CN117298133B - 归知糖疽有效成分配方在制备治疗糖尿病足药物中的应用 - Google Patents
归知糖疽有效成分配方在制备治疗糖尿病足药物中的应用 Download PDFInfo
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Abstract
本发明公开了一种归知糖疽有效成分配方在制备治疗糖尿病足药物中的应用,涉及医药技术领域。其症见足部皮肤疮疡,局部红、肿、热、痛,肢端皮肤色暗,疼痛、麻木、感觉迟钝,伴咽干口渴,心烦或五心烦热,肢体麻木或感觉迟钝,肢体刺痛,腰膝酸软,大便干结,小便黄赤,舌质暗红,或有瘀斑、瘀点,舌苔黄,寸口脉细滑或细数,趺阳脉可触及或减弱,甚至无搏动;将木犀草素、甘草查耳酮A、知母皂苷B‑II、芒果苷、獐牙菜苷、金丝桃苷、马钱子苷、桃叶珊瑚苷按比例组方,制成口服或外用制剂,可适用糖尿病足部溃疡,足踝以下的浅表溃疡,或侵及肌肉组织深部溃疡,或有脓性分泌物者,具有促进皮肤溃疡愈合、消炎止痛的作用。
Description
技术领域
本发明涉及医药技术领域,尤其涉及归知糖疽有效成分配方在制备治疗糖尿病足药物中的应用。
背景技术
糖尿病患者因合并神经病变及各种不同程度末梢血管病变可引起足部软组织及骨关节系统的破坏与畸形,引发糖尿病足。
糖尿病患者血糖控制不理想导致下肢外周血管病变,从而引起下肢供血不足并导致下肢组织细胞缺氧,加上高糖条件下组织修复、伤口愈合能力明显下降,严重时出现组织坏疽、组织缺失甚至死亡,临床上严重患者往往需要截肢。尿病足是糖尿病最常见、最严重并发症之一,具有高发病率、高复发率、高致残率的特点。现代医学治疗该病多采取介入治疗、血管重建、创面敷料外用、负压创面治疗、截肢等方法,但疗效参差不齐,且病程较长,难以达到满意的疗效。
中医认为糖尿病足的病机关键是气血阴阳亏虚,兼夹湿瘀、热毒,与肝、肾、脾、胃等脏腑功能密切相关。内治多从气血阴阳、脏腑论治,注重调补脏腑气血,兼活血化瘀、解毒化湿,同时考虑糖尿病足溃疡的发展过程,亦可根据疮面辨证分期论治。临床采用中药足浴或中药熏洗治疗0级糖尿病足和溃疡早期,随着病程的发展和疮面的变化,采用散剂、油剂、箍围药等不同剂型和功效的外用药作用于疮面,促进疮面愈合。目前虽有大量关于糖尿病足的临床疗效研究,但尚无统一的辨证分类及疗效标准,同时缺乏大样本、多中心的研究文献,且随访周期不长,文献循证等级不高等;在中药熏洗与足浴的文献中,绝大部分为治疗糖尿病足0级的报道,对溃疡期研究的文献较少,我们认为加强中药熏洗与足浴对糖尿病足溃疡期的探索有一定的应用价值。目前关于糖尿病足发病机制的研究文献报道也相对较少,研究不透彻,尚有广阔的发展空间;同类型外用药物间的比较研究较少,药理学证据不够,对单味药物成分及药理学研究文献虽然 较多但不全面,缺乏对药对和以方剂为整体的药理学研究,中药复方作用机制不明确。关于民族医药治疗糖尿病足的文献也较少,仍需进一步开发和研究。中医药治疗糖尿病足发展前景巨大,挖掘其潜力依赖于规范化的临床实践评价系统、严谨的临床试验设计和基础研究、高质量的研究数据及多中心、多学科的联合研究。
而归知糖疽有效成分配方在制备治疗糖尿病足药物中的应用尚未见相关研究。
发明内容
为了克服背景技术的不足,本发明的目的在于提供一种归知糖疽有效成分配方在制备糖尿病足药物中的应用。
本发明是通过以下技术方案实现的:
一种归知糖疽有效成分配方在制备糖尿病足药物中的应用。
进一步地,所述归知糖疽有效成分配方的成分包括木犀草素、甘草查耳酮A、知母皂苷B-II、芒果苷、獐牙菜苷、金丝桃苷、马钱子苷、桃叶珊瑚苷。
进一步地,归知糖疽有效成分配方各成分的质量份数为木犀草素1.9-3.3份,甘草查耳酮A 0.7-1.8份,知母皂苷B-II2.3-5.0份,芒果苷3.0-5.4份,獐牙菜苷0.5-2.0份,金丝桃苷1.5-4.5份,马钱子苷2.3-4.4份,桃叶珊瑚苷1.0-2.6份。
进一步地,归知糖疽有效成分配方各成分的质量比为木犀草素2.6份,甘草查耳酮A 1.2份,知母皂苷B-II3.7份,芒果苷4.2份,獐牙菜苷1.3份,金丝桃苷3份,马钱子苷3.4份,桃叶珊瑚苷1.8份。
进一步地,本发明的配方可与化学药或中药或生物药组成治疗糖尿病足的药物,可采用制剂学的常规方法制备成口服制剂或外用制剂。
进一步地,口服制剂可以是滴丸、颗粒。
进一步地,药物制剂可以是软膏。
本发明具有以下有益效果:
本发明提供了一种归知糖疽中治疗糖尿病足的活性成分配方用于治疗糖尿病足,症见足部皮肤疮疡,局部红、肿、热、痛,肢端皮肤色暗,疼痛、麻木、感觉迟钝,伴咽干口渴,心烦或五心烦热,肢体麻木或感觉迟钝,肢体刺痛,腰膝酸软,大便干结,小便黄赤,舌质暗红,或有瘀斑、瘀点,舌苔黄,寸口脉细滑或细数,趺阳脉可触及或减弱,甚至无搏动;适用于糖尿病足部溃疡,足踝以下的浅表溃疡,或侵及肌肉组织深部溃疡,或有脓性分泌物者;可以有效促进糖尿病足的溃疡局部皮损愈合、消炎止痛、控制血糖的作用,治疗效果显著。
具体实施方式
为了使本发明实现的技术手段、创作特征、达成目的与功效易于明白了解,下面结合具体实施例,进一步阐明本发明,但下述实施例仅为本发明的优选实施例,并非全部。基于实施方式中的实施例,本领域技术人员在没有做出创造性劳动的前提下所获得其它实施例,都属于本发明的保护范围。下述实施例中,若无特殊说明,所用的操作方法均为常规操作方法,所用设备均为常规设备,各个实施例所用设备材料均相同。
本发明提供一种归知糖疽有效成分配方在制备糖尿病足药物中的应用。所述归知糖疽有效成分配方的成分包括木犀草素、甘草查耳酮A、知母皂苷B-II、芒果苷、獐牙菜苷、金丝桃苷、马钱子苷、桃叶珊瑚苷。本发明通过多项实验研究发现,归知糖疽有效成分对糖尿病足的治疗效果显著。
实施例1:归知糖疽有效成分配方
归知糖疽有效成分配方各成分的质量份数为木犀草素1.9份,甘草查耳酮A 0.7份,知母皂苷B-II2.3份,芒果苷3.0份,獐牙菜苷0.5份,金丝桃苷1.5份,马钱子苷2.3份,桃叶珊瑚苷1.0份。
实施例2:归知糖疽有效成分配方
归知糖疽有效成分配方各成分的质量比为木犀草素3.3份,甘草查耳酮A 1.8份,知母皂苷B-II5.0份,芒果苷5.4份,獐牙菜苷2.0份,金丝桃苷4.5份,马钱子苷4.4份,桃叶珊瑚苷2.6份。
实施例3:归知糖疽有效成分配方
归知糖疽有效成分配方各成分的质量比为木犀草素2.6份,甘草查耳酮A 1.2份,知母皂苷B-II3.7份,芒果苷4.2份,獐牙菜苷1.3份,金丝桃苷3份,马钱子苷3.4份,桃叶珊瑚苷1.8份。
实施例4:归知糖疽有效成分配方颗粒剂的制备
取归知糖疽有效成分配方155g,加入糊精45g,微晶纤维素3g,混匀,制粒,干燥,得到技术方案颗粒剂。
实施例5:归知糖疽有效成分配方滴丸的制备
称取聚乙二醇 6000 250g水浴(80℃)加热煮熔,加入实施例1归知糖疽有效成分配方20g,充分搅拌均匀,以液体石蜡为冷却剂,置玻璃管(4*80cm)中,冷却温度为2℃,滴口内外径为7.0/2.0(mm/mm),滴口距液面为2 cm,滴速以每分60滴为最佳条件,用棉布吸干滴丸表面的冷凝剂,即得本发明组合物滴丸。
实施例6:归知糖疽有效成分配方软膏的制备
软膏配比组成见下表1。
表1 100g实验研究用软膏配比
组分 | 用量g | 占比% |
白凡士林 | 11.089 | 11.089 |
羊毛脂 | 32.414 | 32.414 |
液体石蜡 | 13.648 | 13.648 |
甘油 | 15.354 | 15.354 |
十二烷基硫酸钠 | 0.5118 | 0.5118 |
纯化水 | 12.2832 | 12.2832 |
归知糖疽有效成分配方 | 14.7 | 14.7 |
实验用软膏制备方法:将白凡士林、羊毛脂和液体石蜡置于烧杯中,在80℃水浴加热至熔融,得油相;将乳化剂十二烷基硫酸钠加入蒸馏水与甘油混合溶液中直至完全溶解,得水相;将水相水浴加热至与油相同温后,将油相缓缓加入水相中,于水浴加热条件下搅拌30min后取出,加入归知糖疽有效成分配方14.7%持续搅拌至冷凝即得。
实验例7:归知糖疽有效成分配方治疗糖尿病足大鼠试验
1、实验选材
材料:动物SPF雄性SD大鼠,体重180~200 g。
药物及试剂:自制归知糖疽有效成分配方;链尿素佐菌(STZ),美国Sigma公司。
2、造模方法及分组
大鼠,经适应性喂养1周 后,随机分为正常组和造模组两组,正常组给予普通饲料,造模组给予高脂饲料(普通饲料中添 加10%猪油、10%蛋黄粉和20%蔗糖)喂养1个月,禁食16 h后,腹腔注射链脲佐菌素45 mg/kg,注射完成 后第6天,通过尾静脉采血检测血糖浓度,以2次禁食血糖(FBG)≥11.1 mmol/L或(和)随机血糖≥16.8 mmol/L为糖尿病大鼠成模标准,测得血糖符合标准 后,麻醉大鼠,左后肢近足外侧部剪毛,75%乙醇消毒, 切除全层皮肤,范围0.5 cm×1 cm,并于创面注射10μL金黄色葡萄球菌悬浮液,待大鼠创面出现脓液、足部出现红肿者为造模成功。将造模成功大鼠随机分为模型组、抗生素组、中药组(归知糖疽有效成分组,D组、E组、F组、G组、H组),组间体重、血糖水平比较,差异无统计学意义(P>0.05)。中药组予灌胃,每只1.5 g/(kg•d),抗生素组予头孢拉定灌胃,每只0.16 g/(kg•d),正常组及模型组每天灌服生理盐水,每只1 m L/100 g,均1次/d,共干预1周。
表2 归知糖疽有效成分配方组含量表
组别 | 归知糖疽有效成分配方 | 质量比例 |
D组 | 木犀草素∶甘草查耳酮A∶知母皂苷B-II∶芒果苷∶獐牙菜苷∶金丝桃苷∶马钱子苷∶桃叶珊瑚苷 | 2.6:1.2:3.7:4.2:1.3:3:3.4:1.8 |
E组 | 同D组 | 1.9∶0.7∶2.3∶3.0∶0.5∶1.5∶2.3∶1.0 |
F组 | 同D组 | 3.3∶1.8:5.0:5.4:2.0:4.5:4.4:2.6 |
G组 | 同D组 | 1.65∶0.45∶2.05∶2.75∶0.25∶1.25∶2.05∶0.75 |
H组 | 同D组 | 3.55∶2.05∶5.25∶5.65∶2.25∶4.75∶4.65∶2.85 |
3、观察指标及方法
(1)干预前后大鼠体重监测;
(2)干预前后大鼠血糖监测;
(2)干预1周后眼眶静脉丛采血6mL,离心(3 000 r/min、15 min),分离血清,-20℃保存备用,测定血肿瘤坏死因子-α(TNF-α)、血白细胞介素-6(IL-6)、血C反应蛋白(CRP)。
4、统计学方法
采用SPSS 18.0统计软件,计量资料多组间比较采用方差分析,两两比较用LSD法。
5、结果
(1)各组大鼠体重在治疗前后均较正常组低(P<0.05);与干预前比较,模型组、抗生素组大鼠体重明显下降(P<0.05),正常组、中药组大鼠体重未见明显变化(P>0.05)。见表3。
表3 各组大鼠的体重比较(x̅±s)g
组别 | 例数 | 干预前 | 干预后 | P值 |
正常组 | 11 | 401.82±28.45 | 428.27±33.88 | >0.05 |
模型组 | 12 | 355.67±32.89* | 328.67±42.50 * | <0.05 |
归知糖疽有效成分组 | 13 | 368.89±35.74* | 351.69±42.66 * | >0.05 |
D组 | 13 | 369.92±34.59* | 346.43±41.33 * | >0.05 |
E组 | 13 | 363.85±39.74* | 349.58±38.19 * | >0.05 |
F组 | 13 | 361.41±37.31* | 323.15±41.17 * | >0.05 |
G组 | 13 | 358.92±25.77* | 351.69±42.66 * | >0.05 |
H组 | 13 | 352.92±39.79* | 341.69±42.66 * | >0.05 |
D组 | 13 | 374.92±39.79* | 342.69±41.47 * | >0.05 |
抗生素组 | 13 | 358.15±32.56* | 334.23±34.53 * | <0.05 |
*与正常组比较P<0.05
(2)各组大鼠治疗前后血糖情况造模成功后各组 大鼠血糖在治疗前后均较正常组显著升高(P< 0.01),干预后,模型组、中药组、抗生素组血糖水平组间比较,差异无统计学意义(P>0.05),与干预前比较,模型组血糖较干预前升高(P<0.05),正常组血糖较干预前降低(P<0.05),中药组、抗生素组血糖水平与治疗前比较差异无统计学意义(P>0.05)。见表4。
表4各组大鼠的血糖浓度比较(x̅±s)mmol/L
组别 | 例数 | 干预前 | 干预后 | P值 |
正常组 | 11 | 4.97±0.50 | 4.18±0.50 | <0.05 |
模型组 | 12 | 18.57±3.63* | 21.94±4.71 * | <0.05 |
归知糖疽有效成分组 | 13 | 18.84±4.01* | 21.35±7.78 * | >0.05 |
D组 | 13 | 18.82±4.13* | 20.32±7.21 * | >0.05 |
E组 | 13 | 18.88±4.02* | 20.24±7.68 * | >0.05 |
F组 | 13 | 18.47±4.11* | 20.32±7.08 * | >0.05 |
G组 | 13 | 18.52±4.23* | 20.14±7.45* | >0.05 |
H组 | 13 | 18.88±4.11* | 20.32±7.68 * | >0.05 |
抗生素组 | 13 | 21.88±5.35* | 21.51±2.22 * | >0.05 |
*与正常组比较P<0.05
(3)各组大鼠外周血TNF-α、IL-6、CRP的比较 干预1周后,与正常组比较,模型组血TNF-α、IL-6 均明显升高(P<0.01),中药组、抗生素组血TNF-α、IL-6与正常组比较差异无统计学意义(P>0.05);与模型组比较,抗生素组血TNF-α、IL-6均降低(P<0.05),中药组血IL-6降低(P<0.05),血TNF-α差异无统计学意义(P>0.05)。中药组血TNF-α、IL- 6与抗生素组比较差异无统计学意义(P>0.05)。正常组、模型组、中药组、抗生素组各组CRP组间比较差 异无统计学意义(P>0.05)。见表5。
表5 各组大鼠外周血TNF-α、IL-6、CRP水平比较x̅±s
组别 | 例数 | TNF-α (pg/m L) | IL-6 (pg/m L) | CRP (mg/L) |
正常组 | 11 | 1.68±0.13 | 30.68±18.13 | 868.64±146.47 |
模型组 | 12 | 2.12±0.56* △ | 77.71±29.28 *△▲ | 871.28±195.94 |
归知糖疽有效成分组 | 13 | 1.81±0.24 | 34.61±20.30 | 861.29±121.29 |
D组 | 13 | 1.78±0.22 | 34.66±21.10 | 858.29±120.24 |
E组 | 13 | 1.81±0.21 | 34.60±24.23 | 854.29±119.28 |
F组 | 13 | 1.84±0.12 | 34.46±20.11 | 860.24±128.49 |
G组 | 13 | 1.76±0.22 | 34.65±20.23 | 856.52±120.20 |
H组 | 13 | 1.80±0.22 | 34.64±20.30 | 861.29±121.29 |
抗生素组 | 13 | 1.69±0.74 | 24.99±20.65 | 859.55±112.13 |
*与正常组比较P<0.01;△与抗生素组比较P<0.05;▲与中药 组比较P<0.05
6、小结
本实验结果显示,与抗生素相比,归知糖疽有效成分配方不仅可降低大鼠血主要炎症指标、抑制血糖升高,并且可提高大鼠免疫力,抑制体重下降,考虑其机制主要与归知糖疽配方有效成分的抗感染、抗炎、降糖、提高免疫力等作用有关。
实验例8:归知糖疽有效成分配方对链脲霉素糖尿病大鼠的治疗作用
链脲霉素糖尿病动物模型造模:将链脲霉素(STZ)溶于0.1mol/L柠檬酸缓冲液(pH4.5)中,临用前配制。大鼠常用量为70mg/kg(ip)。一次足量给予动物链脲霉素,造成β细胞大量损伤,胰岛素合成和分泌减少,引起糖代谢紊乱,导致糖尿病。将STZ溶液用0.1 mol/L 无菌枸橼酸-枸橼酸钠缓冲液新鲜配制成2%溶液,调节pH至4.5,滤菌器过滤除菌。大鼠禁食10h按60mg/kg 体重腹腔内或尾静脉一次性注射STZ溶液,24h内随机血糖≥16.7 mmol/L,稳定5d即可作为成功模型。
药物:归知糖疽有效成分配方D组、E组、F组、G组、H组。药物配制:研成粉末,各取40mg溶于40ml蒸馏水中,制成混悬液。
表6 归知糖疽有效成分配方组质量表
组别 | 归知糖疽有效成分配方 | 质量比例 |
D组 | 木犀草素∶甘草查耳酮A∶知母皂苷B-II∶芒果苷∶獐牙菜苷∶金丝桃苷∶马钱子苷∶桃叶珊瑚苷 | 2.6:1.2:3.7:4.2:1.3:3:3.4:1.8 |
E组 | 同D组 | 1.9∶0.7∶2.3∶3.0∶0.5∶1.5∶2.3∶1.0 |
F组 | 同D组 | 3.3∶1.8:5.0:5.4:2.0:4.5:4.4:2.6 |
G组 | 同D组 | 1.65∶0.45∶2.05∶2.75∶0.25∶1.25∶2.05∶0.75 |
H组 | 同D组 | 3.55∶2.05∶5.25∶5.65∶2.25∶4.75∶4.65∶2.85 |
阳性药:降糖灵,山东省医药工业研究所制药厂出品。链脲霉素(STREPTOZOCIN,STZ),规格:1g/瓶, SIGMA公司。
仪器:日本京都II型GLUCOCARO血糖仪,全自动生化测定仪,美国产12孔γ-放免测定仪。
试剂:京都血糖仪所用血糖电极片、全自动生化仪所用血脂试剂,天津德普公司(DPC) 提供的胰岛素放免试剂盒。
动物:Wistar大鼠,购于山东省实验动物中心。
链脲霉素糖尿病大鼠的试验:取Wistar大鼠120只,雌雄各半,体重180-200g。稳定饲料1w,期间取血测空腹血糖2次,以3.7-5.3mmol/L为入选动物标准。其中10只作为正常对照备用。其余110只用链脲霉素 (STZ)造模,造模后7-10d复测空腹血糖,以大于14.0mmol/L作为模型成功大鼠。
将链脲霉素性糖尿病(STZ--DM)大鼠110只随机分为造模、归知糖疽有效成分配方D组、E组、F组、G组、H组、降糖灵组,每组各10只,并设正常对照组10只。归知糖疽有效成分配方D组、E组、F组、G组、H组均按2mg/kg给药,降糖灵组9 mg/kg给药,连续口服葡萄糖耐量试验(1.5 g/kg),尾静脉取血分别测空腹、口服葡萄糖后30min,60min,90min,120min的血糖水平,计算空腹血糖及葡萄糖灌胃后60min血糖区线面积(AUC)。
试验结果:
归知糖疽有效成分配方对STZ-DM大鼠空腹血糖升高有明显的降低作用,与造模组比较均有极显著差异。表6结果表明,归知糖疽有效成分配方对STZ-DM大鼠糖代谢有显著的改善作用,对葡萄糖引起的血糖升高有显著的降低作用,明显降低血糖区线面积,与造模组比较均有极显著差异。
表7 各提取物对STZ-DM大鼠空腹血糖的影响 (mmol/L)
组别 | 剂量(mg/kg) | 试验前血糖 | 造模后血糖 | 给药后血糖 |
正常组 | — | 4.8±0.3 | 4.7±0.3 | 4.7±0.4 |
造模组 | — | 4.9±0.6 | 22.7±3.6 | 21.9±4.1 |
归知糖疽有效成分配方D组 | 2 | 4.8±0.4 | 23.2±3.2 | 20.2±2.4 |
归知糖疽有效成分配方E组 | 2 | 4.8±0.5 | 22.8±3.5 | 9.0±1.7** |
归知糖疽有效成分配方F组 | 2 | 4.9±0.4 | 23.4±3.5 | 20.0±2.2 |
归知糖疽有效成分配方G组 | 2 | 4.8±0.5 | 23.3±3.3 | 6.0±1.3** |
归知糖疽有效成分配方H组 | 2 | 4.7±0.4 | 24.7±3.9 | 6.7±1.6** |
降糖灵组 | 9 | 4.8±0.5 | 23.8±3.8 | 7.2±1.7** |
注:与模型组比较:*P<0.05,**P<0.01。
归知糖疽有效成分配方对STZ-DM大鼠胰岛β-细胞功能的影响:给糖负荷前造模组血清胰岛素水平明显低于正常组,说明链脲霉素对胰岛β-细胞造成一定损伤;本技术方案归知糖疽有效成分配方组血清胰岛素水平明显高于造模组,说明归知糖疽有效成分配方对STZ-DM大鼠胰岛β-细胞损伤有一定的修复作用。正常大鼠给糖负荷后30min血清胰岛素分泌增多,60min出现胰岛素分泌高峰,其后逐渐下降;归知糖疽有效成分配方组在给糖负荷30min血清胰岛素水平迅速升高,且明显高于造模组,对于改善STZ-DM的糖代谢有一定的作用。
实施例9:归知糖疽颗粒治疗糖尿病足临床试验研究
2006年9月—2007年3月,跟踪观察0—4级22例29只糖尿病足溃疡临床主要疗效,主要疗效见下表。
表8 归知糖疽颗粒治疗22例29只糖尿病足溃疡临床主要疗效
2008年9月—2010年12月,跟踪观察0—4级76例89只因神经病变、肢端血管病变糖尿病足下肢临床疗效,临床主要疗效见下表。
表9 归知糖疽颗粒治疗76例89只神经病变、肢端血管病变糖尿病足下肢临床主要疗效
实施例10:典型病例
患者陈某某,女,63岁,贵州人。糖尿病病史约19年,间断口服药物及注射胰岛素治疗,自述血糖控制欠佳。平常感到下肢麻、凉,自行口服药酒(具体不详)治疗。
专科检查:双下肢无水肿,浅表感觉减退,皮温低,双侧腘窝动脉可及,较弱,右侧足背动脉未及;足部皮肤色素沉着明显,1趾远节皮肤色暗,趾甲暗黄;第1、2趾趾蹼破溃约1*2cm,少量分泌物渗出;第2趾肿胀,于内侧见直径约0.8cm类圆形溃疡面,色苍白,呈火山口状,无分泌物,基底部见直径约1.5cm类圆形增生组织,色苍白无明显血供。
临床诊断:2型糖尿病;糖尿病足病(右足 wagner 3级);右足骨质破坏伴第2近节趾间关节脱位;中度贫血;类风湿关节炎。
治疗:口服归知糖疽有效成分配方滴丸8周后,溃疡愈合,下肢转温,肢端颜色明显改善,疼痛基本消失。
Claims (4)
1.归知糖疽有效成分配方在制备治疗糖尿病足药物中的应用,其特征在于:所述归知糖疽有效成分配方由以下成分组成:木犀草素2.6份,甘草查耳酮A 1.2份,知母皂苷B-II3.7份,芒果苷4.2份,獐牙菜苷1.3份,金丝桃苷3份,马钱子苷3.4份,桃叶珊瑚苷1.8份。
2.根据权利要求1所述的归知糖疽有效成分配方在制备治疗糖尿病足药物中的应用,其特征在于:所述归知糖疽有效成分配方的药物剂型为口服制剂或外用制剂。
3.根据权利要求2所述的归知糖疽有效成分配方在制备治疗糖尿病足药物中的应用,其特征在于:所述口服制剂为颗粒或滴丸。
4.根据权利要求2所述的归知糖疽有效成分配方在制备治疗糖尿病足药物中的应用,其特征在于:所述外用制剂为软膏。
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002049575A2 (en) * | 2000-12-21 | 2002-06-27 | The Quigley Corporation | Method and composition for the treatment of diabetic neuropathy |
CN101032591A (zh) * | 2007-04-09 | 2007-09-12 | 唐贝宁医药科技(北京)有限公司 | 一种新型纯中药制剂的配方 |
CN101683454A (zh) * | 2008-09-28 | 2010-03-31 | 刘显富 | 一种纯中药制剂 |
CN103656111A (zh) * | 2012-09-06 | 2014-03-26 | 唐贝宁医药科技(北京)有限公司 | 治疗并预防糖尿病足的内服中药制剂及制备方法 |
CN103845435A (zh) * | 2012-11-30 | 2014-06-11 | 唐贝宁医药科技(北京)有限公司 | 一种治疗糖尿病足的外用中药溶液剂及其制备方法 |
CN109528662A (zh) * | 2019-01-11 | 2019-03-29 | 山东万安药业股份有限公司 | 一种治疗糖尿病足溃疡的内服中药颗粒制剂及制备方法 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6555573B2 (en) * | 2000-12-21 | 2003-04-29 | The Quigley Corporation | Method and composition for the topical treatment of diabetic neuropathy |
-
2023
- 2023-11-30 CN CN202311623289.8A patent/CN117298133B/zh active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002049575A2 (en) * | 2000-12-21 | 2002-06-27 | The Quigley Corporation | Method and composition for the treatment of diabetic neuropathy |
CN101032591A (zh) * | 2007-04-09 | 2007-09-12 | 唐贝宁医药科技(北京)有限公司 | 一种新型纯中药制剂的配方 |
CN101683454A (zh) * | 2008-09-28 | 2010-03-31 | 刘显富 | 一种纯中药制剂 |
CN103656111A (zh) * | 2012-09-06 | 2014-03-26 | 唐贝宁医药科技(北京)有限公司 | 治疗并预防糖尿病足的内服中药制剂及制备方法 |
CN103845435A (zh) * | 2012-11-30 | 2014-06-11 | 唐贝宁医药科技(北京)有限公司 | 一种治疗糖尿病足的外用中药溶液剂及其制备方法 |
CN109528662A (zh) * | 2019-01-11 | 2019-03-29 | 山东万安药业股份有限公司 | 一种治疗糖尿病足溃疡的内服中药颗粒制剂及制备方法 |
Non-Patent Citations (5)
Title |
---|
Clinical Outcomes of Diabetic Foot Management with Circulat;J. A. Olalde;PHYTOTHERAPY RESEARCH;第22卷;1292-1298 * |
冯彬彬.中药药理.中国医药科技出版社,2021,(第1版),66-67. * |
基于网络药理和分子对接预测复方紫银软膏治疗糖尿病足溃疡的作用靶点;郭瑞;云南大学学报;第45卷(第2期);538-548 * |
归知糖疽颗粒对I型糖尿病大鼠周围神经和外周血管病变及形态学的影响;洪晓华;中国中药杂志;第37卷(第20期);3126-3129 * |
归知糖疽颗粒对实验性糖尿病大鼠皮肤溃疡的影响;洪晓华;中国实验方剂学杂志;第13卷(第12期);27-30 * |
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