JPWO2019173435A5 - - Google Patents

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JPWO2019173435A5
JPWO2019173435A5 JP2020546395A JP2020546395A JPWO2019173435A5 JP WO2019173435 A5 JPWO2019173435 A5 JP WO2019173435A5 JP 2020546395 A JP2020546395 A JP 2020546395A JP 2020546395 A JP2020546395 A JP 2020546395A JP WO2019173435 A5 JPWO2019173435 A5 JP WO2019173435A5
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cartilage
composition according
bmp
composition
cells
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Priority claimed from PCT/US2019/020893 external-priority patent/WO2019173435A1/en
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ａ）間葉系細胞凝集体（ＣＭＢ）；および
ｂ）ヒドロゲル；
を含む組成物。 a) Mesenchymal cell aggregates (CMB); and b) Hydrogel;
Composition containing. ｃ）１つまたは複数の薬物または成長因子をさらに含む、請求項１に記載の組成物。 c) The composition of claim 1, further comprising one or more drugs or growth factors. ポリマーマイクロスフェアをさらに含み、１つまたは複数の薬物または成長因子がポリマーマイクロスフェアに封入されている、請求項１または請求項２に記載の組成物。 The composition of claim 1 or 2, further comprising a polymer microsphere, wherein one or more drugs or growth factors are encapsulated in the polymer microsphere. 前記ポリマーマイクロスフェアが、乳酸・グリコール酸共重合体（ＰＬＧＡ）、ポリ（乳酸）（ＰＬＡ）、またはＰＬＧＡとＰＬＡの組合せを含む、請求項３に記載の組成物。 The composition according to claim 3, wherein the polymer microsphere contains a lactic acid / glycolic acid copolymer (PLGA), a poly (lactic acid) (PLA), or a combination of PLGA and PLA. 前記ＣＭＢが、結合組織細胞および前駆細胞から選択される細胞を含み、前記前駆細胞は、軟骨細胞、腱細胞、靱帯細胞または半月板細胞を形成することができるものである、請求項１～４のいずれか一項に記載の組成物。 The CMB comprises cells selected from connective tissue cells and precursor cells, wherein the precursor cells can form chondrocytes, tendon cells, ligament cells or meniscus cells , claims 1-4. The composition according to any one of the above. 前記ＣＭＢが、軟骨、腱、靭帯または半月板から分離された細胞を含む、請求項１～４のいずれか一項に記載の組成物。 The composition according to any one of claims 1 to 4, wherein the CMB comprises cells separated from cartilage, tendon, ligament or meniscus. 前記細胞が、軟骨細胞、腱細胞、腱芽細胞、線維細胞または線維芽細胞である、請求項６に記載の組成物。 The composition according to claim 6, wherein the cell is a chondrocyte, a tendon cell, a tendon blast cell, a fibroblast or a fibroblast. 前記ＣＭＢが、間葉系幹細胞（ＭＳＣ）、脂肪由来幹細胞（ＡＤＳＣ）、骨髄由来幹細胞（ＢＭＳＣ）、臍帯血幹細胞（ＵＢ－ＭＳＣ）、神経堤幹細胞、人工多能性幹細胞、胚性幹細胞、および初代軟骨細胞から選択される幹細胞を含む、請求項５に記載の組成物。 The CMBs are mesenchymal stem cells (MSC), adipose-derived stem cells (ADSC), bone marrow-derived stem cells (BMSC), cord blood stem cells (UB-MSC), neural ridge stem cells, artificial pluripotent stem cells, embryonic stem cells, and The composition according to claim 5, which comprises stem cells selected from primary cartilage cells. 前記細胞が、同種供給源または自家供給源に由来する、請求項５に記載の組成物。 The composition according to claim 5, wherein the cells are derived from an allogeneic source or a self-source. 前記細胞が、抗免疫原性および／または免疫抑制性である、請求項５に記載の組成物。 The composition of claim 5, wherein the cells are anti-immunogenic and / or immunosuppressive. 前記ＣＭＢが、約－１℃未満の温度で少なくとも１日凍結保存される、請求項５に記載の組成物。 The composition according to claim 5, wherein the CMB is cryopreserved at a temperature of less than about -1 ° C. for at least 1 day. 前記ＣＭＢが、０℃～３０℃の間の温度で少なくとも１日低温保存される、請求項５に記載の組成物。 The composition according to claim 5, wherein the CMB is stored at a low temperature between 0 ° C. and 30 ° C. for at least 1 day. 前記ＣＭＢ中の細胞が、その細胞表面上に実質的または検出可能な量のヒト白血球抗原（ＨＬＡ）クラスＩＩ、ＣＤ４０、ＣＤ８０、またはＣＤ８６を発現しない、請求項１～１２のいずれか一項に記載の組成物。 13. The composition described. 前記ヒドロゲルが、フィブリン糊、多血小板血漿（ＰＲＰ）、Ｉ型コラーゲン、キトサン、ゼラチン、ポリエチレングリコールジアクリレート、ヒアルロン酸、およびそれらの任意の組合せから選択される、請求項１に記載の組成物。 The composition according to claim 1, wherein the hydrogel is selected from fibrin glue, platelet-rich plasma (PRP), type I collagen, chitosan, gelatin, polyethylene glycol diacrylate, hyaluronic acid, and any combination thereof. 前記成長因子がＴＧＦ－βスーパーファミリーのメンバーである、請求項２に記載の組成物。 The composition according to claim 2, wherein the growth factor is a member of the TGF-β superfamily. 前記成長因子が、ＯＰ－１、ＯＰ－２、ＯＰ－３、ＴＧＦ－β１、ＴＧＦ－β２、ＴＧＦ－β３、ＴＧＦ－β４、ＢＭＰ－１、ＢＭＰ－２、ＢＭＰ－３、ＢＭＰ－４、ＢＭＰ－５、ＢＭＰ－６、ＢＭＰ－８、ＢＭＰ－９、ＢＭＰ－１０、ＢＭＰ－１１、ＢＭＰ－１２、ＢＭＰ－１３、ＢＭＰ－１５、ＢＭＰ－１６、ＢＭＰ－１７、ＢＭＰ－１８、ＤＰＰ、Ｖｇ１、Ｖｇｒ－１、６０Ａタンパク質、ＧＤＦ－１、ＧＤＦ－２、ＧＤＦ－３、ＧＤＦ－５、ＧＤＦ－６、ＧＤＦ－７、ＧＤＦ－８、ＧＤＦ－９、ＧＤＦ－１０、ＧＤＦ－１１、ＧＤＦ－１２、ＣＤＭＰ－１、ＣＤＭＰ－２、ＣＤＭＰ－３、ＮＯＤＡＬ、ＵＮＩＶＩＮ、ＳＣＲＥＷ、ＡＤＭＰ、ＮＥＵＲＡＬからなる群より選択される形態形成タンパク質である、請求項２に記載の組成物。 The growth factors are OP-1, OP-2, OP-3, TGF-β1, TGF-β2, TGF-β3, TGF-β4, BMP-1, BMP-2, BMP-3, BMP-4, BMP. -5, BMP-6, BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-15, BMP-16, BMP-17, BMP-18, DPP, Vg1 , Vgr-1, 60A protein, GDF-1, GDF-2, GDF-3, GDF-5, GDF-6, GDF-7, GDF-8, GDF-9, GDF-10, GDF-11, GDF- 12. The composition according to claim 2, which is a bone morphogenetic protein selected from the group consisting of CDMP-1, CDMP-2, CDMP-3, NODAL, UNIVIN, SCREW, ADMP, and NEURAL. インスリン、トランスフェリン、ヒト血清アルブミン、プロリン、ウシ血清アルブミン、セレン酸、リノール酸、デキサメタゾン、およびアスコルビン酸のうちの１つまたは複数をさらに含む、請求項１～１６のいずれか一項に記載の組成物。 The composition according to any one of claims 1 to 16, further comprising one or more of insulin, transferrin, human serum albumin, proline, bovine serum albumin, selenic acid, linoleic acid, dexamethasone, and ascorbic acid. thing. 前記ＣＭＢが、単細胞を含む懸濁液中にある、請求項１に記載の組成物。 The composition according to claim 1, wherein the CMB is in a suspension containing a single cell. 前記ＣＭＢはサイズが均一または不均一である、請求項１に記載の組成物。 The composition of claim 1, wherein the CMB is uniform or non-uniform in size. 注射可能である、請求項１に記載の組成物。 The composition according to claim 1, which is injectable. 患者における結合組織欠損を治療するための組成物であり、結合組織または結合組織の周囲の領域に投与される、請求項１～２０のいずれか一項に記載の組成物。 The composition according to any one of claims 1 to 20 , which is a composition for treating connective tissue defect in a patient and is administered to the connective tissue or the region around the connective tissue . 患者における軟骨劣化を予防する、または軟骨損傷、軟骨変性疾患もしくは軟骨障害を治療するための組成物であり、軟骨または軟骨の周囲の領域に投与される、請求項１～２０のいずれか一項に記載の組成物。 One of claims 1 to 20 , which is a composition for preventing cartilage deterioration in a patient or treating cartilage damage, cartilage degenerative disease or cartilage disorder, and is administered to cartilage or a region around cartilage. The composition according to . 前記軟骨が関節軟骨である、請求項２２に記載の組成物。 22. The composition of claim 22, wherein the cartilage is articular cartilage. 前記軟骨が非関節軟骨である、請求項２２に記載の組成物。 22. The composition of claim 22, wherein the cartilage is non-articular cartilage. 前記軟骨が、鼻軟骨、耳介軟骨、気管気管支軟骨、肋軟骨、半月板および椎間板からなる群より選択される、請求項２４に記載の組成物。 24. The composition of claim 24, wherein the cartilage is selected from the group consisting of nasal cartilage, auricular cartilage, tracheobronchial cartilage, costal cartilage, meniscus and intervertebral disc. 軟骨欠損、軟骨劣化、軟骨損傷、軟骨変性疾患または軟骨障害の部位に１～２０％（ｗ／ｗ）のグリコサミノグリカン（ＧＡＧ）を含む組織を形成するのに有効である、請求項２１～２５のいずれか一項に記載の組成物。 21. Effective for forming a tissue containing 1 to 20% (w / w) glycosaminoglycan (GAG) at the site of cartilage defect, cartilage deterioration, cartilage damage, cartilage degenerative disease or cartilage disorder. The composition according to any one of 25 to 25. 軟骨欠損、軟骨劣化、軟骨損傷、軟骨変性疾患または軟骨障害の部位に少なくとも０．５％（ｗ／ｗ）のコラーゲンを含む組織を形成するのに有効である、請求項２１～２５のいずれか一項に記載の組成物。 Any of claims 21-25, which is effective in forming a tissue containing at least 0.5% (w / w) collagen at the site of cartilage defect, cartilage deterioration, cartilage damage, cartilage degenerative disease or cartilage disorder. The composition according to paragraph 1. 軟骨欠損、軟骨劣化、軟骨損傷、軟骨変性疾患または軟骨障害の部位に少なくとも１００ｋＰａのヤング率および最大０．８の摩擦係数を有する軟骨を形成するのに有効である、請求項２１～２７のいずれか一項に記載の組成物。 23. The composition according to item 1. 軟骨欠損、軟骨劣化、軟骨損傷、軟骨変性疾患または軟骨障害の部位に軟骨を形成するのに有効であり、その軟骨は、前記部位またはその周囲の任意の隣接する軟骨および軟骨下骨組織と癒合する、請求項２１～２８のいずれか一項に記載の組成物。 It is effective in forming cartilage at sites of cartilage defects, cartilage deterioration, cartilage damage, cartilage degenerative diseases or cartilage disorders, and the cartilage fuses with any adjacent cartilage and subchondral bone tissue at or around the site. The composition according to any one of claims 21 to 28. ｉｎ ｖｉｔｒｏまたはｉｎ ｖｉｖｏで軟骨組織を形成するために使用される、請求項１～２０のいずれか一項に記載の組成物。 The composition according to any one of claims 1 to 20, which is used for forming cartilage tissue in vitro or in vivo . 患者における断裂または破裂した結合組織を治療するための組成物であり、断裂もしくは破裂した結合組織に、または断裂もしくは破裂した結合組織の周囲の領域に投与される、請求項１～２０のいずれか一項に記載の組成物。 Any of claims 1-20 , the composition for treating ruptured or ruptured connective tissue in a patient, administered to the ruptured or ruptured connective tissue or to the area surrounding the ruptured or ruptured connective tissue . The composition according to one item. 前記結合組織が、靭帯、腱または半月板である、請求項３１に記載の組成物。 31. The composition of claim 31, wherein the connective tissue is a ligament, tendon, or meniscus.
JP2020546395A 2018-03-06 2019-03-06 Ready-made injectable cartilage, tendon and ligament repair compositions and how to use them Pending JP2021517121A (en)

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