HRP20211649T1 - Postupak analize glikozaminoglikana, heparina i njihovih derivata nuklearnom magnetskom rezonancijom - Google Patents
Postupak analize glikozaminoglikana, heparina i njihovih derivata nuklearnom magnetskom rezonancijom Download PDFInfo
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- 238000000034 method Methods 0.000 title claims 16
- 229920000669 heparin Polymers 0.000 title claims 9
- 238000005481 NMR spectroscopy Methods 0.000 title claims 6
- 229960002897 heparin Drugs 0.000 title claims 6
- 238000004458 analytical method Methods 0.000 title claims 3
- 229920002683 Glycosaminoglycan Polymers 0.000 title 1
- 150000002772 monosaccharides Chemical group 0.000 claims 12
- 238000004701 1H-13C HSQC Methods 0.000 claims 7
- 238000005160 1H NMR spectroscopy Methods 0.000 claims 6
- 239000002253 acid Substances 0.000 claims 6
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical group OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims 5
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 claims 5
- DQTRACMFIGDHSN-IVMDWMLBSA-N [(3r,4r,5s,6r)-2,4,5-trihydroxy-6-(sulfooxymethyl)oxan-3-yl]sulfamic acid Chemical compound OC1O[C@H](COS(O)(=O)=O)[C@@H](O)[C@H](O)[C@H]1NS(O)(=O)=O DQTRACMFIGDHSN-IVMDWMLBSA-N 0.000 claims 4
- OREAFAJWWJHCOT-UHFFFAOYSA-N dimethylmalonic acid Chemical compound OC(=O)C(C)(C)C(O)=O OREAFAJWWJHCOT-UHFFFAOYSA-N 0.000 claims 4
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 claims 4
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 claims 3
- FYHXSAVCFOFVPI-IVMDWMLBSA-N [(1R,2S,3R,4R)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]octan-4-yl]sulfamic acid Chemical compound O1C2OC[C@]1([H])[C@@H](O)[C@H](O)[C@H]2NS(O)(=O)=O FYHXSAVCFOFVPI-IVMDWMLBSA-N 0.000 claims 3
- FYHXSAVCFOFVPI-CBPJZXOFSA-N [(1R,2S,3R,4S)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]octan-4-yl]sulfamic acid Chemical compound O1C2OC[C@]1([H])[C@@H](O)[C@H](O)[C@@H]2NS(O)(=O)=O FYHXSAVCFOFVPI-CBPJZXOFSA-N 0.000 claims 3
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 claims 2
- 229940110519 bemiparin sodium Drugs 0.000 claims 2
- 229940018872 dalteparin sodium Drugs 0.000 claims 2
- 229960005153 enoxaparin sodium Drugs 0.000 claims 2
- 239000003055 low molecular weight heparin Substances 0.000 claims 2
- 229940127215 low-molecular weight heparin Drugs 0.000 claims 2
- CIJQTPFWFXOSEO-NDMITSJXSA-J tetrasodium;(2r,3r,4s)-2-[(2r,3s,4r,5r,6s)-5-acetamido-6-[(1r,2r,3r,4r)-4-[(2r,3s,4r,5r,6r)-5-acetamido-6-[(4r,5r,6r)-2-carboxylato-4,5-dihydroxy-6-[[(1r,3r,4r,5r)-3-hydroxy-4-(sulfonatoamino)-6,8-dioxabicyclo[3.2.1]octan-2-yl]oxy]oxan-3-yl]oxy-2-(hydroxy Chemical compound [Na+].[Na+].[Na+].[Na+].O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1O)NC(C)=O)O[C@@H]1C(C[C@H]([C@@H]([C@H]1O)O)O[C@@H]1[C@@H](CO)O[C@H](OC2C(O[C@@H](OC3[C@@H]([C@@H](NS([O-])(=O)=O)[C@@H]4OC[C@H]3O4)O)[C@H](O)[C@H]2O)C([O-])=O)[C@H](NC(C)=O)[C@H]1C)C([O-])=O)[C@@H]1OC(C([O-])=O)=C[C@H](O)[C@H]1O CIJQTPFWFXOSEO-NDMITSJXSA-J 0.000 claims 2
- 229940064689 tinzaparin sodium Drugs 0.000 claims 2
- MCHWWJLLPNDHGL-KVTDHHQDSA-N (2r,3s,4s,5r)-2,5-bis(hydroxymethyl)oxolane-3,4-diol Chemical compound OC[C@H]1O[C@H](CO)[C@@H](O)[C@@H]1O MCHWWJLLPNDHGL-KVTDHHQDSA-N 0.000 claims 1
- PURMPUDWXOWORS-LECHCGJUSA-N (2s,3r,4r,5s)-2,3,4-trihydroxy-6-oxo-5-sulfooxyhexanoic acid Chemical compound OC(=O)[C@@H](O)[C@H](O)[C@@H](O)[C@H](OS(O)(=O)=O)C=O PURMPUDWXOWORS-LECHCGJUSA-N 0.000 claims 1
- AEMOLEFTQBMNLQ-YMDCURPLSA-N D-galactopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-YMDCURPLSA-N 0.000 claims 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 claims 1
- AEMOLEFTQBMNLQ-HNFCZKTMSA-N L-idopyranuronic acid Chemical compound OC1O[C@@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-HNFCZKTMSA-N 0.000 claims 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 claims 1
- 125000003047 N-acetyl group Chemical group 0.000 claims 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 claims 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 claims 1
- AJBMJMMLWNUEAC-IVMDWMLBSA-N OC[C@H]1OC(O)[C@H](NS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@@H]1O Chemical compound OC[C@H]1OC(O)[C@H](NS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@@H]1O AJBMJMMLWNUEAC-IVMDWMLBSA-N 0.000 claims 1
- KZWHEHSUEBTKJM-SLPGGIOYSA-N [(2r,3r,4s,5r)-3,4,5,6-tetrahydroxy-1-oxohexan-2-yl]sulfamic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](C=O)NS(O)(=O)=O KZWHEHSUEBTKJM-SLPGGIOYSA-N 0.000 claims 1
- WJFVEEAIYIOATH-RTRLPJTCSA-N [(2r,3s,4r,5r)-5-acetamido-3,4,6-trihydroxyoxan-2-yl]methyl hydrogen sulfate Chemical compound CC(=O)N[C@H]1C(O)O[C@H](COS(O)(=O)=O)[C@@H](O)[C@@H]1O WJFVEEAIYIOATH-RTRLPJTCSA-N 0.000 claims 1
- VPSCBZXJXYLJOH-IVMDWMLBSA-N [(3R,4R,5R,6R)-2,5-dihydroxy-4-sulfooxy-6-(sulfooxymethyl)oxan-3-yl]sulfamic acid Chemical compound OC1O[C@H](COS(O)(=O)=O)[C@@H](O)[C@H](OS(O)(=O)=O)[C@H]1NS(O)(=O)=O VPSCBZXJXYLJOH-IVMDWMLBSA-N 0.000 claims 1
- 150000007513 acids Chemical class 0.000 claims 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 claims 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 claims 1
- 150000001720 carbohydrates Chemical group 0.000 claims 1
- 229940097043 glucuronic acid Drugs 0.000 claims 1
- 229950006780 n-acetylglucosamine Drugs 0.000 claims 1
- 238000011002 quantification Methods 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 238000002495 two-dimensional nuclear magnetic resonance spectrum Methods 0.000 claims 1
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N24/00—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects
- G01N24/08—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects by using nuclear magnetic resonance
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N24/00—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects
- G01N24/08—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects by using nuclear magnetic resonance
- G01N24/087—Structure determination of a chemical compound, e.g. of a biomolecule such as a protein
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R33/00—Arrangements or instruments for measuring magnetic variables
- G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
- G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
- G01R33/46—NMR spectroscopy
- G01R33/4625—Processing of acquired signals, e.g. elimination of phase errors, baseline fitting, chemometric analysis
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R33/00—Arrangements or instruments for measuring magnetic variables
- G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
- G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
- G01R33/46—NMR spectroscopy
- G01R33/4633—Sequences for multi-dimensional NMR
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- Pathology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Signal Processing (AREA)
- Medicinal Chemistry (AREA)
- Food Science & Technology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Investigating Or Analysing Biological Materials (AREA)
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Claims (15)
1. Postupak analize pripravka koji sadrži monosaharidne ostatke prisutne u heparinskim lancima 1H-NMR jednodimenzionalnom nuklearnom magnetskom rezonancijom i/ili 1H-13C HSQC dvodimenzionalnom nuklearnom magnetskom rezonancijom koja se sastoji u koracima:
a) osiguravanja pripravka koji sadrži najmanje jedan monosaharidni ostatak prisutan u heparinskim lancima i dobivanja njegovog spektra 1H-NMR jednodimenzionalne nuklearne magnetske rezonancije i/ili 1H-13C HSQC dvodimenzionalne nuklearne magnetske rezonancije uz upotrebu dimetilmalonske kiseline (DMMA) kao unutarnje reference i D2O kao otapala, te
b) identificiranja u NMR spektru prisutnosti ili odsutnosti najmanje jednog signala iz najmanje jednog ostatka kojeg se bira iz skupine koju čine: 4,5-nezasićena 2-O-sulfo uronska kiselina (ΔU2S), 4,5-nezasićena uronska kiselina (ΔU), 2-N-sulfo-1,6-anhidroglukozamin (1,6-an.A), 2-N-sulfo-1,6-anhidromanozamin (1,6-an.M), 2-N-sulfo-6-O-sulfoglukozamin (ANS6S), 2,5-anhidromanitol, N-sulfoglukozamin, glukuronska kiselina, N-sulfo-6-O-sulfoglukozamin, 2-O-sulfoiduronska kiselina, iduronska kiselina, N-sulfo-3-O-sulfoglukozamin, N-sulfo-3,6-di-O-sulfoglukozamin, galakturonska kiselina, ksiloza, N-acetilglukozamin i N-acetil-6-O-sulfoglukozamin,
naznačen time što prisutnost navedenih NMR signala u određenom relativnom udjelu njihovih normaliziranih integrala u odnosu na DMMA, ili njihova odsutnost, čini uzorak koji omogućuje identificiranje heparina iz kojeg dolazi monosaharidni ostatak usporedbom uzorka dobivenog analizom sa standardnim uzorkom dobivenim ranije za različite heparine u istim uvjetima.
2. Postupak u skladu s patentnim zahtjevom 1, naznačen time što dodatno uključuje:
c) dobivanje normalizirane vrijednosti integrala maksimuma svakog pojedinog od ostataka dijeljenjem vrijednosti integrala maksimuma svakog ostatka s vrijednošću integrala maksimuma za DMMA, te
d) izračunavanje relativnog postotka za svaki pojedini od ostataka prema formuli:
[image]
3. Postupak u skladu s patentnim zahtjevom 1 ili 2, naznačen time što je sljedeći uzorak identificiran u 1H-NMR spektru:
[image]
čime određuje da monosaharidni ostaci dolaze iz enoksaparin-natrija.
4. Postupak u skladu s patentnim zahtjevom 1 ili 2, naznačen time što je sljedeći uzorak identificiran u 1H-13C HSQC NMR spektru:
[image]
gdje je "LC" "granica kvantificiranja",
čime određuje da monosaharidni ostaci dolaze iz enoksaparin-natrija.
5. Postupak u skladu s patentnim zahtjevom 1 ili 2, naznačen time što je sljedeći uzorak identificiran u 1H-NMR spektru:
[image]
čime određuje da monosaharidni ostaci dolaze iz bemiparin-natrija.
6. Postupak u skladu s patentnim zahtjevom 1 ili 2, naznačen time što je sljedeći uzorak identificiran u 1H-13C HSQC NMR spektru:
[image]
čime određuje da monosaharidni ostaci dolaze iz bemiparin-natrija.
7. Postupak u skladu s patentnim zahtjevom 1 ili 2, naznačen time što je sljedeći uzorak identificiran u 1H-NMR spektru:
[image]
čime određuje da monosaharidni ostaci dolaze iz dalteparin-natrija.
8. Postupak u skladu s patentnim zahtjevom 1 ili 2, naznačen time što je sljedeći uzorak identificiran u 1H-13C HSQC NMR spektru:
[image]
čime određuje da monosaharidni ostaci dolaze iz dalteparin-natrija.
9. Postupak u skladu s patentnim zahtjevom 1 ili 2, naznačen time što je sljedeći uzorak identificiran u 1H-NMR spektru:
[image]
čime određuje da monosaharidni ostaci dolaze iz tinzaparin-natrija, ili
što je sljedeći uzorak identificiran u 1H-13C HSQC NMR spektru:
[image]
čime određuje da monosaharidni ostaci dolaze iz tinzaparin-natrija.
10. Postupak u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što se signali koji odgovaraju N-acetilnim skupinama pojavljuju u području između 1,8 i 2,1 ppm kod 1H-NMR spektroskopije.
11. Postupak u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što se signali koji odgovaraju saharidnom prstenu navedenih ostataka pojavljuju u području između 2,8 i 6,0 ppm kod 1H-NMR spektroskopije.
12. Postupak u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što se signali koji odgovaraju anomernim protonima H1, te protonima H4 nereducirajućih krajeva jednog od navedenih ostataka, pojavljuju u području između 4,6 i 6,0 ppm kod 1H-NMR spektroskopije.
13. Postupak u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što se, kod 1H-NMR spektroskopije, signali iz 4,5-nezasićene 2-O-sulfo uronske kiselina (ΔU2S) pojavljuju kod 5,99 i 5,51 ppm, za H4 odnosno anomerni proton, signal iz 4,5-nezasićene uronske kiseline (ΔU) se pojavljuje kod 5,82 ppm za proton H4, signal iz 2-N-sulfo-1,6-anhidroglukozamina (1,6-an.A) se pojavljuje kod 5,62 ppm za anomerni proton, signal iz 2-N-sulfo-1,6-anhidromanozamina (1,6-an.M) se pojavljuje kod 5,57 ppm za anomerni proton, a signali iz 2-N-sulfo-6-O-sulfoglukozamin se pojavljuju kod 5,41 i 4,21-4,34 ppm za proton H1 i H6 odnosno H6’.
14. Postupak u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što se, kod 1H-13C HSQC NMR spektroskopije, signali iz 4,5-nezasićene 2-O-sulfo uronska kiselina (ΔU2S) pojavljuju kod 6,0-109,0 ppm (H4-C4), 5,5-100,2 ppm (H1-C1), 4,6-77,4 ppm (H2-C2) ili 4,3-66,8 ppm (H3-C3), signali iz 4,5-nezasićene uronske kiselina (ΔU) se pojavljuju kod 5,8-110,7 ppm (H4-C4) ili 5,2-103,9 ppm (H1-C1), signali iz 2-N-sulfo-1,6-anhidroglukozamina (1,6-an.A) se pojavljuju kod 5,6-104,2 ppm (H1-C1), 3,2-58,5 ppm (H2-C2) ili 3,8-67,5 ppm (H6-C6), signali iz 2-N-sulfo-1,6-anhidromanozamina (1,6-an.M) se pojavljuju kod 5,6-103,9 ppm (H1-C1), 3,5-55,1 (H2-C2) ili 3,8-67,5 ppm (H6-C6), a signali iz 2-N-sulfo-6-O-sulfoglukozamina se pojavljuju kod 5,4-99,4 ppm (H1-C1), 3,8-80,9 ppm (H4-C4), 3,7 do 3,8-42,3 do 72,5 ppm (H3-C3), 4,1-70,6 do 71,7 ppm (H5-C5) ili 3,3-60,5-60,8 ppm (H2-C2).
15. Postupak u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što uzorak dobiven analizom određuje da monosaharidni ostaci dolaze iz nefrakcioniranog heparina, iz niskomolekulskog heparina (LMWH) ili iz ultraniskomolekulskog heparina (ULMWH).
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP16382350.3A EP3273239A1 (en) | 2016-07-19 | 2016-07-19 | Procedure of analysis of glycosaminoglycans, heparins and their derivatives by nuclear magnetic resonance |
| PCT/EP2017/068285 WO2018015463A1 (en) | 2016-07-19 | 2017-07-19 | Method for the analysis of glycosaminoglycans, heparins and their derivatives by nuclear magnetic resonance |
| EP17749132.1A EP3452827B1 (en) | 2016-07-19 | 2017-07-19 | Method for the analysis of glycosaminoglycans, heparins and their derivatives by nuclear magnetic resonance |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20211649T1 true HRP20211649T1 (hr) | 2022-02-04 |
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| Application Number | Title | Priority Date | Filing Date |
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| HRP20211649TT HRP20211649T1 (hr) | 2016-07-19 | 2017-07-19 | Postupak analize glikozaminoglikana, heparina i njihovih derivata nuklearnom magnetskom rezonancijom |
Country Status (27)
| Country | Link |
|---|---|
| US (2) | US10705037B2 (hr) |
| EP (2) | EP3273239A1 (hr) |
| JP (1) | JP7035007B2 (hr) |
| CN (1) | CN109477829B (hr) |
| AR (1) | AR109099A1 (hr) |
| AU (1) | AU2017299186C1 (hr) |
| BR (1) | BR112019000437A2 (hr) |
| CA (1) | CA3029924A1 (hr) |
| CL (1) | CL2019000038A1 (hr) |
| CO (1) | CO2019000087A2 (hr) |
| CR (1) | CR20190016A (hr) |
| CY (1) | CY1124817T1 (hr) |
| DK (1) | DK3452827T3 (hr) |
| DO (1) | DOP2019000003A (hr) |
| EA (1) | EA037102B1 (hr) |
| ES (1) | ES2894898T3 (hr) |
| HR (1) | HRP20211649T1 (hr) |
| HU (1) | HUE056604T2 (hr) |
| LT (1) | LT3452827T (hr) |
| MA (1) | MA44876A (hr) |
| PL (1) | PL3452827T3 (hr) |
| PT (1) | PT3452827T (hr) |
| SI (1) | SI3452827T1 (hr) |
| UA (1) | UA124466C2 (hr) |
| UY (1) | UY37337A (hr) |
| WO (1) | WO2018015463A1 (hr) |
| ZA (1) | ZA201900143B (hr) |
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| CN112816566A (zh) * | 2019-11-17 | 2021-05-18 | 烟台东诚药业集团股份有限公司 | 一种那屈肝素钙末端结构确认方法 |
| CN111337529B (zh) * | 2020-03-12 | 2023-06-16 | 青岛科技大学 | 一种降低粘度、使水峰偏移的多糖样品制备和测试方法 |
| JP7377937B2 (ja) * | 2021-10-20 | 2023-11-10 | シオノギヘルスケア株式会社 | オリゴ糖の還元末端糖の定量的分析方法 |
| CN117990732B (zh) * | 2024-04-02 | 2024-06-25 | 浙江大学 | 一种基于分离的分段同源多糖组的多糖结构解析方法 |
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| WO2014204929A2 (en) * | 2013-06-17 | 2014-12-24 | The University Of North Carolina At Chapel Hill | Reversible heparin molecules and methods of making and using the same |
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