CN1344153A - 面巾纸组合物以及用于螯合鼻分泌皮肤刺激物的方法 - Google Patents
面巾纸组合物以及用于螯合鼻分泌皮肤刺激物的方法 Download PDFInfo
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- CN1344153A CN1344153A CN99816377A CN99816377A CN1344153A CN 1344153 A CN1344153 A CN 1344153A CN 99816377 A CN99816377 A CN 99816377A CN 99816377 A CN99816377 A CN 99816377A CN 1344153 A CN1344153 A CN 1344153A
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- Materials For Medical Uses (AREA)
Abstract
本发明提供包含薄纸基质、亲水性鼻分泌皮肤刺激物螯合剂和疏水性鼻分泌皮肤刺激物螯合剂的面巾纸。在一个实施方案中,螯合剂由改性的粘土和未改性的粘土组成。本发明还提供螯合鼻分泌皮肤刺激物的方法,它包括给予个体皮肤的角质层面巾纸,该面巾纸含有薄纸基质、鼻分泌皮肤刺激物螯合量的亲水性和疏水性鼻分泌皮肤刺激物螯合剂混合物。在一个实施方案中,皮肤刺激物可与基质上存在的螯合剂结合。在另一实施方案中,皮肤刺激物可与皮肤上存在的螯合剂结合。
Description
本申请要求1998年12月31日申请的美国临时申请号60/114,497和60/114,496的优先权。
发明背景
角质层是皮肤的表皮角质化层,其为水的蒸发提供了屏障,并且本身对地球生命来说是必要的。除防止水分丢失外,角质层还能降低外界环境中不需要分子的渗入。角质层由嵌入富含脂质(脂肪酸、神经酰胺、胆固醇)基质中的死细胞(角质细胞)组成。角质细胞和细胞内脂质均源于表皮的角质细胞。嵌于脂质中的角质细胞结构产生角质层结构和功能的砖(角质细胞)和泥(脂质)模型。皮肤的多种屏障性质都被认为是取决于这种结构。附着于皮肤上的物质必须通过该结构,通过多弯拐的途径才能到达皮肤下的活细胞层。刺激皮肤的物质一经接触到活皮肤细胞,一般即可引发免疫过程的复杂串联。这些过程最终导致皮肤炎症。
鼻唇皮肤比身体的许多其它位置更易于受到皮肤刺激的损伤。这种易损伤性的原因归于:相对于其它身体位置,鼻唇皮肤的屏障性功能降低。通过皮肤的水损失率可被测定出来,它是皮肤屏障性质的指征12。低水平的透皮水损失是正常的。水通过皮肤的运动通常被称为透皮水损失(TEWL),一般表示为g∝ M-2∝hr-1。通常用TEWL读数测定任何给定的时间点处皮肤的的屏障性质13。一般地,可发现不同的解剖学位置之间的TEWL值有显著性差异14。研究表明面部皮肤的屏障性明显低于身体的其它部位。甚至已观察到面部本身的不同部位之间屏障性质的差异14,15。实际上,鼻唇皮肤中得到的TEWL值是面部中得到的最高值。极少例外,发现面部,更具体地讲,鼻唇皮肤具有人体任何皮肤部位的最低屏障性。
关于湿度屏障的皮肤屏障功能(通过TEWL测定)一般还与皮肤排除外源性物质的能力有关14,16。由于对水的屏障降低(TEWL值增加),外源性施加的分子一般更易于渗入到皮肤的活细胞层12。现在认为鼻唇皮肤可更能渗入局部施加的刺激物,因此相对于其它位置更易发炎。
皮肤屏障功能可被多种损伤损害。已知的降低皮肤屏障功能的处理实例包括,但不限于物理性处理(擦伤、胶带条、超声、电场)、酶、溶剂、表面活性剂以及室内湿度升高17,18,19,20,21,22,23。用面巾纸(facialtissue)重复擦拭鼻唇皮肤可因为擦伤而降低皮肤的屏障功能。降低皮肤屏障性功能的损伤通过使透过角质层刺激物的吸收增加,使皮肤易于感染炎症。
患有感冒或过敏的个体的鼻分泌物含有能强烈刺激鼻唇皮肤的各种物质。这些物质包括,但不限于一系列生理活性成分,包括细胞因子、类花生酸、酶和各种毒素。例如,细胞因子白细胞介素-1β(IL-1β)和白细胞介素-8(IL-8)高浓度存在于鼻分泌物中1,2,3。同样地,类花生酸白细胞三烯B4(LTB4)和前列腺素E2(PEG2)也高浓度存在于鼻分泌物中4,5,6,7,8。另外,激酶、类胰蛋白酶、磷脂酶和糖苷酶也存在于鼻分泌物中。最后,鼻分泌物还含有由金黄色葡萄球菌(包括葡萄球菌肠毒素A(SEA)、B(SEB)和中毒性休克综合征毒素-1(TSST-1))产生的超抗原,以及其它细菌副产物。另外,还公开了对局部施加的细胞因子、类花生酸、酶和超抗原的皮肤反应9,10,11。
因此,鼻分泌物中含有多种能在感冒或过敏中产生皮肤炎症的刺激物。这些刺激物附着在鼻唇皮肤上,这个位置一般具有较低的屏障特性。这个解剖学位置的屏障特性可因重复使用面巾纸(在过敏和感冒过程中正常的动作)进一步降低。结果是红且溃疡的鼻子,即一种感冒和过敏患者常经历的症状。
有关鼻分泌物的组成、对鼻分泌物中存在的各种组分的皮肤反应以及鼻唇皮肤的屏障作用等方面,存在多种不相关的研究方法。尽管存在这些不相关的研究领域,但令人奇怪的是尚未说明鼻分泌物诱导皮肤刺激这一概念。因此,尚未有任何技术专门研究有关一般形成皮肤刺激的新原因。本领域至今没有预防或缓解由于鼻分泌物中极其复杂的刺激物混合物引起的皮肤炎症的新机理。
已知多种保护皮肤免受皮肤刺激物作用的方法。实例包括保护服、皮肤保护制剂以及抗炎组合物。
使用保护服是很有效的防止刺激物接触皮肤的方法。但是,即使可获得这样的服装,这种方法也几乎不能使广大的消费者接受用于鼻唇皮肤的服饰。
屏障组合物可产生明显的临床效果。但是,已知虽然许多组合物能阻止一种类型刺激物的渗入,但对其它刺激物并不能提供相似的保护水平24,25。事实表明许多目前可获得的保护剂不能排除很大范围内的在疏水性、大小和/或化学组成上不同的刺激物。因此,许多皮肤保护剂对包含皮肤刺激物复合混合物的生理液体不能提供足够的保护作用。
另一种针对由于接触皮肤刺激物而产生皮肤刺激的方法是使用抗炎化合物。局部应用抗炎化合物并不能保护皮肤避免接触刺激物。而对于许多皮肤刺激物,还出现对皮肤的损伤,但通过抗炎物质可缓解炎症反应。因此,抗炎化合物是通过影响皮肤活细胞的生理学,而不是通过首先阻止诱发炎症的皮肤损伤而发挥作用的。
PCT公布号WO 97/38735说明采用单螯合剂(亲有机物质粘土;用疏水性物质改性的粘土),如quarternium-18皂土,吸收并使粪便蛋白水解酶失活以防止皮肤尿布皮疹。认为其原因是尿布纤维织物可结合分散于超吸收多聚物中的亲有机物质粘土,还可以是其它药学上适合的用于亲有机物质粘土的介质,如洗剂、乳剂、霜剂、凝胶和水溶性介质。该参考文献指出具有8个碳及更长烃链的化合物应不包括在该组合物中。保护组合物特指作为屏障以预防粪便酶接触皮肤的组合物。另外,美国专利Nos.5,017,361和5,702,709中公开采用含有亲有机物质粘土、与季铵化合物交换的离子的洗剂和气雾剂阻断和吸收植物过敏原。另外,本领域存在与皮肤健康无关的目的而将未改性的粘土加入到纸巾制品中的描述(美国专利No.5,611,890和5,830,317)。
增大皮肤屏障性以阻碍外源性刺激物渗入的皮肤保护剂可具有皮肤保健作用。本领域技术人员了解各种实现这些作用的技术方法。本发明的目的是提供保护鼻唇皮肤免受鼻分泌物中存在的皮肤刺激物刺激的必要的新组合物和方法。因此,本发明提供缓解皮肤刺激常见来源的新方法。
本领域需要的是促进皮肤健康的新机理。
本领域需要的是促进鼻唇皮肤健康的新机理。
本领域需要的是缓解或预防由于存在于鼻分泌物中的皮肤刺激物的局部附着引起的鼻唇皮肤刺激或炎症的新机理。需要新的方法,因为鼻分泌物中存在的许多皮肤刺激物对这种生物体液是独特的。
因此,本发明提供通过将鼻分泌物中存在的炎性因子透过角质层渗入并进入到皮肤下活层而引起皮肤炎症的方法。例如,生物活性细胞因子、类花生酸、酶和超抗原可通过角质层渗入到皮肤的活层,并引起不良生物反应,包括皮肤炎症。迄今为止,尚未有鼻分泌物介导的皮肤炎症的概念。因此,本发明提供新的组合物和方法,用以帮助预防由鼻唇皮肤上附着的鼻分泌物引起的不良皮肤症状。
发明概述
本发明提供可阻止皮肤刺激物透过角质层进入皮肤活层的组合物和方法。本发明提供防止鼻分泌物介导的皮肤炎症的组合物和方法。因此,本发明提供促进改善鼻唇皮肤健康的组合物和方法。
本发明的一个实施方案涉及包含薄纸基质的面巾纸,该基质含有对鼻分泌物中存在的皮肤刺激物具有亲和力的螯合剂。本发明的一个实施方案提供薄纸基质,其含有对鼻分泌物中存在的疏水性皮肤刺激物具有亲和力的螯合剂。本发明另一实施方案提供薄纸基质,它含有对鼻分泌物中存在的亲水性皮肤刺激物具有亲和力的螯合剂。在另一替代的实施方案中,本发明提供涉及包含薄纸基质的面巾纸,该基质含有对鼻分泌物中存在的疏水性皮肤刺激物具有亲和力的螯合剂以及对鼻分泌物中存在的亲水性刺激物具有亲和力的螯合剂。
在另一实施方案中,亲水性和疏水性皮肤刺激物螯合剂彼此分开处于在薄纸基质的分隔区域上。
在另一实施方案中,基质的分隔区域可通过各自存在于分离的基质薄片和/或给定的薄片层的亲水性和疏水性螯合剂来限定。
在另一实施方案中,基质的分隔区域可由基质上的图案构型(pattern configutation)所限定,其中亲水性和疏水性螯合剂各自归于基质中图案的分隔区域。
在另一实施方案中,基质的分隔区域可由各自存在于基质的分离纤维上的亲水性和疏水性螯合剂所限定。这些纤维可用螯合剂包衣或填充。以上提到的纤维可包括全部或部分用于制备薄纸基质的所有纤维。
本发明中使用的基质可用多种物质制备。适当的物质包括任何不阻碍螯合剂对鼻分泌皮肤刺激物结合亲和的物质。适当基质的一个实例是用植物纤维制备的薄纸。
为达到有效,螯合剂必须与鼻分泌物中存在的皮肤刺激物结合。鼻分泌物中存在的皮肤刺激物的实例包括,但不限于细胞因子(如白细胞介素-1αα、IL-1β和IL-8)、类花生酸(如PGE2和LTB4)和超抗原(如金黄色葡萄球菌,包括葡萄球菌肠毒素A、B和中毒性休克综合征毒素-1产生的超抗原)。以上所列皮肤刺激物的实例并不代表鼻分泌物中存在的刺激皮肤的所有因素,它们仅作为说明本发明之用。本发明的某些实施方案包括含有对以上所列刺激物具有结合亲和力的亲水性和疏水性螯合剂的面巾纸。
螯合剂可以是任何能与鼻分泌物中存在的皮肤刺激剂结合的物质。螯合剂的实例包括,但不限于改性和未改性的粘土、改性和未改性的二氧化硅、改性和未改性的TiO2以及改性和未改性的高熔点金属氧化物。本发明提供可与亲水性螯合剂(如未改性粘土)结合的亲水性皮肤刺激物(如细胞因子)。同样地,本发明提供可与疏水性螯合剂(如改性粘土)结合的疏水性皮肤刺激物(如类花生酸)。
除提供新的面巾纸外,本发明还提供在角质层最外层上隔绝鼻分泌物中存在的炎症组分的方法。附着于皮肤外层的螯合剂可阻止皮肤刺激物渗入到皮肤下的活细胞层中,因此为皮肤健康提供了益处。在一个实施方案中,通过给予个体鼻唇皮肤有效量的能与鼻分泌物中存在的皮肤刺激物结合的螯合剂而实现这一点。
可通过基质(如面巾纸)将螯合剂传递于皮肤表面,然后通过正常的脱皮过程(正常脱去皮肤的最外层)和/或个人卫生除去。螯合剂从基质至皮肤的转移可通过任何适宜的介质完成,包括,但不限于无水制剂、凝胶、糊剂、霜剂、粉末、洗剂、乳剂或含水制剂或其任何组合。
另外,螯合剂可与面巾纸结合以使与皮肤的相互作用最小。在这种情况下,可通过与存在于面巾纸上的一或多种螯合剂结合,从皮肤上除去刺激物。需清楚的是这两种不同的作用方式(刺激物与附着于皮肤表面的螯合剂结合或者刺激物与面巾纸上存在螯合剂结合,从而将刺激物从皮肤表面移至面巾纸上)并不相互排斥,而是可以结合。
图的简介
图1表示当将鼻分泌物施加于活体人体皮肤模型时出现的促炎反应(IL-1聚集)。
图2表示当将鼻分泌物施加于活体人体皮肤模型时出现的促炎反应(IL-8聚集)。
图3表示各种非改性粘土与皮肤刺激物IL-8螯合的能力。
图4表示通过MTT试验测定表明,施加于皮肤模型的粘土不诱发细胞毒反应。
图5表示粘土预处理可延缓皮肤刺激物IL-8通过体外皮肤模型的渗透。
图6表示粘土与皮肤刺激物IL-8同时使用(co-applied)可延缓IL-8通过体外皮肤的渗透。
图7表示当非改性皂土单独或与其它皮肤刺激物组合存在时,其结合皮肤刺激物白细胞介素-1α的能力。
图8表示当非改性皂土单独或与其它皮肤刺激物组合存在时,其结合皮肤刺激物白细胞介素-1β的能力。
图9表示当非改性皂土单独或与其它皮肤刺激物组合存在时,其结合皮肤刺激物IL-8的能力。
图10表示当非改性皂土单独或与其它皮肤刺激物组合存在时,其结合皮肤刺激物PGE2的能力。
图11表示衍生化粘土和非改性粘土两者与皮肤刺激物IL-8结合的能力。
图12表示衍生化粘土和非改性粘土两者与人的鼻分泌物中皮肤刺激物IL-8结合的能力。
图13表示衍生化粘土和非改性粘土两者与人的鼻分泌物中皮肤刺激物LTB4结合的能力。
图14表示衍生化粘土和非改性粘土两者与人的鼻分泌物中皮肤刺激物PGE2结合的能力。
图15表示当非改性皂土存在于洗剂介质中时,其结合皮肤刺激物IL-8的能力。
图16表示当面巾纸含有或不含非改性皂土时,其结合皮肤刺激物IL-8的能力。
图17表示非改性二氧化硅和TiO2结合皮肤刺激物IL-8的能力。
图18表示皮肤刺激物结合的动力学。
发明详述
本发明提供螯合鼻分泌物中存在的炎性因子以改善鼻唇皮肤健康的组合物和方法。鼻分泌物中存在的皮肤刺激物与皮肤表面(角质层)附着的螯合剂的结合可阻止刺激物渗透到皮肤下层,从而防止皮肤刺激。可通过正常的脱皮过程和/或个人卫生从皮肤除去与皮肤刺激物结合的螯合剂。这种益处还可通过使用结合有螯合剂的纸巾实现。由于立体障碍和/或电荷排斥作用,在一些实施方案中,螯合剂应具有足够的大小或电荷才能抑制皮肤刺激物渗入到活皮肤层。
本发明涉及含有鼻分泌物皮肤刺激物螯合剂的面巾纸,并涉及采用该面巾纸螯合鼻分泌物皮肤刺激物的方法。该面巾纸含有亲水性和疏水性鼻分泌物皮肤刺激物螯合剂。在一个实施方案中,亲水性和疏水性螯合剂通过存在于在面巾纸的不同区域而彼此分隔开来。这种区域性的空间分隔可通过多种不同方法实现。
在本发明的一个实施方案中,亲水性和疏水性螯合剂通过区域分开,其中亲水性和疏水性螯合剂完全地位于面巾纸的分开的区域上。例如,该亲水剂和疏水剂可各自归属于面巾纸的一半部分或者归属于不同区域的更加复杂的图案中,如衍缝(quilted)、网点或栅格。可采用熟知的面巾纸印刷或切口的生产技术,将疏水性和/或亲水性螯合剂传递给本发明的面巾纸中。需清楚的是,在疏水性和亲水性螯合剂区域之间可有一些重叠,但在该实施方案中所设计的至少一些区域,其仅含一种或其它类型的螯合剂。
在另一实施方案中,亲水性和疏水性螯合剂通过区域分开,其中亲水性和疏水性螯合剂各位于面巾纸不同层或表面上。在另一实施方案中,亲水性和疏水性螯合剂通过区域分开,其中该区域为位于基质中分开的纤维上的亲水性和疏水性螯合剂所限制。
此处所用术语“螯合剂”或“螯合物”指对刺激物(生理或其它刺激物)具有亲和力的物质,以使刺激物处于螯合剂附近时,能与该螯合剂共价或非共价结合。在某些实施方案中,对刺激物的亲和力高、快速并不可逆。刺激物与螯合剂相互作用能妨碍或明显降低靶刺激物透过角质层进入到皮下活层的能力。
此处所用术语“螯合作用”是指刺激物对螯合剂的结合。可采用多种熟知的亲和性配体系统达到螯合作用,如吸收性粘土、碳酸钙、滑石粉、二氧化硅、高熔点金属氧化物、二氧化钛(TiO2)、羟基磷灰石、氧化铝、硅酸铝表面活性剂、硅酸钙、活性炭、珍珠粉(pearlstarch)、硫酸钙、抗体、离子交换物质、环糊精、凝集素、Lewis酸/碱物质、活性炭、玻璃微球、硅藻土反应物、衍生物和/或以上物质的混合物。
可用天然、未改性亲水性螯合剂(如粘土、二氧化硅、高熔点金属氧化物和TiO2)结合相对带电荷的蛋白质刺激物。螯合剂,如以天然状态存在的粘土,或者通过化学方法未能使天然态粘土的静电荷明显改变的那些粘土,在此可称为“未改性的”的。未改性粘土是带电荷的,因此具有亲水性。未改性粘土(如皂土)对螯合刺激物,如蛋白质性、亲水性炎症剂等,如细胞因子(如,IL-8)是特别有用的。
本发明提供由于存在疏水性皮肤刺激物,如鼻分泌物中的类花生酸,而通过增加其疏水性对某些螯合剂进行改性方法。疏水性螯合剂,如将天然态粘土通过化学方法使其静电荷明显改变的那些粘土,在此可称为“改性的”。疏水性改性的天然螯合剂(如粘土、二氧化硅和TiO2)优选与相对疏水性的炎性因子(如类花生酸)结合。例如,本发明用于螯合鼻分泌物中存在的类花生酸(如PGE2和LTB4)的改性螯合剂是用季铵化合物改性的皂土。
在某些实施方案中,本发明提供亲水性和疏水性鼻分泌物刺激物螯合剂都存在于其上的面巾纸。体液中以及环境中存在的疏水性和亲水性皮肤刺激物的相对比例随人与人的不同有很大变化。虽然不希望受理论的束缚,但一般认为亲水性皮肤刺激物在刺激物总量中测得的存在量大于疏水性皮肤刺激物的存在量。
因此,面巾纸上的疏水性和亲水性螯合剂的相对比例和位置也可以变化。在某些实施方案中,可使用重量比约1∶100的疏水性螯合剂∶亲水性螯合剂、约1∶20的疏水性螯合剂∶亲水性螯合剂,或约1∶1的疏水性螯合剂∶亲水性螯合剂。同样地,疏水性螯合剂可以以比亲水性螯合剂更大的量存在。因此,在某些实施方案中,可使用重量比约1∶100的亲水性螯合剂:疏水性螯合剂或者约1∶20的亲水性螯合剂∶疏水性螯合剂。
此处所用术语“鼻分泌物刺激物”是指能通过渗入到皮肤角质层从而达到皮肤下活层而刺激鼻唇皮肤的任何组分的鼻分泌物。另外,可降解一或多种角质层组分的物质也被认为是本发明所述的皮肤刺激物。鼻分泌物中存在的皮肤刺激物的实例包括,但不限于细胞因子(如白细胞介素-1α、IL-1β和IL-8)、类花生酸(如PGE2和LTB4)、酶(如胃促胰酶、激酶、胰蛋白酶、磷脂酶和糖苷酶)和超抗原(如金黄色葡萄球菌,包括葡萄球菌肠毒素A、B和中毒性休克综合征毒素-1产生的超抗原)。
此处所用术语“鼻皮肤”是指鼻和鼻周围区域的皮肤。此处所用术语“鼻唇皮肤”为大于鼻皮肤范围的广义术语。它包括鼻皮肤以及唇与鼻孔端侧部分之间的面积。
此处所用术语“亲水性”描述对阳离子性、阴离子性或两亲性带电含氮的分子具有亲和性的物质。另外,术语“亲水性螯合剂”指对亲水性皮肤刺激物比对疏水性螯合剂和/或纸纤维本身具有更大亲和力的螯合剂。能与亲水性螯合剂结合的刺激物的实例包括,但不限于蛋白质性皮肤刺激物,如细胞因子、IL-8、白细胞介素-1α和白细胞介素-1β。
此处所用术语“疏水性”描述能吸引具有明显疏水性区域的脂质分子的物质。另外,术语“疏水性螯合剂”指对疏水性皮肤刺激物比对亲水性螯合剂和/或纸纤维本身具有更大亲和力的螯合剂。能与疏水性螯合剂结合的与鼻分泌物相关的疏水性皮肤刺激物的实例包括,但不限于脂质性皮肤刺激物,如类花生酸、LTB4和PGE2。
此处所用术语“基质”指适于载有螯合剂的物质。基质可包括促使螯合剂传递至皮肤表面的介质。适当的基质实例包括,但不限于织物或非织物,其可包括纸或纤维面巾纸。现有许多有利于将螯合剂传递至皮肤的适当介质。适当的介质是任何可对抗皮肤而将螯合剂传递至皮下的物质。适当介质的实例包括,但不限于无水制剂、含水溶液、洗剂、霜剂、糊剂等。
在本发明的某些实施方案中,要求将疏水性和亲水性螯合剂(如改性和未改性粘土)与亲脂性螯合剂组合物混合。例如,未改性粘土与各种亲脂性螯合剂组合物组合可呈现出协同作用,产生对鼻分泌物皮肤刺激的增加的螯合亲和力。此处所用术语“亲脂性螯合剂组合物”指任何对油比对水具有更高亲和力、并可通过直接与皮肤相互作用以提供皮肤健康益处的物质。这些益处的适当实例包括,但不限于增加皮肤的屏障功能、增加湿度和滋养皮肤。
亲脂性螯合剂组合物可包括硬脂酸、异链烷烃、凡士林及其组合。亲脂性螯合剂组合物还可选自脂肪酸、脂肪酸酯、脂肪醇、三甘油酯、磷脂、矿物油、芳香油、甾醇、甾醇酯、软化剂、蜡及其组合。在某些实施方案中,亲脂性皮肤健康护理剂具有的烃链的平均长度大于8个碳(C-8)。亲脂性皮肤健康护理洗剂组合物的实例为市售提供的凡士林特别护理洗剂(Cheesborough-Ponds,Inc)。
本发明所用适当的亲脂性螯合剂组合物包括,但不限于以下按CTFA命名分类的物质:脂肪和油类:杏仁油、鳄梨油、巴巴苏油、琉璃苣籽油、黄油、C12-C18酸甘油三酯、山茶油、低芥酸菜籽油、辛酸/癸酸/十二烷酸甘油三酯、辛酸/癸酸/亚油酸甘油三酯、辛酸/癸酸/硬脂酸甘油三酯、辛酸/癸酸甘油三酯、胡萝卜油、槚如坚果油、蓖麻油、樱子油、墨西哥油、可可脂、椰子油、鳕油肝油、玉米胚芽油、玉米油、棉子油、C10-C18酸甘油三酯、蛋黄油、环氧化豆油、月见草油、三乙酰基羟基硬脂酸甘油酯、三乙酰基蓖麻酸甘油酯、糖鞘脂、葡萄子油、榛子油、人胚胎脂、混合红花油、混合向日葵子油、氢化蓖麻油、氢化蓖麻油月桂酸酯、氢化椰子油、氢化棉子油、氢化C12-C18酸甘油三酯、氢化鱼油、氢化猪油、氢化鲱油、氢化貂油、氢化橙粗油、氢化棕榈仁油、氢化棕榈油、氢化花生油、氢化鲨鱼肝油、氢化大豆油、氢化牛脂、氢化植物油、羊毛脂和羊毛脂衍生物、猪油、月桂酸/棕榈酸/油酸甘油三酯、雷斯克懒勒油、亚麻子油、胡桃仁油、马来酸酯化大豆油、Meadowfoam子油、鲱油、貂油、辣木油、被孢霉油、牛蹄油、油酸/亚油酸甘油三酯、油酸/棕榈酸/月桂酸/肉豆蔻酸/亚油酸甘油三酯、油硬脂、橄榄壳油、橄榄油、网膜(Omental)脂、粗橙油、棕榈仁油、棕榈油、桃仁油、花生油、
狗脊毛油、奶油树黄油、磷脂、乳香黄连木油、胎盘脂、菜子油、米糠油、红花油、芝麻油、鲨鱼肝油、牛油果脂(Shea Butter)、豆油、鞘脂类、葵花子油、甜杏仁油、松浆油、牛脂、三(二十二烷精)、三癸精、三辛精、三庚精、三羟基甲氧基硬脂精、三羟基硬脂精、三异壬精、三异硬脂精、三月桂精、三亚油精、三亚麻精、三肉豆蔻精、三辛精、三油精、三棕榈精、三脂肪精、三硬脂精、三(十一烷酸精)、植物油、胡桃油、麦糠油、麦胚芽油、Zadoary油等及其混合物。脂肪酸类:花生酸、花生四烯酸、二十二烷酸、癸酸、己酸、辛酸、椰子酸、玉米酸、棉子酸、氢化椰子酸、氢化鲱鱼酸、氢化牛脂酸、氢化硬脂酸、异硬脂酸、月桂酸、亚油酸、亚麻酸、亚麻子酸、肉豆蔻酸、油酸、棕榈酸、棕榈子酸、壬酸、蓖麻油酸、Soy Acid、硬脂酸、松浆油酸、牛脂酸、十一烷酸、十一碳烯酸、麦糠酸等及其混合物。脂肪醇类:二十二烷醇、C9-C11醇、C12-C13醇、C12-C15醇、C12-C16醇、C14-C15醇、辛醇、Cetearyl醇、十六醇、椰子醇、癸醇、氢化牛脂醇、月桂醇、肉豆蔻醇、油醇、棕榈醇、棕榈子醇、硬脂醇、牛脂醇、十三醇等及其混合物。芳香油娄:茴香油、滇荆芥薄荷油、罗勒油、蜂滇荆芥油、香柠檬油、桦木油、苦杏仁油、苦橙油、金盏花油、加利福尼亚肉豆蔻油、蒿子油、小豆蔻油、春黄菊油、肉桂油、鼠尾草油、三叶草油、丁子香油、芫荽油、柏油、桉树油、小茴香油、栀子宁油、香叶油、姜油、葡萄子油、酒花油、山香油、槐蓝灌木油、茉莉油、桧油、弥猴桃油、月桂油、熏衣草油、柠檬草油、柠檬油、椴树油、圆叶当归油、橘子橙油、母菊油、麝香蔷薇油、肉豆蔻油、乳香油、橙花油、橙油、绿叶油、胡薄荷油、薄荷油、松油、松焦油、玫瑰枳子油、迷迭香油、玫瑰油、芸香油、鼠尾草油、接骨木花油、檀香油、黄樟油、银枞油、薄荷油、甘牛至油、香堇菜油、焦油、茶树油、百里香油、野薄荷油、蓍草油、衣兰油等及其混合物。甾醇和/或甾醇衍生物:本发明所用的适当的甾醇及甾醇衍生物包括,但不限于以下物质:在17位上具有尾基(tail)并具有非极性基团的甾醇,如胆甾醇、谷甾醇、豆甾醇和麦角甾醇,以及C10-C30胆甾醇/羊毛甾醇酯、胆钙化甾醇、羟基硬脂酸胆甾醇酯、异硬脂酸胆甾醇酯、硬脂酸胆甾醇酯、7-脱氢胆甾醇、二氢胆甾醇、辛基癸酸二氢胆甾醇酯、二氢羊毛甾醇、十八烷酸二氢羊毛甾醇酯、麦角钙化醇、松浆油甾醇、乙酸大豆甾醇酯、羊毛甾醇、大豆甾醇、鳄梨甾醇、鳄梨精、甾醇酯等及其混合物。润肤剂:本发明所用适当的润肤剂包括,但不限于以下物质:矿物油、矿油胶、凡士林、润肤酯、脂肪酸酯、甘油酯、烷氧基化羧酸、烷氧基化醇、脂肪醇、羊毛脂和羊毛脂衍生物、凡士林基质油、聚硅氧烷、脂肪、氢化植物油、多羟基酯等及其混合物。蜡:本发明所用适当的蜡包括,但不限于以下物质:天然及合成的蜡类,如月桂蜡、蜂蜡、C30烷基二甲基硅氧烷、小烛树蜡、巴西棕榈蜡、地蜡、十六烷基酯、氢化棉子油、氢化霍霍巴油、氢化西蒙得木蜡、氢化微晶蜡、氢化米糠蜡、日本蜡、霍霍巴脂、西蒙得酯、西蒙得木蜡、羊毛脂蜡、微晶蜡、薄荷蜡、二十九烷酸蜡、二十九烷蜡、小冠巴西棕蜡、地黄蜡、石蜡、PEG-6蜂蜡、PEG-8蜂蜡、米糠蜡、紫胶蜡、Spent grain wax、硬脂基(steryl)二甲基硅氧烷合成蜂蜡、合成小烛树蜡、合成巴西棕榈蜡、合成日本蜡、合成西蒙得木蜡、合成蜡等及其混合物。优选蜡包括,但不限于巴西棕榈蜡、地蜡、十六烷基酯、微晶蜡、二十九烷酸蜡、地黄蜡、合成蜡等及其混合物。
所述组合物还包括湿润剂以提供增强的屏障益处和/或皮肤滋润的益处。湿润剂是用于增加皮肤表层水分含量的常用化妆品成分。该组物质包括主要的吸湿性成分。本发明所用适当的湿润剂包括,但不限于以下物质:乙酰胺MEA、芦荟胶、精氨酸PCA、脱乙酰壳多糖PCA、铜PCA、玉米甘油酯、二甲基咪唑啉酮、果糖、葡糖胺、葡萄糖、葡萄糖谷氨酸、葡糖醛酸、谷氨酸、Glycereth-7、Glycereth-12、Glycereth-20、G1ycereth-26、甘油、蜂蜜、氢化蜂蜜、氢化淀粉水解产物、水解玉米淀粉、乳酰胺MEA、乳酸、乳糖赖氨酸PCA、甘露糖醇、甲基Gluceth-10、甲基Gluceth-20、PCA、PEG-2乳酰胺、PEG-10丙二醇、多氨基糖缩合物、PCA钾、丙二醇、丙二醇柠檬酸酯、糖类水解液、异构糖化物、天冬氨酸钠、乳酸钠、PCA钠、山梨糖醇、TEA-乳酰胺、TEA-PCA、脲、木糖醇等及其混合物。
该组合物还可包括乳化表面活性剂。该表面活性剂包括,但不限于脱水山梨醇单油酸酯、脱水山梨醇倍半油酸酯、脱水山梨醇三油酸酯、硬脂酸甘油酯、脱水山梨醇硬脂酸酯、脱水山梨醇三硬脂酸酯等及其混合物。
该组合物还可包括增粘剂。本发明所用适当增粘剂包括,但不限于以下物质:聚烯烃树脂、聚烯烃聚合物、乙烯/乙烯基乙酸酯共聚物、聚乙烯等及其混合物。
亲脂性螯合剂组合物的成分还包括,但不限于湿润剂、表面活性剂和增粘剂,其存在量约为该亲脂性螯合剂组合物总重量的0.1%-10.0%。
本领域技术人员了解本发明组合物可包括所要求的其它物质。实例包括,但不限于可接受的载体、抗炎剂、抗微生物剂、退热剂、皮肤保护剂、缓冲剂、羟基酸、微生物或藻类提取物和/或其组分、酶抑制剂、抗组胺剂、抗氧化剂、镇痛剂、抗氧化剂、收敛剂、香味剂、染料、天然和/或合成维生素衍生物、防晒剂、除臭剂及其混合物。
因此,本发明提供:可用改性和未改性螯合剂颗粒的组合将鼻分泌物中亲水性和疏水性炎性因子螯合于角质层上。该螯合剂可直接从基质中或经可接受的介质被传递至角质层中。可单独用面巾纸或含有一或多种以上提到的介质的面巾纸传递螯合剂。
在某些实施方案中,要求(但不必须)螯合剂颗粒不能有损于终产物的触觉属性。本发明在某些实施方案中提供的螯合剂颗粒直径上限为25μM,更优选小于15μM。在一个实施方案中,螯合剂约占螯合剂/基质组合物总重量的0.001%-5.0%。在另一实施方案中,螯合剂约占螯合剂/基质组合物总重量的0.01%-1.0%。
如上所述,在一个实施方案中,本发明的螯合剂是非改性和改性皂土的组合。本发明所用“未改性”或“非改性”指未经明显化学改变的粘土或其它适当的螯合剂物质,而不是处理和/或纯化该天然物质。本发明将未被修饰为亲有机物质的合成粘土也认为是未改性或非改性的。粘土在其天然状态时,是亲水性的,因此是带电荷的。本发明所用“亲有机物质的”指改性粘土或其它适当的物质,其中通过向该天然物质表面加入相对疏水性物质而明显降低了天然存在的电荷。例如,可采用多种技术,包括用酚、季铵、异丁烯酸甲酯化合物衍生化,完成对粘土的改性。同样地,通过将任意数量的特定组合物加入到非改性螯合剂表面以提供对目标刺激物的增强的亲和性来制备“改性的”螯合剂。一些用于说明的实例包括,但不限于用抗体、外源凝集素或羟基磷灰石包被的颗粒性物质。对专业人员来讲,各种与在此描述的本发明一致的疏水性粒子的改性都是明显的。
可根据各种已知的提供天然物质的疏水性表面特性的方法,通过对天然物质进行改性,实现对相对疏水性刺激物的螯合能力。本领域技术人员非常了解所得到的亲有机物的物质及其制备方法26,27。例如,可采用多种技术,包括用酚、季铵、异丁烯酸甲酯化合物衍生化,完成对粘土的改性28,29,30。同样地,也公开过对二氧化硅表面进行改性的方法31,32,33,34。另外,可采用类似技术对羟基磷灰石进行改性35,36。也可用季铵表面活性剂将二氧化钛衍生化以增强疏水性分子与得到物质相互作用的能力37。这些修饰都适于本发明的疏水性螯合剂。
很显然不同的螯合剂适于与不同刺激物结合。因此,本发明包括采用一或多种螯合剂同时结合多种刺激物的方法。可单独采用单一一种螯合剂(如改性的和亲有机物的物质)以螯合鼻分泌物中存在的皮肤刺激物。另外,基质可包括任何变换的不同天然(非改性)螯合剂、亲有机物质的螯合剂及改性螯合剂的混合物。当然,所有源于单一类别、所有改性的或所有亲有机物质的螯合剂混合物也具有结合鼻分泌物中存在的目标刺激物的能力。
在某些情况下中,要求提供一或多种不同螯合剂的空间分隔以预防所述螯合剂之间的相互作用。这可通过多种方法实现。例如,使一种螯合剂被包裹在纸巾或其它非织造薄片之中,而另一种螯合剂涂于表面。两种或多种螯合剂的图案印刷(patterned printing)也能达到空间分隔。另外,具有存在于不同表面或层或包裹于表面或层之间的螯合剂的多层产品也能提供螯合剂的空间分隔。将不同种螯合剂置于所给层片(ply)和/或不同层片的不同层面上,也可达到不同螯合剂的空间分隔。还可选择和/或修饰用于制备薄片的纤维以提供刺激物螯合性质。不同纤维可承载不同的螯合剂,因此也可提供螯合剂的空间分隔。有可能采用以上各种变换的方法以达到不同螯合剂的空间分隔。
还可要求螯合剂的均匀空间分布以提供更经济地利用螯合剂。例如,可将螯合剂只涂于三层产品的外层或只涂于纸巾表面的中心。对本领域技术人员来讲,其它经济使用螯合剂的空间分布方式是显而易见的。
本发明还提供存在于纸巾或其它非织造或织造材料上的相对大量的一种或多种螯合剂,而一种或多种螯合剂可转移至皮肤上。这种实施方案可使刺激物既与产品结合也能使刺激物与附着在皮肤表面的螯合剂结合。
要将必须应用于皮肤上的改性和/或非改性螯合剂的实际量进行定量是困难的。不同螯合剂具有不同的结合各种刺激物的容量,因此,所述量的多少将取决于所选用的螯合剂。但是,至关重量的是必须使用足以使鼻分泌物引起的刺激明显降低的量。当螯合剂为粘土时,一般用于皮肤的改性或未改性粘土的量为每平方厘米大约0.01μg-100μg的范围。图5和6的结果表明,相当于每cm2皮肤约4.0μg螯合剂的皂土剂量是高度有效的。
本发明方法中所用的粘土一般可以以皮肤病学组合物的形式应用于皮肤上,该组合物包含在可接受的介质中的亲有机物质的和非改性粘土的混悬液。适当的介质包括有机和水溶性液体、无水制剂、洗剂、霜剂、乳液、凝胶等。还可以细分散形式,如与尘粉的混合物,例如与滑石粉或细分散的淀粉粉末的混合物形式使用该亲有机物质的和非改性的粘土。还可将改性粘土用于以上基质的结构中。
局部应用的保护性组合物(介质含有螯合剂)还可用作阻止刺激物接触皮肤的屏障。该介质可含有帮助愈合被刺激皮肤的润肤剂以及保持粘土在混悬液中悬浮的分散剂。该介质应优选对粘土具有惰性,即,它应是避免本身能吸附粘土,从而降低粘土的吸附量而使螯合剂不再有效的物质。
包含本发明螯合剂的非改性的、亲有机物质的和改性的螯合剂可以是适于化妆品应用的任何常用的市售螯合剂。例如,粘土是熟知的物质,在本发明中可用作为螯合剂。其可通过任何已知能在水和/或亲水性溶剂中膨胀形成粘性混悬液的绿类粘土制备。适当的粘土包括天然存在的蒙脱土、皂土、拜来石、锂蒙脱石、皂石或富镁蒙脱石及其合成的对应物,如合成锂皂石。这些粘土具有层片状结构,其中碱金属离子分布于该层片之间。亲水性粘土是天然存在的。将这些粘土用含有主要疏水性区域的长链化合物(如长链季胺)处理可增加该粘土的疏水性,并由此得到亲有机物质的粘土。
用于制备本发明方法中所用的保护皮肤组合物的亲有机物质的改性粘土组分的季铵化合物一般具有1或2个长链取代基(如14-20个碳原子),以及2或3个短链取代基,如甲基。优选的季铵化合物是二甲基二氢化软化剂牛脂氯化铵。由于该牛脂含有大比例的含有18个碳原子的硬脂酸,所以将得到的粘土一般称为quaternium18粘土,如quaternium18皂土或quaternium18锂蒙脱石。这些亲有机物质的粘土的组合物及制备是熟知的。在一个实施方案中,本发明方法中使用的改性的亲有机物质的粘土为quaternium18皂土。
对本发明技术人员来说,本发明可包括所要求的添加剂是显而易见的。实例包括,但不限于可接受的介质、抗炎剂、抗微生物剂、退热剂、皮肤保护剂、脂质、缓冲剂、羟基酸、微生物或藻类提取物和/或其组分、酶抑制剂、湿润剂、抗组胺剂、抗氧化剂、镇痛剂、抗氧化剂、香味剂、染料、天然和/或合成维生素类似物及其混合物。
相对于不含螯合剂的类似组合物,含有螯合剂的这些物质更有益处。由于含有上述添加剂,任何可到达鼻唇皮肤活层的刺激物对皮肤健康很少能产生有害影响。该添加剂能增加抵抗刺激物的可能性,原因是该螯合剂可降低到达皮肤的刺激物的量。
现已发现特别适合的螯合剂是粘土,尤其是皂土。本领域一般技术人员已知皂土是易于得到的、天然存在的粘土。本发明的一个实施方案要求在面巾纸上同时存在亲有机物质和非改性皂土的组合。
在一个实施方案中,亲水性和疏水性螯合剂两者都通过纸纤维薄层传递到皮肤上。制备纸纤维薄层的方法是技术熟练的专业人员已知的,并概述于例如美国专利5,672,248中,结合到本发明中作为参考。
除特别的疏水性和亲水性螯合剂外,本发明规定纸巾基质还可包括填充剂。颗粒状填充剂可选自粘土、碳酸钙、二氧化钛、滑石粉、硅酸铝、硅酸钙、氧化铝三水合物、活性炭、珍珠粉、硫酸钙、玻璃微球、硅藻土及其混合物。
通常,将这些颗粒状填充剂用于造纸过程的水处理结束阶段,通过用阳离子性淀粉将滤液絮凝,再在鼓风机泵出口处用阳离子助留剂进行。絮凝的大小通常是保持纸巾产品理想的不透明水平和强度的重要方面。如果絮凝的粒子太大,虽可得到很好的滞留量,但同时由于空气填充剂与纤维填充剂接触面减少,使强度明显降低且不透明性变差。另一方面,如果絮凝的粒子太小,即使强度未降低且不透明率增大,但滞留量变差。
其它添加剂包括助留剂,本发明使用的该术语是指在造纸过程中用于增加纸巾中螯合剂滞留量的添加剂。本领域中已知有各种阴离子和阳离子助留剂。通常,最常用的阴离子助留剂是带电荷的聚丙烯酸酯,而最常用的阳离子助留剂是带电荷的聚丙烯酰胺。这些助留剂通过采用桥连机理,将混悬的粒子聚结起来。各种各样的分子量和电荷密度的物质均可采用。通常优选带有中等电荷密度的高分子量物质用于絮凝粒子填充剂。该填充物滞留辅助絮凝物很容易通过剪切力粉碎,通常在鼓风机泵开动后加入。
一般采用阳离子淀粉絮凝粘土或其它填充剂颗粒。认为阳离子淀粉在与带阴性电荷的填充剂颗粒结合后变为不溶性的。絮凝的目的是用浓密的淀粉分子覆盖填充剂。淀粉分子为更多的填充剂颗粒的附着提供阳离子表面,从而使絮凝物体积增加。
淀粉填充剂絮凝物的体积是获得强度与光学性质最适平衡的重要因素。絮凝物的体积由淀粉与填充剂混合期间所用的剪切力速率控制。絮凝物一旦形成,不再对剪切力过分地敏感,但随时间的延长或在很高剪切力存在下,它们可被粉碎。
淀粉的电荷特征也是重要的。由于淀粉的使用量通常小于填充剂重量的5%,所以该填充剂-淀粉絮凝物带有负电荷。在这种情况下,采用阳离子助留剂。
有时可使用较高量的淀粉。在这些情况下,填充剂-淀粉絮凝物可实际上带有净正电荷,因此,需要使用阴离子助留剂。
还可使用非颗粒性填充剂。这类非颗粒性填充剂包括热塑胶微球。这些非颗粒性填充剂一般用作处理后期操作中的包衣;但也可在水处理结束阶段使用。当用于
只要不明显或可逆影响螯合剂对皮肤刺激物的结合亲和性,可将其它物质加入到水溶性造纸配料或初期卷纸(embbryonic web)中,以增加产品的其它性质或改进造纸加工。
本领域技术人员将认识到,不仅造纸配料的定性化学组合物对造纸过程很重要,其它因素中的各组分的相对量、加入顺序及时间也是重要的。
实施例:
实施例1
鼻分泌物在人体皮肤模型中诱发的促炎反应
采用EpiDermTM皮肤模型(MatTek Co.;Ashland,MA;目录号EPI-200-HCF)测定鼻分泌物(NS)的促炎(PI)性质。该实验是将收集的NS加入到EpiDermTM模型中,然后将表示皮肤炎症征兆的诱导标记化合物定量。这些标记物包括由EpiDermTM模型中存在的角质细胞产生的初级细胞因子(IL-1α)和二级细胞因子(IL-8)。
从多个个体中得到鼻分泌物,在-70℃下储存至混合。将融化的NS保持在4℃直至用于EpiDerm模型中。将NS样品收集于50ml聚苯乙烯离心管中。混合后,立即以13K Xg将该鼻分泌物离心5分钟。将上清液转移至新的50ml聚苯乙烯离心管中。将沉淀用装备有CV4超声转换器(Vltrasonic Converter)的Virtis Virsonic#475超声波仪超声1分钟。将得到的流体按以上方法离心,将上清液加入到先前的上清液中。将收集的上清液的等份样品在-70℃下储存备用。
按供货商所述操作EpiDermTM模型。将EpiDermTM表面用25μl收集的NS处理,再在37℃下含5%CO2的培养箱中温育24小时。用每次n值为6的处理(每6孔板为一次处理)进行这些实验。每个实验中包括阳性和阴性对照。阴性对照为25μlPBS,阳性对照为25μl浓度为1mg/ml的佛波醇-12-肉豆蔻酸酯-13-乙酸酯(TPA)。在温育期结束时,将条件培养基在-70℃冰箱中储存,以备分析。
用得自R & D Systems,Inc.;Minneapolis,(批号分别为DLA50和D-8050)的ELISA试剂盒测定条件培养基中存在的白细胞介素-1α(IL-1α)和白细胞介素-8(IL-8)的浓度。用Student’s t检验测定各处理间的平均值的差异。显著性水平为P<0.05。
图1表明相对于阴性对照组,在用NS处理的EpiDerm样品的条件培养基中,可检测出明显多的IL-α。图2说明IL-8的相同结果。结果表明当用于活体人体皮肤模型时,NS具有促炎性质。
实施例2
不同粘土作为鼻分泌物中存在的皮肤刺激物的螯合剂的适用性在微量离心管(Eppendorftube)中制备未改性粘土的混悬液(10mg/ml)。用于混悬粘土的流体为含有150mM NaCl、50ng/ml IL-8和0.1%牛血清清蛋白(BSA)的pH 7.4的50mM磷酸盐缓冲液。在各微量离心管中制备各粘土混悬液,皂土(Sigma目录号B-3378)、高岭土(Sigma目录号K-7375)、沸石(Sigma目录号Z-3125)和合成锂皂石粘土(LAP RD MICRO样品号12566-62028;Southern Clay Products,Inc.)。制备只含IL-8溶液不含粘土的对照管。
室温下,将得到的离心管在摇床上温育2小时。然后以10,000rpm速度,在微量离心机Eppendorf5415C上,将离心管离心10分钟,将上清液转移至新离心管中,在-70℃下冷冻供以下分析。
将样品融化,用R & D Systems IL-8 ELISA试剂盒(批号D-8050)测定IL-8含量。将上清液中存在的IL-8的量与缓冲液对照组中回收的IL-8量比较。然后测定作为螯合活性指标的差值(即IL-8损失量)。图3说明各种粘土螯合溶液中的IL-8的能力。结果表明各种粘土对IL-8具有不同的亲和力。对IL-8具有最高亲和力的是皂土,然后依次是高岭土、合成锂皂石和沸石。
实施例3
粘土螯合剂阻止IL-8透过人体皮肤模型
本实验采用的皮肤模型是MatTek’s(Ashland,MA)EpiDermTM皮肤模型(目录号EPI-200-HCF)。使用的粘土为皂土(Sigma目录号B-3378)和高岭土(Sigma K-7375)。
将4个10ug瓶装IL-8(Sigma I-1645)用250μl蒸馏水再水化,各自得到约1.00ml的40μg/ml rhIL-8溶液。
通过将磷酸盐缓冲液加入到预先称重的一定量的粘土中得到20mg/ml皂土和高岭土的混悬液,制备粘土混悬液。通过将原粘土混悬液进行一系列10倍稀释,制备两种粘土的2.0和0.2mg/ml混悬液。
制备2.0x终浓度的白细胞介素-8(IL-8)和粘土两种混悬液。进行共沉淀步骤时,将100μlMIL-8储备液(2x)和100μl粘土混悬液(2x)在1.5ml微量离心管中混合。向微量离心管模型中加入25μl等份样品。进行分步沉淀步骤时,将12.5μl 2.0x粘土混悬液加入到EpiDerm模型中,然后加入12.5μl 2.0x IL-8溶液。在对照组中,将100μlIL-8溶液和100μl磷酸盐缓冲液加入到1.5ml微量离心管中,混合,向EpiDerm模型中加入25μl。
根据制造商的使用说明,但用1.0ml而不是0.9ml的试验培养基,预温育及温育EpiDerm。如上所述处理EpiDerm皮肤模型的表面。在6小时时,抽验50μl培养基,24小时时收集剩余物。收集后,将试管立即置于碎冰中,当收集完所有样品时,立即将其转移至-70℃冷冻箱内,以备分析。
将样品融化并稀释后,用R & D Systems IL-8 ELISA试剂盒(批号D-8050)测定培养基的IL-8含量。
采用添加MTT(溴化3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四唑鎓)的自动售出的(vendor-supplid)试剂盒测定EpiDerm的细胞存活力。存活力结果(示于图4)表明粘土对细胞的存活力没有不利的影响。图5说明用粘土预处理可阻断IL-8的渗入。图6说明与粘土共用可阻断IL-8的渗入。皂土和高岭土都能抑制鼻分泌物中存在的皮肤刺激物IL-8的渗入。在EpiDerm模型中,皂土似乎具有比高岭土更大的作用。
实施例4
白细胞介素-8结合皂土的动力学
测定白细胞介素-8(IL-8)如何快速结合皂土对阐明皮肤上螯合的实际方法是重要的。制备含有150mM NaCl和0.1%牛血清清蛋白(BSA)的50mM磷酸盐缓冲液。在以上缓冲液中,制备浓度为20mg/ml的未改性皂土的双倍浓度(double strength)的混悬液。同样地,通过将10ug瓶装IL-8(Sigma目录号I-1645,批号117H0247)用500μl蒸馏水再水化,制备浓度为500mg/ml的IL-8溶液。将125μl移至4.9ml磷酸盐缓冲液中,使浓度达到500ng/ml。
将500μl 2x粘土缓冲液加入到只装有500μlIL-8的微量离心管中。对照管中只装有500μl磷酸盐缓冲液及500μlIL-8溶液(无粘土)。室温下,将离心管置于摇床上1、2和8分钟(对照管置于摇床上8分钟)。温育完毕后,立即置于Eppendorf5415C微量离心机(室温下,以10,000rpm速度离心5分钟)中以沉淀粘土。移出上清液,转移至新的1.5ml微量离心管中。测定上清液中剩余的IL-8的量。
表1中说明各时间点上粘土上清液中含有的IL-8的量。这些结果表明IL-8对粘土的结合非常快速和完全。表1:
实施例5
时间点(分钟) | 剩余的IL-8(pg/ml) | 剩余的IL-8(对照组的%) |
对照 | 373,000 | 不适用 |
1 | 1,063 | 99.71 |
2 | 792 | 99.78 |
8 | 755 | 99.80 |
多种皮肤刺激物对未改性皂土的同时螯合作用
以上研究表明:采用IL-8作为鼻分泌物相关的皮肤刺激物模型,皂土可从溶液中除去皮肤刺激物。该实验可将本研究范围扩展到包括鼻分泌物中存在的其它公认的皮肤刺激物,包括IL-1α、IL-1β、IL-8和PGE2。评价各螯合剂与单独存在及混合存在的各刺激物的活性。
选择各刺激物的靶浓度以反映鼻分泌物中观测到的最高终浓度。使用的刺激物是PGE2(Calbiochem目录号538904,批号B21932)、IL-1α(R & D Systems 200-LA,批号AC147071)、IL-1β(Sigma I-4019,批号10640049)和IL-8(Sigma I-1645,批号11740247)。使用的螯合剂是皂土(Sigma B-3378,批号67H1576)。制备2个浓度的皂土混悬液(11.11mg/ml和16.67mg/ml分别为工作浓度的1.11x和1.66x)。
制备10x靶浓度的皮肤刺激物溶液。在该方法中,将1份刺激物储备液(10x工作浓度)加入到9份粘土混悬液(1.11x工作浓度)中,得到粘土和刺激物浓度均为1x的混悬液。用于粘土混悬液和刺激物稀释的稀释液是含有150mM NaCl和1%BSA的50mM TRIS缓冲液,pH7.5。
通过将100μl的10x刺激物储备液加入到1.5μl微量离心管中的900μl的1.11x皂土混悬液中,进行特殊刺激物的螯合。室温下,将离心管置于摇床上1小时。以10,000rpm速度,将离心管离心10分钟(微量离心机5415C)。从各管中取出500μl上清液,转移至新离心管中,在-70℃下冷冻直至以后的分析。
按类似方式进行所有四种刺激物的同时螯合,但将100μl各储备液加入到600μl的1.667x皂土溶液中。
按试验混悬液中说明的类似方法,将皂土以10mg/ml浓度混悬于稀释缓冲液中,温育期后将混悬液离心,制备皂土上清液。但是,该过程采用50ml离心管大量进行。以9,000rpm速度,用装备有J-12转子的J-25Ibeckman超离心机,将离心管离心5分钟。将得到的上清液通过装备有低蛋白结合滤器(Gelman Sciences;Ann Arbor,MI)的5μm无菌Acrodisc(Gelman目录号4199)过滤。将900μl等份液置于只装有100μl刺激物储备液(10x)的1.5ml微量离心管中。对各刺激物进行平行操作以保证粘土混悬液螯合剂的组分不干扰以下的ELISA(将“单用缓冲液”与“单用上清液”进行比较)。
用于各刺激物(PGE2、IL-1α、IL-1β和IL-8)的ELISA试剂盒由R&D Systems(Minneapolis,MN)获得并用于对样品中存在的分析物进行定量。
图7说明皂土对IL-1α螯合的结果。图8说明皂土对IL-1β螯合的结果。图9说明皂土对IL-8螯合的结果。图10说明皂土对PGE2螯合的结果。
粘土能有效地从溶液中除去所有的细胞因子。如果向粘土混悬液中单一或混合加入细胞因子,都可除去。用未改性皂土从溶液中除去的PGE2部分没有对细胞因子所估算的那么多。原因可能是由于PGE2的相对疏水性和/或化学组合物。
实施例6
采用未改性和亲有机物质的粘土螯合缓冲液和鼻分泌物中的刺激物
本实验旨在评价各种物质从溶液及人体鼻分泌物中除去(螯合)刺激物的能力。
制备螯合缓冲液(含有150mM NaCl和0.1%牛血清清蛋白(BSA)的50mM磷酸盐缓冲液,pH7.4)。制备浓度为555ng/ml IL-8(SigmaI-1645,批号117H0247)在螯合缓冲液中的1.11X溶液。
为测定缓冲液中IL-8螯合,将9份1.11x IL-8的螯合缓冲液溶液加入到1份10X粘土混悬液中。更详细地讲,将630μlIL-8(@555ng/ml)的螯合缓冲液溶液加入到只装有70μl10x未改性皂土混悬液(100mg/ml)的1.5ml微量离心管中。类似地,采用上述的非改性皂土相同方法,还可用经季铵改性的亲有机物质的蒙脱石粘土(由ClaytoneAPA(Southern Clay Products,Gonzales,TX)获得)进行试验。在这两种情况下,于室温下,将螯合剂IL-8混合物在摇床上温育30分钟,然后以10,000rpm速度,在微量离心管中离心10分钟。收集上清液,在-70℃下冷冻,以备分析。通过将上清液中剩余的IL-8的量与将IL-8加入到相似的无粘土管中所剩余的IL-8的量比较,测定螯合作用。
将先前从个体中收集的未稀释形式的鼻分泌物在-70℃下储存。将其融化,在4℃下,以10,000rpm速度,用装备有JA-12转子的J-25I Beckman超离心机离心10分钟。从各管中移出上清液,收集到洁净的无菌50ml聚苯乙烯离心管中。将沉淀在相似的管中混合,用装备有CV4转换器的Virtis Virsonic 475超声波仪超声处理15秒。然后将超声处理后的物质离心,将得到的上清液加入到先前的上清液中。该过程是处理粘性物质的必要过程。
为测定鼻分泌物中IL-8、PGE2和LTB4螯合,按上述的缓冲液本底测定螯合的方法进行试验。但所用体积不同,将20ul 10X粘土混悬液加入到180μl鼻分泌物中。通过将鼻分泌物上清液中剩余的分析物的量(IL-8、PGE2和LTB4)与鼻分泌物对照组中所剩余的量比较,测定螯合作用。在类似的无粘土管中制备对照品(将20μl无粘土螯合缓冲液加入到180μl鼻分泌物中)。
图11说明非衍生化皂土和Claytone APA对缓冲液中的皮肤刺激物IL-8的除去。结果表明,对除去溶液中的IL-8来说,非改性皂土优于衍生化粘土。发现皂土可除去溶液中99.9%的IL-8,而亲有机物质的粘土(季铵化合物改性的蒙脱土)几乎没有效果,仅能除去溶液中约20%的IL-8。
图12说明非改性皂土能够除去人体鼻分泌物中95%的皮肤刺激物IL-8,而亲有机物质的粘土活性很小,仅能除去约10%的IL-8。
图13提供的证据提示用季铵化合物改性的亲有机物质的粘土可除去人体鼻分泌物中较多的(81%)类花生酸PGE2,而未改性粘土活性很小(除去16%)。类似地,图14表明与未改性粘土相比,亲有机物质粘土对类花生酸LTB4具有更高的亲和力,亲有机物质粘土由于经季铵化合物修饰而相对增加了疏水性,所以可对类花生酸具有增加的亲和性。结果,脂质-衍生的类花生酸对改性粘土具有更高的亲和性。这使改性粘土特别适于结合来自鼻分泌物中的这些特殊的刺激物。实验结果表明利用两种不同螯合剂可同时除去鼻分泌物中存在的两种不同的皮肤刺激物。
实施例7螯合剂存在于原型洗剂介质中时保持的其对鼻分泌物中皮肤刺激物的螯合能力
按以上实施例6中说明的类似实验,测定洗剂螯合溶液中IL-8的能力。为测定洗剂中IL-8的螯合,将9份1.11x IL-8的螯合缓冲液溶液加入到1份试验洗剂(含未改性皂土)、对照洗剂(不含皂土)或10X未改性皂土混悬液中。更详细地讲,将630μl IL-8(@555ng/ml)的螯合缓冲液溶液加入到只装有70μl试验洗剂(1%未改性皂土)、或对照洗剂或10mg/ml未改性皂土混悬液(100mg/ml)的1.5ml微量离心管中。室温下,将螯合剂IL-8混合物在摇床上温育30分钟,然后以10,000rpm速度,在微量离心管中离心10分钟。收集上清液,在-70℃下冷冻,以备分析。通过将上清液中剩余的IL-8的量与将IL-8加入到相似的无洗剂介质或粘土的管中所剩余的IL-8的量比较,测定螯合作用。
制备三种乳液(洗剂A、B和C)。在乳化之前,将粘土(皂土,Sigma目录号B-3378)加入到水和甘油(洗剂A)混合物中,或加入到Polawax和式1混合物(洗剂B)中。当在水/甘油混合液或者Polawax/式1混合液中得到粘土的均匀分散液时,立即用剩余的组分(formulation)(无粘土)乳化,得到最后的洗剂。制备无粘土的对照洗剂(洗剂C)。组分 洗剂Awt% 洗剂Bwt% 洗剂Cwt%水 74 74 75甘油 5 5 5Polawaxa 10 10 10式Ib 10 10 10皂土 1 1 -aPolawax由Corda,LTD.(Parsippany,NJ)获得,按国际化妆品成分命名法(International Nomenclature osmetic Ingredient,INCI)称为乳化蜡NF。b式I含有矿物油(59.8%)、二甲硅油(Dimethicone)(1.0%)、棕榈酸异丙基酯(3.0%)、芦荟提取物(0.1%)、维生素E乙酸酯(0.1%)、地蜡(18%)和硬脂醇(18%)。
图15表明含未改性皂土的洗剂对IL-8螯合的结果。结果表明:如上所述,未改性皂土能结合IL-8并能从溶液中除去它。另外,乳液(1wt%)中含有未改性皂土能从溶液中除去约90%的IL-8,而不含粘土的洗剂未检测出对IL-8的亲和力。
实施例8
用包含粘土的面巾纸原型提供对皮肤刺激物IL-8具有亲和力的面巾纸。
按实验室规模制备薄纸原型(prototypes),得到30gsm加入或未加入非改性皂土的手抄纸。在一个实施方案中,在加入到薄纸上之前,将皂土用沸水预处理(煮过的粘土)。进行手抄纸研究以评估刺激物螯合剂结合进入薄纸结构中的效用。在实验室中,用木纤维(70%bahiaSUL桉树类、30%北方软木牛皮纸)制备薄纸原型。在制备该薄纸时,制备每份原型,要用50克(干重)纤维和大约1950g蒸馏水制备原浆。然后以3000rpm的速率,将原浆用英国纸浆粉碎机(MessmerInstruments Limited Part No.ME 295 Mark IIIC 1mp;KC Item No.:1071274)搅打5分钟。向得到的浆状液中加入2ml 0.5%w/v Kymene(产品编号557LX;Hercules Incorporated;Wilmington,DE)。为制备含有粘土的手抄纸,在继续搅拌下,分次加入625mg皂土。不加入皂土制备对照手抄纸。最后加入粘土之后,再将该浆状液混合1-2分钟。用蒸馏水将得到的浆状液加至8升。然后用Valley Ironwork模板(Voith-Sulzer Papertech;KC Item No.773193),用225ml这种稀释的、混合均匀的浆状液制备8.5平方英寸的薄纸。然后将得到的纸在网板层压(couched off),以每平方英寸75磅的压力,用装备有吸墨纸的压板压制1分钟。将该湿纸用蒸汽干燥机干燥2分钟,然后在约100℃的干燥箱中下干燥至恒重(每平方米30g)。
通过分析方法测定纸巾中存在的粘土量。将预称重的纸巾原型样品在Meker燃烧器中燃烧,在550℃的Muffle加热炉中加热2小时。将得到的灰渣冷却,称重。类似地处理该粘土物质,计算加热过程中因损失的水分或其它易挥发性物质所致的重量损失。从含有粘土的纸巾中存在的灰渣量中减去无粘土对照纸巾中存在的灰渣量。差值即为粘土含量。纸巾原型中检测的粘土量的范围在不可检测至0.38%之间。
采用含有0.1%BSA和150mM NaCl的50mM TRIS缓冲液(@pH7.4)评估纸巾原型螯合皮肤刺激物IL-8的能力。制备终浓度为50ng/ml的IL-8在该缓冲液中的溶液。向置于1.5ml微量离心管中的每mg纸巾中加入100μl IL-8溶液,制成该溶液。室温下,将装有试验纸巾、对照纸巾或仅含有IL-8的缓冲液的离心管在摇床上温育90分钟。温育期结束后,将离心管离心,分析上清液中溶液中剩余的IL-8。通过将对照纸巾中除去的量与缓冲液对照中观测的量以及试验纸巾管中得到的量比较,测定IL-8的螯合作用。
结果(见图16)表明加入非改性皂土可增加纸巾对皮肤刺激物IL-8的亲和力。不含粘土的纸巾从溶液中除去5%的IL-8。但是,带有粘土或煮过的粘土的纸巾分别从溶液中除去82%和92%的IL-8。
实施例9
非粘土螯合剂吸附皮肤刺激物IL-8的能力。
采用上述评估粘土的类似方法,评估二氧化硅和二氧化钛(TiO2)除去鼻分泌物中存在的刺激物(IL-8)的能力。在该实验中,评估平均粒子大小为7nm的热解法二氧化硅(SIGMA S-5130号)、平均粒子大小为1和5μm的二氧化硅以及TiO2。在含有0.1%BSA和150mMNaCl的50mM TRIS缓冲液(@pH 7.4)中,测定这些物质螯合IL-8的能力。制备浓度为35ng/ml的IL-8在该缓冲液中的溶液。通过向置于1.5ml微量离心管中的每mg二氧化硅或TiO2中加入100μl IL-8溶液,测定螯合作用。室温下,将装有试验物质或仅含有IL-8的缓冲液的离心管在摇床上温育60分钟。温育期结束后,将离心管离心,分析上清液中在溶液中剩余的IL-8。通过将管内含试验物质的上清液中IL-8的量与无螯合剂对照管中存在的量比较,测定IL-8的螯合作用。
结果(见图17)表明二氧化硅和TiO2都具有结合皮肤刺激物IL-8的能力。
实施例10
皮肤刺激物(IL-8和PGE2)对非粘土螯合剂的结合动力学。
对二氧化硅和二氧化钛(TiO2)除去鼻分泌物中存在的刺激物(IL-8和PGE2)的能力作为时间的函数进行评估,测定所采用的方法与上述单次60分钟温育评估二氧化硅和TiO2结合皮肤刺激物的方法类似。在该实验中,再次评估平均粒子大小为7nm的热解法二氧化硅(SIGMA S-5130号)、平均粒子大小为1和5μm的二氧化硅以及TiO2。在含有0.1%BSA和150mM NaCl的50mM TRIS缓冲液(@pH7.4)中,测定IL-8和PGE2螯合作用。制备目标浓度为50ng/ml的IL-8在该缓冲液中的溶液。类似地制备PGE2溶液。通过向置于1.5ml微量离心管中的每mg二氧化硅或TiO2中加入100μl刺激物溶液,测定螯合作用。室温下,将装有试验物质或仅含有IL-8缓冲液的离心管在摇床上温育2、5、10和30分钟。平行进行评估PGE2螯合作用的过程。在各个温育期结束时,将离心管离心,分析上清液中在溶液中剩余的IL-8或PGE2。通过将管内含试验物质的上清液中存在的各分析物的量与无螯合剂的对照管中存在的量比较,测定IL-8或PGE2的螯合作用。IL-8的螯合作用的结果概括于图18中。未测定PGE2与二氧化硅或TiO2的结合(数据未示出)。
表2证实IL-8与这些螯合剂的结合是快速的。结果表明二氧化硅和TiO2都具有结合皮肤刺激物IL-8的能力(图18),并且这种结合是快速的(表2)。但是,非改性二氧化硅和TiO2对鼻分泌物中存在的相对疏水性皮肤刺激物PGE2不具有可检测的亲和力(数据未示出)。表2:
时间点(温育分钟) | 热解法二氧化硅剩余的IL-8(pg/ml) | 二氧化硅剩余的IL-8(pg/ml) | TiO2剩余的IL-8(pg/ml) |
对照 | 44,891 | 44,891 | 44,891 |
2 | 9,755 | 1,135 | 1,816 |
5 | 866 | 920 | 732 |
10 | 375 | 827 | 972 |
上述本发明实施方案仅供说明和解释之用。并不打算全部加以说明或者将本发明限定于所公开的精确形式。根据上述,可进行明显的修饰或改变。所选择及说明的实施方案用以提供本发明原理的说明,本领域一般技术人员可将其应用于本发明各种实施方案中,并为适合特别设计的用途进行各种修饰。当根据公平、合法及公正地授权的的范围进行解释时,所有这些修饰或改变都在本发明的范围之内,这可通过所附的权利要求书确认。
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Claims (102)
1.一种面巾纸,其包含薄纸基质、亲水性鼻分泌皮肤刺激物螯合剂和疏水性鼻分泌皮肤刺激物螯合剂。
2.权利要求1的面巾纸,其中所述亲水性和疏水性鼻分泌皮肤刺激物螯合剂彼此分开处于基质的分隔区域上。
3.权利要求2的面巾纸,其中所述基质的分隔区域被限定为基质的分离层。
4.权利要求2的面巾纸,其中所述基质的分隔区域被限定为基质的分离层片。
5.权利要求2的面巾纸,其中所述基质的分隔区域被基质上的图案构型所限定。
6.权利要求2的面巾纸,其中所述基质的分隔区域被基质的分离纤维所限定。
7.权利要求1的面巾纸,其中所述薄纸基质包括纸纤维。
8.权利要求1的面巾纸,其中所述亲水性鼻分泌皮肤刺激物螯合剂结合细胞因子。
9.权利要求8的面巾纸,其中所述细胞因子选自白细胞介素-8、白细胞介素-1α和/或白细胞介素-1β。
10.权利要求1的面巾纸,其中所述疏水性鼻分泌皮肤刺激物螯合剂结合类花生酸。
11.权利要求10的面巾纸,其中所述类花生酸是前列腺素。
12.权利要求11的面巾纸,其中所述前列腺素是E2。
13.权利要求10的面巾纸,其中所述类花生酸是白细胞三烯。
14.权利要求13的面巾纸,其中所述白细胞三烯是白细胞三烯B4。
15.权利要求1的面巾纸,其中所述亲水性鼻分泌皮肤刺激物螯合剂是未改性的粘土、二氧化硅或二氧化钛。
16.权利要求1的面巾纸,其中所述亲水性鼻分泌皮肤刺激物螯合剂是皂土、高岭土、合成锂皂石、沸石、蒙脱土、拜来石、锂蒙脱石、皂石或富镁蒙脱石。
17.权利要求1的面巾纸,其中所述亲水性鼻分泌皮肤刺激物螯合剂是皂土。
18.权利要求1的面巾纸,其中所述亲水性鼻分泌皮肤刺激物螯合剂以面巾纸总重量的0.001%-5.0%重量的量存在于薄纸中。
19.权利要求1的面巾纸,其中所述亲水性鼻分泌皮肤刺激物螯合剂以面巾纸总重量的0.01%-1.0%重量的量存在于薄纸中。
20.权利要求1的面巾纸,其中所述疏水性鼻分泌皮肤刺激物螯合剂是疏水性改性的粘土、疏水性改性的二氧化硅或疏水性改性的二氧化钛。
21.权利要求1的面巾纸,其中所述疏水性鼻分泌皮肤刺激物螯合剂是季铵改性的皂土。
22.权利要求1的面巾纸,其中所述疏水性鼻分泌皮肤刺激物螯合剂是季铵改性的蒙脱土。
23.权利要求1的面巾纸,其中所述疏水性鼻分泌皮肤刺激物螯合剂以面巾纸总重量的0.001%-5.0%重量的量存在于薄纸中。
24.权利要求1的面巾纸,其中所述疏水性鼻分泌皮肤刺激物螯合剂以面巾纸总重量的.01%-1.0%重量的量存在于薄纸中。
25.权利要求1的面巾纸,其中所述皮肤刺激物与基质中存在的螯合剂结合。
26.权利要求1的面巾纸,其中所述皮肤刺激物与皮肤上存在的螯合剂结合。
27.一种面巾纸,其包括薄纸基质和疏水性鼻分泌皮肤刺激物螯合剂。
28.权利要求27的面巾纸,其中所述薄纸基质包括纸纤维。
29.权利要求27的面巾纸,其中所述疏水性鼻分泌皮肤刺激物螯合剂结合类花生酸。
30.权利要求29的面巾纸,其中所述类花生酸选自前列腺素。
31.权利要求30的面巾纸,其中所述前列腺素是E2。
32.权利要求29的面巾纸,其中所述类花生酸是白细胞三烯。
33.权利要求32的面巾纸,其中所述白细胞三烯是白细胞三烯B4。
34.权利要求27的面巾纸,其中所述疏水性鼻分泌皮肤刺激物螯合剂是疏水性改性的粘土、疏水性改性的二氧化硅或疏水性改性的二氧化钛。
35.权利要求27的面巾纸,其中所述疏水性鼻分泌皮肤刺激物螯合剂是季铵改性的皂土。
36.权利要求27的面巾纸,其中所述疏水性鼻分泌皮肤刺激物螯合剂是季铵改性的蒙脱土。
37.权利要求27的面巾纸,其中所述疏水性鼻分泌皮肤刺激物螯合剂以面巾纸总重量的0.001%-5.0%重量的量存在于薄纸中。
38.权利要求27的面巾纸,其中所述疏水性鼻分泌皮肤刺激物螯合剂以面巾纸总重量的.01%-1.0%重量的量存在于薄纸中。
39.一种面巾纸,其包括薄纸基质和亲水性鼻分泌皮肤刺激物螯合剂。
40.权利要求39的面巾纸,其中所述薄纸基质包括纸纤维。
41.权利要求39的面巾纸,其中所述亲水性鼻分泌皮肤刺激物螯合剂结合细胞因子。
42.权利要求39的面巾纸,其中所述细胞因子选自白细胞介素-8、白细胞介素-1α或白细胞介素-1β。
43.权利要求39的面巾纸,其中所述亲水性鼻分泌皮肤刺激物螯合剂是未改性的粘土、二氧化硅或二氧化钛。
44.权利要求39的面巾纸,其中所述亲水性鼻分泌皮肤刺激物螯合剂是皂土、高岭土、合成锂皂石、沸石、蒙脱土、拜来石、锂蒙脱石、皂石或富镁蒙脱石。
45.权利要求39的面巾纸,其中所述亲水性鼻分泌皮肤刺激物螯合剂是皂土。
46.权利要求39的面巾纸,其中所述亲水性鼻分泌皮肤刺激物螯合剂以面巾纸总重量的0.001%-5.0%重量的量存在于薄纸中。
47.权利要求39的面巾纸,其中所述亲水性鼻分泌皮肤刺激物螯合剂以面巾纸总重量的0.1%-1.0%的量存在于薄纸中。
48.权利要求1、27或39的面巾纸,其还包含选自凝胶剂、糊剂、霜剂、粉末剂、洗剂、乳剂或含水制剂及其任意组合的介质。
49.权利要求1或48的面巾纸,其还包含亲脂性螯合剂组合物。
50.权利要求49的面巾纸,其中所述亲脂性螯合剂具有大于8个碳的平均烃链长度。
51.权利要求49的面巾纸,其中所述亲脂性皮肤健康护理剂选自硬脂酸、异链烷烃、凡士林及其任意组合。
52.权利要求49的面巾纸,其中所述亲脂性皮肤健康护理剂选自脂肪酸、脂肪酸酯、脂肪醇、甘油三酯、磷脂、矿物油、芳香油、甾醇、甾醇酯、润肤剂、蜡类及其任意组合。
53.一种螯合鼻分泌刺激物的方法,其包括给予个体皮肤含有薄纸基质、亲水性鼻分泌皮肤刺激物螯合剂和疏水性鼻分泌皮肤刺激物螯合剂的面巾纸。
54.权利要求53的方法,其中所述亲水性和疏水性鼻分泌皮肤刺激物螯合剂彼此分开处于基质的分隔区域上。
55.权利要求54的方法,其中所述基质的分隔区域被限定为基质的分离层。
56.权利要求54的方法,其中所述基质的分隔区域被限定为基质的分离层片。
57.权利要求54的方法,其中所述基质的分隔区域被基质上的图案构型所限定。
58.权利要求54的方法,其中所述基质的分隔区域被基质的分离纤维所限定。
59.权利要求53的方法,其中所述薄纸基质包括纸纤维。
60.权利要求53的方法,其中所述亲水性鼻分泌皮肤刺激物螯合剂结合细胞因子。
61.权利要求60的方法,其中所述细胞因子选自白细胞介素-8、白细胞介素-1α或白细胞介素-1β。
62.权利要求53的方法,其中所述疏水性鼻分泌皮肤刺激物螯合剂结合类花生酸。
63.权利要求62的方法,其中所述类花生酸是前列腺素。
64.权利要求63的方法,其中所述前列腺素是E2。
65.权利要求62的方法,其中所述类花生酸是白细胞三烯。
66.权利要求65的方法,其中所述白细胞三烯是白细胞三烯B4。
67.权利要求53的方法,其中所述亲水性鼻分泌皮肤刺激物螯合剂是未改性的粘土、二氧化硅或二氧化钛。
68.权利要求53的方法,其中所述亲水性鼻分泌皮肤刺激物螯合剂是皂土、高岭土、合成锂皂石、沸石、蒙脱土、拜来石、锂蒙脱石、皂石或富镁蒙脱石。
69.权利要求53的方法,其中所述亲水性鼻分泌皮肤刺激物螯合剂是皂土。
70.权利要求50的方法,其中所述亲水性鼻分泌皮肤刺激物螯合剂以面巾纸总重量的0.001%-5.0%重量的量存在于薄纸中。
71.权利要求53的方法,其中所述亲水性鼻分泌皮肤刺激物螯合剂以面巾纸总重量的0.01%-1.0%重量的量存在于薄纸中。
72.权利要求53的方法,其中所述疏水性鼻分泌皮肤刺激物螯合剂是疏水性改性的粘土、疏水性改性的二氧化硅或疏水性改性的二氧化钛。
73.权利要求53的方法,其中所述疏水性鼻分泌皮肤刺激物螯合剂是季铵改性的皂土。
74.权利要求53的方法,其中所述疏水性鼻分泌皮肤刺激物螯合剂是季铵改性的蒙脱土。
75.权利要求53的方法,其中所述疏水性鼻分泌皮肤刺激物螯合剂以面巾纸总重量的0.001%-5.0%重量的量存在于薄纸中。
76.权利要求53的方法,其中所述疏水性鼻分泌皮肤刺激物螯合剂以面巾纸总重量的.01%-1.0%重量的量存在于薄纸中。
77.一种螯合鼻分泌皮肤刺激物的方法,其包括给予患者皮肤含有薄纸基质和疏水性鼻分泌皮肤刺激物螯合剂的面巾纸。
78.权利要求77的方法,其中所述薄纸基质包括纸纤维。
79.权利要求77的方法,其中所述疏水性鼻分泌皮肤刺激物螯合剂结合类花生酸。
80.权利要求79的方法,其中所述类花生酸是前列腺素。
81.权利要求80的方法,其中所述前列腺素是E2。
82.权利要求79的方法,其中所述类花生酸是白细胞三烯。
83.权利要求82的方法,其中所述白细胞三烯是白细胞三烯B4。
84.权利要求77的方法,其中所述疏水性鼻分泌皮肤刺激物螯合剂是疏水性改性的粘土、疏水性改性的二氧化硅或疏水性改性的二氧化钛。
85.权利要求77的方法,其中所述疏水性鼻分泌皮肤刺激物螯合剂是季铵改性的皂土。
86.权利要求77的方法,其中所述疏水性鼻分泌皮肤刺激物螯合剂是季铵改性的蒙脱土。
87.权利要求77的方法,其中所述疏水性鼻分泌皮肤刺激物螯合剂以面巾纸总重量的0.001%-5.0%重量的量存在于薄纸中。
88.权利要求77的方法,其中所述疏水性鼻分泌皮肤刺激物螯合剂以面巾纸总重量的.01%-1.0%重量的量存在于薄纸中。
89.一种螯合鼻分泌皮肤刺激物的方法,其包括给予患者皮肤含有薄纸基质和亲水性鼻分泌皮肤刺激物螯合剂的面巾纸。
90.权利要求89的方法,其中所述薄纸基质包括纸纤维。
91.权利要求89的方法,其中所述亲水性鼻分泌皮肤刺激物螯合剂结合细胞因子。
92.权利要求91的方法,其中所述细胞因子选自白细胞介素-8、白细胞介素-1α或白细胞介素-1β。
93.权利要求89的方法,其中所述亲水性鼻分泌皮肤刺激物螯合剂是未改性的粘土、二氧化硅或二氧化钛。
94.权利要求89的方法,其中所述亲水性鼻分泌皮肤刺激物螯合剂是皂土、高岭土、合成锂皂石、沸石、蒙脱土、拜来石、锂蒙脱石、皂石或富镁蒙脱石。
95.权利要求89的方法,其中所述亲水性鼻分泌皮肤刺激物螯合剂是皂土。
96.权利要求89的方法,其中所述亲水性鼻分泌皮肤刺激物螯合剂以面巾纸总重量的0.001%-5.0%重量的量存在于薄纸中。
97.权利要求89的方法,其中所述亲水性鼻分泌皮肤刺激物螯合剂以面巾纸总重量的0.1%-1.0%重量的量存在于薄纸中。
98.权利要求53、77或89的方法,其还包含选自凝胶剂、糊剂、霜剂、粉末剂、洗剂、乳剂或含水制剂及其任意组合的介质。
99.权利要求53或98的方法,其还包含亲脂性螯合剂组合物。
100.权利要求99的方法,其中所述亲脂性螯合剂具有大于8个碳的平均烃链长度。
101.权利要求99的方法,其中所述亲脂性螯合剂选自硬脂酸、异链烷烃、凡士林及其任意组合。
102.权利要求99的方法,其中所述亲脂性螯合剂选自脂肪酸、脂肪酸酯、脂肪醇、甘油三酯、磷脂、矿物油、芳香油、甾醇、甾醇酯、润肤剂、蜡类及其任意组合。
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JP3008897B2 (ja) | 1997-07-14 | 2000-02-14 | 日本電気株式会社 | 有機エレクトロルミネッセンス素子 |
US5961992A (en) * | 1997-07-22 | 1999-10-05 | Lever Brothers Company Inc. | Benefit agent compositions comprising mixtures of alpha-hydroxy esters |
US6107537A (en) * | 1997-09-10 | 2000-08-22 | The Procter & Gamble Company | Disposable absorbent articles providing a skin condition benefit |
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EP0937467A1 (en) | 1998-02-17 | 1999-08-25 | The Procter & Gamble Company | Doped odour controlling materials |
IL138146A0 (en) † | 1998-03-12 | 2001-10-31 | Procter & Gamble | Disposable absorbent article having a skin care composition containing an enzyme inhibitor |
US6066673A (en) | 1998-03-12 | 2000-05-23 | The Procter & Gamble Company | Enzyme inhibitors |
US6395955B1 (en) * | 1998-06-29 | 2002-05-28 | The Procter & Gamble Company | Diaper including feces modification agent |
ID27386A (id) * | 1998-06-29 | 2001-04-05 | Procter & Gamble | Benda penyerap yang mencakup suatu zat pereduksi untuk feces |
US6160200A (en) * | 1998-06-29 | 2000-12-12 | The Procter & Gamble Company | Directionally preferential waste passage member for use with disposable absorbent article |
US5998695A (en) * | 1998-06-29 | 1999-12-07 | The Procter & Gamble Company | Absorbent article including ionic complexing agent for feces |
US6436418B1 (en) † | 1999-11-12 | 2002-08-20 | Tyco Healthcare Retail Services Ag | Absorbent article with skin treatment means |
-
1999
- 1999-12-28 CO CO99081140A patent/CO5150202A1/es unknown
- 1999-12-28 CO CO99081136A patent/CO5111023A1/es unknown
- 1999-12-29 AR ARP990106850A patent/AR022161A1/es not_active Application Discontinuation
- 1999-12-29 US US09/474,307 patent/US6521241B1/en not_active Expired - Fee Related
- 1999-12-29 AR ARP990106852A patent/AR022163A1/es not_active Application Discontinuation
- 1999-12-29 US US09/474,490 patent/US6551607B1/en not_active Expired - Fee Related
- 1999-12-29 AR ARP990106855A patent/AR023078A1/es not_active Application Discontinuation
- 1999-12-29 US US09/473,675 patent/US6521240B1/en not_active Expired - Fee Related
- 1999-12-29 CO CO99081364A patent/CO5150154A1/es unknown
- 1999-12-29 US US09/474,581 patent/US6521242B1/en not_active Expired - Fee Related
- 1999-12-30 AU AU22217/00A patent/AU764723C/en not_active Ceased
- 1999-12-30 CN CN99816378A patent/CN1344154A/zh active Pending
- 1999-12-30 TW TW088123275A patent/TWI247610B/zh not_active IP Right Cessation
- 1999-12-30 WO PCT/US1999/031304 patent/WO2000038626A2/en not_active Application Discontinuation
- 1999-12-30 CN CNB998163775A patent/CN1211070C/zh not_active Expired - Fee Related
- 1999-12-30 KR KR1020017008346A patent/KR100661956B1/ko not_active IP Right Cessation
- 1999-12-30 JP JP2000590580A patent/JP2002533366A/ja active Pending
- 1999-12-30 KR KR1020017008334A patent/KR100668019B1/ko not_active IP Right Cessation
- 1999-12-30 JP JP2000590698A patent/JP2004512853A/ja not_active Ceased
- 1999-12-30 US US09/475,535 patent/US6485733B1/en not_active Expired - Fee Related
- 1999-12-30 AU AU27173/00A patent/AU769563B2/en not_active Ceased
- 1999-12-30 RU RU2001121488/15A patent/RU2244565C2/ru not_active IP Right Cessation
- 1999-12-30 JP JP2000590579A patent/JP2002533365A/ja not_active Ceased
- 1999-12-30 WO PCT/US1999/031257 patent/WO2000038625A2/en active IP Right Grant
- 1999-12-30 US US09/475,825 patent/US6517848B1/en not_active Expired - Fee Related
- 1999-12-30 BR BR9916592-9A patent/BR9916592A/pt not_active IP Right Cessation
- 1999-12-30 EP EP99968986A patent/EP1140010B1/en not_active Revoked
- 1999-12-30 AU AU24874/00A patent/AU773120C/en not_active Ceased
- 1999-12-30 DE DE69928690T patent/DE69928690T2/de not_active Revoked
- 1999-12-30 DE DE69925637T patent/DE69925637T2/de not_active Expired - Lifetime
- 1999-12-30 CN CN99816361A patent/CN1335764A/zh active Pending
- 1999-12-30 BR BR9916642-9A patent/BR9916642A/pt not_active IP Right Cessation
- 1999-12-30 EP EP99968203A patent/EP1140009B2/en not_active Expired - Lifetime
- 1999-12-30 WO PCT/US1999/031295 patent/WO2000038747A2/en active IP Right Grant
- 1999-12-30 BR BR9916694-1A patent/BR9916694A/pt not_active IP Right Cessation
- 1999-12-30 TW TW088123274A patent/TW446554B/zh not_active IP Right Cessation
- 1999-12-30 KR KR1020017008348A patent/KR100706142B1/ko not_active IP Right Cessation
- 1999-12-30 DE DE69927288T patent/DE69927288T3/de not_active Expired - Lifetime
- 1999-12-30 TW TW088123272A patent/TWI241196B/zh not_active IP Right Cessation
- 1999-12-30 EP EP99966728A patent/EP1143927B1/en not_active Expired - Lifetime
- 1999-12-30 RU RU2001121485/15A patent/RU2239409C2/ru not_active IP Right Cessation
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111278392A (zh) * | 2017-11-08 | 2020-06-12 | 科洛普拉斯特公司 | 具有中和剂基质的粘性薄片 |
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