技术领域technical field
本发明涉及一种治疗糖尿病的药物，特别涉及一种治疗糖尿病足溃疡的外用中药制剂、制备方法及其应用。The invention relates to a medicine for treating diabetes, in particular to an external Chinese medicinal preparation for treating diabetic foot ulcer, a preparation method and application thereof.
背景技术Background technique
糖尿病足是一种常见的糖尿病并发症，它严重影响患者劳动能力和生活质量。糖尿病足溃疡是糖尿病足的主要临床表现，其截肢率是非糖尿病患者的15-20倍，研究提示糖尿病患者截肢相关的全因死亡率较非糖尿病患者比较升高5倍以上。我国现有糖尿病患者约9千2百万，糖尿病足发病率约为0.9％-14.5％。糖尿病足给社会医疗资源带来了沉重负担。在西方国家，糖尿病足溃疡的花费为16000-27000美元/例患者，截肢的医疗花费高达43000-64000美元/例患者。在发展中国家，糖尿病足耗费了约40％的卫生资源，我国尚无官方数据，根据我科糖尿病足住院患者平均测算，每例糖尿病足患者平均治疗费用约为6-8万人民币。然而糖尿病足的临床治疗却一直缺少有效措施。综合近年来国内外文献对糖尿病足主要有以下治疗方法：Diabetic foot is a common complication of diabetes, which seriously affects the labor ability and quality of life of patients. Diabetic foot ulcer is the main clinical manifestation of diabetic foot, and its amputation rate is 15-20 times that of non-diabetic patients. Studies have shown that the amputation-related all-cause mortality of diabetic patients is more than 5 times higher than that of non-diabetic patients. There are about 92 million diabetic patients in my country, and the incidence of diabetic foot is about 0.9%-14.5%. Diabetic foot has brought a heavy burden to social medical resources. In Western countries, the cost of diabetic foot ulcers is $16,000-27,000 per patient, and the medical cost of amputation is as high as $43,000-64,000 per patient. In developing countries, diabetic foot consumes about 40% of health resources. There is no official data in my country. According to the average calculation of diabetic foot hospitalized patients in our department, the average treatment cost of each diabetic foot patient is about 60,000-80,000 RMB. However, the clinical treatment of diabetic foot has been lack of effective measures. According to the domestic and foreign literature in recent years, there are mainly the following treatment methods for diabetic foot:
(1)控制血糖：与治疗其他并发症一样，治疗糖尿病足溃疡必须首先控制高血糖。糖尿病足溃疡的病理基础是微血管病变，控制高血糖可改善微循环，减少体液和蛋白渗出，使大量白细胞进入组织间增强局部组织的抗感染能力，减轻周围神经病变，增加神经营养供给，有利于感染和坏疽的创面愈合。因此控制高血糖是治疗本病的前提。在糖尿病出现肢端坏疽时，必须改用胰岛素控制血糖。(1) Control blood sugar: Like the treatment of other complications, the treatment of diabetic foot ulcers must first control high blood sugar. The pathological basis of diabetic foot ulcers is microangiopathy. Controlling hyperglycemia can improve microcirculation, reduce body fluid and protein leakage, allow a large number of white blood cells to enter the interstitial space, enhance the anti-infection ability of local tissues, reduce peripheral neuropathy, and increase neurotrophic supply. Conducive to the wound healing of infection and gangrene. Therefore, controlling hyperglycemia is a prerequisite for the treatment of this disease. When diabetic gangrene occurs, insulin must be used to control blood sugar.
(2)改善血液循环：如654-2、川芎嗪、银杏叶提取物、前列腺素E1、尿激酶等药物可扩张全身小动静脉，增加周围微循环血量，降低血流阻力，改善微循环。(2) Improve blood circulation: Drugs such as 654-2, ligustrazine, ginkgo biloba extract, prostaglandin E1, urokinase and other drugs can expand small arteries and veins throughout the body, increase blood volume in the surrounding microcirculation, reduce blood flow resistance, and improve microcirculation .
(3)抗感染：抗感染包括全身感染及局部感染，应选用有效抗菌素控制感染，感染控制的好坏，直接影响血糖及足溃疡愈合。(3) Anti-infection: Anti-infection includes systemic infection and local infection. Effective antibiotics should be used to control infection. The quality of infection control directly affects blood sugar and foot ulcer healing.
(4)外科手术及介入治疗：动脉支架、球囊扩张、动脉斑块消融、动脉斑块旋切术、人造血管搭桥等所需设备精密昂贵，创伤重、风险大、费用高、合并症多、死亡率高、病人依从性差。(4) Surgical operations and interventional therapy: Arterial stents, balloon dilatation, arterial plaque ablation, arterial plaque atherectomy, artificial vascular bypass, etc. require sophisticated and expensive equipment, heavy trauma, high risk, high cost, and many complications , high mortality, and poor patient compliance.
(5)干细胞治疗：所需设备精密昂贵，受到伦理限制，多数医院不能开展，远期疗效有待观察。(5) Stem cell therapy: The equipment required is sophisticated and expensive, and due to ethical restrictions, most hospitals cannot carry out the treatment, and the long-term efficacy remains to be seen.
(6)减压肢具：主要包括全接触石膏、可拆卸行走支具。糖尿病足溃疡的产生与局部压力分布异常密切相关，减压肢具的作用机理是将创面承受的压力转移到正常组织，从而起到保护创面的作用。全接触石膏需要有经验的医师操作，因此在一定程度上影响其临床推广。其缺点是给病人带来不便，对伴有创面感染和骨髓炎的糖尿病足的患者禁用。可拆卸行走支具克服了全接触石膏的缺点，制作更复杂，对操作医生要求更高。(6) Decompression limbs: mainly including full-contact plaster and detachable walking braces. The occurrence of diabetic foot ulcers is closely related to abnormal local pressure distribution. The mechanism of decompression limbs is to transfer the pressure on the wound surface to normal tissues, thereby protecting the wound surface. Full-contact plaster requires experienced physicians to operate, so it affects its clinical promotion to a certain extent. Its disadvantage is that it brings inconvenience to patients, and it is contraindicated for patients with diabetic feet with wound infection and osteomyelitis. The detachable walking brace overcomes the shortcomings of full-contact plaster, and is more complicated to manufacture and requires higher requirements for operating doctors.
(7)生物敷料：随着生物技术的发展，传统的敷料被不断改进，现在已经出现了很多新型的敷料如：半渗透多聚膜敷料具有吸收创面有害渗出液的作用；Promogran是一种含有胶原和氧化再生纤维素的敷料，可以通过降低创面渗液中的降解酶(中性粒细胞酶，纤溶酶，基质金属蛋白酶)改变创面的微环境；藻酸盐敷料是一种可吸收的凝胶状敷料，具有激活慢性创面巨噬细胞的作用；负压治疗装置将创面与敷料之间形成负压，它分为连续负压治疗和间歇负压治疗，负压治疗可以消除慢性水肿，降低小血管的后负荷，增加局部血流量，促进肉芽组织的形成。总之每种敷料均有一种理论支持，但往往多数缺乏有效的临床证据，但其缺点在于稳定性较差和吸收渗液能力不强。(7) Biological dressings: With the development of biotechnology, traditional dressings have been continuously improved, and many new dressings have appeared now such as: semi-permeable polymeric membrane dressings can absorb harmful exudates from wounds; Promogran is a Dressings containing collagen and oxidized regenerated cellulose can change the microenvironment of the wound by reducing degradative enzymes (neutrophil enzymes, plasmin, matrix metalloproteinases) in the wound exudate; alginate dressing is an absorbable The gel-like dressing has the function of activating macrophages in chronic wounds; the negative pressure therapy device forms a negative pressure between the wound and the dressing, which is divided into continuous negative pressure therapy and intermittent negative pressure therapy, and negative pressure therapy can eliminate chronic edema , reduce the afterload of small blood vessels, increase local blood flow, and promote the formation of granulation tissue. In short, each dressing has a theoretical support, but most often lack effective clinical evidence, but its disadvantages are poor stability and poor ability to absorb exudate.
(8)局部细胞移植：人真皮细胞培养移植是将人真皮成纤维细胞种植于生物支架进行培养，2周后可以形成真皮代替物支持表皮细胞的生长。其优点是可以释放与创面愈合有关的生长因子、细胞因子、蛋白酶、血小板释放素、CT-102，CT-102可以释放多种生长因子包括：血小板源性生长因子-BB、表皮生长因子、转化生长因子-β、成纤维细胞生长因子，这些生长因子可以促进肉芽组织形成 和上皮化，加速溃疡愈合。目前美国食品与药品管理局已经允许血小板源性生长因子-BB用于糖尿病足创面的治疗。血小板源性生长因子-BB价钱昂贵。表皮生长因子是剂量依赖型的成纤维细胞有丝分裂原。(8) Local cell transplantation: Human dermal cell culture transplantation is to plant human dermal fibroblasts on biological scaffolds for culture, and after 2 weeks, a dermal substitute can be formed to support the growth of epidermal cells. Its advantage is that it can release growth factors related to wound healing, cytokines, proteases, platelet releasing hormone, CT-102, CT-102 can release a variety of growth factors including: platelet-derived growth factor-BB, epidermal growth factor, transformation Growth factor-β, fibroblast growth factor, these growth factors can promote granulation tissue formation and epithelialization, and accelerate ulcer healing. At present, the US Food and Drug Administration has allowed platelet-derived growth factor-BB to be used in the treatment of diabetic foot wounds. Platelet-derived growth factor-BB is expensive. Epidermal growth factor is a dose-dependent fibroblast mitogen.
(9)粒细胞集落刺激因子(Granulocyte-colony stimulating factor，GCSF)主要应用于糖尿病足创面感染的患者，它可以调节中性粒细胞的增殖、分化、成熟并释放入外周血循环，其缺点是导致血液高凝状态，诱发心肌梗死、血栓形成。(9) Granulocyte-colony stimulating factor (GCSF) is mainly used in patients with diabetic foot wound infection. It can regulate the proliferation, differentiation, maturation and release of neutrophils into the peripheral blood circulation. Its disadvantage is that it leads to Blood hypercoagulation state, induced myocardial infarction, thrombosis.
(10)局部清创术：糖尿病足溃疡是糖尿病全身性疾病在局部一个最严重的表现，此时局部切开引流、清创换药非常重要，糖尿病足的清创术和外科其它疾病的清创术是有重要区别的，外科多采用“鲸吞式清创术”，而糖尿病足的清创术正好相反，多采用“蚕食式清创术”。(10) Local debridement: Diabetic foot ulcer is the most serious local manifestation of diabetic systemic diseases. At this time, local incision and drainage, debridement and dressing change are very important. There is an important difference in wound surgery. Surgery mostly uses "whale debridement", while the debridement of diabetic feet is just the opposite, and "cannibal debridement" is mostly used.
(11)外用中药膏剂：虽然糖尿病足治疗方法较多，但大多数医疗设备昂贵、治疗费用高、疗效不确切、风险大、合并症多，在临床中寻找安全有效、价格合理、风险低、合并症少的治疗方法一直困扰着临床医生。中药治疗是我国传统医学，其在糖尿病足溃疡治疗上已凸显出一定优势，但国内文献报告中药治疗糖尿病足溃疡绝大多数是临床观察，其作用机制还是引用原始的中医理论如：清热解毒、活血化瘀、祛腐生肌、消肿止痛等。(11) Traditional Chinese medicine ointment for external use: Although there are many treatment methods for diabetic foot, most of the medical equipment is expensive, the treatment cost is high, the curative effect is inaccurate, the risk is high, and there are many complications. Treatments with fewer comorbidities have long puzzled clinicians. Chinese medicine treatment is a traditional medicine in my country, and it has highlighted certain advantages in the treatment of diabetic foot ulcers. However, most of the domestic literature reports on the treatment of diabetic foot ulcers with traditional Chinese medicine are clinical observations, and the mechanism of action still refers to the original TCM theory such as: clearing away heat and detoxification, Promoting blood circulation and removing blood stasis, removing putrefaction and promoting granulation, reducing swelling and relieving pain, etc.
根据“国际糖尿病足协作组织”的评价，糖尿病足溃疡的治疗方法中有明确循证医学证据的仅有高压氧和封闭负压吸引治疗，而其它疗法包括各种局部外敷药物尚无循证医学证据支持。中药一直被用于治疗皮肤创伤包括糖尿病足溃疡，其机制为清热解毒、活血化瘀和促进伤口愈合。然而，关于这些疗法的疗效其循证证据不足，尚未得到国际和国内西医界的承认。原因在于：(1)中医药治疗糖尿病足溃疡临床研究的质量不高，其疗效的可重复性差，因而可信度受到质疑；(2)与西医相比，中医在全面评价疗效尤其是客观指标方面与西医比较的优势不明确；(3)中西医结合治疗的效果尚无严格的临床研究证据。According to the evaluation of the "International Diabetic Foot Collaboration Organization", among the treatment methods for diabetic foot ulcers, only hyperbaric oxygen and closed negative pressure suction therapy have clear evidence-based medical evidence, while other treatments, including various topical drugs, have no evidence-based medical evidence. Supported by evidence. Traditional Chinese medicine has been used to treat skin wounds including diabetic foot ulcers, and its mechanism is to clear away heat and detoxify, activate blood circulation and remove blood stasis, and promote wound healing. However, the evidence-based evidence for the efficacy of these therapies is insufficient, and has not yet been recognized by the international and domestic Western medical circles. The reasons are as follows: (1) The quality of clinical research on the treatment of diabetic foot ulcers with traditional Chinese medicine is not high, and the repeatability of its curative effect is poor, so the credibility has been questioned; In one aspect, the advantages compared with Western medicine are not clear; (3) There is no strict clinical research evidence for the effect of integrated traditional Chinese and Western medicine.
现有的用于糖尿病足外敷用的中药虽然有一定疗效，但起效慢，疗程长，安全性和疗效性差。Although the existing traditional Chinese medicines for external application on diabetic feet have a certain curative effect, they have slow onset of action, long course of treatment, poor safety and curative effect.
发明内容Contents of the invention
有鉴于此，本发明的目的在于提供一种治疗糖尿病足溃疡的外用中药制剂、制备方法及其应用，该中药组合物具有疗效显著，起效快，疗程短，安全性高，疗效好。In view of this, the object of the present invention is to provide an external Chinese medicine preparation for treating diabetic foot ulcers, a preparation method and its application. The Chinese medicine composition has significant curative effect, quick onset, short course of treatment, high safety and good curative effect.
本发明的治疗糖尿病足溃疡的外用中药制剂，中药制剂的原料按重量份包括以下组分：黄芪6～20份、全蝎1～10份、赤芍1～10份、川芎3～15份、生蒲黄3～15份、黄柏3～15份、黄连3～15份、大黄1～6份、当归1～7份、茜草1～7份、丹参3～15份、石膏25～40份、知母3～15份、冰片0.1～1份。In the external Chinese medicine preparation for treating diabetic foot ulcer of the present invention, the raw materials of the Chinese medicine preparation include the following components in parts by weight: 6-20 parts of Radix Astragali, 1-10 parts of Scorpion, 1-10 parts of Radix Paeoniae Rubra, 3-15 parts of Rhizoma Chuanxiong, 3-15 parts of raw Puhuang, 3-15 parts of Cortex Phellodendri, 3-15 parts of Coptidis Rhizome, 1-6 parts of Rhubarb, 1-7 parts of Angelica, 1-7 parts of Rubia, 3-15 parts of Salvia, 25-40 parts of Gypsum, Anemarrhena 3 to 15 parts, borneol 0.1 to 1 part.
进一步，中药制剂的原料按重量份包括以下组分：黄芪10～15份、全蝎2～6份、赤芍2～6份、川芎3～10份、生蒲黄3～10份、黄柏3～10份、黄连3～10份、大黄1～4份、当归2～6份、茜草2～6份、丹参3～10份、石膏25～36份、知母3～10份、冰片0.3～1份。Further, the raw materials of the traditional Chinese medicine preparation include the following components by weight: 10-15 parts of astragalus, 2-6 parts of scorpion, 2-6 parts of red peony, 3-10 parts of Chuanxiong, 3-10 parts of raw cattail, 3 parts of Cortex Phellodendri ～10 parts, 3～10 parts of coptis, 1～4 parts of rhubarb, 2～6 parts of angelica, 2～6 parts of madder, 3～10 parts of salvia miltiorrhiza, 25～36 parts of gypsum, 3～10 parts of anemarrhena, 0.3～ borneol 1 serving.
进一步，中药制剂的原料按重量份包括以下组分：黄芪12份、全蝎4份、赤芍4份、川芎6份、生蒲黄6份、黄柏6份、黄连6份、大黄3份、当归4份、茜草4份、丹参6份、石膏31份、知母6份、冰片0.6份。Further, the raw materials of the traditional Chinese medicine preparation include the following components by weight: 12 parts of astragalus, 4 parts of scorpion, 4 parts of red peony, 6 parts of Chuanxiong, 6 parts of raw cattail, 6 parts of Cortex Phellodendri, 6 parts of rhubarb, 3 parts of rhubarb, 4 parts of angelica, 4 parts of madder, 6 parts of salvia miltiorrhiza, 31 parts of gypsum, 6 parts of anemarrhena, and 0.6 part of borneol.
进一步，该中药组合物使用时可加入一种或多种用于改善或治疗兼证的中药；Furthermore, one or more traditional Chinese medicines for improving or treating concurrent syndromes can be added to the Chinese medicine composition when used;
进一步，该中药可加入医学能够接受的药物载体制成的制剂；Further, the traditional Chinese medicine can be added into a preparation made of a medically acceptable drug carrier;
进一步，所述中药制剂为膏剂。Further, the traditional Chinese medicine preparation is an ointment.
本发明还公开一种治疗糖尿病足溃疡的外用中药制剂的制备方法，包括以下步骤：The invention also discloses a preparation method of an externally applied Chinese medicinal preparation for treating diabetic foot ulcers, comprising the following steps:
按设定重量份将黄芪、全蝎、赤芍、川芎、生蒲黄、黄柏、黄连、大黄、当归、茜草、丹参、知母、冰片加入麻油中浸泡后煎煮至微微发苦，然后依次加入净油和白醋以及蜂蜡搅拌至融化溶解后冷却，最后加入研细的石膏，搅拌均匀，冷却成膏；Add astragalus, scorpion, red peony, Chuanxiong, raw puhuang, Phellodendron, Coptidis, rhubarb, angelica, madder, salvia, Anemarrhena, and borneol in sesame oil according to the set weight, then decoct until slightly bitter, and then Add absolute oil, white vinegar and beeswax and stir until melted and dissolved, then cool, and finally add finely ground gypsum, stir evenly, and cool to form a paste;
进一步，按设定重量份将黄芪、全蝎、赤芍、川芎、生蒲黄、黄柏、黄连、大黄、当归、茜草、丹参、知母、冰片加入麻油中浸泡3-8天；Further, adding astragalus, scorpion, red peony root, chuanxiong, raw puhuang, cortex cortex, coptis, rhubarb, angelica, madder, salvia, anemarrhena, and borneol into sesame oil for 3-8 days according to the set weight portion;
进一步，在麻油中浸泡6天。Further, soak in sesame oil for 6 days.
进一步，该外用中药制剂在制备糖尿病足溃疡的药物中的应用。Further, the application of the traditional Chinese medicine preparation for external use in the preparation of medicines for diabetic foot ulcers.
本发明的有益效果：本发明的治疗糖尿病足溃疡的外用中药制剂、制备方法及其应用，血竭为性甘咸平，具有活血散瘀止痛、收敛生肌之功能，有抗真菌的作用。乳香、没药，含树脂、挥发油，有较好的活血祛瘀、消肿镇痛、托毒生肌作用。Beneficial effects of the present invention: The external Chinese medicinal preparation for treating diabetic foot ulcers, the preparation method and its application of the present invention, the dried blood is sweet and salty in nature, has the functions of promoting blood circulation, dispelling blood stasis, relieving pain, astringing and promoting muscle growth, and has antifungal effect. Frankincense and myrrh, containing resin and volatile oil, have better effects of promoting blood circulation and removing blood stasis, reducing swelling and analgesia, detoxifying and promoting granulation.
石膏，性甘、辛、涩、寒，有收湿生肌、敛疮止血之功效，能抑制细菌，尤其对金黄色葡萄球菌、绿脓杆菌敏感，石膏还具有清热、镇痛作用，对末梢毛细血管有扩张作用，可促进局部的血液循环。黄连，清热解毒，降血糖、抗菌。丹参，活血祛瘀、凉血消痈，生新血，去恶血。黄芪与当归、川芎、丹参协同作用，促进溃破及局限作用，同时加快疮面生肌收口，也利于调节血糖。全蝎，性平，味辛，有毒，归肝经，具息风镇痉，攻毒散结，通络止痛之功效。冰片，性凉、味辛苦，归心、肺经，具通诸窍、散郁火、去翳明目、消肿止痛之功效，其香走窜，深入腠理，渗透力强，能促进药物有效成分的吸收，长时间作用于患处达到透皮作用。赤芍，味苦，性微寒，清血分实热，散瘀血留滞。生蒲黄，凉血止血，活血祛瘀，改善局部循环，促进重吸收和降低毛细血管的通透性。黄柏，黄柏有清热燥湿之力，与黄芩、黄连相似，但以除下焦之湿热为佳，可有效的促进血管新生，消除炎症水肿，改善微循环，促进伤口愈合和肉芽组织生成。大黄，具有泻热通肠、凉血解毒，逐瘀通经的功效。茜草，凉血活血，祛瘀。知母，可促进横膈、脂肪组织对葡萄糖的摄取，使横膈中糖元含量轻度增加。油和白醋作为有机溶剂，由于溶解中药中的有效成分。蜂蜡作为塑型剂，可以使制剂冷却后制成膏状.Gypsum, sweet, pungent, astringent, cold in nature, has the effect of reducing dampness and promoting muscle growth, astringing sores and stopping bleeding, and can inhibit bacteria, especially sensitive to Staphylococcus aureus and Pseudomonas aeruginosa. Capillaries have dilation effect, which can promote local blood circulation. Coptis chinensis, heat-clearing and detoxifying, hypoglycemic, antibacterial. Salvia miltiorrhiza promotes blood circulation and removes blood stasis, cools blood and eliminates carbuncle, generates new blood, and removes bad blood. Astragalus, Angelica, Chuanxiong, and Danshen act synergistically to promote ulceration and localization, and at the same time accelerate the healing of sores, and also help regulate blood sugar. Scorpio, flat in nature, pungent in taste, poisonous, returns to the liver meridian, has the effects of calming wind and spasm, attacking poison and dispelling stagnation, dredging collaterals and relieving pain. Borneolum, cool in nature, bitter in taste, Guixin and Lung meridian, has the effects of clearing all orifices, dispersing stagnant fire, removing nebula and improving eyesight, reducing swelling and relieving pain, its fragrance travels, penetrates deep into interstitial muscles, and has strong penetrating power, which can promote the effectiveness of medicine Absorption of ingredients, acting on the affected area for a long time to achieve transdermal effect. Radix Paeoniae Rubra, bitter in taste, slightly cold in nature, clears blood and divides excess heat, dispels blood stasis and stagnant blood. Raw Puhuang, cools blood to stop bleeding, promotes blood circulation and removes blood stasis, improves local circulation, promotes reabsorption and reduces capillary permeability. Cortex Phellodendron, Cortex Phellodendron has the power of clearing away heat and dampness, similar to Scutellaria baicalensis and Coptis chinensis, but it is better for removing dampness and heat in Xiajiao. It can effectively promote angiogenesis, eliminate inflammation and edema, improve microcirculation, and promote wound healing and granulation tissue formation. Rhubarb has the effects of purging heat and dredging intestines, cooling blood and detoxifying, removing blood stasis and stimulating menstruation. Rubia, cooling blood and promoting blood circulation, dispelling blood stasis. Anemarrhena can promote the uptake of glucose by the diaphragm and adipose tissue, and slightly increase the glycogen content in the diaphragm. Oil and white vinegar are used as organic solvents to dissolve the active ingredients in traditional Chinese medicine. Beeswax is used as a plasticizer, which can make the preparation into a paste after cooling.
上述组分物质间协同作用，以黄芪全蝎为君药，以赤芍川芎生蒲黄丹参为臣药，以黄柏黄连大黄为佐药，以茜草石膏知母冰片为使药，各组分合理配制，共起活血化瘀，消肿生肌，清热解毒排脓之功，从而使 瘀消络通，肢端气血畅通，肌肉营养充足，疮消肉长，有效治愈糖尿病引发的足溃疡，通过清热解毒，使全身的血管恢复弹性，由原来供血不足到趋于正常的缓慢过程，中药原料中的基因调节素和有效活性分子进入血液，直达病变部位，在平稳调节过程中，以滋肝补肾为主，修复人体受损的组织器官，逐步控制糖尿病的发病机制，调节人体神经系统，促进血液循环，起到协调与综合治疗功能，从根本上彻底逆转糖尿病发病机制，使身体达到康复；祛腐生肌、温通经脉，益气活血)减轻患肢疼痛，控制疮面感染，改善局部微循环，增强内皮细胞的双向转运机能，提高周围神经的传导速度，促进组织修复及创面的愈合。The synergistic effect of the above components, using Astragalus scorpion as the monarch drug, Chishao Chuanxiong Shengpuhuang Salvia as the minister drug, Phellodendron Coptidis rhubarb as the adjuvant drug, madder gypsum Anemarrhena borneol as the envoy drug, each component is reasonable It is formulated to promote blood circulation and remove blood stasis, reduce swelling and promote muscle growth, clear heat, detoxify and expel pus, so that blood stasis and collaterals can be unblocked, Qi and blood in the extremities can be unblocked, muscle nutrition is sufficient, sores disappear and flesh grows, and it can effectively cure foot ulcers caused by diabetes. Through heat-clearing and detoxification, the blood vessels of the whole body can be restored to elasticity, and the slow process from the original insufficient blood supply to normal, the gene modulators and effective active molecules in the raw materials of traditional Chinese medicine enter the blood, directly reach the lesion, and nourish the liver during the smooth adjustment process. Mainly invigorate the kidney, repair the damaged tissues and organs of the human body, gradually control the pathogenesis of diabetes, regulate the human nervous system, promote blood circulation, play a coordination and comprehensive treatment function, fundamentally reverse the pathogenesis of diabetes, and make the body recover; Relieves putrefaction and promotes granulation, warms meridians, nourishes qi and activates blood) relieves pain in affected limbs, controls sore surface infection, improves local microcirculation, enhances the bidirectional transport function of endothelial cells, increases the conduction velocity of peripheral nerves, and promotes tissue repair and wound healing.
具体实施方式detailed description
本实施例的治疗糖尿病足溃疡的外用中药制剂，中药制剂的原料按重量份包括以下组分：黄芪6～20份、全蝎1～10份、赤芍1～10份、川芎3～15份、生蒲黄3～15份、黄柏3～15份、黄连3～15份、大黄1～6份、当归1～7份、茜草1～7份、丹参3～15份、石膏25～40份、知母3～15份、冰片0.1～1份。The external Chinese medicine preparation for the treatment of diabetic foot ulcer in this embodiment, the raw materials of the Chinese medicine preparation include the following components by weight: 6-20 parts of Radix Astragali, 1-10 parts of Scorpion, 1-10 parts of Radix Paeoniae Rubra, 3-15 parts of Rhizoma Chuanxiong , 3-15 parts of raw cattail, 3-15 parts of cortex, 3-15 parts of rhubarb, 1-6 parts of rhubarb, 1-7 parts of angelica, 1-7 parts of madder, 3-15 parts of salvia miltiorrhiza, 25-40 parts of gypsum , Anemarrhena 3-15 parts, borneol 0.1-1 part.
本实施例中，中药制剂的原料按重量份包括以下组分：黄芪10～15份、全蝎2～6份、赤芍2～6份、川芎3～10份、生蒲黄3～10份、黄柏3～10份、黄连3～10份、大黄1～4份、当归2～6份、茜草2～6份、丹参3～10份、石膏25～36份、知母3～10份、冰片0.3～1份。In this example, the raw materials of the traditional Chinese medicine preparation include the following components by weight: 10-15 parts of Radix Astragali, 2-6 parts of Scorpion, 2-6 parts of Radix Paeoniae Rubra, 3-10 parts of Rhizoma Chuanxiong, and 3-10 parts of Raw Puhuang , Phellodendron 3-10 parts, Coptidis 3-10 parts, Rhubarb 1-4 parts, Angelica 2-6 parts, Rubia 2-6 parts, Salvia miltiorrhiza 3-10 parts, Gypsum 25-36 parts, Anemarrhena 3-10 parts, 0.3-1 portion of borneol.
本实施例中，中药制剂的原料按重量份包括以下组分：黄芪12份、全蝎4份、赤芍4份、川芎6份、生蒲黄6份、黄柏6份、黄连6份、大黄3份、当归4份、茜草4份、丹参6份、石膏31份、知母6份、冰片0.6份。In this example, the raw materials of the traditional Chinese medicine preparation include the following components by weight: 12 parts of astragalus, 4 parts of scorpion, 4 parts of red peony, 6 parts of Chuanxiong, 6 parts of raw cattail, 6 parts of Cortex Phellodendri, 6 parts of rhubarb rhubarb, 3 parts, 4 parts of angelica, 4 parts of madder, 6 parts of salvia miltiorrhiza, 31 parts of gypsum, 6 parts of anemarrhena, and 0.6 part of borneol.
本实施例中，该中药组合物使用时可加入一种或多种用于改善或治疗兼证的中药。In this embodiment, when the traditional Chinese medicine composition is used, one or more traditional Chinese medicines for improving or treating concurrent syndromes can be added.
本实施例中，该中药可加入医学能够接受的药物载体制成的制剂。In this embodiment, the traditional Chinese medicine can be added into a preparation made of a medically acceptable drug carrier.
本实施例中，所述中药制剂为膏剂。In this embodiment, the traditional Chinese medicine preparation is ointment.
本实施例的治疗糖尿病足溃疡的外用中药制剂的制备方法，包括以下步骤：The preparation method of the external Chinese medicine preparation for the treatment of diabetic foot ulcer of the present embodiment comprises the following steps:
按设定重量份将黄芪、全蝎、赤芍、川芎、生蒲黄、黄柏、黄连、大黄、当归、茜草、丹参、知母、冰片加入麻油中浸泡后煎煮至微微发苦，然后依次加入净油和白醋以及蜂蜡搅拌至融化溶解后冷却，最后加入研细的石膏，搅拌均匀，冷却成膏。Add astragalus, scorpion, red peony, Chuanxiong, raw puhuang, Phellodendron, Coptidis, rhubarb, angelica, madder, salvia, Anemarrhena, and borneol in sesame oil according to the set weight, then decoct until slightly bitter, and then Add absolute oil, white vinegar and beeswax and stir until melted and dissolved, then cool, and finally add finely ground gypsum, stir evenly, and cool to form a paste.
本实施例中，按设定重量份将黄芪、全蝎、赤芍、川芎、生蒲黄、黄柏、黄连、大黄、当归、茜草、丹参、知母、冰片加入麻油中浸泡3-8天。In this embodiment, astragalus, scorpion, red peony root, chuanxiong, raw puhuang, cortex cortex, rhubarb rhubarb, rhubarb, angelica, madder, salvia miltiorrhiza, Anemarrhena anemarrhena, and borneol are added to the sesame oil and soaked for 3-8 days according to the set weight portion.
本实施例中，在麻油中浸泡6天。In the present embodiment, soak in sesame oil for 6 days.
本实施例中，该外用中药制剂在制备糖尿病足溃疡的药物中的应用。In this example, the application of the externally used traditional Chinese medicine preparation in the preparation of medicines for diabetic foot ulcers.
下面通过具体实施例对本发明的中药组合物做进一步的阐述：Chinese medicine composition of the present invention is further elaborated below by specific embodiment:
实施例一Embodiment one
本实施例的治疗糖尿病足溃疡的外用中药制剂，中药制剂的原料按重量份包括以下组分：黄芪12份、全蝎4份、赤芍4份、川芎6份、生蒲黄6份、黄柏6份、黄连6份、大黄3份、当归4份、茜草4份、丹参6份、石膏31份、知母6份、冰片0.6份。The external Chinese medicine preparation for the treatment of diabetic foot ulcer of the present embodiment, the raw material of Chinese medicine preparation comprises the following components by weight: 12 parts of Radix Astragali, 4 parts of Scorpion, 4 parts of Radix Paeoniae Rubra, 6 parts of Rhizoma Chuanxiong, 6 parts of Raw Puhuang, Phellodendron Phellodendri 6 parts, 6 parts of coptis, 3 parts of rhubarb, 4 parts of angelica, 4 parts of madder, 6 parts of salvia miltiorrhiza, 31 parts of gypsum, 6 parts of anemarrhena, and 0.6 part of borneol.
将黄芪、全蝎、赤芍、川芎、生蒲黄、黄柏、黄连、大黄、当归、茜草、丹参、知母、冰片加入麻油中浸泡6天后煎煮至微微发苦，然后依次加入净油和白醋以及蜂蜡搅拌至融化溶解后冷却，最后加入研细的石膏，搅拌均匀，冷却成膏。Add astragalus, scorpion, red peony root, Chuanxiong, raw puhuang, Phellodendron cortex, Coptis rhizome, rhubarb, angelica, madder, salvia miltiorrhiza, Anemarrhena anemarrhena, and borneol in sesame oil for 6 days, then decoct until slightly bitter, then add the absolute oil and Stir the white vinegar and beeswax until they melt and dissolve, then cool, then add finely ground gypsum, stir evenly, and cool to form a paste.
实施例二Embodiment two
本实施例的治疗糖尿病足溃疡的外用中药制剂，中药制剂的原料按重量份包括以下组分：黄芪6份、全蝎1份、赤芍1份、川芎3份、生蒲黄3份、黄柏3份、黄连3份、大黄1份、当归1份、茜草1份、丹参3份、石膏25份、知母3份、冰片0.1份。The external Chinese medicine preparation for the treatment of diabetic foot ulcer in this embodiment, the raw materials of the Chinese medicine preparation include the following components by weight: 6 parts of Astragalus, 1 part of Scorpion, 1 part of Radix Paeoniae Rubra, 3 parts of Rhizoma Chuanxiong, 3 parts of Raw Puhuang, Phellodendron Phellodendri 3 parts, 3 parts of coptis, 1 part of rhubarb, 1 part of angelica, 1 part of madder, 3 parts of salvia miltiorrhiza, 25 parts of gypsum, 3 parts of anemarrhena, 0.1 part of borneol.
将黄芪、全蝎、赤芍、川芎、生蒲黄、黄柏、黄连、大黄、当归、茜草、丹参、知母、冰片加入麻油中浸泡3天后煎煮至微微发苦，然后依次加入净油和白醋以及蜂蜡搅拌至融化溶解后冷却，最后加入研细的石膏，搅拌均匀，冷 却成膏。Add astragalus, scorpion, red peony root, Chuanxiong, raw puhuang, cortex cortex, coptis, rhubarb, angelica, madder, salvia miltiorrhiza, Anemarrhena anemarrhena, and borneol into sesame oil, soak for 3 days, decoct until slightly bitter, then add absolute oil and Stir the white vinegar and beeswax until they melt and dissolve, then cool, then add finely ground gypsum, stir evenly, and cool to form a paste.
实施例三Embodiment Three
本实施例的治疗糖尿病足溃疡的外用中药制剂，中药制剂的原料按重量份包括以下组分：黄芪20份、全蝎10份、赤芍10份、川芎15份、生蒲黄15份、黄柏15份、黄连15份、大黄6份、当归7份、茜草7份、丹参15份、石膏40份、知母15份、冰片1份。The external Chinese medicine preparation for the treatment of diabetic foot ulcer of the present embodiment, the raw material of Chinese medicine preparation comprises the following components by weight: 20 parts of Radix Astragali, 10 parts of Scorpion, 10 parts of Radix Paeoniae Rubra, 15 parts of Rhizoma Chuanxiong, 15 parts of Raw Puhuang, Phellodendron Phellodendri 15 parts, 15 parts of coptis, 6 parts of rhubarb, 7 parts of angelica, 7 parts of madder, 15 parts of salvia miltiorrhiza, 40 parts of gypsum, 15 parts of anemarrhena, and 1 part of borneol.
将黄芪、全蝎、赤芍、川芎、生蒲黄、黄柏、黄连、大黄、当归、茜草、丹参、知母、冰片加入麻油中浸泡8天后煎煮至微微发苦，然后依次加入净油和白醋以及蜂蜡搅拌至融化溶解后冷却，最后加入研细的石膏，搅拌均匀，冷却成膏。Add astragalus, scorpion, red peony root, Chuanxiong, raw puhuang, Phellodendron cork, Coptis rhizome, rhubarb, angelica, madder, Salvia miltiorrhiza, Anemarrhena anemarrhena, and borneol in sesame oil for 8 days, then decoct until slightly bitter, then add the absolute oil and Stir the white vinegar and beeswax until they melt and dissolve, then cool, then add finely ground gypsum, stir evenly, and cool to form a paste.
实施例四Embodiment four
本实施例的治疗糖尿病足溃疡的外用中药制剂，中药制剂的原料按重量份包括以下组分：黄芪10份、全蝎2份、赤芍2份、川芎3份、生蒲黄3份、黄柏3份、黄连3份、大黄1份、当归2份、茜草2份、丹参3份、石膏25份、知母3份、冰片0.3份。The external Chinese medicinal preparation for the treatment of diabetic foot ulcer in this embodiment, the raw materials of the Chinese medicinal preparation include the following components by weight: 10 parts of Radix Astragali, 2 parts of Scorpion, 2 parts of Radix Paeoniae Rubra, 3 parts of Rhizoma Chuanxiong, 3 parts of Raw Puhuang, Phellodendron Phellodendri 3 parts, 3 parts of coptis, 1 part of rhubarb, 2 parts of angelica, 2 parts of madder, 3 parts of salvia miltiorrhiza, 25 parts of gypsum, 3 parts of Anemarrhena, and 0.3 part of borneol.
将黄芪、全蝎、赤芍、川芎、生蒲黄、黄柏、黄连、大黄、当归、茜草、丹参、知母、冰片加入麻油中浸泡4天后煎煮至微微发苦，然后依次加入净油和白醋以及蜂蜡搅拌至融化溶解后冷却，最后加入研细的石膏，搅拌均匀，冷却成膏。Add astragalus, scorpion, red peony root, Chuanxiong, raw puhuang, cortex cortex, coptis, rhubarb, angelica, madder, salvia miltiorrhiza, Anemarrhena anemarrhena, and borneol into sesame oil, soak for 4 days, decoct until slightly bitter, then add absolute oil and Stir the white vinegar and beeswax until they melt and dissolve, then cool, then add finely ground gypsum, stir evenly, and cool to form a paste.
实施例五Embodiment five
本实施例的治疗糖尿病足溃疡的外用中药制剂，中药制剂的原料按重量份包括以下组分：黄芪15份、全蝎6份、赤芍6份、川芎10份、生蒲黄10份、黄柏10份、黄连10份、大黄4份、当归6份、茜草6份、丹参10份、石膏36份、知母10份、冰片1份。The external Chinese medicine preparation for the treatment of diabetic foot ulcer of the present embodiment, the raw material of Chinese medicine preparation comprises the following components by weight: 15 parts of Radix Astragali, 6 parts of Scorpion, 6 parts of Radix Paeoniae Rubra, 10 parts of Rhizoma Chuanxiong, 10 parts of Raw Puhuang, Phellodendron Phellodendri 10 parts, 10 parts of coptis, 4 parts of rhubarb, 6 parts of angelica, 6 parts of madder, 10 parts of salvia miltiorrhiza, 36 parts of gypsum, 10 parts of anemarrhena, and 1 part of borneol.
将黄芪、全蝎、赤芍、川芎、生蒲黄、黄柏、黄连、大黄、当归、茜草、丹参、知母、冰片加入麻油中浸泡7天后煎煮至微微发苦，然后依次加入净油和白醋以及蜂蜡搅拌至融化溶解后冷却，最后加入研细的石膏，搅拌均匀，冷 却成膏。Add astragalus, scorpion, red peony root, Chuanxiong, raw puhuang, cortex cortex, coptis, rhubarb, angelica, madder, salvia, anemarrhena, and borneol in sesame oil, soak for 7 days, decoct until slightly bitter, then add the absolute oil and Stir the white vinegar and beeswax until they melt and dissolve, then cool, then add finely ground gypsum, stir evenly, and cool to form a paste.
实施例六Embodiment six
中药制剂的原料按重量份包括以下组分：黄芪18份、全蝎10份、赤芍5份、川芎3份、生蒲黄15份、黄柏8份、黄连8份、大黄6份、当归1份、茜草3份、丹参12份、石膏25份、知母15份、冰片0.8份。The raw materials of the traditional Chinese medicine preparation include the following components by weight: 18 parts of astragalus, 10 parts of scorpion, 5 parts of red peony, 3 parts of Chuanxiong, 15 parts of raw cattail, 8 parts of Cortex Phellodendri, 8 parts of Coptis chinensis, 6 parts of rhubarb, 1 part of angelica 3 parts of madder, 12 parts of salvia miltiorrhiza, 25 parts of gypsum, 15 parts of anemarrhena, 0.8 part of borneol.
该实施例的制备方法同实施例一。The preparation method of this embodiment is the same as embodiment one.
实施例七Embodiment seven
中药制剂的原料按重量份包括以下组分：黄芪10份、全蝎5份、赤芍3份、川芎5份、生蒲黄3份、黄柏10份、黄连5份、大黄1份、当归6份、茜草6份、丹参8份、石膏28份、知母10份、冰片0.3份。The raw materials of the traditional Chinese medicine preparation include the following components by weight: 10 parts of astragalus, 5 parts of scorpion, 3 parts of red peony root, 5 parts of Chuanxiong, 3 parts of raw cattail, 10 parts of Cortex Phellodendri, 5 parts of Coptis chinensis, 1 part of rhubarb, 6 parts of angelica 6 parts of madder, 8 parts of salvia miltiorrhiza, 28 parts of gypsum, 10 parts of anemarrhena, 0.3 parts of borneol.
该实施例的制备方法同实施例二。The preparation method of this embodiment is the same as embodiment two.
上述实施例的治疗糖尿病足溃疡的外用中药制剂，不但可以制成膏状物，还可加入医学能够接受的载体制成制剂，比如通过药物载体制成制成液体洗剂，对患处进行清洗，或者是粉末散剂敷于创口处，当然优选为软膏剂型，这些都能采用现有的工业化生产过程均能实现。应用时，在不影响本中药组合物效果的情况下，可加入一种或多种用于改善或治疗兼证的中药，例如：脾肾阳虚、水湿內停导致的水肿，白术、茯苓、泽泻、车前子通利小便；生姜温散水寒之气；牛膝引药下行，强壮腰膝；若心悸、唇绀，脉虚数或结代，为水邪上逆，淤血内停，益重用附子，肾不纳气，重用人参、蛤蚧、五味子、山萸肉、牡蛎、龙骨，以防喘脱；眩晕：天马、钩藤、石决明平肝潜阳，黄芩、栀子清肝火，牛膝、杜仲、桑寄生补肝肾，夜交藤，伏神养心安神。阴虚较甚者加生地黄、玄参、茯神、夜交藤，加远志、炒枣仁、炙百合以养心安神；若见眩晕欲仆，呕恶，手足麻木或震颤音，有阳动化风之势，加珍珠母、生龙骨、生牡蛎、羚羊角等镇肝息风之品。淋证：方中车前子、萹蓄、瞿麦、滑石通淋利湿。加入甘草可以缓急止痛。The external Chinese medicine preparation for treating diabetic foot ulcer of the above embodiment can not only be made into a paste, but also can be made into a preparation by adding a medically acceptable carrier, such as a liquid lotion made from a drug carrier, to clean the affected part, Or the powder powder is applied to the wound, and of course it is preferably an ointment formulation, which can be realized by existing industrial production processes. During application, without affecting the effect of this traditional Chinese medicine composition, one or more traditional Chinese medicines for improving or treating concurrent syndromes can be added, such as: edema caused by deficiency of spleen and kidney yang, internal stagnation of water dampness, Atractylodes macrocephala, Poria cocos , Alisma, and plantain seeds can facilitate urination; ginger warms and dispels the cold air in water; Achyranthes bidentata is used to strengthen the waist and knees; Use aconite for benefit, if the kidney does not receive qi, use ginseng, gecko, schisandra, cornus, oyster, and keel to prevent asthma; dizziness: Tianma, Uncaria, and Cassia to calm the liver and subdue yang, and scutellaria baicalensis and gardenia to clear liver fire , Achyranthes bidentata, Eucommia ulmoides, Sangjisheng invigorate the liver and kidney, and the vine of night, nourish the heart and calm the nerves. For severe yin deficiency, add rehmannia glutinosa, Scrophulariae scrophulariae, Fushen, Yejiao vine, polygala, fried jujube kernels, and roasted lily to nourish the heart and soothe the nerves; if you experience dizziness, nausea, numbness or tremors in your hands and feet, there is yang To activate the wind, add mother of pearl, raw keel, raw oyster, antelope horn and other products to calm the liver and calm the wind. Drenching Syndrome: In the prescription, psyllium seed, scorpion, fenugreek, and talc can relieve stranguria and dampness. Adding licorice can relieve pain.
临床实验例Clinical Trial Example
对比本发明实施例1中药膏剂加标准外科治疗和单纯标准外科治疗之间对慢性糖尿病足溃疡的有效性和安全性进行评价。Evaluate the effectiveness and safety of Chinese medicine ointment plus standard surgical treatment and standard surgical treatment alone on chronic diabetic foot ulcer in Example 1 of the present invention.
纳入标准：(1)糖尿病患者(1型或2型)；(2)年龄18岁至85岁；(3)糖尿病足溃疡的分级为Wagner分级1-3级；(4)糖尿病病程5年以上，足溃疡在12周以上；(5)能够并愿意知情同意；(6)患者0.7≤ABI≤1.2，和/或患足多普勒波形为二相波或三相波。Inclusion criteria: (1) diabetic patients (type 1 or type 2); (2) aged 18 to 85 years old; (3) diabetic foot ulcers graded as Wagner grade 1-3; (4) diabetic disease duration of more than 5 years , foot ulcers for more than 12 weeks; (5) able and willing to give informed consent; (6) patients with 0.7≤ABI≤1.2, and/or the Doppler waveform of the affected foot is biphasic or triphasic.
排除标准：(1)单纯缺血性溃疡；(2)溃疡在踝关节以上，或在踝关节以下，但合并严重的、威胁生命的感染需要截肢者；(3)妊娠、准备妊娠或哺乳期妇女；(4)严重心肾功能衰竭，或患有精神疾病不能参加治疗和随访者；(5)合并威胁生命的严重原发性疾病如恶性肿瘤、血液系统疾病、HIV阳性者；(6)合并有严重的营养不良或有出血性疾病史者；(7)对糖足愈疡膏中某种成分过敏者。Exclusion criteria: (1) Simple ischemic ulcers; (2) Ulcers above or below the ankle, but combined with serious, life-threatening infections requiring amputation; (3) Pregnant, planning to become pregnant or breastfeeding Women; (4) Severe heart and kidney failure, or those who are mentally ill and unable to participate in treatment and follow-up; (5) Combined with life-threatening serious primary diseases such as malignant tumors, blood system diseases, HIV positive; (6) Those with severe malnutrition or a history of bleeding disorders; (7) those who are allergic to certain ingredients in Tangzuyuyang Ointment.
临床随访的观察指标包括：溃疡(溃疡状况、面积和/或Wagner’s分级)、实验室检测指标(血糖、血常规、尿常规、肝功能、肾功能)和不良事件。实验室检测规定在第0天、第4周、第12周、第24周，允许使用降糖药物、降压药物和调脂药物，但是其它外用药物禁止使用，包括外用抗生素。只要合并深部感染或全身感染症状如发热、血白细胞升高等时允许使用抗生素。The observation indicators of clinical follow-up include: ulcer (ulcer status, area and/or Wagner's grade), laboratory test indicators (blood sugar, blood routine, urine routine, liver function, kidney function) and adverse events. Laboratory tests stipulated that on day 0, week 4, week 12, and week 24, hypoglycemic drugs, antihypertensive drugs, and lipid-lowering drugs were allowed, but other topical drugs, including topical antibiotics, were prohibited. Antibiotics are allowed as long as there are symptoms of deep infection or systemic infection such as fever and elevated white blood cells.
疗效评定:主要有效终点事件：溃疡的完全愈合和溃疡的改善。溃疡的完全愈合定义为溃疡面100％由上皮细胞覆盖，无渗出，也不需要换药治疗。溃疡的改善定义为溃疡Wagner分级降低1个级别以上(包括1个级别)和/或溃疡面积缩小50％以上(包括50％)。次要有效终点事件：溃疡改善的组成成分和愈合时间定义为次要终点事件。Efficacy evaluation: The main effective endpoint events: complete healing of ulcers and improvement of ulcers. Complete ulcer healing is defined as 100% of the ulcer surface covered by epithelial cells, no exudation, and no need for dressing changes. The improvement of ulcer is defined as the reduction of Wagner grade of ulcer by more than 1 grade (including 1 grade) and/or the reduction of ulcer area by more than 50% (including 50%). Secondary effective endpoints: The components of ulcer improvement and healing time were defined as secondary endpoints.
退出机制：(1)患者拒绝进一步采用该方式进行治疗；(2)患者糖尿病足溃疡恶化，无法继续保守治疗，需要外科截肢(趾)等干预者；(3)患者一般情况恶化，出现脓毒血症、死亡等严重并发症等。Withdrawal mechanism: (1) the patient refuses further treatment with this method; (2) the patient's diabetic foot ulcer worsens, unable to continue conservative treatment, and requires intervention such as surgical amputation (toe); (3) the patient's general condition deteriorates and sepsis occurs Serious complications such as anemia and death.
治疗方法：所有纳入的患者均无洗脱期，纳入后的患者立即按照1:1的比例分配至不同治疗组分别接受标准外科治疗(对照组)和标准外科治疗加治疗糖尿病足溃疡的外用中药制剂治疗(治疗组)。治疗组将治疗糖尿病足溃疡的外用 中药制剂涂抹于溃疡表面，与溃疡深度同高。根据实际需要或专家组的建议决定换药时间，一般间隔1到3天，直至溃疡完全愈合(24周观察期愈合的溃疡)或满24周观察期(24周观察期内未愈合的溃疡)。对于溃疡愈合的患者，仍然要继续随访观察直至满24周观察期。Treatment method: There is no wash-out period for all included patients. Immediately after enrollment, patients are assigned to different treatment groups in a 1:1 ratio to receive standard surgical treatment (control group) and standard surgical treatment plus external Chinese medicine for diabetic foot ulcers. Preparation treatment (treatment group). In the treatment group, the external Chinese medicinal preparation for treating diabetic foot ulcers was applied to the surface of the ulcer, at the same height as the depth of the ulcer. Decide when to change the dressing according to actual needs or the recommendations of the expert group, generally at intervals of 1 to 3 days, until the ulcer is completely healed (unhealed ulcer during the 24-week observation period) or the 24-week observation period (unhealed ulcer during the 24-week observation period) . For patients with healed ulcers, follow-up observation is still required until the 24-week observation period is completed.
本研究58名患者按照随机方案分别被分配至治疗组(29例)或对照组(29例)，治疗24周后，溃疡改善率(治疗组vs.对照组)在第4周时为(37.5％vs.29.2％；P＝0.760)，第12周为(79.2％vs.41.7％；P＝0.017)和第24周(91.7％vs.50％；P＝0.003)。治疗组均显效于对照组，提示本发明的治疗糖尿病足溃疡的外用中药制剂治疗组在溃疡改善方面显著优于标准外科治疗组。本项目临床试验证实本发明的治疗糖尿病足溃疡的外用中药制剂对慢性糖尿病足溃疡潜在的疗效和安全性，提示治疗糖尿病足溃疡的外用中药制剂能够加速慢性糖尿病足溃疡的愈合速率。In this study, 58 patients were assigned to the treatment group (29 cases) or the control group (29 cases) according to the random scheme. After 24 weeks of treatment, the ulcer improvement rate (treatment group vs. control group) was (37.5 % vs. 29.2%; P=0.760), week 12 (79.2% vs. 41.7%; P=0.017) and week 24 (91.7% vs. 50%; P=0.003). The treatment groups were all significantly more effective than the control group, suggesting that the external Chinese medicine preparation treatment group for treating diabetic foot ulcers of the present invention was significantly better than the standard surgical treatment group in terms of ulcer improvement. The clinical trials of this project confirmed the potential efficacy and safety of the external Chinese medicine preparation for treating diabetic foot ulcers of the present invention on chronic diabetic foot ulcers, suggesting that the external Chinese medicine preparations for treating diabetic foot ulcers can accelerate the healing rate of chronic diabetic foot ulcers.
安全性:与西药相比，中药的毒副作用和不良反应相对较少，外用中药较口服或者静脉不良作用更少。本发明的中药的鉴定、药品的制备和质量标准检测均由贵州省中国科学院天然产物化学重点实验室的专家指导完成。并采用高效液相色谱法(HPLC)检测其中大黄素和大黄酚的浓度。每批样品均必须进行卫生学检测，只要达到无菌要求的样品方可允许进入临床使用。在本研究6个月的随访期内，患者未出现血液系统疾病、肝功能损害、肾功能损害以及皮肤过敏等副反应。虽然有创面疼痛事件的发生(各2例)，但是其发生率在两治疗组间无显著性差异。这说明本发明的中药组合物在治疗糖尿病足溃疡方面具有可靠的安全性。Safety: Compared with Western medicine, Chinese medicine has relatively less toxic and side effects and adverse reactions, and Chinese medicine for external use has fewer adverse effects than oral or intravenous administration. The identification of the traditional Chinese medicine of the present invention, the preparation of the medicine and the quality standard detection are all completed under the guidance of experts from the Key Laboratory of Natural Product Chemistry of the Chinese Academy of Sciences in Guizhou Province. And the concentration of emodin and chrysophanol in it was detected by high performance liquid chromatography (HPLC). Each batch of samples must be tested for hygiene, and only those that meet the sterility requirements are allowed to enter clinical use. During the 6-month follow-up period of this study, no side effects such as hematological diseases, liver function damage, renal function damage and skin allergies occurred in the patients. Although there were wound pain events (2 cases in each group), there was no significant difference in the incidence between the two treatment groups. This shows that the traditional Chinese medicine composition of the present invention has reliable safety in the treatment of diabetic foot ulcer.
本发明的中药组合物的质量标准研究：为了控制本品的内在质量，确保药效，在贵州省中国科学院天然产物化学重点实验室采用了薄层色谱(TLC)法对黄连、大黄等所含成分进行鉴别实验，并采用高效液相色谱(HPLC)法测定了膏剂中的有效成分大黄素、大黄酚的含量。Quality standard research of the Chinese medicine composition of the present invention: In order to control the intrinsic quality of this product, ensure drug effect, adopted thin-layer chromatography (TLC) method to be contained in coptis rhizome, rhubarb etc. Composition identification experiments were carried out, and the contents of the active ingredients emodin and chrysophanol in the ointment were determined by high performance liquid chromatography (HPLC).
本发明的中药组合物卫生学检测方法:观察所种植的12个培养皿中有无细菌生长。从试验开始到结束所有进入临床使用的药品经按照以上方法的卫生学 检测后均未发现有细菌生长。Hygienic detection method of Chinese medicine composition of the present invention: observe whether there is bacterial growth in 12 petri dishes planted. From the beginning to the end of the test, no bacterial growth was found after the hygienic test according to the above method for all the drugs entering clinical use.
本研究首次采用循证医学系统评价了中医药治疗糖尿病足溃疡的安全性、疗效性和药物种类等。基于系统评价结果研制了一种糖尿病足溃疡外用中药复方制剂。通过临床试验证实了糖足愈疡中药组合物对慢性糖尿病足溃疡潜在的疗效和安全性，提示糖足愈疡中药组合物能够加速慢性糖尿病足溃疡的愈合速率。对糖尿病足溃疡的治疗提供了新的方法和选择，为减轻糖尿病足患者的病痛及减轻医疗负担作出了开创性的工作。This study is the first to use evidence-based medicine to systematically evaluate the safety, efficacy and drug types of traditional Chinese medicine in the treatment of diabetic foot ulcers. Based on the results of systematic review, a compound preparation of traditional Chinese medicine for external use in diabetic foot ulcers was developed. Clinical trials have confirmed the potential efficacy and safety of the Tangzuyuyang traditional Chinese medicine composition on chronic diabetic foot ulcers, suggesting that the Tangzuyuyang traditional Chinese medicine composition can accelerate the healing rate of chronic diabetic foot ulcers. The treatment of diabetic foot ulcers provides new methods and options, and has made pioneering work for alleviating the pain and medical burden of diabetic foot patients.
典型病例Typical cases
1.张XX，女，68岁。主诉患糖尿病20年，左脚趾先麻木，后痛，发紫约半年之久，脚趾发黑破溃4天，吃止疼药和消炎药效果不佳。查体：左足后两脚趾皮肤均破溃。实验室检查：空腹血糖9.2mmol/L。患者要求外用本发明中药，5左右天基本缓解疼痛、麻木；14天后伤口愈合、结痂，并指导患者注意饮食、按时降糖治疗，临床症状完全消失，半年后随访未再复发。1. Zhang XX, female, 68 years old. Suffering from diabetes for 20 years, the left toe was numb first, then painful, purple for about half a year, black and ulcerated for 4 days, and the effect of painkillers and anti-inflammatory drugs was not good. Physical examination: the skin of the rear two toes of the left foot was ulcerated. Laboratory tests: fasting blood glucose 9.2mmol/L. The patient requires external application of the traditional Chinese medicine of the present invention, and the pain and numbness are basically relieved in about 5 days; after 14 days, the wound heals and scabs, and the patient is instructed to pay attention to diet and treat blood sugar on time.
2.李XX，男，68岁。主诉患糖尿病25年，常服二甲双胍治疗糖尿病，仍出现脚趾痛2个月，皮肤发紫10余天，加重3天、抗菌素治疗10天，效果不佳。查体：双足脚趾皮肤发紫、左侧2脚趾皮肤变黑。实验室检查：空腹血糖8.7mmol/L。患者要求外用本发明中药10天，脚趾皮肤变红润，并指导饮食，继续降糖治疗，临床症状完全消失，未再复发。2. Li XX, male, 68 years old. Suffering from diabetes for 25 years, taking metformin to treat diabetes, he still has toe pain for 2 months, skin purple for more than 10 days, aggravated for 3 days, antibiotics for 10 days, the effect is not good. Physical examination: the skin of the toes of both feet turned purple, and the skin of the left 2 toes turned black. Laboratory tests: fasting blood glucose 8.7mmol/L. The patient requires external use of the present invention's Chinese medicine for 10 days, the skin of the toes becomes rosy, and the diet is instructed, and the hypoglycemic treatment is continued, and the clinical symptoms disappear completely without recurrence.
3.孙××，男，70岁，糖尿病史20年，空服血糖14mnol/l,尿检++，左下肢溃疡坏疽3年，溃疡周围麻木，感觉减退，有医院建议截肢，经口服降糖药物，血糖控制在6.5mnol/l左右，后采用本发明中药，局部清创后将本发明膏剂涂敷于创面及灌入窦道，一日换药一次，创面脓性分泌物明显减少，14天后创面开始结痂，30天后窦道闭合，创面愈合。3. Sun ××, male, 70 years old, with a history of diabetes for 20 years, blood sugar 14mnol/l in flight, urine test ++, ulcer and gangrene in left lower limb for 3 years, numbness around the ulcer, decreased sensation, some hospitals suggested amputation, oral hypoglycemia Medicine, blood sugar is controlled at about 6.5mnol/l, adopts the traditional Chinese medicine of the present invention afterwards, after local debridement, the ointment of the present invention is coated on the wound and poured into the sinus, and the dressing is changed once a day, and the purulent secretion of the wound is obviously reduced, 14 Two days later, the wound surface began to scab, and after 30 days, the sinus tract was closed and the wound surface healed.
最后说明的是，以上实施例仅用以说明本发明的技术方案而非限制，尽管参照较佳实施例对本发明进行了详细说明，本领域的普通技术人员应当理解，可以对本发明的技术方案进行修改或者等同替换，而不脱离本发明技术方案的宗旨和范围，其均应涵盖在本发明的权利要求范围当中。Finally, it is noted that the above embodiments are only used to illustrate the technical solutions of the present invention without limitation. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be carried out Modifications or equivalent replacements without departing from the spirit and scope of the technical solution of the present invention shall be covered by the claims of the present invention.
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410292780.1ACN104161961B (en) | 2014-06-25 | 2014-06-25 | The Chinese medicine for outer use for the treatment of diabetic foot ulcer, preparation method and applications |
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410292780.1ACN104161961B (en) | 2014-06-25 | 2014-06-25 | The Chinese medicine for outer use for the treatment of diabetic foot ulcer, preparation method and applications |
| Publication Number | Publication Date |
|---|---|
| CN104161961A CN104161961A (en) | 2014-11-26 |
| CN104161961Btrue CN104161961B (en) | 2017-04-05 |
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410292780.1AExpired - Fee RelatedCN104161961B (en) | 2014-06-25 | 2014-06-25 | The Chinese medicine for outer use for the treatment of diabetic foot ulcer, preparation method and applications |
| Country | Link |
|---|---|
| CN (1) | CN104161961B (en) |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110179936A (en)* | 2018-06-11 | 2019-08-30 | 上海仲圣生物科技有限公司 | A kind of external medicine composition and preparation method thereof for treating diabetes |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101987152A (en)* | 2010-08-24 | 2011-03-23 | 赵建勇 | Ointment for treating diabetes foot ulcer |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009137074A1 (en)* | 2008-05-06 | 2009-11-12 | Indigene Pharmaceuticals, Inc. | Compositions and methods for treating diabetic ulcers |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101987152A (en)* | 2010-08-24 | 2011-03-23 | 赵建勇 | Ointment for treating diabetes foot ulcer |
| Title |
|---|
| 石膏知母汤降糖的临床研究;李晨等;《医学理论与实践》;20121231;第25卷(第7期);第790-191页，尤其是第790页右栏第7段、第791页右栏第3段* |
| 祛瘀生新煎配合按摩治疗糖尿病足部溃疡34例;金远林等;《中国中西医结合外科杂志》;20060630;第12卷(第3期);第241-242页，尤其是第241页左栏第3段、第242页右栏第1段* |
| Publication number | Publication date |
|---|---|
| CN104161961A (en) | 2014-11-26 |
| Publication | Publication Date | Title |
|---|---|---|
| CN103893458B (en) | Diabetic foot ulcer external medicine composition, preparation method and applications | |
| CN105833279B (en) | External medicinal composition for treating various wounds of skin and preparation method thereof | |
| CN106728727A (en) | It is a kind of to treat ointment of sore and preparation method thereof | |
| CN102125634A (en) | Chinese medicinal composition for treating bedsore | |
| CN103230493B (en) | Traditional Chinese medicine composition for treating unhealed wound | |
| CN105535334A (en) | Radix arnebiae and milkvetch root granulation-promoting extract and preparation method | |
| CN101164574B (en) | Medicine for treating burns and scalds and its preparation method | |
| CN105250696A (en) | Traditional Chinese medicine gel capable of promoting skin wound to heal and preparation method of traditional Chinese medicine gel | |
| CN102861287B (en) | Chinese medicinal composition for treating damp-heat invasion blood stasis diabetic foot and preparation method thereof | |
| CN101919927B (en) | Spray for promoting scald healing | |
| CN101703651A (en) | Medicament for treating diabetic gangrene | |
| CN102861217A (en) | External emplastrum for treating malignant boil, sores and carbuncles | |
| CN109602854B (en) | Ointment for treating burns and scalds and preparation method thereof | |
| CN104161961B (en) | The Chinese medicine for outer use for the treatment of diabetic foot ulcer, preparation method and applications | |
| CN102940749B (en) | Traditional Chinese medicine paste for treating diabetic foot | |
| Ji et al. | Sanguis draconis (Daemonorops draco): a case report of treating a chronic pressure ulcer with tunneling | |
| CN114470056A (en) | A kind of traditional Chinese medicine mixed preparation for treating venous ulcer of lower extremity and its preparation and use method | |
| CN105327244A (en) | Traditional Chinese medicine composition containing folium artemisiae argyi and used for treating bedsores and preparing method thereof | |
| CN111544514A (en) | A Chinese medicinal ointment for treating burn and scald, and its preparation method | |
| CN104306707A (en) | Medicament composition for treating bedsore | |
| CN111603537B (en) | Traditional Chinese medicine composition and oil agent for treating carbuncle-abscess sores and ulcers and preparation method and application of traditional Chinese medicine composition and oil agent | |
| CN116036168B (en) | A kind of traditional Chinese medicine composition for treating phlebitis and its application | |
| CN103394009B (en) | Traditional Chinese medicine for treating trauma and diabetes foot ulcer and preparation method | |
| CN108066466A (en) | A kind of Chinese medicine composition for treating burn and scald and preparation method and application | |
| CN108815268A (en) | A kind of external application promotees the Chinese medicine ointment formulation and preparation method thereof of union of wounded skin |
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee | Granted publication date:20170405 Termination date:20180625 |