Ointment for treating diabetic foot and refractory wounds and preparation method thereof

Abstract

The invention relates to ointment for treating diabetic foot and refractory wounds and a preparation method thereof, and belongs to the technical field of ointment. The preparation method of the ointment for treating diabetic foot and refractory wounds comprises the following steps: mixing beeswax, polygonum cuspidatum and sesame oil to obtain a suspension, mixing coptis chinensis, lithospermum erythrorhizon and sesame oil to obtain a coptis chinensis-lithospermum erythrorhizon nano-emulsion, mixing sanguisorba officinalis, golden cypress, scutellaria baicalensis and sesame oil to obtain an enzyme activated compound, adding borneol into the suspension, and uniformly stirring to obtain the ointment for treating diabetic foot and refractory wounds. And mixing while injecting the coptis chinensis-lithospermum nanoemulsion to obtain a mixed system, adding the enzyme activated compound into the mixed system, and mixing to obtain the product. A suspension, a coptis chinensis-lithospermum nanoemulsion and an enzyme activation compound are prepared and then have a synergistic effect with borneol, so that deep penetration of effective components is realized, necrotic tissues are removed, antibacterial and anti-inflammatory effects are achieved, rapid healing of wounds is promoted, and diabetic feet and refractory wounds are effectively treated.

Description

Technical Field

[0001] The present invention belongs to the technical field of ointments, and relates to an ointment for treating diabetic foot and refractory wounds and a preparation method thereof. Background Art

[0002] Diabetic foot is caused by poor blood sugar control in diabetic patients, leading to peripheral neuropathy and blood circulation disorders, resulting in problems such as foot ulcers, infections, and tissue necrosis; in addition to the wounds caused by pathology, there are also refractory wounds in reality that are difficult to heal due to various factors such as scalds, etc. The treatment is difficult and it is easy to affect the patient's quality of life and mental health.

[0003] At present, there are various treatment means for refractory wounds caused by pathology and external factors. Ointments, due to their convenient application method and the characteristic of directly acting on the wound surface, have become one of the important means in treatment. However, there are also certain deficiencies in the application of ointments. For example, the utilization rate of ointments by some patients is relatively low, resulting in the ointments being unable to exert their beneficial effects, and thus the curative effects vary due to individual differences. Summary of the Invention

[0004] The purpose of the present invention is to provide an ointment for treating diabetic foot and refractory wounds and a preparation method thereof. The present invention realizes the deep penetration of active ingredients, clears necrotic tissues, exerts antibacterial and anti-inflammatory effects, promotes the rapid healing of the wound surface, and effectively treats diabetic foot and refractory wounds through the synergistic effect of preparing a suspension, Coptis chinensis-Arnebia euchroma nanoemulsion, enzyme activation complex and borneol.

[0005] The purpose of the present invention can be achieved by the following technical solutions:

[0006] A preparation method of an ointment for treating diabetic foot and refractory wounds, the preparation method of the ointment comprises the following steps:

[0007] Step 1: Mix beeswax, Polygonum cuspidatum and sesame oil to obtain a suspension;

[0008] Step 2: Mix Coptis chinensis, Arnebia euchroma and sesame oil to obtain Coptis chinensis-Arnebia euchroma nanoemulsion;

[0009] Step 3: Mix Sanguisorba officinalis, Phellodendron amurense, Scutellaria baicalensis and sesame oil to obtain an enzyme activation complex;

[0010] Step 4: Add borneol to the suspension, mix and inject the Coptis chinensis-Arnebia euchroma nanoemulsion while mixing to obtain a mixed system;

[0011] Step 5: Add the enzyme activation complex to the mixed system and mix to obtain the product.

[0012] Further, the mixing in Step 1 refers to stirring at a rotation speed of 500 - 520 rpm for 30 - 40 min at 53 - 57°C; the average particle size of the beeswax is 160 - 200 nm.

[0013] Further, the mixing in Step 2 refers to dissolving Coptis chinensis, Arnebia euchroma, and sesame oil uniformly at 58 - 62°C, and then homogenizing at a pressure of 750 - 850 bar and a rotation speed of 2000 - 3000 rpm for 3 - 5 min; the average particle size of the Coptis chinensis - Arnebia euchroma nanoemulsion is 130 - 160 nm.

[0014] Further, the mixing in Step 3 refers to adding 0.1 M HCl solution to adjust the pH to 5.3 - 5.7, stirring at a rotation speed of 700 - 900 rpm at 58 - 62°C for 1 - 1.2 h, and then performing vacuum drying and sieving through a 200 - mesh sieve.

[0015] Further, the borneol in Step 4 is obtained by mixing medicinal borneol and Tween - 80 in a mass ratio of 1:2.8 - 3.2; the mixing refers to stirring at a low speed of 150 - 250 rpm at 38 - 42°C and stopping when the injection of the Coptis chinensis - Arnebia euchroma nanoemulsion is completed; the injection refers to injecting the Coptis chinensis - Arnebia euchroma nanoemulsion at a rate of 0.8 - 1.2 mL / min using a constant - flow pump.

[0016] Further, the mixing in Step 5 refers to stirring evenly at 500 - 1500 rpm, performing defoaming treatment under a vacuum of - 0.08 MPa for 40 - 50 min, and then sieving through a 200 - mesh sieve.

[0017] Further, the sesame oil is uniformly obtained by mixing sesame oil, Tween - 80, and Span - 80 in a mass ratio of 0.25 - 0.35:0.08 - 0.12:1.4 - 1.6; the mass ratio of the sesame oil in Step 1, Step 2, and Step 3 is 1:0.2 - 0.3:0.12 - 0.18.

[0018] Further, the polygonum cuspidatum, coptis chinensis, arnebia euchroma, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis are respectively the alcohol - extracted products of polygonum cuspidatum, coptis chinensis, arnebia euchroma, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis.

[0019] Further, the alcohol - extracted products of the polygonum cuspidatum, coptis chinensis, arnebia euchroma, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis are all obtained through the following steps:

[0020] Step X1: Respectively crush the raw materials of polygonum cuspidatum, coptis chinensis, arnebia euchroma, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis and sieve through a 60 - 100 - mesh sieve to obtain the powders of the corresponding raw materials.

[0021] Step X2: Mix the powders of the corresponding raw materials with 65 - 75wt% ethanol solution at a ratio of 1:9.2 - 10.8 g / mL. Set the ultrasonic temperature at 35 - 45 °C, the ultrasonic frequency at 30 - 40 kHz, and the ultrasonic power at 200 - 400 W. Perform ultrasonic extraction 3 times, with each ultrasonic time being 30 - 40 min. After combining the 3 extraction liquids, concentrate under reduced pressure to a relative density of 1.2 - 1.3 to obtain the product.

[0022] Furthermore, the raw materials of the ointment, by weight, include 18 - 22 parts of beeswax, 10 - 14 parts of sesame oil, 7 - 9 parts of polygonum cuspidatum, 10 - 14 parts of coptis chinensis, 7 - 9 parts of lithospermum erythrorhizon, 13 - 17 parts of sanguisorba officinalis, 8 - 12 parts of phellodendron amurense, 8 - 12 parts of scutellaria baicalensis, and 4 - 6 parts of borneol.

[0023] Advantages of the present invention:

[0024] (1) In the coptis chinensis - lithospermum erythrorhizon nanoemulsion of the present invention, by utilizing the small - molecule characteristics of nanoemulsion and the fatty acids in sesame oil to encapsulate lipophilic components, it helps the active ingredients in coptis chinensis and lithospermum erythrorhizon to efficiently penetrate the skin barrier and reach the deep layer of the wound surface. In addition, the sustained - release characteristics of nanoemulsion enable the drug to be continuously released at the wound surface, maintaining a long - term antibacterial and anti - inflammatory effect.

[0025] (2) In the enzyme - activated complex of the present invention, the tannins in sanguisorba officinalis chelate zinc ions (Zn 2+ is an essential element for the active center of MMPs) to achieve the removal of necrotic tissue. At the same time, sanguisorba saponins stimulate the migration of fibroblasts to synergistically repair the wound surface; berberine in phellodendron amurense achieves tissue repair by inhibiting the excessive activation of pathological elastase and degrading necrotic fibers; baicalin in scutellaria baicalensis enhances the bactericidal ability of lysozyme, regulates the immune microenvironment, effectively clears infections, and promotes wound healing. Further, in the acidic environment of the wound surface, the enzyme - activated complex improves the enzyme balance of the wound surface, reduces the level of inflammatory factors in the wound surface, and synergistically promotes the treatment of diabetic foot and difficult - to - heal wounds with the transdermal penetration of coptis chinensis - lithospermum erythrorhizon nanoemulsion.

[0026] (3) The beeswax in the suspension of the present invention softens to form a semi - solid paste, which, when compounded with polygonum cuspidatum and sesame oil, can closely adhere to the wound surface. Among them, emodin in polygonum cuspidatum can lower the pH of necrotic tissue, and anthraquinone components gently dissolve fibrin in necrotic tissue, thereby improving the efficiency of the enzyme - activated complex. On this basis, the suspension, as a nano - carrier, carries the active ingredients in the ointment, synergistically with borneol to open the skin barrier, and jointly penetrate to the deep layer of necrotic tissue, enhancing drug penetration and accelerating wound healing.

[0027] (4) The sesame oil in the present invention further disperses other components with the help of Tween - 80 and Span - 80, improving the drug permeability; adding Tween - 80 to borneol helps borneol penetrate more quickly to the wound surface, exert better effects, and improve the wound - healing environment. Detailed implementation manners

[0028] To further elaborate on the technical means and effects adopted by the present invention to achieve the intended invention purpose, the following, in combination with embodiments, details the specific implementation manners, structures, features and their effects according to the present invention as follows.

[0029] Embodiment 1

[0030] A preparation method of an ointment for treating diabetic foot and non-healing wounds. The preparation method of the ointment in this embodiment includes the following steps:

[0031] Step 1: Mix beeswax, polygonum cuspidatum and sesame oil to obtain a suspension;

[0032] Step 2: Mix coptis chinensis, lithospermum erythrorhizon and sesame oil to obtain coptis chinensis-lithospermum erythrorhizon nanoemulsion;

[0033] Step 3: Mix sanguisorba officinalis, phellodendron amurense, scutellaria baicalensis and sesame oil to obtain an enzyme activation complex;

[0034] Step 4: Add borneol to the suspension, mix and inject the coptis chinensis-lithospermum erythrorhizon nanoemulsion while mixing to obtain a mixed system;

[0035] Step 5: Add the enzyme activation complex to the mixed system, mix, and then obtain the product.

[0036] The mixing in Step 1 of this embodiment refers to stirring at a speed of 500 rpm for 40 min at 53 °C; the average particle size of beeswax is 160 nm.

[0037] The mixing in Step 2 of this embodiment refers to dissolving coptis chinensis, lithospermum erythrorhizon and sesame oil evenly at 58 °C, and then homogenizing at a pressure of 750 bar and a speed of 2000 rpm for 5 min; the average particle size of the coptis chinensis-lithospermum erythrorhizon nanoemulsion is 130 nm.

[0038] The mixing in Step 3 of this embodiment refers to adjusting the pH to 5.3 by dropping 0.1 M HCl solution, stirring at a speed of 700 rpm at 58 °C for 1.2 h, drying in vacuum and then sieving through a 200-mesh sieve.

[0039] The borneol in Step 4 of this embodiment is obtained by mixing medicinal borneol and tween-80 according to a mass ratio of 1:2.8; the mixing refers to stirring at a low speed of 150 rpm at 38 °C and stopping when the injection of the coptis chinensis-lithospermum erythrorhizon nanoemulsion is completed; the injection refers to injecting the coptis chinensis-lithospermum erythrorhizon nanoemulsion at a rate of 0.8 mL / min using a constant flow pump.

[0040] The mixing in Step 5 of this embodiment refers to stirring evenly at 500 rpm, performing defoaming treatment under a vacuum of -0.08 MPa for 40 min, and then sieving through a 200-mesh sieve.

[0041] The sesame oil in this embodiment is obtained by mixing sesame oil, Tween-80, and Span-80 in a mass ratio of 0.25:0.08:1.4; the mass ratio of the sesame oil in Step 1, Step 2, and Step 3 is 1:0.2:0.12.

[0042] The polygonum cuspidatum, coptis chinensis, lithospermum erythrorhizon, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis in this embodiment are respectively the alcohol extracts of polygonum cuspidatum, coptis chinensis, lithospermum erythrorhizon, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis.

[0043] The alcohol extracts of polygonum cuspidatum, coptis chinensis, lithospermum erythrorhizon, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis in this embodiment are all obtained through the following steps:

[0044] Step X1: Crush the raw materials of polygonum cuspidatum, coptis chinensis, lithospermum erythrorhizon, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis respectively through a 60-mesh sieve to obtain the powders of the corresponding raw materials;

[0045] Step X2: Mix the powders of the corresponding raw materials with a 65wt% ethanol solution in a ratio of 1:9.2 g / mL, set the ultrasonic temperature at 35°C, the ultrasonic frequency at 30 kHz, the ultrasonic power at 200 W, perform ultrasonic extraction 3 times, with each ultrasonic time being 40 min. After combining the 3 extraction liquids, concentrate under reduced pressure to a relative density of 1.2 to obtain the product.

[0046] The raw materials of the ointment in this embodiment are calculated by weight and include 18 parts of beeswax, 10 parts of sesame oil, 7 parts of polygonum cuspidatum, 10 parts of coptis chinensis, 7 parts of lithospermum erythrorhizon, 13 parts of sanguisorba officinalis, 8 parts of phellodendron amurense, 8 parts of scutellaria baicalensis, and 4 parts of borneol.

[0047] Example 2

[0048] A preparation method of an ointment for treating diabetic foot and non-healing wounds. The preparation method of the ointment in this embodiment comprises the following steps:

[0049] Step 1: Mix beeswax, polygonum cuspidatum, and sesame oil to obtain a suspension;

[0050] Step 2: Mix coptis chinensis, lithospermum erythrorhizon, and sesame oil to obtain coptis chinensis-lithospermum erythrorhizon nanoemulsion;

[0051] Step 3: Mix sanguisorba officinalis, phellodendron amurense, scutellaria baicalensis, and sesame oil to obtain an enzyme activation complex;

[0052] Step 4: Add borneol to the suspension, mix, and inject the coptis chinensis-lithospermum erythrorhizon nanoemulsion while mixing to obtain a mixed system;

[0053] Step 5: Add the enzyme activation complex to the mixed system and mix to obtain the product.

[0054] The mixing in Step 1 of this embodiment refers to stirring at a speed of 505 rpm at 54°C for 37 min; the average particle size of beeswax is 170 nm.

[0055] The mixing in Step 2 of this example refers to dissolving Coptis chinensis, Arnebia euchroma, and sesame oil evenly at 59 °C, and then homogenizing at 2200 rpm for 4.5 min under a pressure of 780 bar; the average particle size of the Coptis chinensis-Arnebia euchroma nanoemulsion is 140 nm.

[0056] The mixing in Step 3 of this example refers to adding 0.1 M HCl solution to adjust the pH to 5.4, stirring at 750 rpm at 59 °C for 1.05 h, drying under vacuum, and then passing through a 200-mesh sieve.

[0057] The borneol in Step 4 of this example is obtained by mixing medicinal borneol and Tween-80 in a mass ratio of 1:2.9; the mixing refers to stirring at a low speed of 180 rpm at 39 °C and stopping when the injection of the Coptis chinensis-Arnebia euchroma nanoemulsion is completed; the injection refers to injecting the Coptis chinensis-Arnebia euchroma nanoemulsion at a rate of 0.9 mL / min using a constant flow pump.

[0058] The mixing in Step 5 of this example refers to stirring evenly at 800 rpm, performing defoaming treatment under a vacuum of -0.08 MPa for 47 min, and then passing through a 200-mesh sieve.

[0059] The sesame oil in this example is obtained by mixing sesame oil, Tween-80, and Span-80 in a mass ratio of 0.28:0.09:1.42; the mass ratio of the sesame oil in Steps 1, 2, and 3 is 1:0.23:0.14.

[0060] The polygonum cuspidatum, coptis chinensis, arnebia euchroma, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis in this example are respectively the ethanol extracts of polygonum cuspidatum, coptis chinensis, arnebia euchroma, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis.

[0061] The ethanol extracts of the polygonum cuspidatum, coptis chinensis, arnebia euchroma, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis in this example are all obtained through the following steps:

[0062] Step X1: Crush the raw materials of polygonum cuspidatum, coptis chinensis, arnebia euchroma, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis respectively and pass through a 70-mesh sieve to obtain the powders of the corresponding raw materials;

[0063] Step X2: Mix the powders of the corresponding raw materials with 68 wt% ethanol solution in a ratio of 1:9.6 g / mL respectively, set the ultrasonic temperature at 38 °C, the ultrasonic frequency at 32 kHz, the ultrasonic power at 250 W, perform ultrasonic extraction 3 times, with the ultrasonic time of each time being 37 min, and after combining the 3 extraction solutions, concentrate under reduced pressure to a relative density of 1.22 to obtain.

[0064] The raw materials of the ointment in this example, by weight, include 19 parts of beeswax, 11 parts of sesame oil, 7.8 parts of polygonum cuspidatum, 11 parts of coptis chinensis, 7.5 parts of arnebia euchroma, 14 parts of sanguisorba officinalis, 9.2 parts of phellodendron amurense, 9.6 parts of scutellaria baicalensis, and 4.8 parts of borneol.

[0065] Example 3

[0066] A preparation method of an ointment for treating diabetic foot and non-healing wounds. The preparation method of the ointment in this example comprises the following steps:

[0067] Step 1: Mix beeswax, polygonum cuspidatum, and sesame oil to obtain a suspension;

[0068] Step 2: Mix coptis chinensis, lithospermum erythrorhizon, and sesame oil to obtain coptis chinensis-lithospermum erythrorhizon nanoemulsion;

[0069] Step 3: Mix sanguisorba officinalis, phellodendron amurense, scutellaria baicalensis, and sesame oil to obtain an enzyme activation complex;

[0070] Step 4: Add borneol to the suspension, mix, and inject the coptis chinensis-lithospermum erythrorhizon nanoemulsion while mixing to obtain a mixed system;

[0071] Step 5: Add the enzyme activation complex to the mixed system and mix to obtain the product.

[0072] The mixing in Step 1 of this example means stirring at 55°C at a speed of 510 rpm for 35 min; the average particle size of beeswax is 180 nm.

[0073] The mixing in Step 2 of this example means dissolving coptis chinensis, lithospermum erythrorhizon, and sesame oil evenly at 60°C, and then homogenizing at 2500 rpm under a pressure of 800 bar for 4 min; the average particle size of the coptis chinensis-lithospermum erythrorhizon nanoemulsion is 145 nm.

[0074] The mixing in Step 3 of this example means adding 0.1M HCl solution to adjust the pH to 5.5, stirring at 60°C at a speed of 800 rpm for 1.1 h, drying in vacuum and then passing through a 200-mesh sieve.

[0075] The borneol in Step 4 of this example is obtained by mixing medicinal borneol and tween-80 in a mass ratio of 1:3; the mixing means stirring at a low speed of 200 rpm at 40°C and stopping when the injection of the coptis chinensis-lithospermum erythrorhizon nanoemulsion is completed; the injection means injecting the coptis chinensis-lithospermum erythrorhizon nanoemulsion at a rate of 1 mL / min using a constant flow pump.

[0076] The mixing in Step 5 of this example means stirring evenly at 1000 rpm, then performing defoaming treatment under a vacuum of -0.08 MPa for 45 min, and then passing through a 200-mesh sieve.

[0077] The sesame oil in this example is uniformly obtained by mixing sesame oil, tween-80, and span-80 in a mass ratio of 0.3:0.1:1.5; the mass ratio of the sesame oil in Step 1, Step 2, and Step 3 is 1:0.25:0.15.

[0078] In this embodiment, the polygonum cuspidatum, coptis chinensis, lithospermum erythrorhizon, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis are respectively the ethanol extracts of polygonum cuspidatum, coptis chinensis, lithospermum erythrorhizon, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis.

[0079] The ethanol extracts of polygonum cuspidatum, coptis chinensis, lithospermum erythrorhizon, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis in this embodiment are all obtained by the following steps:

[0080] Step X1: Crush the raw materials of polygonum cuspidatum, coptis chinensis, lithospermum erythrorhizon, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis respectively through an 80-mesh sieve to obtain the powders of the corresponding raw materials;

[0081] Step X2: Mix the powders of the corresponding raw materials with a 70 wt% ethanol solution at a ratio of 1:10 g / mL, set the ultrasonic temperature at 40 °C, the ultrasonic frequency at 35 kHz, the ultrasonic power at 300 W, perform ultrasonic extraction 3 times, with the ultrasonic time of each time being 35 min. After combining the 3 extraction solutions, concentrate under reduced pressure to a relative density of 1.25 to obtain the product.

[0082] The raw materials of the ointment in this embodiment are calculated by weight and include 20 parts of beeswax, 12 parts of sesame oil, 9 parts of polygonum cuspidatum, 12 parts of coptis chinensis, 8 parts of lithospermum erythrorhizon, 15 parts of sanguisorba officinalis, 10 parts of phellodendron amurense, 10 parts of scutellaria baicalensis, and 5 parts of borneol.

[0083] Example 4

[0084] A preparation method of an ointment for treating diabetic foot and refractory wounds. The preparation method of the ointment in this embodiment includes the following steps:

[0085] Step 1: Mix beeswax, polygonum cuspidatum, and sesame oil to obtain a suspension;

[0086] Step 2: Mix coptis chinensis, lithospermum erythrorhizon, and sesame oil to obtain a coptis chinensis-lithospermum erythrorhizon nanoemulsion;

[0087] Step 3: Mix sanguisorba officinalis, phellodendron amurense, scutellaria baicalensis, and sesame oil to obtain an enzyme activation complex;

[0088] Step 4: Add borneol to the suspension, mix, and inject the coptis chinensis-lithospermum erythrorhizon nanoemulsion while mixing to obtain a mixed system;

[0089] Step 5: Add the enzyme activation complex to the mixed system and mix to obtain the product.

[0090] The mixing in Step 1 of this embodiment refers to stirring at a speed of 515 rpm for 32 min at 56 °C; the average particle size of beeswax is 190 nm.

[0091] The mixing in Step 2 of this embodiment refers to dissolving coptis chinensis, lithospermum erythrorhizon, and sesame oil evenly at 61 °C and then homogenizing at a pressure of 820 bar at a speed of 2800 rpm for 3.5 min; the average particle size of the coptis chinensis-lithospermum erythrorhizon nanoemulsion is 150 nm.

[0092] In step 3 of this embodiment, the mixing refers to adding 0.1M HCl solution to adjust the pH to 5.6, stirring at 850 rpm for 1.05 h at 61°C, drying under vacuum, and then passing through a 200-mesh sieve.

[0093] In step 4 of this embodiment, borneol is obtained by mixing medicinal borneol and Tween-80 in a mass ratio of 1:3.1; the mixing refers to stirring at a low speed of 220 rpm at 41°C and stopping when the Coptis chinensis-Arnebia euchroma nanoemulsion is completely injected; the injection refers to injecting the Coptis chinensis-Arnebia euchroma nanoemulsion at a rate of 1.1 mL / min using a constant flow pump.

[0094] In step 5 of this embodiment, the mixing refers to stirring evenly at 1200 rpm, performing defoaming treatment under a vacuum of -0.08 MPa for 42 min, and then passing through a 200-mesh sieve.

[0095] The sesame oil in this embodiment is obtained by mixing sesame oil, Tween-80, and Span-80 in a mass ratio of 0.32:0.11:1.53; the mass ratios of the sesame oil in steps 1, 2, and 3 are 1:0.26:0.17.

[0096] In this embodiment, polygonum cuspidatum, coptis chinensis, arnebia euchroma, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis are respectively the alcohol extracts of polygonum cuspidatum, coptis chinensis, arnebia euchroma, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis.

[0097] The alcohol extracts of polygonum cuspidatum, coptis chinensis, arnebia euchroma, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis in this embodiment are all obtained through the following steps:

[0098] Step X1: Crush the raw materials of polygonum cuspidatum, coptis chinensis, arnebia euchroma, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis respectively and pass through a 90-mesh sieve to obtain the powders of the corresponding raw materials;

[0099] Step X2: Mix the powders of the corresponding raw materials with 72 wt% ethanol solution in a ratio of 1:10.4 g / mL respectively, set the ultrasonic temperature at 42°C, the ultrasonic frequency at 37 kHz, the ultrasonic power at 350 W, perform ultrasonic extraction 3 times, with each ultrasonic time being 32 min, and after combining the 3 extraction solutions, concentrate under reduced pressure to a relative density of 1.27 to obtain the product.

[0100] The raw materials of the ointment in this embodiment are calculated by weight and include 21 parts of beeswax, 13 parts of sesame oil, 8.2 parts of polygonum cuspidatum, 13 parts of coptis chinensis, 8.5 parts of arnebia euchroma, 15.6 parts of sanguisorba officinalis, 11.2 parts of phellodendron amurense, 10.7 parts of scutellaria baicalensis, and 4 - 6 parts of borneol.

[0101] Example 5

[0102] A preparation method of an ointment for treating diabetic foot and non-healing wounds. The preparation method of the ointment in this embodiment includes the following steps:

[0103] Step 1: Mix beeswax, polygonum cuspidatum, and sesame oil to obtain a suspension;

[0104] Step 2: Mix coptis chinensis, lithospermum erythrorhizon, and sesame oil to obtain coptis chinensis-lithospermum erythrorhizon nanoemulsion;

[0105] Step 3: Mix sanguisorba officinalis, phellodendron amurense, scutellaria baicalensis, and sesame oil to obtain an enzyme activation complex;

[0106] Step 4: Add borneol to the suspension, mix, and inject the coptis chinensis-lithospermum erythrorhizon nanoemulsion while mixing to obtain a mixed system;

[0107] Step 5: Add the enzyme activation complex to the mixed system, mix, and you will get it.

[0108] The mixing in Step 1 of this example means stirring at 57 °C at a speed of 520 rpm for 30 min; the average particle size of beeswax is 200 nm.

[0109] The mixing in Step 2 of this example means dissolving coptis chinensis, lithospermum erythrorhizon, and sesame oil evenly at 62 °C, and then homogenizing at 3000 rpm under a pressure of 850 bar for 3 min; the average particle size of the coptis chinensis-lithospermum erythrorhizon nanoemulsion is 160 nm.

[0110] The mixing in Step 3 of this example means adding 0.1 M HCl solution to adjust the pH to 5.7, stirring at 62 °C at a speed of 900 rpm for 1 h, drying under vacuum, and then passing through a 200-mesh sieve.

[0111] The borneol in Step 4 of this example is obtained by mixing medicinal borneol and tween-80 according to a mass ratio of 1:3.2; the mixing means stirring at a low speed of 250 rpm at 42 °C and stopping when the injection of the coptis chinensis-lithospermum erythrorhizon nanoemulsion is completed; the injection means injecting the coptis chinensis-lithospermum erythrorhizon nanoemulsion at a rate of 1.2 mL / min using a constant flow pump.

[0112] The mixing in Step 5 of this example means stirring evenly at 1500 rpm, performing defoaming treatment under a vacuum of -0.08 MPa for 50 min, and then passing through a 200-mesh sieve.

[0113] The sesame oil in this example is all obtained by mixing sesame oil, tween-80, and span-80 according to a mass ratio of 0.35:0.12:1.6; the mass ratio of the sesame oil in Step 1, Step 2, and Step 3 is 1:0.3:0.18.

[0114] The polygonum cuspidatum, coptis chinensis, lithospermum erythrorhizon, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis in this example are respectively the ethanol extracts of polygonum cuspidatum, coptis chinensis, lithospermum erythrorhizon, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis.

[0115] The alcohol extracts of polygonum cuspidatum, coptis chinensis, lithospermum erythrorhizon, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis in this example were all obtained through the following steps:

[0116] Step X1: Crush the raw materials of polygonum cuspidatum, coptis chinensis, lithospermum erythrorhizon, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis respectively through a 100-mesh sieve to obtain the powders of the corresponding raw materials;

[0117] Step X2: Mix the powders of the corresponding raw materials with 75wt% ethanol solution at a ratio of 1:10.8 g / mL, set the ultrasonic temperature at 45°C, the ultrasonic frequency at 40 kHz, the ultrasonic power at 400 W, perform ultrasonic extraction 3 times, with each ultrasonic time being 30 min. After combining the 3 extraction solutions, concentrate under reduced pressure to a relative density of 1.3 to obtain the product.

[0118] The raw materials of the ointment in this example, by weight, include 22 parts of beeswax, 14 parts of sesame oil, 9 parts of polygonum cuspidatum, 14 parts of coptis chinensis, 9 parts of lithospermum erythrorhizon, 17 parts of sanguisorba officinalis, 12 parts of phellodendron amurense, 12 parts of scutellaria baicalensis, and 6 parts of borneol.

[0119] Example 6

[0120] On the basis of Example 3, remove the beeswax in the suspension and replace it with polygonum cuspidatum of equal weight, and keep other conditions the same as in Example 3.

[0121] Example 7

[0122] On the basis of Example 3, remove the polygonum cuspidatum in the suspension and replace it with beeswax of equal weight, and keep other conditions the same as in Example 3.

[0123] Example 8

[0124] On the basis of Example 3, remove the coptis chinensis in the nanoemulsion and replace it with lithospermum erythrorhizon of equal weight, and keep other conditions the same as in Example 3.

[0125] Example 9

[0126] On the basis of Example 3, remove the lithospermum erythrorhizon in the nanoemulsion and replace it with coptis chinensis of equal weight, and keep other conditions the same as in Example 3.

[0127] Example 10

[0128] On the basis of Example 3, remove the sanguisorba officinalis in the enzyme activation complex and replace it with phellodendron amurense of equal weight, and keep other conditions the same as in Example 3.

[0129] Example 11

[0130] On the basis of Example 3, remove the phellodendron amurense in the enzyme activation complex and replace it with scutellaria baicalensis of equal weight, and keep other conditions the same as in Example 3.

[0131] Example 12

[0132] On the basis of Example 3, Scutellaria baicalensis in the enzyme activation complex was removed and replaced with an equal weight of Sanguisorba officinalis, and other conditions were kept the same as those in Example 3.

[0133] Example 13

[0134] On the basis of Example 3, Span - 80 in the sesame oil was removed and replaced with an equal weight of Tween - 80, and other conditions were kept the same as those in Example 3.

[0135] Example 14

[0136] On the basis of Example 3, Tween - 80 in the sesame oil was removed and replaced with an equal weight of Span - 80, and other conditions were kept the same as those in Example 3.

[0137] Example 15

[0138] On the basis of Example 3, Tween - 80 in the borneol was removed and replaced with an equal weight of medicinal borneol, and other conditions were kept the same as those in Example 3.

[0139] Comparative Example 1

[0140] On the basis of Example 3, with other conditions unchanged, the preparation method of the ointment was changed to the following steps:

[0141] Step 1: Beeswax, Polygonum cuspidatum, Coptis chinensis, Lithospermum erythrorhizon, and sesame oil were mixed to obtain a suspension. Here, the mixing means stirring at 55 °C at a speed of 510 rpm for 39 min;

[0142] Step 2: Sanguisorba officinalis, Phellodendron amurense, Scutellaria baicalensis, and sesame oil were mixed to obtain an enzyme activation complex;

[0143] Step 3: Borneol was added to the suspension and mixed to obtain a mixed system. Here, the mixing means stirring evenly at 40 °C at a low speed of 200 rpm;

[0144] Step 4: The enzyme activation complex was added to the mixed system and mixed to obtain the product.

[0145] Comparative Example 2

[0146] On the basis of Example 3, with other conditions unchanged, the preparation method of the ointment was changed to the following steps:

[0147] Step 1: Beeswax, Polygonum cuspidatum, and sesame oil were mixed to obtain a suspension;

[0148] Step 2: Mix Coptis chinensis, Lithospermum erythrorhizon, Sanguisorba officinalis, Phellodendron amurense, Scutellaria baicalensis and sesame oil to obtain a complex. Here, the mixing means adding 0.1M HCl solution to adjust the pH to 5.5, stirring at 800 rpm for 70 min at 60°C, drying in vacuum and then sieving through a 200-mesh sieve;

[0149] Step 3: Add borneol to the suspension and mix to obtain a mixed system. Here, the mixing means stirring evenly at a low speed of 200 rpm at 40°C;

[0150] Step 4: Add the complex to the mixed system and mix to obtain the product.

[0151] Comparative Example 3

[0152] On the basis of Example 3, keeping other conditions unchanged, change the preparation method of the ointment to the following steps:

[0153] Mix beeswax, Polygonum cuspidatum, Coptis chinensis, Lithospermum erythrorhizon, Sanguisorba officinalis, Phellodendron amurense, Scutellaria baicalensis, borneol and sesame oil, stir for 105 min, carry out defoaming treatment under -0.08 MPa vacuum for 45 min, and then sieve through a 200-mesh sieve to obtain the product.

[0154] 1. Skin patch test

[0155] Select 30 healthy volunteers with skin, half male and half female, aged between 20 and 50 years old. All volunteers have no history of skin diseases and no known allergies to the test materials, and have not used any drugs or cosmetics that may affect skin reactions within at least 2 weeks before the test.

[0156] Take the ointments prepared in Examples 1-5 as samples, take 2 mg of the sample and place it in a patch tester, cover the flexor side of the forearm of the subject with a low-allergenic tape, gently press with the palm to make it evenly adhere to the skin, remove the patch tester after 24 hours, observe the skin reactions at 0.5 h, 6 h, 12 h and 24 h after removal respectively, and record the results according to the skin reaction grading standard in the Cosmetics Safety and Technical Specifications.

[0157] Among them, the scoring and grading are divided into levels 0-4. Level 0 is a negative reaction, and level 4 is a very strong positive reaction, accompanied by obvious erythema, severe infiltration, edema, confluent herpes, and the reaction exceeds the test area; the test results are shown in Table 1.

[0158] Table 1 Patch test results

[0159]

[0160] As can be seen from Table 1, the ointment for treating diabetic foot and non-healing wounds prepared by the present invention has no adverse skin reactions during use.

[0161] 2. Diabetic foot mouse test

[0162] Select 57 male Sprague-Dawley rats at 8 weeks old with a weight of 180 - 200 g. Referring to the method in "Study on the Efficacy and Mechanism of Qibai Yuyang Ointment on Diabetic Rat Ulcer Wounds" by Yang Xu et al., establish a diabetic rat model. Make a 2 cm × 2 cm circular full-thickness skin wound on the left side of the midline of the rats' backs, and evenly divide them into 18 experimental groups and 1 model group. The experimental groups use the ointments prepared in Examples 1 - 15 and Comparative Examples 1 - 3 as samples. After disinfection and debridement of the model group, apply normal saline to the wound surface and wrap it with a sterile dressing; after debridement and disinfection of the experimental groups, rinse the wound surface with normal saline, apply the sample to the wound surface, and wrap it with a sterile dressing; change the dressing once a day, the test period is 14 days. Take pictures of the wound surface at 7 and 14 days after drug intervention respectively, calculate the wound surface area with ImageJ software, and calculate the wound healing rate = (initial wound surface area - wound surface area after treatment) / initial wound surface area × 100%. After taking the average value of each group, the results are recorded as shown in Table 2 below.

[0163] Table 2 Test results of wound healing rate

[0164]

[0165]

[0166] As can be seen from Table 2, the ointment prepared by the present invention for treating diabetic foot and difficult-to-heal wounds has a good therapeutic effect on the ulcers formed by diabetic foot.

[0167] 3. Scalded mouse test

[0168] Select 57 male Sprague-Dawley rats at 8 weeks old with a weight of 180 - 200 g. Adopt the electrothermal constant-temperature water bath test tube method. After depilating the backs of the rats, press them tightly against the mouth of a test tube filled with 100 °C water and let it stand for 16 s to construct a scald blister model. Use the ointments prepared in Examples 1 - 15 and Comparative Examples 1 - 3 as samples. Divide 54 model rats into 18 groups corresponding to 18 samples as experimental groups, and the remaining 3 rats without any treatment as the control group. After disinfection and debridement of the blank group, apply normal saline to the wound surface and wrap it with a sterile dressing; after debridement and disinfection of the experimental groups, rinse the wound surface with normal saline, apply the sample to the wound surface, and wrap it with a sterile dressing; change the dressing once a day, the test period is 14 days. Take pictures of the wound surface at 7 and 14 days after drug intervention respectively, calculate the wound surface area with ImageJ software, and calculate the wound healing rate = (initial wound surface area - wound surface area after treatment) / initial wound surface area × 100%. After taking the average value of each group, the results are recorded as shown in Table 3 below.

[0169] Table 3 Test results of scald wound healing rate

[0170]

[0171]

[0172] As can be seen from Table 3, the ointment for treating diabetic foot and refractory wounds prepared by the present invention has a good therapeutic effect on the wounds formed by burns.

[0173] The above are only the preferred embodiments of the present invention, and do not impose any form of limitation on the present invention. Although the present invention has been disclosed above with preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some changes or modifications to equivalent embodiments by using the disclosed technical content within the scope of the technical solution of the present invention. However, as long as it does not depart from the content of the technical solution of the present invention, any indirect modification, equivalent change and modification made to the above embodiments based on the technical essence of the present invention still fall within the scope of the technical solution of the present invention.

Claims

1. A preparation method of an ointment for treating diabetic foot and refractory wounds, characterized in that: The preparation method of the ointment comprises the following steps: Step 1: Mix beeswax, polygonum cuspidatum, and sesame oil to obtain a suspension; Step 2: Mix coptis chinensis, lithospermum erythrorhizon, and sesame oil to obtain coptis chinensis-lithospermum erythrorhizon nanoemulsion; Step 3: Mix sanguisorba officinalis, phellodendron amurense, scutellaria baicalensis, and sesame oil to obtain an enzyme activation complex; Step 4: Add borneol to the suspension, mix, and inject the coptis chinensis-lithospermum erythrorhizon nanoemulsion while mixing to obtain a mixed system; Step 5: Add the enzyme activation complex to the mixed system, mix, and then obtain the product.

2. The preparation method of an ointment for treating diabetic foot and non-healing wounds according to claim 1, wherein: The mixing in Step 1 refers to stirring at a rotation speed of 500-520 rpm for 30-40 min at 53-57 °C; the average particle size of the beeswax is 160-200 nm.

3. The preparation method of an ointment for treating diabetic foot and refractory wounds according to claim 1, wherein: The mixing in Step 2 refers to dissolving coptis chinensis, lithospermum erythrorhizon, and sesame oil uniformly at 58-62 °C, and then homogenizing at a pressure of 750-850 bar and a rotation speed of 2000-3000 rpm for 3-5 min; the average particle size of the coptis chinensis-lithospermum erythrorhizon nanoemulsion is 130-160 nm.

4. The preparation method of an ointment for treating diabetic foot and refractory wounds according to claim 1, characterized in that: The mixing in Step 3 refers to adding 0.1M HCl solution to adjust the pH to 5.3-5.7, stirring at a rotation speed of 700-900 rpm for 1-1.2 h at 58-62 °C, drying under vacuum, and then passing through a 200-mesh sieve.

5. The preparation method of an ointment for treating diabetic foot and refractory wounds according to claim 1, characterized in that: The borneol in Step 4 is obtained by mixing medicinal borneol and tween-80 according to a mass ratio of 1:2.8-3.2; the mixing refers to stirring at a low speed of 150-250 rpm at 38-42 °C and stopping when the injection of the coptis chinensis-lithospermum erythrorhizon nanoemulsion is completed; the injection refers to injecting the coptis chinensis-lithospermum erythrorhizon nanoemulsion at a rate of 0.8-1.2 mL / min using a constant flow pump.

6. The preparation method of an ointment for treating diabetic foot and refractory wounds according to claim 1, characterized in that: The mixing in Step 5 refers to stirring evenly at 500-1500 rpm, performing degassing treatment under a vacuum of -0.08 MPa for 40-50 min, and then passing through a 200-mesh sieve.

7. The preparation method of an ointment for treating diabetic foot and refractory wounds according to claim 1, characterized in that: The sesame oil is uniformly obtained by mixing sesame oil, tween-80, and span-80 according to a mass ratio of 0.25-0.35:0.08-0.12:1.4-1.6; the mass ratio of the sesame oil in Step 1, Step 2, and Step 3 is 1:0.2-0.3:0.12-0.

18.

8. The preparation method of an ointment for treating diabetic foot and refractory wounds according to claim 1, characterized in that: The polygonum cuspidatum, coptis chinensis, lithospermum erythrorhizon, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis are respectively the alcohol extracts of polygonum cuspidatum, coptis chinensis, lithospermum erythrorhizon, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis.

9. The preparation method of an ointment for treating diabetic foot and refractory wounds according to claim 8, characterized in that: The alcohol extracts of the polygonum cuspidatum, coptis chinensis, lithospermum erythrorhizon, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis are all obtained by the following steps: Step X1: Crush the raw materials of polygonum cuspidatum, coptis chinensis, lithospermum erythrorhizon, sanguisorba officinalis, phellodendron amurense, and scutellaria baicalensis respectively and pass through a 60-100-mesh sieve to obtain the powders of the corresponding raw materials; Step X2: Mix the powders of the corresponding raw materials with 65-75 wt% ethanol solution according to a ratio of 1:9.2-10.8 g / mL, set the ultrasonic temperature to 35-45 °C, the ultrasonic frequency to 30-40 kHz, the ultrasonic power to 200-400 W, perform ultrasonic extraction 3 times, with each ultrasonic time being 30-40 min. After combining the 3 extraction solutions, concentrate under reduced pressure to a relative density of 1.2-1.3 to obtain the product.

10. An ointment prepared by the preparation method of the ointment for treating diabetic foot and refractory wound according to any one of claims 1-9, characterized in that, The raw materials of the ointment, by weight, include 18-22 parts of beeswax, 10-14 parts of sesame oil, 7-9 parts of polygonum cuspidatum, 10-14 parts of coptis chinensis, 7-9 parts of lithospermum erythrorhizon, 13-17 parts of sanguisorba officinalis, 8-12 parts of phellodendron amurense, 8-12 parts of scutellaria baicalensis and 4-6 parts of borneol.

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