for 1.5h. Then add 6g of rhubarb and 400g of deionized water, and continue to reflux extract for 0.5h. Filter to obtain the extract. Step 4: Concentrate the extract under reduced pressure to a clear paste with a relative density of 1.30-1.35 (65℃). Add cross-linked polyvinylpyrrolidone (0.25% of the weight of the clear paste), mix well, dry, and pulverize to obtain a dry paste powder. Mix the dry paste powder, inclusion compound I from step 1, and inclusion compound II from step 2. Add an appropriate amount of xylitol and 93% ethanol solution to prepare a soft material. Granulate, dry, and package (10 grams per bag) to obtain the traditional Chinese medicine formula granules.

[0023] Comparative Example 1 Step 1: Grind 12g of Angelica sinensis into a fine powder and set aside. Step 2: Mix 10g of peach kernel, 6g of rhubarb, 6g of cinnamon twig, 6g of prepared licorice root, 15g of poria cocos, 10g of alisma plantago-aquatica, and 15g of salvia miltiorrhiza. Add 10 times the weight of water and decoct twice, 2 hours each time. Combine the decoctions, filter, combine the filtrates, and concentrate to a clear extract with a relative density of 1.30-1.35 (65℃). Then add the above-mentioned fine powder of angelica sinensis and an appropriate amount of dextrin, mix well, make into granules, and package (10g per bag) to obtain the Chinese medicine formula granules.

[0024] Comparative Example 2 Step 1: Crush 12g of Angelica sinensis and 6g of Cinnamomum cassia to obtain a fine mixed powder; add 170g of deionized water to the fine mixed powder, soak at room temperature for 40 minutes, then start heating and steam distillation, keeping it at a gentle boil, and collect the distillate; distill until the distillate no longer increases, let it stand, and separate the volatile oil with a separatory funnel to obtain a mixed volatile oil for later use; the distilled mixture I is for later use. Step 2: Crush 10g of peach kernels to obtain peach kernel powder; add 90g of deionized water to the peach kernel powder, heat for steam distillation, maintain a gentle boil, and collect the distillate; distill until the distillate no longer increases, let stand, and separate the volatile oil using a separatory funnel to obtain peach kernel volatile oil for later use; the distilled mixture II is for later use. Step 3: Mix the distilled mixture I from Step 1 and the distilled mixture II from Step 2, add 6g of licorice, 15g of poria cocos, 10g of alisma plantago-aquatica and 15g of salvia miltiorrhiza, and reflux extract at 80℃ for 1.5h. Then add 6g of rhubarb and 400g of deionized water, and continue to reflux extract for 0.5h. Filter to obtain the extract. Step 4: Concentrate the extract under reduced pressure to a clear paste with a relative density of 1.30-1.35 (65℃), dry and pulverize to obtain dry paste powder; mix the dry paste powder, the mixed volatile oil from Step 1, and the peach kernel volatile oil from Step 2, add an appropriate amount of xylitol and 93% ethanol solution to prepare soft material, granulate, dry, and package (10 grams per bag) to obtain traditional Chinese medicine formula granules.

[0025] Comparative Example 3 Step 1: Crush 12g of Angelica sinensis and 6g of Cinnamomum cassia to obtain a fine mixed powder; add 170g of deionized water (containing 0.034g of L-ascorbic acid palmitate) to the fine mixed powder, soak at room temperature for 40min, then start heating for steam distillation, maintaining a gentle boil, and collect the distillate; distill until the distillate no longer increases, let stand, and separate the volatile oil using a separatory funnel to obtain a mixed volatile oil for later use; weigh the raw materials according to the ratio of β-cyclodextrin:α-lipoic acid:mixed volatile oil = 5:0.04:1 (g / g / mL), first dissolve α-lipoic acid in the mixed volatile oil to obtain a mixture for later use; dissolve β-cyclodextrin in an appropriate amount of hot water, then add the mixture while stirring, keep at 60℃ and stir for 1h to obtain inclusion complex I; distilled mixture I is for later use; Step 2: Crush 10g of peach kernels to obtain peach kernel powder; add 90g of deionized water (containing 0.9g of citric acid) to the peach kernel powder, heat for steam distillation, maintain a gentle boil, and collect the distillate; distill until the distillate no longer increases, let stand, and separate the volatile oil using a separatory funnel to obtain peach kernel volatile oil for later use; weigh the raw materials according to the ratio of β-cyclodextrin to peach kernel volatile oil = 5:1 (g / mL), first dissolve β-cyclodextrin and NaCl in an appropriate amount of hot water, then add the peach kernel volatile oil while stirring, keep warm at 60℃ and stir for 1 hour to obtain inclusion complex II; the distilled mixture II is for later use; Step 3: Mix the distilled mixture I from Step 1 and the distilled mixture II from Step 2, add 6g of licorice, 15g of poria cocos, 10g of alisma plantago-aquatica and 15g of salvia miltiorrhiza, and reflux extract at 80℃ for 1.5h. Then add 6g of rhubarb and 400g of deionized water, and continue to reflux extract for 0.5h. Filter to obtain the extract. Step 4: Concentrate the extract under reduced pressure to a clear paste with a relative density of 1.30 - 1.35 (65°C). Add cross-linked polyvinylpyrrolidone (0.25% of the weight of the clear paste), mix well, dry, and pulverize to obtain dry paste powder. Mix the dry paste powder, inclusion complex I in Step 1, and inclusion complex II in Step 2, add an appropriate amount of xylitol, prepare soft material with 93% ethanol solution, granulate, dry, and package (10 grams per package) to obtain the traditional Chinese medicine formula granules.

[0026] Performance Test I. Effect of Traditional Chinese Medicine Composition on Wound Healing of Diabetic Rat Feet 1. Experimental Design This experiment was completed in the animal center of our hospital. The drugs used in this invention have been verified to have no acute or long-term toxicity. The following experimental contents refer to existing literature.

[0027] Select healthy barrier environment SD rats with a body weight of 200 ± 20 g, license number: SYXK(津)2025 - 0004. The rats were adaptively fed for 7 days before the experiment.

[0028] Modeling method: Feed the rats with a high-sugar and high-fat diet for 4 weeks, then intraperitoneally inject 1% streptozotocin solution (dissolved in citric acid buffer solution with pH 4.5). After injection, measure the blood glucose. If the blood glucose level is ≥16.7 mmol / L for 5 consecutive days, the diabetes model is successfully established.

[0029] Anesthetize the rats with successful diabetes models, shave the hair on their backs, make a 10 mm × 10 mm wound on the back, place a silicone ring around the wound, and cover the wound with a transparent dressing. Disinfect the wound with conventional iodophor every day. When an ulcerated wound is observed, the diabetic foot model is successfully established.

[0030] Select rats with successful diabetic foot models, randomly divide them into a model group, experimental groups 1 - 3, with 10 rats in each group; another 10 rats with successful diabetes models have their backs only shaved without making wounds as the control group.

[0031] The rats in experimental group 1 were intragastrically administered the traditional Chinese medicine formula granules obtained in Example 4, the rats in experimental group 2 were intragastrically administered the traditional Chinese medicine formula granules obtained in Example 5, the rats in experimental group 3 were intragastrically administered the traditional Chinese medicine formula granules obtained in Comparative Example 1, and the rats in experimental group 4 were intragastrically administered the traditional Chinese medicine formula granules obtained in Comparative Example 2; the blank group and the model group were intragastrically administered an equal amount of distilled water. The wound was disinfected with conventional iodophor every day. The administration lasted for 20 days, and the dosage was 2.7 g / kg.

[0032] 2. Detection Indexes During the administration period, observe the wound healing situation every day, and use a vernier caliper to measure the wound width on the 1st, 10th, and 20th days to calculate the wound area and wound healing rate.

[0033] On day 30, after measuring the wound width, blood was collected from the tail vein to determine fasting blood glucose, serum TNF-α, IL-1β, and IL-6 levels.

[0034] 3. Results and Analysis 3.1 Wound healing status in rats As shown in Table 1, the wound area of ​​rats in experimental groups 1 and 2 was significantly reduced and the wound healing was better, which was significantly better than that of experimental group 3. This indicates that the traditional Chinese medicine preparation provided by the present invention can effectively reduce the wound area of ​​diabetic rats and improve the wound healing rate, with obvious effects.

[0035] Table 1. Changes in blood glucose and wound area in rats of each group. Note: This indicates that compared with test group 1, P < 0.05.

[0036] 3.2 Serum levels of inflammatory factors in each group of rats As shown in Table 2, the serum levels of TNF-α, IL-1β, and IL-6 in the model group rats were significantly higher, while the levels of TNF-α, IL-1β, and IL-6 in groups 1-3 of the experiment were significantly lower, with significant differences between groups 1, 2, and 4 and group 3.

[0037] Table 2. Changes in serum inflammatory factor levels in rats of different groups Note: This indicates that compared with test group 1, P < 0.05.

[0038] II. Optimization of Traditional Chinese Medicine Formula Granule Process 1. Routine Examination of Traditional Chinese Medicine Formula Granules The traditional Chinese medicine formula granules obtained in Examples 4-6 and Comparative Examples 1-3 were subjected to routine performance tests, repeated 3 times. The results are shown in Table 3 below.

[0039] As shown in Table 3, the traditional Chinese medicine formula granules prepared in Examples 4-6 of this invention have a high forming rate, high granule quality, short dissolution time, no product precipitation in the later stage, and low water absorption rate. Comparative Example 1 uses a traditional method for preparing traditional Chinese medicine formula granules, which has good quality, but the granules contain fine angelica powder, which cannot be completely dissolved, and the moisture absorption rate is high. In Comparative Example 2, the volatile oil is extracted by traditional steam distillation and directly added to the clear extract. Cross-linked polyvinylpyrrolidone is not added to the clear extract, resulting in a viscous clear extract, low granule forming rate, increased hardness, and difficulty in dissolving. Furthermore, during the standing process after dissolution, the presence of volatile oil causes some components to precipitate, making the liquid turbid. In Comparative Example 3, the preparation method of the volatile oil inclusion complex lacks some components, which prolongs the dissolution time and affects the clarity of the liquid.

[0040] Table 3. Routine inspection results of granules with different formulations 2. Stability Study of Traditional Chinese Medicine Formula Granules The herbal formula granules obtained in Examples 4-6 and Comparative Examples 2-3 were placed in an environment with a temperature of 40±2℃ and a relative humidity of 75±5% after being packaged in commercially available packaging for accelerated testing. Samples were taken at 0 months, 1 month, 2 months, 3 months, 4 months and 6 months to determine the loss rate. The results are shown in Table 4.

[0041] As shown in Table 4, the volatile oil obtained in Comparative Example 2, without the preparation of inclusion complex, experienced a significant loss under accelerated testing conditions. After the inclusion complex was prepared, the loss was reduced. The inclusion complex in Comparative Example 3 had a different composition, and its loss rate was lower than that of Comparative Example 2, but still higher than that of Examples 4-6 of this invention. This indicates that the addition of micronized silica gel, α-lipoic acid, and NaCl can improve the stability of the volatile oil, significantly reduce its loss rate, and improve the stability of the traditional Chinese medicine preparation, thereby ensuring its efficacy.

[0042] Table 4 Comparison of accelerated loss rates of peach kernel volatile oil

Claims

1. A traditional Chinese medicine formula granule for treating gangrene, characterized in that, It is prepared from the following ingredients: Peach kernel 8-15 parts by weight, rhubarb 5-10 parts by weight, cinnamon twig 5-10 parts by weight, prepared licorice root 5-10 parts by weight, poria cocos 10-20 parts by weight, alisma plantago-aquatica 8-15 parts by weight, angelica sinensis 10-15 parts by weight, salvia miltiorrhiza 10-20 parts by weight.

2. The traditional Chinese medicine formula granules as described in claim 1, characterized in that, The method for preparing the traditional Chinese medicine formula granules includes the following steps: Step 1: Crush Angelica sinensis and Cinnamomum cassia to obtain a mixed fine powder; add water containing L-ascorbic acid palmitate to the mixed fine powder, soak, steam distill, collect the distillate and separate the volatile oil to obtain a mixed volatile oil for later use; dissolve α-lipoic acid in the mixed volatile oil, then add micronized silica gel and mix to obtain a mixture for later use; dissolve β-cyclodextrin and add it to the mixture, stir to encapsulate, and obtain inclusion complex I; distilled mixture I is for later use. Step 2: Crush peach kernels to obtain peach kernel powder; add water containing citric acid to the peach kernel powder, steam distill, collect the distillate and separate the volatile oil to obtain peach kernel volatile oil for later use; dissolve β-cyclodextrin and NaCl and add it to the peach kernel volatile oil, stir to encapsulate, and obtain inclusion compound II; distilled mixture II is for later use. Step 3: Mix the mixture I after distillation in Step 1 and the mixture II after distillation in Step 2, add licorice, poria cocos, alisma plantago-aquatica and salvia miltiorrhiza, reflux extract, then add rhubarb and water, continue reflux extract, filter, and obtain the extract; Step 4: Concentrate the extract under reduced pressure to obtain a clear paste, add cross-linked polyvinylpyrrolidone (0.2-0.3% of the weight of the clear paste), mix well, dry and pulverize to obtain a dry paste powder; mix the dry paste powder, inclusion compound I from step 1 and inclusion compound II from step 2, add xylitol and 93% ethanol solution to prepare a soft material, granulate, dry, and package to obtain traditional Chinese medicine formula granules.

3. The traditional Chinese medicine formula granules as described in claim 1, characterized in that, In step 1, the amount of water added is 8-10 times the weight of the mixed fine powder.

4. The traditional Chinese medicine formula granules as described in claim 1, characterized in that, In step 1, the amount of L-ascorbate palmitate added to the water is 0.2 mg / g.

5. The traditional Chinese medicine formula granules as described in claim 1, characterized in that, In step 1, the mass-to-volume ratio of β-cyclodextrin, micronized silica gel, α-lipoic acid, and mixed volatile oil is (4-6):(0.1-0.2):(0.03-0.05):1 (g / g / g / mL).

6. The traditional Chinese medicine formula granules as described in claim 1, characterized in that, In step 2, the amount of water added is 8-10 times the weight of the peach kernel powder.

7. The traditional Chinese medicine formula granules as described in claim 1, characterized in that, In step 2, the amount of citric acid added to the water is 10 mg / g.

8. The traditional Chinese medicine formula granules as described in claim 1, characterized in that, In step 2, the mass-to-volume ratio of β-cyclodextrin, NaCl, and peach kernel volatile oil is (4-6):(0.1-0.2):

1.

9. The traditional Chinese medicine formula granules as described in claim 1, characterized in that, In step 4, the amount of cross-linked polyvinylpyrrolidone added is 0.2-0.3% of the weight of the extract.

Images