JP6094761B2 - 自己タンパク質の製造方法 - Google Patents
自己タンパク質の製造方法 Download PDFInfo
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- JP6094761B2 JP6094761B2 JP2013517009A JP2013517009A JP6094761B2 JP 6094761 B2 JP6094761 B2 JP 6094761B2 JP 2013517009 A JP2013517009 A JP 2013517009A JP 2013517009 A JP2013517009 A JP 2013517009A JP 6094761 B2 JP6094761 B2 JP 6094761B2
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Description
本発明は、以下で例示的な実施例および関連図面を用いてより詳しく説明する。
11人の相異なる患者(番号1−11)の各々から2個の9ml血液サンプルを本発明による容器、すなわち2.7mgの金粒子(1μmの直径を有する)で予め充填された9ml注射器に収集した。同一供給源(患者)から同量の血液サンプルを、いかなる金粒子も含有しない類似する9ml注射器内に収集した。前記サンプルは、相異なる時期に、すなわち血液を取った直後の時間T0、および37℃で24時間培養した後の時間T24において分析した。
前記分析結果を表1に示し、また、図2にグラフで示す。
A)軟質−組織の膨潤
有望な臨床研究の一部として、腱炎(骨に対する付着領域において腱(tendon)に対する退行性変化)による顕著な軟質組織の膨潤を有する8匹の馬を本発明による薬物で処理した。
全ての8個の場合において、3週後ぶりに顕著な膨潤の減少が発見された。6ケ月後および1年後にも、全ての馬は膨潤から完全に自由であった。治療する間にいかなる悪い効果も明らかになっていない。
この研究の結果は図3にグラフで示す。
他の馬研究において、跛行するという臨床症状(12個の肢が影響を受ける)を示す11匹の馬を本発明による薬物で治療した。跛行する症例の医療的な原因は、6個の症例では関節内/関節上での退行性軟骨変化(n=6)であり、また、6個の症例では軟質−組織疾患(n=6)であった。
この研究の結果は図4にグラフで示す。
用いられた金粒子は金粉末であった(粒子大きさ1μm、ミュンヘンに所在するBio−Rad Laboratories)。前記金粒子は、製造者によって推薦されたように先に滅菌される。所望する量の金粒子/金粉末、例えば30mgを1mlの70%エタノールと共に混合し、軽く攪拌(混合器、vortexer)しながら10分間培養し、1分間沈降させてから遠心分離した後に上清を除去した。その次、前記金粒子は、各場合において、1mlの滅菌二重−蒸留した水を用いて3回洗浄した。最終遠心分離によって最後の洗浄過程と上清を抽出した後、前記金粒子を滅菌PBSに再懸濁し、また、所望する濃度、例えば60mg/mlに調節した。連続的な攪拌下で、ピペットを利用して10μlの金粒子溶液を除去し、また、Sarstedt(REF02.1726.001)から得たS−Monovette−中性/9ml(92x16mm)に移した。前記Monovetteは、先ず滅菌作業台(スクリューキャップ)において開き、10μl金−粒子溶液を注射器の内壁に加えた後に再び閉じた。充填されたMonovetteは、使う時まで室温に保存した。本発明による方法を実施する時に使うために、9mlの体液(例えば、血液)を前記製造されたMonovetteに充填し、金−粒子/PBS溶液と混合した。
有望な経時的研究の一部として、放射能的に検出された膝関節症にかかった総9人の患者または13個の関節を登録医師が治療を行った。関節症の程度は、チェルグレン−ローレンス基準に従って等級3−4に評価された(Kellgren J.H.and Lawrence J.S.:「Radiological Assessment of Osteo−Arthrosis」、Ann.rheum.Dis.(1957)、16、494−501)。全ての患者は、先ず金で処理されてから粒子を除去し、本発明による自己血清によって関節腔内注射を各々1週間隔で4回投与を受けた。関節腔内の流出があれば、注射前に各場合において排水され、排水された量を収録し、また、その後の加工のために−20℃で1ml分量(aliquot)で冷凍させた。この治療の臨床結果は、処理前および許可された点数評価システム(同意語:スコア)「KOOS」を利用し、治療してから1、3、6および12ケ月後に記録した(Roos E.M.,Roos H.P.,Lohmander L.S.,Ekdahlc.,Beynnon B.D.:「Knee Injury and Osteoarthritis Outcome Score(KOOS−development of a self−administered outcome measure」、J.Orthop.Sports Phys.Ther.1998、28:88−96)。最大に得ることができる点数は100であった。点数が高いほど、達成した結果がより優れるものであった。結果を図5にグラフで示す。
関節症が発病する間に関節軟骨に対する機械的過負荷の影響は十分に知られている。軟骨移植物に対する機械的荷重の影響を試験する試験管内モデル、例えば、ヒューザーおよびデービスからのモデル(Huser C.A.and Davies M.E.:「Validation of an in vitro single−impact load model of the initiation of osteroarthritis−like changes in articular cartilage」、J Orthop Res.,Apr 2006;24(4):725−732)がよく確立し立証されている。このようなモデルにおいて、軟骨退行の開始に対する良好な指標は、試験された軟骨−骨サンプルの培養培地におけるプロテオグリカン含量の測定である。
●衝撃処理を受けない移植物=「衝撃が加えられない対照群」=「0対照群」
●衝撃処理を受けた移植物=「衝撃が加えられた対照群」=「衝撃対照群」
●衝撃処理された後、本発明により製造されたタンパク質−濃縮された血清と共に培養された移植物。
したがって、この試験は、本発明による薬物の軟骨保護効果に対する証拠を提供する。
Claims (12)
- 血液又は血清および金粒子を含む、血清をつくるための薬物として用いるための物質混合物であって、
ゲルゾリンに対する関連標準血液レベルの少なくとも2倍であるゲルゾリン含量を有する物質混合物。 - 前記薬物は、ゲルゾリンの欠乏と関連する疾病の治療用に好適なものとして考慮される、請求項1に記載の物質混合物。
- 前記薬物は、組織退行と関連する疾病の治療用に好適なものとして考慮される、請求項1に記載の物質混合物。
- 前記疾病は関節症であり、また前記薬物は関節症の治療用に好適なものとして考慮される、請求項3に記載の物質混合物。
- 金粒子を含有する容器内に血清が収集されるステップと、前記血清と金粒子の混合物が培養されるステップと、次に前記金粒子が血清から除去され廃棄されるステップを含む、薬物として用いるためのサイトカイン−濃縮およびゲルゾリン−濃縮された血清を作成する方法。
- ゲルゾリンに対する関連標準血液レベルの少なくとも2倍であるゲルゾリン含量を有する前記血清を作成する、請求項5に記載の方法。
- 前記金粒子および血液細胞および/またはその他の不溶性成分は、血清から除去して廃棄される、請求項5または6に記載の方法。
- 前記金粒子は10nm〜1μmの大きさである、請求項5〜7のうちいずれか1項に記載の方法。
- 前記金粒子は、10ml容器当たり103〜104の金粒子量、または1mlの血液/容器当たり10nm〜1μm直径を有する金粒子量0.3mgで存在する、請求項5〜8のうちいずれか1項に記載の方法。
- 前記薬物は、組織退行と関連する疾病の治療用に好適なものとして考慮される、請求項5〜9のうちいずれか1項に記載の方法。
- 前記疾病は関節症であり、また、前記薬物は関節症の治療用に好適なものとして考慮される、請求項10に記載の方法。
- 前記薬物は、ゲルゾリンの欠乏と関連する疾病の治療用に好適なものとして考慮される、請求項5〜9のうちいずれか1項に記載の方法。
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AU2011282056A1 (en) | 2013-01-24 |
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KR20130139837A (ko) | 2013-12-23 |
DE102010026500A1 (de) | 2012-01-12 |
EP2590659A2 (de) | 2013-05-15 |
WO2012010128A3 (de) | 2012-05-31 |
BR112012033476A2 (pt) | 2016-10-25 |
WO2012010128A2 (de) | 2012-01-26 |
MX353734B (es) | 2018-01-26 |
EP2590659B1 (de) | 2017-11-08 |
JP2013537516A (ja) | 2013-10-03 |
ES2658269T3 (es) | 2018-03-09 |
US20130323200A1 (en) | 2013-12-05 |
MX2013000072A (es) | 2013-05-17 |
AU2011282056B2 (en) | 2015-02-26 |
CN103037873A (zh) | 2013-04-10 |
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