Traditional Chinese medicine spray for diabetic foot and preparation method thereof

Abstract

The present application relates to a kind of traditional Chinese medicine spray for diabetic foot and its preparation method, the prescription of the spray is composed of Huangqi, safflower, cassia, cassia twig, chuanxiong, flying dragon blood tree, frankincense, myrrh and rattan, the present application first uses steam distillation method to extract volatile oil, then uses ultrasonic extraction method to extract water-soluble effective component in Yufuzhang, finally, by adding emulsifier, the volatile oil is evenly dispersed into water extract to prepare uniform and stable spray, the spray prepared by the present application improves clinical efficacy, saves the dosage of medicinal materials, and is convenient for patients to carry, use and store.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of medicine, in particular to a traditional Chinese medicine spray for diabetic foot and a preparation method thereof. BACKGROUND

[0002] Diabetic foot belongs to the category of "mutilation" of peripheral vascular disease, which is a kind of lesion caused by factors such as diabetic vascular disease and / or neuropathy, infection, etc. leading to the destruction of the foot or lower extremity tissue of diabetic patients. Diabetic foot often combines infection and / or different degrees of arterial occlusion of lower extremity, and the incidence of foot ulcer is 4% to 10%, the annual incidence of diabetic foot ulcer in China is 8.1%, and the amputation rate of severe patients is 19.3%. The treatment of diabetic foot is tricky, which leads to long hospitalization period, great pain and high cost for patients. Effective control of infection and improvement of blood circulation can create conditions for ulcer healing. Traditional therapy for diabetic foot is intravascular intervention and intravenous and oral administration of blood-activating and stasis-removing drugs to improve circulation, which can relieve clinical symptoms and create conditions for ulcer healing. However, systemic administration has many contraindications and complications, and is not easy to adhere to, which is prone to recurrence.

[0003] Yufufang is a clinical experience prescription of Guizhou Qian Nan Buyi and Miao Autonomous Prefecture Hospital of Traditional Chinese Medicine, which is composed of Huangqi, Honghua, Rougui, Guizhi, Chuanqiong, Feilongzhangxue, Ruixiang, Mudan, and Pintengteng. It has the effects of warming kidney and warming spleen, activating blood and dredging collaterals, and is used for treating diabetic foot (spleen-kidney yang deficiency and meridian obstruction). The symptoms include foot coolness, pale or dark purple skin, decreased skin temperature, cold pain, difficult to reduce with warming, soreness of waist and knees, persistent numbness below knees, and severe limb pain or persistent pain, and difficult to sleep. In the prescription, Huangqi supplements spleen and qi, raises yang, removes water and swelling, removes stagnation and obstruction, and astringes ulcer and promotes tissue regeneration. Rougui warms kidney, dispels cold and relieves pain, and activates blood and unblocks meridians. Guizhi, Honghua activate blood, remove blood stasis, activate blood and qi, dispel cold and relieve pain. Feilongzhang and Pintengteng activate blood, remove blood stasis, detoxify, relieve pain, and relieve pain. Ruixiang and Mudan activate blood, relieve pain, relieve swelling, promote tissue regeneration, and remove blood stasis. The combination of these drugs can warm kidney and warm spleen, activate blood and dredge collaterals.

[0004] Yufufang has been used in clinic for more than 10 years, and has been used for the treatment of more than 500 patients, with significant effect and high safety. It is intended to be developed into a hospital preparation for clinical use. At present, Yufufang is used in our hospital by decocting and soaking feet, but according to the literature, Honghua, Rougui, Guizhi, Chuanqiong, Feilongzhangxue, Ruixiang and Mudan in the prescription contain volatile oil, which is the main material basis for activating blood and unblocking meridians, removing blood stasis and relieving pain. The original clinical use of water decoction leads to serious loss of effective components due to the failure to collect volatile oil, which inevitably causes serious waste of medicinal materials. In addition, the original prescription is inconvenient to use and carry by water decoction and soaking feet.

[0005] In view of the above technical problems, the invention team of our hospital has carried out a series of researches, first uses water vapor distillation method to extract volatile oil, then uses ultrasonic extraction method to extract water-soluble effective components in Yufuzhong, and finally adds emulsifier to uniformly disperse the volatile oil into the water extract to prepare a uniform and stable spray, which not only enriches the volatile oil in Yufuzhong, but also facilitates the use and carrying of the spray by patients. SUMMARY

[0006] The purpose of the present application is to provide a traditional Chinese medicine spray for diabetic foot.

[0007] Another purpose of the present application is to provide a preparation method of the traditional Chinese medicine spray.

[0008] The prescription of the spray comprises 10-30g of Huangqi, 10-30g of Honghua, 10-30g of Rougui, 10-30g of Guizhi, 5-15g of Chuanqiong, 5-15g of Feilongzhangxue, 3-8g of Ruixiang, 3-8g of Muding, and 5-15g of Bantangteng.

[0009] Preferably, the prescription of the spray comprises 20g of Huangqi, 20g of Honghua, 20g of Rougui, 20g of Guizhi, 10g of Chuanqiong, 10g of Feilongzhangxue, 6g of Ruixiang, 6g of Muding, and 10g of Bantangteng.

[0010] The preparation method comprises the following steps:

[0011] (1) The Honghua, Rougui, Guizhi, Chuanqiong, Feilongzhangxue, Ruixiang and Muding are mixed according to the prescription amount, and are crushed into coarse powder passing through a 10-mesh sieve;

[0012] (2) The coarse powder is taken, 6-10 times the amount of water is added, and distillation extraction is carried out for 0.5-2.5 hours, the distillate is received, the volatile oil is taken after standing, and is prepared for use;

[0013] (3) The Huangqi and Bantangteng are mixed according to the prescription amount, are crushed into coarse powder passing through a 10-mesh sieve, and are added to the water medicine mixture after the extraction of the volatile oil, and ultrasonic extraction is carried out for 10-60 minutes under the condition of an ultrasonic power of 100-400W, and the filtrate is obtained after filtration;

[0014] (4) The filtrate is taken, is concentrated to a clear extract with a ratio of 1:1 to the medicinal materials, ethanol is added to the clear extract to make the alcohol content reach 50-90%, and is left to stand for 24 hours, and the ethanol is recovered and concentrated to a clear extract with a relative density of 1.10-1.20, and is prepared for use;

[0015] (5) The prepared volatile oil is taken, 0.5-3.0% of Tween 80 is added, is uniformly ground, and is added to the prepared clear extract, water is added to 100ml, is uniformly mixed, and is filled into a spray.

[0016] Preferably, the step (2) is: taking the coarse powder, adding 8-10 times amount of water to distill extract for 1.0-2.5 hours, receiving the distillate, standing to take the volatile oil, and reserving for use.

[0017] Further preferably, the step (2) is: taking the coarse powder, adding 8 times amount of water to distill extract for 2.0 hours, receiving the distillate, standing to take the volatile oil, and reserving for use.

[0018] Preferably, the step (3) is: taking the Huangqi and Bantangteng mixed according to the prescription amount, crushing into the coarse powder passing 10 mesh sieve, adding to the water and medicine mixture after extracting the volatile oil, and ultrasonic extracting for 20-40 minutes under the condition of ultrasonic power 200-300 W, filtering to obtain the filtrate.

[0019] Further preferably, the step (3) is: taking the Huangqi and Bantangteng mixed according to the prescription amount, crushing into the coarse powder passing 10 mesh sieve, adding to the water and medicine mixture after extracting the volatile oil, and ultrasonic extracting for 30 minutes under the condition of ultrasonic power 300 W, filtering to obtain the filtrate.

[0020] Preferably, the step (4) is: taking the filtrate, concentrating to the clear extract with the medicine in the ratio of 1:1, adding ethanol in the clear extract to make the alcohol content reach 60-80%, standing for 24 hours, recovering the ethanol and concentrating to the clear extract with the relative density of 1.10-1.20, and reserving for use.

[0021] Further preferably, the step (4) is: taking the filtrate, concentrating to the clear extract with the medicine in the ratio of 1:1, adding ethanol in the clear extract to make the alcohol content reach 70%, standing for 24 hours, recovering the ethanol and concentrating to the clear extract with the relative density of 1.10, and reserving for use.

[0022] Preferably, the step (5) is: taking the reserved volatile oil, adding 2% Tween 80, grinding, and then adding to the reserved clear extract, adding water to 100 ml, mixing, and canning to spray.

[0023] Beneficial effects:

[0024] (1) The water vapor distillation method is adopted to extract the volatile oil, and the volatile oil extraction amount reaches 1.98% of the medicine amount, realizing the enrichment effect of the volatile oil.

[0025] (2) The ultrasonic extraction method is adopted to extract the water-soluble effective components in the Yufuzhifang, and the content of the flavonoid effective components reaches 15.24 mg / ml, which is much higher than 8.65 mg / ml of the original water decoction method, further enriching the water-soluble effective components.

[0026] (3) After the spray is prepared by adding the emulsifier to uniformly disperse the volatile oil into the water extract, the patient is more convenient to carry, use and store.

[0027] (4) The clinical verification test results show that the decoction group and the spray group are significantly different compared with the control group (the total effective rate of the control group is 72.0%, the total effective rate of the decoction group is 82.0%, and the total effective rate of the spray group is 96.0%), wherein the significant effective rate of the spray group is 54.0%, the significant effective rate of the decoction group is 34.0%, and the medicinal material dosage of the spray group is only one third of that of the decoction group. It is shown that the spray prepared by the present application improves the clinical curative effect and saves the medicinal material dosage. DETAILED DESCRIPTION

[0028] The following examples are used to illustrate the present application, but not to limit the scope of the present application.

[0029] Prescription of Example 1

[0030] Radix Astragali 20g, Carthamus tinctorius 20g, Cinnamomum cassia 20g, Ramulus cinnamomi 20g, Ligusticum chuanxiong 10g, Drynaria fortunei 10g, Olibanum 6g, Myrrha 6g, Entada phaseoloides 10g.

[0031] Prescription of Example 2

[0032] Radix Astragali 10g, Carthamus tinctorius 10g, Cinnamomum cassia 10g, Ramulus cinnamomi 10g, Ligusticum chuanxiong 5g, Drynaria fortunei 5g, Olibanum 3g, Myrrha 3g, Entada phaseoloides 5g.

[0033] Prescription of Example 3

[0034] Radix Astragali 30g, Carthamus tinctorius 30g, Cinnamomum cassia 30g, Ramulus cinnamomi 30g, Ligusticum chuanxiong 15g, Drynaria fortunei 15g, Olibanum 8g, Myrrha 8g, Entada phaseoloides 15g.

[0035] Prescription of Example 4

[0036] Radix Astragali 15g, Carthamus tinctorius 15g, Cinnamomum cassia 15g, Ramulus cinnamomi 15g, Ligusticum chuanxiong 8g, Drynaria fortunei 8g, Olibanum 5g, Myrrha 5g, Entada phaseoloides 8g.

[0037] Prescription of Example 5

[0038] Radix Astragali 25g, Carthamus tinctorius 25g, Cinnamomum cassia 25g, Ramulus cinnamomi 25g, Ligusticum chuanxiong 12g, Drynaria fortunei 12g, Olibanum 7g, Myrrha 7g, Entada phaseoloides 12g.

[0039] Prescription of Example 6

[0040] Radix Astragali 20g, Carthamus tinctorius 15g, Cinnamomum cassia 15g, Ramulus cinnamomi 20g, Ligusticum chuanxiong 12g, Drynaria fortunei 10g, Olibanum 5g, Myrrha 6g, Entada phaseoloides 6g.

[0041] The prescriptions of Examples 1-6 are prepared by any one of the following preparation methods of Examples 7-14

[0042] Preparation method of Example 7

[0043] (1) Take safflower, cassia, cassia twig, chuanxiong, dragon blood, frankincense, myrrh by prescription amount, crush into coarse powder through 10 mesh sieve;

[0044] (2) Take coarse powder, add 8 times amount of water to distill extract for 2.0 hours, receive distillate, stand to take volatile oil, reserve;

[0045] (3) Take radix astragali and millettia reticulata by prescription amount, crush into coarse powder through 10 mesh sieve, add to water medicine mixture after extracting volatile oil, ultrasonic extract for 30 minutes under ultrasonic power 300W, filter, get filtrate;

[0046] (4) Take filtrate, concentrate to clear extract with medicine ratio 1:1, add ethanol to make alcohol content reach 70% in clear extract, stand for 24 hours, recover ethanol and concentrate to clear extract with relative density 1.10, reserve;

[0047] (5) Take reserved volatile oil, add 2% tween 80, grind, then add to reserved clear extract, add water to 100ml, mix, jar into spray.

[0048] Preparation method of example 8

[0049] (1) Take safflower, cassia, cassia twig, chuanxiong, dragon blood, frankincense, myrrh by prescription amount, crush into coarse powder through 10 mesh sieve;

[0050] (2) Take coarse powder, add 6 times amount of water to distill extract for 0.5 hours, receive distillate, stand to take volatile oil, reserve;

[0051] (3) Take radix astragali and millettia reticulata by prescription amount, crush into coarse powder through 10 mesh sieve, add to water medicine mixture after extracting volatile oil, ultrasonic extract for 10 minutes under ultrasonic power 100W, filter, get filtrate;

[0052] (4) Take filtrate, concentrate to clear extract with medicine ratio 1:1, add ethanol to make alcohol content reach 50% in clear extract, stand for 24 hours, recover ethanol and concentrate to clear extract with relative density 1.15, reserve;

[0053] (5) Take reserved volatile oil, add 0.5% tween 80, grind, then add to reserved clear extract, add water to 100ml, mix, jar into spray.

[0054] Preparation method of example 9

[0055] (1) Take safflower, cassia, cassia twig, chuanxiong, dragon blood, frankincense, myrrh by prescription amount, crush into coarse powder through 10 mesh sieve;

[0056] (2) Take the coarse powder, add 10 times the amount of water and distill for 2.5 hours, receive the distillate, and take the volatile oil by standing, for standby;

[0057] (3) Mix the Astragalus and Combretum according to the prescription amount, crush into coarse powder through 10-mesh sieve, and add to the water and medicine mixture after extraction of volatile oil, and extract under the condition of ultrasonic power 400W for 60 minutes, filter, and obtain the filtrate;

[0058] (4) Take the filtrate, concentrate to the clear extract with the ratio of 1:1 to the medicine, add ethanol to the clear extract to make the alcohol content reach 90%, stand for 24 hours, recover the ethanol and concentrate to the clear extract with the relative density of 1.20, for standby;

[0059] (5) Take the standby volatile oil, add 3.0% Tween 80, grind evenly, and then add to the standby clear extract, add water to 100ml, mix evenly, and can into spray.

[0060] Preparation method of Example 10

[0061] (1) Mix the safflower, cassia, cassia twig, chuanxiong, dragon blood, frankincense, and myrrh according to the prescription amount, and crush into coarse powder through 10-mesh sieve;

[0062] (2) Take the coarse powder, add 7 times the amount of water and distill for 1.0 hour, receive the distillate, and take the volatile oil by standing, for standby;

[0063] (3) Mix the Astragalus and Combretum according to the prescription amount, crush into coarse powder through 10-mesh sieve, and add to the water and medicine mixture after extraction of volatile oil, and extract under the condition of ultrasonic power 150W for 20 minutes, filter, and obtain the filtrate;

[0064] (4) Take the filtrate, concentrate to the clear extract with the ratio of 1:1 to the medicine, add ethanol to the clear extract to make the alcohol content reach 60%, stand for 24 hours, recover the ethanol and concentrate to the clear extract with the relative density of 1.12, for standby;

[0065] (5) Take the standby volatile oil, add 1.0% Tween 80, grind evenly, and then add to the standby clear extract, add water to 100ml, mix evenly, and can into spray.

[0066] Preparation method of Example 11

[0067] (1) Mix the safflower, cassia, cassia twig, chuanxiong, dragon blood, frankincense, and myrrh according to the prescription amount, and crush into coarse powder through 10-mesh sieve;

[0068] (2) Take the coarse powder, add 8 times the amount of water and distill for 1.5 hours, receive the distillate, and take the volatile oil by standing, for standby;

[0069] (3) Take the safflower and rattan mixed according to the prescription amount, crush into coarse powder through 10 mesh sieve, add to the water medicine mixture after extracting the volatile oil, extract under the condition of ultrasonic power 300W for 40 minutes, filter, get the filtrate;

[0070] (4) Take the filtrate, concentrate to the clear extract with the ratio of 1:1 with medicinal materials, add ethanol to the clear extract to make the alcohol content reach 70%, stand for 24 hours, recover ethanol and concentrate to the clear extract with relative density 1.15, reserve;

[0071] (5) Take the volatile oil reserved, add 2.5% Tween 80, grind evenly, then add to the clear extract reserved, add water to 100ml, mix evenly, can into a spray.

[0072] Preparation method of example 12

[0073] (1) Take the safflower, cassia, cassia twig, chuanxiong, flying dragon blood, frankincense, myrrh mixed according to the prescription amount, crush into coarse powder through 10 mesh sieve;

[0074] (2) Take the coarse powder, distill extract with 9 times amount of water for 1.8 hours, receive the distillate, stand to take the volatile oil, reserve;

[0075] (3) Take the safflower and rattan mixed according to the prescription amount, crush into coarse powder through 10 mesh sieve, add to the water medicine mixture after extracting the volatile oil, extract under the condition of ultrasonic power 150W for 35 minutes, filter, get the filtrate;

[0076] (4) Take the filtrate, concentrate to the clear extract with the ratio of 1:1 with medicinal materials, add ethanol to the clear extract to make the alcohol content reach 65%, stand for 24 hours, recover ethanol and concentrate to the clear extract with relative density 1.16, reserve;

[0077] (5) Take the volatile oil reserved, add 1.8% Tween 80, grind evenly, then add to the clear extract reserved, add water to 100ml, mix evenly, can into a spray.

[0078] Preparation method of example 13

[0079] (1) Take the safflower, cassia, cassia twig, chuanxiong, flying dragon blood, frankincense, myrrh mixed according to the prescription amount, crush into coarse powder through 10 mesh sieve;

[0080] (2) Take the coarse powder, distill extract with 9 times amount of water for 2 hours, receive the distillate, stand to take the volatile oil, reserve;

[0081] (3) Take the safflower and rattan mixed according to the prescription amount, crush into coarse powder through 10 mesh sieve, add to the water medicine mixture after extracting the volatile oil, extract under the condition of ultrasonic power 200W for 30 minutes, filter, get the filtrate;

[0082] (4) Take the filtrate, concentrate to the clear extract with the medicinal material ratio of 1:1, add ethanol to the clear extract to make the alcohol content reach 60%, stand for 24 hours, recover the ethanol and concentrate to the clear extract with the relative density of 1.10, and reserve;

[0083] (5) Take the volatile oil for reservation, add 2% Tween 80, grind, and then add to the clear extract for reservation, add water to 100ml, mix, and then can into a spray.

[0084] Preparation method of example 14

[0085] (1) Take safflower, cassia, cassia twig, chuanxiong, palm blood, frankincense, myrrh according to the prescription amount, and mix, crush into coarse powder passing through 10 mesh sieve;

[0086] (2) Take the coarse powder, add 10 times amount of water, distill and extract for 1 hour, receive the distillate, stand to take the volatile oil, and reserve;

[0087] (3) Take radix astragali and kadsura longipedunculata according to the prescription amount, mix, crush into coarse powder passing through 10 mesh sieve, and add to the water and medicine mixture after the extraction of volatile oil, and ultrasonic extract for 50 minutes under the condition of ultrasonic power 300W, filter, and obtain the filtrate;

[0088] (4) Take the filtrate, concentrate to the clear extract with the medicinal material ratio of 1:1, add ethanol to the clear extract to make the alcohol content reach 60%, stand for 24 hours, recover the ethanol and concentrate to the clear extract with the relative density of 1.10, and reserve;

[0089] (5) Take the volatile oil for reservation, add 2% Tween 80, grind, and then add to the clear extract for reservation, add water to 100ml, mix, and then can into a spray.

[0090] In order to further verify the feasibility of the application, the inventors carried out a series of experiments, as follows:

[0091] 1 Prescription composition, compatibility relationship

[0092] 1.1 Prescription

[0093] Radix astragali 20g, safflower 20g, cassia 20g, cassia twig 20g, chuanxiong 10g, palm blood 10g, frankincense 6g, myrrh 6g, kadsura longipedunculata 10g.

[0094] 1.2 Compatibility relationship

[0095] The prescription of Huangqi Bushen Buqi Shengyang, Lishu Xiaozhong, Xingzhi Tongbi, An'cu Shengji, Rougui Wenshen Sanhan Zhongtong, Guizhi, Honghua Huoxue Huayu, Huoxue Xingqi Sanhan Zhongtong, Feilongzhang, Bentan Teng Xuehuoxue Sanyu Jiedu Zhongtong, Ru Xiang, Mo Yao Huoxue Zhongtong, Xiaozhong Shengji, all the drugs together can warm kidney and spleen, activate blood and dredge collaterals. It is used for treating diabetic foot (spleen and kidney yang deficiency, meridian obstruction) with foot cool, skin pale or dark purple, skin temperature drop, cold pain, difficult to reduce with warming, soreness of waist and knees, continuous numbness below knees, severe pain or continuous pain in extremities, difficult to sleep.

[0096] 2 Preparation method research test

[0097] The prescription of Huangqi Bushen Buqi Shengyang, Lishu Xiaozhong, Xingzhi Tongbi, An'cu Shengji, Rougui Wenshen Sanhan Zhongtong, Guizhi, Honghua Huoxue Huayu, Huoxue Xingqi Sanhan Zhongtong, Feilongzhang, Bentan Teng Xuehuoxue Sanyu Jiedu Zhongtong, Ru Xiang, Mo Yao Huoxue Zhongtong, Xiaozhong Shengji, all the drugs together can warm kidney and spleen, activate blood and dredge collaterals. It is used for treating diabetic foot (spleen and kidney yang deficiency, meridian obstruction) with foot cool, skin pale or dark purple, skin temperature drop, cold pain, difficult to reduce with warming, soreness of waist and knees, continuous numbness below knees, severe pain or continuous pain in extremities, difficult to sleep.

[0098] 2.1 Volatile oil extraction process investigation

[0099] The prescription of Huangqi Bushen Buqi Shengyang, Lishu Xiaozhong, Xingzhi Tongbi, An'cu Shengji, Rougui Wenshen Sanhan Zhongtong, Guizhi, Honghua Huoxue Huayu, Huoxue Xingqi Sanhan Zhongtong, Feilongzhang, Bentan Teng Xuehuoxue Sanyu Jiedu Zhongtong, Ru Xiang, Mo Yao Huoxue Zhongtong, Xiaozhong Shengji, all the drugs together can warm kidney and spleen, activate blood and dredge collaterals. It is used for treating diabetic foot (spleen and kidney yang deficiency, meridian obstruction) with foot cool, skin pale or dark purple, skin temperature drop, cold pain, difficult to reduce with warming, soreness of waist and knees, continuous numbness below knees, severe pain or continuous pain in extremities, difficult to sleep.

[0100] 2.1.1 Water amount multiple investigation

[0101] According to the prescription proportion, the medicinal materials (20g of safflower, 20g of cinnamon, 20g of ramulus cinnamomi, 10g of ligusticum wallichii, 10g of feilongzhang, 6g of frankincense and 6g of myrrh) were weighed, mixed, and distilled with 6 times, 8 times and 10 times of water respectively to extract volatile oil, each for 1 hour, the distillate was received, and after 2 hours of standing, oil-water separation was carried out, and the weight of volatile oil was determined, and the results are shown in Table 1.

[0102] Table 1 Water amount multiple investigation results

[0103]

[0104] From the test results, it can be seen that the amount of volatile oil obtained by adding 6 times of water is low; the amount of volatile oil obtained by adding 8 times and 10 times of water is basically the same, and is higher than that obtained by adding 6 times of water. Considering comprehensively, 8 times of water is selected as the process parameter.

[0105] 2.1.2 Pretreatment method investigation

[0106] The medicinal materials (20g of safflower, 20g of cassia, 20g of ramulus cinnamomi, 10g of ligusticum wallichii, 10g of dragon's blood, 6g of frankincense, and 6g of myrrh) were weighed according to the prescription proportion, mixed, and divided into three parts, each of which was added with 8 times the amount of water. The first part was directly distilled to extract volatile oil for 1 hour, the second part was cold soaked for 1 hour and then distilled to extract volatile oil for 1 hour, and the third part was heated to 80°C for 1 hour and then distilled to extract volatile oil for 1 hour. The distillate was received, and after standing for 2 hours, oil-water separation was performed, and the weight of the volatile oil was determined. The results are shown in Table 2.

[0107] Table 2 Investigation of pretreatment methods

[0108]

[0109]

[0110] According to the test results, the efficiencies of the three distillation extraction methods for volatile oil are not significantly different, so the direct distillation extraction method is selected.

[0111] 2.1.3 Distillation time investigation

[0112] The medicinal materials (20g of safflower, 20g of cassia, 20g of ramulus cinnamomi, 10g of ligusticum wallichii, 10g of dragon's blood, 6g of frankincense, and 6g of myrrh) were weighed according to the prescription proportion, mixed, and divided into five parts, each of which was added with 8 times the amount of water and distilled to extract volatile oil for 0.5 hours, 1.0 hour, 1.5 hours, 2.0 hours, or 2.5 hours. The distillate was received, and after standing for 2 hours, oil-water separation was performed, and the weight of the volatile oil was determined. The results are shown in Table 3.

[0113] Table 3 Investigation of distillation time

[0114]

[0115] According to the test results, the volatile oil content changes little after distillation for 1.5 hours. After comprehensive consideration, it is determined to select distillation for 2.0 hours as the process parameter (according to 92g of medicinal material, distillation for 2.0 hours, the volatile oil extraction amount is 1.98% of the medicinal material feeding amount).

[0116] 2.2 Water extraction method investigation

[0117] The mixed and crushed Astragalus membranaceus and Combretum fruticosum coarse powder with a particle size of 10 mesh were added to the water and medicinal material mixture after the extraction of volatile oil to further extract. The total flavonoid content of the common components of ligusticum wallichii, safflower, Daphne giraldii and cassia in the prescription was used as an index, and the decoction method, ultrasonic extraction method and enzyme extraction method were compared.

[0118] 2.2.1 Decoction method

[0119] The medicinal materials (20g of safflower, 20g of cassia bark, 20g of ramulus cinnamomi, 10g of ligusticum wallichii, 10g of dragon's blood, 6g of frankincense, and 6g of myrrh) are weighed according to the prescription proportion, mixed, 8 times the amount of water is added, and distilled extraction is performed for 1.5 hours. The volatile oil is collected for standby. The mixed and crushed astragalus and paederia foetida coarse powder which is passed through a 10-mesh sieve is added to the water and medicinal material mixture after the volatile oil extraction. Ultrasonic extraction is performed for 30 minutes under the condition of 200W. Filtration is performed. The filtrate is concentrated and constant volume is performed to 250ml. The total flavonoid content is determined. The results are shown in Table 4.

[0120] 2.2.2 Ultrasonic method

[0121] The medicinal materials (20g of safflower, 20g of cassia bark, 20g of ramulus cinnamomi, 10g of ligusticum wallichii, 10g of dragon's blood, 6g of frankincense, and 6g of myrrh) are weighed according to the prescription proportion, mixed, 8 times the amount of water is added, and distilled extraction is performed for 1.5 hours. The volatile oil is collected for standby. The mixed and crushed astragalus and paederia foetida coarse powder which is passed through a 10-mesh sieve is added to the water and medicinal material mixture after the volatile oil extraction. Ultrasonic extraction is performed for 30 minutes under the condition of 200W. Filtration is performed. The filtrate is concentrated and constant volume is performed to 250ml. The total flavonoid content is determined. The results are shown in Table 4.

[0122] 2.2.3 Enzymatic hydrolysis method

[0123] The medicinal materials (20g of safflower, 20g of cassia bark, 20g of ramulus cinnamomi, 10g of ligusticum wallichii, 10g of dragon's blood, 6g of frankincense, and 6g of myrrh) are weighed according to the prescription proportion, mixed, 8 times the amount of water is added, and distilled extraction is performed for 1.5 hours. The volatile oil is collected for standby. The mixed and crushed astragalus and paederia foetida coarse powder which is passed through a 10-mesh sieve is added to the water and medicinal material mixture after the volatile oil extraction. 2% cellulase is added. Enzymatic hydrolysis is performed for 24 hours under the condition of 50℃ and PH value 5.0. Filtration is performed. The filtrate is concentrated and constant volume is performed to 250ml. The total flavonoid content is determined. The results are shown in Table 4.

[0124] Table 4 Investigation results of water extraction method

[0125]

[0126] The test results show that the ultrasonic method has the highest total flavonoid content in the medicinal liquid. Therefore, the ultrasonic method is selected as the extraction method.

[0127] 2.2.4 Process parameter investigation of ultrasonic extraction method

[0128] 2.2.4.1 Ultrasonic power

[0129] The prescription proportion of medicinal materials (20g of safflower, 20g of cassia, 20g of ramulus cinnamomi, 10g of ligusticum wallichii, 10g of dragon's blood, 6g of frankincense, and 6g of myrrh) was weighed, mixed, and divided into 4 parts. 8 times the amount of water was added, and distillation extraction was performed for 2.0 hours. The volatile oil was collected for standby. The mixed and crushed astragalus and embelia laevigata coarse powder which passed a 10-mesh sieve were added to the water and medicine mixture after the extraction of the volatile oil. Ultrasonic extraction was performed for 30 minutes at powers of 100W, 200W, 300W, and 400W, respectively. Filtration was performed, the filtrate was concentrated and constant volume was performed to 250ml, and the total flavonoid content was determined. The results are shown in Table 5.

[0130] Table 5 Ultrasonic power investigation results

[0131]

[0132] The test results show that after the ultrasonic power reaches 200w, the total flavonoid content in the extraction liquid changes little. After comprehensive consideration, the ultrasonic power of 300W is selected as the process parameter.

[0133] 2.2.4.2 Ultrasonic time investigation

[0134] The prescription proportion of medicinal materials (20g of safflower, 20g of cassia, 20g of ramulus cinnamomi, 10g of ligusticum wallichii, 10g of dragon's blood, 6g of frankincense, and 6g of myrrh) was weighed, mixed, and divided into 5 parts. 8 times the amount of water was added, and distillation extraction was performed for 1.5 hours. The volatile oil was collected for standby. The mixed and crushed astragalus and embelia laevigata coarse powder which passed a 10-mesh sieve were added to the water and medicine mixture after the extraction of the volatile oil. Ultrasonic extraction was performed for 10 minutes, 20 minutes, 30 minutes, 40 minutes, and 60 minutes at a power of 200W, respectively. Filtration was performed, the filtrate was concentrated and constant volume was performed to 250ml, and the total flavonoid content was determined. The results are shown in Table 6.

[0135] Table 6 Ultrasonic time investigation results

[0136]

[0137] The test results show that after the extraction time reaches 30 minutes, the total flavonoid content in the extraction liquid changes slowly. After comprehensive consideration, the ultrasonic time of 30 minutes is selected as the process parameter.

[0138] 2.3 Purification process investigation

[0139] Since there are many impurities in the extraction liquid, it is necessary to purify the extraction liquid. Ethanol precipitation is a commonly used method for purifying traditional Chinese medicine extracts. The key factor affecting the purification effect is the alcohol precipitation concentration. In this test, the impurity removal rate and total flavonoid retention rate before and after purification were used as indicators to study the alcohol precipitation concentration.

[0140] The medicinal materials (120g of safflower, 120g of cassia bark, 120g of ramulus cinnamomi, 60g of ligusticum wallichii, 60g of dragon's blood, 36g of frankincense, and 36g of myrrh) are weighed according to the prescription ratio, mixed, 8 times the amount of water is added, and distilled extraction is carried out for 2.0 hours, and the volatile oil is collected for standby, the mixed and crushed astragalus and embelia laevigata coarse powder which is 10 meshes are added to the water medicine mixture after the volatile oil extraction, ultrasonic extraction is carried out for 30 minutes under the power of 300W, filtration is carried out, the filtrate is concentrated to the clear paste of 1:1 of the original medicinal materials, and the average is divided into 6 parts, one part is used to determine the total flavonoid content and the dry paste yield, and the other 5 parts are added with ethanol to make the alcohol content reach 50%, 60%, 70%, 80% and 90% respectively, and the filtration is carried out after 24 hours of standing, the filtrate is concentrated and constant volume is made to 100ml, the total flavonoid content and the dry paste yield are determined, the total flavonoid retention rate and the impurity removal rate are calculated, and the results are shown in Table 7.

[0141] Table 7 results of the purification process investigation

[0142]

[0143] The test results show that the total flavonoid retention rate decreases with the increase of the alcohol precipitation concentration, the impurity removal rate increases with the increase of the alcohol precipitation concentration, and considering comprehensively, 70% is taken as the process parameter, the total flavonoid retention rate is above 85% under the alcohol precipitation concentration, the impurity removal rate is about 50%, and the retention rate and the impurity removal effect are ideal.

[0144] 2.4 Preparation forming process research

[0145] The object of the application is to prepare the Youfu formula extraction and purification into a spray, because the solubility of volatile oil in aqueous solution is poor, it cannot be directly dispersed in the aqueous solution, therefore, an emulsifier needs to be added, and the volatile oil is dissolved in water by means of emulsification. Tween 80 is a commonly used emulsifier, which is a non-ionic surfactant, and can form small micellar structures in water, which wrap the volatile oil molecules and can be uniformly dispersed in water, and at the same time, Tween 80 can also reduce the surface tension between volatile oil and water, so that they can be more easily mixed and dissolved. Therefore, Tween 80 is selected as the emulsifier of the preparation in the research, and the amount is investigated by taking the stability of the preparation and the uniformity of the volatile oil dispersion as indexes, and the test method is as follows.

[0146] The prescription proportion of medicinal materials (Radix Astragali 200g, Safflower 200g, Cinnamon 200g, Ramulus Cinnamomi 200g, Rhizoma Chuanxiong 100g, Dragon Palm Blood 100g, Olibanum 60g, Myrrh 60g, Poison Ivy 100g) is weighed, mixed, 8 times of water is added, distilled and extracted for 2.0 hours, and the volatile oil is collected for standby. The mixed and crushed Radix Astragali and Poison Ivy coarse powder of 10 meshes is added into the water medicine mixture after the extraction of volatile oil, ultrasonic extraction is carried out for 30 minutes under the power of 300W, filtration is carried out, the filtrate is concentrated to the clear paste of 1:1 of the original medicinal materials, ethanol is added to make the alcohol content reach 70%, and the solution is prepared. The solution is evenly divided into 4 parts, each of 250ml, and standby. The volatile oil is also evenly divided into 4 parts, 1.25g, 2.50g, 5.00g and 7.50g of Tween 80 (0.5%, 1.0%, 2.0% and 3.0% of the weight of the water solution) is added respectively, and the mixture is ground, and then added into the above-mentioned 250ml water solution respectively, stirred uniformly, and the dispersion uniformity of the volatile oil is observed. The solution is placed at 4℃ and 37.5℃ respectively for 7 days, and whether the volatile oil is precipitated on the surface of the solution is observed. The results are shown in Table 8.

[0147] Table 8 Results of emulsifier dosage investigation

[0148] Table 8 Results of emulsifier dosage investigation

[0149]

[0150] The test results show that the volatile oil can be uniformly and stably dispersed in the solution by using 2.0% to 3.0% of Tween 80 as the emulsifier, and the ideal spray content is prepared, so that the preparation forming process selects 2.0% of Tween 80 as the process parameter.

[0151] 3 Clinical efficacy verification

[0152] In order to verify the rationality, scientificity and advancement of the preparation process of the application, the Yufufang is prepared into a spray according to the process of the application and applied in the clinic, and the Yufufang decoction and conventional western medicine treatment are used as controls.

[0153] The composition of the Yufufang is Radix Astragali 20g, Safflower 20g, Cinnamon 20g, Ramulus Cinnamomi 20g, Rhizoma Chuanxiong 10g, Dragon Palm Blood 10g, Olibanum 6g, Myrrh 6g, and Poison Ivy 10g, and the use method is to decoct the soup and soak the feet, 1 dose each time, and 1 time each day. The original prescription is prepared into a spray of 100ml according to the application, 3 times each day, 10ml each time, and each dose can be used for 3.3 days. That is, after the Yufufang is prepared into a spray, the dosage of medicinal materials is only one third of the original use method.

[0154] 3.1 Data and methods

[0155] 3.1.1 Clinical data

[0156] 150 cases of diabetic foot patients admitted to our hospital from January 2023 to December 2023 were selected as the research objects, on the basis of informed consent, and were divided into control group, decoction group and spray group, 50 cases in each. The control group included 25 males and 25 females, aged 40-69 years, with an average age of (58.37±5.47) years, a diabetes duration of 3-19 years, an average of (12.38±2.18) years, and a diabetic foot duration of 9 months to 6 years, an average of (4.36±1.27) years. The decoction group included 24 males and 26 females, aged 40-70 years, with an average age of (60.12±4.36) years, a diabetes duration of 2-20 years, an average of (14.84±3.55) years, and a diabetic foot duration of 7 months to 8 years, an average of (6.37±1.39) years. The spray group included 26 males and 24 females, aged 41-70 years, with an average age of (56.74±6.56) years, a diabetes duration of 2-20 years, an average of (15.57±2.54) years, and a diabetic foot duration of 7 months to 7 years, an average of (6.54±1.86) years. There was no statistically significant difference in gender, age and course of disease among the three groups (P>0.05), which was comparable.

[0157] 3.1.2 Inclusion criteria and exclusion criteria

[0158] Inclusion criteria: ① Age 40-70 years; ② Meet the diagnostic criteria of diabetic foot (diabetic peripheral gangrene) in Western medicine; ③ Meet the diagnostic criteria of gangrene in traditional Chinese medicine. Exclusion criteria: ① Combined with other serious diseases; ② Allergic to Chinese herbal medicine in the past; ③ Cognitive dysfunction.

[0159] 3.1.3 Treatment method

[0160] Low-salt low-fat diabetic diet; hypoglycemic and lipid-lowering therapy; anti-infection therapy; improve circulation therapy; wound dressing at regular intervals. Control group: oral administration of Maigu Fukang tablets (Guojia Zhunzi Z12020023, Tianjin Tongren Tang Group Co., Ltd.), 2.4 g / time, 3 times / d. Treatment for 4 weeks.

[0161] Decoction group: in addition to the same treatment as the control group, Yufufang decoction foot bath was added, 1 dose each time, 1 time per day. Treatment for 4 weeks.

[0162] Spray group: in addition to the same treatment as the control group, the spray prepared by the present application was added, 3 times a day, 10 ml each time. Treatment for 4 weeks.

[0163] 3.1.4 Observation index

[0164] ①Comparison of clinical efficacy between the two groups: the main basis for comprehensive evaluation was the changes in skin temperature and color, and the improvement of subjective state, among which, obvious changes in skin temperature and color, and significant improvement of subjective symptoms were considered as marked effect; changes in skin temperature and color, and improvement of subjective symptoms were considered as effective; no changes in skin temperature and color, and no improvement or aggravation of subjective symptoms were considered as ineffective; the total effective rate = marked effect rate + effective rate. ②Comparison of inflammatory factors between the two groups: 5 ml of fasting venous blood was drawn from the two groups of patients respectively, and the levels of serum inflammatory factors, including high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-12 (IL-12), and tumor necrosis factor-α (TNF-α) were compared before and after 4 weeks of treatment. (3) Comparison of intermittent claudication distance (m) and pain score changes between the two groups before and after 4 weeks of treatment: visual analogue score (VAS) was used for evaluation, which was divided into 4 grades: no pain 0 points, mild pain 1-3 points, moderate pain 4-6 points, and severe pain 7-10 points.

[0165] SPSS22.0 statistical software was used for analysis, measurement data was represented by (x±s) and t test, count data was represented by (%) and χ2 test, and P<0.05 was considered as statistically significant difference.

[0166] 3.1.5 Results

[0167] 3.1.5.1 Comparison of inflammatory factor levels between the three groups of patients before and after treatment

[0168] There was no statistically significant difference in the comparison of inflammatory factor levels between the three groups of patients before treatment (P>0.05). After treatment, the levels of inflammatory factors were significantly decreased compared with those before treatment (P<0.05), and the levels of inflammatory factors in the spray group were lower than those in the decoction group after treatment (P<0.05). It is indicated that the curative effect of Yufufang is improved after being made into a spray. See Table 9.

[0169]

[0170]

[0171]

[0172] Note: *P<0.05 for comparison before and after treatment; +P<0.05 for comparison between the decoction group and the spray group after treatment

[0173] 3.1.5.2 Comparison of pain scores and intermittent claudication distances between the three groups of patients

[0174] ​​There was no statistically significant difference in pain score and intermittent claudication distance of the patients in the three groups before treatment (P>0.05). After treatment, the pain score of the patients in the three groups was decreased (P<0.05), and the intermittent claudication distance was increased (P<0.05), and the treatment effect of the spray group was obviously better than that of the decoction group (P<0.05). See Table 10.

[0175] Table 10 Comparison of pain score and intermittent claudication distance of the three groups before and after treatment

[0176]

[0177] Note: *P<0.05 for comparison before and after treatment; +P<0.05 for comparison after treatment between the spray group and the decoction group

[0178] 3.1.5.3 Comparison of clinical effects of the three groups of patients

[0179] The treatment effect of the spray group was obviously better than that of the decoction group and the control group. See Table 11.

[0180] Table 11 Comparison of clinical effects of the three groups of patients

[0181]

[0182] Note: *P<0.05 for comparison with the control group; +P<0.05 for comparison after treatment between the spray group and the decoction group

[0183] Since the crude drug usage amount of the spray is only one third of that of the decoction, and the clinical effect verification result shows that the treatment effect of the spray group is obviously better than that of the decoction group, it is indicated that the application achieves the application target of saving the medicinal material usage amount and being convenient for patients to use.

[0184] Although the application has been described in detail in the foregoing general description, specific embodiments and experiments, some modifications or improvements can be made on the basis of the application, which is obvious to those skilled in the art, and therefore, these modifications or improvements made on the basis of not deviating from the spirit of the application, all belong to the scope of protection claimed by the application.

Claims

1. A traditional Chinese medicine spray for diabetic foot, characterized in that, The spray formulation consists of 10-30g Astragalus membranaceus, 10-30g Carthamus tinctorius, 10-30g Cinnamomum cassia, 10-30g Cinnamomum cassia twig, 5-15g Ligusticum chuanxiong, 5-15g Gynostemma pentaphyllum, 3-8g Boswellia carterii, 3-8g Commiphora myrrha, and 5-15g Clematis armandii.

2. The traditional Chinese medicine spray according to claim 1, characterized in that, The prescription for the spray consists of 20g of Astragalus membranaceus, 20g of Carthamus tinctorius, 20g of Cinnamomum cassia ... twig, 10g of Ligusticum chuanxiong, 10g of Pterocarya stenoptera, 6g of Boswellia carterii, 6g of Commiphora myrrha, and 10g of Caulis Achyranthes bidentata.

3. The method for preparing the traditional Chinese medicine spray according to any one of claims 1-2, characterized in that, The preparation method includes the following steps: (1) Take the prescribed amount of safflower, cinnamon, cassia twig, chuanxiong rhizome, galangal blood, frankincense, and myrrh, mix them together, and grind them into coarse powder that passes through a 10-mesh sieve; (2) Take the coarse powder, add 6-10 times the amount of water and distill for 0.5-2.5 hours, collect the distillate, let it stand and collect the volatile oil for later use; (3) Take the prescribed amount of Astragalus membranaceus and Achyranthes bidentata, mix them, grind them into coarse powder that passes through a 10-mesh sieve, add them to the water-medicine mixture after the volatile oil has been extracted, and extract them by ultrasonic extraction at an ultrasonic power of 100-400 W for 10-60 minutes. Filter to obtain the filtrate. (4) Take the filtrate and concentrate it to a clear extract with a ratio of 1:1 to the medicinal material. Add ethanol to the clear extract to make the alcohol content reach 50-90%. Let it stand for 24 hours, recover the ethanol and concentrate it to a clear extract with a relative density of 1.10-1.20 for later use. (5) Take the prepared volatile oil, add 0.5-3.0% Tween 80, grind evenly, then add it to the prepared clear ointment, add water to 100ml, mix well, and bottle into a spray.

4. The preparation method according to claim 3, characterized in that, The step (2) is as follows: take the coarse powder, add 8-10 times the amount of water and distill for 1.0-2.5 hours, collect the distillate, let it stand and collect the volatile oil for later use.

5. The preparation method according to claim 4, characterized in that, The step (2) is as follows: take the coarse powder, add 8 times the amount of water and distill for 2.0 hours, collect the distillate, let it stand and take the volatile oil for later use.

6. The preparation method according to claim 3, characterized in that, The step (3) is as follows: take the prescribed amount of Astragalus membranaceus and Achyranthes bidentata, mix them, crush them into coarse powder that passes through a 10-mesh sieve, add them to the water-medicine mixture after the volatile oil has been extracted, and extract them by ultrasonic extraction for 20-40 minutes under ultrasonic power of 200-300 W, filter them, and obtain the filtrate.

7. The preparation method according to claim 6, characterized in that, The step (3) is as follows: take the prescribed amount of Astragalus membranaceus and Achyranthes bidentata, mix them, crush them into coarse powder that passes through a 10-mesh sieve, add them to the water-medicine mixture after the volatile oil has been extracted, and extract them by ultrasonic extraction at an ultrasonic power of 300 W for 30 minutes. Filter the mixture to obtain the filtrate.

8. The preparation method according to claim 3, characterized in that, The step (4) is as follows: take the filtrate, concentrate it to a clear paste with a ratio of 1:1 to the medicinal material, add ethanol to the clear paste to make the alcohol content reach 60-80%, let it stand for 24 hours, recover the ethanol and concentrate it to a clear paste with a relative density of 1.10-1.20 for later use.

9. The preparation method according to claim 8, characterized in that, The step (4) is as follows: take the filtrate, concentrate it to a clear paste with a ratio of 1:1 to the medicinal material, add ethanol to the clear paste to make the alcohol content reach 70%, let it stand for 24 hours, recover the ethanol and concentrate it to a clear paste with a relative density of 1.10, and set it aside for later use.

10. The preparation method according to claim 3, characterized in that, The step (5) is as follows: take the prepared volatile oil, add 2% Tween 80, grind it evenly, then add it to the prepared clear ointment, add water to 100ml, mix well, and bottle it into a spray.

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