JPWO2021102084A5 - - Google Patents
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- JPWO2021102084A5 JPWO2021102084A5 JP2022529453A JP2022529453A JPWO2021102084A5 JP WO2021102084 A5 JPWO2021102084 A5 JP WO2021102084A5 JP 2022529453 A JP2022529453 A JP 2022529453A JP 2022529453 A JP2022529453 A JP 2022529453A JP WO2021102084 A5 JPWO2021102084 A5 JP WO2021102084A5
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- acid
- ionic liquid
- choline
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- anion
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- 239000002608 ionic liquid Substances 0.000 claims 30
- 239000000203 mixture Substances 0.000 claims 25
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims 19
- 229960001231 choline Drugs 0.000 claims 18
- 150000001450 anions Chemical class 0.000 claims 14
- 150000001768 cations Chemical class 0.000 claims 14
- 108020004707 nucleic acids Proteins 0.000 claims 10
- 150000007523 nucleic acids Chemical class 0.000 claims 10
- 102000039446 nucleic acids Human genes 0.000 claims 10
- 150000001875 compounds Chemical class 0.000 claims 9
- YYPNJNDODFVZLE-UHFFFAOYSA-N 3-methylbut-2-enoic acid Chemical compound CC(C)=CC(O)=O YYPNJNDODFVZLE-UHFFFAOYSA-N 0.000 claims 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 7
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims 6
- 239000002253 acid Substances 0.000 claims 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 6
- 125000001453 quaternary ammonium group Chemical group 0.000 claims 6
- FEPBITJSIHRMRT-UHFFFAOYSA-N 4-hydroxybenzenesulfonic acid Chemical compound OC1=CC=C(S(O)(=O)=O)C=C1 FEPBITJSIHRMRT-UHFFFAOYSA-N 0.000 claims 5
- 230000002401 inhibitory effect Effects 0.000 claims 5
- XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 claims 4
- GWYFCOCPABKNJV-UHFFFAOYSA-M 3-Methylbutanoic acid Natural products CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 claims 4
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims 4
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims 4
- 125000001931 aliphatic group Chemical group 0.000 claims 4
- -1 aromatic anion Chemical class 0.000 claims 4
- GWYFCOCPABKNJV-UHFFFAOYSA-N beta-methyl-butyric acid Natural products CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims 4
- 235000014113 dietary fatty acids Nutrition 0.000 claims 4
- 229930195729 fatty acid Natural products 0.000 claims 4
- 239000000194 fatty acid Substances 0.000 claims 4
- 150000004665 fatty acids Chemical class 0.000 claims 4
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 claims 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 4
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 claims 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims 4
- XNLWJFYYOIRPIO-UHFFFAOYSA-N 3-phenylbenzoic acid Chemical class OC(=O)C1=CC=CC(C=2C=CC=CC=2)=C1 XNLWJFYYOIRPIO-UHFFFAOYSA-N 0.000 claims 3
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 claims 3
- CMPQUABWPXYYSH-UHFFFAOYSA-N phenyl phosphate Chemical compound OP(O)(=O)OC1=CC=CC=C1 CMPQUABWPXYYSH-UHFFFAOYSA-N 0.000 claims 3
- GYSCBCSGKXNZRH-UHFFFAOYSA-N 1-benzothiophene-2-carboxamide Chemical compound C1=CC=C2SC(C(=O)N)=CC2=C1 GYSCBCSGKXNZRH-UHFFFAOYSA-N 0.000 claims 2
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 claims 2
- CWIRZTNBZZFPSG-UHFFFAOYSA-N 2-phenylpropanoic acid;3-phenylpropanoic acid Chemical compound OC(=O)C(C)C1=CC=CC=C1.OC(=O)CCC1=CC=CC=C1 CWIRZTNBZZFPSG-UHFFFAOYSA-N 0.000 claims 2
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 claims 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N Decanoic acid Natural products CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 claims 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N Gluconic acid Natural products OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 claims 2
- 101001076431 Homo sapiens NF-kappa-B inhibitor zeta Proteins 0.000 claims 2
- 102100026009 NF-kappa-B inhibitor zeta Human genes 0.000 claims 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 claims 2
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 claims 2
- HJJPJSXJAXAIPN-UHFFFAOYSA-N arecoline Chemical compound COC(=O)C1=CCCN(C)C1 HJJPJSXJAXAIPN-UHFFFAOYSA-N 0.000 claims 2
- MVIOINXPSFUJEN-UHFFFAOYSA-N benzenesulfonic acid;hydrate Chemical compound O.OS(=O)(=O)C1=CC=CC=C1 MVIOINXPSFUJEN-UHFFFAOYSA-N 0.000 claims 2
- 150000001735 carboxylic acids Chemical class 0.000 claims 2
- 239000003153 chemical reaction reagent Substances 0.000 claims 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims 2
- 229940074391 gallic acid Drugs 0.000 claims 2
- 235000004515 gallic acid Nutrition 0.000 claims 2
- 239000000174 gluconic acid Substances 0.000 claims 2
- 235000012208 gluconic acid Nutrition 0.000 claims 2
- 230000004968 inflammatory condition Effects 0.000 claims 2
- 239000004310 lactic acid Substances 0.000 claims 2
- 235000014655 lactic acid Nutrition 0.000 claims 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 2
- 239000011976 maleic acid Substances 0.000 claims 2
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims 2
- 239000002105 nanoparticle Substances 0.000 claims 2
- 229920001184 polypeptide Polymers 0.000 claims 2
- 102000004196 processed proteins & peptides Human genes 0.000 claims 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims 2
- 235000019260 propionic acid Nutrition 0.000 claims 2
- DGSDBJMBHCQYGN-UHFFFAOYSA-M sodium;2-ethylhexyl sulfate Chemical compound [Na+].CCCCC(CC)COS([O-])(=O)=O DGSDBJMBHCQYGN-UHFFFAOYSA-M 0.000 claims 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 2
- 201000004681 Psoriasis Diseases 0.000 claims 1
- 108020004459 Small interfering RNA Proteins 0.000 claims 1
- 239000001361 adipic acid Substances 0.000 claims 1
- 235000011037 adipic acid Nutrition 0.000 claims 1
- 239000002775 capsule Substances 0.000 claims 1
- 125000002843 carboxylic acid group Chemical group 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000002601 intratumoral effect Effects 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 239000002736 nonionic surfactant Substances 0.000 claims 1
- 238000007920 subcutaneous administration Methods 0.000 claims 1
- 239000000725 suspension Substances 0.000 claims 1
Claims (20)
（b）4炭素以下の脂肪族鎖を含むカルボン酸、
（c）芳香族アニオン、および/または
（d）1.0未満のLogPを有するアニオン
のうちの少なくとも1つであるアニオン、ならびに
4級アンモニウムを含むカチオン
を含む、少なくとも1つのイオン液体を含む組成物であって、該少なくとも1つのイオン液体が、コリンおよびゲラネート（CAGE）ではない、組成物。 (a) Carboxylic acids that are not fatty acids,
(b) a carboxylic acid containing an aliphatic chain of 4 carbons or less;
an anion that is at least one of (c) an aromatic anion; and/or (d) an anion with a LogP of less than 1.0;
A composition comprising at least one ionic liquid comprising a cation comprising quaternary ammonium, wherein the at least one ionic liquid is not choline and gelanate (CAGE).
1.0未満のLogPを有し、かつ、
a. 脂肪酸ではないカルボン酸、
b. 4炭素以下の脂肪族鎖を含むカルボン酸、または
c. 芳香族アニオン
である、
請求項1記載の組成物。 Anion is
has a LogP less than 1.0, and
a. Carboxylic acids that are not fatty acids,
b. A carboxylic acid containing an aliphatic chain of 4 carbons or less, or
c. is an aromatic anion;
The composition according to claim 1.
4級アンモニウムがNR4 +の構造を有し、かつ1つのR基だけがヒドロキシ基を含む、請求項1～6のいずれか一項記載の組成物。 the quaternary ammonium has the structure NR 4 + and at least one R group contains a hydroxy group, or
Composition according to any one of claims 1 to 6, wherein the quaternary ammonium has the structure NR 4 + and only one R group contains a hydroxy group.
イオン液体が、少なくとも0.1％w/vの、10～70％w/vの、30～50％w/vの、もしくは30～40％w/vの濃度である、請求項1～8のいずれか一項記載の組成物。 the ionic liquid comprises a cation to anion ratio of from about 2:1 to about 1:1, of 2:1, less than 1:1, or in cation excess, and/or the ionic liquid comprises at least 0.1% w 9. The composition according to any one of claims 1 to 8, at a concentration of 10-70% w/v, 30-50% w/v, or 30-40% w/v.
（a）脂肪酸ではないカルボン酸、
（b）4炭素以下の脂肪族鎖を含むカルボン酸、
（c）芳香族アニオン、および/または
（d）1.0未満のLogPを有するアニオン
のうちの少なくとも1つであるアニオン、ならびに
4級アンモニウムを含むカチオン
を含む、組成物。 A composition comprising a plurality of ionic liquids, each ionic liquid comprising (a) a carboxylic acid that is not a fatty acid;
(b) a carboxylic acid containing an aliphatic chain of 4 carbons or less;
an anion that is at least one of (c) an aromatic anion; and/or (d) an anion with a LogP of less than 1.0;
A composition comprising a cation comprising quaternary ammonium.
第1のイオン液体および/または第2のイオン液体が、
（i）カチオンが、コリンと等しいかまたはそれよりも大きいモル質量を有するか；
（ii）4級アンモニウムがNR4 +の構造を有し、かつ少なくとも1つのR基がヒドロキシ基を含むか；
（iii）4級アンモニウムがNR4 +の構造を有し、かつ1つのR基だけがヒドロキシ基を含むか；または
（iv）カチオンがコリン、C1、C6、またはC7であり；
あるいは
各イオン液体がコリンカチオンを有し、かつ/または
第1のイオン液体および第2のイオン液体がそれぞれ異なるアニオンを含むか；
第1のイオン液体および第2のイオン液体がそれぞれ、ゲラン酸；グリコール酸；プロパン酸；イソ酪酸；酪酸；没食子酸；乳酸；マロン酸；マレイン酸；グルタル酸；クエン酸；3,3-ジメチルアクリル酸；ジメチルアクリル酸；グルコン酸；アジピン酸；エチルヘキシル硫酸ナトリウム；デカン酸；ヒドロキシベンゼンスルホン酸；4-ヒドロキシベンゼンスルホン酸（4-フェノールスルホン酸）；イソ吉草酸；ヒドロケイ皮酸（フェニルプロパン酸）；フェニルリン酸；およびビフェニル-3-カルボン酸から選択される異なるアニオンを含み、
あるいは
第1のイオン液体がゲラン酸アニオンを有し、第2のイオン液体がフェニルプロパン酸アニオンを有する、
請求項10記載の組成物。 11. The composition of claim 10, comprising a first ionic liquid and a second ionic liquid,
The first ionic liquid and/or the second ionic liquid are
(i) the cation has a molar mass equal to or greater than choline;
(ii) whether the quaternary ammonium has a structure of NR 4 + and at least one R group contains a hydroxy group;
(iii) the quaternary ammonium has the structure NR 4 + and only one R group contains a hydroxy group; or (iv) the cation is choline, C1, C6, or C7;
or each ionic liquid has a choline cation, and/or the first ionic liquid and the second ionic liquid each contain a different anion;
The first ionic liquid and the second ionic liquid are gellanic acid; glycolic acid; propanoic acid; isobutyric acid; butyric acid; gallic acid; lactic acid; malonic acid; maleic acid; glutaric acid; citric acid; 3,3-dimethyl Acrylic acid; dimethylacrylic acid; gluconic acid; adipic acid; sodium ethylhexyl sulfate; decanoic acid; hydroxybenzenesulfonic acid; 4-hydroxybenzenesulfonic acid (4-phenolsulfonic acid); isovaleric acid; hydrocinnamic acid (phenylpropanoic acid) ); phenyl phosphate; and biphenyl-3-carboxylic acid;
or the first ionic liquid has a gellanate anion and the second ionic liquid has a phenylpropanoate anion;
The composition according to claim 10.
第1のイオン液体が、コリンおよびゲラン酸（CAGE）；コリンおよびジメチルアクリル酸（CADA）；ならびにコリンおよびビフェニル-3-カルボン酸（CABA）からなる群より選択され；かつ第2のイオン液体が、コリンおよびイソ吉草酸（CAVA）；ならびにコリンおよびフェニルプロパン酸（CAPA）からなる群より選択されるか、
あるいは、
第1のイオン液体がコリンおよびゲラン酸（CAGE）であり、第2のイオン液体がコリンおよびフェニルプロパン酸（CAPA）である、
請求項1～11のいずれか一項記載の組成物。 The first and second ionic liquids are choline and gellanic acid (CAGE); choline and dimethylacrylic acid (CADA); choline and isovaleric acid (CAVA); choline and phenylphosphate (CAPP); choline and biphenyl-3 - a different ionic liquid selected from the group consisting of carboxylic acid (CABA); choline and 4-phenolsulfonic acid (CASA); or choline and phenylpropanoic acid (CAPA);
the first ionic liquid is selected from the group consisting of choline and gellanic acid (CAGE); choline and dimethylacrylic acid (CADA); and choline and biphenyl-3-carboxylic acid (CABA); , choline and isovaleric acid (CAVA); and choline and phenylpropanoic acid (CAPA);
or,
the first ionic liquid is choline and gellanic acid (CAGE) and the second ionic liquid is choline and phenylpropanoic acid (CAPA);
A composition according to any one of claims 1 to 11.
または
第1のイオン液体および/または第2のイオン液体が、1：1未満のカチオン対アニオンの比、もしくはカチオン過剰でのカチオン対アニオンの比を含むか、
かつ/または
第1のイオン液体および/または第2のイオン液体が、少なくとも0.1％w/vの濃度で、10～70％w/vの濃度で、30～50％w/vの濃度で、もしくは30～40％w/vの濃度である、
請求項10～12のいずれか一項記載の組成物。 the first ionic liquid and/or the second ionic liquid comprises a cation to anion ratio of about 2:1 to about 1:1, or a cation to anion ratio with a cation excess of 2:1;
or the first ionic liquid and/or the second ionic liquid comprises a cation to anion ratio of less than 1:1 or a cation to anion ratio in cation excess;
and/or the first ionic liquid and/or the second ionic liquid at a concentration of at least 0.1% w/v, at a concentration of 10-70% w/v, at a concentration of 30-50% w/v, or at a concentration of 30-40% w/v,
Composition according to any one of claims 10 to 12.
（ii）1つまたは複数のナノ粒子中に提供され、該1つまたは複数のナノ粒子が、イオン液体を含む組成物中での溶液または懸濁液の状態にあるか；
（iii）分解性カプセル剤中に提供されるか；
および/または
（iv）経皮投与、粘膜への投与、経口投与、皮下投与、皮内投与、非経口投与、腫瘍内投与、または静脈内投与用に製剤化されている、
請求項1～13のいずれか一項記載の組成物。 (i) Is it an admixture;
(ii) provided in one or more nanoparticles, said one or more nanoparticles being in solution or suspension in a composition comprising an ionic liquid;
(iii) provided in a degradable capsule;
and/or (iv) is formulated for transdermal, mucosal, oral, subcutaneous, intradermal, parenteral, intratumoral, or intravenous administration;
Composition according to any one of claims 1 to 13.
活性化合物が抗体または抗体試薬を含むか；
または
活性化合物が核酸を含む、
請求項15記載の組成物。 whether the active compound comprises a polypeptide or a nucleic acid;
whether the active compound includes an antibody or an antibody reagent;
or the active compound comprises a nucleic acid;
16. The composition according to claim 15.
活性化合物が抗体または抗体試薬を含み、かつ活性化合物が、450より大きい分子量または500より大きい分子量を有するか；または
活性化合物が核酸を含み、かつ核酸が、阻害性核酸、またはNFKBIZ、TNFαおよび/もしくはIL-17阻害性核酸、またはsiRNAである、
請求項15または16記載の組成物。 the active compound comprises a polypeptide or a nucleic acid, and the active compound is provided in a dose of 1 to 40 mg/kg;
the active compound comprises an antibody or antibody reagent and the active compound has a molecular weight greater than 450 or greater than 500; or the active compound comprises a nucleic acid and the nucleic acid is an inhibitory nucleic acid, or NFKBIZ, TNFα and/or or is an IL-17 inhibitory nucleic acid, or siRNA,
17. The composition according to claim 15 or 16.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962939088P | 2019-11-22 | 2019-11-22 | |
| US62/939,088 | 2019-11-22 | ||
| PCT/US2020/061185 WO2021102084A1 (en) | 2019-11-22 | 2020-11-19 | Ionic liquids for drug delivery |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2023503899A JP2023503899A (en) | 2023-02-01 |
| JPWO2021102084A5 true JPWO2021102084A5 (en) | 2023-11-28 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022529453A Pending JP2023503899A (en) | 2019-11-22 | 2020-11-19 | Ionic liquids for drug delivery |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US20240016735A1 (en) |
| EP (1) | EP4061338A1 (en) |
| JP (1) | JP2023503899A (en) |
| KR (1) | KR20220104766A (en) |
| CN (1) | CN114980864A (en) |
| AU (1) | AU2020388387A1 (en) |
| CA (1) | CA3158963A1 (en) |
| IL (1) | IL293145A (en) |
| WO (1) | WO2021102084A1 (en) |
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| WO2022256291A1 (en) * | 2021-06-01 | 2022-12-08 | President And Fellows Of Harvard College | Hydrogel devices for drug delivery to the ear |
| CN113637708B (en) * | 2021-08-09 | 2023-07-25 | 中国科学院过程工程研究所 | CRISPR-cas9 gene editing system delivery vector and preparation method and application thereof |
| AU2022359915A1 (en) | 2021-10-08 | 2024-05-02 | President And Fellows Of Harvard College | Ionic liquids for drug delivery |
| CN114042032B (en) * | 2021-11-11 | 2024-04-26 | 武汉瑞佶生物科技有限公司 | Pharmaceutical preparation for realizing nucleic acid skin delivery and preparation method and application thereof |
| CN114642733B (en) * | 2022-03-02 | 2023-08-22 | 中山大学 | Composition for treating androgenetic alopecia and preparation method thereof |
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2020
- 2020-11-19 CA CA3158963A patent/CA3158963A1/en active Pending
- 2020-11-19 IL IL293145A patent/IL293145A/en unknown
- 2020-11-19 CN CN202080094214.3A patent/CN114980864A/en active Pending
- 2020-11-19 JP JP2022529453A patent/JP2023503899A/en active Pending
- 2020-11-19 EP EP20824808.8A patent/EP4061338A1/en active Pending
- 2020-11-19 KR KR1020227020734A patent/KR20220104766A/en unknown
- 2020-11-19 WO PCT/US2020/061185 patent/WO2021102084A1/en unknown
- 2020-11-19 AU AU2020388387A patent/AU2020388387A1/en active Pending
- 2020-11-19 US US17/777,478 patent/US20240016735A1/en active Pending
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