SI2538968T1 - Proces za proizvodnjo in čiščenje rekombinantne lizosomalne alfa-manozidaze - Google Patents
Proces za proizvodnjo in čiščenje rekombinantne lizosomalne alfa-manozidaze Download PDFInfo
- Publication number
- SI2538968T1 SI2538968T1 SI201131374T SI201131374T SI2538968T1 SI 2538968 T1 SI2538968 T1 SI 2538968T1 SI 201131374 T SI201131374 T SI 201131374T SI 201131374 T SI201131374 T SI 201131374T SI 2538968 T1 SI2538968 T1 SI 2538968T1
- Authority
- SI
- Slovenia
- Prior art keywords
- alpha
- human lysosomal
- process according
- manosidase
- lysosomal alpha
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/16—Extraction; Separation; Purification by chromatography
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
-
- 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—Liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/12—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by hydrolysis, i.e. solvolysis in general
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
- C12N9/2477—Hemicellulases not provided in a preceding group
- C12N9/2488—Mannanases
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01024—Alpha-mannosidase (3.2.1.24)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Analytical Chemistry (AREA)
- Biophysics (AREA)
- General Chemical & Material Sciences (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Dispersion Chemistry (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
Claims (20)
- Proces za proizvodnjo in čiščenje rekombinantne lizosomalne alfa-manozidaze PATENTNI ZAHTEVKI1. Proces za čiščenje rekombinantne humane lizosomske alfa-manozidaze iz celične kulture, kjer je frakcija navedene celične kulture, ki obsega rekombinantno humano lizosomsko alfa-manozidazo, podvržena kromatografiji na smoli, ki obsega multi-modalni ligand, pri čemer je omenjeni multi-modalni ligand, vezan na smolo, snov, ki ima karboksilne kisline ali skupine sulfonske kisline.
- 2. Proces po zahtevku 1, kjer je omenjeni del celične kulture, ki obsega rekombinantno humano lizosomalno alfa-manozidazo očiščen nerazredčen pridelek.
- 3. Proces po katerem koli od zahtevkov 1-2, kjer je smolno vezan multi-modalni ligand substanca s formulo (I), (II) ali (III): kjer je R snovi s formulo (II) in (III) funkcionalna skupina s formulo (IV):
- 4. Proces po katerem koli od zahtevkov 1-3, kjer je frakcija celične kulture, naložena na smolo, obsegajoč multimodalni ligand, podvržena vsaj enemu koraku pranja z raztopino, ki obsega izopropanol.
- 5. Proces po zahtevku 4, kjer raztopina vsebuje najmanj 1 % (V:V) izopropanola.
- 6. Proces po katerem koli od zahtevkov 1-5, kjer prvi eluat obsega rekombinantno humano lizosomalno alfa-manozidazo eluiran iz smola, obsegajoč multi-modalni ligand, z uporabo vodne raztopine, ki obsega etilenglikol ali propilenglikol.
- 7. Proces po katerem koli od zahtevkov 1-6, pri čemer je prvi eluat, ki obsega rekombinantno humano lizosomalno alfa-manozidazo dobljen iz smola, obsegajoč multi-modalni ligand, nadalje podvržen procesu, ki obsega korake i) nanašanje frakcije, ki obsega rekombinantno humano lizosomalno alfa-manozidazo na hidrofobno interakcijsko kromatografsko smolo, da dobimo eluat, ki obsega rekombinantno humano lizosomalno alfa-manozidazo, ii) prehajanje frakcije, ki obsega rekombinantno humano lizosomalno alfa-manozidazo preko mešanega-načina ionsko izmenjevalne smole, ki dovoljuje retencijo kontaminatov, da zagotovi pretok skozi obsegajočo rekombinantno humano lizosomalno alfa-manozidazo; in iii) izpostavljanje frakcije, ki obsega rekombinantno humano lizosomalno alfa-manozidazo kromatografiji na anionsko izmenjevalni smoli, da dobimo eluat, ki obsega rekombinantno humano lizosomalno alfa-manozidazo.
- 8. Proces po katerem koli od zahtevkov 1-7, kjer ima rekombinantna humano lizosomalna alfa-manozidaza zaporedje, izbrano iz: A) zaporedja, navedenega v SEQ ID NO 2 B) sekvenco, ki ima vsaj 80% sekvenčne identičnosti s SEQ ID NO 2.
- 9. Sestavek, ki obsega alfa-manozidazo, ki jo lahko dobimo s postopkom čiščenja po katerem koli od zahtevkov 7-8.
- 10. Proces za dovajanje šarže ali kontinuirano proizvodnjo rekombinantne humane lizosomalne alfa-manozidaze, ki obsega naslednje korake: a. inokulacijo produkcijskega reaktorja, ki obsega bazni medij s celicami, ki lahko proizvajajo rekombinantno humano lizosomalno alfa-manozidazo na dan 0, da zagotovimo celično kulturo; b. dodajanje hranilnega medija omenjeni celični kulturi vsaj enkrat od 1. dne; c. prilagajanje temperature navedene celične kulture do največ 35 °C bodisi po 3 dnevu bodisi, ko je viabilno celična gostota večja od 2,1 MVC/ml, kar nastopi prej. d. proces čiščenja po katerem koli od zahtevkov 1-8.
- 11. Proces po zahtevku 10, kjer je celična kultura v bistvu brez dodatkov, pridobljenih iz živali, kot so dodatki olje iz jeter trske.
- 12. Proces po katerem koli od zahtevkov 10-11, pri čemer je proces dovajane šarže ali neprekinjene proizvodnje izveden z volumnom najmanj 30 L.
- 13. Proces po katerem koli od zahtevkov 10-12, kjer ima rekombinantna humana lizosomalna alfa-manozidaza sekvenco, izbrano izmed: A) sekvenco, navedeno v SEQ ID NO 2 B) sekvenco, ki ima vsaj 80% sekvenčne identičnosti s SEQ ID NO 2.
- 14. Proces po katerem koli od zahtevkov 10-13, kjer je korak d) proces čiščenja, kot je definiran v zahtevku 7.
- 15. Sestavek, ki obsega alfa-manozidazo, pridobljeno s proizvodnim procesom po zahtevku 14.
- 16. Sestavek, pripravljen po procesu po zahtevku 14, ki obsega prečiščeno humano lizosomalno alfa-manozidazo očiščen po postopku po zahtevkih 1-8, kjer je vsaj 80% alfa-manozidaze prisoten kot 130 kDa glikoprotein.
- 17. Sestavek po zahtevku 16, kjer rekombinantna alfa-manoszidaza ostane stabilna v tekoči raztopini najmanj 4 dni, če je shranjen pri + 5 °C ali najmanj 24 mesecev, če je shranjena pri -20 °C.
- 18. Sestavek po katerem koli od zahtevkov 16-17, kjer ima alfa-manozidaza sekvenco, izbrano izmed: A) sekvenco, navedeno v SEQ ID NO 2 B) sekvenco, ki ima vsaj 80% sekvenčne identičnosti s SEQ ID NO 2.
- 19. Sestavek po katerem koli od zahtevkov 9 in 15-18 za uporabo kot zdravilo.
- 20. Sestavek po katerem koli od zahtevkov 9 in 15-18 za uporabo pri zdravljenju alfa-manozidoze.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30758710P | 2010-02-24 | 2010-02-24 | |
| DKPA201070067 | 2010-02-24 | ||
| EP11705806.5A EP2538968B1 (en) | 2010-02-24 | 2011-02-23 | Process for production and purification of recombinant lysosomal alpha-mannosidase |
| PCT/DK2011/050054 WO2011103877A1 (en) | 2010-02-24 | 2011-02-23 | Process for production and purification of recombinant lysosomal alpha-mannosidase |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SI2538968T1 true SI2538968T1 (sl) | 2018-04-30 |
Family
ID=43920349
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SI201131925T SI3281636T1 (sl) | 2010-02-24 | 2011-02-23 | Postopek proizvodnje in čiščenja rekombinantne lizosomske alfa-manozidaze |
| SI201131374T SI2538968T1 (sl) | 2010-02-24 | 2011-02-23 | Proces za proizvodnjo in čiščenje rekombinantne lizosomalne alfa-manozidaze |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SI201131925T SI3281636T1 (sl) | 2010-02-24 | 2011-02-23 | Postopek proizvodnje in čiščenja rekombinantne lizosomske alfa-manozidaze |
Country Status (25)
| Country | Link |
|---|---|
| US (3) | US8974780B2 (sl) |
| EP (2) | EP3281636B1 (sl) |
| JP (1) | JP6021647B2 (sl) |
| KR (1) | KR101856260B1 (sl) |
| CN (1) | CN102834111B (sl) |
| AU (1) | AU2011220163B2 (sl) |
| BR (1) | BR112012020934B1 (sl) |
| CA (1) | CA2790786C (sl) |
| CY (1) | CY1123438T1 (sl) |
| DK (2) | DK2538968T3 (sl) |
| EA (1) | EA022220B1 (sl) |
| ES (1) | ES2652330T3 (sl) |
| FR (1) | FR18C1038I2 (sl) |
| HK (1) | HK1179869A1 (sl) |
| HR (1) | HRP20171736T1 (sl) |
| HU (2) | HUE037943T2 (sl) |
| LT (2) | LT2538968T (sl) |
| NL (1) | NL300948I2 (sl) |
| NO (2) | NO2538968T3 (sl) |
| NZ (1) | NZ601790A (sl) |
| PL (2) | PL2538968T3 (sl) |
| PT (1) | PT2538968T (sl) |
| RS (1) | RS60983B1 (sl) |
| SI (2) | SI3281636T1 (sl) |
| WO (1) | WO2011103877A1 (sl) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9169331B2 (en) * | 2012-12-21 | 2015-10-27 | Dionex Corporation | Separation of glycans by mixed-mode liquid chromatography |
| US9310344B2 (en) | 2013-06-14 | 2016-04-12 | Dionex Corporation | HILIC/anion-exchange/cation-exchange multimodal media |
| AR095196A1 (es) | 2013-03-15 | 2015-09-30 | Regeneron Pharma | Medio de cultivo celular libre de suero |
| CN111100196B (zh) * | 2019-11-08 | 2021-07-13 | 上海交通大学 | 一种生物活性多肽qilsvpgwtysr及其制备方法和应用 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL63327A (en) * | 1981-07-16 | 1985-11-29 | Yeda Res & Dev | Production of interferon beta1 and alpha-phage recombinants for its production in host bacteria |
| US5705364A (en) * | 1995-06-06 | 1998-01-06 | Genentech, Inc. | Mammalian cell culture process |
| JP4320870B2 (ja) | 1999-10-18 | 2009-08-26 | 住友化学株式会社 | （＋）−トランス第一菊酸の製造方法 |
| GB0007651D0 (en) * | 2000-03-29 | 2000-05-17 | Ascorbex Ltd | Gene sequence |
| US7138262B1 (en) * | 2000-08-18 | 2006-11-21 | Shire Human Genetic Therapies, Inc. | High mannose proteins and methods of making high mannose proteins |
| AU2002317701A1 (en) * | 2001-06-07 | 2002-12-16 | Hemebiotech A/S | Production of recombinant human lysosomal alpha-mannosidase |
| JP4742191B2 (ja) * | 2001-06-14 | 2011-08-10 | 独立行政法人産業技術総合研究所 | 糖蛋白質およびその製造方法 |
| US7507573B2 (en) * | 2003-11-14 | 2009-03-24 | Vib, Vzw | Modification of protein glycosylation in methylotrophic yeast |
| EP2532742B1 (en) * | 2004-01-30 | 2018-08-08 | Shire Pharmaceuticals Ireland Limited | Recombinant arylsulfatase A for reducing galatosyl sulphatide levels in a subject |
| BRPI0507440A (pt) * | 2004-02-06 | 2007-07-10 | Biomarin Pharm Inc | fabricação de enzimas lisossomais altamente fosforiladas e uso das mesmas |
| PL1740204T3 (pl) | 2004-04-01 | 2018-08-31 | Chiesi Farmaceutici S.P.A. | Lecznicze zastosowanie alfa-mannozydazy |
| SI2628746T1 (sl) * | 2006-04-04 | 2019-04-30 | Chiesi Farmaceutici S.P.A. | Proces za koncentriranje polipeptida |
| CN101410408A (zh) * | 2006-04-04 | 2009-04-15 | 希尔制药爱尔兰有限责任公司 | 用于浓缩多肽的方法 |
| CA2692814A1 (en) * | 2007-07-11 | 2009-01-15 | Novo Nordisk A/S | Purification of factor viii using a mixed-mode or multimodal resin |
-
2011
- 2011-02-23 NO NO11705806A patent/NO2538968T3/no unknown
- 2011-02-23 EA EA201270715A patent/EA022220B1/ru not_active IP Right Cessation
- 2011-02-23 AU AU2011220163A patent/AU2011220163B2/en active Active
- 2011-02-23 DK DK11705806.5T patent/DK2538968T3/en active
- 2011-02-23 SI SI201131925T patent/SI3281636T1/sl unknown
- 2011-02-23 EP EP17192938.3A patent/EP3281636B1/en active Active
- 2011-02-23 DK DK17192938.3T patent/DK3281636T3/da active
- 2011-02-23 JP JP2012554217A patent/JP6021647B2/ja active Active
- 2011-02-23 CA CA2790786A patent/CA2790786C/en active Active
- 2011-02-23 US US13/576,258 patent/US8974780B2/en active Active
- 2011-02-23 EP EP11705806.5A patent/EP2538968B1/en active Active
- 2011-02-23 PT PT117058065T patent/PT2538968T/pt unknown
- 2011-02-23 PL PL11705806T patent/PL2538968T3/pl unknown
- 2011-02-23 PL PL17192938T patent/PL3281636T3/pl unknown
- 2011-02-23 BR BR112012020934-5A patent/BR112012020934B1/pt active IP Right Grant
- 2011-02-23 NZ NZ601790A patent/NZ601790A/en unknown
- 2011-02-23 CN CN201180010683.3A patent/CN102834111B/zh active Active
- 2011-02-23 WO PCT/DK2011/050054 patent/WO2011103877A1/en active Application Filing
- 2011-02-23 ES ES11705806.5T patent/ES2652330T3/es active Active
- 2011-02-23 KR KR1020127022458A patent/KR101856260B1/ko active IP Right Grant
- 2011-02-23 RS RS20201294A patent/RS60983B1/sr unknown
- 2011-02-23 SI SI201131374T patent/SI2538968T1/sl unknown
- 2011-02-23 HU HUE11705806A patent/HUE037943T2/hu unknown
- 2011-02-23 LT LTEP11705806.5T patent/LT2538968T/lt unknown
-
2013
- 2013-06-19 HK HK13107165.9A patent/HK1179869A1/xx unknown
-
2015
- 2015-03-02 US US14/635,681 patent/US20150306186A1/en not_active Abandoned
-
2017
- 2017-06-09 US US15/619,125 patent/US10159718B2/en active Active
- 2017-11-13 HR HRP20171736TT patent/HRP20171736T1/hr unknown
-
2018
- 2018-08-28 NL NL300948C patent/NL300948I2/nl unknown
- 2018-08-28 LT LTPA2018512 patent/LTC2538968I2/lt unknown
- 2018-08-30 HU HUS1800037C patent/HUS1800037I1/hu unknown
- 2018-09-14 FR FR18C1038C patent/FR18C1038I2/fr active Active
- 2018-09-14 NO NO2018032C patent/NO2018032I1/no unknown
-
2020
- 2020-10-09 CY CY20201100951T patent/CY1123438T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HRP20171736T1 (hr) | Postupak proizvodnje i pročišćavanja rekombinantne lizosomske alfa-manozidaze | |
| KR102485898B1 (ko) | 보툴리눔 독소 함유 용액으로부터 보툴리눔 독소를 분리하는 방법 | |
| RU2011102437A (ru) | Способ очистки фактора свертывания крови viii | |
| Taylor et al. | Microphytobenthic extracellular polymeric substances (EPS) in intertidal sediments fuel both generalist and specialist EPS‐degrading bacteria | |
| CN102040675B (zh) | 一种羟丙基-β-环糊精的制备方法 | |
| CN105392795B (zh) | 生产肉毒杆菌毒素的方法 | |
| DE202015009782U1 (de) | Trennung von 2'-O-Fucosyllactose aus Fermentationsbrühe | |
| AU2019201315A1 (en) | Method for producing botulinum toxin | |
| RU2012146084A (ru) | Способ очистки витамин-к-зависимых белков, таких как коагуляционный фактор ix | |
| JPWO2014192877A1 (ja) | 洗浄用組成物、タンパク質精製方法、及びタンパク質 | |
| Kobayashi et al. | A simple recovery process for biodegradable plastics accumulated in cyanobacteria treated with ionic liquids | |
| RU2013112276A (ru) | СПОСОБ ПОЛУЧЕНИЯ КОМПОЗИЦИИ IgG ПОСРЕДСТВОМ ТЕПЛОВОЙ ОБРАБОТКИ | |
| BR112012014699A2 (pt) | método para recuperação de componentes orgânicos a partir de soluções aquosas diluídas | |
| ES2780367T3 (es) | Nuevo método de purificación eficiente de albumina sérica humana | |
| CN105400791B (zh) | 斑马鱼防御素defbl3的优化基因及其重组蛋白的制备方法 | |
| CN105111285A (zh) | 一种达托霉素的提取方法 | |
| KR20180121040A (ko) | 디올의 제조 방법 | |
| CN111662944A (zh) | 一种人血清白蛋白的制备方法及其纯化方法 | |
| RU2014108241A (ru) | Способ катион- и анионобменной хроматографии | |
| HRP20201757T1 (hr) | Postupak za proizvodnju i pročišćavanje rekombinantne lizozomske alfa-manozidaze | |
| CN102964400B (zh) | 一种不含去氢林可霉素的盐酸林可霉素制备方法 | |
| CN105061575B (zh) | 一种金枪鱼肝脏抗菌肽及其制备方法和用途 | |
| CN104530210A (zh) | 一种精制硫酸鱼精蛋白的方法 | |
| CN103695497B (zh) | 纳洛酮的酶法制备及其药物组合物 | |
| CN107686168A (zh) | 一种改性缓释净水材料及其制备方法和应用 |