Pharmaceutical composition for treating diabetic foot ulcer as well as preparation method and application thereof

Abstract

The invention provides a pharmaceutical composition for treating diabetic foot ulcer as well as a preparation method and application thereof, and the pharmaceutical composition for treating diabetic foot ulcer is prepared by taking angelica sinensis, honeysuckle and scutellaria baicalensis as raw materials through pretreatment, extraction and post-treatment. The pharmaceutical composition for treating diabetic foot ulcer disclosed by the invention has a good curative effect on diabetic foot ulcer diseases; especially, an oral prescription and an external prescription are matched for use, so that the curative effect is better.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceuticals, and particularly to a pharmaceutical composition for treating diabetic foot ulcers, a preparation method thereof, and an application thereof. Background Art

[0002] Diabetic foot (DF) is one of the severe complications of diabetes. It is a peripheral arterial vascular disease of the foot caused by the co - lesions of peripheral nerves and motor nerves around the foot due to hyperglycemia. Clinically, in the early stage, symptoms such as numbness, coolness, pain, and skin chapping can be seen. As the peripheral arterial vascular lesion of diabetic foot gradually worsens, a series of severe complications such as foot skin ulcers, tendon degeneration and necrosis, and gangrene may occur in the later stage, which can seriously lead to amputation or even endanger life. The occurrence and development process of diabetic foot is relatively complex, and various damage mechanisms are mutually causal. Currently, the generally recognized pathogenesis is the damage of peripheral blood vessels and / or peripheral nerves to varying degrees and the severe infections evolved therefrom. Other pathogenesis such as oxidative stress, related pathways, gene mutations, and genetics also participate.

[0003] The effective treatment of diabetic foot is still a thorny problem at present. The wound healing of diabetic foot is a dynamic, complex, and ever - changing biological process, which is an overlap of four stages: hemostasis, inflammation, proliferation, and remodeling. Numerous cell types, extracellular components, growth factors, and cytokines are involved in these stages. Western medicine treatment is mostly comprehensive, mainly based on effectively controlling blood sugar, blood pressure, and blood lipid levels, timely improving microcirculation disorders, giving neurotrophic drugs, jointly using sufficient and sensitive antibiotics, and symptomatic treatment of infection symptoms. Other treatment methods such as dressing change, drainage, or surgery are selected according to the patient's condition. However, there are many adverse reactions, with limitations, and the overall treatment effect is not good.

[0004] Therefore, it is very necessary to develop a product that can solve the above - mentioned technical problems. Summary of the Invention

[0005] The first object of the present invention is to provide a pharmaceutical composition for treating diabetic foot ulcers; the second object is to provide a preparation method of the pharmaceutical composition for treating diabetic foot ulcers; the third object is to provide an application of the pharmaceutical composition for treating diabetic foot ulcers.

[0006] The first object of the present invention is achieved as follows: The pharmaceutical composition for treating diabetic foot ulcers is prepared from angelica, honeysuckle, and scutellaria baicalensis through pretreatment, extraction, and post - treatment.

[0007] In the pharmaceutical composition for treating diabetic foot ulcer, angelica sinensis is sweet, pungent and warm in nature, and enters the liver, heart and spleen meridians, and has the effect of nourishing blood or activating blood circulation. Modern pharmacological studies have confirmed that the polysaccharide components in angelica sinensis can promote angiogenesis, resist platelet aggregation and thus improve microcirculation. In this prescription, as the main drug, it improves the blood circulation of diabetic foot ulcers by virtue of its blood circulation activating effect, and promotes the recovery and healing of inflammation. Honeysuckle is the minister, and its sweet and cold nature enters the lung, heart and stomach meridians. Its heat-clearing and detoxifying effect is helpful for the treatment of diabetic foot ulcers, and modern pharmacological studies have shown that honeysuckle is rich in chlorogenic acid, luteolin and other ingredients, has antibacterial and anti-inflammatory effects, and is helpful for resisting diabetic foot ulcers. Scutellaria baicalensis is the adjuvant, and enters the lung and gallbladder meridians with its bitter and cold nature. "Medical Origin" records that Scutellaria baicalensis can "drain the fire evil in the lungs" and clear the dampness and heat in the lower jiao; and modern pharmacological studies have shown that baicalin can reduce tissue damage by regulating the VEGF pathway and blocking TLR4 / NF-KB inflammatory signals. Therefore, the use of Scutellaria baicalensis in the prescription is to regulate the damp-heat environment in the lower part of the body of patients with diabetic foot ulcers, so as to facilitate the anti-diabetic foot ulcer effect of Angelica sinensis and honeysuckle. In summary, the synergistic use of Angelica sinensis, honeysuckle and Scutellaria baicalensis in the above prescription reflects the characteristics of "mutual transformation of qi and blood, balance of cold and heat": Angelica sinensis replenishes blood and creates new blood, laying a material foundation; honeysuckle penetrates evil and detoxifies, and is combined with Scutellaria baicalensis to dry dampness and clear heat, and removes the superficial excess, so as to promote blood circulation and replenish blood; while Angelica sinensis is sweet and warm in nature, which can reconcile the coldness of honeysuckle and Scutellaria baicalensis to prevent qi and blood stagnation; Scutellaria baicalensis is bitter and dry, which can restrain the warmness of Angelica sinensis and prevent heat; the three form an interactive balance of "nourishing blood without promoting heat, clearing heat without hurting the body". The above-mentioned pharmaceutical composition in the present invention combines the blood-nourishing essence of Danggui Buxue Decoction with the detoxification wisdom of Xianfang Huoming Drink. It is the inheritance of traditional Chinese medicine theory, and is also in line with the multi-target effects revealed by modern pharmacology research that it has synergistic improvements in microcirculation (Danggui promotes VEGF secretion - Honeysuckle inhibits vascular proliferation - Scutellaria regulates vascular permeability), anti-fibrosis (Danggui blocks TGF-β1 - Scutellaria interrupts Smad3 pathway) and bacterial and viral treatment (Honeysuckle breaks biofilm - Scutellaria strengthens immune phagocytosis - Danggui enhances local disease resistance). It is suitable for blood deficiency and collateral heat syndromes such as diabetic ulcers. In clinical practice, the ratio of honeysuckle to Scutellaria can be adjusted according to the degree of dampness and heat. If blood stasis is severe, add earthworms, salvia miltiorrhiza and other collateral-draining herbs.

[0008] The raw materials of the oral pharmaceutical composition are composed of 20-40 parts by weight of angelica sinensis, 20-40 parts of honeysuckle, 10-20 parts of scutellaria baicalensis, 20-40 parts of astragalus, 5-15 parts of scalded leech, 10-20 parts of earthworm, 5-15 parts of peach kernel, 3-7 parts of safflower, 10-20 parts of chuanxiong, 10-20 parts of achyranthes bidentata and 15-25 parts of corydalis.

[0009] Diabetic foot ulcer belongs to the category of "gangrene" in traditional Chinese medicine. Its pathogenesis is long-term thirst, deficiency of both qi and yin as the root cause, blood stasis blocking the collaterals as the symptom, and dampness, heat and toxicity accumulation. This prescription is based on treating both the root cause and the symptom, integrating the three methods of replenishing qi and unblocking the collaterals, promoting blood circulation and removing blood stasis, and clearing away heat and removing dampness, reflecting the dialectical thinking of "replenishing qi to circulate blood, removing blood stasis to unblock the meridians, and detoxifying to protect the collaterals".

[0010] The sovereign drugs are Astragalus membranaceus and Angelica sinensis, which are used in combination. Astragalus membranaceus greatly invigorates the qi of the spleen and lungs. When qi is abundant, blood circulation is promoted. "Medical Compendium of Chinese and Western Medicine" states that it "is good at promoting urination and dredging blood vessels". Modern research has confirmed that it can improve microcirculation and promote ulcer healing. Angelica sinensis nourishes blood and harmonizes the nutrient system. When combined with Astragalus membranaceus, it follows the meaning of "Angelica Blood-Building Decoction", supplementing qi to generate blood to nourish the four limbs. These two drugs target the essence of qi and yin depletion caused by long-term consumption in diabetes mellitus. When qi is sufficient, blood circulation is powerful; when yin is restored, tendons and vessels are moistened. Together, they are the foundation for treating the root cause. The ministerial drug group consists of four herbs: Hirudo, Pheretima aspergillum, Prunus persica, and Carthamus tinctorius. Hirudo is good at breaking stasis and dredging collaterals. "Hundred Kinds of Records of Materia Medica" states that it "runs through the blood phase, reaching everywhere". Its hirudin component can inhibit platelet aggregation; Pheretima aspergillum dredges collaterals and relieves spasm, and together with Prunus persica and Carthamus tinctorius, they achieve the effect of promoting blood circulation and dredging vessels. This group of drugs targets the characteristic of "long-term disease entering the collaterals" in diabetic foot. The combination of insect drugs and plant-based blood-activating drugs, with static and dynamic combination, can not only expel deep-seated stasis but also prevent excessive blood-breaking from damaging healthy qi. Modern pharmacology has confirmed that such drugs can improve the endothelial function of lower limb blood vessels and reduce blood viscosity. Flos Lonicerae Japonicae and Scutellaria baicalensis Georgi are used as adjuvant drugs, following the meaning of clearing heat and detoxifying in Simiao Yong'an Decoction. Patients with diabetes mellitus have insufficient healthy qi, and dampness and stasis accumulated for a long time are likely to transform into heat and toxins. Flos Lonicerae Japonicae expels pathogenic factors and detoxifies without damaging the stomach qi, and Scutellaria baicalensis Georgi clears heat and dries dampness and can also strengthen yin. The two combined can clear and resolve local damp-heat toxins and prevent secondary infections. Research has found that these two drugs have an inhibitory effect on common wound pathogens such as Staphylococcus aureus and can also reduce the inflammatory response. The envoy drugs are Ligusticum chuanxiong, Achyranthes bidentata, and Corydalis yanhusuo. Ligusticum chuanxiong is a qi-regulating drug in blood, ascending to the head and descending to the blood sea. When combined with Achyranthes bidentata, it guides all the drugs downward, forming a trend of "dredging collaterals and guiding". Corydalis yanhusuo promotes qi circulation, activates blood circulation, and relieves pain, targeting the symptomatic manifestation of "pain due to obstruction". The three drugs cooperate synergistically, not only helping the sovereign and ministerial drugs to reach the disease site but also taking into account the improvement of pain symptoms. Modern research shows that tetramethylpyrazine can dilate peripheral blood vessels, and tetrahydropalmatine has a central analgesic effect. The overall compatibility of the formula reflects the characteristics of "combining supplementation and elimination, and mutual promotion of ascending and descending": the ascending and supplementing effect of Astragalus membranaceus is paired with the descending effect of Achyranthes bidentata, the moistening effect of Angelica sinensis is combined with the bitter-drying effect of Scutellaria baicalensis Georgi, and the drastic effect of Hirudo is assisted by the sweet-soothing effect of Astragalus membranaceus, forming a dynamic balance. This formula inherits the essence of Bu Yang Huan Wu Decoction in supplementing qi and dredging collaterals, integrates the essence of Simiao Yong'an Decoction in detoxifying and protecting yin, and combines the research results of modern pharmacology. It not only follows the traditional treatment principle of "benefiting qi and nourishing yin, promoting blood circulation to remove stasis, and detoxifying", but also conforms to the pathological characteristics of diabetic foot of "hypercoagulability, hyperglycemia, and high inflammation", reflecting the diagnostic and treatment characteristics of "combining disease and syndrome" in traditional Chinese medicine.

[0011] The described external pharmaceutical composition is composed of 50 - 70 parts by weight of Angelica sinensis, 90 - 110 parts by weight of Flos Lonicerae Japonicae, 50 - 70 parts by weight of Scutellaria baicalensis Georgi, 90 - 110 parts by weight of Lithospermum erythrorhizon, 50 - 70 parts by weight of Angelica dahurica, 50 - 70 parts by weight of Coptis chinensis, and 5 - 15 parts by weight of Borneol.

[0012] In the external medicine composition, Lithospermum erythrorhizon is sweet and cold, clearing heat and resolving toxicity, lubricating and promoting diuresis, salty in flavor and purple in color, entering the blood, heart and liver meridians, being good at clearing heat and detoxifying, promoting eruption and resolving macules, clearing heat and cooling blood to resolve internal heat-toxicity, promoting blood circulation and removing stasis to quickly disperse macule stasis, integrating cooling blood, promoting blood circulation, detoxifying and promoting eruption of macules. For all diseases of macules, pox and toxin, when there is blood heat and toxin abundance, dull color, or accompanied by high fever, it can be selected, especially suitable for purple-black macules. Flos Lonicerae is sweet and cold, clearing heat and discharging fire, light and spreading, clearing and dispersing, entering the lung, stomach and large intestine meridians, being good at clearing heat and detoxifying, and also good at dispersing wind-heat, with strong medicinal power but not purging severely, being a good medicine for resolving heat-toxicity, mainly clearing heat and also dispersing externally, applicable to all heat-toxicity and wind-heat. These two herbs are the monarch herbs together; Scutellaria baicalensis is bitter and cold, clearing heat and discharging fire, drying dampness, mainly entering the lung and large intestine meridians, also entering the gallbladder, spleen and stomach meridians. It can both clear heat and purge fire, cool blood and stop bleeding, clear heat and detoxify, and dry dampness and resolve damp-heat toxin. It is a key medicine for treating damp-heat fire-toxin, widely used in diseases of damp-heat fire-toxin. Coptis chinensis is extremely bitter and cold, clearing heat and discharging fire, drying dampness, descending pure yin, mainly entering the heart, stomach and spleen meridians, also entering the liver, gallbladder and large intestine meridians. It can both clear heat and purge fire, and dry dampness and resolve damp-heat toxin. It is a key medicine for treating damp-heat fire-toxin, widely used in diseases of damp-heat fire-toxin. These three herbs, with Scutellaria baicalensis and Coptis chinensis as ministerial herbs, clear and discharge damp-heat fire-toxin; Angelica sinensis is sweet and can tonify and moisten, pungent and warm in nature, dispersing and promoting circulation, mainly entering the liver and heart meridians, also entering the spleen meridian, being good at enriching blood, promoting blood circulation, dredging meridians and relieving pain, and also being able to dispel cold and astringe sores, commonly used in surgery and traumatology for detumescence and treating injuries. Angelica dahurica is pungent, dispersing, warm and drying, mainly entering the yangming stomach meridian, also entering the taiyin lung meridian, expelling wind and relieving pain, detumescing and discharging pus, being good at dispersing wind-cold, removing dampness pathogen, relieving pain, inducing sweating, and also being able to disperse masses and promote the discharge of pus. These two herbs are assistant herbs; Borneol is for clearing heat and relieving pain, detumescing and astringing sores as the guiding herb. The whole formula together exerts the effects of clearing heat and detoxifying, discharging pus and detumescence, relieving pain, removing necrosis and promoting granulation.

[0013] The second object of the present invention is achieved as follows. The preparation method of the pharmaceutical composition for treating diabetic foot ulcers includes pretreatment and extraction steps, specifically including: A. Pretreatment: Crush Angelica sinensis, Flos Lonicerae and Scutellaria baicalensis according to the formula ratio through a 10-mesh sieve and mix evenly to obtain material a; B. Extraction: Add an ethanol solution with a volume percentage concentration of 90 - 98% to material a, soak it, and then perform percolation. The percolate is concentrated under reduced pressure by recovery to obtain extract b; C. Post-treatment: Crush extract b through a sieve to obtain the target pharmaceutical composition for treating diabetic ulcers.

[0014] The specific operation is as follows: The above three flavors, namely honeysuckle flower, scutellaria root, and angelica root, are crushed into coarse powder, soaked in 95% ethanol for 24 hours, then percolated according to the percolation method, and the percolate is collected. The ethanol is recovered under reduced pressure and concentrated into an extract with a relative density of 1.10 - 1.20 (60 °C). Take the extract, propylene glycol, glycerol, ethylparaben, sodium lauryl sulfate, and purified water, heat to 80 °C to prepare the aqueous phase, and slowly add it to the oil phase prepared by heating glyceryl mono- and distearate, stearyl alcohol, cetyl alcohol, and lanolin to the same temperature. Stir in the same direction while adding, continuously stir for 1 hour under the constant temperature condition of 80 °C, then cancel the constant temperature condition. When the temperature drops to about 70 °C, add fine powder of borneol, mix well, and continuously stir until the temperature is below 30 °C to prepare 1000 g, and then divide it into packages to obtain the product.

[0015] The preparation method of the oral pharmaceutical composition described above is to crush the raw materials in the formula ratio and mix them evenly to obtain the target oral pharmaceutical composition.

[0016] The specific operation is as follows: A. If it is formula granules: Raw material preparation: Select Chinese medicinal materials that meet the pharmacopoeia standards according to the requirements of the above prescription, and carry out technological processes such as crushing, screening, and cleaning to obtain powder raw materials.

[0017] Cell wall breaking: For some Chinese herbal medicine powders, such as leech (parched) and earthworm, their cell walls may be too hard, which is not conducive to human absorption and utilization. Therefore, mechanical cell wall breaking technologies, such as ultrasonic cell wall breaking and granulator cell wall breaking, need to be adopted to effectively break the cell walls of Chinese medicine powders, thereby improving their medicinal efficacy.

[0018] Ratio preparation: According to the composition of the prescription and the requirements of pharmaceutical technology, weigh and mix the processed raw material powders evenly according to a certain ratio and quality.

[0019] Mixing: Place the prepared various powder raw materials in a mixing device, and continuously stir and mix them evenly by methods such as folding, rolling, and shaking, so that each component is fully and evenly distributed in the granules, thereby avoiding dose fluctuations and ensuring that the granules are truly stable and uniform.

[0020] Granulation: Add the evenly mixed granular raw materials to a special granulation machine, and through setting appropriate process parameters and process flows, the medicinal material powders are gradually compressed, heated, melted, cooled and other process processes to form granular substances of a certain size.

[0021] Packaging: The granulated medicinal materials enter the packaging process. Using a sealed packaging method, the granule raw materials are divided into bags according to the dosage, making it convenient for patients to take.

[0022] Quality control: During the entire preparation process, strict quality control is required to ensure that each batch of formula granules meets the standards, with definite and stable curative effects.

[0023] Dosage method: Pour each bag of medicine in one dose (the daily dose) into the same cup. First, moisten it with a small amount of warm water for 1 - 2 minutes, then dissolve it with an appropriate amount of boiling water, stir well, seal it for 2 - 3 minutes until it is fully dissolved, and take it in 3 times, one hour after meals.

[0024] B. If it is a decoction: Prepare the herbs: Weigh the required herb formula according to the prescription requirements.

[0025] Soak in cold water: Put the herbs into the decocting pot and add enough cold water to soak. The water level should be 1 - 3 cm higher than the herb surface. The soaking time is generally 20 - 30 minutes to allow the herbs to fully absorb water.

[0026] Heat and decoct: First, bring the herbs to a boil over high heat, then turn to low heat and simmer slowly.

[0027] Filter and extract: After the decocting is completed, pour the herb decoction into a clean container, and you can use gauze or filter paper to filter out the dregs.

[0028] Take in portions: Generally, decoct twice. Add about 200 - 300 ml of water for the first time, and the water added for the second time is 1 / 3 - 1 / 2 of the first time. Mix the two decocted liquid and drink it.

[0029] Storage and administration: Divide the extracted herb decoction into the required dosage, one dose per day, 150 ml each time, drink it 3 times a day, one hour after meals.

[0030] The preparation method of the external medicinal composition described above includes pretreatment, extract preparation, and post - treatment steps, specifically including: A. Pretreatment: 1) Grind the raw material borneol in the formula ratio to obtain material a; 2) Crush and mix the raw materials honeysuckle, scutellaria baicalensis, coptis chinensis, angelica dahurica, and Chinese angelica in the formula ratio to obtain material b; 3) Mix vaseline and liquid paraffin, heat and melt them to obtain a mixed solution c. Add the raw material lithospermum root with the formula ratio wetted with water at a temperature of 50-70°C into the mixed solution c and fry to obtain a lithospermum root frying solution d; 4) Add glyceryl monostearate, stearyl alcohol, cetyl alcohol and lanolin to the lithospermum root frying solution to prepare an oil phase e; B. Extract preparation: 1) Add an ethanol solution with a volume percentage concentration of 90-98% to material b, soak it, and then perform percolation. The percolate is recovered under reduced pressure and concentrated to obtain an extract f; 2) Add propylene glycol, glycerol, ethylparaben, sodium lauryl sulfate and purified water to the extract e to prepare an aqueous phase g; C. Post-treatment: Add the aqueous phase g to the oil phase e at a temperature of 70-90°C, stir constantly at a constant temperature for 50-70 min, and when the temperature is lowered to 60-80°C, add material a, stir and mix evenly to obtain the target external pharmaceutical composition.

[0031] The specific operation is as follows: For the above seven herbs, grind borneol into fine powder for later use. Separately, take honeysuckle, scutellaria baicalensis, coptis chinensis, angelica dahurica and angelica sinensis, crush them into coarse powder, use 95% ethanol as the solvent, soak for 24 hours, then perform percolation according to the percolation method, collect the percolate, recover ethanol under reduced pressure and concentrate it into an extract with a relative density of 1.10-1.20 (60°C). Mix 400 g of vaseline and 400 g of liquid paraffin, heat and melt them with a slow fire. At 60°C, add the lithospermum root wetted with water to the mixed solution and fry. Control the frying temperature at 120°C until the medicinal materials are dry, remove the residue and filter. Take the extract, propylene glycol, glycerol, ethylparaben, sodium lauryl sulfate, purified water, heat to 80°C to prepare an aqueous phase, and slowly add it to the oil phase prepared from the lithospermum root frying solution, glyceryl monostearate, stearyl alcohol, cetyl alcohol and lanolin heated to the same temperature. Stir in the same direction while adding. After continuously stirring for 1 hour under the condition of constant temperature at 80°C, cancel the constant temperature condition. When the temperature drops to about 70°C, add the fine powder of borneol, mix evenly, and continuously stir until the temperature is below 30°C, make 1000 g, and divide into packages to obtain the product. Description of the Drawings

[0032] Figure 1 It is a schematic diagram of the preparation process of the external pharmaceutical composition purple silver ointment of the present invention; Figure 2 It is a schematic diagram of the comparison of the effects of the basic formula, oral formula, external formula, and oral and external formula of the present invention on the wound healing rate of diabetic skin injury mice; Figure 3 It is a schematic diagram of the histopathological comparison of the treatment of diabetic skin injury mice by the basic formula, oral formula, external formula, and oral and external formula of the present invention. Detailed Embodiments

[0033] The following further describes the present invention in conjunction with embodiments, but does not limit the present invention in any way. Any transformation or substitution based on the teachings of the present invention falls within the protection scope of the present invention.

[0034] The pharmaceutical composition for treating diabetic foot ulcers according to the present invention is prepared from angelica sinensis, honeysuckle flower, and scutellaria baicalensis as raw materials through pretreatment, extraction, and post-treatment.

[0035] The raw materials are composed of 20 - 40 parts by weight of angelica sinensis, 20 - 40 parts by weight of honeysuckle flower, and 10 - 20 parts by weight of scutellaria baicalensis.

[0036] The preparation method of the pharmaceutical composition for treating diabetic foot ulcers according to the present invention includes pretreatment and extraction steps, specifically including: A. Pretreatment: Angelica sinensis, honeysuckle flower, and scutellaria baicalensis in the formula ratio are respectively crushed and passed through a 10-mesh sieve and then mixed evenly to obtain material a; B. Extraction: An ethanol solution with a volume percentage concentration of 90 - 98% is added to material a, soaked, and then percolated. The percolate is concentrated under reduced pressure to obtain extract b; C. Post-treatment: Extract b is crushed and screened to obtain the target pharmaceutical composition for treating diabetic ulcers.

[0037] The application of the pharmaceutical composition for treating diabetic foot ulcers according to the present invention is the application of the pharmaceutical composition for treating diabetic foot ulcers in the preparation of drugs for treating diabetic foot ulcer diseases.

[0038] The raw materials of the pharmaceutical composition for treating diabetic foot ulcers according to the present invention as the raw materials of the oral pharmaceutical composition of the basic formula are composed of 20 - 40 parts by weight of angelica sinensis, 20 - 40 parts by weight of honeysuckle flower, 10 - 20 parts by weight of scutellaria baicalensis, 20 - 40 parts by weight of astragalus membranaceus, 5 - 15 parts by weight of leech (processed), 10 - 20 parts by weight of pheretima aspergillum, 5 - 15 parts by weight of peach kernel, 3 - 7 parts by weight of safflower, 10 - 20 parts by weight of ligusticum wallichii, 10 - 20 parts by weight of achyranthes bidentata, and 15 - 25 parts by weight of Corydalis yanhusuo.

[0039] The preparation method of the oral pharmaceutical composition according to the present invention is to crush each raw material in the formula ratio and mix them evenly to obtain the target oral pharmaceutical composition.

[0040] The application of the oral pharmaceutical composition according to the present invention is the application of the oral pharmaceutical composition in the preparation of oral drugs for treating diabetic foot ulcer diseases.

[0041] The raw materials of the pharmaceutical composition for treating diabetic foot ulcers according to the present invention as the raw materials of the external pharmaceutical composition are composed of 50 - 70 parts by weight of angelica sinensis, 90 - 110 parts by weight of honeysuckle flower, 50 - 70 parts by weight of scutellaria baicalensis, 90 - 110 parts by weight of lithospermum erythrorhizon, 50 - 70 parts by weight of angelica dahurica, 50 - 70 parts by weight of coptis chinensis, and 5 - 15 parts by weight of borneol.

[0042] The preparation method of the external drug composition described in the present invention includes pretreatment, extract extraction and post-treatment steps, specifically including: A. Pretreatment: 1) Grind the raw material borneol in the formula ratio to obtain material a; 2) Crush and mix the raw materials honeysuckle, scutellaria baicalensis, coptis chinensis, dahurian angelica root and Chinese angelica in the formula ratio to obtain material b; 3) Mix vaseline and liquid paraffin and heat to melt to obtain a mixed liquid c. Add the raw material lithospermum root moistened with water at 50-70°C to the mixed liquid c and fry to obtain a lithospermum root frying liquid d; 4) Add glyceryl monostearate, stearyl alcohol, cetyl alcohol and lanolin to the lithospermum root frying liquid to prepare an oil phase e; B. Extract extraction: 1) Add an ethanol solution with a volume percentage concentration of 90-98% to material b, soak it and then perform percolation. The percolate is concentrated under reduced pressure by recovery to obtain an extract f; 2) Add propylene glycol, glycerin, ethylparaben, sodium lauryl sulfate and purified water to the extract e to prepare an aqueous phase g; C. Post-treatment: Add the aqueous phase g to the oil phase e at 70-90°C, stir constantly at a constant temperature for 50-70 min, and when the temperature drops to 60-80°C, add material a and stir and mix evenly to obtain the target external drug composition.

[0043] The application of the external drug composition described in the present invention is the application of the external drug composition in the preparation of an external drug for treating diabetic foot ulcers.

[0044] The following further illustrates the present invention with specific examples: Example 1

[0045] Weigh 200 g of Chinese angelica, 200 g of honeysuckle and 100 g of scutellaria baicalensis, crush them respectively through a 10-mesh sieve and mix evenly to obtain material a; add an ethanol solution with a volume percentage concentration of 90% to material a, soak it and then perform percolation. The percolate is concentrated under reduced pressure by recovery to obtain an extract b; crush and sieve the extract b to obtain the basic formula of the drug composition for treating diabetic ulcers as the target.

[0046] Example 2

[0047] Weigh 400 g of Chinese angelica, 400 g of honeysuckle and 200 g of scutellaria baicalensis, crush them respectively through a 10-mesh sieve and mix evenly to obtain material a; add an ethanol solution with a volume percentage concentration of 98% to material a, soak it and then perform percolation. The percolate is concentrated under reduced pressure by recovery to obtain an extract b; crush and sieve the extract b to obtain the basic formula of the drug composition for treating diabetic ulcers as the target.

[0048] Example 3

[0049] Weigh 300 g of Angelica sinensis, 300 g of honeysuckle and 150 g of Scutellaria baicalensis, crush them respectively through a 10-mesh sieve, and mix them evenly to obtain material a; add an ethanol solution with a volume percentage concentration of 95% to material a, soak it, and then perform percolation. The percolate is concentrated under reduced pressure to obtain extract b; crush extract b through a sieve to obtain the basic formula of the drug composition for treating diabetic ulcers, the target product.

[0050] Example 4

[0051] Weigh 200 g of Angelica sinensis, 200 g of honeysuckle, 100 g of Scutellaria baicalensis, 200 g of Astragalus membranaceus, 50 g of leech (processed with hot water), 100 g of Pheretima aspergillum, 50 g of Prunus persica, 30 g of Carthamus tinctorius, 100 g of Ligusticum chuanxiong, 100 g of Achyranthes bidentata and 150 g of Corydalis yanhusuo, crush them respectively through a 100-mesh sieve, and mix them evenly to obtain the oral formula, the target product.

[0052] Example 5

[0053] Weigh 400 g of Angelica sinensis, 400 g of honeysuckle, 200 g of Scutellaria baicalensis, 400 g of Astragalus membranaceus, 150 g of leech (processed with hot water), 200 g of Pheretima aspergillum, 150 g of Prunus persica, 70 g of Carthamus tinctorius, 200 g of Ligusticum chuanxiong, 200 g of Achyranthes bidentata and 250 g of Corydalis yanhusuo, crush them respectively through a 100-mesh sieve, and mix them evenly to obtain the oral formula, the target product.

[0054] Example 6

[0055] Weigh 300 g of Angelica sinensis, 300 g of honeysuckle, 150 g of Scutellaria baicalensis, 300 g of Astragalus membranaceus, 100 g of leech (processed with hot water), 150 g of Pheretima aspergillum, 100 g of Prunus persica, 50 g of Carthamus tinctorius, 150 g of Ligusticum chuanxiong, 150 g of Achyranthes bidentata and 200 g of Corydalis yanhusuo, crush them respectively through a 100-mesh sieve, and mix them evenly to obtain the oral formula, the target product.

[0056] Example 7

[0057] Prescription: Frying liquid of Lithospermum erythrorhizon: 550 g Alcohol extract: 50 g Borneol: 10 g Glycerol monostearate: 80 g Stearyl alcohol: 20 g Cetyl alcohol: 20 g Lanolin: 20 g Propylene glycol: 25 g Glycerol: 25 g Ethylparaben: 1 g Sodium lauryl sulfate: 10 g Purified water: 189 g.

[0058] Preparation method: Preparation of the oil phase: Take the fried Lithospermum erythrorhizon liquid, lanolin, stearyl alcohol, cetyl alcohol and glyceryl monostearate, place them in a water bath and heat to 80°C until melted, keep warm for standby; Preparation of the water phase: Take ethylparaben and add it to purified water, heat to dissolve, add glycerol and propylene glycol, mix well, then add the remaining purified water and sodium lauryl sulfate, stir evenly, heat to 80°C, keep warm for standby.

[0059] Preparation of fine borneol powder: Take borneol and crush it into fine powder for standby.

[0060] Preparation of the cream: Slowly add the water phase to the oil phase while stirring. After adding all the water phase and stirring evenly, slowly add the heated ethanol extract while stirring, stir evenly, and finally add the fine borneol powder and stir evenly to obtain the target external preparation.

[0061] Example 8

[0062] Prescription: Fried Lithospermum erythrorhizon liquid: 500 g Ethanol extract: 55 g Borneol: 10 g Glyceryl monostearate: 80 g Stearyl alcohol: 20 g Cetyl alcohol: 20 g Lanolin 20 g Propylene glycol 25 g Glycerol 25 g Ethylparaben 1 g Sodium lauryl sulfate 10 g Purified water 234 g.

[0063] Preparation method: Preparation of the oil phase: Take the fried Lithospermum erythrorhizon liquid, lanolin, stearyl alcohol, cetyl alcohol and glyceryl monostearate, place them in a water bath and heat to 80°C until melted, keep warm for standby; Preparation of the water phase: Take ethylparaben and add it to purified water, heat to dissolve, add glycerol and propylene glycol, mix well, then add the remaining purified water and sodium lauryl sulfate, stir evenly, heat to 80°C, keep warm for standby.

[0064] Preparation of fine borneol powder: Take borneol and crush it into fine powder for standby.

[0065] Preparation of the cream: Slowly add the water phase to the oil phase while stirring. After adding all the water phase and stirring evenly, slowly add the heated ethanol extract while stirring, stir evenly, and finally add the fine borneol powder and stir evenly to obtain the target external preparation.

[0066] Example 9

[0067] Prescription: Fried Lithospermum erythrorhizon liquid: 600 g Alcohol extract: 55 g Borneol: 10 g Glycerol monostearate: 80 g Stearyl alcohol: 20 g Cetyl alcohol: 20 g Lanolin 20 g Propylene glycol 25 g Glycerol 25 g Ethylparaben 1 g Sodium lauryl sulfate 10 g Purified water 134 g.

[0068] Preparation method: Prepare the oil phase: Take the Lithospermum erythrorhizon frying solution, lanolin, stearyl alcohol, cetyl alcohol and glycerol monostearate, place them on a water bath and heat to 80°C until melted, and keep warm for later use; Prepare the water phase: Separately take ethylparaben and add it to purified water, heat to dissolve, add glycerol and propylene glycol, mix well, then add the remaining purified water and sodium lauryl sulfate, stir evenly, heat to 80°C, and keep warm for later use.

[0069] Prepare the fine powder of borneol: Crush borneol into fine powder for later use.

[0070] Prepare the cream: Slowly add the water phase to the oil phase while stirring. After adding all the water phase and stirring evenly, slowly add the heated alcohol extract, stir evenly, and finally add the fine powder of borneol and stir evenly to obtain the target external preparation.

[0071] Example 10

[0072] Use the basic formula, oral formula and external formula prepared in Example 3, Example 6 and Example 9 respectively for testing. The tests are as follows: (1)Maximum oral gavage dose test in mice 1.1 Test method From preliminary tests, it was found that for ICR mice, when gavaged with the maximum volume, the L-day could not be measured for the basic formula extract, external formula extract and oral formula. 50, so the acute toxicity reaction was investigated by the maximum dose test of single gavage. During the test, after 2 days of adaptive feeding of the animals, 40 mice weighing 18 - 21 g after 8 hours of fasting but with free access to water were selected, with 20 males and 20 females. They were randomly divided into a normal saline control group, a basic formula extract group, an external application formula extract group, and an oral formula group according to gender and weight, with 5 males and 5 females in each group. Each group of animals was gavaged with normal saline, basic formula extract, external application formula extract, and oral formula at a volume of 40 mL / kg, and the acute toxicity reaction of each group of animals after administration was observed. The main toxicity observation endpoints included: death / imminent death observation, clinical observation, and body weight. All surviving animals were dissected at the end of the observation period (15 days), and the volume, color, texture, etc. of each tissue and organ were macroscopically examined for abnormalities. If any abnormalities were found, tissue samples should be taken immediately for histopathological examination.

[0073] 1.2 Test Results The mice were given a single gavage of the basic formula extract, external application formula extract, and oral formula at the maximum volume of 40 mL / kg. The activity of each group of animals increased significantly 20 minutes after administration. After 1 - 1.5 hours, drug-like feces began to be excreted, suspected of diarrhea. After about 3 hours, there was no significant difference in activity compared with the control group. No deaths were observed in each group the next day. During the continuous 14-day observation period, the body weights of the mice in each group continued to increase. Except that the body weight gains of male animals in the basic formula extract group, external application formula extract group, and oral formula group were significantly lower than those of the control group on the 1st and 3rd days after administration, the body weight gains of the other groups at each time point were not significantly different from those of the control group, as shown in Table 1.

[0074] Table 1 Body Weight Changes in the Maximum Tolerated Dose Test by Gavage in Mice

[0075] 2.3 Conclusions The minimum lethal dose of the basic formula extract, external application formula extract, and oral formula by oral gavage in mice was 40 mL / kg; the maximum tolerated dose of the basic formula extract, external application formula extract, and oral formula by oral gavage was 40 mL / kg.

[0076] (2) Repair Effect on Skin Ulcers in Diabetic Mice 2.1 Animal Modeling and Grouping One hundred SPF-grade male ICR mice, 7 - 8 weeks old and weighing 28 - 32 g, were selected. After 3 days of adaptive feeding, 8 mice were randomly selected as the normal control group. The remaining animals were fasted for 16 h, and then an STZ solution prepared with sterile citric acid - sodium citrate buffer at 0.1 mol / L and pH 4.5 was injected within 30 minutes after preparation. It was injected twice via the tail vein at a dose of 60, 60 mg / kg (with an interval of 3 days), and the injection volume was 10 mL / kg each time. Five days after modeling, the fasting blood glucose of the mice was measured with a blood glucose test strip. Mice with a blood glucose value > 11.1 mmol / L and showing symptoms of polydipsia, polyphagia, and polyuria were considered to have successful modeling. A total of 65 diabetic mice were obtained in this experiment, and the modeling success rate was 70.65%. After anesthetizing the diabetic mice with isoflurane, the hair on the back was shaved with a clipper in the midline, with an area of approximately 2.5 * 2.5 cm 2 ; After routinely disinfecting the shaved area, a circle with a diameter of 1.0 cm was drawn in the midline of the back of each mouse under sterile conditions, and the whole layer of skin was cut along the line with ophthalmic scissors to the subcutaneous fascia layer to form a skin wound with a roughly equivalent area, and those in poor condition were excluded. The diabetic mice with skin injuries were randomly divided into 6 groups according to blood glucose value, body weight, and surgical injury conditions: model control group, basic formula (oral), basic formula (topical), oral formula, topical formula, oral and topical, with 8 mice in each group. After the operation, the mice were housed in cages according to the groups, with no more than 6 mice in each cage, and they were allowed to eat and drink freely. The bedding was changed frequently and the cages were cleaned to keep the cages clean and the bedding dry.

[0077] 2.2 Administration and Observation On the day after the operation, the three groups of basic formula (oral), oral formula, and oral and topical were given the corresponding preparations orally at 20 mL / kg respectively. The groups of Zicao Ointment, basic formula (topical), topical formula, and oral and topical were evenly applied with about 0.2 g of the corresponding ointment on the wound surface once a day for 14 consecutive days; the normal and model control groups were not given oral medications and the wound surfaces were not dressed. On the 3rd, 7th, 10th, and 15th days after administration, the transverse and longitudinal diameters of the wound surfaces of each mouse were measured, the body weight was weighed, and blood was collected from the tail to measure the fasting blood glucose values at 0, 3, 6, 9, and 14 days after administration. The wound surface area and wound healing rate of the skin injury of the mice were calculated according to the following formulae.

[0078] Wound surface area = 3.14 × [(transverse diameter + longitudinal diameter) / 4] 2 Wound healing rate = (original wound surface area - unhealed wound surface area) ÷ original wound surface area × 100 % 2.3 Sampling and Determination After the last measurement of the wound diameter and body weight, the mice were sacrificed by cervical dislocation. Part of the skin tissue was taken from the right side of the skin of each mouse, fixed in 10% neutral formalin solution, embedded, sectioned, stained, and the histopathological conditions at different magnifications were observed in detail under a light microscope. The congestion, stasis, hemorrhage, edema, degeneration, necrosis, hyperplasia, fibrosis, organization, granulation tissue, inflammatory changes, etc. were described in words, and the typical lesion sites were imaged and marked with arrows. The pathological evaluation criteria are as follows: Table 2 Histopathological evaluation criteria Note: Based on this standard, if there are pathological changes not mentioned in other standards, they will be added to the table and judged according to the level of lesion severity.

[0079] 2.4 Test results 2.4.1 General observation Before modeling, the general conditions of the mice in the normal group and the group to be modeled were good, and there were no significant differences in body weight and blood glucose levels (P > 0.05). After diabetes modeling (before skin injury modeling), the hair of the mice in the model group was messy and their movements were slow. Compared with the normal control, the blood glucose value increased significantly (P < 0.01), and the body weight decreased significantly (P < 0.01) (Table 1); after grouping after wound modeling, there were no significant differences in body weight and blood glucose levels among the model animals (P > 0.05) (Table 3).

[0080] During the drug administration period, there were no obvious changes in the general conditions of the mice in the normal skin injury group. The body weight increased over time, and there was no significant difference in the blood glucose value compared with that before drug administration (P > 0.05); compared with the normal control group, the body weight of the mice in the diabetic skin injury model group continued to decrease, the blood glucose value continued to increase, and there were symptoms such as polyuria, polydipsia, and polyphagia, indicating that the diabetes model was stable during the experiment; compared with the diabetic skin injury model group, except for the model control, the dampness of the bedding of the mice in each drug administration group was reduced to some extent, the body weight loss had a certain slowing trend, and the blood glucose value was stable, but there was only a decreasing trend compared with the model control group without statistical significance (P > 0.05), suggesting that after the external treatment with each test substance, the general conditions of the diabetic skin injury mice had a certain improvement trend. The results are shown in Tables 3 and 4.

[0081] Table 3 Effects on the body weight of diabetic skin injury mice ( ± S days, g)

[0082] Table 4 Effects on the blood glucose value of diabetic skin injury mice ( ± S days ， mmol / L)

[0083] 2.4.2 Wound healing Before drug administration, the skin injury areas of mice in the normal group and the diabetic model groups were roughly equivalent. During the drug administration period, the wounds of mice in the normal control group gradually shrank and were almost completely healed after 14 days. Compared with the normal control group, the wounds in the model group were red and swollen and had obvious inflammatory exudation 2 days after modeling. The redness and swelling of the wounds subsided 7 days after modeling, and the edges dried and shrank slowly. It was not completely healed until 15 days. The wound healing rates at 7, 10, and 15 days after drug administration were significantly lower than those in the normal control group (P < 0.01). Compared with the model group, the wound healing rates of mice in each drug administration group at 7, 10, and 15 days after modeling were significantly increased (P < 0.05 / 0.01), indicating that each drug administration group can significantly promote wound healing in diabetic mice. Among them, the efficacy of the oral formula group was equivalent to that of the external formula group, and the efficacy of the oral and external group was slightly better than that of the oral formula group at 10 and 15 days after drug administration, but there was no statistical difference between the two groups. Results are shown in Figure 2 and Table 5.

[0084] Table 5 Effects on wound healing rate of diabetic skin injury mice ( ± S days, %)

[0085] 2.4.3 Histopathology The results of H&E staining reflected the regeneration of the epidermis and dermis. After the 15th day of treatment, the sections of the wounds in each group showed obvious new epidermis and dermis, with some skin appendages, and the dermis in each group was relatively dense. The epidermis of the wound skin tissue of the mice in the normal control group was intact, and the structures of each layer were clear; the connective tissue of the dermis was neatly arranged; the subcutaneous tissue was located below the dermis, composed of loose connective tissue and adipose tissue, the muscle fibers of the muscular layer were tightly arranged, the hair follicles of the skin appendages and sebaceous glands were scattered, and no obvious inflammatory cell infiltration was observed. However, wounds that did not recover normally were still observed in the model group. Small-scale squamous epithelial hyperplasia, mild thickening of the spinous layer, granulation tissue, a large number of fibroblasts, fibroblasts and collagen fibers were staggered in the dermis, the number of hair follicles and sebaceous glands of the skin appendages decreased, new hair follicles were occasionally seen, mild bleeding, a small number of new blood vessels appeared, and no obvious nerve structures were observed; the inflammatory reaction was severe, and a large number of inflammatory cell infiltrations, mainly granulocytes and lymphocytes, could be seen. The wound recovery of the treatment group was almost close to natural tissue. The epidermis of the regenerated area was even and flat, and the thickness and structure of the dermis were similar to those of normal skin tissue. Some skin appendages appeared, including hair follicles and blood vessels, with a large number of fibroblasts and new capillaries, and the infiltration of inflammatory cells was significantly reduced. Figure 3 .

[0086] (3) No allergenicity to guinea pig skin 3.1 Method Thirty SPF - level Hartley guinea pigs were selected, with an equal number of males and females. The body weight of males ranged from 336.3 g to 398.5 g, and that of females ranged from 322.6 g to 368.1 g. They were randomly divided into 5 groups according to gender and body weight, with 3 animals of each gender in each group. The experiment was divided into two stages: the first stage was the sensitization period, and the second stage was the challenge period. Groups 1 - 5 were the positive drug group (1 - chloro - 2,4 - dinitrobenzene), negative control group (0.9% sodium chloride injection), basic formula group, oral formula group, and topical formula group respectively. Each group of drugs was administered by percutaneous application, and the dosage was 0.5 mL / depilated area or 0.5 g / depilated area. The body weight of each animal in each group was measured and recorded before animal grouping, on the day of initial sensitization (before sensitization), on the day of the last sensitization (before sensitization), and on the day of challenge (before challenge). After challenge (after washing the drug), the allergic reaction symptoms of each animal were observed in detail at 0 hour, 24 hours, 48 hours, and 72 hours according to the symptoms listed in the experimental protocol, and the appearance and disappearance times of the symptoms were recorded. The systemic sensitization of the animals was evaluated and scored according to the observed results (refer to Tables 6 and 7), and the incidence of allergic reactions was calculated.

[0087] Table 6 Scoring criteria for the degree of skin allergic reactions

[0088] Table 7 Evaluation criteria for skin sensitization

[0089] 3.2 Results All experimental animals survived until the end of the experiment, and the body weights of the animals increased within the normal range during the experiment. After challenge, all animals in the positive control group showed allergic reactions such as erythema and edema, while no obvious abnormalities were observed in the other groups. The sensitization incidence rate of the positive control group was 6 / 6 = 100%, which was extremely sensitizing. The sensitization incidence rate of the other groups was 0, indicating no sensitization. Therefore, under the conditions of this experiment, the test articles (basic formula, oral formula, and topical formula) did not cause active cutaneous anaphylaxis in guinea pigs. See Table 8.

[0090] Table 8 Scoring of guinea pig skin allergy test

[0091] (4) Non - irritating to rabbit skin 4.1 Method Sixteen New Zealand rabbits, ordinary grade, half male and half female. The body weights of male animals were measured to be 2.74 - 3.12 kg, and those of female animals were 2.56 - 3.12 kg. They were grouped into four groups, namely vehicle (blank sample of external formulation matrix), basic formula, oral formula, and external formula, with 4 rabbits in each group, half male and half female, through a simple randomization assignment step according to their gender and body weight. One day before the first administration of the test animals, the hair on the right side of the back spine, 4 cm × 4 cm, was removed, and a 3 cm × 3 cm drug administration area was marked. After checking that the skin was intact, 0.5 g of the test substance was applied to the 3 cm × 3 cm skin area, and after 1 - 2 minutes, it was fixed with cellophane and non-irritating adhesive tape for 4 hours, and then the residue was washed off. For multiple administrations, it was at the same position, for a fixed time, and the hair was removed according to hair growth. Once a day for 28 consecutive days, and observed until 72 hours after the last administration. During the test process, all the administered animals were observed clinically in detail 1 - 2 times a day. The observation contents included: drug administration site, skin, hair, eyes, ears, nose, mouth, chest, abdomen, external genitalia, limbs, respiratory and circulatory systems, autonomic effects (such as salivation), and nervous system (such as tremors, convulsions, stress responses, and abnormal behaviors). The skin reactions at the application site were observed 1 h after each washing to remove the drug, before each administration, and at 30 - 60 min, 24 h, 48 h, and 72 h after the last removal of the drug on the 28th day, and the skin irritation reaction scores were made according to Table 9.

[0092] Table 9 Skin Irritation Reaction Scores

[0093] 4.2 Results Calculate the integral value of each animal per day during the observation period, and calculate the average integral value of each group. The irritation intensity was evaluated according to Table 10 based on the average integral value of each group.

[0094] All the experimental animals survived until the end of the experiment. Mild erythema was observed in both male and female animals in the test article groups during the drug administration period. As the drug administration time prolonged, it could recover at the end of the recovery period (see Table 11 for details). In addition, mild erythema was also observed in the vehicle group. It was considered that the irritating symptoms in male and female animals in the test article groups might be related to the irritation caused by experimental operations and / or their own activities. Under the conditions of this test, continuous contact of the drug administration site (skin) of New Zealand rabbits with each test article for 28 days did not cause local skin irritation reactions in rabbits.

[0095] Table 10 Skin Irritation Intensity Evaluation Criteria

[0096] Table 11 Average Scores and Skin Irritation Intensities in the Skin Irritation Test of Rabbits ( ± SD , n = 4)

[0097] Example 11

[0098] The basic formula, oral formula and external formula prepared in Example 1, Example 2, Example 4, Example 5, Example 7, and Example 8 were used for tests respectively. The method was the same as that in Example 10. The results all showed that the basic formula, oral formula and external formula of the present invention all had good curative effects on diabetic foot ulcer diseases; especially, the combined use of the oral formula and the external formula had better curative effects.

Claims

1. A pharmaceutical composition for treating diabetic foot ulcers, characterized in that, The described pharmaceutical composition for treating diabetic foot ulcers is prepared from Angelica sinensis, Lonicera japonica, and Scutellaria baicalensis through pretreatment, extraction, and post-treatment.

2. The pharmaceutical composition for treating diabetic foot ulcers according to claim 1, wherein, The raw materials consist of 20 - 40 parts by weight of Angelica sinensis, 20 - 40 parts by weight of Lonicera japonica, and 10 - 20 parts by weight of Scutellaria baicalensis.

3. A method for preparing the pharmaceutical composition for treating diabetic foot ulcers according to claim 1 or 2, characterized in that, It includes pretreatment and extraction steps, specifically including: A. Pretreatment: Crush Angelica sinensis, Lonicera japonica, and Scutellaria baicalensis according to the formula ratio through a 10-mesh sieve and mix them evenly to obtain material a; B. Extraction: Add an ethanol solution with a volume percentage concentration of 90 - 98% to material a, soak it, and then perform percolation. The percolate is concentrated under reduced pressure to obtain extract b; C. Post-treatment: Crush extract b through a sieve to obtain the target pharmaceutical composition for treating diabetic ulcers.

4. Use of the pharmaceutical composition for treating diabetic foot ulcers according to claim 1 or 2, characterized in that, The application of the described pharmaceutical composition for treating diabetic foot ulcers in the preparation of drugs for treating diabetic foot ulcer diseases.

5. An oral pharmaceutical composition based on the raw materials of the pharmaceutical composition for treating diabetic foot ulcers described in claim 1 or 2, characterized in that, The raw materials of the described oral pharmaceutical composition consist of 20 - 40 parts by weight of Angelica sinensis, 20 - 40 parts by weight of Lonicera japonica, 10 - 20 parts by weight of Scutellaria baicalensis, 20 - 40 parts by weight of Astragalus membranaceus, 5 - 15 parts by weight of Hirudo nipponia (parched), 10 - 20 parts by weight of Pheretima aspergillum, 5 - 15 parts by weight of Prunus persica, 3 - 7 parts by weight of Carthamus tinctorius, 10 - 20 parts by weight of Ligusticum chuanxiong, 10 - 20 parts by weight of Achyranthes bidentata, and 15 - 25 parts by weight of Corydalis yanhusuo.

6. A method for preparing the oral pharmaceutical composition according to claim 5, characterized in that, It is to crush each raw material drug according to the formula ratio and mix them evenly to obtain the target oral pharmaceutical composition.

7. Use of the oral pharmaceutical composition according to claim 5, characterized in that, The application of the described oral pharmaceutical composition in the preparation of oral drugs for treating diabetic foot ulcer diseases.

8. An external pharmaceutical composition based on the raw materials of the pharmaceutical composition for treating diabetic foot ulcers described in claim 1 or 2, characterized in that, The described external-use pharmaceutical composition consists of 50 - 70 parts by weight of Angelica sinensis, 90 - 110 parts by weight of Lonicera japonica, 50 - 70 parts by weight of Scutellaria baicalensis, 90 - 110 parts by weight of Lithospermum erythrorhizon, 50 - 70 parts by weight of Angelica dahurica, 50 - 70 parts by weight of Coptis chinensis, and 5 - 15 parts by weight of Borneol.

9. A method for preparing the external pharmaceutical composition according to claim 8, characterized in that, It includes pretreatment, extract extraction, and post-treatment steps, specifically including: A. Pretreatment: 1) Grind the raw material Borneol according to the formula ratio to obtain material a; 2) Crush and mix evenly the raw materials Lonicera japonica, Scutellaria baicalensis, Coptis chinensis, Angelica dahurica, and Angelica sinensis according to the formula ratio to obtain material b; 3) Mix Vaseline and liquid paraffin and heat them to melt to obtain a mixed liquid c. Add the raw material Lithospermum erythrorhizon moistened with water at a temperature of 50 - 70°C to the mixed liquid c and fry it to obtain a Lithospermum erythrorhizon frying liquid d; 4) Add glyceryl monostearate, stearyl alcohol, cetyl alcohol, and lanolin to the Lithospermum erythrorhizon frying liquid to prepare an oil phase e; B. Extract extraction: 1) Add an ethanol solution with a volume percentage concentration of 90 - 98% to material b, soak it, and then perform percolation. The percolate is concentrated under reduced pressure to obtain extract f; 2) Add propylene glycol, glycerol, ethylparaben, sodium lauryl sulfate, and purified water to extract e to prepare an aqueous phase g; C. Post-treatment: Add the aqueous phase g to the oil phase e at a temperature of 70 - 90°C, stir at a constant temperature for 50 - 70 min, cool to 60 - 80°C, and then add material a and stir evenly to obtain the target external-use pharmaceutical composition.

10. Use of the external pharmaceutical composition according to claim 9, characterized in that, The application of the described external-use pharmaceutical composition in the preparation of external drugs for treating diabetic foot ulcer diseases.

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