CN105307647A - 用于治疗口腔粘膜炎的口腔杀菌组合物 - Google Patents
用于治疗口腔粘膜炎的口腔杀菌组合物 Download PDFInfo
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- CN105307647A CN105307647A CN201380072195.4A CN201380072195A CN105307647A CN 105307647 A CN105307647 A CN 105307647A CN 201380072195 A CN201380072195 A CN 201380072195A CN 105307647 A CN105307647 A CN 105307647A
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- oral mucositis
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Abstract
本发明涉及一种用于治疗口腔粘膜的疼痛损伤和不同来源的溃疡性和炎性损伤的药物杀菌组合物。本发明还涉及口腔粘膜炎和口腔炎的治疗和/或预防。
Description
技术领域
本发明涉及药物组合物,这类组合物的用途及其方法,用于口腔粘膜的疼痛损伤、溃疡性损伤例如口疮性溃疡等、不同来源的炎性损伤的治疗,以及,特别是用于在抗癌疗法中口腔粘膜炎的治疗和/或预防。具体地,本发明提供口腔药物组合物用于在抗癌疗法中治疗和/或预防口腔粘膜炎和口腔炎的用途。另外,本发明提供一种与抗癌疗法相关的口腔粘膜炎和口腔炎的治疗方法。
发明背景
口疮性口炎是一种涉及形成一种或多种溃疡的口腔障碍,其会持续数周并在愈合后留下疤痕。这类溃疡可能会在几年后再次出现,持续返回并带来新的损伤,甚至当以前的损伤还没有愈合的时候。后一种情况称为复发性口疮性口炎,以及当感染变成慢性时可能会发生极端情况。口疮性口炎影响两种性别以及,最近,注意力已经被吸引到在健康患者和患有***性疾病例如癌症或糖尿病的患者中这一病理学的治疗和预防,自接受他们各自的治疗疗法后,已经观察到他们中的大约95%显示出一定严重等级的口腔炎,从而显著影响生活质量。
另一方面,口腔粘膜炎为炎性疾病,会消弱口腔粘膜,通常显示为红斑以及在嘴中的疼痛溃疡性损伤和,在口咽粘膜炎的情况下,还会侵袭咽喉和食道。其为在包含放疗和/或化疗的抗癌治疗中的常见并发症,以及其可在接受这一治疗的高达60%的患者中出现。
临床上,粘膜炎的发展经过下列阶段:
1、与粘膜的疼痛红斑相关的萎缩变化,其与局部麻醉有关。
2、疼痛性溃疡伴随着伪膜的形成以及在骨髓抑制治疗的情况下,会发生全身脓毒症,需要抗生素治疗。通常,这样的疼痛强度需要施用***来肠胃外镇痛。
3、自然愈合,通常发生在完成抗癌治疗2至3周后。
其发生率依赖于所诊断瘤的类型及其治疗、患者的年龄以及口腔健康而变化。年轻的患者存在较高的发生率可能是由于更快的上皮细胞再生,以及由此对细胞毒性药物的敏感性。
在化疗治疗的情况下,发生率与这类试剂的选择有关。已经观察到,试剂卡莫司汀(BICNU)、苯丁酸氮芥(Leukeran)、顺铂(Platinol)、阿糖胞苷、阿霉素(Adriamycin)、氟尿嘧啶(5-FU)、甲氨蝶呤(Mexate)和普卡霉素(Mithracin),具有直接潜在的细胞毒性,以及因此它们具有很高的口腔粘膜炎的发生率。积极的管理方案的使用增加也与口腔粘膜炎的发生率增加有关。
在使用放疗治疗的患者中,例如那些诊断为脑和颈部癌的患者,通常会给每日约200cGy的放射剂量,连续5-7周。实施的研究显示,几乎全部的患者发展出一定程度的口腔粘膜炎。
两个最近的研究显示,在对照组中至少94%至96%的患者发展为一定程度的口腔粘膜炎(WHO评定量表)。然后,在来自这两个研究的66%的患者中发展出了相当于依照WHO等级的3和4级的多个口腔粘膜炎。
当前,还没有在接受化疗或放疗患者中用于预防或治疗口腔粘膜炎的普遍接受的治疗方案,因此,缓和治疗对于这种状况是标准程序以及可包括:
·温和冲洗,例如0.9%生理盐水、碳酸氢钠溶液或0.9%生理盐水与碳酸氢钠的组合;
·局部麻醉,例如,包含利多卡因的粘性组合物、软膏和喷雾剂、包含苯佐卡因的喷雾剂或凝胶、0.5%或1%的达克罗宁氯化物或苯海拉明溶液;
·粘膜包衣剂,例如氢氧化铝悬浮液、碱式水杨酸铋悬浮液、包含成膜剂的产品、氰基丙烯酸酯
·镇痛剂,例如苯甲酰胺(benzinamida)氯化物的局部冲洗或通过口服或静脉注射阿片类药物(例如大药丸、连续输注)、经由贴片透皮或穿粘膜;
·生长因子,例如角质细胞生长因子(KGF),也称为帕利夫明。
口腔粘膜炎,尤其是当严重时(依照WHO等级为3-4级),导致对患者嘴巴的日常和常规性能、包括交流和进食方面有显著的负面影响。对于接受脑和颈部癌放疗的大多数患者,口腔粘膜炎导致由于粘膜疼痛而无法经由口腔进食,以及因此,患者被指导经由胃造口管或静脉注射进食。因此,其也显示出患有口腔粘膜炎的患者更有可能有由于治疗和与体重减轻有关的严重疼痛。
另一方面,这种情况可能危害患者经受抗肿瘤治疗的患者的能力,需要限制放射和/或化疗剂量,其可对癌症治疗的不适当的治疗有影响。
基于全部这些,需要提供新的稳定组合物用于治疗和预防粘膜炎,以及特别是由用于癌症治疗的试剂引起的口腔粘膜炎。同样地,需要提供与癌症治疗相关的口腔粘膜炎的治疗或预防的新用途和方法。
现有技术
在现有技术中已经评估了许多用于预防和治疗口腔粘膜炎的化合物。当前的治疗包括冷冻疗法以减少疼痛和炎症、镇静剂以控制疼痛以及抗菌剂以控制由机会性致病菌导致的疾病。镇痛剂,例如基于利多卡因的漱口剂对于疼痛短时间内是有效的,但随着时间推移,会再次出现不适。
在市场上已知的用于缓和治疗口腔粘膜炎的产品为: 和其他基于帕利夫明组合物(人角质细胞生长因子,KGF)的用途;细胞因子,以及其他炎症反应改性剂,例如IL-1、IL-11、TGF-β-3;用氨基酸、维生素补充给药以及激光疗法。
文献US6,509,028公开了包含粘膜粘着剂、局部麻醉剂和阿片类药物(例如***或其可药用盐)的组合物。其公开了这样的组合物用于局部给药,例如用于口腔粘膜或鼻腔的液体喷雾剂,以引起粘膜麻醉,例如在口腔粘膜炎的情况下。
智利专利44471描述了漱口剂形式的制剂和其他用于治疗牙周疾病和口臭的有用的形式。其不包含任何乙醇,以及要求保护治疗牙周疾病,另外防止噬菌斑形成、减少龋齿形成和抑制牙石形成。
因此,存在提供组合物以及特别是所述组合物在治疗口腔粘膜炎和有关症状的新用途的需要,其有效、稳定,以及没有不需要的副作用或不耐性。
发明简述
已经观察到成功治疗粘膜炎的最理想的解决办法是组合使用焦点在于减少炎症、控制病菌和减少疼痛的治疗策略。
本发明组合将这三种治疗效果,也就是抗菌、抗炎症和镇痛效果的使用组合在单一药物形式中。
这种药物组合物的使用显示出,开始为漱口剂形式,可用于治疗或预防口腔粘膜的炎性、溃疡性和疼痛口腔损伤以及尤其是由化疗和/或放疗试剂导致的口腔粘膜炎。所述组合物包含一系列的组分,其为现有技术中已知的允许有效预防和改进患有口腔粘膜炎的患者中的状况的组合物带来改善的效果而没有不希望的副作用。
优选地,本发明的组合物包含一种或多种下列组分,连同可药用赋形剂或添加剂:至少一种杀菌剂和/或抗菌剂;至少一种镇痛组分;至少一种抗炎剂,以及任选的至少一种植物提取物、至少一种甜味剂和一种调味剂。
特别地,本发明涉及本文中限定的组合物在治疗和/或预防尤其是与抗癌治疗相关的口腔粘膜炎、口腔炎和/或口疮损伤的用途,以及治疗或预防口腔粘膜炎、口腔炎和/或口疮损伤的方法,包含向患者施用上述的组合物。
发明详述
本发明涉及包含上述活性组分以及一种或多种可药用赋形剂的组合物的用途。
本发明的组合物可以是任何方便的外形,但优选在给药时为流体形式,例如漱口剂。
尽管依照本发明的漱口剂包含一定量本领域已知的组分,但现有技术并没有公开组合有本文中描述的组分的组合物的用途,其量在后面也是要求保护的,以及在单一组合物中,其已经被证实有效预防、治疗和治愈与由抗肿瘤治疗导致的口腔粘膜炎有关的病症,正如在所附的实施例中展示的那些。
优选地,本发明的组合物包含一种或多种下列组分,连同可药用赋形剂或佐剂:至少一种杀菌剂和/或至少一种抗菌剂;至少一种精油;至少一种酚类杀菌剂;至少一种抗炎剂以及,任选的,至少一种植物提取物、至少一种甜味剂和调味剂。
本发明组合物的组分和比例在下面详述:
本发明的组合物包含至少一种抗菌或杀菌物质,其中所述抗菌或杀菌物质是对于口腔应用无毒的物质。
在本文中使用时,术语“口腔无毒和杀菌物质”是指当按照指示给药时在推荐剂量下是安全的杀菌剂(不会导致不想要的副作用)。例如,当用于漱口剂中时,当用所述漱口剂漱嘴时,无毒性杀菌剂应该是无毒的,即使一部分试剂被吞下。
有许多物质具有抗菌或杀菌性质,其能够破坏或预防病菌的生长。依照本发明的这类抗菌或杀菌物质或试剂的实例包括醇的衍生物,例如乙醇、异丙醇,对羟基苯甲酸酯的衍生物,例如对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丁酯、对羟基苯甲酸丙酯,过氧化物的衍生物,例如过氧化氢、过氧化脲以及其它抗菌或杀菌剂,例如氯己定、葡萄糖酸氯己定、十六烷基吡啶鎓氯化物、三氯生、次氯酸钠等。
依照本发明,抗菌或杀菌剂选自乙醇,其以0.001至0.08%w/w范围、以及优选0.02%w/w的量加入到本发明的组合物中;异丙醇,其添加量的范围为0.001%至0.5%w/w,以及优选0.1%w/w的量,对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丁酯和对羟基苯甲酸丙酯的添加量分别以0.001%至0.1%w/w,以及优选0.06%w/w的量;过氧化氢和/或以过氧化脲的其等效物,其添加量为0.001%至1%w/w,优选0.01至0.1%之间的量以及更优选0.05%w/w的量;氯己定,其添加量为0.1至0.3%w/w,优选0.11%w/w的量;十六烷基吡啶鎓氯化物,其添加量为0.005%至5%w/w,优选0.02至2.5%w/w的量,以及三氯生,其添加量为0.05%至1%w/w,或它们的混合物。
其它杀菌物质的实例包括金属化合物、季铵化合物、碘、或酚类化合物。可用于依照本发明的金属化合物的实例包括硝酸银和磺胺嘧啶银。可用于依照本发明的季铵化合物的实例包括二乙基苄基氯化铵、双十二烷基二甲基氯化铵和苯扎氯铵。可用于依照本发明的酚类化合物的实例包括苯酚、对氯间二甲苯酚(xilenol)、对氯苯酚、甲酚和己基间苯二酚。
化合物硝酸银和磺胺嘧啶银彼此分别的加入量为约0.5至2%w/w,优选为1%w/w的量。化合物二乙基苄基氯化铵、二甲基双十二烷基氯化铵和苯扎氯铵彼此分别的加入量为0.1%至2%w/w,优选为1%w/w的量。酚类化合物,对氯间二甲苯酚、对氯苯酚、甲酚和己基间苯二酚彼此分别的加入量为0.001%至0.1%w/w,优选0.003%至0.08%w/w的量,以及更优选为0.004%w/w的量。
本发明的组合物也可包含可给患者提供益处的其他试剂,例如抗菌素、锌盐和/或氟化物衍生物。另外,本发明的组合物包含至少一种精油,选自百里酚(还称为桉油精)、薄荷醇、丁香酚和水杨酸甲酯,其另外包含抗菌性;它们为患者提供镇痛和清爽的感觉。
百里酚,或桉油精,在本发明组合物中的添加量范围为0.001至0.08%w/w,以及优选为0.02%w/w的量。水杨酸甲酯的加入量范围为0.001%至0.5%w/w,以及优选为0.1%w/w的量。薄荷油的加入量范围为0.001%至0.1%w/w,以及优选为0.06%w/w的量。丁香酚的加入量为0.005%至0.04%w/w,以及优选为0.008%至0.03%w/w的量,和更优选为0.01%w/w的量。
本发明的组合物进一步包含至少一种天然消炎剂,例如樟脑。所述试剂的加入量范围为0.006至0.05%w/w,优选为0.009至0.02%w/w之间的量以及更优选为0.012%w/w的量。
本发明的组合物任选包含至少一种植物提取物,其与其它活性成分相组合提供减少或抑制口腔粘膜表面上细菌生长的协同作用,以及减少由抗癌治疗导致的粘膜炎症。
依据本发明的优选实施方案,植物提取物选自甘菊提取物,具有镇痉、润肤、消炎、收敛、防腐作用的植物物质、和促进成粒状和上皮形成的伤口愈合刺激物。植物提取物,在本发明的组合物中的加入量范围为0.05至0.5%w/w,以及优选为0.1%w/w的量。
本发明的组合物进一步包含调味剂,其可以选自允许增加组合物味道的任意化合物或其混合物。依照本发明的适宜的调味剂为在嘴中提供芳香和/或其他感觉效应的成分,例如清爽或温暖的感觉。这样的成分包括但不限于薄荷醇、乙酸甲酯、乳酸甲酯、樟脑、桉树油、桉油精、噁烷酮、桔子香精、樱桃香精、茴芹、木瓜,等。一种或多种调味剂在本发明的组合物中的存在量为0.01至5%w/w。
本发明的组合物进一步包含可药用载体或赋形剂。一种或多种可药用载体优选包含润湿剂,以改善产品在嘴中的感觉以及防止脱水,以及溶解某些活性成分,并为组合物提供主体和质地。依照本发明的润湿剂的实例包括甘油、山梨醇和二醇,例如丙二醇和聚乙二醇及其混合物。甘油在本发明的组合物中的加入量范围为0.05至0.5%w/w,以及优选为0.1%w/w的量。
本发明的组合物进一步包含甜味剂。这些用于口腔组合物的甜味剂包括例如糖精、右旋糖、木糖醇、蔗糖、蔗糖素、甜菊糖及类似物以及添加量为0.01至15%w/w。
依照本发明的组合物也可用于制备治疗口疮性损伤的药物。
依照本发明的组合物也可用于制备治疗口腔粘膜炎的药物。
本发明的口腔组合物的pH在范围6.0至7.2之间,优选6.5至7.2。本领域的技术人员可通过添加足够量的氢氧化钠、盐酸、磷酸盐缓冲液或缓冲液组合或其它适宜试剂,借助本领域已知的方法来调节组合物的pH至优选范围。
本发明的组合物可通过混合每一种成分和将它们加入到适量的水中来制备。
本领域的技术人员会理解用于本发明组合物中的全部成分(组分)的总和为组合物总重量最高100%。而且,除非另外指出,本文中描述的全部的百分比为基于组合物总重量的百分比。
本发明进一步提供组合物在治疗和/或预防口腔粘膜炎或口腔炎中的用途。
本发明提供了组合物在治疗和/或预防特别是与包含放疗和/或化疗的抗癌治疗有关的口腔粘膜炎或口腔炎中的用途。
特别地,本发明涉及本文中描述的任一种组合物在制备用于治疗和/或预防特别是与包含放疗和/或化疗的抗癌治疗有关的口腔粘膜炎或口腔炎的药物中的用途。
特别地,本发明提供了本文中描述的组合物治疗口腔炎的用途。
同样的,本发明提供了治疗和/或预防特别是与抗癌治疗有关的口腔粘膜炎或口腔炎的方法,其包含下面的步骤:
a.提供一种口腔药物组合物,其包含:
i.至少一种杀菌剂,选自:选自乙醇、异丙醇的醇衍生物,选自对羟基苯甲酸甲酯和对羟基苯甲酸乙酯、对羟基苯甲酸丁酯、对羟基苯甲酸丙酯的对羟基苯甲酸酯衍生物,选自过氧化氢、过氧化脲的过氧化物的衍生物,以及也选自氯己定、葡萄糖酸氯己定、十六烷基吡啶鎓氯化物、三氯生和次氯酸钠;
ii.精油,选自百里酚、薄荷醇、丁香酚和水杨酸甲酯;
iii.酚类杀菌剂,选自苯酚、对-氯间二甲苯酚、对氯苯酚、甲酚和己基间苯二酚;
iv.具有消炎性质的试剂,选自樟脑;
v.调味剂,选自薄荷醇、乙酸甲酯、乳酸甲酯、樟脑、桉树油、桉油精、噁烷酮;和
vi.可药用赋形剂。
b.在口腔中施用药物。
依据本发明的方法,包含施用所述组合物至少2至3天,每天至少3次,优选每天至少5次,优选每周至少4次。
下面的实施例是示例性的以及不应该认为是在任何情况下限制本发明。本领域的技术人员会理解可以施用在权利要求的精神和范围内的本发明的多种变化。
实施例1:用于漱口剂的水溶液制备。
根据如下制备组合物:
1.在烧杯中加入800ml的去矿物质水。
2.随后,以上述量加入组分蔗糖素、樟脑、过氧化氢、对氯苯酚、甘油、丁香酚、甘菊提取物、木糖醇、蓝色染料和薄荷调味剂。
3.然后,加入去离子水使总体积为950mL。
4.然后使用0.1NHCl或0.1NNaOH,或适宜的缓冲液,例如苯甲酸盐/苯甲酸调节pH为7.00,以及用去矿物质水使混合物重量为1000g。
实施例2:组合物用于治疗经历化疗的患者的口腔粘膜炎的用途
在化疗的第二周期,诊断为非霍奇金淋巴瘤的40岁女人,接受高剂量甲氨蝶呤和美法仑组合的癌症治疗。在临床评估期间,口腔粘膜炎的状况依据WHO等级(表1)被诊断为2级。指示了实施例1(III)的组合物的口腔冲洗应用,10ml,每天5次,每次2分钟。
在第三天观察患者,其显示损伤完全缓解以及不存在炎性特征特点或疼痛,将其最初粘膜炎再次分类为依据WHO等级(表1)的0级。
这一治疗在整个周期中持续进行,没有显示出新的口腔损伤。
在下一个化疗周期,给药阿霉素、长春新碱和环磷酰胺,接着给予上一周期的漱口剂,直到治疗的最后也没有显示出口腔损伤。
表1:用于评估口腔粘膜炎的WHO分类
等级 | 描述 |
0 | 没有症状 |
1 | 疼痛和红斑 |
2 | 红斑,溃疡,能够吞咽固体食物 |
3 | 溃疡,广泛的红斑,需要液体食物 |
4 | 因为溃疡不能喂食,需要静脉进食或胃管进食 |
实施例3:组合物用于治疗伴随化学-放射治疗的患者的口腔粘膜炎的用途
男性患者,诊断为扁桃体癌,规定为接受放疗和化疗(顺铂)的组合治疗。
在治疗的第四天,患者发展为依据WHO等级(表1)的2级口腔粘膜炎。用实施例1(III)指示的组合物治疗,10ml,2分钟,每天5次。在第四天检查他的口腔状况,显示炎症完全缓解以及疼痛减少,粘膜炎再次分类为依据WHO等级(表1)的0级。
实施例4:组合物用于治疗放射治疗患者的口腔粘膜炎的用途
男性患者,诊断为鼻咽癌。开始了放疗治疗,每周期5,000cGy。
在一周放疗治疗后,患者有了疼痛溃疡以及口腔损伤,妨碍了其喂食。依据WHO等级(表1)诊断为3级口腔粘膜炎,以及指示用实施例1(III)的组合物进行扶持性治疗,10ml,每天5次,2分钟,在五天后,显示损伤和疼痛缓解,其口腔状况重新分类为口腔粘膜炎依据WHO等级(表1)为0级。
实施例5:组合物用于治疗复发性口疮性口炎的用途
男性患者,40岁。在口腔检查期间,观察到4个疼痛和伤残性溃疡损伤,2个在舌下区以及另2个在面颊的前庭粘膜处,约3至4mm大小以及其被诊断为复发性口疮性口炎,因为患者报告一年内多次患有这些损伤。
开始全部的刮治术治疗和预防,以及每天使用实施例1(III)指示的组合物,每2小时10ml,进行3天。
在第一天,患者立即报告疼痛减轻以及在第四天仅存在少量的原始疼痛的溃疡性损伤。在第七天,患者完全恢复。
Claims (19)
1.一种口腔药物组合物,其用于制备用于治疗和/或预防特别是与抗癌治疗有关的口腔粘膜炎或口腔炎的药物,所述组合物包含:
a.至少一种杀菌剂,其选自:选自乙醇、异丙醇的醇的衍生物,选自对羟基苯甲酸甲酯和对羟基苯甲酸乙酯、对羟基苯甲酸丁酯、对羟基苯甲酸丙酯的对羟基苯甲酸酯的衍生物,选自过氧化氢、过氧化脲的过氧化物的衍生物,以及选自其它杀菌剂,所述其它杀菌剂选自氯己定、葡萄糖酸氯己定、十六烷基吡啶鎓氯化物、三氯生和次氯酸钠;
b.精油,其选自百里酚、薄荷醇、丁香酚和水杨酸甲酯;
c.酚类杀菌剂,其选自苯酚、对-氯间二甲苯酚、对氯苯酚、甲酚和己基间苯二酚;
d.具有抗炎性质的试剂,其选自樟脑;
e.可药用赋形剂。
2.依据权利要求1的口腔药物组合物,其用于制备用于治疗和/或预防特别是与抗癌治疗有关的口腔粘膜炎或口腔炎的药物,其中杀菌剂优选选自过氧化氢和过氧化脲,以及杀菌剂的存在量为0.001%至1%w/w,优选0.01至0.1%的量,以及更优选0.05%w/w。
3.依据权利要求1至2中任一项的口腔药物组合物,其用于制备用于治疗和/或预防特别是与抗癌治疗有关的口腔粘膜炎或口腔炎的药物,其中精油优选选自丁香酚,以及精油的存在量为0.005%至0.04%w/w,以及优选为0.008%至0.03%w/w的量,和更优选为0.01%w/w的量。
4.依据权利要求1至3中任一项的口腔药物组合物,其用于制备用于治疗和/或预防特别是与抗癌治疗有关的口腔粘膜炎或口腔炎的药物,其中酚类杀菌剂优选选自对氯苯酚,以及酚类杀菌剂的存在量为0.001%至0.1%w/w,优选为0.003%至0.08%w/w的量,和更优选为0.004%w/w的量。
5.依据权利要求1至4中任一项的口腔药物组合物,其用于制备用于治疗和/或预防特别是与抗癌治疗有关的口腔粘膜炎或口腔炎的药物,其中抗炎剂优选选自樟脑,以及抗炎剂的存在量为0.006至0.05%w/w,优选为0.009至0.02%w/w之间的量,和更优选为0.012%w/w的量。
6.依据权利要求1至5中任一项的口腔药物组合物,其用于制备用于治疗和/或预防特别是与抗癌治疗有关的口腔粘膜炎或口腔炎的药物,其中所述组合物还以0.05至0.5%w/w范围内的量、优选0.1%w/w的量包含植物提取物,所述植物提取物优选选自甘菊。
7.依据权利要求1至6中任一项的口腔药物组合物,其用于制备用于治疗和/或预防特别是与抗癌治疗有关的口腔粘膜炎或口腔炎的药物,其中所述组合物还包含选自薄荷醇、乙酸甲酯、乳酸甲酯、樟脑、桉树油、桉油精、噁烷酮的调味剂,其存在量为0.01至5%w/w。
8.依据权利要求1至7中任一项的组合物,其用于制备用于治疗由抗肿瘤治疗导致的口腔粘膜炎的药物,其中抗癌治疗选自化疗和/或放疗。
9.依据权利要求8的组合物,其中化疗选自但不限于美法仑、甲氨蝶呤、顺铂、5-氟尿嘧啶、环磷酰胺、氟达拉滨、阿霉素、长春新碱、异环磷酰胺、依托泊苷、卡莫司汀、阿糖胞苷、吉西他滨。
10.依据权利要求1-9中任一项的组合物,其用于制备用于治疗口疮损伤的药物。
11.一种治疗和/或预防特别是与抗癌治疗有关的口腔粘膜炎或口腔炎的方法,其包含下面的步骤:
a.提供一种口腔药物组合物,其包含:
i.至少一种杀菌剂,其选自:选自乙醇、异丙醇的醇衍生物,选自对羟基苯甲酸甲酯和对羟基苯甲酸乙酯、对羟基苯甲酸丁酯、对羟基苯甲酸丙酯的对羟基苯甲酸酯衍生物,选自过氧化氢、过氧化脲的过氧化物的衍生物,以及也选自氯己定、葡萄糖酸氯己定、十六烷基吡啶鎓氯化物、三氯生和次氯酸钠;
ii.精油,其选自百里酚、薄荷醇、丁香酚和水杨酸甲酯;
iii.酚类杀菌剂,其选自苯酚、对-氯间二甲苯酚、对氯苯酚、甲酚和己基间苯二酚;
iv.具有抗炎性质的试剂,其选自樟脑;
v.调味剂,其选自薄荷醇、乙酸甲酯、乳酸甲酯、樟脑、桉树油、桉油精、噁烷酮;和
vi.可药用赋形剂;
b.在口腔中施用药物。
12.依据权利要求11的方法,其中杀菌剂优选选自过氧化氢和过氧化脲,以及杀菌剂的存在量为0.001%至1%w/w,优选0.01至0.1%w/w的量,以及更优选0.05%w/w。
13.依据权利要求11的方法,其中精油优选选自丁香酚,以及精油的存在量为0.005%至0.04%w/w,以及优选为0.008%至0.03%w/w的量,和更优选为0.01%w/w的量。
14.依据权利要求11的方法,其中酚类杀菌剂优选选自对氯苯酚,以及酚类杀菌剂的存在量为0.001%至0.1%w/w,优选为0.003%至0.08%w/w的量,和更优选为0.004%w/w的量。
15.依据权利要求11的方法,其中抗炎剂优选选自樟脑,以及抗炎剂的存在量为0.006至0.05%w/w,优选为0.009至0.02%w/w之间的量,和更优选为0.012%w/w的量。
16.依据权利要求11的方法,其中所述组合物还以0.05至0.5%w/w范围内的量、优选0.1%w/w的量包含植物提取物,所述植物提取物优选选自甘菊。
17.依据权利要求11的方法,其中口腔粘膜炎是由抗肿瘤治疗导致的,其中抗肿瘤治疗选自化疗和放疗。
18.依据权利要求17的方法,其中化疗选自但不限于美法仑、甲氨蝶呤、顺铂、5-氟尿嘧啶、环磷酰胺、氟达拉滨、阿霉素、硫酸长春新碱、异环磷酰胺、依托泊苷、卡莫司汀、阿糖胞苷、吉西他滨。
19.依据权利要求11的方法,其中施用所述组合物至少2至3天,每天至少3次,优选每天至少5次,优选每周至少4次。
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ITUB20160100A1 (it) * | 2016-01-26 | 2017-07-26 | Alessandro Stacchini | Composizione muco adesiva per il risciacquo della bocca, utile nella prevenzione trattamento di mucositi. |
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SG11201908629WA (en) * | 2017-04-19 | 2019-10-30 | Otsuka Pharma Factory Inc | Anti-inflammatory agent |
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WO2020227422A1 (en) * | 2019-05-06 | 2020-11-12 | Greenology Products, Llc | Plant extract compositions |
WO2022099182A1 (en) * | 2020-11-09 | 2022-05-12 | Rucker Capital Advisors | Oral rinse, nasal spray and methods for prevention of covid-19 by lowering viral load of covid-19 |
RU2768593C1 (ru) * | 2021-02-04 | 2022-03-24 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Саратовский национальный исследовательский государственный университет имени Н.Г. Чернышевского" | Способ фототерапии хронического рецидивирующего афтозного стоматита |
AU2021453060A1 (en) * | 2021-07-02 | 2024-02-15 | True Node Sciences, Inc. | Oral pharmaceutical composition for preventing and/or treating diseases of the soft and hard tissues surrounding the tooth in the oral cavity |
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CA2900379A1 (en) | 2014-08-14 |
MX2015010139A (es) | 2016-04-11 |
DK2957282T3 (en) | 2021-07-05 |
EP2957282A4 (en) | 2016-10-05 |
BR112015018827B1 (pt) | 2022-06-14 |
US9801916B2 (en) | 2017-10-31 |
RU2640301C2 (ru) | 2017-12-27 |
EP2957282B1 (en) | 2021-04-14 |
ES2885449T3 (es) | 2021-12-13 |
RU2015137455A (ru) | 2017-03-13 |
PT2957282T (pt) | 2021-08-12 |
JP2016507534A (ja) | 2016-03-10 |
MX354123B (es) | 2018-02-14 |
CN105307647B (zh) | 2019-06-28 |
EP2957282A1 (en) | 2015-12-23 |
WO2014121411A1 (es) | 2014-08-14 |
CA2900379C (en) | 2021-08-31 |
JP6300828B2 (ja) | 2018-03-28 |
US20150374772A1 (en) | 2015-12-31 |
AU2013377736A1 (en) | 2015-08-20 |
BR112015018827A2 (pt) | 2017-07-18 |
AU2013377736B2 (en) | 2018-04-19 |
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