JP2022159334A - コーティングされたマイクロニードルアレイのための亜鉛組成物 - Google Patents
コーティングされたマイクロニードルアレイのための亜鉛組成物 Download PDFInfo
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- JP2022159334A JP2022159334A JP2022119509A JP2022119509A JP2022159334A JP 2022159334 A JP2022159334 A JP 2022159334A JP 2022119509 A JP2022119509 A JP 2022119509A JP 2022119509 A JP2022119509 A JP 2022119509A JP 2022159334 A JP2022159334 A JP 2022159334A
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- zinc
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- mammal
- zinc compound
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- 239000000203 mixture Substances 0.000 title claims abstract description 107
- 239000011701 zinc Substances 0.000 title claims abstract description 42
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 title claims abstract description 40
- 229910052725 zinc Inorganic materials 0.000 title claims abstract description 40
- 238000003491 array Methods 0.000 title description 19
- 150000003752 zinc compounds Chemical class 0.000 claims abstract description 84
- 241000124008 Mammalia Species 0.000 claims abstract description 39
- 239000013543 active substance Substances 0.000 claims abstract description 34
- 150000003839 salts Chemical class 0.000 claims abstract description 30
- 238000000034 method Methods 0.000 claims abstract description 20
- 239000011248 coating agent Substances 0.000 claims abstract description 16
- 238000000576 coating method Methods 0.000 claims abstract description 16
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 34
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- 239000011592 zinc chloride Substances 0.000 claims description 17
- 235000005074 zinc chloride Nutrition 0.000 claims description 17
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 15
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- 229940101027 polysorbate 40 Drugs 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 229960003127 rabies vaccine Drugs 0.000 description 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- 229940126583 recombinant protein vaccine Drugs 0.000 description 1
- 239000003488 releasing hormone Substances 0.000 description 1
- BXNMTOQRYBFHNZ-UHFFFAOYSA-N resiquimod Chemical compound C1=CC=CC2=C(N(C(COCC)=N3)CC(C)(C)O)C3=C(N)N=C21 BXNMTOQRYBFHNZ-UHFFFAOYSA-N 0.000 description 1
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- 230000000241 respiratory effect Effects 0.000 description 1
- 229960003131 rubella vaccine Drugs 0.000 description 1
- OVVGHDNPYGTYIT-BNXXONSGSA-N rutinose Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)O1 OVVGHDNPYGTYIT-BNXXONSGSA-N 0.000 description 1
- 229940049703 saccharin sodium dihydrate Drugs 0.000 description 1
- 229940043230 sarcosine Drugs 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229940083538 smallpox vaccine Drugs 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
- 235000010378 sodium ascorbate Nutrition 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
- HVFAVOFILADWEZ-UHFFFAOYSA-M sodium;2-[2-(dodecanoylamino)ethyl-(2-hydroxyethyl)amino]acetate Chemical compound [Na+].CCCCCCCCCCCC(=O)NCCN(CCO)CC([O-])=O HVFAVOFILADWEZ-UHFFFAOYSA-M 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- HIWPGCMGAMJNRG-RTPHMHGBSA-N sophorose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)OC(O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HIWPGCMGAMJNRG-RTPHMHGBSA-N 0.000 description 1
- 229940057429 sorbitan isostearate Drugs 0.000 description 1
- 229950006451 sorbitan laurate Drugs 0.000 description 1
- 235000011067 sorbitan monolaureate Nutrition 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- UQZIYBXSHAGNOE-XNSRJBNMSA-N stachyose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@@H]3[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O3)O)O2)O)O1 UQZIYBXSHAGNOE-XNSRJBNMSA-N 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000008362 succinate buffer Substances 0.000 description 1
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- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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- 238000009736 wetting Methods 0.000 description 1
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Abstract
Description
7.45%のrhPTH(1-34)(Bachem,Bubendorf,Switzerlandから入手可能)、塩化亜鉛(0.19%)、ヒドロキシエチルセルロース100cP溶液(2.07%)、スクロース(39.88%)及び注射用水(50.41%)からなるコーティング調合物を調製した。液状結晶ポリマーから作製した中実のマイクロニードルアレイを、米国特許第9,339,956号に記載の通りに調製した。アレイは、直径が12.7mmであり、高さが500ミクロンで先端から先端が550ミクロン空いている、316本の正四角錘のニードルを有していた。アレイを、コーティング調合物中に浸して、先端がコーティングされたアレイを調製し、これは米国特許第8,741,377号に記載の通りとした。コーティングされたアレイを、HPLCによってrhPTH(1-34)の含有量について分析したところ、93mcg(n=6)の平均含有量を有していた。sMTS貼付剤を、アレイを接着剤に直径27mm重ねて付けることにより調製した。
7.22%のrhPTH(1-34)(Bachem,Bubendorf,Switzerlandから入手可能)、ヒドロキシエチルセルロース100cP溶液(2.00%)、スクロース(40.71%)及び注射用水(50.06%)からなるコーティング調合物を調製した。sMTS貼付剤を、実施例1に記載の通りに調製した。コーティングされたアレイを、rhPTH(1-34)の含有量についてHPLCにより分析したところ、平均含有量66mcg(n=6)を有していた。正味の送達用量は56mcgであった。動物試験及び分析を、実施例1に記載の通りに実施した。Cmaxにより正規化した血漿の平均レベル(n=3)を、図3に点線で示す。
1.3%のrhGH(ProSpec-Tany TechnoGene Ltd.,Ness Ziona、Israelから入手可能)、塩化亜鉛(0.014%)、ヒドロキシエチルセルロース100cP溶液(2.4%)、スクロース(39.85%)及び注射用水(56.4%)からなるコーティング調合物を調製した。液状結晶ポリマーから作製した中実のマイクロニードルアレイを、米国特許第9,339,956号に記載の通りに調製した。アレイは、直径が12.7mmであり、高さが500ミクロンで先端から先端が550ミクロン空いている、316本の正四角錘のニードルを有していた。アレイを、コーティング調合物中に浸して、先端がコーティングされたアレイを調製し、これは米国特許第8,741,377号に記載の通りとした。コーティングされたアレイを、rhGHの含有量についてHPLCにより分析したところ、平均含有量1.8mcg(n=6)を有していた。6つの貼付剤を1回用量として各ブタに適用し、総用量10.5mcgとした。sMTS貼付剤を、アレイを接着剤に直径27mmで重ねて付けることにより調製した。
1.3%のrhGH(ProSpec-Tany TechnoGene Ltd.,Ness Ziona,Israelから入手可能)、ヒドロキシエチルセルロース100cP溶液(2.3%)、スクロース(40.0%)及び注射用水(56.5%)からなるコーティング調合物を調製した。sMTS貼付剤を、実施例2に記載の通りに調製した。コーティングされたアレイを、rhGHの含有量についてHPLCにより分析したところ、平均含有量1.8mcg(n=6)を有していた。6つの貼付剤を1回用量として各ブタに適用し、総用量は11.0mcgとした。正味の送達用量は10.7mcgとした。動物試験及び分析を、実施例1に記載の通りに実施した。Cmaxにより正規化した血漿の平均レベル(n=4)を、図4に点線で示す。
本開示の実施態様の一部を以下の[項目1]-[項目16]に記載する。
[項目1]
治療有効量の活性薬剤を含む組成物と、
亜鉛、医薬として許容される亜鉛の塩、及びそれらの混合物からなる群から選択される亜鉛化合物と、
マイクロニードルのアレイとを備え、
前記組成物の少なくとも一部が前記マイクロニードルの少なくとも一部の上のコーティングとして存在する、医療デバイス。
[項目2]
前記亜鉛化合物が、亜鉛の無機塩を含む、項目1に記載の医療デバイス。
[項目3]
前記亜鉛化合物が、亜鉛の二価塩を含む、項目1又は2に記載の医療デバイス。
[項目4]
前記亜鉛化合物が、塩化亜鉛又は酢酸亜鉛を含む、項目1~3のいずれか一項に記載の医療デバイス。
[項目5]
亜鉛化合物の、活性薬に対するモル比が、0.1~2.0である、項目1~4のいずれか一項に記載の医療デバイス。
[項目6]
亜鉛化合物の、活性薬に対するモル比が、0.2~1.5である、項目1~5のいずれか一項に記載の医療デバイス。
[項目7]
亜鉛化合物の、活性薬に対するモル比が、0.25~1.0である、項目1~6のいずれか一項に記載の医療デバイス。
[項目8]
前記活性薬剤が、タンパク質又はペプチドである、項目1~7のいずれか一項に記載の医療デバイス。
[項目9]
前記活性薬剤が、ヒト成長ホルモン(hGH)、組織プラスミノーゲン活性化因子(TPA)、カルシトニン遺伝子関連ペプチド(CGRP)、黄体形成ホルモン放出ホルモン(LHRH)、LHRH類似体(例えばゴセレリン、ロイプロリド、ブセレリン、トリプトレリン)、ゴナドレリン及びナプファレリン、メノトロピン(卵胞刺激ホルモン(FSH)及び黄体形成ホルモン(LH))、ヒト閉経期ゴナドトロピン(hMG)、ヒト絨毛性ゴナドトロピン(hCG)、バソプレシン、デスモプレシン、インスリン、副腎皮質刺激ホルモン(ACTH)、ACTH類似体、例えばACTH(1-24)、カルシトニン、パラチロイドホルモン(PTH)、パラチロイドホルモン拮抗剤、パラチロイドホルモン関連タンパク質(PTHrP)、オキシトシン、デアミノ[Val4,D-Arg8]アルギニンバソプレシン、インターフェロンα、インターフェロンβ、インターフェロンγ、腫瘍壊死因子(TNF)、エリスロポエチン(EPO)、顆粒球マクロファージコロニー刺激因子(GM-CSF)、顆粒球コロニー刺激因子(G-CSF)、インターロイキン、IL-2(IL-2)、インターロイキン-10(IL-10)、グルカゴン及び成長ホルモン放出因子(GRF)からなる群から選択される、項目1~7のいずれか一項に記載の医療デバイス。
[項目10]
前記組成物の50重量%よりも多くが、前記マイクロニードル上のコーティングとして存在する、項目1~9のいずれか一項に記載の医療デバイス。
[項目11]
前記組成物の75重量%よりも多くが、前記マイクロニードル上のコーティングとして存在する、項目1~10のいずれか一項に記載の医療デバイス。
[項目12]
前記組成物の90重量%よりも多くが、前記マイクロニードル上のコーティングとして存在する、項目1~11のいずれか一項に記載の医療デバイス。
[項目13]
治療活性薬剤を哺乳動物に送達する方法であって、項目1~12のいずれか一項に記載のデバイスを前記哺乳動物の皮膚表面に適用すること、前記デバイスを前記皮膚とある時間接触させて前記活性薬剤の一部を前記哺乳動物の前記皮膚内に移行させること、及び続いて前記哺乳動物から前記デバイスを取り外すことを含む、方法。
[項目14]
前記哺乳動物において達成されるCmaxが、亜鉛化合物を含まない組成物を有する同様のデバイスを前記哺乳動物に前記ある時間適用した場合に達成されるCmaxよりも大きい、項目13に記載の治療活性薬剤を哺乳動物に送達する方法。
[項目15]
前記哺乳動物において達成されるAUCが、亜鉛化合物を含まない組成物を有する同様のデバイスを前記哺乳動物に前記ある時間適用した場合に達成されるCmaxよりも大きい、項目13又は14に記載の治療活性薬剤を哺乳動物に送達する方法。
[項目16]
前記活性薬剤が、PTHrP類似体ではない、項目1~15のいずれか一項に記載の医療デバイス又は方法。
Claims (16)
- 治療有効量の活性薬剤を含む組成物と、
亜鉛、医薬として許容される亜鉛の塩、及びそれらの混合物からなる群から選択される亜鉛化合物と、
マイクロニードルのアレイとを備え、
前記組成物の少なくとも一部が前記マイクロニードルの少なくとも一部の上のコーティングとして存在する、医療デバイス。 - 前記亜鉛化合物が、亜鉛の無機塩を含む、請求項1に記載の医療デバイス。
- 前記亜鉛化合物が、亜鉛の二価塩を含む、請求項1又は2に記載の医療デバイス。
- 前記亜鉛化合物が、塩化亜鉛又は酢酸亜鉛を含む、請求項1~3のいずれか一項に記載の医療デバイス。
- 亜鉛化合物の、活性薬に対するモル比が、0.1~2.0である、請求項1~4のいずれか一項に記載の医療デバイス。
- 亜鉛化合物の、活性薬に対するモル比が、0.2~1.5である、請求項1~5のいずれか一項に記載の医療デバイス。
- 亜鉛化合物の、活性薬に対するモル比が、0.25~1.0である、請求項1~6のいずれか一項に記載の医療デバイス。
- 前記活性薬剤が、タンパク質又はペプチドである、請求項1~7のいずれか一項に記載の医療デバイス。
- 前記活性薬剤が、ヒト成長ホルモン(hGH)、組織プラスミノーゲン活性化因子(TPA)、カルシトニン遺伝子関連ペプチド(CGRP)、黄体形成ホルモン放出ホルモン(LHRH)、LHRH類似体(例えばゴセレリン、ロイプロリド、ブセレリン、トリプトレリン)、ゴナドレリン及びナプファレリン、メノトロピン(卵胞刺激ホルモン(FSH)及び黄体形成ホルモン(LH))、ヒト閉経期ゴナドトロピン(hMG)、ヒト絨毛性ゴナドトロピン(hCG)、バソプレシン、デスモプレシン、インスリン、副腎皮質刺激ホルモン(ACTH)、ACTH類似体、例えばACTH(1-24)、カルシトニン、パラチロイドホルモン(PTH)、パラチロイドホルモン拮抗剤、パラチロイドホルモン関連タンパク質(PTHrP)、オキシトシン、デアミノ[Val4,D-Arg8]アルギニンバソプレシン、インターフェロンα、インターフェロンβ、インターフェロンγ、腫瘍壊死因子(TNF)、エリスロポエチン(EPO)、顆粒球マクロファージコロニー刺激因子(GM-CSF)、顆粒球コロニー刺激因子(G-CSF)、インターロイキン、IL-2(IL-2)、インターロイキン-10(IL-10)、グルカゴン及び成長ホルモン放出因子(GRF)からなる群から選択される、請求項1~7のいずれか一項に記載の医療デバイス。
- 前記組成物の50重量%よりも多くが、前記マイクロニードル上のコーティングとして存在する、請求項1~9のいずれか一項に記載の医療デバイス。
- 前記組成物の75重量%よりも多くが、前記マイクロニードル上のコーティングとして存在する、請求項1~10のいずれか一項に記載の医療デバイス。
- 前記組成物の90重量%よりも多くが、前記マイクロニードル上のコーティングとして存在する、請求項1~11のいずれか一項に記載の医療デバイス。
- 治療活性薬剤を哺乳動物に送達する方法であって、請求項1~12のいずれか一項に記載のデバイスを前記哺乳動物の皮膚表面に適用すること、前記デバイスを前記皮膚とある時間接触させて前記活性薬剤の一部を前記哺乳動物の前記皮膚内に移行させること、及び続いて前記哺乳動物から前記デバイスを取り外すことを含む、方法。
- 前記哺乳動物において達成されるCmaxが、亜鉛化合物を含まない組成物を有する同様のデバイスを前記哺乳動物に前記ある時間適用した場合に達成されるCmaxよりも大きい、請求項13に記載の治療活性薬剤を哺乳動物に送達する方法。
- 前記哺乳動物において達成されるAUCが、亜鉛化合物を含まない組成物を有する同様のデバイスを前記哺乳動物に前記ある時間適用した場合に達成されるCmaxよりも大きい、請求項13又は14に記載の治療活性薬剤を哺乳動物に送達する方法。
- 前記活性薬剤が、PTHrP類似体ではない、請求項1~15のいずれか一項に記載の医療デバイス又は方法。
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WO2023281447A1 (en) | 2021-07-07 | 2023-01-12 | Radius Health, Inc. | Methods of treating a cardiovascular ischemic event |
US11877848B2 (en) | 2021-11-08 | 2024-01-23 | Satio, Inc. | Dermal patch for collecting a physiological sample |
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