CN101199609B - Chinese medicine for treating chemo-treatment medicament derived peripheral nerve toxicity - Google Patents

Chinese medicine for treating chemo-treatment medicament derived peripheral nerve toxicity Download PDF

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CN101199609B
CN101199609B CN 200710143569 CN200710143569A CN101199609B CN 101199609 B CN101199609 B CN 101199609B CN 200710143569 CN200710143569 CN 200710143569 CN 200710143569 A CN200710143569 A CN 200710143569A CN 101199609 B CN101199609 B CN 101199609B
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司马蕾
娄彦妮
贾立群
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贾立群
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Abstract

The peripheral neurotoxicity caused by chemotherapy medicament is a common side reaction in chemotherapy, which will affect the physical function when going severe, reduce the quality of life and even stop the chemotherapy. At present, the safe and effective clinic curing medicament has not been invented, and chemotherapy patients have difficulty in using the peroral dosage form medicine due to the alimentary canal symptoms accompanying the disease. Proven by animal pharmacology experimental research and clinical observation, the invention has advantages of good therapeutic effect for curing peripheral neurotoxicity by chemotherapy medicament, convenient use, high safety and broad application prospect by preparing herba epimedii, geranium, radix aconiti, hemlock parsley and safflower intopowder for external use.

Description

治疗化疗药物引起的周围神经毒性的外用中药 Peripheral nerve toxicity of Chinese herbs chemotherapy drug-induced

一技术领域 A technical field

[0001] 本发明涉及一种有效治疗化疗药物引起的周围神经毒性的外用中药浸剂。 [0001] The present invention relates to an effective treatment of Chinese herbs infusion peripheral neurotoxicity caused by chemotherapy. 二背景技术 Two Background

[0002] 伴随着医学模式的改变,以人为本的思想贯穿医疗活动。 [0002] With the medical model of change, people-oriented thinking through medical activities. 人们在追求疗效的同时,更注重生存质量的提高。 People in the pursuit of efficacy, more focus on improving the quality of life. 化疗药物引起的周围神经毒性(Chemotherapy-induced peripheral neurotoxicity/Chemotherapy-induced peripheral neuropathy, CIPN)是化疗较常见的副反应,严重时影响肢体功能,导致痛性残疾,降低生活质量,还可使化疗中断。 Peripheral nerve toxicity of chemotherapy (Chemotherapy-induced peripheral neurotoxicity / Chemotherapy-induced peripheral neuropathy, CIPN) drug-induced is more common side effects of chemotherapy, severe impact of physical function, resulting in pain and disability, reduced quality of life, but also to interrupt chemotherapy . 与化疗常见的消化系统和血液系统毒性相比,CIPN具有出现时间晚、症状持续时间长、治疗效果差等特点。 Compared with common digestive and blood toxicity of chemotherapy, CIPN have appeared late, long duration of symptoms, the treatment effect poor characteristics. CIPN首先影响感觉神经和植物神经,进一步发展则影响运动神经功能。 CIPN first affect the sensory and autonomic nervous system, affect the further development of motor nerve function. 感觉神经中,无髓的细神经纤维更容易受累,表现为烧灼或电击样疼痛、麻木、皮肤过敏、痛觉或温度觉丧失,由四肢远端逐渐向近心端发展;而粗神经纤维受累则引起震动觉、本体感觉、 腱反射丧失,肌无力以及神经传导速度的下降,腱反射消失常为首发症状。 Sensory nerve, the nerve fibers of fine unmyelinated more easily affected, due to burning or electric shock-like pain, numbness, skin irritation, loss of pain or temperature, and gradually developed from the proximal end to the distal extremities; and thick nerve fibers are affected cause vibration sense, proprioception, loss of tendon reflexes, decreased muscle weakness and nerve conduction velocity, tendon reflexes often the first symptom. 植物神经中毒表现为心律失常、体位性低血压、神经性腹泻腹痛、顽固性便秘、麻痹性肠梗阻、尿潴留及勃起功能障碍。 Autonomic poisoning manifested as arrhythmia, orthostatic hypotension, nervous diarrhea, abdominal pain, intractable constipation, paralytic ileus, urinary retention and erectile dysfunction. 停止用药后症状仍将持续数月,甚至会继续加重,称为“滑行”(coasting)现象, 与药物长时间蓄积有关。 After the medication is stopped the symptoms will continue for several months, or even continue to increase, called a "glide" (coasting) phenomenon, drug-related accumulation of a long time. CIPN呈剂量依赖性,多引起轴索变性,部分变性具有可逆性,但也有许多患者仅能部分恢复神经功能甚至完全不可逆转,这与药物种类、连续使用时间以及累积剂量有关,还与机体已存在的病理状态如糖尿病神经病变或酒精性神经损伤有关。 CIPN dose-dependent manner, causing multiple axonal degeneration, partially denatured reversible, but there are many patients only partially or even completely irreversible neurologic recovery, and this type of drug, the continuous use time and cumulative dose-related, and the body further has presence of pathological conditions such as diabetic neuropathy, or nerve damage associated alcohol.

[0003] 以草酸钼(Oxaliplatin)为代表的钼类化合物(Platinum drug)在消化道肿瘤的治疗中占有重要位置,但同时伴发的慢性累积性神经毒性发生率为16%,当累积剂量在780-850mg/m2时,发生率接近30%。 [0003] In molybdenum oxalate (Oxaliplatin) a molybdenum compound represented by (Platinum drug) occupies an important position in the treatment of gastrointestinal tumors, but also associated with chronic cumulative neurotoxicity was 16%, when the cumulative dose when 780-850mg m2 / incidence of nearly 30%. 其临床特点主要表现为以冷刺激诱发加重的感觉过敏或感觉超敏为主。 The clinical features mainly cold feeling evoked the feeling of aggravating allergies or hypersensitivity-based. 病人往往主诉麻木、胀痛、感觉异常(如蚁走感),持物不能,稍冷或热的温度刺激都会加重病情,由于回避日常活动可能进一步导致肌萎缩。 Patients often complain of numbness, pain, paresthesia (such as formication), can not hold things, a little cold or hot thermal stimulation will aggravate the disease, due to the avoidance of daily activities may cause further muscle atrophy. 肌电图显示感觉神经动作电位波幅降低90%以上,甚至不能测出。 EMG sensory nerve action potential amplitude decreased more than 90%, or even can not be measured.

[0004] 紫杉醇(Paclitaxel)和长春碱类(Vincristin)是另外两类常用化疗药,主要用于肺癌、乳腺癌及生殖系统肿瘤。 [0004] Taxol (Paclitaxel) and vinca alkaloids (Vincristin) is another two commonly used chemotherapy drugs, mainly for lung, breast and reproductive system tumors. 据统计,50%以上的病人接受紫杉醇剂量超过250mg/m2 时,出现感觉异常,症状多发生于给药后24-72小时,可持续数日甚至数月。 According to statistics, more than 50% of patients receiving paclitaxel doses greater than 250mg / m2, paresthesia, symptoms occur in 24 to 72 hours after administration, for several days or even months. 许多病人可有典型的手套状和袜状感觉,伴有微小的运动技巧障碍。 Many patients may have typical sock-like feel and a glove-like, accompanied by a small motor skills disorders.

[0005] 卡培他滨(capecitabine),商品名希罗达(Xeloda),是一种对肿瘤细胞有选择性活性的口服细胞毒制剂,主要用于大肠癌、乳腺癌治疗,其周围神经毒性特异性表现为手足综合征(Palmar PlantarErythrodysesthesia,PPE/Hand-Foot-Syndrome,HFS)。 [0005] capecitabine (capecitabine), trade Mingxiluoda (Xeloda), there is an oral formulation of a selective cytotoxic activity against tumor cells, mainly used for colon cancer, breast cancer, its peripheral neurotoxicity specific performance of hand-foot syndrome (Palmar PlantarErythrodysesthesia, PPE / Hand-Foot-syndrome, HFS). 表现为对称性指(趾)麻木、感觉迟钝、痛性或无痛性肿胀、红斑,严重者发展至脱屑、溃疡和剧烈疼痛。 The performance of symmetry (toe) numbness, sensation, painful or painless swelling, erythema, desquamation to the development of severe, ulcers and severe pain. 病理表现是表皮基底层血管扩张变性、朗罕氏细胞减少、细胞肿胀、基底角质细胞空泡变性、皮肤血管周围淋巴细胞浸润,角质细胞凋亡。 Pathology is degeneration of the basal layer vasodilation, decrease of Langerhans cells, cell swelling, cell vacuolar degeneration of basal keratinocytes, vascular lymphocytic infiltration surrounding skin, keratinocytes apoptosis. 超过半数患者会发生不同程度HFS,病变3-4 度达10%。 More than half of patients will occur in varying degrees HFS, 3-4 lesions of 10%.

[0006] 多数情况下具有神经毒性的几种药物合用会导致神经毒性的增加。 The [0006] most cases several drugs neurotoxic combination leads to increased neurotoxicity. 欧洲III期临床报道草酸钼联合5-FU/CF的神经毒性发生率高达68%,国内文献也有报道发生率高达90. 5%。 European Phase III clinical reports molybdenum oxalate joint 5-FU / CF incidence of neurotoxicity as high as 68%, the domestic literature have reported incidence as high as 90.5%. 紫杉醇与顺钼合用较单药使用能引起更快速的神经病理改变,粗的有髓神经纤维受累更为明显。 Paclitaxel combined with cis-molybdenum than the single use of drugs can cause more rapid neuropathological changes, thick myelinated nerve fibers affected more obvious. 在802例卵巢癌患者中进行泰素与钼类合用方案化疗与钼类单药化疗对比发现,前者2-3级神经毒性发生率为20%,后者为1%。 For Taxol in combination with molybdenum-based chemotherapeutic comparison with single-agent chemotherapy programs found molybdenum, 2-3 neurotoxicity former was 20% at 802 patients with ovarian cancer, the latter of 1%. 长春新碱联合紫杉醇化疗后,引发严重而逆转非常缓慢的运动神经症状如全身无力。 After vincristine in combination with paclitaxel chemotherapy, causing very serious and reversal of neurological symptoms such as slow movement of general weakness. 化疗药物与放疗合用时,放疗可能通过损伤少突胶质细胞和血管内皮细胞两种机制进一步加重CIPN。 When combined chemotherapy and radiation therapy, radiation therapy may further aggravate the injury by CIPN oligodendrocytes and endothelial cells two mechanisms.

[0007] 目前研究较多的化疗药物保护剂(Chemoprotectants)主要有生长因子、抗氧化剂等。 [0007] The present study more chemotherapeutic agents protecting agent (Chemoprotectants) There are growth factors, antioxidants. 给予外源性神经生长因子NGF可明显增加坐骨神经NGF mRNA表达,改善神经传导速度,但是为了在神经系统达到有效的生物利用度,给予高剂量药物所造成的局部或全身的副作用限制了癌症患者直接使用NGF ;作为糖尿病周围神经病变的保护剂,促红细胞生成素EPO具有非特异性的神经保护作用,但作用机制和作用位点尚不十分清楚,长期使用有明显升高血细胞比容的危险;还原型谷胱甘肽中的巯基能与体内自由基结合,促进自由基代谢,同时阻止P53蛋白在细胞内的积聚,中止细胞的程序化死亡;乙酰-L-肉毒碱(acetyl L carnitine)可提高线粒体内乙酰辅酶A生物利用度和中枢基因编码的P75NGFK转运速率, 从而提高NGF生物利用度;ASCO年会曾报道局部使用角质软化剂如尿素霜可缓解手足综合症症状;C0X2特异性抑制剂塞来昔布200mg bid,也可减轻HFS,但与C0X2特异性抑制 Administration of exogenous nerve growth factor NGF sciatic nerve significantly increased expression of NGF mRNA, improve nerve conduction velocity, but in the nervous system to achieve effective bioavailability, administration of high doses of the drug caused by local or systemic side effects limit the direct cancer patients use of NGF; protecting agent as diabetic peripheral neuropathy, erythropoietin EPO has nerve protective effect of non-specific, but the mechanism and site of action is not yet clear, long-term use significantly increased risk of hematocrit; further glutathione mercapto group capable of binding with free radicals in vivo, to promote the metabolism of free radicals, while preventing the accumulation of P53 protein in the cells, the suspension programmed cell death; acetyl -L- carnitine (acetyl L carnitine) may be enhance bioavailability mitochondrial genes encoding acetyl-coenzyme a and central P75NGFK transport rate, thereby increasing the bioavailability NGF; ASCO annual reported keratolytic agent for topical application, such as hand-foot syndrome urea cream may relieve the symptoms; C0X2 specific inhibitor celecoxib 200mg bid, also reduce HFS, but C0X2 specific inhibition 相关的心血管发生危险率增高使I/II期试验处于停滞阶段。 Associated cardiovascular risk of increasing the rate of phase I / II trial at a standstill phase.

[0008] 总而言之,目前临床尚无安全有效的治疗CIPN药物,一些药物尚处于临床研究前期。 [0008] In summary, there is no clinically safe and effective treatment CIPN drugs, some drugs is still in pre-clinical studies. 神经损伤和神经再生涉及免疫-神经-内分泌网络共同作用的复杂过程,越来越多的证据表明,单纯营养神经或抑制神经元活动的药物疗效并不理想。 Nerve damage and nerve regeneration involves immuno - neuro - endocrine network complex process of interaction, more and more evidence that the efficacy of pure neurotrophic or inhibit neuronal activity of the drug is not ideal. 另外,化疗病人往往伴发较严重的消化道症状,口服剂型的使用比较困难,临床上迫切需要切实有效的药物和给药途径。 In addition, chemotherapy patients often associated with more severe gastrointestinal symptoms, oral dosage forms difficult, urgent clinical need for effective drug and route of administration.

三发明内容 Three SUMMARY

[0009] 1发明目的 [0009] One object of the invention

[0010] 本发明目的是提出一种有效治疗化疗药物周围神经毒性的中药外治方法。 [0010] The object of the present invention is to provide a method of external medicine therapies effective chemotherapy drugs peripheral neurotoxicity.

[0011] 2技术方案 [0011] Technical Solution 2

[0012] 本发明提出一种治疗化疗药物引起的周围神经毒性的外用中药,其特征在于它是由下述重量份的中药制成的药剂:淫羊藿15-25g,老鹳草10-20g,川乌15-25g,川芎10-20g,红花10-20g。 [0012] The present invention provides a method of treating peripheral neurotoxicity caused by chemotherapy Chinese herbs, characterized in that it is formed by the following parts agent by weight of Traditional Chinese Medicine: Epimedium 15-25g, 10-20g Geranium , Aconitum 15-25g, Chuanxiong 10-20g, safflower 10-20g.

[0013] 本发明所说的治疗化疗药物引起的周围神经毒性的中药,其中所述的重量份的最佳配比是:淫羊藿20g,老鹳草15g,川乌20g,川芎15g,红花IOgo [0013] peripheral neurotoxicity of the medicine of the present invention said treatment of chemotherapy-induced, wherein parts by weight of the best ratio is: Epimedium 20g, Geranium 15g, Chuanwu 20g, Chuanxiong 15g, red flower IOgo

[0014] 本发明所述的药物,其特征在于所说的是外用浸剂。 [0014] The medicament according to the present invention, which is characterized in that said external infusion.

[0015] 本发明所述的药物,其制备方法特征在于上述药物水煮煎3次,每次lh,滤过,合并煎液,减压浓缩至相对密度为1. 15-1. 20 (50°C)的清膏,减压干燥得到干膏,粉碎,过5号筛,加糊精适量,混勻,以85%乙醇制粒,干燥,整粒,分装即得。 [0015] The medicament of the present invention, methods for their preparation wherein said medicament fried boiled three times, each time LH, filtered and concentrated, combined decoction, was reduced to a relative density of 1. 15-1. 20 (50 ° C) clear paste, and dried under reduced pressure to obtain a dry extract, pulverized, passed through a No. 5 sieve, add appropriate amount of dextrin, mixing, granulating 85% ethanol, dried, sieved, to obtain the packaging. [0016] 周围神经在中医属于经络范畴,周围神经毒性变属于络病。 [0016] In the peripheral nervous Chinese medicine are visible meridian, peripheral neurotoxicity becomes complex disease belongs. 病机为络脉瘀闭,不通则痛。 Pathogenesis of collaterals stasis closed, no pain. 治疗原则是通络止痛。 Principle of treatment is Tongluozhitong. 络脉不仅涵盖了微循环的范畴,更包含具有广泛生理功能的机体调节系统,包括神经、免疫、内分泌和循环等多系统的整体功能。 It encompasses not only visible collaterals microcirculation, further comprising a body having a wide range of physiological functions of the control system, including the nervous, immune, endocrine, and multiple circulation system as a whole functions. 该方即是根据上述原贝U,多角度调节免疫和微循环功能,提供更多、比例更符合正常生理需求的生长活性因子的微环境。 The party that is based on the original shell U, multi-angle modulation of immune function and microcirculation, more, more in line with the proportion of active growth factor microenvironment normal physiological needs. 通过经皮给药系统(transdermaltherapeutic systems,TTS),经由皮肤吸收进入全身血液循环并达到有效血药浓度。 By transdermal delivery system (transdermaltherapeutic systems, TTS), absorbed through the skin into the systemic circulation and to achieve an effective blood concentration. 避免肝脏的首过效应及胃肠道的破坏,降低药物毒性和副作用,达到内病外治、靶向治疗目的。 To avoid damage to the liver and gastrointestinal first-pass effect, lower toxicity and side effects, to achieve the disease outside the government, targeted therapeutic purposes. 本方中淫羊藿温阳补气,具有多重免疫活性,为君药。 This Epimedium Warming Yang Fang Qi, with multiple immune activity, King and medicine. 老鹳草祛风活血,主要成分鞣质老鹳草素(G素)具有免疫调节等多种药理活性;川乌辛温大毒,主要成分乌头总碱镇痛作用强,为臣药。 Geranium expelling blood, the main component of tannin Geraniin (G element) having immunomodulatory and other pharmacological activities; Chuanwu Xin temperature big drug, the main component of Aconitum strong analgesic effects of total alkaloids, Chen medicine. 佐以川芎、红花通经活络。 Combined with safflower through the meridians. 老鹳草同时具有透皮性,将上述药理活性成分靶向导入。 Geranium transdermal property while having the above-described pharmacologically active ingredient targeting introduced.

[0017] 本发明动物药理实验研究及临床观察证明: [0017] Animal Clinical Pharmacology and Experimental Study of the present invention is demonstrated:

[0018] (1)治疗后大鼠50%缩足阈(50%Paw withdrawal threshold, 50% PffT)中药组较模型组提高(P <0.01)。 [0018] (1) 50% rat paw withdrawal threshold after treatment (50% Paw withdrawal threshold, 50% PffT) Medicines improved than the model group (P <0.01).

[0019] (2)热缩足反射潜伏期(Thermal withdrawal latency, TffL)中药组较模型组明显下降(P < 0. 01)。 [0019] (2) thermal withdrawal latency (Thermal withdrawal latency, TffL) TCM was significantly lower than the model group (P <0. 01).

[0020] (3)冷刺激引起的缩足反射潜伏期:中药组较模型组明显下降(P < 0. 01)。 Reduced withdrawal latency [0020] (3) cold stimulation: Chinese group than in model group was significantly decreased (P <0. 01).

[0021] (4)中药组外周血神经生长因子与模型组比较明显升高(P < 0. 01)。 [0021] (4) Medicines Peripheral NGF model group increased significantly (P <0. 01).

[0022] (5)中药组表皮内神经纤维(Intra印idermal nerve fiber, IENF)密度较模型组升高(P < 0. 05)。 [0022] (5) Medicines epidermal nerve fibers (Intra printed idermal nerve fiber, IENF) increased density than the model group (P <0. 05).

[0023] (6)中药组表皮内疼痛介质P物质(Substance P,SP)较模型组降低(P < 0. 01)。 [0023] (6) substance P in the Pain medium Medicines epidermis (Substance P, SP) than the model group (P <0. 01).

[0024] (7)临床上对奥沙利钼、卡培他滨、紫杉醇等多种化疗药物引起的周围神经毒性具有显著疗效,且无不良反应。 Of oxaliplatin molybdenum, peripheral neurotoxicity capecitabine, paclitaxel and other chemotherapeutic agents have a significant effect on [0024] (7) clinical, and no adverse reactions.

[0025] 3有益效果 [0025] Advantageous Effects 3

[0026] 从以上药理实验结果显示,本发明具有以下优点: [0026] From the foregoing pharmacological test results show that the present invention has the following advantages:

[0027] (1)本药物对于CIPN治疗效果较好,具有良好的应用前景。 [0027] (1) The medicament is preferably for the treatment of CIPN has good application prospect.

[0028] (2)外用给药方式使用方便,减少药物胃肠道副反应。 [0028] (2) easy to use topical administration, the pharmaceutical reduced gastrointestinal side effects.

[0029] (3)经济成本较低,易于患者接受。 [0029] (3) a lower economic cost, easy to patients.

[0030] (4)本药物能够明显减轻机械刺激和温度刺激引起的感觉过敏。 [0030] (4) The pharmaceutical can significantly reduce the temperature and mechanical stimulation sensory stimulation allergy.

[0031] (5)药物能够提高外周血神经生长因子水平。 [0031] (5) a drug capable of raising peripheral nerve growth factor.

[0032] (6)神经病理结果显示,本药物能够降低疼痛介质过度表达,促进表皮内神经纤维再生。 [0032] (6) neuropathological results show that the drug can reduce the pain of the present medium overexpression, the epidermis to promote nerve fiber regeneration.

[0033] 四具体实施方法 [0033] DETAILED DESCRIPTION four methods

[0034] 实施例1中药对化疗药物引起的机械感觉过敏的影响 [0034] Example 1 mechanosensation medicine Chemotherapy-induced allergic effects

[0035] 1材料与方法 [0035] Materials and methods

[0036] (1)实验动物与分组 [0036] (1) Experimental animals and group

[0037] Wistar大鼠雌性45只(北京维通利华动物实验中心提供),SPF级,合格证号SCXK9(京)2007-0001。 [0037] 45 female Wistar rats (Beijing Vital River Experimental Animal Center), SPF grade, Certificate of Conformity SCXK9 (Beijing) 2007-0001. 体重约210g。 Weighing about 210g. 实验组30只,按标准模型Homles J,Stanko J, Varchenko, M. et al.Comparativeneurotoxicity of oxaliplatin, cisplatin, and ormaplatin in affistar rat model. Toxicological Sciences. 1998,46 :342_351.腹腔注射钼类化疗药草酸钼4mg/kg,每周2次,连续4周(共9次)。 30 experimental groups, according to standard model Homles J, Stanko J, Varchenko, M. et al.Comparativeneurotoxicity of oxaliplatin, cisplatin, and ormaplatin in affistar rat model Toxicological Sciences 1998,46:... 342_351 intraperitoneal chemotherapy drugs molybdenum oxalate molybdenum 4mg / kg, twice per week, for 4 weeks (total of 9). 其中模型组15只:第2周开始,室温自来水浸泡四肢及尾部,eOmin/次,Bid,连续3周冲药组15只:中药(IOg/袋) 加入自来水200ml配制成浸剂浸泡四肢及尾部,方法同前;对照组15只,腹腔注射等容积5%葡萄糖。 15 wherein the model group: 2 weeks, soaked in water at room temperature limbs and tail, eOmin / times, Bid, 3 weeks punch drug group 15: Chinese (IOg / bag) was added 200ml water formulated infusion soak limbs and tail , with the former method; control group, 15 rabbits were injected volume 5% glucose.

[0038] (2)药品及实验仪器 [0038] (2) experimental instruments and drugs

[0039] 中药颗粒制剂10g,溶于IOOml室温水中,即刻使用。 [0039] Chinese granular preparation 10g, was dissolved in water at room temperature IOOml, used immediately. 草酸钼(批号H20000337,江苏恒瑞医药股份有限公司):50mg溶解于5%葡萄糖溶液,终浓度lmg/ml。 Molybdenum oxalate (Lot H20000337, Jiangsu Hengrui Medicine Co., Ltd.): 50mg dissolved in 5% glucose solution, a final concentration of lmg / ml. Von Frey纤维丝:美国North Coast Medical公司。 Von Frey filaments: United States North Coast Medical Company. BME-410C型全自动热痛刺激仪:中国医学科学院生物医学工程研究所。 BME-410C automatic Analgesia Tester: Institute of Biomedical Engineering, Chinese Academy of Medical Sciences. Tissue-Tek TEC5冷台:日本樱花精机株式会社。 Tissue-Tek TEC5 cooling stage: Sakura Seiki Co., Ltd. of Japan.

[0040] (3)行为学观察:均在用中药用药后2h进行。 [0040] (3) Observation of behavior: 2h are carried out after treatment with traditional Chinese medicine. 实验开始时测定行为学指标,各组之间无差异。 Determination of behavioral indicators beginning of the experiment, no differences between the groups.

[0041] ①50%缩足阈:将大鼠置于金属网上,盖以透明的有机玻璃罩,先让大鼠适应环境15min,待梳理探究活动基本消失后,用一系列标准化的Von Frey纤维丝刺激后肢足底中心部位。 [0041] ①50% paw withdrawal threshold: rats are placed in the metal mesh, covered with a transparent organic glass, let acclimatization rats 15min, be carded inquiry disappeared after a series of Von Frey filaments standardized stimulate the center of the hind foot. 刺激从2g开始,最大力度15g,根据公式推算出50%缩足阈值。 2g stimulus from the start, the maximum intensity of 15g, calculate the 50% paw withdrawal threshold according to the formula.

[0042] ②热缩足反射潜伏期:将装有大鼠的有机玻璃箱置于3mm厚的玻璃板上,用热痛刺激仪照射大鼠后肢足底。 [0042] ② thermal withdrawal latency: Rats with plexiglass box placed on a glass plate 3mm thick, with a heat pain irradiated stimulator plantar hind limb. 记录从照射开始至大鼠出现抬足的时间,自动切断时间40s。 To start recording from the irradiated rats had time enough to lift automatically off time 40s.

[0043] ③冷刺激引起的缩足反射潜伏期:用改良的冷板试验(Cold platetest)测定冷刺激引起的感觉过敏。 [0043] ③ cold stimulation induced contraction withdrawal latency: measured using a modified cold plate test (Cold platetest) sensory stimulation cold allergy. 将大鼠放于_4 士1°C的冷台上,罩以透明带孔玻璃罩。 Rats are placed in a cold stage _4 persons of 1 ° C, the perforated transparent cover glass. 记录从后肢接触冷台到出现抬足或舔足时间。 Cool contact records from station to appear hind foot lifting or licking time. 自动切断时间3min。 Auto-off time 3min.

[0044] (4)外周血NGF含量:实验结束时,最后一次草酸钼给药后24h,l%戊巴比妥50mg/kg腹腔麻醉大鼠,抗凝管采集各组大鼠腹腔静脉血2ml,采用双抗夹心ELISA法测定血浆NGF含量。 [0044] (4) Peripheral NGF content: At the end of the experiment, after the last administration molybdenum oxalate 24h, l% pentobarbital 50mg / kg intraperitoneally anesthetized rats, the rats intraperitoneally anticoagulant 2ml blood collection tube plasma NGF concentrations were determined by double antibody sandwich ELISA.

[0045] (5)表皮内神经纤维和表皮P物质:实验结束时,以大鼠后肢足底第一、五趾根部足垫连线中点为中心,取0.5X0. 3cm组织,沿长轴连续切片各5张,厚4μπι, HE染色及EnVison 二步法免疫组化。 [0045] (5) intraepidermal nerve fibers and substance P in the skin: the end of the experiment, to a first rat hind foot, toe root footpad midpoint centered taken 0.5X0 3cm tissue, along the long axis. each serial sections 5 thick 4μπι, HE EnVison two-step staining and immunohistochemistry. 石蜡切片常规脱蜡至水,分别加入多克隆兔抗体PGP9. 5(1 : 2000,CHEMICON)和SP (1 : 5000,DAK0),通用型二抗(DAKO)室温2. 5h 孵育, DAB显色分别为5min,2min。 Paraffin sections were dewaxed to water, respectively 加入多克隆 rabbit antibody PGP9 5. (1: 2000, CHEMICON), and SP (1: 5000, DAK0), universal secondary antibody (DAKO) at room temperature 2. 5h incubation, DAB color They were 5min, 2min. 记录单位长度下IENF数量。 IENF record the number of unit length. BX51正置光学显微镜(OLYMPUS) 下每张切片随机取5个视野,ImagePro-Plus5. 0图像分析软件测定SP积分光密度I0D。 Each slice at randomly selected five fields BX51 upright optical microscope (OLYMPUS), ImagePro-Plus5. 0 SP image analysis software integrated optical density measured I0D.

[0046] 2 结果 [0046] 2 Results

[0047] 实验组大鼠50% PffT在第3次给药后较对照组下降,即动物出现机械感觉超敏, 与对照组比较P <0.01。 [0047] 50% PffT experimental group after the third dose decreased than the control group, i.e., the feeling of a mechanical hypersensitivity animals, compared with control group P <0.01. 表现为快速缩足、甩肢和舔足。 It showed rapid paw withdrawal, rejection limb and foot licking. 模型组痛行为稳定并持续存在直至试验结束。 Model group and stable pain behavior persisted until the end of the trial. 中药组治疗2周后50% PWT升高,3周后与模型组比较差异具有显著性(P <0.01)(附图1)。 50% PWT TCM treatment group increased after 2 weeks, 3 weeks after significant difference compared with the model group (P <0.01) (Fig. 1).

[0048] 实施例2中药对化疗药物引起的热刺激感觉过敏的影响 [0048] Example 2 Chinese chemotherapy-induced thermal hypersensitivity The effect of stimulation of

[0049] 1材料与方法(同实施例1) [0049] Materials and Methods (in Example 1)

[0050] 2 结果 [0050] 2 Results

[0051] 实验组大鼠第3次给药后TWL较对照组明显下降(P < 0. 01),即动物出现热刺激引起的感觉过敏。 [0051] After administration TWL third experimental group was significantly decreased compared with control group (P <0. 01), i.e., animals developed thermal sensory stimulation allergy. 模型组痛行为稳定并持续存在直至试验结束。 Model group and stable pain behavior persisted until the end of the trial. 中药组治疗1周后TWL有所延长,3周后与模型组比较有明显差异,P < 0. 01 (附图2)。 After one week of treatment Medicines TWL been extended, three weeks after comparison with the model group were significantly different, P <0. 01 (FIG. 2).

[0052] 实施例3中药对化疗药物引起的冷刺激感觉过敏的影响 [0052] Example 3 cold medicine Chemotherapy-induced effects stimulus hyperesthesia

[0053] 1材料与方法(同实施例1) [0053] Materials and Methods (in Example 1)

[0054] 2 结果[0055] 实验组大鼠第3次给药后冷刺激引起的缩足反射潜伏期下降(与对照组比较,P [0054] RESULTS [0055] After the third group of rats administered the experimental paw reflection decrease latency cold stimulation (compared with the control group, P

< 0. 01),即动物出现冷刺激引起的感觉过敏。 <0.01), that animals feel the cold stimuli appear allergies. 模型组痛行为稳定并持续至试验结束。 Pain behavior model group continued to stabilize and end of the trial. 中药组治疗2周后有所好转,3周后与模型组比较差异有显著性(P < 0. 01)(附图3)。 After 2 weeks of treatment Medicines improved after three weeks compared with the model group have significance (P <0. 01) (FIG. 3).

[0056] 实施例4中药对神经生长因子含量的影响 Example 4 Effect of nerve growth factor in medicine of [0056] Embodiment

[0057] 1材料与方法(同实施例1) [0057] Materials and Methods (in Example 1)

[0058] 2 结果 [0058] 2 Results

[0059] 实验结束时,模型组外周血NGF 39. 4士8. 9pg/ml,与对照组55. 6士11.2pg/ml 比较,下降28. 6 %,P < 0. 05 ;中药组77. 9士13. 5pg/ml,与模型组比较,升高97. 4 %,P [0059] At the end of the experiment, the model of peripheral blood Disabled NGF 39. 4 8. 9pg / ml, with the control group 55.6 Disabled 11.2pg / ml compared dropped 28. 6%, P <0. 05; 77 Medicines 9. Shi 13. 5pg / ml, compared with model group, increased 97. 4%, P

< 0. 01。 <0.01.

[0060] 实施例5中药表皮下神经纤维再生的作用 Nerve fiber regeneration in Chinese epidermal Example 5 [0060] Embodiment

[0061] 1材料与方法(同实施例1) [0061] Materials and Methods (in Example 1)

[0062] 2 结果 [0062] 2 Results

[0063] 实验结束时模型组IENF202. 8 士23. 1/cm,较对照组379. 3 士22. 2/cm降低,P < 0. 01 ;中药组262. 1 士25. 2/cm,较模型组升高,P < 0. 05(附图4)。 . [0063] At the end of the experimental model group Disabled IENF202 8 23. 1 / cm, compared with the control group Disabled 379.3 22. 2 / cm decreased, P <0. 01; Disabled Medicines 262.1 25. 2 / cm, compared with model group increased, P <0. 05 (Figure 4).

[0064] 实施例6中药对疼痛介质的影响 Example 6 Effect on pain medicine medium [0064] Embodiment

[0065] 1材料与方法(同实施例1) [0065] Materials and Methods (in Example 1)

[0066] 2 结果 [0066] 2 Results

[0067] 免疫组化图像积分光密度值半定量分析,表皮免疫阳性物质模型组269. 14士26. 12,明显大于对照组37. 56士6. 08 (P < 0. 01),中药组152. 51 士49. 06,低于模型组(P <0.01)(附图5)。 [0067] Immunohistochemical images IOD semi-quantitative analysis of immunoreactive substance in the skin model group 269.14 26.12 disabilities, significantly greater than in the control group 37.56 disabilities 6. 08 (P <0. 01), Medicines 152.51 49.06 disabilities compared with the model group (P <0.01) (Fig. 5).

[0068] 实施例7临床治疗前后周围神经毒性和手足综合征的症状体征的变化,有效率, 安全性分析 Peripheral neurotoxicity Example 7 changes before and after treatment and the clinical signs and symptoms of hand-foot syndrome [0068] embodiment, efficiency, safety analysis

[0069] 1材料与方法 [0069] Materials and methods

[0070] (1)病例纳入标准 [0070] (1) Case inclusion criteria

[0071] 2005年10月至2007年3月中日友好医院中医肿瘤科的住院或门诊患者,符合下列条件: [0071] October 2005 to mid-March 2007 Japanese Friendship Hospital of Traditional Chinese oncology inpatient or outpatient, meet the following conditions:

[0072] ①接受化疗后出现1级以上神经毒性或手足综合征者; [0072] neurotoxicity or more stages 1 hand-foot syndrome ① after chemotherapy;

[0073] ②年龄18〜80岁; [0073] ② aged 18~80 years old;

[0074] ③Karnofsky评分60分以上; [0074] ③Karnofsky score 60 points or more;

[0075] ④预计生存3个月以上; [0075] ④ expected to survive more than 3 months;

[0076] ⑤了解并同意接受该治疗。 [0076] ⑤ understand and agree to the treatment.

[0077] (2)排除病例标准 [0077] (2) Case exclusion criteria

[0078] ①不符合上述纳入标准者; [0078] ① who do not meet the inclusion criteria above;

[0079] ②因脑转移或肢体转移而出现神经压迫症状,或因电解质紊乱及其他系统性疾病(如严重糖尿病)致神经系统病变者; [0079] ② limb due to cerebral metastasis or metastasis occurs symptoms of nerve compression, or by other electrolyte disorders and systemic diseases (such as severe diabetes) were induced neuropathy;

[0080] ③存在手足皮肤病变或有药物接触过敏史者。 [0080] ③ hand-foot skin lesions or the presence of drug exposure history of allergy.

[0081] (3)治疗方法 [0081] (3) Treatment method

[0082] 患者从入组第1天开始,中药散剂外用洗/浸患部,温浴(以不引起患者不适为度),每次20分钟,每日早晚各1次,连用7天为1个观察周期。 [0082] Patients enrolled starting on day 1, external medicine powder washing / leaching affected, a warm bath (so as not to cause discomfort to the patient degrees), every 20 minutes, once a day, morning and evening, for 7 days to observe a cycle. [0083] (4)观察指标 [0083] (4) Observation index

[0084] ①治疗前、后周围神经毒性和手足综合征不良反应的分级变化。 [0084] ① prior to treatment, peripheral nerve toxicity grade change and hand-foot syndrome adverse reactions. 周围神经毒性分级参照NCI标准: Referring to peripheral nerve toxicity grading criteria of the NCI:

[0085] [0085]

[0086] 手足综合征分级参照加拿大国立癌症研究所CTG常用毒性分级标准: [0086] Referring to hand-foot syndrome grade Canadian National Cancer Institute common toxicity grading standards CTG:

[0087] [0087]

[0088] ②有效率 [0088] ② efficient

[0089] 疗效评定方法(参照分级标准比较治疗前、后周围神经毒性及手足综合征的症状、体征)。 [0089] The evaluation method (refer to Comparative grading before treatment, peripheral nerve toxicity and hand-foot syndrome symptoms, signs). 治愈:用药后较用药前降为0级或其症状、体征完全或基本消失。 Cure: after treatment than before treatment reduced to 0 or symptoms, signs or completely disappeared. 有效:用药后较用药前下降1级及以上。 Effective: decreased after treatment than before treatment Level 1 and above. 无效:症状、体征均无改善或症状稍有改善但体征无改善。 Invalid: symptoms, signs or symptoms were not improving slightly improved but signs of improvement. (*总有效率=有效率+治愈率) (* = Total effective rate + effective cure rate)

[0090] ③起效时间 [0090] ③ onset time

[0091] 观察患者在治疗后达到“有效”评价标准所需的时间。 [0091] observation of the patient after the treatment time necessary to achieve an "effective" evaluation criteria.

[0092] ④自身对照观察 [0092] ④ self-control observation

[0093] 选取在入组之前已行多个周期奥沙利钼化疗、存在慢性累积性神经毒性者为观察对象,以中药外用治疗前的上一个化疗周期后出现周围神经毒性症状的持续时间作为对照组,以本次进行中药干预后症状的持续时间作为治疗组,对同一患者进行自身对照观察。 [0093] Before the selected group has a plurality of rows of molybdenum oxaliplatin chemotherapy cycles, the presence of chronic cumulative neurotoxicity were observed target, to a chemotherapy cycle after topical treatment medicine occur before the duration of symptoms as peripheral neurotoxicity group, a duration of symptoms after the Chinese intervention for the treatment group, were compared to the same patient observed itself.

[0094] ⑤安全性 [0094] ⑤ security

[0095] 观察有无皮疹、过敏或患者自觉不适的情况存在。 [0095] observe whether the skin rashes, allergic situation or patient discomfort conscious existence.

[0096] 2 结果 [0096] 2 Results

[0097] (1)符合纳入标准者27例患者,其中男性15例,女性12例,中位年龄56. 8岁(32 〜79 岁)。 [0097] (1) met the inclusion criteria were 27 patients, 15 males and 12 females, with a median age of 56.8 years old (32 years old ~79).

[0098] 疾病诊断情况:(例) [0098] where :( Example diagnosis)

[0099] [0099]

[0100] 化疗方案选择情况:(例) [0100] Example chemotherapeutic regimen selected case :()

[0101] [0101]

[0102] 化疗副反应情况:出现周围神经毒性反应1级10例、2级7例、3〜4级5例,手足综合征3级3例、4级2例。 [0102] chemotherapy side effects: The neurotoxicity appears around 10 cases of level 1, level 2 7 Example 3 ~ 4 5 cases, three cases of grade 3 hand-foot syndrome, grade 42 cases.

[0103] (2)25例患者的不良反应的程度较治疗前明显减轻,见表1。 [0103] (2) before the extent of adverse reactions compared with 25 patients treatment significantly reduced (Table 1).

[0104] 表1.治疗前、后周围神经毒性及手足综合征的分级变化(单位:例) [0104] Table 1 prior to treatment, peripheral neurotoxicity and grade change after hand-foot syndrome (unit: Example)

[0105] [0105]

[0106] 经Wilcoxon Two-Sample分析,两组比较有显著性差异(P < 0. 01) [0106] by the Wilcoxon Two-Sample Analysis, compare the two groups was significant difference (P <0. 01)

[0107] (3)总有效率92. 6% (25/27),治愈率66. 7% (18/27),见表2。 [0107] (3) The total efficiency of 92.6% (25/27), the cure rate of 66.7% (18/27), see Table 2.

[0108] 表2.疗效评价 [0108] Table 2. Evaluation

[0109] [0109]

[0110] (4)安全性分析:在治疗及随后的临床随访中均未见皮疹、过敏及患者自觉不适的副反应。 [0110] (4) Security Analysis: In clinical treatment and subsequent follow-up showed no skin rashes, allergies and adverse reactions in patients conscious discomfort.

[0111] 实施例8奥沙利钼致周围神经毒性的18例患者治疗效果 [0111] Example 18 patients molybdenum treatment of peripheral neurotoxicity induced by oxaliplatin embodiment 8

[0112] 1材料与方法(同实施例7) [0112] Materials and methods (as described in Example 7)

[0113] 2 结果 [0113] 2 Results

[0114] (1)起效时间 [0114] (1) onset time

[0115] 统计18例患者在治疗时奥沙利钼的累积剂量和治疗后达到“有效”评价标准的起效时间,见表3。 [0115] Statistics in the treatment of 18 patients reached the "valid" evaluation criteria onset time after a cumulative dose of oxaliplatin treatment and molybdenum, are shown in Table 3.

[0116] 表3. 18例患者在治疗后达到“有效”评价标准的起效时间平均值 [0116] Table 3. 18 patients after treatment to achieve an "effective" evaluation criteria average onset time

[0117] [0117]

[0118] [01]

[0119] (2)自身对照观察 [0119] (2) self-control observation

[0120] 在本组观察的18例患者中,有9例为在此次中药干预前已行多个周期奥沙利钼化疗者,对同一患者进行自身对照观察,以中药外用治疗前的上一个化疗周期后出现周围神经症状的持续时间作为对照组,以本次进行中药干预后周围神经症状的持续时间作为治疗组,结果见表4。 [0120] In this group of 18 patients observed in 9 patients as the plurality of line periods prior Chinese intervention chemotherapy oxaliplatin, molybdenum, and the same patient itself controlled observation, on the front in the topical treatment medicine a duration of peripheral nerve symptoms occur after chemotherapy cycle as the control group, after a duration of this herbal medicinal therapy for peripheral nerve symptoms treatment group, results shown in Table 4.

[0121] 表4. 9例患者在中药干预前、后周围神经毒性持续时间的自身对照 [0121] Table 4. Nine patients before Chinese intervention, peripheral neurotoxicity own control after duration

[0122] [0122]

[0123] **表示经t检验两组比较有显著性差异(P < 0.01) [0123] * denotes the two groups by t test there was a significant difference (P <0.01)

[0124] 实施例9卡培他滨致手足综合征的5例患者治疗效果 [0124] Example 9 capecitabine induced therapeutic effect hand-foot syndrome in 5 patients

[0125] 1材料与方法(同实施例7) [0125] Materials and methods (as described in Example 7)

[0126] 2 结果 [0126] 2 Results

[0127] 本组观察病例中的5例手足综合征均为3级以上(3级3例、4级2例),治疗后疗效评价治愈1例,有效3例,无效1例,治疗有效病例的起效时间为1. 3士0. 6天,症状持续时间为10. 3士2. 5天,短于文献报道的13天的3级手足综合征的中位持续时间。 [0127] observed in this group of cases in 5 cases were of grade 3 or more hand-foot syndrome (grade 33 cases, grade 42 patients), evaluating the effect of treatment were cured one case, effective in 3 cases, and 1 case, the therapeutically effective cases the onset time of 0.6 days 1.3 disabilities, duration of symptoms was 10.3 2.5 days disabilities, median duration of 13 days shorter than the stage 3 hand-foot syndrome reported in the literature.

[0128] 实施例10典型病例 [0128] Typical cases EXAMPLE 10

[0129] 1材料与方法(同实施例7)[0130] 2 结果 [0129] Materials and methods (as described in Example 7) [0130] 2 Results

[0131] 典型病例一(草酸钼周围神经毒性) [0131] Typical cases a (peripheral neurotoxicity molybdenum oxalate)

[0132] 患者曹某某,男,70岁,于2006年6月前来就诊。 [0132] Patients Cao Moumou, male, 70 years old, in June 2006 to come for treatment. 主诉:手足麻木、瘀斑伴畏风1 周。 Chief Complaint: numbness, bruising with fear the wind 1 week. 现病史:患者乙状结肠癌术后半年,发现肝脏转移,遂行肝脏介入化疗及全身静脉化疗, 具体用药:肝脏介入化疗选用L-OHP和5-Fu,其中L-OHP选用乐沙定150mg/次,每6周重复;在介入化疗的中间追加1疗程的全身静脉化疗,方案同介入治疗。 History of present illness: patients with sigmoid colon cancer after six months, found that liver metastases, liver carry out interventional chemotherapy and intravenous chemotherapy, specific medication: liver arterial chemotherapy selection of L-OHP and 5-Fu, where L-OHP selection of Eloxatin 150mg / times, repeated every 6 weeks; interposition additional chemotherapy course of intravenous chemotherapy 1, with the intervention programs. 在介入化疗2周期后, 患者出现手足麻木,上肢过肘,下肢及膝,感觉减退,伴手足部皮肤瘀斑,色紫暗,极度畏寒, 遇风即有过电感,影响日常生活(持物不能、行走不便),不能生活自理。 After the intervention 2 cycles of chemotherapy, patients with hand, foot numbness, upper limb over the elbow, leg and knee, hypoesthesia, with hand-foot skin bruising, dark purple color, extreme chills, that is the case of wind through the inductor, affect their daily lives (holding things can not walk properly), we can not take care of themselves. 经停用化疗、热敷无明显改善,为寻求中西医结合治疗来诊。 By disabling chemotherapy, heat or no significant improvement, seeking to Integrative Medicine clinic.

[0133] 诊断:1.乙状结肠癌术后,肝转移(IV期)2.化疗性周围神经病(3〜4级) [0133] Diagnosis:. 1 after sigmoid colon cancer, liver metastasis (IV s) 2 chemotherapy peripheral neuropathy (grade 3 to 4)

[0134] 治疗:中药颗粒制剂10g,溶于200ml室温水中,即刻洗/浸患部,温浴,每次20分钟,每日早晚各1次,连用7天,并嘱其注意保暖,避免冷刺激(包括接触冰冷物体及喝冷饮等)。 [0134] Treatment: 10g medicine granular preparation, was dissolved in 200ml of water at room temperature, immediately wash / leaching affected, a warm bath, 20 minutes, 1 daily morning and evening, for 7 days, and to urge their keep warm and avoid cold stimulation ( comprising contacting an object and ice-cold drinks, etc.). [0135] 治疗效果:治疗第2天后,患者自觉遇风时麻刺、过电感程度较前减轻;治疗第5 天后,患者可自行拿水杯喝水以及自己吃饭,大部分生活可自理,手足麻木已明显减轻;治疗1周期后,手足瘀斑范围渐缩小,颜色转淡,患者未再诉麻木,可完全生活自理。 [0135] Treatment: 2 days after treatment, when the patient is conscious tingling case of wind, over the previous mitigate the extent of the inductor; 5 days of treatment, patients can take their own cup to drink water and eat their own, most life can take care of themselves, numbness has been reduced significantly; after 1 cycle, hand, foot and bruising gradually narrow range, color slowed, patients with no further complaint numb, completely self-care.

[0136] 典型病例二(手足综合征) [0136] Typical Case II (hand-foot syndrome)

[0137] 患者马某某,男,79岁,于2006年10月来诊。 [0137] patients Moumou, male, 79 years old, in October 2006 for consultation. 主诉:手足皮肤脱皮、皲裂伴疼痛5 天。 Chief Complaint: hand-foot skin peeling, chapped with pain for five days. 现病史:患者2006年4月因结肠腺癌行结肠癌根治术,术后口服希罗达辅助化疗,具体用法为1500mg Bid,连用14天、休息7天为1周期。 History of present illness: The patient in April 2006 due to colon adenocarcinoma line colon cancer surgery, postoperative oral Xeloda adjuvant chemotherapy, the specific use for the 1500mg Bid, once every 14 days, 7 days a rest period. 目前在服用希罗达第5个治疗周期,出现:手掌和足底皮肤粗糙、皲裂,干性脱皮,患者自觉双手足肿胀、感觉迟钝,疼痛剧烈,严重影响睡眠,还可见皮肤色素沉着,颜色紫暗;同时指趾活动受限不能弯曲,无法持物,不能站立及行走;伴见口腔多发溃疡,进食疼痛,消瘦。 Xeloda is currently taking the fifth treatment cycle occurs: the palms and soles rough skin, chapped, dry peeling, conscious patients with swelling hands and feet, sensation, severe pain, seriously affecting sleep, also visible skin pigmentation, color dark purple; limited mobility while digit can not be bent, not who was not standing and walking; see with multiple oral ulcers, eating pain, weight loss. 经停用希罗达、外用保湿乳剂及口服吗啡类止痛药物仍不能缓解,慕名前来中日友好医院寻求中西医结合治疗。 Xeloda was disabled, topical moisturizing cream and oral morphine analgesic drugs can not alleviate, come to Japan Friendship Hospital to seek Integrative Medicine.

[0138] 诊断:1.结肠癌根治术后化疗后(IV期);2.手足综合征(4级);3. 口腔溃疡(多发)。 [0138] Diagnosis: 1 after surgery for colorectal cancer chemotherapy (IV s); 2 hand-foot syndrome (level 4); 3 oral ulcers (multiple)....

[0139] 治疗:中药颗粒制剂10g,溶于200ml室温水中,即刻洗/浸患部,温浴,每次20分钟,每日早晚各1次,连用7天;另予自制“溃疡油,,涂抹口腔溃疡处,每日3〜4次。嘱其注意局部防护,避免摩擦、受压、外伤等。 [0139] Treatment: 10g medicine granular preparation, was dissolved in 200ml of water at room temperature, immediately wash / leaching affected, a warm bath, 20 minutes, 1 day, morning and evening, for 7 days; I made other "oil ,, applicator oral ulcer ulcer, 3 to 4 times daily. urge their attention to local protection, avoid friction, pressure, and other trauma.

[0140] 治疗效果:第1天治疗后,患者即觉手足和口腔疼痛明显减轻,手指可做握拳动作,夜间睡眠质量明显改善;此后患者症状日渐减轻,可逐渐床边短时间站立、短距离行走; 至治疗1周期后,手足局部可见新生上皮组织,手掌和足底皮肤颜色转淡,患者未诉肿胀及疼痛,可正常进行日常活动;另口腔溃疡痊愈,体重较前亦稍有增加。 [0140] Treatment: Day 1 after the treatment, i.e., patients with hand, foot and mouth feel pain significantly reduced, fingers do fist operation, significant improvement in the quality of nighttime sleep; increasing thereafter to alleviate symptoms, short bed gradually stand, a short distance walking; to 1 cycle after treatment, hand, foot and partially visible new epithelial tissue, skin color slowed palms and soles, the patient is not complained of pain and swelling, normal daily activities can be carried out; the other mouth ulcers healed, also a slight increase in body weight than before.

附图说明: BRIEF DESCRIPTION OF:

[0141] 图1是50%缩足阈:实验组大鼠50% PffT在第3次给药后较对照组下降,与对照组比较P <0.01。 [0141] FIG. 1 is a 50% paw withdrawal threshold: 50% pfft experimental group after the third dose decreased than the control group, compared with control group P <0.01. 模型组痛行为稳定并持续存在直至试验结束。 Model group and stable pain behavior persisted until the end of the trial. 中药组治疗2周后50% PWT升高,3周后与模型组比较差异具有显著性(P < 0. 01)。 TCM treatment group increased 50% PWT after 2 weeks after 3 weeks was significant (P <0. 01) compared with the model group.

[0142] 图2是热缩足反射潜伏期:实验组大鼠第3次给药后TWL较对照组明显下降(P< ο. 01),模型组痛行为稳定并持续存在直至试验结束。 [0142] FIG. 2 is a thermal withdrawal latency: after the third dose TWL experimental group than the control group significantly decreased (P <ο 01.), Model group and the persistence of pain behavior and stable until the end of the experiment. 中药组治疗1周后TWL有所延长,3周后与模型组比较有明显差异,P < 0. 01。 Medicines TWL 1 week after treatment has been extended, three weeks after comparison with the model group have significant difference, P <0. 01.

[0143] 图3是冷刺激引起的缩足反射潜伏期:实验组大鼠第3次给药后冷刺激引起的缩足反射潜伏期下降(与对照组比较,P < 0.01),模型组痛行为稳定并持续至试验结束。 [0143] FIG. 3 is a latency of paw withdrawal cold stimulation reflection: reflecting flinching after the third dose experimental group induced decrease latency cold stimulation (compared with control group, P <0.01), model group pain behavior stabilization and continuing until the end of the test. 中药组治疗2周后有所好转,3周后与模型组比较差异有显著性(P < 0. 01)。 After 2 weeks of treatment Medicines improved after 3 weeks there was a significant (P <0. 01) compared with the model group.

[0144] 图4是表皮内神经纤维(EnVissionX400):模型组IENF较对照组降低,P < 0. 01。 [0144] FIG. 4 is a intraepidermal nerve fibers (EnVissionX400): IENF model group was lower than the control group, P <0. 01. 中药组较模型组升高,Ρ < 0. 05。 TCM group than in model group increased, Ρ <0. 05. 光镜下棕色细小神经纤维在表皮内及真皮浅层分布丰富, 中药组再生纤维较纤细。 Light microscope brown small nerve fibers in the epidermis and superficial dermis rich distribution, regenerated fibers Medicines more slender. A是对照组,B是模型组,C是中药组。 A is a control group, B is a model group, C is the Chinese groups.

[0145] 图5是表皮内SP的表达(EnViSSiOnX400):正常皮肤仅在小汗腺组织内偶见SP 样物质,其它部位未见特异性染色。 [0145] FIG. 5 is the expression of the epidermal SP (EnViSSiOnX400): Normal skin only occasionally SP-like substance in the eccrine tissue, no other site-specific staining. 模型组表皮内有大量棕色的SP免疫阳性神经末梢。 A large number of model group brown SP immunoreactive nerve terminals in the skin. 这些神经末梢主要位于表皮基底层内,呈串珠状分布,长短不一,可见神经分叉。 These nerve endings primarily located in the basal layer of epidermis, beaded distribution, of varying lengths, visible nerve bifurcation. A是对照组, B是模型组,C是中药组。 A is a control group, B is a model group, C is the Chinese groups. 箭头所指为SP免疫阳性神经末梢。 Arrows indicate SP immunoreactive nerve terminals.

Claims (4)

  1. 一种治疗化疗药物引起的周围神经毒性的外用中药,其特征在于它是由下述重量的原料药制成的药剂:淫羊藿15-25g 老鹳草10-20g 川乌15-25g 川芎10-20g红花10-20g。 A method of treating peripheral neurotoxicity caused by chemotherapy Chinese herbs, characterized in that it is made of a pharmaceutical drug substance by weight of the following: Geranium Epimedium 15-25g 10-20g 15-25g Chuanxiong 10 Chuanwu -20g safflower 10-20g.
  2. 2.根据权利要求1所述的外用中药,其中各原料药的重量是: 淫羊藿20g 老鹳草15g 川乌20g 川芎15g 红花10g。 2. Chinese herbs according to claim 1, wherein the weight of each drug are: Geranium Epimedium 20g 15g 15g safflower Chuanwu Chuanxiong 20g 10g.
  3. 3.根据权利要求1或2所述的外用中药,其特征在于是外用浸剂。 3 or the Chinese herbs according to claim 1, characterized by being external infusion.
  4. 4.根据权利要求1或2所述的外用中药,其制备方法是:将上述原料药水煮煎3次,每次lh,滤过,合并煎液,减压浓缩至50°C时相对密度为1. 15-1. 20的清膏,减压干燥得到干膏,粉碎,过5号筛,加糊精适量,混勻,以85%乙醇制粒,干燥,整粒,分装即得。 Chinese herbs according to claim 1 or claim 2, which is prepared: the raw material medicine fried boiled three times, each time LH, filtered, decoctions were combined, concentrated under reduced pressure to 50 ° C when the relative density clear paste 1. 15-1. 20, dried under reduced pressure to obtain a dry extract, pulverized, passed through a No. 5 sieve, add appropriate amount of dextrin, mixing, granulating 85% ethanol, dried, sieved, to obtain the packaging.
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CN103099862B (en) * 2013-01-28 2014-04-09 山西医科大学 External preparation for treating rheumatism pain disease, as well as preparation method and application thereof
CN103263488B (en) * 2013-05-10 2015-01-21 李玲 Chinese medicine fumigation-washing decoction for treating capecitabine extremities syndrome
CN104587339A (en) * 2015-01-04 2015-05-06 顾岩 Traditional Chinese medicine soaking agent for treating chemotherapy-related peripheral nerve toxicity
CN105147811B (en) * 2015-10-19 2019-02-01 中国中医科学院广安门医院 A kind of external medicine composition and preparation method thereof for preventing and treating hand-foot syndrome
CN105395844A (en) * 2015-11-19 2016-03-16 许红云 Traditional Chinese medicine external lotion for treating peripheral nerve toxicity related to chemotherapy and nursing method
CN105943595A (en) * 2016-06-17 2016-09-21 贾立群 Medicine for treating chemotherapy induced hand-foot syndromes and targeted therapy induced hand-foot skin reactions and preparation method thereof

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CN1139565A (en) 1995-07-04 1997-01-08 上海华联制药公司 Nourishing medicine for preventing and curing toxic and side effect after tumor radiotherapy and chemotherapy and preparation method
CN1200282A (en) 1997-05-26 1998-12-02 陈本洪 Medicine for eliminating toxicity and side-effect casused by chemotherapy during treating cancer

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CN1139565A (en) 1995-07-04 1997-01-08 上海华联制药公司 Nourishing medicine for preventing and curing toxic and side effect after tumor radiotherapy and chemotherapy and preparation method
CN1200282A (en) 1997-05-26 1998-12-02 陈本洪 Medicine for eliminating toxicity and side-effect casused by chemotherapy during treating cancer

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