WO2022004816A1 - 胎児付属物由来組織細胞培養上清を含む脳神経障害治療剤 - Google Patents

胎児付属物由来組織細胞培養上清を含む脳神経障害治療剤 Download PDF

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WO2022004816A1
WO2022004816A1 PCT/JP2021/024837 JP2021024837W WO2022004816A1 WO 2022004816 A1 WO2022004816 A1 WO 2022004816A1 JP 2021024837 W JP2021024837 W JP 2021024837W WO 2022004816 A1 WO2022004816 A1 WO 2022004816A1
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derived
cells
fetal
cranial nerve
culture supernatant
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Japanese (ja)
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▲祐▼輔 相良
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Kochi University NUC
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Priority to CN202180047221.2A priority Critical patent/CN115811981A/zh
Priority to US18/003,425 priority patent/US20230242870A1/en
Priority to JP2022534097A priority patent/JPWO2022004816A1/ja
Priority to EP21832276.6A priority patent/EP4173629A4/en
Publication of WO2022004816A1 publication Critical patent/WO2022004816A1/ja
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    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06Animal cells or tissues; Human cells or tissues
    • C12N5/0602Vertebrate cells
    • C12N5/0603Embryonic cells ; Embryoid bodies
    • C12N5/0605Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly
    • AHUMAN NECESSITIES
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    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/28Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
    • AHUMAN NECESSITIES
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    • A61K35/48Reproductive organs
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    • A61K35/48Reproductive organs
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    • A61K35/48Reproductive organs
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    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
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    • C12N2501/00Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20Cytokines; Chemokines
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    • C12N2501/20Cytokines; Chemokines
    • C12N2501/23Interleukins [IL]
    • C12N2501/2306Interleukin-6 (IL-6)

Definitions

  • Perinatal cerebral disorders that cause cerebral palsy include hypoxic-ischemic encephalopathy, cerebral hemorrhage, and periventricular leukomalacia, and the main pathological conditions of these are intracellular Ca elevation and active oxygen resulting from mitochondrial dysfunction. It is an inflammatory condition called hypercytokine palsy associated with the increase in macrophage activation. In particular, cerebral hemorrhage is more likely to occur in premature infants, with the most severe symptoms and poor prognosis.
  • Non-Patent Document 1 Clinical studies have been conducted in which autologous bone marrow-derived mesenchymal cells are directly administered to patients with cerebral palsy, and their effectiveness has been reported.
  • Non-Patent Document 2 Although there are reports of administration of umbilical cord-derived cells, some motor functions have not been significantly improved (Non-Patent Document 2).
  • the cranial nerve regeneration promoter is a cranial nerve progenitor cell proliferation / survival promoter, a cranial nerve progenitor cell homing promoter, a cranial nerve progenitor cell differentiation / maturation promoter, or a combination thereof.
  • the cranial nerve regeneration promoting agent according to any one item.
  • the cranial nerve regeneration promoting agent according to any one of (13) to (16) which comprises a cytokine and a chemokine in the culture supernatant.
  • the cranial nerve regeneration promoting agent according to any one of (13) to (17) which comprises IL-6, CXCL1, CXCL7, CXCL8 and CCL2.
  • the "fetal appendage-derived tissue” (also referred to as “postpartum-derived tissue”) means a group of tissues excised during labor, such as the umbilical cord and fetal membrane (amniotic membrane, chorion, etc.). Includes umbilical cord), placenta, etc.
  • the fetal appendage-derived tissue of the present invention is not particularly limited as long as it is a fetal appendage-derived tissue collected from a mammal, and is, for example, a fetal appendage-derived tissue of a primate mammal. More preferably, it is a tissue derived from human fetal appendages.
  • the fetal appendage-derived tissue cell culture supernatant since the fetal appendage-derived tissue cell culture supernatant according to the present disclosure has a risk of infection by a contaminating virus or the like, it is preferable not to mix and culture the fetal appendage-derived tissue cells from the majority of donors. It should be noted that the culture supernatant of fetal appendage-derived tissue cells from a plurality of donors is advantageous in that it can be produced as a homogeneous therapeutic agent for cranial neuropathy.
  • the administration of the therapeutic agent for cranial nerve disorders is preferably parenteral administration, and the parenteral administration may be systemic administration or local administration.
  • parenteral administration may be systemic administration or local administration.
  • the method for administering the therapeutic agent for cranial neuropathy are not limited to the condition that the expected therapeutic effect is maintained, but for example, intravenous administration, intraarterial administration, intraportal administration, intradermal administration, and subcutaneous administration. Examples thereof include administration, intramuscular administration, intraperitoneal administration, transpulmonary administration (transpulmonary absorption), intraventricular administration, intrathecal administration, and nasal administration. Of these, nasal administration and the like are minimally invasive and are preferable.
  • a neural progenitor cells were seeded human neuroblastoma strains SH-SY5Y (ATCC, No. CRL-2226) in 96-well plastic plates at 2xl0 5 cells / mL in DMEM culture medium by 100 [mu] L. 100 ⁇ L of the various culture supernatants prepared in Example 1 were added, and the cells were cultured at 37 ° C. under 5% CO2 for 5 days. As a control, the same amount of the medium used for preparing various culture supernatants was added and cultured. After culturing, the images were taken with a phase-contrast microscope, and the length of the neurites was measured using the analysis software ImageJ (NIH).
  • Factors contained in the culture supernatant Factors contained in the culture supernatant of Walton collagen-derived mesenchymal cells, amniotic membrane-derived mesenchymal cells, and chorion-derived mesenchymal cells prepared in Example 1 are antibody arrays.
  • N 3 examined by (Human Cytokine Array C5, manufactured by RayBiotech).
  • cytokines such as IL-6
  • chemokines such as CCL2, CXCL1, CXCL5, CXCL7, CXCL8, GROa / b / g
  • growth factors such as BDNF and EGF
  • osteopontin are contained in the culture supernatant.

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PCT/JP2021/024837 2020-06-30 2021-06-30 胎児付属物由来組織細胞培養上清を含む脳神経障害治療剤 Ceased WO2022004816A1 (ja)

Priority Applications (4)

Application Number Priority Date Filing Date Title
CN202180047221.2A CN115811981A (zh) 2020-06-30 2021-06-30 包含胎儿附属物来源组织细胞培养上清的脑神经损伤治疗剂
US18/003,425 US20230242870A1 (en) 2020-06-30 2021-06-30 Cranial nerve disorder therapeutic agent including culture supernatant of tissue cells derived from fetal appendage
JP2022534097A JPWO2022004816A1 (https=) 2020-06-30 2021-06-30
EP21832276.6A EP4173629A4 (en) 2020-06-30 2021-06-30 THERAPEUTIC AGENT FOR CRANIAL NERVE DISEASE USING CULTURE SUPERNATANT OF TISSUE CELLS FROM THE FETAL APPENDIX

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JP2020113456 2020-06-30
JP2020-113456 2020-06-30
JP2020-149878 2020-09-07
JP2020149878A JP6967308B1 (ja) 2020-06-30 2020-09-07 胎児付属物由来組織細胞培養上清を含む脳神経障害治療剤

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EP (1) EP4173629A4 (https=)
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JP6967308B1 (ja) * 2020-06-30 2021-11-17 国立大学法人高知大学 胎児付属物由来組織細胞培養上清を含む脳神経障害治療剤
CN117679520A (zh) * 2022-09-09 2024-03-12 北京达尔文细胞生物科技有限公司 用于防治后遗症期面神经麻痹的药物组合物及其应用
WO2025100424A1 (ja) * 2023-11-10 2025-05-15 国立大学法人 東京大学 急性脳症治療剤及び急性脳症の治療方法
WO2025182103A1 (ja) * 2024-02-28 2025-09-04 セルソース株式会社 脳梗塞の機能予後改善用組成物

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JPWO2022004816A1 (https=) 2022-01-06
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