CN1939928A - Alkali salt of partial neusaponin compound - Google Patents
Alkali salt of partial neusaponin compound Download PDFInfo
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- CN1939928A CN1939928A CN 200510011044 CN200510011044A CN1939928A CN 1939928 A CN1939928 A CN 1939928A CN 200510011044 CN200510011044 CN 200510011044 CN 200510011044 A CN200510011044 A CN 200510011044A CN 1939928 A CN1939928 A CN 1939928A
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- Prior art keywords
- subsalt
- bisnosaponin compound
- compound
- bisnosaponin
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- 150000001875 compounds Chemical class 0.000 title claims description 57
- 150000001447 alkali salts Chemical class 0.000 title 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229910052700 potassium Inorganic materials 0.000 claims abstract description 8
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 8
- -1 compound basic salt Chemical class 0.000 claims abstract description 7
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 3
- 229910052749 magnesium Inorganic materials 0.000 claims abstract description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 3
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 3
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 3
- 238000002360 preparation method Methods 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 12
- 239000003513 alkali Substances 0.000 claims description 10
- 238000000967 suction filtration Methods 0.000 claims description 8
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- WQZGKKKJIJFFOK-RWOPYEJCSA-N beta-D-mannose Chemical compound OC[C@H]1O[C@@H](O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-RWOPYEJCSA-N 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- SYYHBUHOUUETMI-UHFFFAOYSA-N Pennogenin Natural products O1C2CC3C4CC=C5CC(O)CCC5(C)C4CCC3(C)C2(O)C(C)C21CCC(C)CO2 SYYHBUHOUUETMI-UHFFFAOYSA-N 0.000 claims description 3
- 150000001340 alkali metals Chemical class 0.000 claims description 3
- NHUFMXNVSAWNTO-GDVKPPGWSA-N (2S,3R,4S,5S,6R)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO.O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO NHUFMXNVSAWNTO-GDVKPPGWSA-N 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- NHUFMXNVSAWNTO-NMYAFYTPSA-N OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O.OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O.OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O NHUFMXNVSAWNTO-NMYAFYTPSA-N 0.000 claims description 2
- FCWGWLOPJJISML-BWIHTRQJSA-N O[C@@H]1[C@@H](O)[C@@H](O)[C@H](O)CO1.O[C@@H]1[C@@H](O)[C@@H](O)[C@H](O)CO1 Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@H](O)CO1.O[C@@H]1[C@@H](O)[C@@H](O)[C@H](O)CO1 FCWGWLOPJJISML-BWIHTRQJSA-N 0.000 claims description 2
- FCWGWLOPJJISML-UJZJUORMSA-N O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)CO1.O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)CO1 Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)CO1.O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)CO1 FCWGWLOPJJISML-UJZJUORMSA-N 0.000 claims description 2
- ULRLBFXUAILOJZ-KQYRWNSJSA-N O[C@@H]1[C@H](O)[C@H](O)[C@H](O1)CO.O[C@@H]1[C@H](O)[C@H](O)[C@H](O1)CO Chemical compound O[C@@H]1[C@H](O)[C@H](O)[C@H](O1)CO.O[C@@H]1[C@H](O)[C@H](O)[C@H](O1)CO ULRLBFXUAILOJZ-KQYRWNSJSA-N 0.000 claims description 2
- FCWGWLOPJJISML-OAEDQPMSSA-N O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)CO1.O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)CO1 Chemical compound O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)CO1.O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)CO1 FCWGWLOPJJISML-OAEDQPMSSA-N 0.000 claims description 2
- ULRLBFXUAILOJZ-PWMXBFSXSA-N O[C@H]1[C@H](O)[C@H](O)[C@H](O1)CO.O[C@H]1[C@H](O)[C@H](O)[C@H](O1)CO Chemical compound O[C@H]1[C@H](O)[C@H](O)[C@H](O1)CO.O[C@H]1[C@H](O)[C@H](O)[C@H](O1)CO ULRLBFXUAILOJZ-PWMXBFSXSA-N 0.000 claims description 2
- LPQOADBMXVRBNX-UHFFFAOYSA-N ac1ldcw0 Chemical compound Cl.C1CN(C)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN3CCSC1=C32 LPQOADBMXVRBNX-UHFFFAOYSA-N 0.000 claims description 2
- 238000013019 agitation Methods 0.000 claims description 2
- 150000004703 alkoxides Chemical class 0.000 claims description 2
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 claims description 2
- GZCGUPFRVQAUEE-UHFFFAOYSA-N alpha-D-galactose Natural products OCC(O)C(O)C(O)C(O)C=O GZCGUPFRVQAUEE-UHFFFAOYSA-N 0.000 claims description 2
- SRBFZHDQGSBBOR-LECHCGJUSA-N alpha-D-xylose Chemical compound O[C@@H]1CO[C@H](O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-LECHCGJUSA-N 0.000 claims description 2
- SHZGCJCMOBCMKK-SXUWKVJYSA-N alpha-L-fucose Chemical compound C[C@@H]1O[C@@H](O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-SXUWKVJYSA-N 0.000 claims description 2
- 239000002585 base Substances 0.000 claims description 2
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 claims description 2
- WQZGKKKJIJFFOK-FPRJBGLDSA-N beta-D-galactose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-FPRJBGLDSA-N 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 150000002016 disaccharides Chemical class 0.000 claims description 2
- WQMLFJWIKARBFW-BKKMTDGVSA-N evomonoside Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C[C@@H](CC[C@H]2[C@]3(CC[C@@H]([C@@]3(C)CC[C@H]32)C=2COC(=O)C=2)O)[C@]3(C)CC1 WQMLFJWIKARBFW-BKKMTDGVSA-N 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 150000003538 tetroses Chemical class 0.000 claims description 2
- 150000004043 trisaccharides Chemical class 0.000 claims description 2
- 229960003487 xylose Drugs 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000005516 engineering process Methods 0.000 description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 7
- 239000006185 dispersion Substances 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 2
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- SHZGCJCMOBCMKK-HGVZOGFYSA-N alpha-L-rhamnopyranose Chemical compound C[C@@H]1O[C@@H](O)[C@H](O)[C@H](O)[C@H]1O SHZGCJCMOBCMKK-HGVZOGFYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- OPVIFYCKRBJEDI-UHFFFAOYSA-N C1(CCCCC1)O.[O] Chemical compound C1(CCCCC1)O.[O] OPVIFYCKRBJEDI-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- 241000234272 Dioscoreaceae Species 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- LWNOIQJAJMHMSM-UHFFFAOYSA-N Pariphyllin Natural products O1C2(OCC(C)CC2)C(C)C(C2(CCC3C4(C)CC5)C)C1CC2C3CC=C4CC5OC(C(C1OC2C(C(O)C(CO)O2)O)O)OC(CO)C1OC1OC(C)C(O)C(O)C1O LWNOIQJAJMHMSM-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 150000002243 furanoses Chemical class 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- SYYHBUHOUUETMI-WJOMMTHPSA-N pennogenin Chemical compound C([C@@]12[C@H]([C@@]3([C@@]4(C)CC[C@@H]5[C@@]6(C)CC[C@H](O)CC6=CC[C@H]5[C@@H]4C[C@@H]3O2)O)C)C[C@@H](C)CO1 SYYHBUHOUUETMI-WJOMMTHPSA-N 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 150000003214 pyranose derivatives Chemical class 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A partial nosaponin compound basic salt and its production are disclosed. In the structural general formula, R2=H, CH3, CH2OH and CH2, X=O, N and S; R3=Na, K, Mg, Ca, triethylamino and tert-butylamine. It has better water soluble performance and biological utilization.
Description
Technical field
The present invention relates to have a compounds of formula.
Background technology
Chinese patent 03135589.7 discloses the purification of pariphyllin compounds.Chinese patent 85108520 discloses two kinds of bisnosaponin compound application aspect gynecologic blood diseases.But prior art all is saponin(es of the molecular conformation that obtains from natural phant, and water-soluble fluidity is poor, and bioavailability is low.Because natural plant resource is limited, so make progress synthesizing of bisnosaponin compound, salt-forming reaction is very necessary.
Summary of the invention
The object of the present invention is to provide bisnosaponin compound (pennogenin) subsalt that a kind of solubleness in water is higher, bioavailability is good.
Another object of the present invention is to provide the preparation method of this bisnosaponin compound subsalt.
Bisnosaponin compound subsalt of the present invention, its general structure is:
In the general formula:
R
2＝H，CH
3，CH
2OH，＝CH
2
X=O, N, S, R
3=Na, K, Mg, Ca, triethyamino, TERTIARY BUTYL AMINE base
C
17-OR
3Be R-configuration or S-configuration
R
1=by monose, disaccharide, trisaccharide, tetrose, pentasaccharides, six sugar, the straight chain sugar chain of the various types that seven sugar are formed or side chain sugar chain, the sugar composed type of its sugar chain comprise β-D-glucose (β-D-glucose), alpha-D-glucose (α-D-glucose), α-L-rhamnosyl (α-L-rhamnose), β-D-semi-lactosi (β-D-galactose), α-D-semi-lactosi (α-D-galactose), β-D-seminose (β-D-mannose), α-D-seminose (β-D-mannose), α-D-pectinose (α-D-aradinose), β-D-pectinose (α-D-aradinose), alpha-D-xylose (α-D-xylose), β-D-wood sugar (α-D-xylose), α-D-ribose (α-D-ribose), β-D-ribose (β-D-ribose), α-D-lyxose (α-D-lyxose), β-D-lyxose (β-D-lyxose), α-L-husband sugar (α-L-fucose).
Comprise 4 bisnosaponin compound that activity is stronger: X=O, R
2=H, R
3=Na or K
[I]R
1＝-3-O-α-L-rha·py(1→4)-α-L-rha·py(1→4)-[α-L-rha-py(1→2)]-β-D-glc·py
[II]R
1＝-3-O-α-L-rha·py(1→2)-[α-L-rha·py(1→4)]-β-D-glc·py
[III]R
1＝-3-O-α-L-ara·fura-(1→4)-[α-L-rha·py(1→2)]-β-D-glc·py
[IV]R
1＝-3-O-α-L-rha·py(1→2)-β-D-glc·py。
" fura " represents five yuan of oxygen cyclohexanol, claims " furanose "; " py " the hexa-atomic oxygen cyclohexanol of expression, claim " pyranose ".
The preparation method of bisnosaponin compound subsalt of the present invention is made up of following steps:
One, bisnosaponin compound is placed-20 ℃ to 90 ℃ solvents to dissolve, agitation condition drips alkali down, reaction times is 0.5-20 hour, bisnosaponin compound: the mol ratio of alkali valency is 1: 0.6-2, when pH value is 9-12, be terminal point, described pennogenin compound, general structure is:
R in the general formula
2, X, R
1Same as described above;
Two, filtered while hot, the most of solvent of reclaim under reduced pressure, cooling treats that the subsalt of bisnosaponin compound is separated out, suction filtration obtains the solid subsalt, with identical cold cut matchmaker soak on a small quantity, suction filtration for several times, must white bisnosaponin compound subsalt.
Bisnosaponin compound in the above-mentioned steps: the preferred ratio of the mol ratio of alkali valency is 1: 0.8-1.5; Preferably 40 ℃ to 70 ℃ of described temperature of reaction; Preferably 1-4 hour reaction times; The weight ratio of bisnosaponin compound and solvent is 1: 1-30, optimization be 1: 5-20; Described solvent is that the various carbon numbers that contain are at the lower alcohol below 6 and 6, as methyl alcohol, ethanol, n-propyl alcohol, Virahol etc.; And other organic solvent methyl-sulphoxide, benzene,toluene,xylene, cyclopropane, chloroform; And water.Second alcohol and water preferably.Described cold cut matchmaker is meant below the room temperature, the solvent of the above temperature of solid-state zero pour.
Because the bisnosaponin compound of molecular conformation is water-soluble extremely low, what therefore be absorbed by the body and utilize is few.Pharmacokinetic studies shows that bisnosaponin compound enters blood with original shape, and bioavailability is extremely low, discharges from ight soil via stomach and intestine with original shape more than 90%.It is water-soluble to press for raising.Bisnosaponin compound belongs to amphoteric substance, becomes acid salt or subsalt all can.Water-soluble increase behind the salify becomes a kind of better pharmaceutical raw material and replaces the bisnosaponin compound of molecular conformation.Particularly useful for the salt-forming reaction of synthesis method production bisnosaponin compound.The present invention is intended to screen water-soluble high bisnosaponin compound salt, as the higher medicine material of a kind of bioavailability on the pharmaceutics.
Described alkali is meant acceptable alkali on the Human Physiology, as alkali-metal oxyhydroxide, salt of weak acid such as carbonate, supercarbonate or alkoxide, for example sodium hydroxide, potassium hydroxide, magnesium hydroxide, yellow soda ash, sodium bicarbonate, triethylamine, TERTIARY BUTYL AMINE, potassium tert.-butoxide, sodium tert-butoxide.Preferably sodium hydroxide and potassium hydroxide.
Theoretical foundation of the present invention is that 17 hydroxyls of bisnosaponin compound are both sexes groups, can with acid combine and can with the alkali salify. be present in Dioscoreaceae, the liliaceous plant with molecular form at the occurring in nature bisnosaponin compound, be insoluble in water, bioavailability is extremely low.In order to improve the bioavailability of bisnosaponin compound, application solid-state molecular dispersion technology, liquid molecular dispersion technology, the diffusing technology of differential and resulting product of parenteral medicine-feeding technology and effect in patent 200510010874.6,2005100873.1,2005100872.7,200510010875.0,200510010855.3,200510010859.1,200510010928.9,200510010902.4,200510010903.9, have been mentioned respectively.But above technical matters complexity, auxiliary material price height, and adopt the product stability of dispersion technology relatively poor is aging easily or separate out crystallization and cause dispersion effect to reduce.Though the technology of purification bisnosaponin compound is ripe from plant in theory, see Chinese patent 03135589.7, but since extraction with separate, the purifying cost is too high, the salt-forming reaction of in fact natural bisnosaponin compound does not possess the condition of suitability for industrialized production.Comparatively Xian Shi scheme is artificial semi-synthetic bisnosaponin compound.The semi-synthetic of bisnosaponin compound achieved success in the laboratory fortunately, in detail can be referring to Chinese patent 02150907.7,200410024930.7.Compare with aforementioned techniques, salt-forming reaction technology is simple, and cost is low, and it is water-soluble but but can improve significantly, significantly increases absorption of human body, is a kind of good pharmaceutical raw material.Certainly the salt of bisnosaponin compound is applicable to above dispersion technology and parenteral medicine-feeding technology too.
Embodiment
Because the synthetic of bisnosaponin compound IV molecule original shape obtained success at first in the laboratory, thus following examples indication be bisnosaponin compound IV.Following give an actual example all can very fast understanding in various equivalent modifications, therefore only as to elaboration of the present invention rather than limitation of the present invention.Detect water-soluble, the fusing point of each salt, and follow the tracks of detection with thin layer.
Embodiment 1:
1 mole of bisnosaponin compound, with 60 ℃ of dissolvings of 20 times of weight ethanol, under continuous condition of stirring, splash into 5mol/L sodium hydroxide or potassium hydroxide solution until PH=11.5, consume sodium hydroxide solution 0.2L approximately, filtered while hot, reclaim under reduced pressure 90% ethanol is cooled to 5-10 ℃, the sodium salt of bisnosaponin compound is separated out, suction filtration obtains solid sodium salt, with 5-10 ℃ of ethanol soak on a small quantity, suction filtration for several times, white bisnosaponin compound sodium salt.Solubleness 0.3g/ml in the water, fusing point 263-267 ℃.
Embodiment 2:
1 mole of bisnosaponin compound, 90 ℃ of water of 30 times of weight of adding are under continuous condition of stirring, splash into the 5mol/L TERTIARY BUTYL AMINE, observe bisnosaponin compound and dissolve gradually, this moment, PH was about 10, consume TERTIARY BUTYL AMINE solution 0.22L approximately, filtered while hot, reclaim under reduced pressure 90% water is cooled to 5-10 ℃, the sodium salt of bisnosaponin compound is separated out, suction filtration obtains solid sodium salt, with 5-10 ℃ of water soak on a small quantity, suction filtration for several times, white bisnosaponin compound sodium salt.Solubleness 0.3g/ml in the water, fusing point 262-266 ℃.
Claims (15)
1, a kind of bisnosaponin compound subsalt, its general structure is:
In the general formula:
R
2＝H，CH
3，CH
2OH，＝CH
2
X=O, N, S, R
3=Na, K, Mg, Ca, triethyamino, TERTIARY BUTYL AMINE base
C
17-OR
3Be R-configuration or S-configuration
R
1=by monose, disaccharide, trisaccharide, tetrose, pentasaccharides, six sugar, the straight chain sugar chain of the various types that seven sugar are formed or side chain sugar chain, the sugar composed type of its sugar chain comprise β-D-glucose (β-D-glucose), alpha-D-glucose (α-D-glucose), α-L-rhamnosyl (α-L-rhamnose), β-D-semi-lactosi (β-D-galactose), α-D-semi-lactosi (α-D-galactose), β-D-seminose (β-D-mannose), α-D-seminose (β-D-mannose), α-D-pectinose (α-D-aradinose), β-D-pectinose (α-D-aradinose), alpha-D-xylose (α-D-xylose), β-D-wood sugar (α-D-xylose), α-D-ribose (α-D-ribose), β-D-ribose (β-D-ribose), α-D-lyxose (α-D-lyxose), β-D-lyxose (β-D-lyxose), α-L-husband sugar (α-L-fucose).
2, bisnosaponin compound subsalt as claimed in claim 1 is characterized in that X=O in its general structure, R
2=H, R
3=Na or K, R
1=-3-O-α-L-rhapy (1 → 4)-α-L-rhapy (1 → 4)-[α-L-rha-py (1 → 2)]-β-D-glcpy.
3, bisnosaponin compound subsalt as claimed in claim 1 is characterized in that X=O in its general structure, R
2=H, R
3=Na or K, R
1=-3-O-α-L-rhapy (1 → 2)-[α-L-rhapy (1 → 4)]-β-D-glcpy.
4, bisnosaponin compound subsalt as claimed in claim 1 is characterized in that X=O in its general structure, R
2=H, R
3=Na or K, R
1=-3-O-α-L-arafura-(1 → 4)-[α-L-rhapy (1 → 2)]-β-D-glcpy.
5, bisnosaponin compound subsalt as claimed in claim 1 is characterized in that X=O in its general structure, R
2=H, R
3=Na or K, R
1=-3-O-α-L-rhapy (1 → 2)-β-D-glcpy.
6, the preparation method of bisnosaponin compound subsalt as claimed in claim 1 is characterized in that being made up of following steps:
One, bisnosaponin compound is placed-20 ℃ to 90 ℃ solvents to dissolve, agitation condition drips alkali down, reaction times is 0.5-20 hour, bisnosaponin compound: the mol ratio of alkali valency is 1: 0.6-2, when pH value is 9-12, be terminal point, described pennogenin compound, general structure is:
R2, X in the general formula, R1 are same as described above;
Two, filtered while hot, the most of solvent of reclaim under reduced pressure, cooling treats that the subsalt of bisnosaponin compound is separated out, suction filtration obtains the solid subsalt, with identical cold cut matchmaker soak on a small quantity, suction filtration for several times, must white bisnosaponin compound subsalt.
7, the preparation method of bisnosaponin compound subsalt as claimed in claim 6 is characterized in that bisnosaponin compound in the above-mentioned steps: the preferred ratio of the mol ratio of alkali valency is 1: 0.8-1.5.
8, the preparation method of bisnosaponin compound subsalt as claimed in claim 6 is characterized in that described temperature of reaction is 40 ℃ to 70 ℃.
9, the preparation method of bisnosaponin compound subsalt as claimed in claim 6 is characterized in that the reaction times is 1-4 hour.
10, the preparation method of bisnosaponin compound subsalt as claimed in claim 6, the weight ratio that it is characterized in that bisnosaponin compound and solvent is 1: 1-30.
11, the preparation method of bisnosaponin compound subsalt as claimed in claim 10, the weight ratio that it is characterized in that bisnosaponin compound and solvent is 1: 5-20.
12, the preparation method of the described bisnosaponin compound subsalt of claim 6 is characterized in that described solvent is to contain carbon number at the lower alcohol below 6 and 6.
13, the preparation method of the described bisnosaponin compound subsalt of claim 6 is characterized in that described solvent is an organic solvent.
14, the preparation method of the described bisnosaponin compound subsalt of claim 6 is characterized in that described solvent is a water.
15, the preparation method of the described bisnosaponin compound subsalt of claim 6 is characterized in that described alkali is alkali-metal oxyhydroxide, alkali-metal salt of weak acid, alkali-metal supercarbonate or alkoxide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510011044 CN1939928A (en) | 2005-09-29 | 2005-09-29 | Alkali salt of partial neusaponin compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510011044 CN1939928A (en) | 2005-09-29 | 2005-09-29 | Alkali salt of partial neusaponin compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1939928A true CN1939928A (en) | 2007-04-04 |
Family
ID=37958482
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200510011044 Pending CN1939928A (en) | 2005-09-29 | 2005-09-29 | Alkali salt of partial neusaponin compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1939928A (en) |
-
2005
- 2005-09-29 CN CN 200510011044 patent/CN1939928A/en active Pending
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