Abstract: The present invention provides a novel sulfated polysaccharide having an anticoagulant activity. Specifically, the present invention provides the polysaccharide comprising a repetitive structure of a disaccharide unit composed of a hexuronic acid (HexA) residue and a a-D-glucosamine (GlcN) residue and having 13% or higher of a 3-0-sulfation rate in GlcN residues.
1. A polysaccharide having an anticoagulant activity, comprising a repetitive structure of a disaccharide unit shown in a following general formula (I): wherein Ri to R5 meet following conditions; Ri, R2, R4 and R5 each independently represent a hydrogen or a sulfate group; R3 represents a hydrogen, a sulfate group or an acetyl group; at least a part of R3 is a sulfate group; a rate of the sulfate group in R4 is 13% or more; and a rate of the sulfate group in R5 is 50% or more.
2. The polysaccharide according to claim 1, wherein a content rate of said disaccharide unit is 90% or more.
3. The polysaccharide according to claim 1 or 2, wherein 50% or more sugar chains in total number of sugar chains that constitute said polysaccharide are composed of a structure shown in a following general formula (II): wherein Ri to R5 are the same as Ri to R5 in said general formula (I); and n is 3 to 30 as an average value.
4. The polysaccharide according to any one of claims 1 to 3, wherein 50% or more sugar chains in total number of sugar chains that constitute said polysaccharide are composed of a structure shown in a following general formula (II): wherein Ri to R5 are the same as Ri to R5 in said general formula (I); and n is 3 to 15 as the average value.
5. The polysaccharide according to any one of claims 1 to 4, wherein an average number of linked sugar residues is 6 to 60.
6. The polysaccharide according to any one of claims 1 to 5, wherein an average number of linked sugar residues is 6 to 30.
7. The polysaccharide according to any one of claims 1 to 6, wherein a number average molecular weight measured by gel permeation chromatography using pullulan as a standard is 8000 to 60000.
8. The polysaccharide according to any one of claims 1 to 7, wherein a number average molecular weight measured by gel permeation chromatography using pullulan as a standard is 12000 to 40000.
9. The polysaccharide according to any one of claims 1 to 8, wherein a weight average molecular weight measured by gel permeation chromatography using pullulan as a standard is 10000 to 100000.
10. The polysaccharide according to any one of claims 1 to 9, wherein a weight average molecular weight measured by gel permeation chromatography using pullulan as a standard is 15000 to 50000.
11. The polysaccharide according to any one of claims 1 to 10, wherein a rate of iduronic acid residues in hexuronic acid residues in said disaccharide unit is 0% to 70%.
12. The polysaccharide according to any one of claims 1 to 11, wherein a rate of a sulfate group in Ri is 0% to 80%.
13. The polysaccharide according to any one of claims 1 to 12, wherein a rate of a sulfate group in Ri in a iduronic acid residues 0% to 100%.
14. The polysaccharide according to any one of claims 1 to 13, wherein a rate of a sulfate group in Ri in glucuronic acid residues 0% to 50%.
15. The polysaccharide according to any one of claims 1 to 14, wherein a rate of a sulfate group in R2 is less than 1%.
16. The polysaccharide according to any one of claims 1 to 15, wherein a rate of a sulfate group in R3 is 70% to 100%.
17. The polysaccharide according to any one of claims 1 to 16, wherein a rate of a acetyl group in R3 is 0 to 33%.
18. The polysaccharide according to any one of claims 1 to 17, wherein a rate of a sulfate group in R4 is 45% or less.
19. The polysaccharide according to any one of claims 1 to 18, wherein a rate of a sulfate group in R5 is 70% to 100%.
20. The polysaccharide according to any one of claims 1 to 19, comprising one or more disaccharide units selected from GlcA-GlcN(NS3S6S), GlcA(2S)-GlcN(NS6S), IdoA(2S)-GlcN(NS6S) , GlcA-GlcN(NS6S), IdoA(2S)-GlcN(NS), IdoA(2S)-GlcN(NS3S) , IdoA-GlcN(NS6S), and GlcA-GlcN(NS) at a total content rate of 50% or more.
21. The polysaccharide according to any one of claims 1 to 20, wherein a ratio of anti-factor Xa activity/anti-factor Ila activity is 1.5 or more.
22. The polysaccharide according to any one of claims 1 to 21, wherein a ratio (Mw/Mn) of a weight average molecular weight (Mw) to a number average molecular weight (Mn) measured by gel permeation chromatography using pullulan as a standard is 1.5 or less.
23. The polysaccharide according to any one of claims 1 to 22, which is a free form, or a pharmacologically acceptable salt, or a mixture thereof.
24. The polysaccharide according to any one of claims 1 to 23, which said salt is selected from an ammonium salt, a sodium salt, a lithium salt, and a calcium salt.
25. A pharmaceutical composition comprising the polysaccharide according to any one of claims 1 to 24.
26. The composition according to claim 25, which is used for prevention, amelioration and/or treatment of a symptom attributed to blood coagulation.
27. The composition according to claim 26, wherein said symptom is disseminated intravascular coagulation syndrome, thrombotic embolism, blood coagulation in artificial dialysis or blood coagulation in extracorporeal circulation.
WE CLAIM:
1. A polysaccharide having an anticoagulant activity,
comprising a repetitive structure of a disaccharide unit
shown in a following general formula (I):
wherein
Ri to R5 meet following conditions;
Ri, R2, R4 and R5 each independently represent a hydrogen or
a sulfate group;
R3 represents a hydrogen, a sulfate group or an acetyl
group;
at least a part of R3 is a sulfate group;
a rate of the sulfate group in R4 is 13% or more; and
a rate of the sulfate group in R5 is 50% or more.
2. The polysaccharide according to claim 1, wherein a content rate of said disaccharide unit is 90% or more.
3. The polysaccharide according to claim 1 or 2, wherein 50% or more sugar chains in total number of sugar chains that constitute said polysaccharide are composed of a structure shown in a following general formula (II):
wherein
Ri to R5 are the same as Ri to R5 in said general formula
(I); and
n is 3 to 30 as an average value.
4. The polysaccharide according to any one of claims 1 to 3, wherein 50% or more sugar chains in total number of sugar chains that constitute said polysaccharide are composed of a structure shown in a following general formula (II):
wherein
Ri to R5 are the same as Ri to R5 in said general formula
(I); and
n is 3 to 15 as the average value.
5. The polysaccharide according to any one of claims 1 to
4, wherein an average number of linked sugar residues is 6
to 60.
6. The polysaccharide according to any one of claims 1 to
5, wherein an average number of linked sugar residues is 6
to 30.
7. The polysaccharide according to any one of claims 1 to
6, wherein a number average molecular weight measured by
gel permeation chromatography using pullulan as a standard
is 8000 to 60000.
8. The polysaccharide according to any one of claims 1 to
7, wherein a number average molecular weight measured by
gel permeation chromatography using pullulan as a standard
is 12000 to 40000.
9. The polysaccharide according to any one of claims 1 to
8, wherein a weight average molecular weight measured by
gel permeation chromatography using pullulan as a standard
is 10000 to 100000.
10. The polysaccharide according to any one of claims 1 to
9, wherein a weight average molecular weight measured by
gel permeation chromatography using pullulan as a standard
is 15000 to 50000.
11. The polysaccharide according to any one of claims 1 to
10, wherein a rate of iduronic acid residues in hexuronic
acid residues in said disaccharide unit is 0% to 70%.
12. The polysaccharide according to any one of claims 1 to
11, wherein a rate of a sulfate group in Ri is 0% to 80%.
13. The polysaccharide according to any one of claims 1 to
12, wherein a rate of a sulfate group in Ri in a iduronic
acid residues 0% to 100%.
14. The polysaccharide according to any one of claims 1 to
13, wherein a rate of a sulfate group in Ri in glucuronic
acid residues 0% to 50%.
15. The polysaccharide according to any one of claims 1 to
14, wherein a rate of a sulfate group in R2 is less than 1%.
16. The polysaccharide according to any one of claims 1 to
15, wherein a rate of a sulfate group in R3 is 70% to 100%.
17. The polysaccharide according to any one of claims 1 to
16, wherein a rate of a acetyl group in R3 is 0 to 33%.
18. The polysaccharide according to any one of claims 1 to
17, wherein a rate of a sulfate group in R4 is 45% or less.
19. The polysaccharide according to any one of claims 1 to
18, wherein a rate of a sulfate group in R5 is 70% to 100%.
20. The polysaccharide according to any one of claims 1 to
19, comprising one or more disaccharide units selected from
GlcA-GlcN(NS3S6S), GlcA(2S)-GlcN(NS6S), IdoA(2S)-GlcN(NS6S) ,
GlcA-GlcN(NS6S), IdoA(2S)-GlcN(NS), IdoA(2S)-GlcN(NS3S) ,
IdoA-GlcN(NS6S), and GlcA-GlcN(NS) at a total content rate
of 50% or more.
21. The polysaccharide according to any one of claims 1 to
20, wherein a ratio of anti-factor Xa activity/anti-factor
Ila activity is 1.5 or more.
22. The polysaccharide according to any one of claims 1 to
21, wherein a ratio (Mw/Mn) of a weight average molecular
weight (Mw) to a number average molecular weight (Mn)
measured by gel permeation chromatography using pullulan as
a standard is 1.5 or less.
23. The polysaccharide according to any one of claims 1 to
22, which is a free form, or a pharmacologically acceptable
salt, or a mixture thereof.
24. The polysaccharide according to any one of claims 1 to
23, which said salt is selected from an ammonium salt, a
sodium salt, a lithium salt, and a calcium salt.
25. A pharmaceutical composition comprising the polysaccharide according to any one of claims 1 to 24.
26. The composition according to claim 25, which is used for prevention, amelioration and/or treatment of a symptom attributed to blood coagulation.
27. The composition according to claim 26, wherein said symptom is disseminated intravascular coagulation syndrome, thrombotic embolism, blood coagulation in artificial dialysis or blood coagulation in extracorporeal circulation.
| # | Name | Date |
|---|---|---|
| 1 | 201847027122-TRANSLATIOIN OF PRIOIRTY DOCUMENTS ETC. [20-07-2018(online)].pdf | 2018-07-20 |
| 2 | 201847027122-STATEMENT OF UNDERTAKING (FORM 3) [20-07-2018(online)].pdf | 2018-07-20 |
| 3 | 201847027122-SEQUENCE LISTING(PDF) [20-07-2018(online)].pdf | 2018-07-20 |
| 4 | 201847027122-SEQUENCE LISTING [20-07-2018(online)].txt | 2018-07-20 |
| 5 | 201847027122-PROOF OF RIGHT [20-07-2018(online)].pdf | 2018-07-20 |
| 6 | 201847027122-PRIORITY DOCUMENTS [20-07-2018(online)].pdf | 2018-07-20 |
| 7 | 201847027122-POWER OF AUTHORITY [20-07-2018(online)].pdf | 2018-07-20 |
| 8 | 201847027122-FORM 1 [20-07-2018(online)].pdf | 2018-07-20 |
| 9 | 201847027122-DECLARATION OF INVENTORSHIP (FORM 5) [20-07-2018(online)].pdf | 2018-07-20 |
| 10 | 201847027122-COMPLETE SPECIFICATION [20-07-2018(online)].pdf | 2018-07-20 |
| 11 | 201847027122-CLAIMS UNDER RULE 1 (PROVISIO) OF RULE 20 [20-07-2018(online)].pdf | 2018-07-20 |
| 12 | Correspondence by Agent_Form 1_02-08-2018.pdf | 2018-08-02 |
| 13 | 201847027122-FORM 3 [20-11-2018(online)].pdf | 2018-11-20 |
| 14 | 201847027122-FORM 3 [30-08-2019(online)].pdf | 2019-08-30 |
| 15 | 201847027122-FORM 18 [30-08-2019(online)].pdf | 2019-08-30 |
| 16 | 201847027122-FORM 4(ii) [05-08-2021(online)].pdf | 2021-08-05 |
| 17 | 201847027122-FER.pdf | 2021-10-17 |
| 18 | 201847027122-OTHERS [01-11-2021(online)].pdf | 2021-11-01 |
| 19 | 201847027122-FORM 3 [01-11-2021(online)].pdf | 2021-11-01 |
| 20 | 201847027122-FER_SER_REPLY [01-11-2021(online)].pdf | 2021-11-01 |
| 21 | 201847027122-CLAIMS [01-11-2021(online)].pdf | 2021-11-01 |
| 22 | 201847027122-US(14)-HearingNotice-(HearingDate-25-08-2022).pdf | 2022-07-25 |
| 23 | 201847027122-REQUEST FOR ADJOURNMENT OF HEARING UNDER RULE 129A [19-08-2022(online)].pdf | 2022-08-19 |
| 24 | 201847027122-US(14)-ExtendedHearingNotice-(HearingDate-26-09-2022).pdf | 2022-08-24 |
| 25 | 201847027122-Information under section 8(2) [20-09-2022(online)].pdf | 2022-09-20 |
| 26 | 201847027122-REQUEST FOR ADJOURNMENT OF HEARING UNDER RULE 129A [21-09-2022(online)].pdf | 2022-09-21 |
| 27 | 201847027122-US(14)-ExtendedHearingNotice-(HearingDate-31-10-2022).pdf | 2022-09-26 |
| 28 | 201847027122-Correspondence to notify the Controller [20-10-2022(online)].pdf | 2022-10-20 |
| 29 | 201847027122-Written submissions and relevant documents [15-11-2022(online)].pdf | 2022-11-15 |
| 30 | 201847027122-Retyped Pages under Rule 14(1) [15-11-2022(online)].pdf | 2022-11-15 |
| 31 | 201847027122-FORM 3 [15-11-2022(online)].pdf | 2022-11-15 |
| 32 | 201847027122-Annexure [15-11-2022(online)].pdf | 2022-11-15 |
| 33 | 201847027122-2. Marked Copy under Rule 14(2) [15-11-2022(online)].pdf | 2022-11-15 |
| 34 | 201847027122-PatentCertificate16-11-2022.pdf | 2022-11-16 |
| 35 | 201847027122-IntimationOfGrant16-11-2022.pdf | 2022-11-16 |
| 1 | SEARCHSTRATEGY1E_03-02-2021.pdf |