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RELIEF FROM OSTEOARTHRITIS PAIN BY TARGETING MICRORNA-21 NEW_EN

Foreign code F190009983
File No. (S2018-0473-N0)
Posted date Oct 28, 2019
Country WIPO
International application number 2019JP009867
International publication number WO 2019176901
Date of international filing Mar 12, 2019
Date of international publication Sep 19, 2019
Priority data
  • P2018-044744 (Mar 12, 2018) JP
Title RELIEF FROM OSTEOARTHRITIS PAIN BY TARGETING MICRORNA-21 NEW_EN
Abstract An objective of the present invention is to elucidate the cause of pain in osteoarthritis and to contribute to the development of a therapeutic agent for alleviating the pain of osteoarthritis. An agent for relieving pain from osteoarthritis, the agent including an MiR-21 inhibitor as the active ingredient, or an agent for relieving pain from osteoarthritis, the agent including a TLR antagonist as the active ingredient.
Outline of related art and contending technology BACKGROUND ART
Osteoarthritis (osteoarthritis: OA) is a high prevalence, and has the chronic disease. Heisei 25th Life of the population based care insurance perspective view of the support according to the investigation of care is required at 1 the main cause of the pain of a joint, the joint of the subjective symptom of the population in the upper limb and the pain. Osteoarthritis drug therapies for pain alleviation of non-steroidal anti-inflammatory drug or acetaminophen, opioid or the like is used, the effectiveness is insufficient due to the artificial joint replacement in the case where a therapy such as surgery on the increase. Of an existing drug therapy may have many adverse effects of acute, chronic for deleterious effect associated with the use, the development of new analgesic has been desired. In the cause of the pain of osteoarthritis is still not clear, for the development of new analgesic osteoarthritis in the cause of the pain is required.
In recent years, a variety of diseases in pain associated with the importance of the microRNA has been reported that, in the pain of osteoarthritis of the little report microRNA function.
In a recent study, extracellular microRNA Toll-like receptor cell in the 7 after binding (Toll like receptor; TLR), a variety of physiological functions have been reported. TLR7 Is, the sensation of pain associated with the function of the spinal cord dorsal root ganglia (DRG) smaller neuronal (sensory) and expressed, and pain involved in the control are known.
Patent Document 1 is (US 9267139 B2), as an example of a musculo-skeletal diseases illustrated in osteoarthritis, as a treatment method, attention is paid to the miRNA, or reduces the expression of miR-29b-1 discloses a method for controlling. However, 29 years-41 years of age from the patient's bone marrow mesenchymal stem cells (BMSCs) 64 of the age of-73 years as compared to the change in microRNA BMSCs remains being examined, and possibly also adaptive disease is likely to be as long as the relationship between the disease and is not intended to be written, an agent involved in the expression of microRNA (microRNA inhibitors and the like) not to mention whether or not to control pain, an agent involved in the expression of microRNA expression of the microRNA to the actual change is not to confirm. Further, the fact that the treatment of osteoarthritis, or whether the treatment of pain treatment of cartilage degeneration is not expressly recited.
Patent Document 2 (WO 2013/151058) is, by controlling the expression of the miR-140, osteoarthritis or degenerative disc disease of the cartilage such as the method for treating a disease is disclosed, this is, the pain of osteoarthritis therapeutic agent but, by controlling the differentiation of cartilage, in the treatment of osteoarthritis. Cartilage degeneration does not correlate with the number of reports that the pain is present, although the present invention are different.
Patent Document 3 (JP Patent Application 2012-504651) is, by inhibiting the activity of TLR3, and a method for treating inflammatory conditions, one aspect of the osteoarthritis are listed, only, but only listed.
Patent Document 4 (JP Patent Application 2011-502170) is, the disease treatment or prevention of osteoarthritis TLR4 antagonist for use. TLR4 Is activated, due to an increase in the release of inflammatory cytokines, osteoarthritis inflammatory response by the onset of the disease that is linked to the present invention, TLR7, 8, 9 is not of interest.
Patent Document 5 (JP Patent Application 2016-512561) is, in order to reduce the pain and TLR4 antagonist is noted that the present invention. As a disease, and osteoarthritis However, TLR7, 8, 9 is not of interest. In addition, lower back pain, pain in the vulva, trigeminal neuralgia, such as migraine test is performed for, for osteoarthritis, no test is not performed.
TLR antagonists it is needless to say, the type of receptor is different from that of the site of action, in a completely different.
Scope of claims (In Japanese)[請求項1]
 miR-21阻害薬を有効成分として含む変形性関節症による疼痛の緩和薬。

[請求項2]
 miR-21阻害薬がmiR-21に結合し機能阻害する核酸である、請求項1に記載の変形性関節症による疼痛の緩和薬。

[請求項3]
 miR-21阻害薬が、配列番号1で表される塩基配列の全部または連続した一部配列に相補的な配列を含む配列からなる核酸である、請求項1に記載の変形性関節症による疼痛の緩和薬。

[請求項4]
 TLR拮抗薬を有効成分として含む変形性関節症による疼痛の緩和薬。

[請求項5]
 TLR拮抗薬がTLR7、TLR8またはTLR9の拮抗薬である、請求項4記載の変形性関節症による疼痛の緩和薬。

[請求項6]
 TLR拮抗薬が、inhibitoryオリゴデオキシヌクレオチドである、請求項4または5に記載の変形性関節症による疼痛の緩和薬。

[請求項7]
 請求項1~3のいずれか1項に記載のmiR-21阻害薬を有効成分として含む変形性関節症による疼痛の緩和薬と請求項4~6のいずれか1項に記載のTLR拮抗薬を有効成分として含む変形性関節症による疼痛の緩和薬とを組合せた、変形性関節症による疼痛の緩和薬。
  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • NIPPON MEDICAL SCHOOL FOUNDATION
  • Inventor
  • HOSHIKAWA Naoya
  • SAKAI Atsushi
  • SUZUKI Hidenori
  • TAKAI Shinro
IPC(International Patent Classification)
Specified countries National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DJ DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JO JP KE KG KH KN KP KR KW KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN ST TD TG

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