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US-20260124154-A1 - LIPID NANOPARTICLE LYOPHILIZED COMPOSITION

US20260124154A1US 20260124154 A1US20260124154 A1US 20260124154A1US-20260124154-A1

Abstract

A lyophilized composition capable of encapsulating any nucleic acid with high efficiency and easily is provided. A lyophilized composition of lipid nanoparticles not containing a nucleic acid but containing an ionic lipid, a sterol, a PEG lipid, an acidic buffer component that shows a buffering action at pH 1-6, and a cryoprotectant, wherein a weight ratio of the cryoprotectant and a total lipid is 10:1-1000:1.

Inventors

  • Kota TANGE
  • Yuta Nakai
  • Shinya TAMAGAWA
  • Sakura TANEICHI
  • Ayano Koike
  • Hidetaka Akita
  • Hiroki Tanaka
  • Daiki SHIRANE
  • Shinya Hagiwara

Assignees

  • NOF CORPORATION
  • NATIONAL UNIVERSITY CORPORATION CHIBA UNIVERSITY

Dates

Publication Date
20260507
Application Date
20251230
Priority Date
20190926

Claims (20)

  1. 1 . A lyophilized composition of lipid nanoparticles not comprising a nucleic acid but comprising an ionic lipid, a sterol, a PEG lipid, an acidic buffer component that shows a buffering action at pH 1-6, and a cryoprotectant, wherein a weight ratio of the cryoprotectant and a total lipid is 10:1-1000:1.
  2. 2 . The lyophilized composition according to claim 1 , further comprising a phospholipid.
  3. 3 . The lyophilized composition according to claim 1 , wherein the weight ratio of the cryoprotectant and the total lipid is 30:1-1000:1.
  4. 4 . The lyophilized composition according to claim 1 , wherein a concentration of the cryoprotectant in the composition before lyophilizing is 80-800 mg/mL.
  5. 5 . The lyophilized composition according to claim 1 , wherein a concentration of the cryoprotectant in the composition before lyophilizing is 160-800 mg/mL.
  6. 6 . The lyophilized composition according to claim 1 , wherein the ionic lipid is a compound represented by the formula (1): (in the formula (1), R 1a and R 1b are each independently an alkylene group having 1 to 6 carbon atoms, X a and X b are each independently an acyclic alkyl tertiary amino group having 1 to 6 carbon atoms and 1 tertiary amino group, or a cyclic alkylene tertiary amino group having 2 to 5 carbon atoms and 1 or 2 tertiary amino groups, R 2a and R 2b are each independently an alkylene group having 1 to 8 carbon atoms or an oxydialkylene group having 2 to 8 carbon atoms, Y a and Y b are each independently an ester bond, an amide bond, a carbamate bond, an ether bond, or a urea bond, Z a and Z b are each independently a divalent group derived from an aromatic compound having 3 to 16 carbon atoms, at least one aromatic ring, and optionally having a heteroatom, R 3a is (ia) a monovalent group having 10 to 50 carbon atoms, one carbonyl group, and at least one unsaturated bond selected from the group consisting of an olefinic carbon-carbon double bond and a carbon-carbon triple bond (excluding a monovalent group containing a residue of a liposoluble vitamin having a hydroxy group and a residue of a sterol derivative having a hydroxy group), (iia) a monovalent group having 10 to 50 carbon atoms and at least two carbonyl groups (excluding a monovalent group containing a residue of a liposoluble vitamin having a hydroxy group and a residue of a sterol derivative having a hydroxy group), (iiia) a monovalent group represented by the formula (2): (in the formula (2), * is a bonding position, R 4 is an alkylene group having 1 to 10 carbon atoms, X 1 is a carbamate bond, a carbonate bond, or an amide bond, and R 5 is an alkyl group having 1 to 25 carbon atoms, and R 5 is optionally substituted by a substituent selected from the group consisting of a halogen atom and a hydroxy group), (iva) a monovalent group represented by the formula (3): (in the formula (3), * is a bonding position, R 6 is an alkylene group having 1 to 10 carbon atoms, and R 7 is an alkyl group having 1 to 25 carbon atoms and substituted by at least one halogen atom), (va) a monovalent group represented by the formula (4): (in the formula (4), * is a bonding position, R 8 and R 9 are each independently an alkylene group having 1 to 10 carbon atoms, an alkenediyl group having 2 to 10 carbon atoms, or an alkynediyl group having 2 to 10 carbon atoms, R 10 to R 12 are each independently a hydrogen atom, a benzyl group, or a *—Si(R 13 )(R 14 )(R 15 ) group (wherein * is a bonding position, and R 13 to R 15 are each independently an alkyl group having 1 to 4 carbon atoms or a phenyl group)), (via) a monovalent group represented by the formula (5): (in the formula (5), * is a bonding position, X 2 is a nitrogen atom or a trivalent group represented by the formula (6): (in the formula (6), * is a bonding position with R 16 , and ** is a bonding position with R 17 or R 18 ), when X 2 is a nitrogen atom, R 16 is an alkylene group having 1 to 10 carbon atoms, an alkenediyl group having 2 to 10 carbon atoms, or an alkynediyl group having 2 to 10 carbon atoms, and R 16 is optionally substituted by a substituent selected from the group consisting of a halogen atom and a hydroxy group, when X 2 is a trivalent group represented by the formula (6), R 16 is an alkylene group having 1 to 10 carbon atoms, and R 16 is optionally substituted by a substituent selected from the group consisting of a halogen atom and a hydroxy group, when X 2 is a nitrogen atom, R 17 and R 18 are each independently an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 2 to 10 carbon atoms, or an alkynyl group having 2 to 10 carbon atoms, and R 17 and R 18 are each independently optionally substituted by a substituent selected from the group consisting of a halogen atom and a hydroxy group, and when X 2 is a trivalent group represented by the formula (6), R 17 and R 18 are each independently an alkyl group having 1 to 10 carbon atoms, and R 17 and R 18 are each independently optionally substituted by a substituent selected from the group consisting of a halogen atom and a hydroxy group), (viia) a monovalent group represented by the formula (7): (in the formula (7), * is a bonding position, and R 19 is a hydrogen atom, a benzyl group, or a *—Si(R 13 )(R 14 )(R 15 ) group (wherein * is a bonding position, and R 13 to R 15 are each independently an alkyl group having 1 to 4 carbon atoms or a phenyl group), or a *—CO—R 20 group (wherein * is a bonding position, and R 20 is an alkyl group having 1 to 9 carbon atoms)), (viiia) a monovalent group represented by the formula (8): (in the formula (8), * is a bonding position, and R 21 and R 22 are each independently a hydrogen atom, a benzyl group, or a *—Si(R 13 )(R 14 )(R 15 ) group (wherein * is a bonding position, and R 13 to R 15 are each independently an alkyl group having 1 to 4 carbon atoms or a phenyl group)), (ixa) a monovalent group represented by the formula (9): (in the formula (9), * is a bonding position, and R 23 is a hydrogen atom, a benzyl group, or a *—Si(R 13 )(R 14 )(R 15 ) group (wherein * is a bonding position, and R 13 to R 15 are each independently an alkyl group having 1 to 4 carbon atoms or a phenyl group)), (xa) a monovalent group represented by the formula (10): (in the formula (10), * is a bonding position, R 24 is an alkylene group having 1 to 10 carbon atoms, an alkenediyl group having 2 to 10 carbon atoms, or an alkynediyl group having 2 to 10 carbon atoms, and R 25 is an alkyl group having 1 to 30 carbon atoms, an alkenyl group having 2 to 30 carbon atoms, or an alkynyl group having 2 to 30 carbon atoms), (xia) a monovalent group represented by the formula (11): (in the formula (11), * is a bonding position, and R 26 is an alkylene group having 1 to 10 carbon atoms, an alkenediyl group having 2 to 10 carbon atoms, or an alkynediyl group having 2 to 10 carbon atoms, and R 27 and R 28 are each independently an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 2 to 10 carbon atoms, or an alkynyl group having 2 to 10 carbon atoms), or (xiia) a monovalent group represented by the formula (12): (in the formula (12), * is a bonding position, R 29 is an alkylene group having 1 to 10 carbon atoms, and R 30 and R 31 are each independently an alkyl group having 1 to 10 carbon atoms), R 3b is (ib) a monovalent group having 10 to 50 carbon atoms, one carbonyl group, and at least one unsaturated bond selected from the group consisting of an olefinic carbon-carbon double bond and a carbon-carbon triple bond (excluding a monovalent group containing a residue of a liposoluble vitamin having a hydroxy group and a residue of a sterol derivative having a hydroxy group), (iib) a monovalent group having 10 to 50 carbon atoms and at least two carbonyl groups (excluding a monovalent group containing a residue of a liposoluble vitamin having a hydroxy group and a residue of a sterol derivative having a hydroxy group), (iiib) a monovalent group represented by the formula (2), (ivb) a monovalent group represented by the formula (3), (vb) a monovalent group represented by the formula (4), (vib) a monovalent group represented by the formula (5), (viib) a monovalent group represented by the formula (7), (viiib) a monovalent group represented by the formula (8), (ixb) a monovalent group represented by the formula (9), (xb) a monovalent group represented by the formula (10), (xib) a monovalent group represented by the formula (11), (xiib) a monovalent group represented by the formula (12), (xiiib) a monovalent group which is an alkyl group having 1 to 30 carbon atoms, an alkenyl group having 2 to 20 carbon atoms, or an alkynyl group having 2 to 20 carbon atoms, in which one ethylene group in the alkyl group is optionally replaced by one ester bond, or (xivb) an R 3c —CO—(CH 2 ) p — group (wherein R 3c is a residue of a liposoluble vitamin having a hydroxy group or a residue of a sterol derivative having a hydroxy group, and p is an integer of 1 to 8), and R 3a and R 3b may be the same or different).
  7. 7 . The lyophilized composition according to claim 1 , wherein the ionic lipid is a compound represented by the formula (2A): (in the formula (2A), R 1 and R 2 are each independently an alkyl group having 1 to 6 carbon atoms, or any carbon atoms of R 1 and R 2 are optionally bonded to each other to form a heterocycle containing nitrogen atom, and R 3 and R 4 are each independently an aliphatic hydrocarbon group having 1 to 35 carbon atoms optionally substituted by a substituent selected from Substituent Group α, provided that at least one selected from the group consisting of R 3 and R 4 is an aliphatic hydrocarbon group having 5 to 35 carbon atoms optionally substituted by a substituent selected from Substituent Group α, wherein Substituent Group α consists of a hydroxy group, an alkoxy group, a sulfanyl group, an alkylthio group, and an alkoxycarbonyl group).
  8. 8 . The lyophilized composition according to claim 1 , wherein the cryoprotectant is disaccharide.
  9. 9 . The lyophilized composition according to claim 1 , wherein the cryoprotectant is sucrose.
  10. 10 . A method for producing a nucleic acid-encapsulating lipid nanoparticle, comprising the following steps: a) a step of mixing an alcohol solution containing an ionic lipid, a sterol, and a PEG lipid, and an acidic buffer showing a buffering action at pH 1-6 to prepare a suspension of lipid nanoparticles not containing a nucleic acid, b) a step of mixing the suspension of the lipid nanoparticles not containing a nucleic acid and a cryoprotectant to give a mixture with pH 1-6 and containing the cryoprotectant at 80-800 mg/mL, c) a step of lyophilizing the mixture obtained in step b to give a lyophilized composition, d) a step of mixing the lyophilized composition and an aqueous solution containing a nucleic acid and optionally containing alcohol at 0-25 v/v %, and optionally incubating the mixture at 0-95° C. for 0-60 min to give nucleic acid-encapsulating lipid nanoparticles, and e) a step of exchanging an external aqueous phase of the obtained nucleic acid-encapsulating lipid nanoparticles with a neutral buffer by dialysis, ultrafiltration, or dilution.
  11. 11 . The method according to claim 10 , wherein the step a further comprises a step of exchanging the external aqueous phase with another acidic buffer showing a buffering action at pH 1-6, by dialysis, ultrafiltration, or dilution, after preparing the suspension of lipid nanoparticles.
  12. 12 . The method according to claim 10 , wherein the alcohol solution further comprises a phospholipid in step a.
  13. 13 . The method according to claim 10 , wherein a concentration of the cryoprotectant in the mixture in step b is 160-800 mg/mL.
  14. 14 . The method according to claim 10 , wherein the ionic lipid is a compound represented by the formula (1): (in the formula (1), R 1a and R 1b are each independently an alkylene group having 1 to 6 carbon atoms, X a and X b are each independently an acyclic alkyl tertiary amino group having 1 to 6 carbon atoms and 1 tertiary amino group, or a cyclic alkylene tertiary amino group having 2 to 5 carbon atoms and 1 or 2 tertiary amino groups, R 2a and R 2b are each independently an alkylene group having 1 to 8 carbon atoms or an oxydialkylene group having 2 to 8 carbon atoms, Y a and Y b are each independently an ester bond, an amide bond, a carbamate bond, an ether bond, or a urea bond, Z a and Z b are each independently a divalent group derived from an aromatic compound having 3 to 16 carbon atoms, at least one aromatic ring, and optionally having a heteroatom, R 3a is (ia) a monovalent group having 10 to 50 carbon atoms, one carbonyl group, and at least one unsaturated bond selected from the group consisting of an olefinic carbon-carbon double bond and a carbon-carbon triple bond (excluding a monovalent group containing a residue of a liposoluble vitamin having a hydroxy group and a residue of a sterol derivative having a hydroxy group), (iia) a monovalent group having 10 to 50 carbon atoms and at least two carbonyl groups (excluding a monovalent group containing a residue of a liposoluble vitamin having a hydroxy group and a residue of a sterol derivative having a hydroxy group), (iiia) a monovalent group represented by the formula (2): (in the formula (2), * is a bonding position, R 4 is an alkylene group having 1 to 10 carbon atoms, X 1 is a carbamate bond, a carbonate bond, or an amide bond, and R 5 is an alkyl group having 1 to 25 carbon atoms, and R 5 is optionally substituted by a substituent selected from the group consisting of a halogen atom and a hydroxy group), (iva) a monovalent group represented by the formula (3): (in the formula (3), * is a bonding position, R 6 is an alkylene group having 1 to 10 carbon atoms, and R 7 is an alkyl group having 1 to 25 carbon atoms and substituted by at least one halogen atom), (va) a monovalent group represented by the formula (4): (in the formula (4), * is a bonding position, R 8 and R 9 are each independently an alkylene group having 1 to 10 carbon atoms, an alkenediyl group having 2 to 10 carbon atoms, or an alkynediyl group having 2 to 10 carbon atoms, R 10 to R 12 are each independently a hydrogen atom, a benzyl group, or a *—Si(R 13 )(R 14 )(R 15 ) group (wherein * is a bonding position, and R 13 to R 15 are each independently an alkyl group having 1 to 4 carbon atoms or a phenyl group)), (via) a monovalent group represented by the formula (5): (in the formula (5), * is a bonding position, X 2 is a nitrogen atom or a trivalent group represented by the formula (6): (in the formula (6), * is a bonding position with R 16 , and ** is a bonding position with R 17 or R 18 ), when X 2 is a nitrogen atom, R 16 is an alkylene group having 1 to 10 carbon atoms, an alkenediyl group having 2 to 10 carbon atoms, or an alkynediyl group having 2 to 10 carbon atoms, and R 16 is optionally substituted by a substituent selected from the group consisting of a halogen atom and a hydroxy group, when X 2 is a trivalent group represented by the formula (6), R 16 is an alkylene group having 1 to 10 carbon atoms, and R 16 is optionally substituted by a substituent selected from the group consisting of a halogen atom and a hydroxy group, when X 2 is a nitrogen atom, R 17 and R 18 are each independently an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 2 to 10 carbon atoms, or an alkynyl group having 2 to 10 carbon atoms, and R 17 and R 18 are each independently optionally substituted by a substituent selected from the group consisting of a halogen atom and a hydroxy group, and when X 2 is a trivalent group represented by the formula (6), R 17 and R 18 are each independently an alkyl group having 1 to 10 carbon atoms, and R 17 and R 18 are each independently optionally substituted by a substituent selected from the group consisting of a halogen atom and a hydroxy group), (viia) a monovalent group represented by the formula (7): (in the formula (7), * is a bonding position, and R 19 is a hydrogen atom, a benzyl group, or a *—Si(R 13 )(R 14 )(R 15 ) group (wherein * is a bonding position, and R 13 to R 15 are each independently an alkyl group having 1 to 4 carbon atoms or a phenyl group), or a *—CO—R 20 group (wherein * is a bonding position, and R 20 is an alkyl group having 1 to 9 carbon atoms)), (viiia) a monovalent group represented by the formula (8): (in the formula (8), * is a bonding position, and R 21 and R 22 are each independently a hydrogen atom, a benzyl group, or a *—Si(R 13 )(R 14 )(R 15 ) group (wherein * is a bonding position, and R 13 to R 15 are each independently an alkyl group having 1 to 4 carbon atoms or a phenyl group)), (ixa) a monovalent group represented by the formula (9): (in the formula (9), * is a bonding position, and R 23 is a hydrogen atom, a benzyl group, or a *—Si(R 13 )(R 14 )(R 15 ) group (wherein * is a bonding position, and R 13 to R 15 are each independently an alkyl group having 1 to 4 carbon atoms or a phenyl group)), (xa) a monovalent group represented by the formula (10): (in the formula (10), * is a bonding position, R 24 is an alkylene group having 1 to 10 carbon atoms, an alkenediyl group having 2 to 10 carbon atoms, or an alkynediyl group having 2 to 10 carbon atoms, and R 25 is an alkyl group having 1 to 30 carbon atoms, an alkenyl group having 2 to 30 carbon atoms, or an alkynyl group having 2 to 30 carbon atoms), (xia) a monovalent group represented by the formula (11): (in the formula (11), * is a bonding position, and R 26 is an alkylene group having 1 to 10 carbon atoms, an alkenediyl group having 2 to 10 carbon atoms, or an alkynediyl group having 2 to 10 carbon atoms, and R 27 and R 28 are each independently an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 2 to 10 carbon atoms, or an alkynyl group having 2 to 10 carbon atoms), or (xiia) a monovalent group represented by the formula (12): (in the formula (12), * is a bonding position, R 29 is an alkylene group having 1 to 10 carbon atoms, and R 30 and R 31 are each independently an alkyl group having 1 to 10 carbon atoms), R 3b is (ib) a monovalent group having 10 to 50 carbon atoms, one carbonyl group, and at least one unsaturated bond selected from the group consisting of an olefinic carbon-carbon double bond and a carbon-carbon triple bond (excluding a monovalent group containing a residue of a liposoluble vitamin having a hydroxy group and a residue of a sterol derivative having a hydroxy group), (iib) a monovalent group having 10 to 50 carbon atoms and at least two carbonyl groups (excluding a monovalent group containing a residue of a liposoluble vitamin having a hydroxy group and a residue of a sterol derivative having a hydroxy group), (iiib) a monovalent group represented by the formula (2), (ivb) a monovalent group represented by the formula (3), (vb) a monovalent group represented by the formula (4), (vib) a monovalent group represented by the formula (5), (viib) a monovalent group represented by the formula (7), (viiib) a monovalent group represented by the formula (8), (ixb) a monovalent group represented by the formula (9), (xb) a monovalent group represented by the formula (10), (xib) a monovalent group represented by the formula (11), (xiib) a monovalent group represented by the formula (12), (xiiib) a monovalent group which is an alkyl group having 1 to 30 carbon atoms, an alkenyl group having 2 to 20 carbon atoms, or an alkynyl group having 2 to 20 carbon atoms, in which one ethylene group in the alkyl group is optionally replaced by one ester bond, or (xivb) an R 3c —CO—(CH 2 ) p — group (wherein R 3c is a residue of a liposoluble vitamin having a hydroxy group or a residue of a sterol derivative having a hydroxy group, and p is an integer of 1 to 8), and R 3a and R 3b may be the same or different).
  15. 15 . The method according to claim 10 , wherein the ionic lipid is a compound represented by the formula (2A): (in the formula (2A), R 1 and R 2 are each independently an alkyl group having 1 to 6 carbon atoms, or any carbon atoms of R 1 and R 2 are optionally bonded to each other to form a heterocycle containing nitrogen atom, and R 3 and R 4 are each independently an aliphatic hydrocarbon group having 1 to 35 carbon atoms optionally substituted by a substituent selected from Substituent Group α, provided that at least one selected from the group consisting of R 3 and R 4 is an aliphatic hydrocarbon group having 5 to 35 carbon atoms optionally substituted by a substituent selected from Substituent Group α, wherein Substituent Group α consists of a hydroxy group, an alkoxy group, a sulfanyl group, an alkylthio group, and an alkoxycarbonyl group).
  16. 16 . The method according to claim 10 , wherein the cryoprotectant is disaccharide.
  17. 17 . The method according to claim 10 , wherein the cryoprotectant is sucrose.
  18. 18 . A method for producing a lyophilized composition of lipid nanoparticles, comprising a step of lyophilizing a composition of lipid nanoparticles not containing a nucleic acid but containing an ionic lipid, a sterol, a PEG lipid, an acidic buffer that shows a buffering action at pH 1-6, and a cryoprotectant at 80-800 mg/mL.
  19. 19 . The method according to claim 18 , wherein the composition of lipid nanoparticles further comprises a phospholipid.
  20. 20 . The method according to claim 18 , wherein a concentration of the cryoprotectant in the composition before lyophilizing is 160-800 mg/mL.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This patent application is a continuation-in-part of co-pending U.S. patent application Ser. No. 17/762,259, filed on Mar. 21, 2022, which is the U.S. national phase of International Patent Application No. PCT/JP2020/036196, filed on Sep. 25, 2020, which claims the benefit of Japanese Patent Application No. 2019-176253 filed on Sep. 26, 2019, which are incorporated by reference in their entireties herein. INCORPORATION-BY-REFERENCE OF MATERIAL ELECTRONICALLY SUBMITTED Incorporated by reference in its entirety herein is a computer-readable nucleotide/amino acid sequence listing submitted concurrently herewith and identified as follows: 10,642 bytes Extensible Markup Language (xml) file named “P11805WOUS-01.xml,” created Dec. 8, 2025. TECHNICAL FIELD The present invention relates to a lyophilized composition of lipid nanoparticles not containing a nucleic acid and a method for producing nucleic acid-encapsulating lipid nanoparticles by using same. BACKGROUND ART For practicalization of nucleic acid therapy using oligonucleic acids such as siRNA, and gene therapy using mRNA, pDNA, and the like, an effective and safe nucleic acid delivery carrier is demanded. While virus vectors are nucleic acid delivery carriers with good expression efficiency, the development of non-viral nucleic acid delivery carriers that can be used more safely is ongoing. Since cationic liposomes using cationic lipids with quaternary amine are positively charged, they can form a complex (lipoplex) by electrostatic interaction with negatively-charged nucleic acids, and can deliver nucleic acids into cells. Utilizing the electrostatic interaction of quaternary amine with nucleic acid, it is also possible to prepare a lyophilized composition of cationic liposomes not containing nucleic acids and form a lipoplex by rehydration with an aqueous solution of nucleic acid. Thus, it has been shown that use thereof as a gene transfer reagent is available (Patent Literatures 1 and 2). However, it is difficult to control the particle size of lipoplex produced by such method, and cytotoxicity derived from positively-charged cationic lipids becomes a problem. Therefore, lipid nanoparticles (LNP) using ionic lipids having a tertiary amine—which is positively charged under acidic conditions and has no electric charge under near neutral conditions—in the molecule were developed, and have become non-viral nucleic acid delivery carriers most generally used at present (Non Patent Literature 1). As lipid nanoparticles using an ionic lipid having a tertiary amine in the molecule, an example also exists in which a degradable group is added to the ionic lipid (Patent Literature 3). As described, various non-viral carriers have been developed. However, since nucleic acids are generally unstable compounds, there are still problems with their stability as pharmaceutical preparations. As one of the methods for improving the stability as a pharmaceutical preparation, attempts have been made to lyophilize lipid nanoparticles encapsulating nucleic acid and rehydrate them at the time of use to reconstitute the lipid nanoparticles (Patent Literature 4 and Non Patent Literature 2). Although these methods are useful as a method for enhancing the storage stability of lipid nanoparticles encapsulating a specific nucleic acid, there is a problem as a method for more easily encapsulating any nucleic acid in lipid nanoparticles. As a method for more easily encapsulating any nucleic acid in lipid nanoparticles, a method of preparing a lyophilized composition not containing a nucleic acid and then rehydrating same with an aqueous solution of nucleic acid, like the methods described in Patent Literatures 1 and 2, can be mentioned. However, lipid nanoparticles obtained using ionic lipid having tertiary amine in the molecule do not electrostatically interact with nucleic acid because the surface charge after preparation is weakly negative to neutral. Thus, the method of preparing a lyophilized composition not containing a nucleic acid and then rehydrating same with an aqueous solution of nucleic acid, disclosed in Patent Literatures 1 and 2, cannot prepare nucleic acid-encapsulating lipid nanoparticles. As described above, no means were available for easily encapsulating any nucleic acid in lipid nanoparticles with a high nucleic acid encapsulation rate. CITATION LIST Patent Literatures [PTL 1] JP-B-4919397 [PTL 2] JP-B-4598908 [PTL 3] JP-B-6093710 [PTL 4] WO 2017/218704 Non Patent Literatures [NPL 1] Gene Therapy 6:271-281, 1999 [NPL 2] Biol. Pharm. Bull. 41, 1291-1294(2018) SUMMARY OF INVENTION Technical Problem The problems of the present invention are provision of a lyophilized composition capable of encapsulating any nucleic acid with high efficiency and easily, which could not be achieved by the prior art, and a production method of nucleic acid-encapsulating lipid nanoparticles by using the composition. Solution to Problem The present in