WO2018121674A1 - 一种利用红外光增加rna序列在皮肤中生物活性的给药方法 - Google Patents

一种利用红外光增加rna序列在皮肤中生物活性的给药方法 Download PDF

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WO2018121674A1
WO2018121674A1 PCT/CN2017/119409 CN2017119409W WO2018121674A1 WO 2018121674 A1 WO2018121674 A1 WO 2018121674A1 CN 2017119409 W CN2017119409 W CN 2017119409W WO 2018121674 A1 WO2018121674 A1 WO 2018121674A1
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rna sequence
skin
infrared light
administration
biological activity
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殷卫海
张铭超
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Shanghai Jiao Tong University
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
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    • A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

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  • the invention relates to the field of life sciences, in particular to a method for administering biological activity of an RNA sequence in the skin by using infrared light.
  • RNA sequence will eventually be degraded, and it is difficult for biomacromolecules to pass through the gastrointestinal membrane.
  • Intravenous administration results in a very high pain in the patient, and the RNA sequence is metabolized or excreted before it reaches the skin.
  • One of these traditional methods of administration did not have a significant effect.
  • the most commonly used method of skin administration is to directly deliver the RNA sequence to the skin, thereby regulating the gene expression of the skin tissue in situ, thereby achieving a therapeutic effect.
  • RNA sequence Due to the tight structure of the stratum corneum and the epidermal layer, it is an important factor for the significant decrease in the permeability of the drug. Therefore, it is particularly important to improve the permeability of the skin, so that the RNA sequence enters the skin and has a therapeutic effect.
  • chemical enhancers uses nanomaterials, liposomes, and the like to increase the permeability of the RNA sequence to the skin.
  • Such enhancers have high requirements on the length and structure of the RNA sequence, and the preparation process is cumbersome and complicated.
  • Researches on popular physical enhancers include microneedle administration and electrical administration. However, microneedle administration and electrical administration can cause great pain to the patient.
  • the object of the present invention is to overcome the above deficiencies of the prior art and to provide a method for effectively and significantly enhancing the biological activity of exogenous RNA sequences such as small interfering RNA or small activating RNA sequences in the skin, which has great clinical significance. .
  • RNAa small activating RNA
  • a specific technical solution of the present invention is: a method for administering biological activity of an RNA sequence in the skin by using infrared light, comprising the following steps:
  • step (3) mixing the solutions of step (1) and step (2), and allowing to stand;
  • step (3) dissolving the solution of step (3) in a carrier solution
  • the solution of the step (4) is uniformly applied to the irradiation position; the infrared light wavelength ranges from 1500 nm to 2000 nm.
  • the ratio of the liposome to the optimized culture solution can be adjusted according to the administration effect.
  • the ratio of the RNA sequence to the optimized culture solution can be adjusted according to the administration effect.
  • the ratio of the liposome to the RNA sequence can be adjusted according to the administration effect.
  • the infrared light has a wavelength ranging from 1500 nm to 2000 nm.
  • the invention utilizes infrared light to illuminate the skin, increases the biological activity of the small interfering RNA sequence on the skin, and establishes a basis for the clinical use of the small interfering RNA sequence to treat the skin disease, so that the patient can obtain more effective treatment.
  • the RNA sequence is a small interfering RNA sequence or a small activating RNA sequence.
  • the present invention also discloses an application of infrared light for increasing the biological activity of an RNA sequence in the skin, characterized in that a dose of infrared light is applied to the site where the skin needs to be administered to increase the biological activity of the RNA sequence in the skin.
  • the infrared light has a wavelength in the range of 1500 nm to 2000 nm.
  • the RNA sequence is administered in a topical manner.
  • the topical administration is a site in which an RNA sequence dissolved in a liposome is externally applied to infrared light.
  • the RNA sequence is a small interfering RNA sequence or a small activating RNA sequence.
  • Figure 1 shows a fluorescent three-view of a fluorescently labeled small interfering RNA sequence into the skin.
  • Figure 2 shows a fluorescent projection of a fluorescently labeled small interfering RNA sequence into the skin.
  • Figure 2 shows that the small interfering RNA sequence reduces the amount of expression of the target protein.
  • Figure 3 is a graph showing the biological effects of small interfering RNA sequences reducing damage after exposure to ultraviolet light.
  • Example 1 A novel skin small interfering RNA sequence administration method
  • mice male C57 mice are used, and the weight is in the range of 15-25 g.
  • the mice are reared in the animal room under the conditions of 22-24 ° C, 12 hours of light/dark cycle. Free access to water.
  • RNA sequences Mouse skin using fluorescently labeled RNA sequences was imaged using a laser confocal microscope within 24 hours.
  • mouse skin using the RNA sequence of the target protein was detected for target protein content analysis.
  • Ultraviolet light damage was applied to the skin of the mouse within 24 hours to examine the biological effects of using the RNA sequence.
  • Quantification was performed on the target protein content of the skin.
  • Figure 1 Fluorescent three-view of fluorescently labeled small interfering RNA sequences entering the skin, with infrared light-treated skin, fluorescently labeled small interfering RNA sequences enter more.
  • Figure 2 Fluorescence projection of fluorescently labeled small interfering RNA sequences into the skin. With infrared light treated skin, fluorescently labeled small interfering RNA sequences enter more.
  • FIG. 3 Skin treated with infrared light, the amount of target protein expression decreased significantly.
  • Figure 4 Skin treated without infrared light has no protective effect on damage. Small interfering RNA sequences have a protective effect on skin damage after treatment with infrared light.
  • the present invention is based on this finding and establishes a method of administering infrared light to increase the biological activity of small interfering RNA sequences in the skin.
  • the method includes the following steps:
  • step (3) mixing the solutions of step (1) and step (2) and allowing to stand for a certain period of time;
  • step (3) dissolving the solution of step (3) in a carrier solution
  • the solution of the step (4) is uniformly applied to the irradiation position; the wavelength of the infrared light is in the range of 1500 nm to 2000 nm.
  • the ratio of the small interfering RNA sequence to the optimized culture solution can be adjusted according to the administration effect.
  • the ratio of the liposome to the optimized culture solution can be adjusted according to the administration effect.
  • the ratio of the small interfering RNA sequence to the liposome can be adjusted according to the administration effect.
  • the present invention is based on the use of a certain band of infrared light to illuminate the skin, thereby significantly increasing the biological effects of a mixture of liposomes and small interfering RNA sequences on the skin. This effect was confirmed by methods such as detection of the content of the RNA silencing target protein and detection of the fluorescence of the target protein. This method can significantly increase the effect of small interfering RNA sequences on the treatment of skin diseases.
  • Example 2 A novel skin small activating RNA sequence administration method
  • mice male C57 mice are used, and the weight is in the range of 15-25 g.
  • the mice are reared in the animal house under the condition of 22-24 ° C, 12 hours of light/darkness. Cycle and free to eat and take water.
  • RNA sequences Mouse skin using fluorescently labeled RNA sequences was imaged using a laser confocal microscope within 24 hours.
  • mouse skin using the RNA sequence of the target protein was detected for target protein content analysis.
  • Ultraviolet light damage was applied to the skin of the mouse within 24 hours to examine the biological effects of using the RNA sequence.
  • Quantification was performed on the target protein content of the skin.
  • Fluorescently labeled small activating RNA sequences enter the skin's fluorescent three-view, with infrared light-treated skin, and fluorescently labeled small activating RNA sequences enter more.
  • Fluorescently labeled small activating RNA sequences enter the skin's fluorescent projections, and with infrared light-treated skin, fluorescently labeled small activating RNA sequences enter more.
  • the present invention establishes a method of administering infrared light to increase the small activating RNA (RNAa) sequence into the skin and producing biological activity, the method comprising the steps of:
  • step (3) mixing the solutions of step (1) and step (2) and allowing to stand for a certain period of time;
  • step (3) dissolving the solution of step (3) in a carrier solution
  • the solution of the step (4) is uniformly applied to the irradiation position; the wavelength of the infrared light is in the range of 1500 nm to 2000 nm.
  • the ratio of the small activating RNA sequence to the optimized culture solution can be adjusted according to the administration effect.
  • the ratio of the liposome to the optimized culture solution can be adjusted according to the administration effect.
  • the ratio of the small activating RNA sequence to the liposome can be adjusted according to the administration effect.
  • the present invention is based on the use of a certain band of infrared light to illuminate the skin, thereby significantly increasing the mixture of liposome and small activating RNA sequences into the skin and exerting a biological effect on the skin. This effect was confirmed by methods such as detection of the content of the target protein and detection of fluorescence generated by the target protein. This method can significantly increase the effect of small activating RNA on skin diseases.

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Abstract

提供了一种依据于特定波段红外激光照射皮肤，显著增加外源性RNA序列进入皮肤后产生的生物学效应的方法。利用特定波段红外光照射皮肤，可以显著地提高脂质体和RNA序列的混合物对皮肤的生物学效应。该方法可以增加RNA序列治疗皮肤疾病的效果。

Description

一种利用红外光增加RNA序列在皮肤中生物活性的给药方法
相关申请的交叉引用
本发明要求2016年12月29日提交的中国专利申请号201611243422.7和申请号CN201611243421.2的优先权，其全部内容通过引用并入本文。
技术领域
本发明涉及生命科学领域，具体涉及一种利用红外光增加RNA序列在皮肤中生物活性的给药方法。
背景技术
一些小干扰RNA和小激活RNA已经被证明可以用来治疗如皮肤黑素瘤、先天性厚甲、皮肤炎症、皮肤癌等皮肤疾病。但是由于胃肠道中复杂的生理环境，最终会导致RNA序列降解，而且生物大分子很难通过胃肠道膜。静脉注射的给药方法，会造成病人极强的疼痛感，同时RNA序列在到达皮肤前，还会被代谢或者排泄。一次这些传统的给药方法都没有显著疗效。目前最常用的皮肤给药方法是直接将RNA序列给到皮肤，从而调控原位的皮肤组织的基因表达，从而起到治疗效果。
由于角质层以及表皮层的紧密结构，是药物的通透性大幅降低的重要因素。所以提高皮肤的通透性，从而使RNA序列进入皮肤起到治疗效果，显得尤为重要。目前比较研究比较多的提高皮肤通透性的方法主要分为化学性增强剂和物理学增强剂。化学性增强剂是使用纳米材料、脂质体等从而提高RNA序列对皮肤的通透性。这类增强剂对RNA序列的长度，结构要求很高，同时制备工艺繁琐复杂。研究比较热门的物理性增强剂有微针给药，电学给药等方法。但微针给药和电学给药会给病人造成极大的疼痛感。
至今在对于运用激光增强小干扰RNA或小激活RNA序列对皮肤通 透性的研究方面，没有任何报道称可以运用激光有效地提升RNA序列在皮肤中的生物活性。这些生物活性只有通过RNA沉默目标蛋白的含量检测、目标蛋白产生的荧光检测等方法才能够获得证明。因此发明出可以有效、显著地提升外源性RNA序列在皮肤中的生物活性的方法，具有重大的临床意义。
发明内容
本发明的目的是克服上述现有技术的不足，提出一种可以有效、显著地提升外源性RNA序列例如小干扰RNA或小激活RNA序列在皮肤中的生物活性的方法，具有重大的临床意义。
本发明人研究发现，皮肤经过红外光照射后，显著增加小干扰RNA序列或小激活RNA(RNAa)序列对皮肤产生生物学作用。该作用通过RNA沉默目标蛋白或过表达目标蛋白的含量检测、目标蛋白产生的荧光的检测获得了证明。因此，本发明基于这一全新发现，突破了现有技术的难题，找到了一种可以提高小干扰RNA序列或小激活RNA序列对皮肤生物学效应的方法。
本发明的具体技术方案是：一种利用红外光增加RNA序列在皮肤中生物活性的给药方法，包括以下步骤：
(1)将脂质体溶于优化培养液中，静置；
(2)将RNA序列溶于优化培养液中，静置；
(3)将步骤(1)和步骤(2)的溶液混合，静置；
(4)将步骤(3)的溶液溶解于载体溶液中；
(5)对皮肤需要给药位置，使用一定剂量红外光照射后，将步骤(4)所述溶液均匀涂在照射位置上；所述红外光波长范围为1500nm-2000nm。
进一步的，所述脂质体与优化培养液的比例，可以根据给药效果 调节。
进一步的，所述RNA序列与优化培养液的比例，可以根据给药效果调节。
进一步的，所述脂质体与所述RNA序列的比例，可以根据给药效果调节。
进一步的，所述所有静置时间，可以根据给药效果调节。
进一步的，所述红外光波长范围为1500nm-2000nm。
本发明利用红外光照射皮肤，增加小干扰RNA序列对皮肤的生物学活性，为临床使用小干扰RNA序列治疗皮肤疾病建立基础，可以使患者得到更有效的治疗。
在本发明中，所述RNA序列是小干扰RNA序列或小激活RNA序列。
本发明还公开了一种红外光在增加RNA序列在皮肤中生物活性中的应用，其特征在于，对皮肤需要给药位置使用一定剂量红外光照射以增加RNA序列在皮肤中生物活性。
在一个实施例中，所述红外光的波长范围为1500nm-2000nm。
在一个实施例中，所述RNA序列的给药方式是外用给药。
在一个实施例中，所述外用给药是将溶解于脂质体的RNA序列经过外用涂抹于红外光照射的部位。
在一个实施例中，所述RNA序列为小干扰RNA序列或小激活RNA序列。
本领域技术人员根据本发明的内容，可以预期依据于本方法可以设计出来以提高siRNA转运入皮肤的效率的各种小型、便携或大型的仪器。
附图说明
图1示出荧光标记的小干扰RNA序列进入皮肤的荧光三视图。
图2示出荧光标记的小干扰RNA序列进入皮肤的荧光投影图
图2示出小干扰RNA序列使目标蛋白的表达量降低。
图3示出小干扰RNA序列降低经过紫外光照射后损伤的生物效应图。
具体实施方式
下面将通过具体描述，对本发明作进一步的说明。
除非另有限定，本文中所使用的所有技术和科学术语具有与本发明所属技术领域的普通技术人员通常理解相同的含义。
实施例1：一种新型的皮肤小干扰RNA序列给药治疗方法
确定了红外光可以增加小干扰RNA序列在皮肤中生物活性，建立了一种新型的皮肤小干扰RNA序列给药治疗方法。
根据本发明，使用雄性C57小鼠，重量在15-25g范围之间，RNA序列给药完成后，小鼠在动物房中进行饲养，条件为22-24℃，12小时的明/暗循环，并可自由进食取水。
24小时内，使用激光共聚焦显微镜对使用荧光标记的RNA序列的小鼠皮肤进行成像。
24小时内，检测使用目标蛋白的RNA序列的小鼠皮肤进行目标蛋白含量分析。
24小时内，对小鼠皮肤进行紫外光损伤，检测使用RNA序列的生物学效果。
皮肤组织的储存：皮肤取出后，取出适量组织浸泡于4％多聚甲醛，用于制作石蜡切片，剩余组织用铝箔纸包裹好，使用液氮冷冻，之后转移到-80℃冰箱长期保存。
针对皮肤目标蛋白含量，进行量化。
统计分析：所有数据按照平均值±标准差的方式给出，数据使用单因素方差分析进行评估，P值小于0.05认为是统计学显著的。
小鼠实验的结果如下所述：
图1：荧光标记的小干扰RNA序列进入皮肤的荧光三视图，用红外光处理的皮肤，荧光标记的小干扰RNA序列进入了更多。
图2：荧光标记的小干扰RNA序列进入皮肤的荧光投影图，用红外光处理的皮肤，荧光标记的小干扰RNA序列进入了更多。
图3：用红外光处理的皮肤，目标蛋白表达量显著下降。
图4：不用红外光处理的皮肤，对于损伤没有保护效果。用红外光处理的皮肤之后，小干扰RNA序列对皮肤损伤具有保护效果。
由以上实验可以得出，皮肤经过红外光照射后，增加小干扰RNA 序列对皮肤产生生物学作用。因此，可以使用这种方法进行更有效的皮肤疾病治疗。
本发明基于这一发现，建立了一种利用红外光增加小干扰RNA序列在皮肤中生物活性的给药方法。该方法包括以下步骤：
(1)将脂质体溶于优化培养液中，静置一定时间；
(2)将小干扰RNA序列溶于优化培养液中，静置一定时间；
(3)将步骤(1)和步骤(2)的溶液混合，静置一定时间；
(4)将步骤(3)的溶液溶解于载体溶液中；
(5)对皮肤需要给药位置，使用一定剂量红外光照射后，将步骤(4)所述溶液均匀涂在照射位置上；所述红外光的波长范围为1500nm-2000nm。
本发明小干扰RNA序列配制方法中，所述小干扰RNA序列与优化培养液的比例，可以根据给药效果调节。
本发明小干扰RNA序列配制方法中，所述脂质体与优化培养液的比例，可以根据给药效果调节。
本发明小干扰RNA序列配制方法中，所述小干扰RNA序列与脂质体的比例，可以根据给药效果调节。
本发明是基于运用一定波段的红外光照射皮肤，从而显著地提高脂质体和小干扰RNA序列的混合物对皮肤的生物学效应。该作用通过RNA沉默目标蛋白的含量检测、目标蛋白产生的荧光的检测等方法获得了证明。该方法可以显著增加小干扰RNA序列治疗皮肤疾病的效果。
实施例2：一种新型的皮肤小激活RNA序列给药治疗方法
确定了红外光可以增加小激活RNA序列在皮肤中生物活性，建立了一种新型的皮肤小激活RNA序列给药治疗方法。
根据本发明，使用雄性C57小鼠，重量在15-25g范围之间，小激活RNA序列给药完成后，小鼠在动物房中进行饲养，条件为22-24℃，12小时的明/暗循环，并可自由进食取水。
24小时内，使用激光共聚焦显微镜对使用荧光标记的RNA序列的小鼠皮肤进行成像。
24小时内，检测使用目标蛋白的RNA序列的小鼠皮肤进行目标蛋白含量分析。
24小时内，对小鼠皮肤进行紫外光损伤，检测使用RNA序列的生物学效果。
皮肤组织的储存：皮肤取出后，取出适量组织浸泡于4％多聚甲醛，用于制作石蜡切片，剩余组织用铝箔纸包裹好，使用液氮冷冻，之后转移到-80℃冰箱长期保存。
针对皮肤目标蛋白含量，进行量化。
统计分析：所有数据按照平均值±标准差的方式给出，数据使用单因素方差分析进行评估，P值小于0.05认为是统计学显著的。
小鼠实验的结果如下所述：
荧光标记的小激活RNA序列进入皮肤的荧光三视图，用红外光处 理的皮肤，荧光标记的小激活RNA序列进入了更多。
荧光标记的小激活RNA序列进入皮肤的荧光投影图，用红外光处理的皮肤，荧光标记的小激活RNA序列进入了更多。
由以上实验可以得出，皮肤经过红外光照射后，增加小激活RNA序列对皮肤产生生物学作用。因此，可以使用这种方法进行更有效的皮肤疾病治疗。
本发明基于这一发现，建立了一种红外光增加小激活RNA(RNAa)序列进入皮肤并产生生物活性的给药方法，该方法包括以下步骤：
(1)将脂质体溶于优化培养液中，静置一定时间
(2)将小激活RNA序列溶于优化培养液中，静置一定时间；
(3)将步骤(1)和步骤(2)的溶液混合，静置一定时间；
(4)将步骤(3)的溶液溶解于载体溶液中；
(5)对皮肤需要给药位置，使用一定剂量红外光照射后，将步骤(4)所述溶液均匀涂在照射位置上；所述红外光的波长范围为1500nm-2000nm。
本发明小激活RNA序列配制方法中，所述小激活RNA序列与优化培养液的比例，可以根据给药效果调节。
本发明小激活RNA序列配制方法中，所述脂质体与优化培养液的比例，可以根据给药效果调节。
本发明小激活RNA序列配制方法中，所述小激活RNA序列与脂质体的比例，可以根据给药效果调节。
本发明基于运用一定波段的红外光照射皮肤，从而显著地提高脂 质体和小激活RNA序列的混合物进入皮肤，并对皮肤起到生物学效应。该作用通过目标蛋白的含量检测、目标蛋白产生的荧光的检测等方法获得了证明。该方法可以显著增加小激活RNA治疗皮肤疾病的效果。
本领域的技术人员应当明了，尽管为了举例说明的目的，本文描述了本发明的具体实施方式，但可以对其进行各种修改而不偏离本发明的精神和范围。因此，本发明的具体实施方式和实施例不应当视为限制本发明的范围。本发明仅受所附权利要求的限制。本申请中引用的所有文献均完整地并入本文作为参考。

Claims (14)

  1. 一种利用红外光增加RNA序列在皮肤中生物活性的给药方法，包括以下步骤：
    (1)将脂质体溶于优化培养液中，静置一定时间；
    (2)将RNA序列溶于优化培养液中，静置一定时间；
    (3)将步骤(1)和步骤(2)的溶液混合，静置一定时间；
    (4)将步骤(3)的溶液溶解于载体溶液中；
    (5)对皮肤需要给药位置，使用一定剂量红外光照射后，将步骤(4)所述溶液均匀涂在照射位置上。
  2. 如权利要求1所述的方法，其特征在于，所述脂质体与优化培养液的比例，可以根据给药效果调节。
  3. 如权利要求1所述的方法，其特征在于，所述RNA序列与优化培养液的比例，可以根据给药效果调节。
  4. 如权利要求1所述的方法，其特征在于，所述脂质体与所述RNA序列的比例，可以根据给药效果调节。
  5. 如权利要求1所述的方法，其特征在于，所述所有静置时间，可以根据给药效果调节。
  6. 如权利要求1所述的方法，其特征在于，所述红外光波长范围为1500nm-2000nm。
  7. 如权利要求1至6任一项所述的方法，其特征在于，所述RNA序列为小干扰RNA序列或小激活RNA序列。
  8. 一种红外光在增加RNA序列在皮肤中生物活性中的应用，其 特征在于，对皮肤需要给药位置使用一定剂量红外光照射以增加RNA序列在皮肤中生物活性。
  9. 如权利要求8所述的应用，其中，所述红外光的波长范围为1500nm-2000nm。
  10. 如权利要求8所述的应用，其中，所述RNA序列的给药方式是外用给药。
  11. 如权利要求9所述的应用，其中，所述外用给药是将溶解于脂质体的RNA序列经过外用涂抹于红外光照射的部位。
  12. 如权利要求8至11任一项所述的方法，其特征在于，所述RNA序列为小干扰RNA序列或小激活RNA序列。
  13. 一种仪器，使用如权利要求1至6任一项所述的方法，其可以提高RNA序列转运入皮肤的效率。
  14. 如权利要求13所述的方法，其特征在于，所述RNA序列为小干扰RNA序列或小激活RNA序列。
PCT/CN2017/119409 2016-12-29 2017-12-28 一种利用红外光增加rna序列在皮肤中生物活性的给药方法 Ceased WO2018121674A1 (zh)

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Publication number Priority date Publication date Assignee Title
CN102179011A (zh) * 2011-03-04 2011-09-14 赵广 红外线-紫外线复合治疗仪
CN102625853A (zh) * 2009-09-02 2012-08-01 欧莱雅 表皮分化微小rna标记及其应用
CN106798727A (zh) * 2016-12-29 2017-06-06 上海交通大学 一种利用红外光增加小干扰rna序列在皮肤中生物活性的给药方法
CN106821981A (zh) * 2016-12-29 2017-06-13 上海交通大学 一种红外光增加激活性RNA（RNAa）序列进入皮肤并产生生物活性的给药方法
WO2017115991A1 (ko) * 2015-12-31 2017-07-06 한국과학기술원 항암제-인도시아닌 그린-리포좀 복합체를 포함하는 암 치료용 조성물

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CN102625853A (zh) * 2009-09-02 2012-08-01 欧莱雅 表皮分化微小rna标记及其应用
CN102179011A (zh) * 2011-03-04 2011-09-14 赵广 红外线-紫外线复合治疗仪
WO2017115991A1 (ko) * 2015-12-31 2017-07-06 한국과학기술원 항암제-인도시아닌 그린-리포좀 복합체를 포함하는 암 치료용 조성물
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