CN1972704A - P物质的抗衰老作用 - Google Patents
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Abstract
可以将P物质或其类似物给予人，以逆转或延缓与成人衰老有关的各种生物学过程。在毛发颜色、肌肉或关节疼痛、记忆丧失、睡眠状态和视力调节方面可以观察到逆转或延缓。
Description
本申请要求于2004年4月26日提交的临时专利申请第60/565,021号的优先权，在此完全并入其公开内容。
技术领域
本发明涉及用于延缓衰老作用的治疗。
背景技术
衰老过程对人有许多负面影响，尽管比其他情况要好一些。大多数老年人在智力、学习能力、短期记忆和反应时间等方面的能力减退。大脑中与衰老有关的结构变化包括重量下降、神经元减少、神经元萎缩和额叶中的突触减少。Ageing and its implications：an on-line primerfor healthcare professionals and carers(衰老及其并发症：医疗保健专业和护理人员在线入门)，
http://www.healthandage.com/html/res/primer/ index.htm。
衰老对人的毛发和形象有复杂的影响。随着年龄增加，毛囊中的黑色素减少(灰发)或丧失(白发)。毛发变灰或脱落发生的年龄是由遗传决定的。女人和男人随着年龄增长都会脱发。随着年龄增长，毛发可能变得更脆、更柔软，从终毛到毫毛变化，并且生长更加缓慢。老龄妇女的下颚和嘴唇上方的毫毛会转变成终毛。老年人可能会注意到耳、鼻孔和眉处的毛发增多。见上。
衰老对眼也有负面作用。一般，晶状体变厚，弹性降低。这会降低聚焦能力，尤其是对近物聚焦的能力(老花眼)。瞳孔的直径减小，围绕其的虹膜纤维增生。因此，眼睛对光和黑暗变化的反应更加迟缓。相对年轻人，老年人达到最佳视力需要增加光照的亮度。见上。
衰老还会影响肌肉、关节和骨骼。这经常会引起疼痛并导致运动性问题。剧烈运动可以引起延迟性(residual)疼痛，即运动后感受到疼痛。见上。
类风湿性关节炎是关节的炎症。它可能会非常突然和严重地引起慢性和/或极度的疼痛。见上。
老年人的睡眠质量经常会改变。典型地，睡眠变短、变轻，睡眠中断增加。打鼾很常见，可能会影响睡眠。见上。
在老年病学领域中，这些和其他的衰老相关特征是公知的。在本领域需要有能够减轻、减少和/或缓解人类衰老特征的治疗方法。
发明内容
在本发明的第一个实施方式中，提供了延缓或逆转衰老相关性变化的方法。将有效量的P物质或选自下列物质的生物活性类似物给予成年人：[Met-OH11]-P物质、[Met-OMe11]-P物质、[Nle11]-P物质、[Pro9]-P物质、[Sar9]-P物质、[Tyr8]-P物质、[p-Cl-Phe 7，8]-P物质、和[Sar9，Met(O2)11]-P物质。由此使一种或多种衰老相关特征延缓或逆转。
本发明的第二个实施方式是减小人头皮上的灰发或白发与完全着色毛发比例的方法。将有效量的P物质或选自下列物质的生物活性类似物给予头发正在变灰的人：[Met-OH11]-P物质、[Met-OMe11]-P物质、[Nle11]-P物质、[Pro9]-P物质、[Sar9]-P物质、[Tyr8]-P物质、[p-Cl-Phe7，8]-P物质、和[Sar9，Met(O2)11]-P物质。因此增加了人头皮上着色头发与灰色头发的比例或头发中的色素量。
本发明的第三个实施方式提供了一种改善人睡眠状态的方法。将有效量的P物质或选自下列物质的生物活性类似物给予睡眠状态紊乱的人：[Met-OH11]-P物质、[Met-OMe11]-P物质、[Nle11]-P物质、[Pro9]-P物质、[Sar9]-P物质、[Tyr8]-P物质、[p-Cl-Phe7，8]-P物质、和[Sar9，Met(O2)11]-P物质。从而降低人的睡眠中断。
本发明的第四个实施方式是缓解运动后延迟性肌肉疼痛的方法。将有效量的P物质或选自下列物质的生物活性类似物给予经受运动后延迟性肌肉疼痛的人：[Met-OH11]-P物质、[Met-OMe11]-P物质、[Nle11]-P物质、[Pro9]-P物质、[Sar9]-P物质、[Tyr8]-P物质、[p-Cl-Phe7，8]-P物质、和[Sar9，Met(02)11]-P物质。从而缓解了人在运动后发生的延迟性肌肉疼痛。
本发明的另一个方面是减轻短期记忆丧失的方法。将有效量的P物质或选自下列物质的生物活性类似物给予有短期记忆丧失的人：[Met-OH11]-P物质、[Met-OMe11]-P物质、[Nle11]-P物质、[Pro9]-P物质、[Sar9]-P物质、[Tyr8]-P物质、[p-Cl-Phe7，8]-P物质、和[Sar9，Met(02)11]-P物质。从而减轻短期记忆丧失。
本发明的再另一个方面是改善人视力调节的方法。将有效量的P物质或选自下列物质的生物活性类似物给予视力调节减弱的人：[Met-OH11]-P物质、[Met-OMe11]-P物质、[Nle11]-P物质、[Pro9]-P物质、[Sar9]-P物质、[Tyr8]-P物质、[p-Cl-Phe7，8]-P物质、和[Sar9，Met(02)11]-P物质。从而改善人的视力调节。
本发明的再另一个方面是增加人肌肉强度的方法。将有效量的P物质或选自下列物质的生物活性类似物给予人：[Met-OH11]-P物质、[Met-OMe11]-P物质、[Nle11]-P物质、[Pro9]-P物质、[Sar9]-P物质、[Tyr8]-P物质、[p-Cl-Phe7，8]-P物质、和[Sar9，Met(O2)11]-P物质。从而增加了人的肌肉强度。
根据本发明的再另一个方面，提供了减轻人由于关节炎引起的疼痛的方法。将有效量的P物质或选自下列物质的生物活性类似物给予患关节炎的人：[Met-OH11]-P物质、[Met-OMe11]-P物质、[Nle11]-P物质、[Pro9]-P物质、[Sar9]-P物质、[Tyr8]-P物质、[p-Cl-Phe7，8]-P物质、和[Sar9，Met(O2)11]-P物质。从而减轻了人由于关节炎引起的疼痛。
本发明的这些和其他实施方式将为本领域提供拮抗一定程度衰老作用的手段。
具体实施方式
本发明者发现，P物质及其生物活性类似物，如Sar9、Met(O2)11-P物质是治疗与衰老过程有关的各种特征的有益治疗物质。这些症状包括：有色毛发与无色毛发的比例下降、睡眠模式状态、运动后延迟性肌肉疼痛、短期记忆丧失、和视力调节丧失。另外，还可以减轻由于关节炎引起的疼痛(常常与衰老有关)。
P物质(RPKPQQFFGLM-NH2；SEQ ID NO：1)或其生物活性类似物如Sar9、Met(O2)11-P物质可以用于治疗ARDS、SARS、呼吸道冠状病毒和冠状病毒样病毒感染。生物活性类似物可以选自[Met-OH11]-P物质、[Met-OMe11]-P物质、[Nle11]-P物质、[Pro9]-P物质、[Sar9]-P物质、[Tyr8]-P物质、Sar9，Met(O2)11]-P物质、和[p-Cl-Phe7，8]-P物质。其他以相同方式发挥功能的化合物可以通过与P物质竞争结合其受体的能力(NK-1、NK-2、和NK-3)或识别NK-1受体的能力进行鉴别。这种活性的常规测定方法是本领域公知的，并可以使用。
不拘泥于任何具体的作用机制或理论限制，相信Sar9、Met(O2)11-P物质、P物质及其生物活性类似物影响着daf-2和sir-2基因的表达，以及随后胰岛素生长因子的表达。这两种基因被认为与衰老过程有关。
P物质或类似物可以通过本领域公知的任何方法给药，包括经气雾剂(aerosol)吸入。可以还使用静脉内、局部、气管内、支气管内、肌肉内、舌下、和口服给药。优选的给药剂量包括0.05至5nmol(nanomolar)P物质或类似物，优选为0.1至2nmol，更优选为0.5至1.5nmol。对于气雾剂给药，剂量包括0.05至5μmol P物质或类似物，优选为0.1至2μmol，更优选为0.5至1.5μmol。
以气雾剂给药的P物质或其生物活性类似物的典型浓度为0.001至10μM。作为液体给药的浓度有利地为大约0.1至10μM。局部给药的浓度为1μM至50μM。给药量通常为1μM和10μM。
根据本发明的生物活性类似物是通过与SP受体(NK-1受体)结合而起到SP竞争性抑制剂作用的物质。类似物可以是NK-1受体或其他神经激肽受体的激动剂。可以使用本领域公知的其他衍生物和市售的衍生物(如购自Sigma)。另外，还可使用P物质片段和衍生化P物质的片段。对类似物进行1至8个氨基酸残基，优选1至3个氨基酸残基的取代、删除或插入，可以使其通过常规方法检测其生物学活性。另外，可以再保留相同氨基酸主链的情况下对SP上的功能基团进行修饰。再次进行常规检测，确定这些修饰不会对生物学活性造成不利影响。
适于给予本发明的气雾剂的合适装置包括雾化器以及手持式气雾剂“喷出”装置。根据本发明治疗方法的合适治疗方案包括每天或每天多次使用气雾剂治疗。其他的治疗方式包括定期局部敷用、连续透皮给药、静脉内注射、肌肉内、舌下、皮下注射和口服给药。P物质合适的给药剂型可以是其中P物质保留其生物学活性的任何药物可接受剂型。通常，这种剂型是溶解在正常无菌盐水中的P物质。可使用改变吸收和半衰期特性的其他剂型，包括凝胶、脂质体剂型和缓释剂型。一般用于皮肤应用的媒介物可以用于配制P物质及其类似物。
衰老相关的特征或特性以统计学上显著的数量减少。可测特征或特性的变化可以为至少10％、15％、20％、25％、30％、35％、40％、或50％。优选更大程度的降低。
实施例
将[Sar9，Met(O2)11]-P物质配制成浓度0.001mg/mld的毛发定型胶(hair styling gel)，每天涂施大约2ml于头皮。数月后，感知到毛发总体颜色变得更象本人原来的褐色，即，与开始使用P物质类似物之前相比，褐色毛发的比例更高。推测大约40％的毛发更深色。这一观察结果与放射线照射过的已接受P物质类似物的小鼠上观察到的结果一致。接受放射线照射后，毛发脱落的小鼠再生出丧失的毛发，新生毛发比未照射区域的毛发颜色要深。
另外还观察到，在经过重体力劳动后通常发生的延迟性肌肉疼痛得以很大程度的缓解。我跑了5英里，有4次150M加速跑，并首次投掷了6Kg铅球。之后进行了一组举重。在用P物质类似物治疗之前，我在工作日每天服用至少两次AdvilTM以预防肌肉疼痛。但是，服用类似物后，在重体力劳动后没有经受肌肉疼痛、投掷铅球的右臂/肩也没有紧张或酸痛。
在服用类似物后，“感觉”在150M加速跑中比以前更快。实际上，当在200M跑中计时时，成绩明显提高。
我的规律睡眠是6小时。大约1周前，每天服用类似物2周后，睡眠变成5小时。睡眠似乎更深，做梦也更生动，不太“易醒”。现在已恢复每晚6小时的睡眠。但是，生动的梦境和很少醒来仍在延续。
因为我应用类似物，我似乎少了很多“中年”记忆问题。我可以很容易地记起很多人的名字和电话号码。
远程和近程之间的视力调节时间变短，并继续减少。用药97天后，感知到远和近视力之间的调节时间几乎没有了。
Claims (11)
1.一种改善人睡眠状态的方法，该方法包括：
将有效量的P物质或选自下列物质的生物活性类似物给予睡眠状态紊乱的人：[Met-OH11]-P物质、[Met-OMe11]-P物质、[Nle11]-P物质、[Pro9]-P物质、[Sar9]-P物质、[Tyr8]-P物质、[p-Cl-Phe7，8]-P物质、和[Sar9，Met(O2)11]-P物质，从而减少人的睡眠中断。
2.一种减少运动后延迟性肌肉疼痛的方法，该方法包括：
将有效量的P物质或选自下列物质的生物活性类似物给予发生运动后延迟性肌肉疼痛的人：[Met-OH11]-P物质、[Met-OMe11]-P物质、[Nle11]-P物质、[Pro9]-P物质、[Sar9]-P物质、[Tyr8]-P物质、[p-Cl-Phe7，8]-P物质、和[Sar9，Met(O2)11]-P物质，从而减少在运动后延迟性肌肉疼痛。
3.一种减轻短期记忆丧失的方法，该方法包括：
将有效量的P物质或选自下列物质的生物活性类似物给予患有短期记忆丧失的人：[Met-OH11]-P物质、[Met-OMe11]-P物质、[Nle11]-P物质、[Pro9]-P物质、[Sar9]-P物质、[Tyr8]-P物质、[p-Cl-Phe7，8]-P物质、和[Sar9，Met(O2)11]-P物质，从而减轻所述的记忆丧失。
4.一种改善人视力调节的方法，该方法包括：
将有效量的P物质或选自下列物质的生物活性类似物给予视力调节减弱的人：[Met-OH11]-P物质、[Met-OMe11]-P物质、[Nle11]-P物质、[Pro9]-P物质、[Sar9]-P物质、[Tyr8]-P物质、[p-Cl-Phe7，8]-P物质、和[Sar9，Met(O2)11]-P物质，从而改善所述的调节。
5.一种增加人肌肉强度的方法，该方法包括：
将有效量的P物质或选自下列物质的生物活性类似物给予人：[Met-OH11]-P物质、[Met-OMe11]-P物质、[Nle11]-P物质、[Pro9]-P物质、[Sar9]-P物质、[Tyr8]-P物质、[p-Cl-Phe7，8]-P物质、和[Sar9，Met(O2)11]-P物质，从而增加人的肌肉强度。
6.一种减轻人由于关节炎引起的疼痛的方法，该方法包括：
将有效量的P物质或选自下列物质的生物活性类似物给予患有关节炎的人：[Met-OH11]-P物质、[Met-OMe11]-P物质、[Nle11]-P物质、[Pro9]-P物质、[Sar9]-P物质、[Tyr8]-P物质、[p-Cl-Phe7，8]-P物质、和[Sar9，Met(O2)11]-P物质，从而减轻人由于关节炎引起的疼痛。
7.根据权利要求1-6中任意一项所述的方法，其中将所述的P物质局部给药。
8.根据权利要求1-6中任意一项所述的方法，其中将所述的P物质经由气雾剂给药。
9.根据权利要求1-6中任意一项所述的方法，其中将所述的P物质在凝胶中为皮肤给药。
10.根据权利要求1-6中任意一项所述的方法，其中将所述的P物质经舌下给药。
11.根据权利要求1-6中任意一项所述的方法，其中将所述的P物质经肌肉内给药。
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| RU2549667C1 (ru) * | 2014-02-24 | 2015-04-27 | Борис Николаевич Анисимов | Способ коррекции биологического возраста организма как профилактика преждевременного старения |
| US10849340B2 (en) * | 2018-07-10 | 2020-12-01 | Louise Wilkie | Humic and fulvic mineral extraction method and beverage for human consumption |
| US10758077B1 (en) * | 2019-04-07 | 2020-09-01 | Louise Wilkie | Fulvic acid-humic acid coffee brewer method and devices |
| KR102225547B1 (ko) * | 2019-05-28 | 2021-03-10 | 주식회사 바이오솔루션 | 물질 p를 포함하는 피부 미백용 화장료 조성물 |
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