Systems and methods for manufacturing liposomes
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-009/127
A61K-031/7088
A61K-048/00
출원번호
US-0495150
(2006-07-27)
등록번호
US-9005654
(2015-04-14)
발명자
/ 주소
MacLachlan, Ian
Jeffs, Lloyd B.
Yaworski, Edward
Lam, Kieu
출원인 / 주소
Protiva Biotherapeutics, Inc.
대리인 / 주소
Kilpatrick, Townsend & Stockton LLP
인용정보
피인용 횟수 :
6인용 특허 :
16
초록▼
The present invention provides apparatus and processes for producing liposomes. By providing a buffer solution in a first reservoir, and a lipid solution in a second reservoir, continuously diluting the lipid solution with the buffer solution in a mixing chamber produces a liposome. A therapeutic ag
The present invention provides apparatus and processes for producing liposomes. By providing a buffer solution in a first reservoir, and a lipid solution in a second reservoir, continuously diluting the lipid solution with the buffer solution in a mixing chamber produces a liposome. A therapeutic agent, such as nucleic acid, is included in one of the buffer solution or the lipid solution. Upon mixing a liposome encapsulating the therapeutic product is substantially instantaneously formed. Thereafter the liposome solution formed is immediately diluted with buffer solution to enhance homogeneity and maintain small particle size.
대표청구항▼
1. A method of producing a lipid vesicle encapsulating a therapeutic product, said method comprising: providing an aqueous solution in a first reservoir;providing an organic lipid solution in a second reservoir, wherein one of the aqueous solution and the organic lipid solution includes a therapeuti
1. A method of producing a lipid vesicle encapsulating a therapeutic product, said method comprising: providing an aqueous solution in a first reservoir;providing an organic lipid solution in a second reservoir, wherein one of the aqueous solution and the organic lipid solution includes a therapeutic product;mixing said aqueous solution with said organic lipid solution in a first mixing region to produce a lipid vesicle solution, wherein said organic lipid solution mixes with said aqueous solution so as to substantially instantaneously produce a lipid vesicle encapsulating the therapeutic product, wherein mixing includes introducing the aqueous solution and the organic lipid solution into the first mixing region at substantially equal flow rates, wherein the first mixing region includes a first T-connector, and wherein the aqueous solution and the organic lipid solution are introduced into the first T-connector as opposing flows at substantially 180° relative to each other; andmixing said lipid vesicle solution with a buffer solution to produce a diluted lipid vesicle solution, wherein mixing said lipid vesicle solution with the buffer solution includes mixing in a second mixing region, wherein the lipid vesicle solution formed in the first mixing region is immediately and directly diluted with the buffer solution in the second mixing region less than two seconds after the lipid vesicle solution is formed, wherein the second mixing region includes a second T-connector, wherein the lipid vesicle solution and the buffer solution are introduced into the second T-connector at about 27° to about 180° relative to each other, and wherein the lipid vesicle is less than 100 nm in diameter. 2. The method of claim 1, wherein said lipid vesicle solution has a concentration of about 20% v/v to about 55% v/v organic solvent. 3. The method of claim 2, wherein the diluted lipid vesicle solution has a concentration of less than about 25% v/v organic solvent. 4. The method of claim 1, wherein said therapeutic product is selected from the group consisting of a protein, a plasmid, an aptamer, a nucleic acid, an antisense nucleic acid, a ribozyme, tRNA, snRNA, siRNA, shRNA, ncRNA, pre-condensed DNA and an antigen. 5. The method of claim 1, wherein said therapeutic product is a nucleic acid. 6. The method of claim 1, wherein said therapeutic product is an siRNA. 7. The method of claim 1, wherein said lipid vesicle is a stable nucleic acid-lipid particle (SNALP). 8. The method of claim 1, wherein the lipids present in said organic lipid solution are solubilized in an organic solvent. 9. The method of claim 8, wherein the organic solvent comprises a lower alkanol. 10. The method of claim 9, wherein said lower alkanol is selected from the group consisting of methanol, ethanol, propanol, butanol, pentanol, isomers thereof, and combinations thereof. 11. The method of claim 9, wherein said lower alkanol comprises 100% v/v ethanol. 12. The method of claim 1, wherein the lipids present in said organic lipid solution comprise a phospholipid, cholesterol, a PEG-lipid, and a cationic lipid. 13. The method of claim 1, wherein the aqueous solution includes said therapeutic product. 14. The method of claim 12, wherein the aqueous solution has a pH of about 4 to about 6. 15. The method of claim 2, wherein the diluted lipid vesicle solution has a concentration of about 17% v/v to about 25% v/v organic solvent. 16. The method of claim 1, wherein the lipid vesicle solution formed in the first mixing region is immediately and directly diluted with the buffer solution in the second mixing region less than one second after the lipid vesicle solution is formed.
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