RU2019110848A - Наночастицы на основе триблочных полипептидов для доставки гидрофильных лекарственных средств - Google Patents

Наночастицы на основе триблочных полипептидов для доставки гидрофильных лекарственных средств Download PDF

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RU2019110848A
RU2019110848A RU2019110848A RU2019110848A RU2019110848A RU 2019110848 A RU2019110848 A RU 2019110848A RU 2019110848 A RU2019110848 A RU 2019110848A RU 2019110848 A RU2019110848 A RU 2019110848A RU 2019110848 A RU2019110848 A RU 2019110848A
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amino acid
acid sequence
seq
molecule
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RU2019110848A
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Ашутош Чилкоти
Джайанта Бхаттачария
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Дьюк Юниверсити
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    • C—CHEMISTRY; METALLURGY
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    • C12N15/09—Recombinant DNA-technology
    • C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/645—Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
    • A61K47/6455—Polycationic oligopeptides, polypeptides or polyamino acids, e.g. for complexing nucleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/0002—General or multifunctional contrast agents, e.g. chelated agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5107—Excipients; Inactive ingredients
    • A61K9/513—Organic macromolecular compounds; Dendrimers
    • A61K9/5169—Proteins, e.g. albumin, gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/001—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof by chemical synthesis
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

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  • Gastroenterology & Hepatology (AREA)
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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)

Claims (31)

1. Композиция, содержащая агрегат из самособираемых полипептидов, где самособираемый полипептид содержит:
(a) первую аминокислотную последовательность (X1GVPG)x (SEQ ID NO:1), где X1 представляет собой аминокислоту и x составляет от 20 до 240;
(b) вторую аминокислотную последовательность (X2Gm)y (SEQ ID NO:2), где X2 представляет собой Y, F или W, m составляет от 0 до 3, и y составляет от 1 до 50;
(c) третью аминокислотную последовательность (CGG)z (SEQ ID NO:3), где z больше чем 1; и
(d) по меньшей мере, одна молекула присоединена к третьей аминокислотной последовательности через цистеиновую группу, где молекула имеет коэффициент распределения октанол-вода (logD), менее чем или равный 1,5 при pH 7,4.
2. Композиция по п. 1, где молекула представляет собой химиотерапевтическое или визуализирующее средство.
3. Композиция по п. 1, где молекула представляет собой гемцитабин.
4. Композиция по п. 1, где приблизительно от 2 до приблизительно 15 молекул присоединены к третьей аминокислотной последовательности.
5. Композиция по п. 1, где молекула присоединена к третьей аминокислотной последовательности через тиоловую группу.
6. Композиция по п. 1, где первая аминокислотная последовательность представляет собой (X1GVPG)m (SEQ ID NO:11), и где m составляет от 120 до 200.
7. Композиция по п. 1, где вторая аминокислотная последовательность представляет собой (X2G)n (SEQ ID NO:4), и где n составляет от 4 до 8.
8. Композиция по п. 1, где третья аминокислотная последовательность представляет собой (CGG)p (SEQ ID NO:5), и где p составляет от 4 до 12.
9. Композиция по п. 1, где X1 представляет собой A.
10. Композиция по п. 1, где X2 представляет собой Y.
11. Композиция по п. 1, где первая аминокислотная последовательность представляет собой (AGVPG)160 (SEQ ID NO:6).
12. Композиция по п. 1, где вторая аминокислотная последовательность представляет собой (YG)6 (SEQ ID NO:7).
13. Композиция по п. 1, где третья аминокислотная последовательность представляет собой (CGG)8 (SEQ ID NO:8).
14. Композиция по п. 1, где каждый самособираемый полипептид отдельно имеет молекулярную массу приблизительно от 20 кДа до приблизительно 300 кДа.
15. Композиция по п. 1, где агрегат из самособираемых полипептидов представляет собой наночастицу.
16. Композиция по п. 15, где молекула расположена в ядре наночастицы.
17. Композиция по п. 15, где наночастица имеет средний гидродинамический радиус приблизительно от 20 нм до приблизительно 200 нм.
18. Композиция по п. 15, где наночастица является стержнеобразной или сферической.
19. Композиция по п. 15, где наночастица содержит приблизительно от 50 до приблизительно 1000 самособираемых полипептидов на частицу.
20. Композиция по п. 1, дополнительно включающая фармацевтически приемлемый носитель.
21. Способ уничтожения множества злокачественных клеток, включающий контакт множества злокачественных клеток с композицией по п. 1.
22. Способ по п. 21, где множество злокачественных клеток присутствует у человека или собаки.
23. Способ по п. 21, где множество злокачественных клеток находится in vitro.
24. Способ лечения заболевания или нарушения у индивидуума, включающий введение индивидууму композиции по п. 1.
25. Способ по п. 24, где заболевание или нарушение представляет собой злокачественную опухоль.
26. Способ по п. 24, где индивидуум является человеком или собакой.
27. Способ по п. 21, где злокачественная опухоль включает солидные опухоли.
RU2019110848A 2016-09-14 2017-09-14 Наночастицы на основе триблочных полипептидов для доставки гидрофильных лекарственных средств RU2019110848A (ru)

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Application Number Priority Date Filing Date Title
US201662394662P 2016-09-14 2016-09-14
US62/394,662 2016-09-14
PCT/US2017/051661 WO2018053201A1 (en) 2016-09-14 2017-09-14 Triblock polypeptide-based nanoparticles for the delivery of hydrophilic drugs

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RU2019110848A3 RU2019110848A3 (ru) 2020-12-14

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