JP5076374B2 - 医薬組成物 - Google Patents
医薬組成物 Download PDFInfo
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- JP5076374B2 JP5076374B2 JP2006178118A JP2006178118A JP5076374B2 JP 5076374 B2 JP5076374 B2 JP 5076374B2 JP 2006178118 A JP2006178118 A JP 2006178118A JP 2006178118 A JP2006178118 A JP 2006178118A JP 5076374 B2 JP5076374 B2 JP 5076374B2
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Description
Biopolymers (2004) volume 76, 196-203 Experimental Cell Research (2001) volume 269, 237-244
(1)Leu−Leu−Ile−Ile−Leu−Arg−Arg−Arg−Ile−Arg−Lys−Gln−Ala−His−Ala−His−Ser−Lysのアミノ酸配列からなる、天然型アミノ酸で構成されるペプチド。
(2)(1)のアミノ酸配列において1もしくは2個のアミノ酸が欠失、置換または付加された配列からなり、かつインスリンを腸管内から血中に移行させる、天然型アミノ酸で構成されるペプチド。
<方法>
1.インスリン溶液の調製
ヒトリコンビナントインスリン(和光純薬)1.923mg(=50IU=0.33μmol)を秤量し、0.1M 塩酸50μlに溶解した。これにメチルセルロース(MC)添加リン酸生理緩衝液pH7.4(PBS)1.2mlおよび0.1M NaOH溶液50μlを加えて中和し、さらにMC添加PBS1.2mlを加えて総容量を2.5mlとした。(インスリン濃度0.769mg/ml=20IU/ml)。
pVEC(シグマジェノシス社にて合成、配列:Leu−Leu−Ile−Ile−Leu−Arg−Arg−Arg−Ile−Arg−Lys−Gln−Ala−His−Ala−His−Ser−Lys)0.609mg(0.25μmol)を秤量し、上記1で作製したインスリン溶液0.5ml(インスリン0.385mg=0.066μmol)を添加して溶解し、pVEC−インスリン混合溶液とした。コントロール(pVEC無し)については、インスリン溶液そのものを投与に用いた。
24時間絶食した体重約200gのSD系雄性ラットにペントバルビタールナトリウム50mg/kgを腹腔内注射することにより麻酔した後、正中線に沿って開腹し、腸管を露出した。回盲接合部から2−3cm回腸よりの部分からシリコンチューブを、およびその上部約10cmの部分からゾンデを挿入し、さらに内側6cmの部分に縫合糸を通した。
コントロールのインスリン単独の投与時と比較して、pVECを同時投与することにより、血中インスリン濃度の明らかな上昇、および血糖値の明らかな低下が認められた(図1および図2)。
Claims (2)
- 経口または経腸投与したインスリンを腸管内から血中に移行させる医薬組成物であって、成分として該インスリンおよび以下の(1)または(2)のペプチドを含有することを特徴とする医薬組成物。
(1)Leu−Leu−Ile−Ile−Leu−Arg−Arg−Arg−Ile−Arg−Lys−Gln−Ala−His−Ala−His−Ser−Lysのアミノ酸配列からなる、天然型アミノ酸で構成されるペプチド。
(2)(1)のアミノ酸配列において1もしくは2個のアミノ酸が欠失、置換または付加された配列からなり、かつインスリンを腸管内から血中に移行させる、天然型アミノ酸で構成されるペプチド。 - インスリンと前記(1)または(2)のペプチドが共有結合で連結されていないことを特徴とする、請求項1記載の医薬組成物。
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