Traditional Chinese medicine ointment as well as preparation method and application thereof

Abstract

The invention discloses a traditional Chinese medicine ointment as well as a preparation method and application thereof. The preparation method of the traditional Chinese medicine ointment provided by the invention comprises the following steps: adding a gamboge medicinal material into water, carrying out reflux cooking, filtering filtrate, concentrating into paste, drying and crushing to obtain gamboge powder; sulfur powder and realgar powder are added into tung oil for paste refining; cooling the obtained paste, adding gamboge powder and pearl powder, blending, and sterilizing; cooling the obtained ointment body, adding musk, and mixing to obtain the traditional Chinese medicine ointment. The traditional Chinese medicine ointment provided by the invention has the advantages of small proportion of three yellow, small toxicity and strong drug effect, can significantly reduce the ulcer area and promote ulcer healing in a short time, and has a significant effect.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine preparation, and particularly relates to a traditional Chinese medicine ointment, a preparation method thereof and an application thereof. Background Art

[0002] At present, the traditional Chinese medicine ointments sold on the market for treating skin wounds mainly have the following problems: (1) The ingredients are complex, and some traditional formulas contain up to dozens of medicinal materials; (2) The functions are single, and they are only used to treat some types of wounds; (3) The curative effects are limited, the effective rate for third-degree burns is low, and the need for deep tissue repair cannot be met.

[0003] CN1141132A discloses an external burn, wound and frostbite ointment and its preparation process, which is made from 495-505 grams of tung oil, 38-42 grams of sulfur, 14-17 grams of realgar, 0.8-1.2 grams of gamboge, 0.8-1.2 grams of musk, and 0.8-1.2 grams of pearls. The preparation process of this ointment is as follows: Heat the tung oil to 231°C - 235°C, add the mixture of sulfur powder, realgar powder and gamboge powder. After the reaction is completed, boil until it forms beads when dropped into water. Spray cold water on the surface to remove water toxicity, then add musk powder and pearl powder and stir, and cool to obtain the ointment. This ointment has unique functions and curative effects for treating burns, wounds, frostbite and residual wounds of chronic skin ulcers. However, the proportion of the three yellows in this ointment is relatively large, and it has strong irritation to the skin during use, and the patient experience is not good and other problems.

[0004] In view of this, the present invention is particularly proposed. Summary of the Invention

[0005] The purpose of the present invention is to provide a preparation method of a traditional Chinese medicine ointment. The ointment prepared by this method can obtain a higher therapeutic effect with a relatively small proportion of the three yellows, can significantly reduce the ulcer area and promote ulcer healing in a relatively short time, and the effect is remarkable. At the same time, the toxicity and irritation are relatively smaller, which is more conducive to reducing the adverse feelings of patients.

[0006] In order to achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0007] In the first aspect, the present invention provides a preparation method of a traditional Chinese medicine ointment, including the following steps:

[0008] S1. Add gamboge medicinal materials to water, reflux and steam, filter the filtrate and concentrate it to a paste state, dry it, and pulverize it to obtain gamboge powder;

[0009] S2. Add sulfur powder and realgar powder to tung oil for ointment refining;

[0010] S3. After cooling the paste obtained in step S2, add gamboge powder and pearl powder for blending and sterilization;

[0011] S4. Cool down the paste obtained in step S3, add musk, and mix to obtain the traditional Chinese medicine ointment.

[0012] In the present invention, the weight parts of each medicinal material are as follows: sulfur 45 - 65 weight parts, realgar 5 - 25 weight parts, gamboge 1 - 3 weight parts, pearl 1 - 3 weight parts, musk 1 - 3 weight parts.

[0013] As a specific embodiment of the present invention, the mass ratio of sulfur : realgar : gamboge : pearl : musk = (27 - 28) : (7 - 8) : 1 : 1 : 1. Specifically, it can be 27.5 : 7.5 : 1 : 1 : 1.

[0014] The particle sizes of the sulfur powder, realgar powder, gamboge powder, and pearl powder are all greater than 150 mesh.

[0015] In step S1, the time for reflux cooking is 4 - 7 h;

[0016] The mesh number of the sieve used for filtration is 150 mesh;

[0017] The conditions for concentration are: temperature is 75 - 85 °C, and vacuum degree is -0.04 - -0.10 MPa;

[0018] The conditions for drying are: temperature is 75 - 85 °C;

[0019] The mesh number of the sieve used for crushing is 150 mesh.

[0020] In step S2, the ointment refining is carried out according to the following operations: Add tung oil into the ointment refining tank, add sulfur powder and realgar powder, stir while adding, the stirring speed is 20 - 30 r / min, and close the feeding port; Open the jacket valve of the ointment refining tank, turn on the heat conduction oil heating, turn on the dust removal, smoke exhaust buttons and the smoke exhaust valve, heat up to 260 - 270 °C, stop heating, and continue to stir for 25 - 35 min.

[0021] Step S3 is carried out according to the following operations: When the paste obtained in step S2 is cooled down to 150 - 160 °C, add gamboge powder and pearl powder, and stir for 25 - 30 min; Pass the obtained material through a 120 - mesh sieve and pump it into a blending tank with an internal pressure of -0.04 - -0.05 MPa. After the pumping is completed, close the discharge valve of the ointment refining tank, remove the remaining vacuum in the blending tank, then close the inlet valve of the blending tank and the discharge valve of the ointment refining tank, turn on the stirring of the blending tank, and the stirring speed is 25 - 30 r / min; Open the smoke exhaust valve of the blending tank, turn on the heat conduction oil of the blending tank and the stirring of the blending tank, keep the blending tank at 150 - 160 °C, and keep warm for 50 - 60 min for sterilization.

[0022] The step S4 is carried out according to the following operations: Turn on the cooling oil, cool the paste obtained in step S3 to 50-60 °C, add musk, and stir for 25-30 min.

[0023] In a second aspect, the present invention provides a traditional Chinese medicine ointment obtained by the preparation method.

[0024] In a third aspect, the present invention provides the application of the traditional Chinese medicine ointment in the preparation of a drug for treating skin wounds.

[0025] The wounds include: burn and scald wounds, pressure sore wounds, diabetic foot ulcers.

[0026] Among them, the pressure sores are stage II, III, and IV pressure sores.

[0027] The formula explanation of the traditional Chinese medicine ointment of the present invention is as follows: Sulfur is hot in nature, detoxifying, bactericidal, antipruritic, antifungal, and dissolving cutin; Realgar dispels wind and dampness, kills insects and detoxifies, antibacterial, antiviral, and anti-tumor; Garcinia is bitter, astringent, and toxic, eroding sores and detoxifying, breaking blood and dispersing nodules, anti-inflammatory, anti-microbial, and anti-tumor; Pearl calms the mind, detoxifies and promotes granulation, resists fatigue, improves immunity, and is anti-inflammatory; Musk is anti-inflammatory and inhibits the proliferation of Staphylococcus aureus and Escherichia coli.

[0028] Compared with the prior art, the beneficial effects achieved by the present invention are:

[0029] Compared with CN1141132A, the proportion of the three yellows in the traditional Chinese medicine ointment provided by the present invention is less, the toxicity and irritation are smaller, and at the same time, the efficacy of treating skin wounds is better. It can significantly reduce the ulcer area and promote ulcer healing in a shorter time, and the effect is remarkable. Detailed implementation manners

[0030] The present invention will be further described below in conjunction with specific embodiments, but the present invention is not limited to the following embodiments.

[0031] The experimental methods used in the following embodiments are all conventional methods unless otherwise specified.

[0032] The reagents, materials, instruments, etc. used in the following embodiments can all be obtained from commercial channels unless otherwise specified.

[0033] Example 1

[0034] This example provides an external traditional Chinese medicine ointment, and its formula is: 55 kg of sulfur, 15 kg of realgar, 2 kg of garcinia, 2 kg of pearl, and 2 kg of musk. That is, the mass ratio of sulfur:realgar:garcinia:pearl:musk = 27.5:7.5:1:1:1.

[0035] Among them, the realgar powder is prepared by the water separation method.

[0036] The preparation method of the above-mentioned external-use traditional Chinese medicine ointment is as follows:

[0037] (1) Raw material pretreatment process

[0038] Gamboge powder: Add 2 kg of weighed gamboge medicinal materials into the extraction tank, add 48.00 kg of purified water, heat and stir simultaneously to dissolve all the materials, and reflux and cook for 4 - 7 hours; pump the filtrate filtered through a 150-mesh sieve into the vacuum decompression concentrator, then concentrate it to a paste under the conditions of controlling the temperature at about 80°C and the vacuum degree at -0.07 MPa, and collect the paste; then spread the extract on a plastic film and place it in the drying tray of the oven, control the oven temperature at about 80°C for drying operation, and then crush the dried paste into powder, pass it through a 150-mesh sieve, and reserve it.

[0039] Sulfur powder: Uniformly put 55 kg of weighed sulfur medicinal materials into the feeding hopper of the crusher, crush them into fine powder, pass it through a 150-mesh sieve, and reserve it.

[0040] (2) Ointment refining: Add the weighed tung oil into the ointment refining tank, then add sulfur powder and realgar powder into the ointment refining tank, stir while adding, with the stirring speed of 25 r / min, to make the materials fully mixed, and close the feeding port; open the jacket valve of the ointment refining tank, turn on the heat conduction oil heating, turn on the dust removal, smoke exhaust buttons and the smoke exhaust valve, heat up to 265°C, turn off the heating, and continue to stir for 30 minutes to make the materials fully react. Turn on the cooling oil, when the material temperature drops to 165°C, turn off the cooling oil, and when the material temperature drops to 155°C, add gamboge powder and pearl powder, and stir for 28 minutes to make the materials evenly mixed.

[0041] (3) Blending: Check the sealing of the blending tank, and at the same time make the pressure in the blending tank reach -0.045 MPa, open the discharge valve of the ointment refining tank, pump the materials into the blending tank through a 120-mesh sieve, close the discharge valve of the ointment refining tank after pumping, remove the remaining vacuum in the blending tank, then close the feed valve of the blending tank and the discharge valve of the ointment refining tank, turn on the stirring of the blending tank, with the stirring speed of 28 r / min; open the smoke exhaust valve of the blending tank, turn on the heat conduction oil of the blending tank and the stirring of the blending tank, keep the blending tank at 155°C, and keep warm for 55 min for sterilization.

[0042] (4) Turn on the cooling oil, when the temperature drops to 55°C, add artificial musk to the sterilized paste through a laminar flow vehicle, and stir for 28 minutes to make it evenly mixed.

[0043] Comparative example

[0044] Taking Example 1 in CN1141132A as an example, its raw materials are: 40 grams of sulfur powder, 15 grams of realgar powder, 1 gram of gamboge powder, 1 gram of pearl powder, and 1 gram of musk powder. That is, the mass ratio of sulfur:realgar:gamboge:pearl:musk = 40:15:1:1:1.

[0045] Comparing Example 1 with the above Comparative Example, it can be seen that in Example 1, the dosage of the three herbs is less, so the toxicity is smaller and the irritation to the patient's skin is smaller.

[0046] Example 2

[0047] The preparation method is the same as that of Example 1, except that the weight parts of each medicinal material are as follows: sulfur 45 weight parts, realgar 5 weight parts, gamboge 2 weight parts, pearl 2 weight parts, and musk 2 weight parts.

[0048] Example 3

[0049] The preparation method is the same as that of Example 1, except that the weight parts of each medicinal material are as follows: sulfur 65 weight parts, realgar 25 weight parts, gamboge 2 weight parts, pearl 2 weight parts, and musk 2 weight parts.

[0050] Pharmacodynamic experiment 1. Clinical trial research on traditional Chinese medicine for treating pressure sores

[0051] I. Inclusion criteria for subjects

[0052] (1) Be aware of the basic information of the clinical study and sign the informed consent form in writing by oneself;

[0053] (2) Aged 18 - 95 years old, inpatients or outpatients;

[0054] (3) The pressure sore is graded as stage II - IV;

[0055] (4) 1 cm 2 ≤ total wound area ≤ 100 cm 2 , if there are multiple wounds, select the largest one as the target wound.

[0056] II. Treatment plan for subjects

[0057] (1) Experimental group:

[0058] Topically apply the traditional Chinese medicine ointment of Example 1. When using, first clean the ulcer surface with normal saline, and perform debridement if necessary. Then take a photo, and after taking the photo, apply an appropriate amount of the medicine to the sterile gauze. Determine the dosage (i.e., thickness) according to the wound area, with the thickness not less than 1 mm, and apply it to the wound surface. Change the dressing once every 1 - 2 days. The intervention does not exceed 21 days.

[0059] ((2) Control group:

[0060] Topically apply recombinant human basic fibroblast growth factor. When using, first clean the ulcer surface with normal saline, and perform debridement if necessary. Then take a photo, and after taking the photo, apply an appropriate amount of the medicine to the sterile gauze. Determine the dosage (i.e., thickness) according to the wound area, with the thickness not less than 1 mm, and apply it to the wound surface. Change the dressing once every 1 - 2 days. The intervention does not exceed 21 days.

[0061] III. Efficacy research

[0062] 1. Changes in the target ulcer area at each treatment time point compared with the baseline

[0063] Table 1 Changes in the target ulcer area (software method) at each time point compared with the baseline (cm 2 , FAS)

[0064] Project Index item Experimental group Control group Statistical method and statistic P Ulcer on the 7±1d N (missing) 27(1) 22(0) t＝-0.586 0.561 Area decrease value Mean 2.32 3.13 Standard deviation 3.59 6.03 Min - Max -1.46-17.77 -1.60-22.69 Ulcer on the 14±2d N (missing) 23(5) 18(4) t＝-0.580 0.565 Area decrease value Mean 3.31 4.38 Standard deviation 3.79 7.76 Min - Max 0.58-16.32 -3.5-26.97 Ulcer on the 21±3d N (missing) 26(2) 19(3) t＝-0.675 0.503 Area decrease value Mean 4.29 5.62 Standard deviation 4.45 8.63 Min - Max 0.85-18.8 -3.5-27.93

[0065] Table 2 Changes in the target ulcer area (software method) at each time point compared with the baseline (cm 2 , PPS)

[0066] Project Index item Experimental group Control group Statistical method and statistic P Ulcer on the 7±1d N (missing) 25(1) 19(0) t＝-0.586 0.561 Area decrease value Mean 1.79 3.64 Standard deviation 1.88 6.34 Min - Max -1.46-17.77 0.16-22.69 Ulcer on the 14±2d N (missing) 23(3) 17(2) t＝-0.644 0.524 Area decrease value Mean 3.31 4.53 Standard deviation 3.79 7.97 Min - Max 0.58-16.32 -3.5-26.97 Ulcer on the 21±3d N (missing) 25(0) 17(2) t＝-0.681 0.503 Area decrease value Mean 4.28 5.83 Standard deviation 4.54 8.83 Min - Max 0.85-18.8 -3.5-27.93

[0067] The decrease in ulcer area in the two groups of subjects at 7±1 days, 14±2 days, and 21±3 days after drug administration showed no statistically significant difference between groups. The FAS dataset and the PPS dataset showed the same trend.

[0068] Table 3 Changes in the target ulcer area (software method) at each time point compared with the baseline (%, FAS)

[0069]

[0070]

[0071] Table 4 Changes in the target ulcer area (software method) at each time point compared with the baseline (%, PPS)

[0072] Project Index item Experimental group Control group Statistical method and statistic P Ulcer on the 7±1d N (missing) 25(1) 19(0) t＝0.609 0.546 Area decrease rate Mean 0.44 0.37 Standard deviation 0.46 0.23 Min - Max -0.95-1.00 0.12-0.90 Ulcer on the 14±2d N (missing) 23(3) 17(2) t＝1.119 0.270 Area decrease rate Mean 0.67 0.52 Standard deviation 0.36 0.50 Min - Max 0.18-1.00 -1.24-1.00 Ulcer on the 21±3d N (missing) 25(1) 18(1) t＝0.574 0.071 Area decrease rate Mean 0.74 0.67 Standard deviation 0.29 0.52 Min - Max 0.20-1.00 -1.24-1.00

[0073] The ulcer area reduction rates in the two groups of subjects at 7±1 days, 14±2 days, and 21±3 days after drug administration showed no statistically significant difference between groups. The FAS dataset and the PPS dataset showed the same trend.

[0074] Table 5 Target ulcer area (software method) at each time point (cm 2 , FAS)

[0075] Project Index item Experimental group Control group Statistical method and statistic P Ulcer area N (missing) 28(0) 22(0) t＝0.128 0.899 (Baseline) Mean 10.60 9.90 Standard deviation 18.80 12.36 Min - Max 1.1-65.87 1.00-29.44 Ulcer area N (missing) 27(1) 22(0) t＝0.511 0.611 (On the 7±1st day) Mean 5.24 4.09 Standard deviation 9.82 4.45 Min - Max 0-48.10 0.55-17.50 Ulcer area N (missing) 25(3) 20(2) t＝0.703 0.486 (On the 14±2nd day) Mean 4.56 2.79 Standard deviation 10.87 3.14 Min - Max 0-54.02 0-10.6 Ulcer area N (missing) 26(2) 19(3) t＝0.897 0.375 (On the 21±3rd day) Mean 3.69 1.59 Standard deviation 9.92 2.57 Min - Max 0-50.50 0-10.40

[0076] Table 6 Target ulcer area (software method) at each time point (cm 2 , PPS)

[0077]

[0078]

[0079] There was no significant difference in the ulcer area (software method) between the two groups of subjects at baseline, 7±1 days after medication, 14±2 days, and 21±3 days. The FAS dataset and the PPS dataset showed the same trend.

[0080] Table 7 Target ulcer area (length×width) at each time point (cm 2 , FAS)

[0081] Project Index item Experimental group Control group Statistical method and statistic P Ulcer area N (missing) 28(0) 22(0) t＝0.151 0.880 (Baseline) Mean 10.60 9.90 Standard deviation 18.80 12.36 Min - Max 0.9-96.46 1.01-38.88 Ulcer area N (missing) 26(2) 22(0) t＝0.225 0.823 (On the 7±1st day) Mean 8.07 7.19 Standard deviation 15.61 10.58 Min - Max 0-75.23 0.84-45.00 Ulcer area N (missing) 20(8) 18(4) t＝0.339 0.736 (On the 14±2nd day) Mean 5.99 2.79 Standard deviation 5.99 3.48 Min - Max 0-23.17 0-10.35 Ulcer area N (missing) 26(2) 20(2) t＝0.905 0.370 (On the 21±3rd day) Mean 5.27 2.10 Standard deviation 15.17 4.15 Min - Max 0-77.43 0-18.00

[0082] Table 8 Target ulcer area (length×width) at each time point (cm 2 , PPS)

[0083] Project Index item Experimental group Control group Statistical method and statistic P Ulcer area N (missing) 26(0) 19(0) t＝-0.559 0.579 (Baseline) Mean 7.47 9.18 Standard deviation 8.70 11.79 Min - Max 0.90-96.46 1.01-38.88 Ulcer area N (missing) 24(2) 19(0) t＝-0.059 0.953 (On the 7±1st day) Mean 5.40 5.53 Standard deviation 7.80 6.87 Min - Max 0-75.23 0.84-27.42 Ulcer area N (missing) 20(6) 17(2) t＝0.323 0.749 (On the 14±2nd day) Mean 3.34 2.80 Standard deviation 5.99 3.59 Min - Max 0-23.17 0-10.35 Ulcer area N (missing) 25(1) 19(0) t＝0.931 0.357 (On the 21±3rd day) Mean 5.47 2.07 Standard deviation 15.45 4.26 Min - Max 0-77.43 0-18.00

[0084] There was no significant difference in the ulcer area (length×width) between the two groups of subjects at baseline, 7±1 days after medication, 14±2 days, and 21±3 days. The FAS dataset and the PPS dataset showed the same trend.

[0085] 2. Healing status of the target ulcer area at each treatment time point

[0086] Table 9 Analysis of ulcer healing status (FAS)

[0087]

[0088]

[0089] Table 10 Analysis of ulcer healing status (PPS)

[0090] Project Index item Experimental group Control group Statistical method and statistic P Number of ulcer healings Healing quantity (%) 6(23.08) 0(0.00) chisq = 5.509 0.024 (On the 7±1st day) Non - healing quantity (%) 20(76.92) 19(100.00) Total 26(0) 19(0) Number of ulcer healings Healing quantity (%) 12(48.00) 2(11.11) chisq = 6.486 0.011 (On the 14±2nd day) Non - healing quantity (%) 13(52.00) 16(88.89) Total 25(1) 18(1) Number of ulcer healings Healing quantity (%) 12(48.00) 5(27.78) chisq = 1.790 0.181 (On the 21±3rd day) Non - healing quantity (%) 13(52.00) 13(72.22) Total 25(1) 18(1)

[0091] There was a significant difference in the ulcer healing status between the two groups of subjects at 7±1 days and 14±2 days after medication. There was no significant difference in the ulcer healing status between the two groups at 21±3 days after medication. The FAS dataset and the PPS dataset showed the same trend.

[0092] 3. Changes in the Bates-Jensen Wound Assessment Tool

[0093] Table 11 Scores of the Bates-Jensen Wound Assessment Tool at each time point (FAS)

[0094] Project Index item Experimental group Control group Statistical method and statistic P Bates - Jensen score N (missing) 23(5) 18(4) t＝-0.919 0.364 (Baseline) Mean 26.39 28.06 Standard deviation 6.32 4.93 Min - Max 16-40 19-38 Bates - Jensen score N (missing) 27(1) 22(0) t＝-2.463 0.017 (On the 7±1st day) Mean 21.74 27.91 Standard deviation 9.78 7.19 Min - Max 7-39 14-47 Bates - Jensen score N (missing) 20(8) 18(4) t＝-2.430 0.020 (On the 14±2nd day) Mean 15.50 22.00 Standard deviation 9.48 6.57 Min - Max 7-37 7-32 Bates - Jensen score N (Missing) 25(3) 19(3) t＝-1.343 0.186 (Day 21±3) Mean 15.64 19.47 Standard Deviation 9.47 9.24 Min - Max 6-34 7-34

[0095] Table 12 Scores of the Bates-Jensen Wound Assessment Tool at each time point (PPS)

[0096]

[0097]

[0098] The scores of the Bates-Jensen Wound Assessment Tool for the two groups of subjects at 7±1 days and 14±2 days after drug administration showed statistically significant differences between groups. There was no statistically significant difference between groups at baseline and 21±3 days after drug administration. The FAS dataset and the PPS dataset showed the same trend.

[0099] 4. Changes in ulcers on the pressure ulcer healing scale

[0100] Table 13 Analysis of ulcer healing (FAS)

[0101] Item Index Item Experimental Group Control Group Statistical Method and Statistic P Pressure Ulcer Healing Scale 3 0 2 chisq = 8.050 0.328 (Baseline) 4 8 4 5 4 6 6 2 2 7 7 2 8 2 0 9 3 4 10 2 2 Total 28 22 Pressure Ulcer Healing Scale 0 6 0 chisq = 9.551 0.298 (Day 7±1) 2 4 2 3 0 2 4 4 7 5 3 3 6 2 2 7 2 2 8 4 4 9 1 1 Total 26 22 Pressure Ulcer Healing Scale 0 12 2 chisq = 14.583 0.042 (Day 14±2) 2 0 2 3 0 3 4 3 5 5 1 2 7 3 3 8 3 1 10 1 0 Total 23 18 Pressure Ulcer Healing Scale 0 13 5 chisq = 13.947 0.083 (Day 21±3) 2 0 2 3 1 5 4 4 3 5 1 2 7 3 0 8 3 1 9 0 1 10 1 0 Total 26 19

[0102] Table 14 Analysis of ulcer healing (PPS)

[0103] Item Score Experimental Group Control Group Statistical Method and Statistic P Pressure Ulcer Healing Scale 3 0 2 chisq = 9.724 0.205 (Baseline) 4 8 3 5 4 6 6 2 2 7 6 1 8 2 0 9 3 3 10 1 2 Total 26 19 Pressure Ulcer Healing Scale 0 6 0 chisq = 11.818 0.156 (Day 7±1) 2 4 2 3 0 2 4 4 7 5 3 3 6 2 0 7 1 1 8 4 4 9 1 0 Total 25 19 Pressure Ulcer Healing Scale 0 12 2 chisq = 13.219 0.040 (Day 14±2) 2 0 2 3 0 3 4 3 5 5 1 1 7 3 3 8 3 1 Total 22 17 Pressure Ulcer Healing Scale 0 12 5 chisq = 12.081 0.098 (Day 21±3) 2 0 2 3 1 5 4 4 3 5 1 1 7 3 0 8 3 1 9 0 1 Total 24 18

[0104] The scores of the ulcer area on the pressure ulcer healing scale for the two groups of subjects at 14±2 days showed statistically significant differences between groups. There was no statistically significant difference between groups at baseline, 7±1 days after drug administration, and 21±3 days after drug administration. The FAS dataset and the PPS dataset showed the same trend.

[0105] 5. Patients who withdrew prematurely due to poor efficacy or adverse events

[0106] During the study, 1 subject in the control group gave up treatment and withdrew prematurely due to poor efficacy. There were no related cases in the experimental group.

[0107] 6. Summary of effectiveness

[0108] (1) The decrease values of the ulcer area for the two groups of subjects at 7±1 days, 14±2 days, and 21±3 days after drug administration showed no statistically significant differences between groups. The FAS dataset and the PPS dataset showed the same trend.

[0109] (2) The ulcer areas (software method) of the two groups of subjects at baseline, 7±1 days, 14±2 days, and 21±3 days after drug administration all decreased steadily, with no statistically significant differences between groups. The FAS dataset and the PPS dataset showed the same trend. Calculating the ulcer area using the length×width of the ulcer surface showed the same trend as the software method.

[0110] (3) The ulcer healing conditions of the two groups of subjects at 7±1 days and 14±2 days after medication showed statistically significant differences between the groups. There was no statistically significant difference in the ulcer healing conditions between the groups at 21±3 days after medication. The FAS dataset and the PPS dataset showed the same trend.

[0111] (4) The scores of the Bates-Jensen Wound Assessment Tool of the two groups of subjects at 7±1 days and 14±2 days after medication showed statistically significant differences between the groups. There was no statistically significant difference between the groups at baseline and 21±3 days after medication. The FAS dataset and the PPS dataset showed the same trend.

[0112] (5) The ulcer area scores of the pressure ulcer healing scale of the two groups of subjects at 14±2 days showed statistically significant differences between the groups. There was no statistically significant difference between the groups at baseline, 7±1 days after medication, and 21±3 days after medication. The FAS dataset and the PPS dataset showed the same trend.

[0113] (6) During the research process, 1 subject in the control group gave up treatment and withdrew from the study in advance due to poor efficacy. There were no related cases in the experimental group.

[0114] Analysis:

[0115] The ulcer areas (software method) of the two groups of subjects at baseline, 7±1 days, 14±2 days, and 21±3 days after medication all decreased steadily, indicating that both groups could better promote wound healing. The ulcer healing conditions of the two groups of subjects at 7±1 days and 14±2 days after medication showed statistically significant differences between the groups, suggesting that the experimental group could promote wound healing in a shorter time.

[0116] There was no statistically significant difference in the ulcer healing conditions between the two groups of subjects at 21±3 days after medication, suggesting that the wound healing condition of the control group gradually increased after 21 days of treatment. However, from the actual data, as of 21±3 days, 12 / 28 subjects in the experimental group had achieved wound healing, while 5 / 22 subjects in the control group had achieved wound healing. The difference between the two was obvious, mainly because the sample size factor led to the failure to show the difference. The results of the FAS dataset and the PPS dataset showed a trend. The scores of the Bates-Jensen Wound Assessment Tool and the ulcer area scores of the pressure ulcer healing scale also showed the same trend. This feature is consistent with the characteristics of the traditional Chinese medicine ointment in Example 1, which can detoxify and reduce swelling, remove necrotic tissue and promote granulation.

[0117] There was no statistically significant difference in the ulcer areas of the two groups of subjects at 7±1 days, 14±2 days, and 21±3 days after medication. The FAS dataset and the PPS dataset showed the same trend. This is different from the above trend.

[0118] The ulcer area reduction values and reduction rates of the two groups of subjects at 7±1 days, 14±2 days, and 21±3 days after medication showed no statistically significant differences between groups. The FAS dataset and the PPS dataset showed the same trend. The reduction values of the experimental group were lower than those of the control group, which may be related to the slightly higher mean ulcer area value of the control group at the time of enrollment. From the perspective of the reduction rate, the reduction rates of the experimental group were higher than those of the control group, which is related to the rapid wound healing of the cases in the experimental group.

[0119] The above results all suggest that the wound healing situation of the experimental group is better than that of the control group, especially for subjects with a smaller wound area (ulcer area less than 5 cm 2 ), and this feature is more obvious.

[0120] Pharmacodynamic experiment 2. Clinical trial research on traditional Chinese medicine in the treatment of diabetic foot

[0121] I. Inclusion criteria for subjects

[0122] (1) Be aware of the basic information of the clinical study and sign the informed consent form in writing by oneself;

[0123] (2) Aged 18 - 90 years old, with a medical history of type 2 diabetes or newly diagnosed diabetes patients during the medical interview, and glycated hemoglobin (HbA1c < 10.0%) at the time of screening;

[0124] (3) The ulcer on the foot has occurred for ≥28 days, and at the time of screening, 1 cm 2 ≤ the ulcer wound area after debridement ≤ 25 cm 2 (For those with multiple lesions, select the largest ulcer area below the ankle as the target lesion, and the distance between this target lesion and other wounds ≥ 2 cm);

[0125] (4) 0.7 ≤ ankle / brachial index (ABI) of the target lesion side ≤ 1.3;

[0126] (5) The ulcer condition is classified as grade 1 - 2 according to the Wagner classification and ≤ grade 2 according to the mild infection standard of diabetic foot of the International Working Group on the Diabetic Foot (IWGDF).

[0127] II. Treatment plan for subjects

[0128] (1) Experimental group:

[0129] Implement Example 1 of the ointment for external use. When using it, first clean the ulcer surface with normal saline, perform debridement if necessary, then take pictures, apply an appropriate amount of the medicine to a sterile gauze after taking pictures, and apply it to the wound surface, and change the dressing once every 1 - 2 days. The intervention does not exceed 84 days.

[0130] (2) Control group:

[0131] Recombinant Human Acidic Fibroblast Growth Factor for External Use. When using, first clean the ulcer surface with normal saline, and perform debridement if necessary. Then take a photo. After taking the photo, apply an appropriate amount of the medicine to a sterile gauze and apply it to the wound surface. Change the dressing once every 1-2 days. The intervention should not exceed 84 days.

[0132] III. Efficacy Study

[0133] 1. Percentage change in the target ulcer area compared to the baseline at the end of treatment

[0134] Table 15 Change in the target ulcer area (software method) compared to the baseline at the end of treatment (%, FAS)

[0135]

[0136] Table 16 Inter-group comparison of the percentage change in the target ulcer area compared to the baseline at the end of treatment (%, PPS)

[0137]

[0138] There was no statistically significant difference in the percentage change in the target ulcer area between the two groups of subjects compared to the baseline at the end of treatment. The results of the PPS dataset and the FAS data showed the same trend.

[0139] 2. Percentage change in the target ulcer area compared to the baseline at each time point of treatment

[0140] Table 17 Change in the target ulcer area (software method) compared to the baseline at each time point (%, FAS)

[0141]

[0142]

[0143] Table 18 Percentage change in the target ulcer area compared to the baseline at different visit points (PPS)

[0144] Index Item Control Group Experimental Group Total Test Method Test Statistic P - value 7±1d N (Nmiss) 63(4) 60(3) 123(7) Wilcoxon 0.613 0.540 Mean(SD) 35.4(57.7) 46(33.1) 40.6(47.4) Rank Sum Test CL95 20.9～49.9 37.4～54.5 32.1～49 Min~Max -226.9～100 -14.6～100 -226.9～100 14±2d N (Nmiss) 67(0) 63(0) 130(0) Wilcoxon 0.449 0.653 Mean(SD) 61.3(43.3) 67.4(31.8) 64.3(38.1) Rank Sum Test CL95 50.7～71.9 59.4～75.4 57.6～70.9 Min~Max -128.1～100 -27.3～100 -128.1～100 21±2d N (Nmiss) 61(6) 60(3) 121(9) Wilcoxon -0.134 0.894 Mean(SD) 73.5(44.4) 80.8(26) 77.1(36.5) Rank Sum Test CL95 62.1～84.9 74.1～87.5 70.6～83.7 Min~Max -85.2～100 -4.5～100 -85.2～100 28±3d N (Nmiss) 67(0) 63(0) 130(0) Wilcoxon -0.096 0.923 Mean(SD) 77.9(40.2) 87.8(18.9) 82.7(31.9) Rank Sum Test CL95 68.1～87.7 83～92.5 77.1～88.2 Min~Max -71.4～100 27.1～100 -71.4～100 56±3d N (Nmiss) 67(0) 63(0) 130(0) Wilcoxon 0.725 0.469 Mean(SD) 90.2(22.1) 95.4(14.1) 92.8(18.7) Rank Sum Test CL95 84.9～95.6 91.9～99 89.5～96 Min~Max 4.7～100 33.3～100 4.7～100 84±7d N (Nmiss) 67(0) 63(0) 130(0) Wilcoxon 1.431 0.152 Mean(SD) 91.4(23.4) 96.9(13.8) 94(19.5) Rank Sum Test CL95 85.7～97.1 93.4～100.3 90.7～97.4 Min~Max -31～100 16.5～100 -31～100

[0145] There was no statistically significant difference in the percentage change in the target ulcer area between the two groups of subjects compared to the baseline at each visit point of 7±1d, 14±2d, 21±2d, 28±3d, 56±3d, and 84±7d. The results of the PPS dataset and the FAS data showed the same trend.

[0146] 3. Target ulcer area and change compared to the baseline at each time point of treatment

[0147] Table 19 Inter-group comparison of the target ulcer area (cm 2 , FAS)

[0148]

[0149]

[0150] Table 20 Inter-group comparison of target ulcer area (cm 2 , PPS)

[0151]

[0152]

[0153] Table 21 Inter-group comparison of reduction values of target ulcer area (FAS)

[0154]

[0155] Table 22 Inter-group comparison of reduction values of target ulcer area (PPS)

[0156]

[0157] Table 23 Intra-group comparison of differences in target ulcer area before and after treatment (FAS)

[0158]

[0159]

[0160] Table 24 Comparison of differences in target ulcer area before and after treatment (PPS)

[0161]

[0162] There were no statistically significant differences in the target ulcer area and its change values from the baseline between the two groups of subjects at the follow-up points of 7±1d, 14±2d, 21±2d, 28±3d, 56±3d, 84±7d, etc. When comparing within each group with before treatment, there were statistically significant differences at all follow-up points outside the baseline.

[0163] 4. Ulcer healing status

[0164] Table 25 Inter-group comparison of complete healing proportion (FAS)

[0165] Visit Point Whether Completely Healed Control Group Experimental Group Total Test Method Test Statistic P - value 14±2d Yes 25(36.2％) 22(34.4％) 47(35.3％) Chi - square Test 0.05 0.823 No 44(63.8％) 42(65.6％) 86(64.7％) Total 69(100％) 64(100％) 133(100％) 28±3d Yes 45(65.2％) 36(57.1％) 81(61.4％) Chi - square Test 0.906 0.341 No 24(34.8％) 27(42.9％) 51(38.6％) Total 69(100％) 63(100％) 132(100％) 56±3d Yes 53(76.8％) 52(82.5％) 105(79.6％) Chi - square Test 0.664 0.415 No 16(23.2％) 11(17.5％) 27(20.5％) Total 69(100％) 63(100％) 132(100％) 84±7d Yes 55(79.7％) 57(90.5％) 112(84.9％) Chi - square Test 2.969 0.085 No 14(20.3％) 6(9.5％) 20(15.2％) Total 69(100％) 63(100％) 132(100％)

[0166] Table 26 Inter-group comparison of complete healing proportion (PPS)

[0167] Visit Point Whether Completely Healed Control Group Experimental Group Total Test Method Test Statistic P - value 14±2d Yes 25(37.3％) 22(34.9％) 47(36.2％) Chi - square Test 0.081 0.777 No 42(62.7％) 41(65.1％) 83(63.9％) Total 67(100％) 63(100％) 130(100％) 28±3d Yes 45(67.2％) 36(57.1％) 81(62.3％) Chi - square Test 1.388 0.239 No 22(32.8％) 27(42.9％) 49(37.7％) Total 67(100％) 63(100％) 130(100％) 56±3d Yes 53(79.1％) 52(82.5％) 105(80.8％) Chi - square Test 0.247 0.619 No 14(20.9％) 11(17.5％) 25(19.2％) Total 67(100％) 63(100％) 130(100％) 84±7d Yes 55(82.1％) 57(90.5％) 112(86.2％) Chi - square Test 1.914 0.167 No 12(17.9％) 6(9.5％) 18(13.9％) Total 67(100％) 63(100％) 130(100％)

[0168] Table 27 Inter-group comparison of healing degree (FAS)

[0169] Visit Point Degree of Healing Control Group Experimental Group Total Test Method Test Statistic P - value 14±2d Completely Healed 25(36.2％) 22(34.4％) 47(35.34％) Wilcoxon -0.208 0.836 Ulcer Area Reduction ≥ 50% 19(27.5％) 22(34.4％) 41(30.8％) Rank Sum Test The ulcer area is reduced by < 50% 25(36.2％) 20(31.3％) 45(33.8％) Total 69(100％) 64(100％) 133(100％) 28±3d Completely Healed 45(65.2％) 36(57.1％) 81(61.36％) Wilcoxon 0.053 0.958 Ulcer Area Reduction ≥ 50% 10(14.5％) 25(39.7％) 35(26.5％) Rank Sum Test The ulcer area is reduced by < 50% 14(20.3％) 2(3.2％) 16(12.1％) Total 69(100％) 63(100％) 132(100％) 56±3d Completely Healed 53(76.8％) 52(82.5％) 105(79.55％) Wilcoxon -0.914 0.362 Ulcer Area Reduction ≥ 50% 10(14.5％) 9(14.3％) 19(14.4％) Rank Sum Test The ulcer area is reduced by < 50% 6(8.7％) 2(3.2％) 8(6.1％) Total 69(100％) 63(100％) 132(100％) 84±7d Completely Healed 55(79.7％) 57(90.5％) 112(84.85％) Wilcoxon -1.715 0.089 Ulcer Area Reduction ≥ 50% 9(13％) 4(6.4％) 13(9.9％) Rank Sum Test The ulcer area is reduced by < 50% 5(7.3％) 2(3.2％) 7(5.3％) Total 69(100％) 63(100％) 132(100％)

[0170] Table 28 Inter-group comparison of healing degree (PPS)

[0171] Visit Point Degree of Healing Control Group Experimental Group Total Test Method Test Statistic P - value 14±2d Completely Healed 25(37.3％) 22(34.9％) 47(36.15％) Wilcoxon -0.208 0.836 Ulcer Area Reduction ≥ 50% 18(26.9％) 22(34.9％) 40(30.77％) Rank Sum Test The ulcer area is reduced by < 50% 24(35.8％) 19(30.2％) 43(33.08％) Total 67(100％) 63(100％) 130(100％) 28±3d Completely Healed 45(67.2％) 36(57.1％) 81(62.31％) Wilcoxon 0.238 0.812 Ulcer Area Reduction ≥ 50% 8(11.9％) 25(39.7％) 33(25.38％) Rank Sum Test The ulcer area is reduced by <50% 14(20.9％) 2(3.2％) 16(12.31％) Total 67(100％) 63(100％) 130(100％) 56±3d Completely Healed 53(79.1％) 52(82.5％) 105(80.77％) Wilcoxon -0.535 0.594 Ulcer Area Reduction ≥ 50% 8(11.9％) 9(14.3％) 17(13.08％) Rank Sum Test The ulcer area is reduced by < 50% 6(9％) 2(3.2％) 8(6.15％) Total 67(100％) 63(100％) 130(100％) 84±7d Completely Healed 55(82.1％) 57(90.5％) 112(86.15％) Wilcoxon -1.394 0.166 Ulcer Area Reduction ≥ 50% 7(10.5％) 4(6.4％) 11(8.46％) Rank Sum Test The ulcer area is reduced by < 50% 5(7.5％) 2(3.2％) 7(5.38％) Total 67(100％) 63(100％) 130(100％)

[0172] There was no significant difference in the proportion of complete healing and the degree of healing between the two groups of subjects at 14±2d, 28±3d, 56±3d, and 84±7d. The trend of the PPS dataset was the same as that of the FAS data.

[0173] 5. Changes in TCM syndrome scores

[0174] Table 29 Inter-group comparison of changes in TCM syndrome scores (FAS)

[0175]

[0176]

[0177] Table 30 Inter-group comparison of changes in TCM syndrome scores (PPS)

[0178] Index Item Control Group Experimental Group Total Test Method Test Statistic P - value 7±1d N (Nmiss) 62(5) 59(4) 121(9) Wilcoxon 1.096 0.273 Mean(SD) 5.76(5.32) 7.08(5.53) 6.4(5.44) Rank Sum Test Median(Q1 - Q3) 5(2-8) 5(4-9) 5(3-9) CL95 4.41～7.11 5.64～8.53 5.43～7.38 Min~Max -3～20 0～24 -3～24 14±2d N (Nmiss) 67(0) 61(2) 128(2) Wilcoxon 0.502 0.616 Mean (SD) 11.39(7.66) 11.66(7.39) 11.52(7.5) Rank sum test Median (Q1 - Q3) 10(5-19) 10(6-17) 10(6-18.5) CL95 9.52～13.26 9.76～13.55 10.2～12.83 Min~Max 0～31 -6～27 -6～31 21±2d N (Nmiss) 60(7) 58(5) 118(12) Wilcoxon 0.337 0.736 Mean (SD) 14.7(7.99) 15.47(6.63) 15.08(7.33) Rank sum test Median (Q1 - Q3) 16.5(8-20) 15(10-21) 16(9-20) CL95 12.64～16.76 13.72～17.21 13.74～16.41 Min~Max -2～31 2～33 -2～33 28±3d N (Nmiss) 118(12) 67(0) 60(3) Wilcoxon 0.218 0.828 Mean (SD) 15.08(7.33) 16.28(8.14) 16.93(6.79) Rank sum test Median (Q1 - Q3) 16(9-20) 18(9-22) 17(12-22) CL95 13.74～16.41 14.3～18.27 15.18～18.69 Min~Max -2～33 -2～31 2～33 56±3d N (Nmiss) 67(0) 62(1) 129(1) T - test -1.270 0.207 Mean (SD) 17.66(7.27) 19.24(6.88) 18.42(7.1) Median (Q1 - Q3) 19(13-22) 20.5(15-23) 20(14-23) CL95 15.88～19.43 17.49～20.99 17.18～19.66 Min~Max -1～31 2～33 -1～33 84±7d N (Nmiss) 67(0) 60(3) 127(3) T - test -1.760 0.082 Mean (SD) 18.31(6.67) 20.28(5.88) 19.24(6.36) Median (Q1 - Q3) 19(14-22) 21(17-23.5) 20(16-23) CL95 16.69～19.94 18.76～21.8 18.13～20.36 Min~Max 1～31 6～33 1～33

[0179] In the FAS dataset, there was a significant difference in the change values of TCM syndrome scores between the two groups of subjects at 84±7d, and the reduction value in the experimental group was greater than that in the control group. There was no significant difference at 7±1d, 14±2d, 21±2d, 28±3d, and 56±3d.

[0180] In the PPS dataset, there was no significant difference in the change values of TCM syndrome scores between the two groups of subjects at 7±1d, 14±2d, 21±2d, 28±3d, 56±3d, and 84±7d.

[0181] 6. Condition of the foot ulcer scale

[0182] Table 31 Inter-group comparison of Wangner grades (FAS)

[0183]

[0184]

[0185] Table 32 Inter-group comparison of Wangner grades (PPS)

[0186] Index Item Control group Experimental group Total Test method Test statistic P - value 0d Grade 0 0(0％) 0(0％) 0(0％) Wilcoxon -0.442 0.658 Grade 1 23(34.3％) 24(38.1％) 47(36.2％) Rank sum test Grade 2 44(65.7％) 39(61.9％) 83(63.9％) Grade 3 0(0％) 0(0％) 0(0％) Grade 4 0(0％) 0(0％) 0(0％) Grade 5 0(0％) 0(0％) 0(0％) Total 67(100％) 63(100％) 130(100％) 7±1d Grade 0 6(9.7％) 9(15.3％) 15(12.4％) Wilcoxon 1.326 0.185 Grade 1 29(46.8％) 24(40.7％) 53(43.8％) Rank sum test Grade 2 26(41.9％) 25(42.4％) 51(42.2％) Grade 3 0(0％) 1(1.7％) 1(0.8％) Grade 4 1(1.6％) 0(0％) 1(0.83％) Grade 5 0(0％) 0(0％) 0(0％) Total 62(100％) 59(100％) 121(100％) 14±2d Grade 0 25(37.9％) 22(34.9％) 47(36.4％) Wilcoxon 0.202 0.840 Grade 1 20(30.3％) 21(33.3％) 41(31.8％) Rank sum test Grade 2 20(30.3％) 19(30.2％) 39(30.2％) Grade 3 0(0％) 1(1.6％) 1(0.8％) Grade 4 1(1.5％) 0(0％) 1(0.78％) Grade 5 0(0％) 0(0％) 0(0％) Total 66(100％) 63(100％) 129(100％) 21±2d Grade 0 35(58.3％) 30(50.9％) 65(54.6％) Wilcoxon 0.575 0.565 Grade 1 14(23.3％) 19(32.2％) 33(27.7％) Rank sum test Grade 2 10(16.7％) 9(15.3％) 19(16％) Grade 3 0(0％) 1(1.7％) 1(0.8％) Grade 4 1(1.7％) 0(0％) 1(0.84％) Grade 5 0(0％) 0(0％) 0(0％) Total 60(100％) 59(100％) 119(100％)

[0187] Table 33 Inter-group comparison of IWGDF / IDSA grades of diabetic foot infection (FAS)

[0188]

[0189]

[0190] Table 34 Inter-group comparison of IWGDF / IDSA classification for diabetic foot infection (PPS)

[0191] Index Item Control group Experimental group Total Test method Test statistic P - value 0d Uninfected 9(13.4％) 8(12.7％) 17(13.1％) Wilcoxon 0.507 0.613 Infected 11(16.4％) 8(12.7％) 19(14.6％) Rank sum test Mild infection 47(70.2％) 47(74.6％) 94(72.3％) Moderate infection 0(0％) 0(0％) 0(0％) Severe infection 0(0％) 0(0％) 0(0％) Total 67(100％) 63(100％) 130(100％) 7±1d Uninfected 19(30.7％) 23(39％) 42(34.7％) Wilcoxon -0.545 0.587 Infected 7(11.3％) 5(8.5％) 12(9.9％) Rank sum test Mild infection 35(56.5％) 28(47.5％) 63(52.1％) Moderate infection 1(0.83％) 3(5.1％) 4(3.3％) Severe infection 0(0％) 0(0％) 0(0％) Total 62(100％) 59(100％) 121(100％) 14±2d Uninfected 35(52.2％) 35(55.6％) 70(53.9％) Wilcoxon -0.519 0.605 Infected 6(9％) 7(11.1％) 13(10％) Rank sum test Mild infection 22(32.8％) 18(28.6％) 40(30.8％) Moderate infection 4(3.08％) 3(4.8％) 7(5.4％) Severe infection 0(0％) 0(0％) 0(0％) Total 67(100％) 63(100％) 130(100％) 21±2d Uninfected 46(76.7％) 41(69.5％) 87(73.1％) Wilcoxon 0.637 0.525 Infected 1(1.7％) 7(11.9％) 8(6.7％) Rank sum test Mild infection 13(21.7％) 10(17％) 23(19.3％) Moderate infection 0(0％) 1(1.7％) 1(0.8％) Severe infection 0(0％) 0(0％) 0(0％) Total 60(100％) 59(100％) 119(100％)

[0192] Table 35 Inter-group comparison of Texas classification (FAS)

[0193]

[0194]

[0195] Table 36 Inter-group comparison of Texas classification (PPS)

[0196] Index Item Control group Experimental group Total Test method Test statistic P - value 0d Grade 0 0(0％) 0(0％) 0(0％) Wilcoxon -0.109 0.914 Grade 1 30(44.8％) 30(47.6％) 60(46.2％) Rank sum test Grade 2 36(53.7％) 30(47.6％) 66(50.8％) Grade 3 1(1.5％) 3(4.8％) 4(3.1％) Total 67(100％) 63(100％) 130(100％) 7±1d Grade 0 7(11.3％) 9(15.5％) 16(13.3％) Wilcoxon 0.112 0.911 Grade 1 32(51.6％) 25(43.1％) 57(47.5％) Rank sum test Grade 2 22(35.5％) 23(39.7％) 45(37.5％) Grade 3 1(1.6％) 1(1.7％) 2(1.7％) Total 62(100％) 58(100％) 120(100％) 14±2d Grade 0 26(38.8％) 21(33.3％) 47(36.2％) Wilcoxon 0.265 0.791 Grade 1 22(32.8％) 26(41.3％) 48(36.9％) Rank sum test Grade 2 19(28.4％) 15(23.8％) 34(26.2％) Grade 3 0(0％) 1(1.6％) 1(0.8％) Total 67(100％) 63(100％) 130(100％) 21±2d Grade 0 34(56.7％) 29(49.2％) 63(52.9％) Wilcoxon 0.862 0.391 Grade 1 18(30％) 20(33.9％) 38(31.9％) Rank sum test Grade 2 8(13.3％) 9(15.3％) 17(14.3％) Grade 3 0(0％) 1(1.7％) 1(0.8％) Total 60(100％) 59(100％) 119(100％)

[0197] Table 37 Inter-group comparison of Texas staging (FAS)

[0198]

[0199]

[0200] Table 38 Inter-group comparison of Texas staging (PPS)

[0201] Index Item Control group Experimental group Total Test method Test statistic P - value 0d Phase A 10(14.9％) 8(12.7％) 18(13.9％) Wilcoxon 1.039 0.301 Phase B 40(59.7％) 34(54％) 74(56.9％) Rank sum test Phase C 7(10.5％) 6(9.5％) 13(10％) Phase D 10(14.9％) 15(23.8％) 25(19.2％) Total 67(100％) 63(100％) 130(100％) 7±1d Phase A 22(36.1％) 22(37.3％) 44(36.7％) Wilcoxon 0.154 0.878 Phase B 30(49.2％) 26(44.1％) 56(46.7％) Rank sum test Phase C 6(9.8％) 7(11.9％) 13(10.8％) Phase D 3(4.9％) 4(6.8％) 7(5.8％) Total 61(100％) 59(100％) 120(100％) 14±2d Phase A 40(59.7％) 38(60.3％) 78(60％) Wilcoxon -0.005 0.996 Phase B 22(32.8％) 19(30.2％) 41(31.5％) Rank sum test Phase C 1(1.5％) 4(6.4％) 5(3.9％) Phase D 4(6％) 2(3.2％) 6(4.6％) Total 67(100％) 63(100％) 130(100％) 21±2d Phase A 47(78.3％) 46(78％) 93(78.2％) Wilcoxon 0.081 0.936 Phase B 9(15％) 8(13.6％) 17(14.3％) Rank sum test Phase C 1(1.7％) 2(3.4％) 3(2.5％) Phase D 3(5％) 3(5.1％) 6(5％) Total 60(100％) 59(100％) 119(100％)

[0202] Table 39 Inter-group comparison of Wound classification (FAS)

[0203]

[0204]

[0205] Table 40 Inter-group comparison of Wound classification (PPS)

[0206] Index Item Control group Experimental group Total Test method Test statistic P - value 0d Grade 0 0(0％) 0(0％) 0(0％) Wilcoxon 0.586 0.559 Grade 1 38(56.7％) 32(50.8％) 70(53.9％) Rank sum test Grade 2 28(41.8％) 31(49.2％) 59(45.4％) Grade 3 1(1.5％) 0(0％) 1(0.8％) Total 67(100％) 63(100％) 130(100％) 7±1d Grade 0 6(9.7％) 9(15.3％) 15(12.4％) Wilcoxon 0.499 0.619 Grade 1 39(62.9％) 28(47.5％) 67(55.4％) Rank sum test Grade 2 16(25.8％) 21(35.6％) 37(30.6％) Grade 3 1(1.6％) 1(1.7％) 2(1.7％) Total 62(100％) 59(100％) 121(100％) 14±2d Grade 0 26(38.8％) 22(34.9％) 48(36.9％) Wilcoxon 0.471 0.638 Grade 1 27(40.3％) 26(41.3％) 53(40.8％) Rank sum test Grade 2 13(19.4％) 15(23.8％) 28(21.5％) Grade 3 1(1.5％) 0(0％) 1(0.8％) Total 67(100％) 63(100％) 130(100％) 21±2d Grade 0 34(56.7％) 30(50.9％) 64(53.8％) Wilcoxon 0.244 0.807 Grade 1 20(33.3％) 21(35.6％) 41(34.5％) Rank sum test Grade 2 6(10％) 8(13.6％) 14(11.8％) Grade 3 0(0％) 0(0％) 0(0％) Total 60(100％) 59(100％) 119(100％)

[0207] Table 41 Inter-group comparison of Ischemia classification (FAS)

[0208] Index Item Control group Experimental group Total Test method Test statistic P - value 0d Grade 0 59(84.3％) 48(71.6％) 107(78.1％) Wilcoxon 1.827 0.068 Grade 1 8(11.4％) 12(17.9％) 20(14.6％) Rank sum test Grade 2 3(4.3％) 7(10.5％) 10(7.3％) Grade 3 0(0％) 0(0％) 0(0％) Total 70(100％) 67(100％) 137(100％) 7±1d Grade 0 24(66.7％) 23(65.7％) 47(66.2％) Wilcoxon 0.000 1.000 Grade 1 10(27.8％) 11(31.4％) 21(29.6％) Rank sum test Grade 2 2(5.6％) 1(2.9％) 3(4.2％) Grade 3 0(0％) 0(0％) 0(0％) Total 36(100％) 35(100％) 71(100％) 14±2d Grade 0 27(73％) 27(75％) 54(74％) Wilcoxon -0.245 0.806 Grade 1 8(21.6％) 8(22.2％) 16(21.9％) Rank sum test Grade 2 2(5.4％) 1(2.8％) 3(4.1％) Grade 3 0(0％) 0(0％) 0(0％) Total 37(100％) 36(100％) 73(100％) 21±2d Grade 0 22(73.3％) 23(76.7％) 45(75％) Wilcoxon 0.343 0.732 Grade 1 6(20％) 6(20％) 12(20％) Rank sum test Grade 2 2(6.7％) 1(3.3％) 3(5％) Grade 3 0(0％) 0(0％) 0(0％) Total 30(100％) 30(100％) 60(100％)

[0209] Table 42 Inter-group comparison of Ischemia classification (PPS)

[0210] Index Item Control group Experimental group Total Test method Test statistic P - value 0d Grade 0 57(85.1％) 45(71.4％) 102(78.5％) Wilcoxon 1.948 0.054 Level 1 8(11.9％) 12(19.1％) 20(15.4％) Rank sum test Level 2 2(3％) 6(9.5％) 8(6.2％) Level 3 0(0％) 0(0％) 0(0％) Total 67(100％) 63(100％) 130(100％) 7±1d Level 0 22(66.7％) 23(65.7％) 45(66.2％) Wilcoxon -0.067 0.947 Level 1 10(30.3％) 11(31.4％) 21(30.9％) Rank sum test Level 2 1(3％) 1(2.9％) 2(2.9％) Level 3 0(0％) 0(0％) 0(0％) Total 33(100％) 35(100％) 68(100％) 14±2d Level 0 26(74.3％) 27(75％) 53(74.7％) Wilcoxon 0.061 0.952 Level 1 8(22.9％) 8(22.2％) 16(22.5％) Rank sum test Level 2 1(2.9％) 1(2.8％) 2(2.8％) Level 3 0(0％) 0(0％) 0(0％) Total 35(100％) 36(100％) 71(100％) 21±2d Level 0 21(75％) 23(79.3％) 44(77.2％) Wilcoxon 0.361 0.720 Level 1 6(21.4％) 5(17.2％) 11(19.3％) Rank sum test Level 2 1(3.6％) 1(3.5％) 2(3.5％) Level 3 0(0％) 0(0％) 0(0％) Total 28(100％) 29(100％) 57(100％)

[0211] Table 43 Inter-group comparison of Foot Infection classification (FAS)

[0212] Index Item Control group Experimental group Total Test method Test statistic P value 0d Level 0 10(14.3％) 8(11.8％) 18(13％) Wilcoxon 0.930 0.352 Level 1 49(70％) 45(66.2％) 94(68.1％) Rank sum test Level 2 11(15.7％) 15(22.1％) 26(18.8％) Level 3 0(0％) 0(0％) 0(0％) Total 70(100％) 68(100％) 138(100％) 7±1d Level 0 20(30.8％) 22(36.7％) 42(33.6％) Wilcoxon -0.476 0.634 Level 1 37(56.9％) 30(50％) 67(53.6％) Rank sum test Level 2 8(12.3％) 8(13.3％) 16(12.8％) Level 3 0(0％) 0(0％) 0(0％) Total 65(100％) 60(100％) 125(100％) 14±2d Level 0 39(56.5％) 34(53.1％) 73(54.9％) Wilcoxon 0.226 0.821 Level 1 23(33.3％) 25(39.1％) 48(36.1％) Rank sum test Level 2 7(10.1％) 5(7.8％) 12(9％) Level 3 0(0％) 0(0％) 0(0％) Total 69(100％) 64(100％) 133(100％) 21±2d Level 0 48(77.4％) 42(70％) 90(73.8％) Wilcoxon 0.847 0.397 Level 1 12(19.4％) 17(28.3％) 29(23.8％) Rank sum test Level 2 2(3.2％) 1(1.7％) 3(2.5％) Level 3 0(0％) 0(0％) 0(0％) Total 62(100％) 60(100％) 122(100％)

[0213] Inter-group comparison of the Foot Infection grading in Table 44 (PPS)

[0214]

[0215]

[0216] There were no statistically significant differences in the Wagner scores, IWGDF / IDSA grading, Texas grading, Texas staging, and WIFI wound scores of the two groups of subjects at 0 d, 7±1 d, 14±2 d, and 21±2 d. The result trends of the PPS dataset and the FAS dataset were the same.

[0217] 7. Summary of efficacy

[0218] (1) Intra-group comparison of the ulcer areas of the two groups with those before treatment showed statistically significant differences at all follow-up points outside the baseline.

[0219] (2) There were no statistically significant differences in the percentage changes in the target ulcer areas of the two groups of subjects compared with the baseline at the follow-up points of 7±1 d, 14±2 d, 21±2 d, 28±3 d, 56±3 d, and 84±7 d. The result trends of the PPS dataset and the FAS dataset were the same.

[0220] (3) There were no statistically significant differences in the target ulcer areas of the two groups of subjects and their changes from the baseline at the follow-up points of 7±1 d, 14±2 d, 21±2 d, 28±3 d, 56±3 d, and 84±7 d.

[0221] (4) There were no statistically significant differences in the proportions and degrees of complete healing of the two groups of subjects at 14±2 d, 28±3 d, 56±3 d, and 84±7 d. The result trends of the PPS dataset and the FAS dataset were the same.

[0222] (5) In the FAS dataset, there was a statistically significant difference in the change values of the TCM syndrome scores of the two groups of subjects at 84±7 d, and the reduction value of the experimental group was greater than that of the control group. There were no statistically significant differences at 7±1 d, 14±2 d, 21±2 d, 28±3 d, and 56±3 d. In the PPS dataset, there were no statistically significant differences in the change values of the TCM syndrome scores of the two groups of subjects at 7±1 d, 14±2 d, 21±2 d, 28±3 d, 56±3 d, and 84±7 d.

[0223] (6) There were no statistically significant differences in the Wagner scores, IWGDF / IDSA grades, Texas grades, Texas stages, and WIFI wound scores between the two groups of subjects at 0 d, 7±1 d, 14±2 d, and 21±2 d. The results trends of the PPS dataset and the FAS dataset were the same.

[0224] (7) In the FAS dataset, there were no statistically significant differences in the proportions of patients who withdrew early due to poor efficacy and adverse events between the two groups of subjects. In the PPS dataset, there were no subjects who withdrew due to poor efficacy in both groups.

[0225] (8) There were no statistically significant differences in the inflammation-related indicators (white blood cells, percentage of neutrophils, C-reactive protein) between the two groups of subjects at 7±1 d, 14±2 d, 21±2 d, 28±3 d, 56±3 d, and 84±7 d. The results trends of the PPS dataset and the FAS dataset were the same.

[0226] (9) In the FAS dataset, skin grafting and suturing did not occur in both groups of subjects, and there were no statistically significant differences in debridement, amputation, or toe amputation between the groups. There was no amputation or toe amputation in the PPS dataset, and the trend of debridement was the same as that of the FAS dataset. During the study period, 2 subjects in the control group received amputation or toe amputation.

[0227] Analysis:

[0228] (1) When comparing within each group between the two groups and the ulcer area before treatment, there were statistically significant differences at all follow-up points outside the baseline. This indicates that both groups can effectively improve the ulcer area.

[0229] The change values and change percentages of the target ulcer area of the two groups of subjects compared with the baseline gradually increased with the extension of the treatment time, indicating that the treatment drugs of both groups can better improve the ulcer. When comparing between the groups, there were no statistically significant differences at each follow-up point of 7±1 d, 14±2 d, 21±2 d, 28±3 d, 56±3 d, and 84±7 d. The results trends of the PPS dataset and the FAS dataset were the same. This indicates that under the current sample size, there was no obvious difference in the efficacy between the two groups.

[0230] There were no statistically significant differences in the Wagner scores, IWGDF / IDSA grades, Texas grades, Texas stages, WIFI wound scores, and inflammation-related indicators (white blood cells, percentage of neutrophils, C-reactive protein) between the two groups of subjects at 0 d, 7±1 d, 14±2 d, and 21±2 d. The results trends of the PPS dataset and the FAS dataset were the same. These all strengthened the above conclusions.

[0231] Although the experimental group showed a statistically significant difference between the two groups in terms of traditional Chinese medicine syndromes in the FAS dataset at 84±7 days, the same trend was not shown in the PPS dataset. This further strengthens the above view.

[0232] (2) There was no statistically significant difference in the proportion and degree of complete healing between the two groups of subjects at 14±2 days, 28±3 days, 56±3 days, and 84±7 days. The PPS dataset had the same trend as the FAS data results. However, based on the research data, the healing rate of the experimental group was significantly higher than that of the control group at 56±3 days and 84±7 days. This suggests that with the expansion of the sample size, there may be a statistically significant difference between the two groups, and the healing rate of the experimental group may be higher than that of the control group. In terms of the reduction value and reduction rate of the ulcer area throughout the study, the data of the experimental group were greater than those of the control group throughout the study, which also strengthens this conclusion.

[0233] (3) During the study period, 2 cases (2.9%) in the control group underwent amputation or toe amputation, while this data was 0 in the experimental group. This strengthens the opinion in point (2), that is, the treatment of the experimental group may be superior to that of the control group in terms of wound healing.

[0234] (4) This study is a small-sample exploratory study on the expansion of indications. From the perspective of complete wound healing, at 84±7 days, the experimental group showed a trend of being superior to the control group in terms of numerical value. At this point, no superior effect was compared between the two groups, which may be related to the sample size. In future research, it is recommended to increase the observed sample size, use wound healing as the main efficacy evaluation index, and expand a certain number of case populations, such as further drug administration observation for healed wound cases, to further evaluate the effect of the medicament paste of Example 1.

[0235] In addition, based on a similar effect to the above experiment, the traditional Chinese medicine medicament paste prepared in Example 1 of the present invention can also be used to treat burn and scald wounds.

[0236] Although the present invention has been described in detail above with general descriptions and specific embodiments, some modifications or improvements can be made based on the present invention, which are obvious to those skilled in the art. Therefore, these modifications or improvements made without departing from the spirit of the present invention all fall within the scope of protection required by the present invention.

Claims

1. A method for preparing a traditional Chinese medicine ointment, comprising the following steps: S1. Add gamboge medicinal materials into water, reflux and steam, filter the filtrate, concentrate it to a paste state, dry it, and pulverize it to obtain gamboge powder; S2. Add sulfur powder and realgar powder into tung oil to make ointment; S3. After cooling the ointment obtained in step S2, add gamboge powder and pearl powder for blending and sterilization; S4. After cooling the paste obtained in step S3, add musk and mix to obtain the traditional Chinese medicine ointment.

2. The preparation method according to claim 1, characterized in that, The weight parts of each medicinal material are as follows: 45 - 65 weight parts of sulfur, 5 - 25 weight parts of realgar, 1 - 3 weight parts of gamboge, 1 - 3 weight parts of pearl, and 1 - 3 weight parts of musk.

3. The preparation method according to claim 1 or 2, characterized in that, The particle sizes of the sulfur powder, realgar powder, gamboge powder, and pearl powder are all greater than 150 mesh.

4. The preparation method according to any one of claims 1-3, characterized in that, In step S1, the reflux steaming time is 4 - 7h; The mesh number of the sieve used for filtration is 150 mesh; The concentration conditions are: temperature 75 - 85°C, vacuum degree -0.04 - -0.10 MPa; The drying conditions are: temperature 75 - 85°C; The mesh number of the sieve used for pulverization is 150 mesh.

5. The preparation method according to any one of claims 1-4, characterized in that, In step S2, the ointment making is carried out according to the following operations: Add tung oil into the ointment making tank, add sulfur powder and realgar powder, stir while adding, the stirring speed is 20 - 30 r / min, and close the feeding port; Open the jacket valve of the ointment making tank, turn on the heat conduction oil heating, turn on the dust removal, smoke exhaust buttons and smoke exhaust valves, heat up to 260 - 270°C, stop heating, and continue stirring for 25 - 35 min.

6. The preparation method according to any one of claims 1-5, characterized in that [[ID=X]]The step S3 is carried out according to the following operations: When the ointment obtained in step S2 is cooled to 150 - 160°C, add gamboge powder and pearl powder, and stir for 25 - 30 min; Pass the obtained material through a 120 - mesh sieve and pump it into a blending tank with an internal pressure of -0.04 - -0.05 MPa. After the pumping is completed, close the discharge valve of the ointment making tank, remove the remaining vacuum in the blending tank, then close the feed valve of the blending tank and the discharge valve of the ointment making tank, turn on the stirring of the blending tank, and the stirring speed is 25 - 30 r / min; Open the smoke exhaust valve of the blending tank, turn on the heat conduction oil of the blending tank and the stirring of the blending tank, keep the blending tank at 150 - 160°C, and keep warm for 50 - 60 min for sterilization.

7. The preparation method according to any one of claims 1-6, characterized in that, The step S4 is carried out according to the following operations: Turn on the cooling oil, cool the paste obtained in step S3 to 50 - 60°C, add musk, and stir for 25 - 30 min.

8. A traditional Chinese medicine ointment obtained by the preparation method according to any one of claims 1 - 7.

9. Use of the traditional Chinese medicine ointment according to claim 8 in the preparation of a drug for treating skin wounds.

10. The application according to claim 9, wherein, The wounds include: burn and scald wounds, pressure sore wounds, diabetic foot ulcers.

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