ES2660846T3 - Composiciones poliplex de quitosano-ácido nucleico de alta concentración - Google Patents
Composiciones poliplex de quitosano-ácido nucleico de alta concentración Download PDFInfo
- Publication number
- ES2660846T3 ES2660846T3 ES08833604.5T ES08833604T ES2660846T3 ES 2660846 T3 ES2660846 T3 ES 2660846T3 ES 08833604 T ES08833604 T ES 08833604T ES 2660846 T3 ES2660846 T3 ES 2660846T3
- Authority
- ES
- Spain
- Prior art keywords
- nucleic acid
- polypelex
- compositions
- high concentration
- chitosan
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/02—Heterocyclic radicals containing only nitrogen as ring hetero atoms
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
Abstract
Una composición que comprende poliplex de quitosano-ácido nucleico hidratados y estables y un inhibidor de agregación, en el que dicha composición tiene una concentración de ácido nucleico mayor que o igual a 0.5 mg/ml, y dicha composición está libre de precipitado de poliplex, y además dicho inhibidor de agregación es un azúcar
Description
Los compuestos de la invención también se pueden administrar directamente al ojo u oído, típicamente en forma de gotas. Otras formulaciones adecuadas para la administración ocular y auditiva incluyen ungüentos, implantes biodegradables (por ejemplo, esponjas de gel absorbibles, colágeno) y no biodegradables (por ejemplo, silicona), obleas, lentes y sistemas de partículas. Las formulaciones también pueden administrarse por iontoforesis.
5 Las formulaciones para administración ocular/aural se pueden formular para que sean de liberación inmediata y/o modificada. Las formulaciones de liberación modificada incluyen liberación retardada, sostenida, pulsada, controlada, dirigida o programada.
Ejemplo 1: Preparación poliplex de hasta 250 µg/ml seguido de concentración hasta >1 mg/ml.
Ver figura 1 y descripción a continuación para descripciones a modo de ejemplo de reactivos, concentraciones y 15 proporciones.
Se probó un simple aparato de mezclado en línea a pequeña escala utilizando bombas de jeringa y bombas peristálticas de alta velocidad, tubos de silicona y uniones en T de polipropileno. Este proceso se usó para hacer poliplex con una concentración final de ADN de hasta 250 µg/mL con una proporción N/P de 20 utilizando 20 23mero/98% de DDA quitosano (es decir, polímeros de quitosano con un promedio de 23 monómeros (glucosamina), y 98% de desacetilación). Los resultados mostraron que el tamaño de partícula y el PDI de los poliplex podían controlarse estrechamente controlando las concentraciones de materia prima, las proporciones de mezcla volumétrica y las velocidades de flujo de las soluciones de ADN y quitosano. Además, se encontró que la incorporación de sacarosa en las materias primas de ADN y quitosano ayudaba al proceso de fabricación al reducir
25 el tamaño de partícula y PDI. La inclusión de sacarosa también evitó la agregación de partículas durante el proceso de concentración. Los poliplex congelados con una concentración de ADN de aproximadamente 1 mg/mL y que contienen hasta un 15% de sacarosa fueron estables durante al menos 1 mes. Además, el proceso de mezcla en línea se ajustó fácilmente desde 50 mL hasta 2 L con valores bajos de desviación estándar relativa (RSD): tamaño de partícula = ±9%, PDI = ±6%.
30
- Material
- Proveedor Catálogo #
- Quitosano (23 mer, 98% DDA)
- Biosyntech N/A
- pADN (pCHS4-3xFLAG-CMV-SEAP-attB)
- enGene Inc. N/A
- pADN (pCMV-INT)
- enGene Inc. N/A
- pADN (gWIZ-SEAP)
- Aldevron LLC 5005
- pADN (gWIZ-Luciferasa)
- Aldevron LLC 5001
- Sacarosa, grado ACS
- Fisher Scientific S5-3
- Tubo de silicona curado con Pt, 1/16 “ID
- Cole-Parmer 95802-02
- Conexiones en T PP, ID de 3/32 “
- Cole-Parmer 30623-57
- Jeringas PP, 3 mL
- B-D 309585
- Jeringas PP, 10 mL
- B-D 309604
- Jeringas PP, 20 mL
- B-D 309661
- Jeringas PP, 30 mL
- B-D 309650
- Conexiones Luer PP, ID de 1/8“
- Cole-Parmer 45500-04
- Filtros de jeringa de 25 mm, membrana Supor de 0.2 µm
- Pall 4612
- Filtros de jeringa de 32 µm de membrana de Supor 0.2 µm
- Pall 4652
- Cubetas desechables, PS, semi-micro de 1.5 ml
- Plastibrand 759075D
13
- Células Zeta capilares dobladas
- Malvern Instruments DTS 1060
- Cartucho TFF, 73 cm2, 1 mm ID, 100K MWCO
- GE Healthcare 56-4101-14
- Material
- Proveedor Catálogo #
- Cartucho TFF, 850 cm2, 1 mm ID, 100K MWCO
- GE Healthcare 56-4102-15
- Cartucho TFF, 73 cm2, 1 mm ID, 500K MWCO
- GE Healthcare 56-4101-18
- Kit de ensayo PicoGreen Quant-iT ds DNA HS
- Invitrogen Q32854
- enzima EcoR1, 20,000 U/mL
- New England BioLabs R0101S
- Tampón EcoR1, 10X
- New England BioLabs B0101S
- Enzima quitosanasa, 62 U/mL
- Sigma C0794
- Escalera de ADN superentorchada
- Invitrogen 15622-012
- tampón de carga Cian/Amarillo, 6X
- Invitrogen 10482-035
- Bromuro de Etidio
- EM Science 4410
- Agarosa, Ultra-Pura
- Invitrogen 15510-027
- Línea xcelular 293T-K
- Dr. Kieffer at UBC N/A
- Medio Eagle modificado por Dulbecco
- VWR X16777-128
- Suero Bovino fetal
- Wisent 080150
- Penicilina/Estreptomicina
- Invitrogen 15140-122
- Solución salina amortiguada por fosfato
- Invitrogen 21600-010
- Tripsina
- Invitrogen 25300-062
- Opti-mem
- Invitrogen 31985-070
- Ensayo quimioluminescente SEAP
- Roche 1779842
- Enzima de fosfatasa alcalina de la placenta
- Sigma P-3895
- Sero albúmina bovina (BSA)
- Sigma A9418
- Glicerol
- Sigma G5516
- Placa de 96 pozos de fondo plano blanca Microlite-1
- VWR 7417
- Equipo
- Fabricante
- Bomba de jeringa, NE-1000
- New Era Pump Systems Inc.
- Bomba de jeringa, NE-1000
- New Era Pump Systems Inc.
- Bombas peristálticas, Bomba Materflex L/S activada con cabezales de bomba L/S Easy-Load II
- Cole Parmer
- Medidor de tamaño de partícula Zetasizer Nano (ZEN 3600)
- Malvern Instruments
- pH Metro, Accumet AB15
- Fisher Scientific
- Espectrofotometro UV, Ultrospec 2100 pro
- Biochrom Ltd.
- Fluorómetro Qubit, cat # Q32857
- Invitrogen
14
Claims (1)
-
imagen1 imagen2
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US97631607P | 2007-09-28 | 2007-09-28 | |
| US976316P | 2007-09-28 | ||
| PCT/CA2008/001714 WO2009039657A1 (en) | 2007-09-28 | 2008-09-26 | High concentration chitosan-nucleic acid polyplex compositions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2660846T3 true ES2660846T3 (es) | 2018-03-26 |
Family
ID=40510712
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES08833604.5T Active ES2660846T3 (es) | 2007-09-28 | 2008-09-26 | Composiciones poliplex de quitosano-ácido nucleico de alta concentración |
Country Status (20)
| Country | Link |
|---|---|
| US (3) | US8722646B2 (es) |
| EP (1) | EP2195035B1 (es) |
| JP (2) | JP5650533B2 (es) |
| KR (2) | KR20100077155A (es) |
| CN (1) | CN101873867B (es) |
| AU (1) | AU2008302979B2 (es) |
| BR (1) | BRPI0817725A2 (es) |
| CA (1) | CA2700842C (es) |
| DK (1) | DK2195035T3 (es) |
| ES (1) | ES2660846T3 (es) |
| IL (1) | IL204677A (es) |
| MX (1) | MX2010003323A (es) |
| NO (1) | NO2195035T3 (es) |
| PL (1) | PL2195035T3 (es) |
| PT (1) | PT2195035T (es) |
| RU (1) | RU2010116775A (es) |
| SG (1) | SG187403A1 (es) |
| SI (1) | SI2195035T1 (es) |
| WO (1) | WO2009039657A1 (es) |
| ZA (1) | ZA201002169B (es) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK2195035T3 (en) | 2007-09-28 | 2018-03-12 | Engene Inc | CHITOSAN NUCLEIC ACID POLYPLEX COMPOSITIONS WITH HIGH CONCENTRATION |
| WO2010111787A1 (en) * | 2009-03-31 | 2010-10-07 | Engene, Inc. | Highly acidic chitosan-nucleic acid polyplex compositions |
| MX345885B (es) * | 2010-12-07 | 2017-02-22 | Hoffmann La Roche | Dispositivo de mezclado de alimentacion y su uso. |
| PT2828332T (pt) * | 2012-03-21 | 2017-08-10 | Engene Inc | Nanopartículas de quitosano duplamente derivado e métodos para produzir e utilizar as mesmas para transferência de gene in vivo |
| ITTO20121107A1 (it) * | 2012-12-19 | 2014-06-20 | Idea Medical Devices S R L | Composizione a base di polidesossiribonucleotidi e relativi usi |
| PT3049473T (pt) | 2013-09-25 | 2021-12-21 | Engene Inc | Nanopartículas de quitosana duplamente derivada e métodos de produção e utilização das mesmas para transferência de genes in vivo |
| EP3107549B1 (en) | 2014-02-20 | 2020-07-01 | B.G. Negev Technologies and Applications Ltd. | Anionic polyplexes for use in the delivery of nucleic acids |
| EP3283059B1 (en) | 2015-04-13 | 2024-01-03 | CureVac Manufacturing GmbH | Method for producing rna compositions |
| KR101710639B1 (ko) * | 2016-06-07 | 2017-03-08 | 주식회사 파마리서치프로덕트 | 핵산, 키토산 및 히알루론산을 포함하는 조직 증강용 충전 조성물 및 이의 제조방법 |
| CN109310800B (zh) * | 2016-07-29 | 2022-01-07 | 医药研究有限公司 | 包含核酸和壳聚糖的肩袖撕裂修复用组合物 |
| RU2697527C1 (ru) * | 2018-06-06 | 2019-08-15 | Федеральное государственное учреждение "Федеральный исследовательский центр "Фундаментальные основы биотехнологии" Российской академии наук" (ФГУ ФИЦ Биотехнологии РАН) | Иммуноадъювантная композиция для вакцин против инфекционных агентов вирусной и бактериальной природы |
| EP3693024A1 (en) * | 2019-02-05 | 2020-08-12 | Altona Diagnostics GmbH | Control for nucleic acid preparation and/or detection methods |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6184037B1 (en) * | 1996-05-17 | 2001-02-06 | Genemedicine, Inc. | Chitosan related compositions and methods for delivery of nucleic acids and oligonucleotides into a cell |
| JP2000514086A (ja) | 1996-07-10 | 2000-10-24 | ダンバイオシスト、ユーケー、リミテッド | 内皮への標的のための遺伝子治療送達系 |
| WO1999040771A2 (en) * | 1998-02-13 | 1999-08-19 | Selective Genetics, Inc. | Concurrent flow mixing for preparing compositions comprising gene therapy vectors |
| US6534483B1 (en) * | 1998-08-14 | 2003-03-18 | Valentis, Inc. | Protected one-vial formulation for nucleic acid molecules, methods of making the same by in-line mixing, and related products and methods |
| US6251599B1 (en) * | 1998-11-06 | 2001-06-26 | Selective Genetics, Inc. | Stabilized nucleic acid compositions and methods of preparation and use thereof |
| DE10141971A1 (de) | 2001-08-28 | 2003-03-27 | Siemens Ag | Adaptive Kanalschätzung in einem OFDM-basierten Mobilfunksystem durch Variation der Anzahl der Pilotsymbole |
| EP1306127B2 (en) * | 2001-10-26 | 2011-09-07 | OctoPlus PolyActive Sciences B.V. | Method for the preparation of purified microparticles |
| NO317654B1 (no) * | 2002-05-03 | 2004-11-29 | Stiftelsen Biopolymer | Formulering som inneholder en nukleinsyre og et kitosan, fremgangsmate for fremstilling av formuleringen, samt anvendelser derav. |
| NO317653B1 (no) * | 2002-05-03 | 2004-11-29 | Stiftelsen Biopolymer | Formulering som omfatter komplekser av kitosanoligomerer og nukleinsyre, fremgangsmate for a fremstille formuleringen samt anvendelser derav. |
| KR100613734B1 (ko) * | 2004-09-07 | 2006-08-22 | 굿젠 주식회사 | 키토산을 이용한 ｄｎａ 보관방법 및 분석방법 및 이를이용한 ｄｎａ 제품 |
| DK2195035T3 (en) * | 2007-09-28 | 2018-03-12 | Engene Inc | CHITOSAN NUCLEIC ACID POLYPLEX COMPOSITIONS WITH HIGH CONCENTRATION |
-
2008
- 2008-09-26 DK DK08833604.5T patent/DK2195035T3/en active
- 2008-09-26 AU AU2008302979A patent/AU2008302979B2/en active Active
- 2008-09-26 PL PL08833604T patent/PL2195035T3/pl unknown
- 2008-09-26 MX MX2010003323A patent/MX2010003323A/es active IP Right Grant
- 2008-09-26 RU RU2010116775/15A patent/RU2010116775A/ru unknown
- 2008-09-26 CN CN200880117777.9A patent/CN101873867B/zh active Active
- 2008-09-26 NO NO08833604A patent/NO2195035T3/no unknown
- 2008-09-26 ES ES08833604.5T patent/ES2660846T3/es active Active
- 2008-09-26 EP EP08833604.5A patent/EP2195035B1/en active Active
- 2008-09-26 JP JP2010526123A patent/JP5650533B2/ja active Active
- 2008-09-26 PT PT88336045T patent/PT2195035T/pt unknown
- 2008-09-26 SI SI200831923T patent/SI2195035T1/en unknown
- 2008-09-26 US US12/680,527 patent/US8722646B2/en active Active
- 2008-09-26 CA CA2700842A patent/CA2700842C/en active Active
- 2008-09-26 BR BRPI0817725A patent/BRPI0817725A2/pt not_active IP Right Cessation
- 2008-09-26 KR KR1020107006747A patent/KR20100077155A/ko active Application Filing
- 2008-09-26 SG SG2012096111A patent/SG187403A1/en unknown
- 2008-09-26 KR KR1020157026865A patent/KR101761289B1/ko active IP Right Grant
- 2008-09-26 WO PCT/CA2008/001714 patent/WO2009039657A1/en active Application Filing
-
2010
- 2010-03-23 IL IL204677A patent/IL204677A/en active IP Right Grant
- 2010-03-26 ZA ZA2010/02169A patent/ZA201002169B/en unknown
-
2014
- 2014-04-30 US US14/266,584 patent/US9850323B2/en active Active
- 2014-07-11 JP JP2014143568A patent/JP2014208696A/ja active Pending
-
2017
- 2017-12-20 US US15/849,595 patent/US10647785B2/en active Active
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