CN103656668A - Bortezomib sustained-release preparation and preparation method thereof - Google Patents
Bortezomib sustained-release preparation and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a bortezomib sustained-release preparation and a preparation method thereof, and belongs to the field of nano-materials and nano drug carriers. The preparation employs carbon quantum dot labeled chitosan as a carrier. The preparation method comprises the following steps: conducting esterification reaction on peptidylborate radicals of bortezomib and hydroxy of chitosan to obtain peptidyl borate ester, thus grafting bortezomib to chitosan nanoparticles; carrying out electrostatic adsorption on surface carboxyl groups of carbon quantum dots and amino groups on chitosan in the chitosan nanoparticles, thus loading the carbon quantum dots into the chitosan nanoparticle system and preparing chitosan nanoparticle bortezomib sustained-release preparation adsorbed with carbon quantum dots and coupled with bortezomib. Compared with the prior art, the bortezomib sustained-release preparation provided by the invention and the preparation method thereof have the characteristics of feasible process, simple operation, and good targeting and controlled release properties, and have important application values in biological sensing, biomedical functional nano-materials, especially controlled release of drug carriers or preparations.
Description
Technical field
The present invention relates to nano material and pharmaceutical carrier field, specifically a kind of bortezomib slow releasing preparation and preparation method thereof.
Background technology
According to World Health Organization's recent statistics, to the year two thousand twenty whole world cancer morbidity, will increase by 50%, number of the infected increases to 1,500 ten thousand.Estimate that the year two thousand twenty China will have 4,000,000 people to die from cancer every year.Therefore method or the medicine of, inquiring into a kind of effective treatment cancer have become one of focus of current research.
Bortezomib (Bortezomib, BTZ), as a kind of new protease inhibitor, mainly as the choice drug for the treatment of multiple myeloma, also has certain therapeutic effect to other tumor in recent years simultaneously.When bortezomib is used for the treatment of tumor separately, tool has certain effect, but the caused whole body toxic and side effects of conventional route administration has limited the effect of its clinical practice.Chemotherapeutics topical application, especially local sustained release have become the study hotspot of current entity tumor chemotherapy.Existing bortezomib preparation slow-release auxiliary material used more or less can cause burst drug release, unbalanced release when discharging, or discharged and make slowly local active drug concentration not enough, thereby can not effectively kill tumor cell, if discharge too fast or prominent releasing, can as regular injection, cause the toxic reaction of whole body.
In the preparation research of existing bortezomib, the methods such as liposome entrapment, antibodies, medication combined, freeze-dried powder, aminoacid doping have been adopted.For example, S
.bundle Lipsky etc. generates the polyol reaction of boronic acid compounds and liposome entrapment borate and is loaded in (patent publication No.: CN101094648) in liposome by bag.D
.a Faer etc. have developed the method (patent publication No.: CN101686971) of the medication combined bortezomib for treating multiple myeloma based on anti-cs 1 antibodies.Hou Hongchun etc. have prepared the anti-cancer composition (patent publication No.: CN101301469) containing nitrosourea medicament and bortezomib.Chen Qingcais etc. have made a kind of freeze-dried composition (patent publication No.: CN103070835A) containing bortezomib by adding mannitol or the tert-butyl alcohol.Li Cuiyan etc. have studied the preparation (patent publication No.: CN103142509A) of a kind of bortezomib and aminoacid doping.
Although adopt above method can obtain the pharmaceutical preparation of bortezomib, but still exist some crucial technical problem urgently to be resolved hurrily, if preparation technology and cost, the biocompatibility of preparation are, the controllability of the stability of slow releasing preparation, targeting and drug release etc.Therefore, develop the bortezomib slow releasing agent of the performances such as a kind of reasonable in design, feasible process, simple to operate, drug targeting and controllable release, in association areas such as biology, medical science, materials, all there is very important Research Significance and using value.Up to now, there is not yet bortezomib by the hydroxyl reaction of peptide boric acid root and chitosan, generate peptide boric acid ester and obtain the chitosan nano of load bortezomib, also there is not yet by carbon quantum dot surface carboxyl and the chitosan nano inside amino of load bortezomib and carry out the relevant report that the bortezomib slow releasing agent of carbon quantum dot-chitosan composite nano-granule is prepared in Electrostatic Absorption self assembly.
Summary of the invention
Technical assignment of the present invention is for above-mentioned the deficiencies in the prior art, and the bortezomib slow releasing preparation of the function admirables such as a kind of feasible process, simple to operate, targeting and controllable release is provided.
The further technical assignment of the present invention is to provide the preparation method of above-mentioned preparation.
Technical assignment of the present invention is realized in the following manner: bortezomib slow releasing preparation, is characterized in usining that the quantum dot-labeled chitosan of carbon is as slow-released carrier.
The preparation method of above-mentioned slow releasing preparation comprises:
The hydroxyl generation esterification of the peptide boric acid root of bortezomib and chitosan obtains peptide boric acid ester, thus bortezomib is grafted to chitosan nano;
Carbon quantum dot carries out Electrostatic Absorption by the amino on chitosan in surperficial carboxyl and above-mentioned chitosan nano, thereby the load of carbon quantum dot is entered in chitosan nano system, make the chitosan nano bortezomib slow releasing preparation of absorption carbon quantum dot and coupling bortezomib.
Further, above-mentioned preparation method comprises the following steps:
(1) with appropriate acetic acid, add chitosan powder to dissolve, and then add methanol and dissolve, obtain chitosan methanol dispersion liquid;
(2) take a certain amount of bortezomib, under magnetic agitation and supersonic vibration jointly, add methanol to dissolve, then add step (1) gained chitosan methanol dispersion liquid, add pH value regulator, regulator solution, to alkalescence, carries out esterification, obtain the peptide boric acid ester based on bortezomib and chitosan, the bortezomib percent grafting of chitosan is 5 ~ 20 %;
(3) with Polyethylene Glycol, fully dissolve glucose, then proceed to microwave reactor reaction certain hour, make surperficial carboxylic carbon quantum dot;
(4) carbon quantum dot is dispersed in methanol, adds step (2) gained peptide boric acid ester, and electrostatic adsorption occurs, and makes the chitosan nano bortezomib slow releasing preparation of absorption carbon quantum dot and coupling bortezomib.
Described in step (1), the molecular weight of chitosan is 4 ~ 100,000, and the concentration of chitosan methanol dispersion liquid is 0.1 ~ 1 g/L.
In step (2), add pH value regulator, regulator solution pH is 9 ~ 12.Described pH value regulator is the nonpolar reagent of tetramethylammonium hydroxide series, as four hydration Tetramethylammonium hydroxide, and five hydration Tetramethylammonium hydroxide and six hydration Tetramethylammonium hydroxide etc.
In step (3), the polyglycol solution concentration of glucose is 40 ~ 1000 mg/mL, and the microwave reaction time is 1 ~ 10 min.
The molar concentration rate of the carbon quantum dot described in step (4) and peptide boric acid ester is 1:1 ~ 1:10.
Bortezomib slow releasing preparation of the present invention and preparation method thereof compared with prior art has following beneficial effect highlightedly:
(1) average-size of bortezomib slow releasing preparation (being carbon quantum dot-bortezomib-chitosan composite nano-granule) is 100 ~ 200 nm, there is biocompatibility, have no side effect, the character such as fluorescent tracing and pH sensitivity, at bio-sensing, bio-medical material, function nano material, especially the control release aspect of pharmaceutical carrier or preparation, has important Research Significance and using value;
(2) preparation method has the features such as feasible process, simple to operate, easy control of reaction system, and utilization is applied.
Accompanying drawing explanation
Accompanying drawing 1 is the schematic diagram of preparing of bortezomib (BTZ) and chitosan (Chitosan, CS) nano-complex;
Accompanying drawing 2 is the schematic diagram of preparing of bortezomib (BTZ)-chitosan (CS)-carbon quantum dot (Carbon quantum dot, CQD) nano-complex (BTZ-CS-CQD);
Accompanying drawing 3 is that the hydrodynamics distribution of sizes of BTZ-CS-CQD nanoparticle distributes and average-size;
Accompanying drawing 4 is engulfed for BTZ-CS-CQD nanoparticle the fluorescence imaging photo entering after L929 cell;
Accompanying drawing 5 discharges the concentration curve of BTZ for BTZ-CS-CQD nanoparticulate carriers under different pH.
The specific embodiment
With reference to Figure of description, with specific embodiment, bortezomib slow releasing preparation of the present invention and preparation method thereof is described in detail below.
If no special instructions, the content of following each composition used content that is weight percentage.
Embodiment mono-,
Bortezomib (BTZ)-chitosan (CS)-carbon quantum dot (CQD) composite nano-granule (BTZ-CS-CQD), be the preparation (preparation process is as shown in accompanying drawing 1,2) of bortezomib slow releasing preparation: first, take 50mg CS(molecular weight 40,000), dripping 2mL acetic acid dissolves, then add 98 mL absolute methanols to continue to dissolve, form the methanol dispersion liquid (0.5g/L) of CS.Then, add 10mg BTZ and fully dissolve, mixed liquor is warming up to 60 ℃, dropwise adding five hydration Tetramethylammonium hydroxide to regulate pH is 10, keeps magnetic agitation 1h, obtains BTZ percent grafting and be 10% CS nanoparticle.Then, with proceeding to microwave reactor after 5mL Polyethylene Glycol dissolving 1g glucose, under 540W power, react 5min, prepare CQD.Finally, in the methanol dispersion liquid of BTZ-CS nanoparticle (0.5g/L), add carbon quantum dot (0.1g/L), by Electrostatic Absorption, obtain BTZ-CS-CQD composite nano-granule.
Performance study:
Above-mentioned product, by bag filter dialysis, to remove unreacted monomer and impurity, is then prepared to certain concentration (0.1g/L) and is dispersed in phosphate buffer (pH7.4) standby.
Adopt dynamic light scattering to measure hydrodynamics size and the distribution of above-mentioned BTZ-CS-CQD composite nano-granule, average-size is 190.5nm and narrow distribution (as seen as shown in accompanying drawing 3); Adopt the fluorescence imaging photo after this nanoparticle of fluorescence microscope is engulfed by L929 cancerous cell, the fluorescent tracing ability (as shown in Figure 4) of the carbon quantum dot in confirmation nanoparticle in tumor cell; The BTZ concentration that adopts high effective liquid chromatography for measuring to discharge, studies this nanoparticle as the responsive releasing properties (as shown in Figure 5) of pH of BTZ preparation or carrier.
Embodiment bis-:
Bortezomib (BTZ)-chitosan (CS)-carbon quantum dot (CQD) composite nano-granule (BTZ-CS-CQD), be the preparation of bortezomib slow releasing preparation: first, take 40mg CS(molecular weight 60,000), dripping 2mL acetic acid dissolves, then add 98 mL absolute methanols to continue to dissolve, form the methanol dispersion liquid (0.4g/L) of CS.Then, add 10mg BTZ and fully dissolve, mixed liquor is warming up to 60 ℃, dropwise adding five hydration Tetramethylammonium hydroxide to regulate pH is 11, keeps magnetic agitation 1h, obtains BTZ percent grafting and be 5% CS nanoparticle.Then, with proceeding to microwave reactor after 10mL Polyethylene Glycol dissolving 2g glucose, under 540W power, react 5min, prepare CQD.Finally, in the methanol dispersion liquid of BTZ-CS nanoparticle (0.5g/L), add carbon quantum dot (0.2g/L), by Electrostatic Absorption, obtain BTZ-CS-CQD composite nano-granule.
The performance characterization of this nanoparticulate carriers and research method are all identical with embodiment mono-.
Embodiment tri-:
Bortezomib (BTZ)-chitosan (CS)-carbon quantum dot (CQD) composite nano-granule (BTZ-CS-CQD), be the preparation of bortezomib slow releasing preparation: first, take 80mg CS(molecular weight 80,000), dripping 2mL acetic acid dissolves, then add 98 mL absolute methanols to continue to dissolve, form the methanol dispersion liquid (0.8g/L) of CS.Then, add 10mg BTZ and fully dissolve, mixed liquor is warming up to 60 ℃, dropwise adding five hydration Tetramethylammonium hydroxide to regulate pH is 11, keeps magnetic agitation 1h, obtains BTZ percent grafting and be 15% CS nanoparticle.Then, with proceeding to microwave reactor after 15mL Polyethylene Glycol dissolving 3g glucose, under 540W power, react 5min, prepare CQD.Finally, in the methanol dispersion liquid of BTZ-CS nanoparticle (1.0g/L), add carbon quantum dot (0.2g/L), by Electrostatic Absorption, obtain BTZ-CS-CQD composite nano-granule.
The performance characterization of this nanoparticulate carriers and research method are all identical with embodiment mono-.
Embodiment tetra-:
Bortezomib (BTZ)-chitosan (CS)-carbon quantum dot (CQD) composite nano-granule (BTZ-CS-CQD), be the preparation of bortezomib slow releasing preparation: first, take 100mg CS(molecular weight 80,000), dripping 2mL acetic acid dissolves, then add 98 mL absolute methanols to continue to dissolve, form the methanol dispersion liquid (1.0g/L) of CS.Then, add 10mg BTZ and fully dissolve, mixed liquor is warming up to 60 ℃, dropwise adding five hydration Tetramethylammonium hydroxide to regulate pH is 12, keeps magnetic agitation 1h, obtains BTZ percent grafting and be 20% CS nanoparticle.Then, with proceeding to microwave reactor after 20mL Polyethylene Glycol dissolving 4g glucose, under 540W power, react 5min, prepare CQD.Finally, in the methanol dispersion liquid of BTZ-CS nanoparticle (1.0g/L), add carbon quantum dot (0.5g/L), by Electrostatic Absorption, obtain BTZ-CS-CQD composite nano-granule.
The performance characterization of this nanoparticulate carriers and research method are all identical with embodiment mono-.
Embodiment five:
Bortezomib (BTZ)-chitosan (CS)-carbon quantum dot (CQD) composite nano-granule (BTZ-CS-CQD), be the preparation of bortezomib slow releasing preparation: first, take 80mg CS(molecular weight 100,000), dripping 2mL acetic acid dissolves, then add 98 mL absolute methanols to continue to dissolve, form the methanol dispersion liquid (0.8g/L) of CS.Then, add 10mg BTZ and fully dissolve, mixed liquor is warming up to 60 ℃, dropwise adding five hydration Tetramethylammonium hydroxide to regulate pH is 11, keeps magnetic agitation 1h, obtains BTZ percent grafting and be 15% CS nanoparticle.Then, with proceeding to microwave reactor after 25mL Polyethylene Glycol dissolving 5g glucose, under 540W power, react 5min, prepare CQD.Finally, in the methanol dispersion liquid of BTZ-CS nanoparticle (1.0g/L), add carbon quantum dot (1.0g/L), by Electrostatic Absorption, obtain BTZ-CS-CQD composite nano-granule.
The performance characterization of this nanoparticulate carriers and research method are all identical with embodiment mono-.
Claims (10)
1. bortezomib slow releasing preparation, is characterized in that: said preparation is usingd the quantum dot-labeled chitosan of carbon as slow-released carrier, and its preparation method comprises:
The hydroxyl generation esterification of the peptide boric acid root of bortezomib and chitosan obtains peptide boric acid ester, thus bortezomib is grafted to chitosan nano;
Carbon quantum dot carries out Electrostatic Absorption by the amino on chitosan in surperficial carboxyl and above-mentioned chitosan nano, thereby the load of carbon quantum dot is entered in chitosan nano system, make the chitosan nano bortezomib slow releasing preparation of absorption carbon quantum dot and coupling bortezomib.
2. bortezomib slow releasing preparation according to claim 1, is characterized in that: the preparation method of said preparation comprises the following steps:
(1) with appropriate acetic acid, add chitosan powder to dissolve, and then add methanol and dissolve, obtain chitosan methanol dispersion liquid;
(2) take a certain amount of bortezomib, under magnetic agitation and supersonic vibration jointly, add methanol to dissolve, then add step (1) gained chitosan methanol dispersion liquid, add pH value regulator, regulator solution, to alkalescence, carries out esterification, obtains the peptide boric acid ester based on bortezomib and chitosan;
(3) with Polyethylene Glycol, fully dissolve glucose, then proceed to microwave reactor reaction certain hour, make surperficial carboxylic carbon quantum dot;
(4) carbon quantum dot is dispersed in methanol, adds step (2) gained peptide boric acid ester, and electrostatic adsorption occurs, and makes the chitosan nano bortezomib slow releasing preparation of absorption carbon quantum dot and coupling bortezomib.
3. bortezomib slow releasing preparation according to claim 2, is characterized in that: described in step (1), the molecular weight of chitosan is 4 ~ 100,000, and the concentration of chitosan methanol dispersion liquid is 0.1 ~ 1 g/L.
4. bortezomib slow releasing preparation according to claim 2, is characterized in that: in step (2), add pH value regulator, regulator solution pH is 9 ~ 12.
5. bortezomib slow releasing preparation according to claim 4, is characterized in that: described pH value regulator is the nonpolar reagent of tetramethylammonium hydroxide series.
6. bortezomib slow releasing preparation according to claim 2, is characterized in that: in step (3), the polyglycol solution concentration of glucose is 40 ~ 1000 mg/mL, and the microwave reaction time is 1 ~ 10 min.
7. bortezomib slow releasing preparation according to claim 1, is characterized in that: the molar concentration rate of the carbon quantum dot described in step (4) and peptide boric acid ester is 1:1 ~ 1:10.
8. the preparation method of bortezomib slow releasing preparation, is characterized in that: comprising:
The hydroxyl generation esterification of the peptide boric acid root of bortezomib and chitosan obtains peptide boric acid ester, thus bortezomib is grafted to chitosan nano;
Carbon quantum dot carries out Electrostatic Absorption by the amino on chitosan in surperficial carboxyl and above-mentioned chitosan nano, thereby the load of carbon quantum dot is entered in chitosan nano system, make the chitosan nano bortezomib slow releasing preparation of absorption carbon quantum dot and coupling bortezomib.
9. preparation method according to claim 8, is characterized in that: comprise the following steps:
(1) with appropriate acetic acid, add chitosan powder to dissolve, and then add methanol and dissolve, obtain chitosan methanol dispersion liquid;
(2) take a certain amount of bortezomib, under magnetic agitation and supersonic vibration jointly, add methanol to dissolve, then add step (1) gained chitosan methanol dispersion liquid, add pH value regulator, regulator solution, to alkalescence, carries out esterification, obtains the peptide boric acid ester based on bortezomib and chitosan;
(3) with Polyethylene Glycol, fully dissolve glucose, then proceed to microwave reactor reaction certain hour, make surperficial carboxylic carbon quantum dot;
(4) carbon quantum dot is dispersed in methanol, adds step (2) gained peptide boric acid ester, and electrostatic adsorption occurs, and makes the chitosan nano bortezomib slow releasing preparation of absorption carbon quantum dot and coupling bortezomib.
10. preparation method according to claim 9, is characterized in that:
Described in step (1), the molecular weight of chitosan is 4 ~ 100,000, and the concentration of chitosan methanol dispersion liquid is 0.1 ~ 1 g/L;
In step (2), add pH value regulator, regulator solution pH is 9 ~ 12, and described pH value regulator is the nonpolar reagent of tetramethylammonium hydroxide series;
In step (3), the polyglycol solution concentration of glucose is 40 ~ 1000 mg/mL, and the microwave reaction time is 1 ~ 10 min;
The molar concentration rate of the carbon quantum dot described in step (4) and peptide boric acid ester is 1:1 ~ 1:10.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104958769A (en) * | 2015-07-17 | 2015-10-07 | 中国科学院长春应用化学研究所 | Oxidized dextran-bortezomib-adriamycin bonded chemical and preparation method thereof |
| CN104958768A (en) * | 2015-07-17 | 2015-10-07 | 中国科学院长春应用化学研究所 | Glucosan-bortezomib bonding medicine and preparation method thereof |
| CN105462583A (en) * | 2015-11-03 | 2016-04-06 | 南京工业大学 | Preparation method and application of ethanol solution containing fluorescent nano-carbon quantum dots |
| CN109045272A (en) * | 2018-08-01 | 2018-12-21 | 厦门市壳聚糖生物科技有限公司 | A kind of bortezomib phosphatide complexes and the preparation method and application thereof |
| CN109758666A (en) * | 2018-05-22 | 2019-05-17 | 蔡毓旻 | A kind of equipment of adjuvant therapy rheumatoid arthritis |
| CN110492175A (en) * | 2019-08-13 | 2019-11-22 | 中北大学 | All solid state alkali metal battery organic nano composite electrolyte membrane and preparation method thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8137697B1 (en) * | 2004-10-05 | 2012-03-20 | Gp Medical, Inc. | Nanoparticles for protein/peptide delivery and delivery means thereof |
| CN102516606A (en) * | 2011-11-25 | 2012-06-27 | 上海交通大学 | Preparation method of nitrogen oxide donor - quantum dots compound |
| CN102698294A (en) * | 2012-06-28 | 2012-10-03 | 天津城市建设学院 | Chitosan-supported hydroxycamptothecine-quantum dot FRET (Fluorescence Resonance Energy Transfer) composite probe |
| CN102973948A (en) * | 2012-12-03 | 2013-03-20 | 上海交通大学 | Method for preparing drug carrier based on magnetic carbon quantum dot/chitosan composite microsphere |
| CN103224654A (en) * | 2013-05-02 | 2013-07-31 | 上海交通大学 | Silver sulfide quantum dot-chitosan nanometer complex preparation method |
-
2013
- 2013-12-06 CN CN201310646984.6A patent/CN103656668B/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8137697B1 (en) * | 2004-10-05 | 2012-03-20 | Gp Medical, Inc. | Nanoparticles for protein/peptide delivery and delivery means thereof |
| CN102516606A (en) * | 2011-11-25 | 2012-06-27 | 上海交通大学 | Preparation method of nitrogen oxide donor - quantum dots compound |
| CN102698294A (en) * | 2012-06-28 | 2012-10-03 | 天津城市建设学院 | Chitosan-supported hydroxycamptothecine-quantum dot FRET (Fluorescence Resonance Energy Transfer) composite probe |
| CN102973948A (en) * | 2012-12-03 | 2013-03-20 | 上海交通大学 | Method for preparing drug carrier based on magnetic carbon quantum dot/chitosan composite microsphere |
| CN103224654A (en) * | 2013-05-02 | 2013-07-31 | 上海交通大学 | Silver sulfide quantum dot-chitosan nanometer complex preparation method |
Non-Patent Citations (1)
| Title |
|---|
| KEN-TYE YONG ET AL.: "Preparation of Quantum Dot/Drug Nanoparticle Formulations for Traceable Targeted Delivery and Therapy", 《THERANOSTICS》, vol. 2, no. 7, 27 July 2012 (2012-07-27), pages 681 - 694 * |
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| CN104958769A (en) * | 2015-07-17 | 2015-10-07 | 中国科学院长春应用化学研究所 | Oxidized dextran-bortezomib-adriamycin bonded chemical and preparation method thereof |
| CN104958768A (en) * | 2015-07-17 | 2015-10-07 | 中国科学院长春应用化学研究所 | Glucosan-bortezomib bonding medicine and preparation method thereof |
| CN105462583A (en) * | 2015-11-03 | 2016-04-06 | 南京工业大学 | Preparation method and application of ethanol solution containing fluorescent nano-carbon quantum dots |
| CN109758666A (en) * | 2018-05-22 | 2019-05-17 | 蔡毓旻 | A kind of equipment of adjuvant therapy rheumatoid arthritis |
| CN109045272A (en) * | 2018-08-01 | 2018-12-21 | 厦门市壳聚糖生物科技有限公司 | A kind of bortezomib phosphatide complexes and the preparation method and application thereof |
| CN110492175A (en) * | 2019-08-13 | 2019-11-22 | 中北大学 | All solid state alkali metal battery organic nano composite electrolyte membrane and preparation method thereof |
| CN110492175B (en) * | 2019-08-13 | 2020-12-15 | 中北大学 | Organic nano composite electrolyte membrane for all-solid-state alkali metal battery and preparation method thereof |
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