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CN102596253A - 含有维生素b 亚结构的粘膜粘着聚合物 - Google Patents

含有维生素b 亚结构的粘膜粘着聚合物 Download PDF

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CN102596253A
CN102596253A CN2010800405370A CN201080040537A CN102596253A CN 102596253 A CN102596253 A CN 102596253A CN 2010800405370 A CN2010800405370 A CN 2010800405370A CN 201080040537 A CN201080040537 A CN 201080040537A CN 102596253 A CN102596253 A CN 102596253A
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sulfydryl
nicotiamide
disulphide
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pyridoxol
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CN102596253B (zh
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J·莱尔雷
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THIOMATRIX FORSCHUNGS-UND BERATUNGS GmbH
ThioMatrix Forschungs und Beratungs GmbH
Croma Pharma GmbH
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Croma Pharma GmbH
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Abstract

由于与粘液糖蛋白形成二硫桥，通过使硫醇亚结构共价连接至聚合物化合物可显著改善所述化合物的粘膜粘着特性。通过将此类聚合物上的游离硫醇基转化为含有巯基烟酰胺或巯基吡哆醇的二硫化物，这些硫醇基变得相对更活跃，而使得所述聚合物的粘膜粘着特性显著更高。此外，包含含有巯基烟酰胺或巯基吡哆醇的二硫化物亚结构的聚合物无需被保护以抵抗氧化，并且它们显示出相对更高的渗透增强特性。

Description

含有维生素B 亚结构的粘膜粘着聚合物
粘膜粘着聚合物是在粘膜上显示出相对高的粘着能力的聚合物化合物。粘膜粘着聚合物是例如下列化合物：(交联的)聚(甲基)丙烯酸酯，(三甲基化)壳聚糖，透明质酸，藻酸盐，果胶和纤维素衍生物。聚(甲基)丙烯酸酯的交联是通过在聚合过程中加入包含至少两个乙烯基亚结构的化合物(例如二乙烯醇或季戊四醇丙烯醚)实现的。具有粘膜粘着特性的纤维素衍生物特别是羧甲基纤维素钠、羟乙基纤维素、乙基纤维素、甲基纤维素和羟丙基甲基纤维素。通过活性物质递送系统在粘膜(例如小肠粘膜)上改善的粘着(由此吸收活性物质)，活性物质能够在血液循环中相对更有效且更可持续地渗透。粘膜粘着聚合物与目前所应用的活性物质递送系统相比的这一巨大优势已在各种研究中被明确证实[例如Akiyama et al.，J.Pharm.Pharmacol.50(1998)159-166]。
通过使硫醇亚结构与此类聚合物共价结合，还可使其粘膜粘着特性进一步显著改善，因为这些硫醇基团能够与粘液中的硫醇亚结构形成二硫桥形式的共价键[Muco-adhesive polymers，use thereof andmethod for producing the same.EP 1126881]。含有硫醇亚结构的聚合物-称为thiomer(硫醇化聚合物)-在各种粘膜上显示出超过100倍的改善的粘着能力[例如Roldoetal.，Eur.J.Pharm.Biopharm.，57，115-121]。
然而，尽管有硫醇化作用，聚合物的粘膜粘着特性常常不足以达到希望的效果。在本申请中所呈递的发明因此是基于这样的任务：克服上文所描述的现有技术的问题以及提供具有优越特性的粘膜粘着聚合物。
根据本发明，此任务通过根据权利要求1-7的聚合物化合物，根据权利要求8至9的聚合物化合物的用途，以及根据权利要求10的组合物被解决。根据本发明，维生素B衍生物(例如巯基(异)烟酰胺或巯基吡哆醇)以二硫桥的形式与硫醇化聚合物的游离硫醇基偶联，如图1中关于6-巯基烟酰胺所示的。通过这些亚结构与硫醇化聚合物的偶联，它们显著更快地且以相对更高的百分比与粘液糖蛋白的硫醇基团或与硫醇化聚合物本身的游离硫醇基团反应。除了巯基(异)烟酰胺和巯基吡哆醇之外，巯基烟酸也适于此目的。然而，由于其导致许多副作用(例如血管舒张或脂肪代谢的改变)，巯基烟酰胺和巯基吡哆醇-即维生素B 3衍生物和维生素B6衍生物-根据本发明是优选的。适合作为本发明的起始聚合物的特别是硫醇化的(交联)聚(甲基)丙烯酸酯，例如聚丙烯酸-半胱胺缀合物[Hombach et al.，J Pharm Sci.98(2009)555-564]或聚卡波非-半胱氨酸缀合物[Vetter et al.，JPharm Sci.99(2010)1427-1439]；硫醇化的壳聚糖，例如壳聚糖-巯基乙酸缀合物[Bernkop-Schnürch and Hopf Sci.Pharm.，69(2001)109-118]，壳聚糖-巯基烟酸缀合物[Millotti et al.，Biomacromolecules，10(2009)3023-3027]或壳聚糖-谷胱甘肽缀合物[Kafedjiiski et al.，Pharm Res.，22(2005)1480-1488]；硫醇化的果胶，例如果胶-半胱氨酸缀合物[Majzoob et al.，J.Pharm.Pharmacol.，58(2006)1601-1610]或果胶-4-巯基氨基苯酚缀合物[Perera et al.，AAPS PharmSciTech.，11(2010)174-180]；硫醇化的藻酸盐，例如藻酸盐-半胱氨酸缀合物[Bernkop-Schnürch etal.，J.Control.Release，71(2001)277-285]；硫醇化的透明质酸例如透明质酸-半胱氨酸乙酯缀合物[Kafedjiiski et al.，Int.J.Pharm.，343，(2007)48-58]；硫醇化的聚烯丙胺，例如聚烯丙胺-巯基乙酸缀合物；硫醇化的聚赖氨酸；硫醇化的聚鸟氨酸；硫醇化的聚氨基酰胺；硫醇化的纤维素衍生物，例如羧甲基纤维素-半胱氨酸缀合物[Bernkop-Schnürch，Int.J.Pha rm.，194，(2000)239-247]；硫醇化的(交联)聚乙烯基吡咯烷酮，其是通过在乙烯吡咯烷酮的聚合过程中添加携带经S-保护的硫醇基团的乙烯基化合物(例如S-乙酰-半胱氨酸-丙烯酰胺)而产生的；以及能够以类似于硫醇化的聚乙烯吡咯烷酮的方式制备的硫醇化的(交联)(甲基)丙烯酸/丙烯酸乙酯共聚物。此外，除了单体烯丙胺、乙烯吡咯烷酮、(甲基)丙烯酸和丙烯酸乙酯之外，包含乙烯基亚结构的其它单体(例如乙烯醇，乙烯基咪唑，乙烯己内酯或(甲基)丙烯酰胺)也可与携带经S-保护的硫醇基团的乙烯基化合物以所述各种单体的任何比例聚合。适合作为携带硫醇基团的配体的还有巯基苯甲酸，N-乙酰基-半胱氨酸，同型半胱氨酸，3-硫代丙酸，4-硫代丁酸，硫代丁基脒以及硫代乙基脒[Kafedjiiski etal.，Biomaterials，27(2006)127-135]。介由氧化作用，通过在各硫醇化聚合物与各维生素B衍生物的游离硫醇基之间形成二硫桥而使巯基烟酰胺或巯基吡哆醇与这些粘膜粘着聚合物共价结合。其中根据本发明的优选实施方案，一摩尔过量的巯基烟酰胺或巯基吡哆醇相对于聚合物的游离硫醇基是有利的。通过加入过氧化脲和马来酸酐，可使此氧化过程被进一步加速，如Kamari所描述的[Karami et al.，Molecules，10(2005)1385-63]。此外，在优选的实施方案中，也可通过加入过氧化氢而加速氧化反应。通常，在较高的pH值时氧化过程进行得更快。本发明的聚合物含有10-1000μmol的巯基(异)烟酰胺或巯基吡哆醇亚结构，优选100-1000μmol的巯基(异)烟酰胺或巯基吡哆醇亚结构/克聚合物。可通过每种所加入的维生素B衍生物的量来控制未与配体形成二硫桥的剩余硫醇基的数目。
适合用于本发明的巯基烟酰胺特别是2-巯基烟酰胺和6-巯基烟酰胺以及2-和6-巯基异烟酰胺。在实施例1中描述了6-巯基烟酰胺的合成。以类似的方式进行上文所述的其它衍生物的合成。适合用于本发明的巯基吡哆醇特别是6-巯基吡哆醇。其生产起始于6-氯吡哆醇，由Blackwood等人描述了其合成[Blackwood et al.，J.Am.Chem.Soc.，80(1958)6244-6249]。通过巯基取代氯是根据实施例1中描述的方法进行的。
备选于这种制备方法，根据一个优选的实施方案，含有携带乙烯基的化合物的S-(2-或6-巯基(异)烟酰胺二硫化物或S-(6-巯基吡哆醇)二硫化物(例如半胱氨酸-丙烯酰胺)也可与任何其它携带乙烯基的单体(例如(甲基)丙烯酸，乙烯吡咯烷酮，乙烯醇或丙烯酸乙酯)聚合。
合成本发明的聚合物的另一种可能性是使S-(2-或6-巯基(异)烟酰胺二硫化物或S-(6-巯基吡哆醇)-二硫化物与聚合物上经预活化的配体共价结合。例如，在形成酰胺键的情况下，N-琥珀酰亚胺3-(2-烟酰胺二硫)-丙酸酯可非常有效地与含有伯氨基的聚合物(例如聚烯丙胺，壳聚糖)偶联。
以这种方式制备的化合物的另一个优势是，通过将游离的硫醇基转化为含有巯基烟酰胺或巯基吡哆醇的二硫化物，它们对于氧化反应不再敏感，因为硫醇基已经是以经氧化的形式存在。将本发明的聚合物与含有游离硫醇基团的聚合物相组合，使得在这两种聚合物之间形成二硫桥，从而引起相对快的粘度增加。当不是硫醇化聚合物上所有的硫醇基均被转化为含有巯基烟酰胺或巯基吡哆醇的二硫化物时，也可实现这种效果。
由于这种粘膜粘着特性或提高的稳定性，本发明的聚合物适于广泛的应用，特别是在药学和美容领域中，以及在保健产品中。因此，本发明还提供了本发明的粘膜粘着聚合物作为药物产品、美容产品以及保健产品的应用。此外，本发明提供组合物，其包含一种或多种本发明的聚合物、以及活性物质、助剂和/或溶剂。
除了所述提高的粘膜粘着特性之外，通过根据本发明的(异)烟酰胺-二硫化物侧链或吡哆醇-二硫化物侧链还显著提高了硫醇化聚合物的渗透加速特性。例如，根据
Figure BDA0000142750230000041
等人所描述的方法[
Figure BDA0000142750230000042
et al.，Amino Acids，35(2008)233-241]，不添加聚合物时，经荧光标记的葡聚糖(分子量：4.4kDa；FD4)在新鲜切除的大鼠肠粘膜上的渗透系数(Papp)被确定为9.6±3.5x 10-7cm/s；而通过加入0.5％(m/v)壳聚糖-巯基乙酸缀合物(分子量：450kDa；234μmol硫醇基/克聚合物)其提高了1.8倍；并且通过加入0.5％(m/v)相同的聚合物(其中全部的游离硫醇都在之前被转化为了含有6-巯基烟酰胺的二硫化物)其甚至提高了5.3倍。
本发明的聚合物适于在药学领域中作为片剂中的活性物质载体基质、作为半固体和液体制剂中的胶凝剂、作为粘性伤口敷料、作为组织工程领域中的支架结构、以及用于制备微颗粒和纳米颗粒活性物质递送系统。在美容领域，其特别用作下列应用：头发护理物质(例如头发定型凝胶)，固定剂，着色剂，洗涤剂以及用于头发、睫毛、眉毛的涂覆物质，因为头发、指甲以及皮肤的蛋白质结构中存在硫醇亚结构，其能够与根据本发明的聚合物反应。在指甲油、化妆品以及止汗剂中的应用也是有利的。因为蛋白质中的半胱氨酸亚结构，在皮革中也存在游离硫醇基，因而本发明的聚合物也可适用于皮革浸渍。将本发明的聚合物应用在漆中以及各种清洁剂和润滑剂中也是可能的。
本发明包括下列实施方案：
(1)含有硫醇亚结构的聚合物化合物，其以含有2-或6-巯基(异)烟酰胺的二硫化物的形式存在。
(2)根据(1)的聚合物化合物，其特征在于，所述聚合物化合物是在旋转筒粘膜粘着测试中以具有5mm直径、30mg的测试片剂形式粘着在猪小肠粘膜上超过8小时(特别是超过24小时)的粘膜粘着聚合物。
(3)根据(1)或(2)的聚合物化合物，其特征在于，所述聚合物化合物为(交联)聚(甲基)丙烯酸，(三甲基化)壳聚糖，透明质酸，果胶，藻酸盐，甲基纤维素，羟乙基纤维素或羧甲基纤维素钠。
(4)根据(1)至(3)的聚合物化合物，其特征在于，所述聚合物化合物与含有多于一个硫醇基的化合物的组合引起粘性的增加。
(5)根据(1)至(4)的聚合物化合物，其特征在于，在权利要求3中所述的聚合物的硫醇化是通过与半胱氨酸，半胱胺，N-乙酰半胱氨酸，巯基乙酸，巯基苯甲酸，巯基烟酸，谷胱甘肽或巯基苯胺形成酰胺键实现的。
(6)根据(1)至(5)的聚合物化合物，其特征在于，存在10-1000μmol的巯基(异)烟酰胺亚结构，并且特别是100-1000μmol的巯基(异)烟酰胺亚结构/克聚合物。
(7)根据(1)至(6)的聚合物化合物，其特征在于，所述聚合物化合物在药学、美容或保健产品中用作助剂。
(8)根据(1)至(6)的聚合物化合物，其特征在于，所述聚合物化合物用于皮革浸渍。
实施例：
下列实施例是示例性的，并且将阐示本文中所公开的发明。可在所示专利权利要求的框架内对下列实施例进行改变和变化。
实施例1
6-巯基烟酰胺的合成
将5.0g 6-氯烟酰胺(31.9mmol)和2.65g硫脲(34.8mmol)悬浮于无水乙醇(50ml)中并在回流下加热(浴温度：约90℃)6小时，其中反应混合物随时间变为黄色。然后，将所述反应混合物冷却至室温。滤出所产生的S-(5-氨基甲酰-2-吡啶基)硫脲鎓氯并使其干燥。作为黄色粉末分离了6.7g粗制品(90％)。1H-NMR(200MHz，DMSO-d6，δ)：7.76(br s，1H)；7.83(d，1H，J＝8.4Hz)；8.33(dd，1H，J＝8.4Hz，J＝2.0Hz)；8.38(br s，1H)；9.05(d，1H，J＝2.0Hz)；9.69(br s，4H)。将所述6.7gS-(5-氨基甲酰-2-吡啶基)硫脲鎓氯(28.8mmol)悬浮于水(30ml)中，并加入20ml 5M的NaOH。在室温下将悬浮液搅拌30分钟，随后用冰醋酸小心地酸化(pH 4.9)。滤出粗产物并从适当的溶剂(例如水)中重结晶。获得黄色粉末形式的3.4g产物(69％，以6-氯烟酰胺计算)。1H-NMR(200MHz，DMSO-d6，δ)：7.29(d，1H，J＝9.1Hz)；7.46(br s，1H)；7.76(dd，1H，J＝9.1Hz，J＝2.2Hz)；7.95(br s，1H)；8.13(d，1H，J＝2.2Hz)；13.74(br s，1H)。
实施例2
聚丙烯酸-半胱氨酸-6-巯基烟酰胺缀合物的合成
将1克聚丙烯酸450kDa(Sigma-Aldrich，Vienna)在200ml去矿物质水中水合并通过加入1M NaOH将pH调节至5。通过在室温下加入1-乙基-3-(3-二甲基氨基丙基)碳化二亚胺盐酸(终浓度200mM)，并搅拌30分钟而预活化所述聚合物的羧酸基团。加入1g半胱氨酸后，任选地用HCl或NaOH将溶液的pH值重新调节至5，并且在室温下将反应混合物搅拌6小时。相对于含水的1mM盐酸溶液透析所产生的聚丙烯酸-半胱氨酸缀合物，相对于相同的透析介质(但是还含有1％NaCl)透析两次，并且最后于10℃、在光排除的条件下相对于水彻底透析。此后，用1M NaOH将缀合物的pH值调节至5。在-30℃将分离的缀合物冻干。保存在4℃。用Ellman试剂确定共价结合的硫醇基团的浓度。
如此合成的硫醇化聚合物含有50-250μmol共价结合的硫醇基团/克聚合物。
将2.50g如上文所述而合成的缀合物(65μmol SH/克聚合物)溶解在水(200ml)中。用1M NaOH将溶液碱化至pH 6，并加入50mg的6-巯基烟酰胺或2-巯基烟酰胺(溶解在5ml的DMSO和5ml水中)以及20mg的过氧化脲和30mg的马来酸酐(共同溶解在10ml的水中)。在室温下搅拌所述溶液24小时。此后，使其相对于去矿物质水彻底透析并随后将其冻干。
实施例3
壳聚糖-巯基乙酸-2-或-6-巯基烟酰胺-缀合物的合成
使1克壳聚糖在10ml的1M HCl中水合，随后用去矿物质水稀释为1％(m/v)的终浓度。加入1g的巯基乙酸和1-乙基-3-(3-二甲基氨基丙基)碳化二亚胺盐酸(终浓度为200mM)，并且任选地用1M HCl或1M NaOH将pH重新调节至5。在室温下将反应混合物搅拌6小时。使缀合物相对于含水的1mM盐酸溶液透析，相对于相同的透析介质(但是还含有1％NaCl)透析两次，并且最后于10℃、在光排除的条件下相对于水彻底透析。此后，用1M NaOH将缀合物的pH值调节至5。在-30℃将分离的缀合物冻干。保存在4℃。用Ellman试剂确定共价结合的硫醇基团的浓度。
将2.50g壳聚糖-TGA(550μmol SH/g聚合物)溶解在水(200ml)中。用1M NaOH将溶液调节至pH 6，并加入215mg的6-巯基烟酰胺或2-巯基烟酰胺(溶解在5ml的DMSO+5ml的水中)以及130mg的过氧化脲(溶解在10ml的水中)。在室温下将溶液搅拌24小时。此后，使所述缀合物相对于去矿物质水彻底透析，然后将其冻干。
实施例4
果胶-4-巯基苯胺-2-巯基烟酰胺-缀合物的合成
将1克果胶溶解于250ml的水/二噁烷(2+1)中。在持续加入0.2g溶解于3ml二噁烷中的4-巯基苯胺后，用0.5M NaOH将pH值调节至4.5，并加入1-乙基-3-(3-二甲基氨基丙基)碳化二亚胺盐酸(终浓度为200mM)。在室温下搅拌3小时后，将pH值调节至7.5并加入0.2g的氢硼化钠。在4℃下将反应混合物搅拌一小时。此后，我们通过用乙酸乙酯萃取反应混合物数次而去除未结合的4-巯基苯胺。通过加入异丙醇而沉淀所产生的缀合物并且用纯的异丙醇和丙酮清洗沉淀物。在除湿器中干燥所纯化的缀合物。
将0.5克的果胶-4-巯基苯胺缀合物(420μmol SH/g聚合物)浸在水(200ml)中。用1M NaOH将溶液调节至pH 6.5，并加入500mg的2-巯基烟酰胺(在25ml DMSO+25ml水中)。在室温下将所述溶液搅拌24小时。此后，使所述缀合物相对于去矿物质水彻底透析，然后将其冻干。
实施例5
粘液粘着测试
根据Bernkop-Schnürch等人描述的方法[Bernkop-Schnürch etal.，Int.J.Pharm.，260(2003)229-237]确定根据实施例3制备的聚合物的粘膜粘着特性。为此将含有和不含有巯基烟酰胺亚结构的聚合物压缩成具有5mm直径的片剂(30mg)。随后，以低的压力将它们附着在新鲜切除的猪小肠粘膜上(其被铺展在钢筒上)。对所述筒进行根据欧洲药典的分解测试，其在50mM磷酸盐缓冲液(pH 6.5)中、在37℃下、以100转/分钟的转动进行。目测片剂从粘膜上脱离的时刻。此研究的结果以图形显示在图2中(平均值±标准偏差；n＝4)。
实施例6
流变学研究
首先，使0.25g壳聚糖-巯基乙酸-6-巯基烟酰胺在50ml去矿物质水中水合。将所产生的凝胶加入50ml 0.5％(m/v)的壳聚糖-巯基乙酸溶液中。将反应混合物均质化并将pH调节至6.0。在图3中所示的时刻测量凝胶的粘度(以1Hz的恒定频率进行振荡测量)。如图3中所示，在数小时内粘性增加超过1000倍(平均值±标准偏差；n＝4)。
实施例7
片剂的制备
将含有1g咪康唑的20g聚丙烯酸-半胱氨酸-6-巯基烟酰胺(实施例2)均质化并直接压制为重0.2g的片剂。这些片剂显示出足够高的粘结以及对抗真菌剂的受控释放。
实施例8
鼻滴剂的制备
将0.1g壳聚糖-巯基乙酸-6-巯基烟酰胺(实施例3)和0.05g盐酸羟甲唑啉溶解于100ml去矿物质水中，并将其装入带有滴口的10ml容器中。任选地加入苯扎氯铵(终浓度为0.015％(m/v))和乙二胺四乙酸(0.05％(m/v))作为防腐剂。
实施例9
发胶的制备
将0.25g壳聚糖-巯基乙酸-6-巯基烟酰胺(实施例3)和0.25g壳聚糖-巯基乙酸(实施例3)浸泡在100ml水/异丙醇(9+1)中。任选地用1M HCl或1M NaOH将pH值重新调节至6.0。将所产生的凝胶以各10ml装入铝/塑料复合物的袋中。打开所述袋并分布在毛发上之后，凝胶的粘性大大增加，从而产生了提供结构和支撑的作用。

Claims (10)

1.聚合物化合物，其包含2-(异)烟酰胺-二硫化物侧链、6-(异)烟酰胺-二硫化物侧链或6-吡哆醇-二硫化物侧链。
2.根据权利要求1的聚合物化合物，其中共价结合2-(异)烟酰胺-二硫化物侧链、6-(异)烟酰胺-二硫化物侧链或6-吡哆醇-二硫化物侧链的聚合物化合物为由下列组成的(交联)均聚物或共聚物：(甲基)丙烯酸，(甲基)丙烯酸酯，(甲基)丙烯酰胺，乙烯基吡咯烷酮，乙烯醇，乙烯咪唑，乙烯基己内酰胺，烯丙胺，(三甲基化)壳聚糖，透明质酸，果胶，藻酸盐，(交联)聚烯丙胺，聚赖氨酸，聚鸟氨酸，聚氨基酰胺，甲基纤维素，乙基纤维素，羟乙基纤维素，羟丙基甲基纤维素，或羧甲基纤维素钠，其可任选地包含游离硫醇基作为侧链。
3.根据权利要求1或2的聚合物化合物，其中涉及
S-(2-或6-巯基(异)烟酰胺)-或S-(6-巯基吡哆醇)-(同型)半胱氨酸-二硫化物侧链，
S-(2-或6-巯基(异)烟酰胺)-或S-(6-巯基吡哆醇)-半胱胺-二硫化物侧链，
S-(2-或6-巯基(异)烟酰胺)-或S-(6-巯基吡哆醇)-N-乙酰半胱氨酸-二硫化物侧链，
S-(2-或6-巯基(异)烟酰胺)-或S-(6-巯基吡哆醇)-巯基乙酸-二硫化物侧链，
S-(2-或6-巯基(异)烟酰胺)-或S-(6-巯基吡哆醇)-3-巯基丙酸-二硫化物侧链，
S-(2-或6-巯基(异)烟酰胺)-或S-(6-巯基吡哆醇)-4-巯基丁酸-二硫化物侧链，
S-(2-或6-巯基(异)烟酰胺)-或S-(6-巯基吡哆醇)-巯基苯甲酸-二硫化物侧链，
S-(2-或6-巯基(异)烟酰胺)-或S-(6-巯基吡哆醇)-巯基烟酸-二硫化物侧链，
S-(2-或6-巯基(异)烟酰胺)-或S-(6-巯基吡哆醇)-谷胱甘肽-二硫化物侧链，
S-(2-或6-巯基(异)烟酰胺)-或S-(6-巯基吡哆醇)-硫代乙基脒-二硫化物侧链，
S-(2-或6-巯基(异)烟酰胺)-或S-(6-巯基吡哆醇)-4-硫代丁基脒-二硫化物侧链，
或
S-(2-或6-巯基(异)烟酰胺)-或S-(6-巯基吡哆醇)-巯基苯胺-二硫化物侧链
所述侧链通过酰胺键、脒键或酯键与所述聚合物连接。
4.根据权利要求1-3中任一项的聚合物化合物，其中每克聚合物中存在10-1000μmol巯基(异)烟酰胺或巯基吡哆醇-亚结构。
5.根据权利要求1-4中任一项的聚合物化合物，其中每克聚合物中存在100至1000μmo 1巯基(异)烟酰胺或巯基吡哆醇-亚结构。
6.根据权利要求1-5中任一项的聚合物化合物，其中所述聚合物化合物是在旋转筒粘膜粘着测试中以具有5mm直径、30mg的测试片剂形式粘着在猪小肠粘膜上超过8小时、特别是超过24小时的粘膜粘着聚合物。
7.根据权利要求1-6中任一项的聚合物化合物，其中其与包含多于一个硫醇基的化合物相组合而引起粘性的增加。
8.根据权利要求1-7中任一项的聚合物化合物在药学、美容或保健产品中作为活性成分或助剂的用途。
9.根据权利要求1-7中任一项的聚合物化合物用于浸渍皮革、粘着剂、清洁剂或润滑剂的用途。
10.组合物，其包含一种或多种根据权利要求1-7中任一项的聚合物化合物、其它活性物质、助剂和/或溶剂。
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