A preparation for treating or preventing diabetic foot and a method for preparing the same

Abstract

The application belongs to the field of traditional Chinese medicines, and provides a preparation for treating or preventing diabetic foot and a preparation method thereof. The preparation contains Rhizoma polygonati, Caulis Spatholobi, Radix Angelicae Pubescentis, Notopterygium, Lumbricus, Hirudo, Asarum, Schizonepeta, Saposhnikovia divaricata, Carthamus tinctorius L., Cortex Moutan, Curcuma, Astragalus, and Kadsura. The traditional Chinese medicine composition promotes angiogenesis of diabetic foot, reduces blood viscosity, and promotes healing of ulcer wounds. The traditional Chinese medicine composition has a good therapeutic effect on treating diabetic foot. The traditional Chinese medicine composition has a simple preparation process, small side effects, and low recurrence rate.

Description

Technical Field

[0001] This invention relates to the use of traditional Chinese medicine compositions in the preparation of drugs for the prevention and treatment of diabetic foot, and belongs to the field of traditional Chinese medicine. Background Technology

[0002] Diabetic foot is a disease characterized by foot abnormalities, ulcers, infections, and gangrene caused by peripheral neuropathy and peripheral vascular disease. It is a serious and common complication of diabetes. Symptoms of diabetic foot include foot neuropathy, foot vascular disease, deep tissue destruction, weakened tissue repair capacity, soft tissue deformities of the foot, destruction of the musculoskeletal system, high pressure on the plantar surface of the foot, joint disease, poor blood supply, foot ulcers, ischemia, infection, gangrene, and tissue inflammation.

[0003] Diabetic foot has a poor prognosis, often leading to amputation and severely impacting patients' quality of life. Modern medicine currently treats diabetic foot primarily through medication and surgery. Medication includes basic symptomatic treatments such as lowering blood sugar, lowering lipids, lowering blood pressure, improving microcirculation, fighting infection, and nourishing nerves. Surgical treatments include wound debridement and healing-promoting procedures, interventional procedures on the affected limb, and amputation.

[0004] Traditional Chinese medicine believes that the basic pathological nature of diabetic foot is deficiency in the root and excess in the branch. It is caused by long-term thirst, internal blood stasis and obstruction of the collaterals, resulting in poor circulation of qi, blood, yin and yang, and the appearance of qi stagnation, phlegm dampness, damp heat, cold dampness, etc. These pathological changes further lead to difficulty in the mutual penetration of body fluids and blood, bone dryness and marrow depletion, eventually resulting in "gangrene".

[0005] To better treat diabetic foot, it is extremely important to develop and research a combination of traditional Chinese medicines prepared from natural herbs that has few toxic side effects, good safety, and significant efficacy. Summary of the Invention

[0006] This invention discloses the application of a composition in the preparation of a drug for treating / preventing diabetic foot. The traditional Chinese medicine composition of this invention has a simple preparation process, few side effects, and a low recurrence rate, and exhibits good therapeutic effects for diabetic foot.

[0007] Specifically, the technical objective of this invention is achieved through the following technical solutions:

[0008] The purpose of this invention is to provide a traditional Chinese medicine composition for treating diabetic foot, the composition being made from Dioscorea hypoglauca, Spatholobus suberectus, Angelica pubescens, Notopterygium incisum, Pheretima aspergillum, Hirudo medicinalis, Asarum heterotropoides, Schizonepeta tenuifolia, Saposhnikovia divaricata, Carthamus tinctorius, Paeonia suffruticosa, Curcuma longa, Astragalus membranaceus, and Piper kadsura.

[0009] Specifically, the traditional Chinese medicine composition comprises the following raw materials in parts by weight:

[0010] Dioscorea hypoglauca 30-70 parts, Spatholobus suberectus 55-90 parts, Angelica pubescens 15-25 parts, Notopterygium incisum 15-25 parts, Pheretima aspergillum 3-8 parts, Hirudo medicinalis 3-8 parts, Asarum heterotropoides 3-8 parts, Schizonepeta tenuifolia 12-25 parts, Saposhnikovia divaricata 12-25 parts, Carthamus tinctorius 15-30 parts, Paeonia suffruticosa 10-20 parts, Curcuma longa 10-20 parts, Astragalus membranaceus 10-30 parts, Piper kadsura 4-11 parts.

[0011] In some embodiments, the traditional Chinese medicine composition comprises the following raw materials in parts by weight:

[0012] Dioscorea hypoglauca 40-60 parts, Spatholobus suberectus 65-80 parts, Angelica pubescens 18-23 parts, Notopterygium incisum 18-23 parts, Pheretima aspergillum 4-6 parts, Hirudo medicinalis 4-6 parts, Asarum heterotropoides 4-6 parts, Schizonepeta tenuifolia 15-22 parts, Saposhnikovia divaricata 15-22 parts, Carthamus tinctorius 20-25 parts, Paeonia suffruticosa 12-18 parts, Curcuma longa 12-18 parts, Astragalus membranaceus 15-25 parts, Piper kadsura 6-9 parts.

[0013] In one embodiment, the traditional Chinese medicine composition comprises the following raw materials in parts by weight:

[0014] 50 parts of Dioscorea hypoglauca, 75 parts of Spatholobus suberectus, 21 parts of Angelica pubescens, 21 parts of Notopterygium incisum, 5 parts of Pheretima aspergillum, 5 parts of Hirudo medicinalis, 5 parts of Asarum heterotropoides, 18 parts of Schizonepeta tenuifolia, 18 parts of Saposhnikovia divaricata, 22 parts of Carthamus tinctorius, 14 parts of Paeonia suffruticosa, 14 parts of Curcuma longa, 20 parts of Astragalus membranaceus, and 7 parts of Piper kadsura.

[0015] Furthermore, the symptoms of diabetic foot described in this invention include one or more of the following: foot neuropathy, foot vascular disease, deep tissue damage, weak tissue repair capacity, foot soft tissue deformity, musculoskeletal system damage, plantar hypertension, joint disease, poor blood supply, foot ulcer, ischemia, infection, gangrene, and tissue inflammation.

[0016] More preferably, the symptoms of diabetic foot include one or more of poor blood supply and foot ulcers.

[0017] Preferably, the traditional Chinese medicine composition of the present invention promotes angiogenesis in the tissue of diabetic foot ulcers, reduces blood viscosity, and promotes ulcer healing.

[0018] The present invention also provides a formulation of the above-mentioned traditional Chinese medicine composition, wherein the traditional Chinese medicine composition is prepared into an oral formulation or a topical formulation.

[0019] Preferably, the traditional Chinese medicine composition is an oral preparation.

[0020] Preferably, the oral preparation is a decoction, pill, gel, tablet, mixture, capsule, granule, powder, or ointment, and more preferably a tablet.

[0021] Furthermore, the present invention also provides a method for preparing the aforementioned traditional Chinese medicine composition:

[0022] A. Take earthworms and leeches, and crush them to a particle size of less than 100μm;

[0023] B. Dioscorea hypoglauca, Spatholobus suberectus, Asarum heterotropoides, Angelica pubescens, and Notopterygium incisum are extracted with 65-85% ethanol 1-2 times, each extraction lasting 1.5-3.5 hours. The mixture is then filtered, and the ethanol is recovered from the filtrate. The extract is then concentrated under reduced pressure to a relative density of 1.05-1.10.

[0024] C. Extract the volatile oil from peony bark, sea pine, turmeric, astragalus, schizonepeta, saposhnikovia, and safflower with water. Add half the prescription amount of earthworm and leech to the remaining liquid and dregs, decoct 1-2 times, each time for 1.5-3.5 hours, filter, recover ethanol from the filtrate, and concentrate to an extract with a relative density of 1.15-1.20 for later use.

[0025] D. Mix the remaining 1 / 2 of the prescription amount of earthworm and leech with the alcohol extract from step B and the water extract from step C, and prepare a clinically acceptable dosage form by directly or by adding pharmaceutically acceptable excipients through conventional procedures.

[0026] This invention possesses a complete set of principal, assistant, adjuvant, and guiding herbs, with appropriate combinations and a precise understanding of the underlying mechanisms. The principal herbs are: Dioscorea hypoglauca and Spatholobus suberectus, which are the core components of the formula for unblocking meridians. The assistant herbs are: Pheretima aspergillum, Hirudo medicinalis, Asarum heterotropoides, Angelica pubescens, and Notopterygium incisum, which play a supporting role in treatment and enhance efficacy. The adjuvant herbs are: Paeonia suffruticosa, Curcuma longa, Astragalus membranaceus, Schizonepeta tenuifolia, Saposhnikovia divaricata, and Carthamus tinctorius; the guiding herb is Piper kadsura, which harmonizes the properties of the herbs, increases drug stability, and promotes absorption.

[0027] Compared with the prior art, the present invention has the following advantages:

[0028] (1) The traditional Chinese medicine composition of the present invention promotes the healing of ulcers in diabetic foot.

[0029] (2) The herbal composition of the present invention upregulates the expression of VEGF in ulcer tissue, promotes angiogenesis in granulation tissue, and reduces angiogenesis in wound.

[0030] (3) The raw materials of traditional Chinese medicine in this invention are readily available and low in cost. The preparation method is simple and easy to operate. The resulting traditional Chinese medicine composition has a definite curative effect on the prevention and treatment of diabetic foot, with no toxic side effects. Patients are less likely to relapse after recovery. It can provide new candidate drugs for the treatment of diabetic foot. Attached Figure Description

[0031] Figure 1 This invention demonstrates the effect of the traditional Chinese medicine composition on plasma viscosity in diabetic foot model rats. (n=15), compared with the normal group * P < 0.05 ** P < 0.01; compared with the model group,& P < 0.05 && P < 0.01; Comparative example: 5 groups compared. @ P < 0.05 @@ P < 0.01.

[0032] Figure 2 This indicates the effect of the traditional Chinese medicine composition of the present invention on the fibrinogen (Fib) value in diabetic foot model rats. (n=15), compared with the normal group * P < 0.05 ** P < 0.01; compared with the model group, & P < 0.05 && P < 0.01; Comparative example: 5 groups compared. @ P < 0.05 @@ P < 0.01.

[0033] Figure 3 This invention demonstrates the effect of the traditional Chinese medicine composition on serum VEGF levels in diabetic foot model rats. (n=15), compared with the normal group * P < 0.05 ** P < 0.01; compared with the model group, & P < 0.05 && P < 0.01; Comparative example: 5 groups compared. @ P < 0.05 @@ P < 0.01. Detailed Implementation

[0034] To verify the efficacy of the traditional Chinese medicine composition of this invention, the inventors conducted pharmacodynamic experiments. It should be noted that the drugs selected for the pharmacodynamic experiments of this invention are those obtained from the representative formulations and preparation methods of this invention. Due to space limitations, the experiments and results related to drugs obtained from other formulations and preparation methods included in this invention are not exhaustively listed here.

[0035] Example 1: A pill for treating or preventing diabetic foot

[0036] The traditional Chinese medicine composition comprises the following raw materials in parts by weight:

[0037] 40 parts of Dioscorea hypoglauca, 80 parts of Spatholobus suberectus, 18 parts of Angelica pubescens, 23 parts of Notopterygium incisum, 4 parts of Pheretima aspergillum, 4 parts of Hirudo medicinalis, 6 parts of Asarum heterotropoides, 15 parts of Schizonepeta tenuifolia, 22 parts of Saposhnikovia divaricata, 20 parts of Carthamus tinctorius, 12 parts of Paeonia suffruticosa, 18 parts of Curcuma longa, 15 parts of Astragalus membranaceus, and 6 parts of Piper kadsura.

[0038] The preparation method is as follows:

[0039] A. Take earthworms and leeches, and crush them to a particle size of less than 100μm;

[0040] B. Dioscorea hypoglauca, Spatholobus suberectus, Angelica pubescens, Notopterygium incisum, and Asarum heterotropoides were extracted three times with 60% ethanol for 2 hours each time. The mixture was filtered, and the ethanol was recovered from the filtrate. The extract was then concentrated under reduced pressure to a relative density of 1.10.

[0041] C. Extract the volatile oil from Schizonepeta, Saposhnikovia divaricata, Carthamus tinctorius, Paeonia suffruticosa, Curcuma longa, Astragalus membranaceus, and Piper kadsura with water. Add half the prescription amount of earthworm and leech to the remaining liquid and residue, decoct twice, 1.5 hours each time, filter, recover the ethanol from the filtrate, and concentrate to an extract with a relative density of 1.10 for later use.

[0042] D. Mix the remaining 1 / 2 of the prescription amount of earthworm and leech with the alcohol extract from step B and the water extract from step C, and then add pharmaceutically acceptable excipients through conventional procedures to prepare pills.

[0043] Example 2: A capsule for the treatment or prevention of diabetic foot

[0044] The traditional Chinese medicine composition comprises the following raw materials in parts by weight:

[0045] Dioscorea hypoglauca 30 parts, Spatholobus suberectus 55 parts, Angelica pubescens 25 parts, Notopterygium incisum 25 parts, Pheretima aspergillum 3 parts, Hirudo medicinalis 8 parts, Asarum heterotropoides 8 parts, Schizonepeta tenuifolia 12 parts, Saposhnikovia divaricata 25 parts, Carthamus tinctorius 30 parts, Paeonia suffruticosa 10 parts, Curcuma longa 20 parts, Astragalus membranaceus 30 parts, Piper kadsura 4 parts.

[0046] The preparation method is as follows:

[0047] A. Take earthworms and leeches, and crush them to a particle size of less than 100μm;

[0048] B. Dioscorea hypoglauca, Spatholobus suberectus, Angelica pubescens, Notopterygium incisum, and Asarum heterotropoides were extracted three times with 60% ethanol for 2 hours each time. The mixture was filtered, and the ethanol was recovered from the filtrate. The extract was then concentrated under reduced pressure to a relative density of 1.05.

[0049] C. Extract the volatile oil from Schizonepeta tenuifolia, Saposhnikovia divaricata, Carthamus tinctorius, Paeonia suffruticosa, Curcuma longa, Astragalus membranaceus, and Piper kadsura with water. Add half the prescription amount of earthworm and leech to the remaining liquid and dregs, decoct twice with water, each time for 1.5 hours, filter, recover the ethanol from the filtrate, and concentrate to an extract with a relative density of 1.05 for later use.

[0050] D. Mix the remaining 1 / 2 of the prescription amount of earthworm and leech with the alcohol extract from step B and the water extract from step C, and then add pharmaceutically acceptable excipients through conventional procedures to prepare capsules.

[0051] Example 3: A tablet for treating or preventing diabetic foot

[0052] The traditional Chinese medicine composition comprises the following raw materials in parts by weight:

[0053] 50 parts of Dioscorea hypoglauca, 75 parts of Spatholobus suberectus, 21 parts of Angelica pubescens, 21 parts of Notopterygium incisum, 5 parts of Pheretima aspergillum, 5 parts of Hirudo medicinalis, 5 parts of Asarum heterotropoides, 18 parts of Schizonepeta tenuifolia, 18 parts of Saposhnikovia divaricata, 22 parts of Carthamus tinctorius, 14 parts of Paeonia suffruticosa, 14 parts of Curcuma longa, 20 parts of Astragalus membranaceus, and 7 parts of Piper kadsura.

[0054] The preparation method is as follows:

[0055] A. Take earthworms and leeches, and crush them to a particle size of less than 100μm;

[0056] B. Dioscorea hypoglauca, Spatholobus suberectus, Angelica pubescens, Notopterygium incisum, and Asarum heterotropoides were extracted twice with 75% ethanol for 3 hours each time. The extracts were filtered, and the ethanol was recovered from the filtrate. The extracts were then concentrated under reduced pressure to a relative density of 1.05.

[0057] C. Extract the volatile oil from Schizonepeta tenuifolia, Saposhnikovia divaricata, Carthamus tinctorius, Paeonia suffruticosa, Curcuma longa, Astragalus membranaceus, and Piper kadsura with water. Add half the prescription amount of earthworm and leech to the remaining liquid and dregs and decoct once for 3.5 hours each time. Filter, recover the ethanol from the filtrate, and concentrate to an extract with a relative density of 1.05 for later use.

[0058] D. Mix the remaining 1 / 2 of the prescription amount of earthworm and leech with the alcohol extract from step B and the water extract from step C, and then add pharmaceutically acceptable excipients through conventional procedures to prepare tablets.

[0059] Example 4: A tablet for treating or preventing diabetic foot

[0060] The traditional Chinese medicine composition comprises the following raw materials in parts by weight:

[0061] Dioscorea hypoglauca 60 parts, Spatholobus suberectus 80 parts, Angelica pubescens 23 parts, Notopterygium incisum 18 parts, Pheretima aspergillum 6 parts, Hirudo medicinalis 6 parts, Asarum sieboldii 4 parts, Schizonepeta tenuifolia 22 parts, Saposhnikovia divaricata 15 parts, Carthamus tinctorius 25 parts, Paeonia suffruticosa 18 parts, Curcuma longa 12 parts, Astragalus membranaceus 25 parts, Piper kadsura 9 parts.

[0062] The preparation method is as follows:

[0063] A. Take earthworms and leeches, and crush them to a particle size of less than 100μm;

[0064] B. Dioscorea hypoglauca, Spatholobus suberectus, Angelica pubescens, Notopterygium incisum, and Asarum heterotropoides were extracted twice with 75% ethanol for 3 hours each time. The extracts were filtered, and the ethanol was recovered from the filtrate. The extracts were then concentrated under reduced pressure to a relative density of 1.05.

[0065] C. Extract the volatile oil from Schizonepeta tenuifolia, Saposhnikovia divaricata, Carthamus tinctorius, Paeonia suffruticosa, Curcuma longa, Astragalus membranaceus, and Piper kadsura with water. Add half the prescription amount of earthworm and leech to the remaining liquid and dregs and decoct once for 3.5 hours each time. Filter, recover the ethanol from the filtrate, and concentrate to an extract with a relative density of 1.05 for later use.

[0066] D. Mix the remaining 1 / 2 of the prescription amount of earthworm and leech with the alcohol extract from step B and the water extract from step C, and then add pharmaceutically acceptable excipients through conventional procedures to prepare tablets.

[0067] Example 5: A pill for treating or preventing diabetic foot

[0068] The traditional Chinese medicine composition comprises the following raw materials in parts by weight:

[0069] Dioscorea hypoglauca 65 parts, Spatholobus suberectus 75 parts, Angelica pubescens 16 parts, Notopterygium incisum 24 parts, Pheretima aspergillum 8 parts, Hirudo medicinalis 7 parts, Asarum heterotropoides 4 parts, Schizonepeta tenuifolia 25 parts, Saposhnikovia divaricata 12 parts, Carthamus tinctorius 20 parts, Paeonia suffruticosa 10 parts, Curcuma longa 20 parts, Astragalus membranaceus 28 parts, Piper kadsura 11 parts.

[0070] The preparation method is as follows:

[0071] A. Take earthworms and leeches, and crush them to a particle size of less than 100μm;

[0072] B. Dioscorea hypoglauca, Spatholobus suberectus, Angelica pubescens, Notopterygium incisum, and Asarum heterotropoides were extracted twice with 65% ethanol for 4 hours each time. The extracts were filtered, and the ethanol was recovered from the filtrate. The extracts were then concentrated under reduced pressure to a relative density of 1.05.

[0073] C. Extract the volatile oil from Schizonepeta, Saposhnikovia divaricata, Carthamus tinctorius, Paeonia suffruticosa, Curcuma longa, Astragalus membranaceus, and Piper kadsura with water. Add half the prescription amount of earthworm and leech to the remaining liquid and residue, decoct twice, each time for 3 hours, filter, recover the ethanol from the filtrate, and concentrate to an extract with a relative density of 1.05 for later use.

[0074] D. Mix the remaining 1 / 2 of the prescription amount of earthworm and leech with the alcohol extract from step B and the water extract from step C, and then add pharmaceutically acceptable excipients through conventional procedures to prepare pills.

[0075] Example 6: A tablet for treating or preventing diabetic foot

[0076] The traditional Chinese medicine composition comprises the following raw materials in parts by weight:

[0077] Dioscorea hypoglauca 35 parts, Spatholobus suberectus 80 parts, Angelica pubescens 23 parts, Notopterygium incisum 22 parts, Pheretima aspergillum 6 parts, Hirudo medicinalis 5 parts, Asarum heterotropoides 7 parts, Schizonepeta tenuifolia 15 parts, Saposhnikovia divaricata 23 parts, Carthamus tinctorius 13 parts, Paeonia suffruticosa 18 parts, Curcuma longa 18 parts, Astragalus membranaceus 15 parts, Piper kadsura 6 parts.

[0078] The preparation method is as follows:

[0079] A. Take earthworms and leeches, and crush them to a particle size of less than 100μm;

[0080] B. Dioscorea hypoglauca, Spatholobus suberectus, Angelica pubescens, Notopterygium incisum, and Asarum heterotropoides were extracted three times with 80% ethanol for 2 hours each time. The mixture was filtered, and the ethanol was recovered from the filtrate. The extract was then concentrated under reduced pressure to a relative density of 1.05.

[0081] C. Extract the volatile oil from Schizonepeta tenuifolia, Saposhnikovia divaricata, Carthamus tinctorius, Paeonia suffruticosa, Curcuma longa, Astragalus membranaceus, and Piper kadsura with water. Add half the prescription amount of earthworm and leech to the remaining liquid and dregs and decoct once for 2.5 hours each time. Filter, recover the ethanol from the filtrate, and concentrate to an extract with a relative density of 1.05 for later use.

[0082] D. Mix the remaining 1 / 2 of the prescription amount of earthworm and leech with the alcohol extract from step B and the water extract from step C, and then add pharmaceutically acceptable excipients through conventional procedures to prepare tablets.

[0083] Example 7: A capsule for the treatment or prevention of diabetic foot

[0084] The traditional Chinese medicine composition comprises the following raw materials in parts by weight:

[0085] 70 parts of Dioscorea hypoglauca, 80 parts of Spatholobus suberectus, 22 parts of Angelica pubescens, 23 parts of Notopterygium incisum, 6 parts of Pheretima aspergillum, 8 parts of Hirudo medicinalis, 3 parts of Asarum heterotropoides, 12 parts of Schizonepeta tenuifolia, 25 parts of Saposhnikovia divaricata, 18 parts of Carthamus tinctorius, 17 parts of Paeonia suffruticosa, 15 parts of Curcuma longa, 16 parts of Astragalus membranaceus, and 9 parts of Piper kadsura.

[0086] The preparation method is as follows:

[0087] A. Take earthworms and leeches, and crush them to a particle size of less than 100μm;

[0088] B. Dioscorea hypoglauca, Spatholobus suberectus, Angelica pubescens, Notopterygium incisum, and Asarum heterotropoides were extracted three times with 85% ethanol for 2 hours each time. The mixture was filtered, and the ethanol was recovered from the filtrate. The extract was then concentrated under reduced pressure to a relative density of 1.05.

[0089] C. Extract the volatile oil from Schizonepeta, Saposhnikovia divaricata, Carthamus tinctorius, Paeonia suffruticosa, Curcuma longa, Astragalus membranaceus, and Piper kadsura with water. Add half the prescription amount of earthworm and leech to the remaining liquid and residue, decoct twice, 3.5 hours each time, filter, recover ethanol from the filtrate, and concentrate to an extract with a relative density of 1.0 for later use.

[0090] D. Mix the remaining 1 / 2 of the prescription amount of earthworm and leech with the alcohol extract from step B and the water extract from step C, and then add pharmaceutically acceptable excipients through conventional procedures to prepare capsules.

[0091] Example 8: A pill for treating or preventing diabetic foot

[0092] The traditional Chinese medicine composition comprises the following raw materials in parts by weight:

[0093] Dioscorea hypoglauca 30 parts, Spatholobus suberectus 55 parts, Angelica pubescens 25 parts, Notopterygium incisum 15 parts, Pheretima aspergillum 8 parts, Hirudo medicinalis 3 parts, Asarum heterotropoides 6 parts, Schizonepeta tenuifolia 15 parts, Saposhnikovia divaricata 18 parts, Carthamus tinctorius 20 parts, Paeonia suffruticosa 15 parts, Curcuma longa 15 parts, Astragalus membranaceus 20 parts, Piper kadsura 6 parts.

[0094] The preparation method is as follows:

[0095] A. Take earthworms and leeches, and crush them to a particle size of less than 100μm;

[0096] B. Dioscorea hypoglauca, Spatholobus suberectus, Angelica pubescens, Notopterygium incisum, and Asarum heterotropoides were extracted twice with 85% ethanol for 2 hours each time. The mixture was filtered, and the ethanol was recovered from the filtrate. The extract was then concentrated under reduced pressure to a relative density of 1.05.

[0097] C. Extract the volatile oil from Schizonepeta tenuifolia, Saposhnikovia divaricata, Carthamus tinctorius, Paeonia suffruticosa, Curcuma longa, Astragalus membranaceus, and Piper kadsura with water. Add half the prescription amount of earthworm and leech to the remaining liquid and residue, decoct twice, 2.5 hours each time, filter, recover the ethanol from the filtrate, and concentrate to an extract with a relative density of 1.05 for later use.

[0098] D. Mix the remaining 1 / 2 of the prescription amount of earthworm and leech with the alcohol extract from step B and the water extract from step C, and then add pharmaceutically acceptable excipients through conventional procedures to prepare pills.

[0099] Example 9: A gel for treating or preventing diabetic foot

[0100] Dioscorea hypoglauca 30 parts, Spatholobus suberectus 55 parts, Angelica pubescens 25 parts, Notopterygium incisum 15 parts, Pheretima aspergillum 8 parts, Hirudo medicinalis 3 parts, Asarum heterotropoides 6 parts, Schizonepeta tenuifolia 15 parts, Saposhnikovia divaricata 18 parts, Carthamus tinctorius 20 parts, Paeonia suffruticosa 15 parts, Curcuma longa 15 parts, Astragalus membranaceus 20 parts, Piper kadsura 6 parts.

[0101] The preparation method is as follows:

[0102] A. Take earthworms and leeches, and crush them to a particle size of less than 100μm;

[0103] B. Dioscorea hypoglauca, Spatholobus suberectus, Angelica pubescens, Notopterygium incisum, and Asarum heterotropoides were extracted twice with 85% ethanol for 2 hours each time. The mixture was filtered, and the ethanol was recovered from the filtrate. The extract was then concentrated under reduced pressure to a relative density of 1.05.

[0104] C. Extract the volatile oil from Schizonepeta tenuifolia, Saposhnikovia divaricata, Carthamus tinctorius, Paeonia suffruticosa, Curcuma longa, Astragalus membranaceus, and Piper kadsura with water. Add half the prescription amount of earthworm and leech to the remaining liquid and residue, decoct twice, 2.5 hours each time, filter, recover the ethanol from the filtrate, and concentrate to an extract with a relative density of 1.05 for later use.

[0105] D. Mix the remaining 1 / 2 of the prescription amount of earthworm and leech with the alcohol extract from step B and the water extract from step C, and prepare a gel by adding pharmaceutically acceptable excipients through standard procedures.

[0106] Comparative Example 1: A tablet for the treatment or prevention of diabetic foot

[0107] The traditional Chinese medicine composition comprises the following raw materials in parts by weight:

[0108] Atractylodes lancea 50 parts, Spatholobus suberectus 75 parts, Angelica pubescens 21 parts, Notopterygium incisum 21 parts, Pheretima aspergillum 5 parts, Hirudo medicinalis 5 parts, Asarum sieboldii 5 parts, Schizonepeta tenuifolia 18 parts, Saposhnikovia divaricata 18 parts, Carthamus tinctorius 22 parts, Paeonia suffruticosa 14 parts, Curcuma longa 14 parts, Astragalus membranaceus 20 parts, Piper kadsura 7 parts.

[0109] The preparation method is as follows:

[0110] A. Take earthworms and leeches, and crush them to a particle size of less than 100μm;

[0111] B. Atractylodes lancea, Spatholobus suberectus, Angelica pubescens, Notopterygium incisum, and Asarum heterotropoides were extracted twice with 75% ethanol for 3 hours each time. The extracts were filtered, and the ethanol was recovered from the filtrate. The extracts were then concentrated under reduced pressure to a relative density of 1.05.

[0112] C. Extract the volatile oil from Schizonepeta tenuifolia, Saposhnikovia divaricata, Carthamus tinctorius, Paeonia suffruticosa, Curcuma longa, Astragalus membranaceus, and Piper kadsura with water. Add half the prescription amount of earthworm and leech to the remaining liquid and dregs and decoct once for 3.5 hours each time. Filter, recover the ethanol from the filtrate, and concentrate to an extract with a relative density of 1.05 for later use.

[0113] D. Mix the remaining 1 / 2 of the prescription amount of earthworm and leech with the alcohol extract from step B and the water extract from step C, and then add pharmaceutically acceptable excipients through conventional procedures to prepare tablets.

[0114] Comparative Example 2: A tablet for the treatment or prevention of diabetic foot

[0115] The traditional Chinese medicine composition comprises the following raw materials in parts by weight:

[0116] Dioscorea hypoglauca 50 parts, Angelica sinensis 75 parts, Angelica pubescens 21 parts, Notopterygium incisum 21 parts, Pheretima aspergillum 5 parts, Hirudo medicinalis 5 parts, Asarum heterotropoides 5 parts, Schizonepeta tenuifolia 18 parts, Saposhnikovia divaricata 18 parts, Carthamus tinctorius 22 parts, Paeonia suffruticosa 14 parts, Curcuma longa 14 parts, Astragalus membranaceus 20 parts, Piper kadsura 7 parts.

[0117] The preparation method is as follows:

[0118] A. Take earthworms and leeches, and crush them to a particle size of less than 100μm;

[0119] B. Dioscorea hypoglauca, Angelica sinensis, Angelica pubescens, Notopterygium incisum, and Asarum heterotropoides were extracted twice with 75% ethanol for 3 hours each time. The mixture was filtered, and the ethanol was recovered from the filtrate. The extract was then concentrated under reduced pressure to a relative density of 1.05.

[0120] C. Extract the volatile oil from Schizonepeta tenuifolia, Saposhnikovia divaricata, Carthamus tinctorius, Paeonia suffruticosa, Curcuma longa, Astragalus membranaceus, and Piper kadsura with water. Add half the prescription amount of earthworm and leech to the remaining liquid and dregs and decoct once for 3.5 hours each time. Filter, recover the ethanol from the filtrate, and concentrate to an extract with a relative density of 1.05 for later use.

[0121] D. Mix the remaining 1 / 2 of the prescription amount of earthworm and leech with the alcohol extract from step B and the water extract from step C, and then add pharmaceutically acceptable excipients through conventional procedures to prepare tablets.

[0122] Comparative Example 3: A tablet for the treatment or prevention of diabetic foot

[0123] The traditional Chinese medicine composition comprises the following raw materials in parts by weight:

[0124] Angelica pubescens 21 parts, Notopterygium incisum 21 parts, Pheretima aspergillum 5 parts, Hirudo medicinalis 5 parts, Asarum sieboldii 5 parts, Schizonepeta tenuifolia 18 parts, Saposhnikovia divaricata 18 parts, Carthamus tinctorius 22 parts, Paeonia suffruticosa 14 parts, Curcuma longa 14 parts, Astragalus membranaceus 20 parts, Piper kadsura 7 parts.

[0125] The preparation method is as follows:

[0126] A. Take earthworms and leeches, and crush them to a particle size of less than 100μm;

[0127] B. Angelica pubescens, Notopterygium incisum, and Asarum heterotropoides were extracted twice with 75% ethanol for 3 hours each time. The mixture was filtered, and the ethanol was recovered from the filtrate. The extract was then concentrated under reduced pressure to a relative density of 1.05.

[0128] C. Extract the volatile oil from Schizonepeta tenuifolia, Saposhnikovia divaricata, Carthamus tinctorius, Paeonia suffruticosa, Curcuma longa, Astragalus membranaceus, and Piper kadsura with water. Add half the prescription amount of earthworm and leech to the remaining liquid and dregs and decoct once for 3.5 hours each time. Filter, recover the ethanol from the filtrate, and concentrate to an extract with a relative density of 1.05 for later use.

[0129] D. Mix the remaining 1 / 2 of the prescription amount of earthworm and leech with the alcohol extract from step B and the water extract from step C, and then add pharmaceutically acceptable excipients through conventional procedures to prepare tablets.

[0130] Comparative Example 4: A tablet for the treatment or prevention of diabetic foot

[0131] The traditional Chinese medicine composition comprises the following raw materials in parts by weight:

[0132] 50 parts of Ligusticum chuanxiong, 75 parts of Spatholobus suberectus, 21 parts of Angelica pubescens, 21 parts of Cinnamomum cassia, 5 parts of Uncaria rhynchophylla, 5 parts of Scolopendra subspinipes, 5 parts of Ephedra sinica, 18 parts of Schizonepeta tenuifolia, 18 parts of Saposhnikovia divaricata, 22 parts of Carthamus tinctorius, 14 parts of Paeonia suffruticosa, 14 parts of Curcuma longa, 20 parts of Astragalus membranaceus, and 7 parts of Piper kadsura.

[0133] The preparation method is as follows:

[0134] A. Take Uncaria rhynchophylla and centipede, and crush them to make the particle size less than 100μm;

[0135] B. Dioscorea hypoglauca, Spatholobus suberectus, Angelica pubescens, Cinnamomum cassia, and Ephedra sinica were extracted twice with 75% ethanol for 3 hours each time. The mixture was filtered, and the ethanol was recovered from the filtrate. The extract was then concentrated under reduced pressure to a relative density of 1.05.

[0136] C. Extract the volatile oil from Schizonepeta, Saposhnikovia divaricata, Carthamus tinctorius, Paeonia suffruticosa, Curcuma longa, Astragalus membranaceus, and Piper kadsura with water. Add half the prescription amount of Uncaria rhynchophylla and Scolopendra subspinipes to water and decoct once, each time for 3.5 hours. Filter, recover the ethanol from the filtrate, and concentrate to an extract with a relative density of 1.05 for later use.

[0137] D. Mix the remaining 1 / 2 of the prescription amount of Uncaria rhynchophylla and Scolopendra subspinipes with the alcohol extract from step B and the water extract from step C, and then add pharmaceutically acceptable excipients through conventional procedures to prepare tablets.

[0138] Comparative Example 5: A tablet for the treatment or prevention of diabetic foot

[0139] The traditional Chinese medicine composition comprises the following raw materials in parts by weight:

[0140] Dioscorea hypoglauca 75 parts, Spatholobus suberectus 50 parts, Angelica pubescens 30 parts, Notopterygium incisum 10 parts, Pheretima aspergillum 10 parts, Hirudo medicinalis 2 parts, Asarum heterotropoides 10 parts, Schizonepeta tenuifolia 10 parts, Saposhnikovia divaricata 30 parts, Carthamus tinctorius 12 parts, Paeonia suffruticosa 22 parts, Curcuma longa 8 parts, Astragalus membranaceus 33 parts, Piper kadsura 3 parts.

[0141] The preparation method is as follows:

[0142] A. Take earthworms and leeches, and crush them to a particle size of less than 100μm;

[0143] B. Atractylodes lancea, Spatholobus suberectus, Angelica pubescens, Notopterygium incisum, and Asarum heterotropoides were extracted twice with 75% ethanol for 3 hours each time. The extracts were filtered, and the ethanol was recovered from the filtrate. The extracts were then concentrated under reduced pressure to a relative density of 1.05.

[0144] C. Extract the volatile oil from Schizonepeta tenuifolia, Saposhnikovia divaricata, Carthamus tinctorius, Paeonia suffruticosa, Curcuma longa, Astragalus membranaceus, and Piper kadsura with water. Add half the prescription amount of earthworm and leech to the remaining liquid and dregs and decoct once for 3.5 hours each time. Filter, recover the ethanol from the filtrate, and concentrate to an extract with a relative density of 1.05 for later use.

[0145] D. Mix the remaining 1 / 2 of the prescription amount of earthworm and leech with the alcohol extract from step B and the water extract from step C, and then add pharmaceutically acceptable excipients through conventional procedures to prepare tablets.

[0146] Comparative example 6, Gu Butang, comes from the Qing Dynasty book "True Interpretation of Surgery".

[0147] Take 30 grams each of Astragalus membranaceus, Dendrobium nobile, Angelica sinensis, Lonicera japonica, Achyranthes bidentata, and Viola yedoensis; 15 grams each of Taraxacum mongolicum and Chrysanthemum morifolium; and 9 grams each of Ginseng and Glycyrrhiza uralensis. Decocted in water and taken orally.

[0148] Pharmacological Example 1: Experimental study on the therapeutic effect of the traditional Chinese medicine composition of the present invention on diabetic foot.

[0149] 1. Establishment of a rat model of diabetic foot

[0150] The experimental animals were 110 SPF-grade Wistar rats, weighing 160-200g, with free access to water and food. The room temperature was maintained at 25±1℃, and the light-dark cycle was 12 hours.

[0151] After one week of acclimatization feeding, 10 Wistar rats were selected as the normal wound group, and the remaining 100 rats had their blood glucose measured. They were then injected intraperitoneally with urezosin at a dose of 75 mg / kg and fed a high-fat diet for another week. Blood glucose levels were measured again afterward. Rats with blood glucose levels above 16.7 mmol / L, accompanied by polyphagia, polydipsia, polyuria, and weight loss, were considered to have successfully established a diabetic rat model. The successfully modeled rats were divided into the diabetic wound group, Example 1 group, Example 2 group, Example 3 group, Comparative Example 1 group, Comparative Example 2 group, Comparative Example 3 group, Comparative Example 4 group, Comparative Example 5 group, and Gubudang group.

[0152] Two weeks after administration of urezosin, wounds were created, and this day was defined as day 0. Wounds were created on the right hind paw (foot) of each rat. Each rat was anesthetized by intraperitoneal injection of 10% chloral hydrate (0.3 ml / 100 g). A rectangular pattern was marked on the dorsal surface of the right hind paw (foot) using a flexible transparent plastic template, and then a standard area of ​​approximately 2 mm × 5 mm of full-thickness skin was removed. After inducing diabetic wounds, the following administrations were performed in each group:

[0153] In Example 1 group, 1.5 g / kg of the composition of Example 1 was administered by gavage daily.

[0154] In Example 2 group, 1.5 g / kg of the Composition of Example 2 was administered by gavage daily.

[0155] In Example 3, the group was given 1.5 g / kg of the Composition of Example 3 by gavage daily.

[0156] Comparative Example 1 group was given 1.5 g / kg of the Comparative Example 1 composition by gavage daily.

[0157] Comparative Example 2 was administered 1.5 g / kg of the Comparative Example 2 composition by gavage daily.

[0158] Comparative Example 3 groups were administered 1.5 g / kg of the Comparative Example 3 composition by gavage daily.

[0159] Comparative Example 4 groups were administered 1.5 g / kg of the Comparative Example 4 composition by gavage daily.

[0160] Comparative Example 5 groups were administered 1.5 g / kg of the Comparative Example 5 composition by gavage daily.

[0161] The Gu Bu Tang group was given 1.5g / kg of Gu Bu Tang via gavage, compared to the control group 6.

[0162] Rats with diabetic wounds were administered 10 mg / kg of physiological saline by gavage.

[0163] A separate rat group without diabetes induction also maintained wound formation, defined as the normal wound group, and these rats were administered physiological saline by gavage at a dose of 10 mg / kg.

[0164] Each group was given gavage once a day for 21 consecutive days.

[0165] 2. Statistical Methods

[0166] Data processing was performed using SPSS 22.0 software. The obtained data are expressed as mean ± standard deviation (x ± s). Normality and homogeneity of variance tests were performed on each group of data, meeting the requirements of Pearson's test. One-way ANOVA was used for comparisons between groups. A p-value < 0.05 was considered statistically significant.

[0167] 3. Experimental Results

[0168] Wound closure % = -100 × [(WN - W0) / W0]; W0 = wound area on day 0; WN = wound area on days 3, 7, 14, and 21. The wound closure rate in the diabetic wound control group was negative, indicating an increased wound area and wound deterioration. The wound closure rate in the normal wound group and the treatment group using the composition of this invention was positive, indicating a decreased wound area and wound healing.

[0169] The experimental results are shown in Table 1.

[0170] Table 1. Effect of the herbal composition of the present invention on wound closure rate (%) in a diabetic foot model.

[0171]

[0172]

[0173] Note: Compared with the normal wound group. * P < 0.05 ** P < 0.01,*** P < 0.001;

[0174] Compared with the diabetic wound group, & P < 0.05 && P < 0.01, &&& P < 0.001;

[0175] Comparative Example 1: @ P < 0.05 @@ P < 0.01;

[0176] Compared with the Gubutang group, # P < 0.05.

[0177] On days 7, 14, and 21 after treatment, the wounds of Examples 1-3 of the present invention and the Gubudang group showed varying degrees of repair. The longer the time, the better the healing. Among them, the wound closure effect of Example 3 of the present invention was the best.

[0178] Compared with the model group, the wound closure rate of rats in the Examples 1-3 groups was higher on days 7, 14, and 21 after treatment, and the difference was statistically significant (P < 0.01 or P < 0.001), further demonstrating the successful modeling of the present invention.

[0179] Compared with Comparative Example 1, the wound closure rate of rats in Examples 1-3 was significantly improved.

[0180] Compared with Gu Bu Tang, the wound closure rate of rats in Examples 1-3 was higher, and the difference was statistically significant (P<0.05).

[0181] Pharmacological Example 2: Effects of the herbal composition of the present invention on diabetic foot model rats

[0182] 1. Materials

[0183] SD rats, weighing 160-200g, were housed in an environment with a temperature of (24±1)℃, relative humidity of 45%-55%, and a 12h light-dark cycle, with free access to water and food.

[0184] 2. Experimental Procedure

[0185] SD rats were acclimatized for one week and fed a high-fat diet (containing 51% carbohydrates, 14% protein, and 35% fat) for four consecutive weeks. After fasting for one day, the rats were intraperitoneally injected with 55 mg / kg of citrate-sodium citrate buffer containing 1% streptozotocin. Three days after administration, rats with blood glucose ≥16.7 mmol / L were randomly selected as diabetic rats. Fifteen normal rats were designated as the normal control group, and another 45 diabetic rats were randomly divided into a model group, three example groups, and five control groups, with 15 rats in each group. Except for the normal control group, the remaining rats were intraperitoneally injected with 2% sodium pentobarbital (dosage: 0.3 ml / 100 g), and a 3 mm * 3 mm rectangular wound was created on the dorsal side of the right paw.

[0186] Example 3 group: 1.5 g / kg of the composition of Example 3 administered by gavage;

[0187] Comparative Example 5 groups were administered 1.5 g / kg of the Comparative Example 5 composition by gavage;

[0188] The model group and the normal group were given the same volume of physiological saline.

[0189] 2.2 Statistical Analysis

[0190] Data processing was performed using SPSS 22.0 software. The obtained data are expressed as mean ± standard deviation (x ± s). Normality and homogeneity of variance tests were performed on each group of data, meeting the requirements of Pearson's test. One-way ANOVA was used for comparisons between groups. A p-value < 0.05 was considered statistically significant.

[0191] 3. Methods and Results

[0192] 3.1 Effects of the herbal composition of the present invention on serum of diabetic foot rats

[0193] Eight weeks after administration, blood was collected from the inner eyelids of rats in each group. Plasma viscosity and fibrinogen (Fib) values ​​were measured using a blood viscometer. Results are shown below. Figure 1 , Figure 2 .

[0194] Compared with the normal group, the plasma viscosity and Fib value of rats in the model group were significantly increased, and the difference was statistically significant (P<0.01). Compared with the model group, the plasma viscosity and Fib value of rats in Example 3 of this invention were lower than those in the model group, and the difference between Example 3 and the model group was statistically significant. Compared with Comparative Example 5, the plasma viscosity and Fib value of rats in Example 3 of this invention were significantly decreased, and the difference was statistically significant.

[0195] like Figure 3As shown, compared with the normal group, the VEGF content in the serum of rats in the model group was significantly decreased, and the difference was statistically significant (P<0.01). Compared with the model group, the VEGF content in the serum of rats in Example 3 of this invention was higher than that in the model group, and the difference between Example 3 and the model group was statistically significant. Compared with Comparative Example 5, the VEGF content in the serum of rats in Example 3 of this invention was significantly increased, and the difference was statistically significant.

[0196] The above experimental results show that the herbal composition of the present invention promotes angiogenesis in the ulcer tissue of diabetic foot rats, reduces blood viscosity, and has a significant therapeutic effect on diabetic foot.

[0197] The above embodiments are not intended to limit the present invention in any way. For those skilled in the art, any modifications or substitutions made within the scope of the present invention based on its technical essence shall still fall within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for the prevention or treatment of diabetic foot, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: Dioscorea hypoglauca 30-70 parts, Spatholobus suberectus 55-90 parts, Angelica pubescens 15-25 parts, Notopterygium incisum 15-25 parts, Pheretima aspergillum 3-8 parts, Hirudo medicinalis 3-8 parts, Asarum heterotropoides 3-8 parts, Schizonepeta tenuifolia 12-25 parts, Saposhnikovia divaricata 12-25 parts, Carthamus tinctorius 15-30 parts, Paeonia suffruticosa 10-20 parts, Curcuma longa 10-20 parts, Astragalus membranaceus 10-30 parts, Piper kadsura 4-11 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: Dioscorea hypoglauca 40-60 parts, Spatholobus suberectus 65-80 parts, Angelica pubescens 18-23 parts, Notopterygium incisum 18-23 parts, Pheretima aspergillum 4-6 parts, Hirudo medicinalis 4-6 parts, Asarum heterotropoides 4-6 parts, Schizonepeta tenuifolia 15-22 parts, Saposhnikovia divaricata 15-22 parts, Carthamus tinctorius 20-25 parts, Paeonia suffruticosa 12-18 parts, Curcuma longa 12-18 parts, Astragalus membranaceus 15-25 parts, Piper kadsura 6-9 parts.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 50 parts of Dioscorea hypoglauca, 75 parts of Spatholobus suberectus, 21 parts of Angelica pubescens, 21 parts of Notopterygium incisum, 5 parts of Pheretima aspergillum, 5 parts of Hirudo medicinalis, 5 parts of Asarum heterotropoides, 18 parts of Schizonepeta tenuifolia, 18 parts of Saposhnikovia divaricata, 22 parts of Carthamus tinctorius, 14 parts of Paeonia suffruticosa, 14 parts of Curcuma longa, 20 parts of Astragalus membranaceus, and 7 parts of Piper kadsura.

4. The traditional Chinese medicine composition according to any one of claims 1-3, characterized in that, The preparation method of the traditional Chinese medicine composition is as follows: A. Take earthworms and leeches, and crush them to a particle size of less than 100μm; B. Dioscorea hypoglauca, Spatholobus suberectus, Asarum heterotropoides, Angelica pubescens, and Notopterygium incisum are extracted with 65-85% ethanol 1-2 times, each extraction lasting 1.5-3.5 hours. The mixture is then filtered, and the ethanol in the filtrate is recovered and concentrated under reduced pressure to an extract with a relative density of 1.05-1.

10. C. Extract the volatile oil from peony bark, sea pine, turmeric, astragalus, schizonepeta, saposhnikovia, and safflower with water. Add half the prescription amount of earthworm and leech to the remaining liquid and dregs, decoct 1-2 times, each time for 1.5-3.5 hours, filter, recover ethanol from the filtrate, and concentrate to an extract with a relative density of 1.15-1.20 for later use. D. Mix the remaining 1 / 2 of the prescription amount of earthworm and leech with the alcohol extract from step B and the water extract from step C, and prepare a clinically acceptable dosage form by directly or by adding pharmaceutically acceptable excipients through conventional procedures.

5. Use of the traditional Chinese medicine composition according to any one of claims 1-3 in the preparation of a medicament for treating diabetic foot.

6. The use according to claim 5, characterized in that, The symptoms of diabetic foot are selected from one or more of the following: foot neuropathy, foot vascular disease, deep tissue damage, weak tissue repair ability, foot soft tissue deformity, musculoskeletal system damage, plantar hypertension, joint disease, poor blood supply, foot ulcer, ischemia, infection, gangrene, and tissue inflammation.

7. The use according to claim 5, characterized in that, The herbal composition promotes angiogenesis, reduces blood viscosity, and promotes the healing of ulcers.

8. A formulation prepared from the traditional Chinese medicine composition according to any one of claims 1-3.

9. The formulation according to claim 8, characterized in that, The traditional Chinese medicine composition can be prepared into a pharmaceutically acceptable dosage form, and the preparation is selected from decoctions, pills, tablets, gels, mixtures, capsules, granules, powders or ointments.

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