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WO2025076771A1 - Lipide ionisable, composition pharmaceutique le contenant et son utilisation - Google Patents

Lipide ionisable, composition pharmaceutique le contenant et son utilisation Download PDF

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Publication number
WO2025076771A1
WO2025076771A1 PCT/CN2023/124286 CN2023124286W WO2025076771A1 WO 2025076771 A1 WO2025076771 A1 WO 2025076771A1 CN 2023124286 W CN2023124286 W CN 2023124286W WO 2025076771 A1 WO2025076771 A1 WO 2025076771A1
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Prior art keywords
unsubstituted
branched
compound
substituted
independently
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PCT/CN2023/124286
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English (en)
Chinese (zh)
Inventor
宋相容
魏霞蔚
魏于全
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Westgene Biopharma Co Ltd
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Westgene Biopharma Co Ltd
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Priority to PCT/CN2023/124286 priority Critical patent/WO2025076771A1/fr
Publication of WO2025076771A1 publication Critical patent/WO2025076771A1/fr
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    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
    • C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings

Definitions

  • the invention belongs to the field of biotechnology, and in particular, the invention relates to a compound and the compound used as an ionizable lipid in liposomes or lipid nanoparticles, drug carriers, complexes and pharmaceutical compositions.
  • mRNA vaccine is an emerging nucleic acid vaccine that has shown outstanding advantages of rapidity and high efficiency in responding to the global COVID-19 caused by the new coronavirus infection.
  • the working principle of mRNA vaccine is to directly introduce mRNA encoding specific antigenic proteins into somatic cells, and synthesize antigenic proteins through the expression system of host cells, inducing the host immune system to produce B and T cell-specific immune responses to the antigen and other effects, effectively playing a therapeutic and preventive role in the disease.
  • mRNA vaccines Compared with DNA nucleic acid vaccines and traditional protein/peptide vaccines, mRNA vaccines have the advantages of rapid research and development, simple production process, and high safety. It is a new type of anti-tumor nucleic acid vaccine with more clinical application prospects.
  • nucleic acid delivery systems mainly include two categories: viral vectors and non-viral vectors. Liposomes, as a representative of non-viral vectors, are regarded as ideal nucleic acid delivery systems because of their low immunogenicity, good biocompatibility, and high transfection efficiency.
  • non-viral vectors used for nucleic acid delivery LNP is a representative and has been used in three approved nucleic acid drugs (Patisiran, BNT162b2, and mRNA-1273).
  • Their ionizable lipids are SM-102 and ALC-0135, respectively. Both deliver mRNA to the liver to express antigenic proteins. Although they can activate the body's immune response, they still have the problem of insufficient immunogenicity.
  • the best delivery target organs are immune organs such as the spleen; other ionizable lipid compounds disclosed in the prior art are also mainly delivered to the liver to express antigenic proteins; therefore, it is urgent to develop lipid compounds with high delivery efficiency and good spleen organ targeting.
  • the present invention provides a compound of formula (I) or its stereoisomers, tautomers, solvates, pharmaceutically acceptable salts or deuterated compounds:
  • n, p, q are each independently any integer of 1, 2, 4;
  • X 1 , X 2 , X 3 and X 4 are each independently a substituted or unsubstituted C 2 -C 10 alkylene group or hydrogen, and X 1 , X 2 , X 3 and X 4 are not hydrogen at the same time;
  • the present invention provides a compound of formula (I) or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated compound thereof, characterized in that:
  • R 1 , R 2 , R 3 and R 4 are each independently substituted or unsubstituted C 6 -C 18 straight or branched alkyl, substituted or unsubstituted C 6 -C 18 straight or branched heteroalkyl, substituted or unsubstituted C 6 -C 18 straight or branched alkenyl, substituted or unsubstituted C 6 -C 18 straight chain or branched chain heteroalkenyl or absent;
  • the present invention provides a compound of formula (I) or a stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated compound thereof, characterized in that m, n, p, q are each independently selected from 1 or 2.
  • n, p, q are each independently 2;
  • X 1 , X 2 , X 3 and X 4 are each independently an unsubstituted C 2 -C 10 alkylene group;
  • X 1 and X 2 are each independently selected from unsubstituted C 2 -C 10 alkylene, X 3 and X 4 are each independently selected from hydrogen; Y 3 and Y 4 are absent, and R 3 and R 4 are absent;
  • X 1 , X 2 , and X 3 are each independently selected from unsubstituted C 2 -C 10 alkylene, X 4 is hydrogen, Y 4 is absent, and R 4 is absent;
  • X 1 , X 2 , X 3 , and X 4 are each independently an unsubstituted C 2 -C 10 alkylene group.
  • n and p are each independently 1, and m and q are each independently 2;
  • X 1 , X 2 , and X 3 are each independently an unsubstituted C 2 -C 10 alkylene group
  • Y 1 , Y 2 , and Y 3 are each independently -C( ⁇ O)O-, -OC( ⁇ O)-, -NH-, -SS-, -C( ⁇ O)N(R a )-, or -(R a )NC( ⁇ O)-, wherein R a is hydrogen;
  • R 1 , R 2 and R 3 are each independently an unsubstituted C 6 -C 18 straight or branched alkyl group, an unsubstituted C 6 -C 18 straight or branched heteroalkyl group, an unsubstituted C 6 -C 18 straight or branched alkenyl group, or an unsubstituted C 6 -C 18 straight or branched heteroalkenyl group.
  • the compound of formula (I) or its stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated compound provided by the present invention when A is absent, has one of the following characteristics:
  • X 1 and X 2 are each independently selected from unsubstituted C 2 -C 10 alkylene, X 3 is hydrogen; Y 3 is absent, and R 3 is absent;
  • X 1 , X 2 , and X 3 are each independently an unsubstituted C 2 -C 10 alkylene group.
  • the compound provided by the present invention or its stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated compound is characterized in that when Y 1 , Y 2 , Y 3 and Y 4 exist, Y 1 , Y 2 , Y 3 and Y 4 are selected from the same group.
  • the compound provided by the present invention or its stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated compound is characterized in that when R 1 , or any one of R 2 , R 3 , and R 4 exists, each independently has a structure represented by formula (II):
  • s is any integer from 1 to 10, preferably s is 1, 2, or 3;
  • R5 and R6 are each independently H, substituted or unsubstituted C1 - C18 straight or branched alkyl, substituted or unsubstituted C1 - C18 straight or branched heteroalkyl, substituted or unsubstituted C2 - C18 straight or branched alkenyl, substituted or unsubstituted C2 - C18 straight or branched heteroalkenyl, wherein the substituted groups are each independently selected from one or more halogen, -OH, -SH, -NH 2 , -NO 2 , cyano or C 1 -C 3 alkyl, -C( ⁇ O)OR 7 , -OC( ⁇ O)R 7 , -C( ⁇ O)NHR 7 , -NHC( ⁇ O)R 7 , -S-SR 7 ; wherein R 7 is selected from C 6 -C 18 straight chain or branched chain alkyl, C 6 -C 18 straight chain or branched chain al
  • the compound provided by the present invention or its stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated compound is characterized in that when R 1 , or R 2 , R 3 , R 4 exist, said R 1 , R 2 , R 3 , R 4 each independently has at least one of the following structures:
  • the compound provided by the present invention or its stereoisomer, tautomer, solvate, pharmaceutically acceptable salt or deuterated compound is characterized in that when R 1 , R 2 , R 3 , and R 4 exist, said R 1 , R 2 , R 3 , and R 4 are selected from the same group.
  • the present invention provides the use of the above-mentioned compound or its stereoisomers, tautomers, solvates, pharmaceutically acceptable salts or deuterated compounds in the preparation of liposomes, lipid nanoparticles, drug carriers or complexes.
  • the pharmaceutically active molecule is selected from DNA, ASO, siRNA, miRNA, mRNA, ribozyme, nucleic acid aptamer or a combination thereof; preferably mRNA.
  • composition wherein the pharmaceutical composition is prepared as lipid nanoparticles.
  • the compounds of the invention can be administered in the form of crude Chemical administration, or can be formulated as a pharmaceutical composition.
  • the pharmaceutical composition of the present invention comprises a compound of structure (I) and one or more pharmaceutically acceptable carriers, diluents or excipients.
  • the compound of structure (I) is present in the composition in an amount effective to form liposomes and deliver the biologically active ingredient, for example, for treating a specific disease or condition of interest. Appropriate concentrations and dosages can be readily determined by those skilled in the art.
  • the present invention provides liposomes or lipid nanoparticles comprising the aforementioned compounds.
  • the liposomes or lipid nanoparticles of the invention can be effectively delivered to organs such as the heart, liver, spleen, lungs and kidneys, especially to the spleen, which can effectively activate the body's immunity and increase the level of specific antibodies in the animal body.
  • the present invention provides a drug carrier.
  • the drug carrier comprises the aforementioned compound or the aforementioned liposome or lipid nanoparticle.
  • the aforementioned compound is an ionizable lipid
  • the drug carrier is an ionizable carrier
  • the aforementioned compound or liposome or lipid nanoparticle can be used to load the drug and deliver the drug into the cell.
  • the present invention proposes a pharmaceutical composition.
  • the pharmaceutical composition comprises the aforementioned compound or comprises the aforementioned liposome or lipid nanoparticle or the aforementioned drug carrier or the aforementioned complex.
  • the aforementioned compound, liposome or lipid nanoparticle, drug carrier and complex have the advantages of strong delivery ability and good immune activation effect.
  • the aforementioned compound, liposome or lipid nanoparticle or drug carrier is loaded with biologically active ingredients, and the biologically active ingredients can be delivered into the body, which is beneficial for the loaded biologically active ingredients to exert their efficacy and be used for the treatment of diseases.
  • pharmaceutically acceptable excipients are also included.
  • the present invention proposes a pharmaceutical use.
  • the present invention proposes the use of the aforementioned compound or the aforementioned liposome or lipid nanoparticle or the aforementioned drug carrier or the aforementioned complex or the aforementioned pharmaceutical composition in the preparation of a drug.
  • the aforementioned compound, liposome or lipid nanoparticle, drug carrier and complex have the advantages of low cytotoxicity, good biocompatibility, strong delivery ability and good immune activation effect.
  • the aforementioned compound, liposome or drug carrier is loaded with biologically active ingredients, and the biologically active ingredients can be delivered into the body, which is beneficial for the loaded biologically active ingredients to exert their efficacy and be used for the treatment of diseases.
  • the present invention provides a method for preparing a compound. According to an embodiment of the present invention, the present invention provides a method for preparing the aforementioned compound.
  • Figure 1 Line graph of the changes in particle size and polydispersity coefficient of 4N4R@mRNA stored at different temperatures for 4, 7 and 28 days;
  • Figure 2 The results of in vivo expression of 4N4R@mRNA after storage at different temperatures for 4, 7 and 28 days; A is a statistical bar graph of the expression of 4N4R@mRNA in mice; B is an actual image of the expression of 4N4R@mRNA in mice;
  • Figure 3 is a graph showing the positive rate of GFP fluorescence signals of compounds
  • FIG4 is a graph showing the in vivo expression distribution of compound LNP S ;
  • the compounds of the present invention comprising the aforementioned isotopes and/or other isotopes of other atoms and pharmaceutically acceptable salts of the compounds are all included within the scope of the present invention.
  • Isotope-labeled compounds of the present invention such as radioactive isotopes, such as 3 H and 14 C are incorporated into the compounds of the present invention and can be used for drug and/or substrate tissue distribution analysis. Due to ease of preparation and detection, tritiated, i.e. 3 H, and carbon-14, i.e. 14 C, isotopes are particularly preferred.
  • substitution with heavy isotopes, such as deuterium, i.e. 2 H can provide some therapeutic advantages derived from greater metabolic stability, such as increased in vivo half-life or reduced dosage requirements. Therefore, it may be preferred in some cases.
  • stereochemical definitions and conventions used herein are generally in accordance with SP Parker, Ed., McGraw-Hill Dictionary of Chemical Terms (1984) McGraw-Hill Book Company, New York; and Eliel, E. and Wilen, S., "Stereochemistry of Organic Compounds", John Wiley & Sons, Inc., New York, 1994.
  • the compounds of the present invention may contain asymmetric centers or chiral centers and therefore exist in different stereoisomeric forms. It is contemplated that all stereoisomeric forms of the compounds of the present invention, including but not limited to diastereomers, enantiomers and atropisomers and mixtures thereof, such as racemic mixtures, are also included within the scope of the present invention.
  • the compounds of the invention may exist in the form of one of the possible isomers or a mixture thereof, for example as pure optical isomers, or as isomer mixtures, such as racemic and diastereomeric mixtures, depending on the number of asymmetric carbon atoms.
  • Optically active (R)- or (S)-isomers may be prepared using chiral synthons or chiral agents, or resolved using conventional techniques. If the compound contains a double bond, the substituents may be in the E or Z configuration; if the compound contains a disubstituted cycloalkyl group, the cycloalkyl substituents may be in the cis- or trans- configuration.
  • the compounds of the present invention may contain asymmetric centers or chiral centers and therefore exist in different stereoisomeric forms. It is contemplated that all stereoisomeric forms of the compounds of the present invention, including but not limited to diastereomers, enantiomers and atropisomers and geometric (or conformational) isomers and mixtures thereof, such as racemic mixtures, are within the scope of the present invention.
  • the compounds of the present invention may exist in the form of one or a mixture of possible isomers (including cis and trans isomers, optical isomers (such as R and S enantiomers), diastereomers, geometric isomers, rotational isomers, atropisomers), for example, substantially pure Geometric (cis or trans) isomers, diastereomers, optical isomers (enantiomers), racemates or mixtures thereof.
  • Any resulting mixtures of isomers can be separated on the basis of the physicochemical differences of the components into the pure or substantially pure geometric or optical isomers, diastereomers, racemates, for example, by chromatography and/or fractional crystallization.
  • tautomer or “tautomeric form” refers to structural isomers of different energies that are interconvertible via a low energy barrier. If tautomerism is possible (such as in solution), a chemical equilibrium of the tautomers can be achieved.
  • proton tautomers also known as prototropic tautomers
  • Valence tautomers include interconversions that occur via reorganization of some of the bonding electrons.
  • pharmaceutically acceptable means that the substance or composition must be compatible with other ingredients and/or or is chemically and/or toxicologically compatible with the mammal to be treated therewith.
  • pharmaceutically acceptable salt refers to organic and inorganic salts of the compounds of the present invention.
  • Pharmaceutically acceptable salts are well known in the art, as described in the literature: SM Berge et al., describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66: 1-19.
  • Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium and N + (C 1 -C 4 alkyl) 4 salts.
  • the present invention also contemplates quaternary ammonium salts formed by any compound containing N groups. Water-soluble or oil-soluble or dispersible products can be obtained by quaternization.
  • Alkali metal or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, etc.
  • the term "one or more” means It means “one, two, three, four or five, especially one, two, three or four, more especially one, two or three, even more especially one or two".
  • halogen refers to a fluorine, chlorine, bromine or iodine atom.
  • the minimum and maximum values of the carbon atom content in the hydrocarbon group are indicated by prefixes, for example, the prefix Ca - Cb refers to “a” to “b” carbon atoms.
  • the prefix Ca - Cb refers to "a” to "b” carbon atoms.
  • C1 - Cn refers to a straight or branched saturated/unsaturated carbon chain containing 1, 2, 3, 4, 5, ...
  • n-Pr methyl, ethyl, n - propyl (n-Pr, -CH2CH2CH3 ), isopropyl ( i -Pr, -CH( CH3 ) 2 ), n - butyl (n- Bu , -CH2CH2CH2CH3 ), isobutyl (i-Bu, -CH2CH ( CH3 ) 2 ), sec-butyl (s-Bu, -CH( CH3 ) CH2CH3 ), tert-butyl (t- Bu , -C( CH3 ) 3 ), n-pentyl ( -CH2CH2CH2CH2CH3 ), 2 -pentyl (-CH( CH3 ) CH2CH2CH3 ), 3 - pentyl (-CH( CH2CH3 ) 2 ) , 2-methyl - 2 -butyl (-C ( CH3 ) 2CH2CH3 )
  • C2 - C40 alkynyl refers to a linear or branched monovalent hydrocarbon group having 2, 3, 4, 5, ... or 40 carbon atoms, wherein at least one position CC is in an unsaturated state of sp triple bond, wherein the alkynyl group may be independently unsubstituted or substituted with one or more substituents described in the present invention, and specific examples include but are not limited to alkynylethyl ( -C ⁇ CH2 ), propargyl ( -CH2C ⁇ CH ), 1-propynyl (-C ⁇ C- CH3 ), etc.
  • ionizable lipids include cationic lipids, ionizable lipids and their derivatives.
  • treatment refers to the use of drugs to obtain a desired pharmacological and/or physiological effect.
  • the effect may be preventive in terms of completely or partially preventing a disease or its symptoms, and/or therapeutic in terms of partially or completely curing a disease and/or the adverse effects caused by the disease.
  • Treatment covers diseases in mammals, particularly humans, and includes: (a) preventing a disease or condition from occurring in an individual who is susceptible to the disease but has not yet been diagnosed with the disease; (b) inhibiting a disease, such as preventing or (c) alleviate the disease, such as reducing the symptoms associated with the disease.
  • treatment covers any administration of a drug or compound to an individual to treat, cure, alleviate, improve, mitigate or inhibit a disease in the individual, including but not limited to administering a drug containing a compound described herein to an individual in need thereof.
  • the complex or pharmaceutical composition of the present invention can be incorporated into a drug suitable for parenteral administration (e.g., intravenous, subcutaneous, intraperitoneal, intramuscular).
  • parenteral administration e.g., intravenous, subcutaneous, intraperitoneal, intramuscular
  • these drugs can be prepared in various forms.
  • liquid, semisolid and solid dosage forms including but not limited to liquid solutions (e.g., injection solutions and infusion solutions) or lyophilized powders.
  • Typical drugs are injection solutions.
  • the aforementioned complex or pharmaceutical composition can be administered by intravenous infusion or injection or intramuscular injection or subcutaneous injection.
  • 1,4,7,10-tetraazacyclododecane 1c (0.17 g, 1.0 equiv.), potassium carbonate (0.70 g, 5.0 equiv.), potassium iodide (0.08 g, 0.5 equiv.) and compound 1 (2.10 g, 5.0 equiv.) were added to a pressure tube. After adding an appropriate amount of acetonitrile, stratification occurred. The mixture was placed in an 80°C oil bath and reacted for 24 hours. An appropriate amount of dichloromethane was added and the yellow insoluble matter was removed by suction filtration to obtain a clear and transparent yellow liquid. The orange oily liquid was obtained by rotary evaporation as a crude product.
  • Solution preparation Dissolve ionizable lipids (compounds prepared by the present invention), DOPE, cholesterol (Chol), and DMG-PEG2000 in anhydrous ethanol to obtain lipid solutions.
  • Particle size potential measurement The particle size potential of the LNPs@Fluc of the compound of the present invention was measured using a Malvern laser particle size analyzer. A certain volume of the newly prepared LNPs@Fluc solution was diluted 10 times with pure water, and its particle size and potential were measured using a Malvern laser particle size analyzer. Each sample was measured three times in parallel, and the measurement temperature was 25°C.
  • the compounds of the present invention have excellent performance when prepared into LNPs preparations and can be further used in the development of nanoformulations.
  • HEK 293T cell suspension was adjusted to an appropriate concentration with 1640 complete medium, and plated on a 24-well plate at 5 ⁇ 10 5 /500 ⁇ L/well. The cells were cultured in an incubator at 37°C and 5% CO 2 for 24 h.
  • the experimental results are shown in Figure 4.
  • the LNP constructed by the ionizable lipid compound of the present invention can deliver mRNA to mice in a targeted manner, thereby expressing the encoded protein.
  • the highest expression intensity of 4N4R@Fluc mRNA was observed in the spleen of mice, which can be used to construct a spleen-targeted mRNA anti-tumor vaccine.
  • the activation effect of the LNPs@OVA mRNA vaccine prepared using the compounds of the present invention on BMDC cells and the antigen presentation effect of BMDC on the LNPs@OVA mRNA vaccine of the present invention were further investigated to verify the effectiveness of the vaccine.
  • BMDC cell suspension was adjusted to an appropriate concentration with 1640 complete medium, and plated on a 24-well plate at 5 ⁇ 10 5 /500 ⁇ L/well. The cells were cultured in a 37°C, 5% CO 2 incubator for 4 h.
  • LNPs 4N4R@OVA mRNA and positive control preparation SM-102-LNPs@OVA mRNA were prepared according to the method of Example 3, and the mRNA concentration of the administration preparation was controlled to be 0.05 ⁇ g/ ⁇ L. 20 ⁇ L was administered to each well, i.e., 1 ⁇ g/well, and incubated in an incubator at 37°C and 5% CO2 for 24 h.
  • the experimental results are shown in Figure 5.
  • the LNP (4N4R@OVA mRNA) constructed using the 4N4R ionizable lipid of the present invention can promote the rapid maturation and activation of BMDC, and its antigen presentation rate (61.42%) is much higher than the ionizable lipid SM-102 (33.62%) used in the Moderna COVID-19 vaccine.
  • the tumor volume observation results in Figure 6 show that compared with the Control and Moderna SM-102@OVA mRNA vaccine obtained by the vector containing SM-102, the mRNA vaccine constructed by the compound 4N4R of the present invention showed better anti-tumor effect in different groups with dosages of 5 ⁇ g and 15 ⁇ g.

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Abstract

La présente invention appartient au domaine technique de la biologie. Sont divulgués un lipide ionisable, une composition pharmaceutique le contenant et son utilisation. La présente invention concerne un composé représenté par la formule (I), ou un stéréoisomère, un tautomère, un solvate, un sel pharmaceutiquement acceptable ou un composé deutéré de celui-ci, qui sert de lipide ionisable, corrigeant le défaut technique selon lequel d'autres composés lipidiques ionisables dans l'état de la technique sont tous principalement administrés au foie pour l'expression de protéines antigéniques et ne peuvent pas être administrés à la rate. Le composé représenté par la formule (I), selon la présente invention, présente les caractéristiques d'une bonne propriété de ciblage d'organe de la rate, d'une efficacité d'administration élevée, etc. Le composé représenté par la formule (I) selon la présente invention peut être utilisé pour la préparation de liposomes, de nanoparticules lipidiques, de vecteurs ou de complexes de médicament, et utilisé pour l'administration de médicaments à base d'acide nucléique.
PCT/CN2023/124286 2023-10-12 2023-10-12 Lipide ionisable, composition pharmaceutique le contenant et son utilisation Pending WO2025076771A1 (fr)

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CN112437767A (zh) * 2018-05-24 2021-03-02 川斯勒佰尔公司 硫酯阳离子脂质
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Publication number Priority date Publication date Assignee Title
CN112437767A (zh) * 2018-05-24 2021-03-02 川斯勒佰尔公司 硫酯阳离子脂质
WO2023166511A1 (fr) * 2022-03-02 2023-09-07 Barcode Nanotech Ltd. Lipides ionisables et compositions les comprenant

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SOLFRID BUØEN, JOHANNES DALE, SYNNØVE LIAAEN-JENSEN, DAVID R. CURTIS, POVL KROGSGAARD-LARSEN, RAGNAR RYHAGE, ROLAND ISAKSSON: "Twelve-ring Azacrowns with 2-Alkoxyethyl Side-Arms.", ACTA CHEMICA SCANDINAVICA, MUNKSGAARD, vol. 40b, 1 January 1986 (1986-01-01), pages 278 - 282, XP055086567, ISSN: 0904213X, DOI: 10.3891/acta.chem.scand.40b-0278 *
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