CN107397759A - Phosphate binder, its preparation method and its application of the carbohydrate of hydroxide-degraded based on iron - Google Patents
Phosphate binder, its preparation method and its application of the carbohydrate of hydroxide-degraded based on iron Download PDFInfo
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- CN107397759A CN107397759A CN201610338265.1A CN201610338265A CN107397759A CN 107397759 A CN107397759 A CN 107397759A CN 201610338265 A CN201610338265 A CN 201610338265A CN 107397759 A CN107397759 A CN 107397759A
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- Prior art keywords
- carbohydrate
- degraded
- phosphate binder
- iron
- molecular weight
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- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 title claims abstract description 112
- 239000002694 phosphate binding agent Substances 0.000 title claims abstract description 69
- 150000001720 carbohydrates Chemical class 0.000 title claims abstract description 67
- 229910052742 iron Inorganic materials 0.000 title claims abstract description 56
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims abstract description 35
- 239000011574 phosphorus Substances 0.000 claims abstract description 35
- 229910052698 phosphorus Inorganic materials 0.000 claims abstract description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims abstract description 19
- 239000000203 mixture Substances 0.000 claims description 47
- 238000000034 method Methods 0.000 claims description 37
- 239000000843 powder Substances 0.000 claims description 7
- 238000000926 separation method Methods 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 5
- 238000001694 spray drying Methods 0.000 claims description 5
- 238000005243 fluidization Methods 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- OQUFOZNPBIIJTN-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;sodium Chemical compound [Na].OC(=O)CC(O)(C(O)=O)CC(O)=O OQUFOZNPBIIJTN-UHFFFAOYSA-N 0.000 claims 1
- 238000002474 experimental method Methods 0.000 abstract description 12
- 230000000694 effects Effects 0.000 abstract description 9
- 235000014633 carbohydrates Nutrition 0.000 description 48
- 239000000047 product Substances 0.000 description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
- 239000000243 solution Substances 0.000 description 34
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 28
- 238000001556 precipitation Methods 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- 230000033228 biological regulation Effects 0.000 description 17
- 238000003756 stirring Methods 0.000 description 15
- 230000007062 hydrolysis Effects 0.000 description 13
- 238000006460 hydrolysis reaction Methods 0.000 description 13
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 12
- 239000008194 pharmaceutical composition Substances 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 11
- 239000001509 sodium citrate Substances 0.000 description 11
- 235000011083 sodium citrates Nutrition 0.000 description 11
- 235000013325 dietary fiber Nutrition 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 9
- 235000006040 Prunus persica var persica Nutrition 0.000 description 8
- 239000002775 capsule Substances 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 235000013305 food Nutrition 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 8
- 235000010489 acacia gum Nutrition 0.000 description 7
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 7
- 239000003513 alkali Substances 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 244000144730 Amygdalus persica Species 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
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- 238000009472 formulation Methods 0.000 description 5
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 5
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- 239000000126 substance Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- LUEWUZLMQUOBSB-FSKGGBMCSA-N (2s,3s,4s,5s,6r)-2-[(2r,3s,4r,5r,6s)-6-[(2r,3s,4r,5s,6s)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2r,4r,5s,6r)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@@H](O[C@@H]2[C@H](O[C@@H](OC3[C@H](O[C@@H](O)[C@@H](O)[C@H]3O)CO)[C@@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O LUEWUZLMQUOBSB-FSKGGBMCSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 230000008859 change Effects 0.000 description 4
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- 230000010438 iron metabolism Effects 0.000 description 4
- NCNCGGDMXMBVIA-UHFFFAOYSA-L iron(ii) hydroxide Chemical compound [OH-].[OH-].[Fe+2] NCNCGGDMXMBVIA-UHFFFAOYSA-L 0.000 description 4
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- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000206575 Chondrus crispus Species 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
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- 229910002588 FeOOH Inorganic materials 0.000 description 3
- 229920001503 Glucan Polymers 0.000 description 3
- 229920002907 Guar gum Polymers 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 230000032683 aging Effects 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000006196 drop Substances 0.000 description 3
- 238000001976 enzyme digestion Methods 0.000 description 3
- 229940044631 ferric chloride hexahydrate Drugs 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000000665 guar gum Substances 0.000 description 3
- 235000010417 guar gum Nutrition 0.000 description 3
- 229960002154 guar gum Drugs 0.000 description 3
- 229920000591 gum Polymers 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 201000005991 hyperphosphatemia Diseases 0.000 description 3
- 150000002505 iron Chemical class 0.000 description 3
- NQXWGWZJXJUMQB-UHFFFAOYSA-K iron trichloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].Cl[Fe+]Cl NQXWGWZJXJUMQB-UHFFFAOYSA-K 0.000 description 3
- 210000002429 large intestine Anatomy 0.000 description 3
- 239000007937 lozenge Substances 0.000 description 3
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- 230000035484 reaction time Effects 0.000 description 3
- 210000000813 small intestine Anatomy 0.000 description 3
- 235000010413 sodium alginate Nutrition 0.000 description 3
- 239000000661 sodium alginate Substances 0.000 description 3
- 229940005550 sodium alginate Drugs 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 235000013599 spices Nutrition 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
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- 239000000375 suspending agent Substances 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical class [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
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- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
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- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 235000000396 iron Nutrition 0.000 description 1
- 235000014413 iron hydroxide Nutrition 0.000 description 1
- RUTXIHLAWFEWGM-UHFFFAOYSA-H iron(3+) sulfate Chemical compound [Fe+3].[Fe+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O RUTXIHLAWFEWGM-UHFFFAOYSA-H 0.000 description 1
- 229910000360 iron(III) sulfate Inorganic materials 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000012263 liquid product Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000007102 metabolic function Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 238000011369 optimal treatment Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 201000006409 renal osteodystrophy Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/26—Iron; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/191—Carboxylic acids, e.g. valproic acid having two or more hydroxy groups, e.g. gluconic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/736—Glucomannans or galactomannans, e.g. locust bean gum, guar gum
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Fodder In General (AREA)
Abstract
The invention provides a kind of phosphate binder, its preparation method and its application of the carbohydrate of hydroxide-degraded based on iron, specifically, the invention provides a kind of phosphate binder, including：The hydroxide of iron；With the carbohydrate of degraded；Wherein, with total restatement of the phosphate binder, the mass ratio of iron is 5 45%；Also, the number-average molecular weight of the carbohydrate of the degraded is 1000 300000Da；The number-average molecular weight D1 of the carbohydrate of degraded and the carbohydrate number-average molecular weight D2 before degraded ratio (D1/D2) are 0.05-0.8.Experiment shows that the phosphate binder has the effect for being significantly reduced serium inorganic phosphorus concentration, thus is with a wide range of applications.
Description
Technical field
The present invention relates to a kind of phosphate binder, in particular it relates to a kind of carbon hydrate based on molysite-degraded
Phosphate binder, its preparation method and its application of thing.
Background technology
Hyperphosphatemia is one of major complications of chronic renal insufficiency (CKD), serium inorganic phosphorus concentration increase with
CKD mortalities are closely related, and serium inorganic phosphorus concentration increases renal function can be caused further to fail, be secondary
Property thyroid function resists into, angiosteosis and mineral matter, bone metabolism disturbance.Modern times generally believe regulation phosphorus generation
It is the key for reducing cardiovascular complication, improving dialysis patient quality of life, reducing disability rate and the death rate to thank.
Constantly there is new phosphate binder to come out in recent years.Wherein, iron content phosphate binder is proved to be a kind of high
Imitate phosphate binder, and heterotopic calcification will not be caused and can improve thyroid function resist into.Meanwhile have
Help correct CKD anemia states, and internal iron metabolism is not influenceed significantly.
Due to containing substantial amounts of phosphorus in the daily diet of patient, and the phosphorus adsorption capacity mistake of existing phosphate binder
It is low, therefore in order to control serium inorganic phosphorus concentration normal horizontal to one, patient needs to use substantial amounts of phosphoric acid daily
Bonding agent, and excessive use can bring other side effects to patient.
Therefore, this area can increase substantially phosphorus adsorption capacity there is an urgent need to develop one kind, reduce side effect
Phosphate binder.
The content of the invention
It is an object of the invention to provide one kind can increase substantially phosphorus adsorption capacity, reduce the phosphorus knot of side effect
Mixture.
First aspect present invention provides a kind of phosphate binder, including：
The hydroxide of iron；With
The carbohydrate of degraded；
Wherein, with total restatement of the phosphate binder, the mass ratio of iron is 5-45wt%；Also, the degraded
The number-average molecular weight of carbohydrate is 1000-300000Da；The number-average molecular weight D1 of the carbohydrate of degraded
Ratio (D1/D2) with the carbohydrate number-average molecular weight D2 before degraded is 0.05-0.8.
In another preference, the mass ratio of iron is 22-35wt%, it is preferred that 25-31.5wt%, with the phosphorus
Total restatement of bonding agent.
In another preference, the number-average molecular weight of the carbohydrate of the degraded is 10000-100000Da,
It is preferred that 10000-90000Da.
In another preference, number-average molecular weight D1 and the carbohydrate before degraded of the carbohydrate of degraded
Number-average molecular weight D2 ratio (D1/D2) is 0.1-0.7, it is preferred that 0.2-0.5.
In another preference, the hydroxide of the iron is selected from the group：Iron hydroxide, FeOOH,
The oxide of iron or its combination.
In another preference, the carbohydrate includes soluble or insoluble carbohydrate.
In another preference, the carbohydrate is water miscible dietary fiber.
In another preference, the carbohydrate is difficult absorption or non-absorbent in vivo.
In another preference, the carbohydrate is selected from the group：Arabic gum, peach gum, guar gum,
Konjac glucomannan, carragheen, sodium alginate, pectin, glucan or its combination.
In another preference, the carbohydrate obtains by either physically or chemically degraded.
In another preference, the physical method is selected from the group：High-temperature heating, microwave radiation or its group
Close.
In another preference, the chemical method is selected from the group；Sour water solution, basic hydrolysis, oxydrolysis,
Enzyme hydrolysis or its combination.
In another preference, when the chemical method is sour water solution, the carbohydrate is in aqueous
Mass fraction be 0.01-20%.
In another preference, the carbohydrate is purified or without purifying.
In another preference, the hydroxide of the iron passes through hydrogen bond or suction-operated and carbohydrate shape
Into stable structure.
Second aspect of the present invention provides the purposes of phosphate binder described in first aspect present invention, presses down for preparing
The elevated composition of serium inorganic phosphorus concentration processed.
In another preference, the composition is additionally operable to (i) and improves immunity of organisms；And/or (i i)
Treatment or prevention hyperphosphatemia, hyperparathyroidism, calcium-phosphorus product change, vitamin D metabolism barrier
Hinder, the disease that renal osteodystrophy and cardiovascular complication are related.
In another preference, the composition include pharmaceutical composition, health composition, food compositions,
Or its combination.
In another preference, the composition includes the hydroxide of (i) iron of safe and effective amount；(i i)
The carbohydrate and pharmaceutically acceptable carrier of degraded.
In another preference, described composition is oral formulations.
In another preference, described composition is the preparation being selected from the group：Last agent, powder, tablet,
Sugar-coat agent, capsule, granule, suspending agent, solution, syrup, drops, sublingual lozenge.
In another preference, described composition contain the molysite of therapeutically effective amount, carbohydrate, with
And the additive being selected from the group：Flavouring, preservative, dispersant, colouring agent, spices, capsule shells, help
Solvent, disintegrant, lubricant, glidant, or its combination.
Third aspect present invention provides the preparation method of phosphate binder described in first aspect present invention, including step：
(a) carbohydrate of a degraded is provided；
(b) carbohydrate that above-mentioned steps obtain is mixed with the hydroxide of iron, obtains the present invention the
Phosphate binder described in one side.
In another preference, the hydroxide of the iron has been prepared or now matched somebody with somebody.
In another preference, the carbohydrate is degraded either physically or chemically lower.
In another preference, the physical method is selected from the group：High-temperature heating, microwave radiation or its group
Close.
In another preference, the chemical method is selected from the group；Sour water solution, basic hydrolysis, oxydrolysis,
Enzyme hydrolysis or its combination.
In another preference, when the chemical method is sour water solution, the carbohydrate is in aqueous
Mass fraction be 0.01-20%.
In another preference, the acid-hydrolyzed catalyst is selected from the group：It is hydrochloric acid, sulfuric acid, acetic acid, right
Toluenesulfonic acid, trifluoroacetic acid or its combination.
In another preference, the acid-hydrolyzed catalyst is hydrochloric acid, concentration of hydrochloric acid 0.01M-1M.
In another preference, the carbohydrate of the degraded is prepared with the following method：
(a1) a undegradable carbohydrate is provided；
(b1) in acid condition, the undegradable carbohydrate is degraded, described in acquisition
The carbohydrate of degraded.
In another preference, the reaction temperature of the step (b1) is 20-100 DEG C, and the reaction time is
1-240h。
In another preference, in addition to step (c1), the catabolite that purification step (b1) must all is (i.e.
The carbohydrate of degraded).
In another preference, the purifying includes the precipitation method (such as ethanol precipitation) purifying.
In another preference, the catabolite that can obtain step (b1) is not purified, is directly used in
Subsequent reactions.
In another preference, in step (b), including step (b2), step (a) can be obtained
To carbohydrate mixed with molysite in water, add alkali to produce precipitation, precipitation and separation, obtain the present invention the
Phosphate binder described in one side.
In another preference, the step (b2) has one or more following characteristics：
(a) heating-up temperature is 20-100 DEG C, it is preferred that 60-90 DEG C, more preferably, 70-80 DEG C；
(b) reaction time is 1-240h, it is preferred that 4-48h, more preferably, 8-20h；
(c) chilling temperature is 0-40 DEG C, it is preferred that 10-30 DEG C；
(d) pH is adjusted to 6-13, it is preferred that 7-10, more preferably, 8-9.
In another preference, in step (b), including step (b3), step (a) can be obtained
To catabolite and alkali mixed in water, add molysite and alkali, add ethanol produce precipitation, precipitation and separation, obtain
To the phosphate binder described in first aspect present invention.
In another preference, the step (b3) has one or more following characteristics：
(a) reaction temperature is 30-100 DEG C, it is preferred that 60-95 DEG C, more preferably, 80-90 DEG C；
(b) reaction time is 1-24h, it is preferred that 4-16h；
(c) chilling temperature is 0-40 DEG C；
(d) pH is adjusted to 5-12, it is preferred that 7-9.
In another preference, the step (b2) also includes heating and cooling step.
In another preference, the step (b3) also includes stirring and cooling step.
In another preference, in step (b2) and (b3), the molysite is selected from the group：Ferrous iron
Salt, trivalent iron salt or its combination.
In another preference, in step (b2) and step (b3), the molysite is trivalent iron salt,
It is selected from the group：Iron chloride, ferric nitrate, ferric sulfate, ironic citrate or its combination.
In another preference, in step (b2) and (b3), the alkali is selected from the group：From hydroxide
Sodium, potassium hydroxide, ammoniacal liquor, sodium carbonate, potassium carbonate, sodium citrate, potassium citrate, sodium acid carbonate, carbon
Sour ammonium, ammonium hydrogen carbonate, saleratus or its combination.
In another preference, methods described also includes step (c), passes through spray drying or fluidization spray
Separation product is dried, to obtain the phosphate binder of dry powder form.
Fourth aspect present invention provides a kind of composition, including：Phosphorus described in first aspect present invention combines
Agent；With
Pharmaceutically acceptable carrier.
In another preference, the composition also includes sodium citrate.
In another preference, the composition include pharmaceutical composition, health composition, food compositions,
Or its combination.
In another preference, described composition is oral formulations.
In another preference, described composition is the preparation being selected from the group：Last agent, powder, tablet,
Sugar-coat agent, capsule, granule, suspending agent, solution, syrup, drops, sublingual lozenge.
In another preference, described composition contain the molysite of therapeutically effective amount, carbohydrate, with
And the additive being selected from the group：Flavouring, preservative, dispersant, colouring agent, spices, capsule shells, help
Solvent, disintegrant, lubricant, glidant, or its combination.
In another preference, in the composition, containing 0.0001-99wt%, preferably 0.1-90wt%
Described phosphate binder, with the gross weight meter of the composition.
In another preference, described composition is unit dosage form (an a piece of, capsule or a bottle), often
The quality of composition described in individual unit dosage form is 0.05-5g, preferably 0.5-1.5g.
Fifth aspect present invention provides a kind of suppression elevated method of serium inorganic phosphorus concentration, has to suppressing object administration
Phosphate binder described in the first aspect present invention of effect amount, or the composition described in fourth aspect present invention.
In another preference, the object includes people or non-human mammal.
In another preference, the non-human mammal includes rodent, such as mouse, rat.
It should be understood that within the scope of the present invention, above-mentioned each technical characteristic of the invention and below (such as implementation
Example) in specifically describe each technical characteristic between can be combined with each other, so as to form new or preferable skill
Art scheme.As space is limited, no longer tire out one by one herein and state.
Embodiment
The present inventor's in-depth study by long-term, it has unexpectedly been found that, by molysite and the carbon of certain molecular weight
Hydrate (being preferably the dietary fiber through degraded) is mixed with certain proportion, has significant drop
The effect of low serum p concentration.Also, experiment shows, the phosphate binder of the present invention and sodium citrate are combined,
Also the absorption efficiency to phosphorus can be dramatically increased.On this basis, the present inventor completes the present invention.
The hydroxide of iron
The hydroxide of the iron of the present invention is not particularly limited, and a kind of hydroxide of preferable iron is hydroxide
Iron, FeOOH, the oxide of iron.
In the present invention, in phosphate binder, the mass ratio of iron is not particularly limited, a kind of preferable mass ratio
For 5-45wt%, it is preferred that 22-35wt%；More preferably, 25-31.5wt%, with total restatement of phosphate binder.
The carbohydrate of degraded
In the present invention, described " carbohydrate of degraded " refers to physics (such as high-temperature heating, microwave radiation)
Or the method for chemical (such as sour water solution, basic hydrolysis, oxydrolysis, enzyme hydrolysis) is degraded to carbohydrate,
The catabolite obtained from.
In the present invention, the carbohydrate of degraded contains relatively low number-average molecular weight, and a kind of preferable number is divided equally
Son amount is 1000-300000Da, it is preferred that 10000-100000Da, more preferably, 10000-90000Da.
The carbohydrate of the degraded of the present invention has no particular limits, a kind of carbohydrate typically degraded
For water miscible dietary fiber, a kind of carbohydrate preferably degraded is Arabic gum, peach gum, guar gum,
Konjac glucomannan, carragheen, sodium alginate, pectin, glucan.
The water miscible dietary fiber of the present invention due to its unique structure can not by the hydrochloric acid in gastric juice of alimentary canal and
Enzymic digestion, can go directly large intestine, therefore can not be decomposed in the stomach and small intestine of human body, thus will not be right
Iron metabolism in interfering bodies.
The phosphate binder of the present invention and its preparation
Generally, in order to obtain the hydroxide for the iron with good phosphate binding capacity that can be used as medicine
Thing is, it is necessary to obtain the stable compound based on iron.The hydroxide of known iron, especially ferric hydrogen
Oxide is very unstable, and aging can occur with the time, cause the molecule of initial random distribution to reconfigure, and
Form substantially regular array of crystal lattice.Aging may also lead to the phosphate binder release iron based on iron, from iron content medicine
Release iron may cause the worry to security in thing, because excessive iron is poisonous to organ.
The iron that human body daily intakes should be no more than 20mg, due to the inappropriate increase that enteron aisle iron absorbs, cause excessive
Iron be stored in the substantial cellulars such as liver, heart and pancreas, cause histoorgan retrogression and diffuse
Property fibrosis, metabolism and malfunction.
A kind of typical phosphate binder is preventing iron with solvable carbohydrate (as starch and sugarcane are risen)
The aging of hydroxide.
In the present invention, " phosphate binder of the invention " includes the hydroxide and carbohydrate of iron, wherein,
Carbohydrate is method (such as sour water solution, the buck with physics (such as high-temperature heating, microwave radiation) or chemistry
Solution) degraded carbohydrate, the carbohydrate of degraded contains relatively low number-average molecular weight, a kind of preferable number
Average molecular weight is 1000-300000Da, it is preferred that 10000-100000Da, more preferably, 10000-90000Da.
The carbohydrate of the degraded of the present invention has no particular limits, a kind of carbohydrate typically degraded
For water miscible dietary fiber, a kind of carbohydrate preferably degraded is Arabic gum, peach gum, guar gum,
Konjac glucomannan, carragheen, sodium alginate, pectin, glucan.
The water miscible dietary fiber of the present invention due to its unique structure can not by the hydrochloric acid in gastric juice of alimentary canal and
Enzymic digestion, can go directly large intestine, therefore can not be decomposed in the stomach and small intestine of human body, thus will not be right
Iron metabolism in interfering bodies.
The hydroxide of the iron of the present invention is not particularly limited, and a kind of hydroxide of preferable iron is hydroxide
Iron, FeOOH, the oxide of iron.
In the present invention, in phosphate binder, the mass ratio of iron is not particularly limited, a kind of preferable mass ratio
For 5-45wt%, it is preferred that 22-35wt%；More preferably, 25-31.5wt%, with total restatement of phosphate binder.
The phosphate binder of the present invention has very high phosphorus binding ability.In the present invention, the carbohydrate of degraded
The number-average molecular weight 3.2 ten thousand of (such as peach gum), and the mass ratio of the hydroxide iron content of iron be 32.4% when, this
The phosphate binder of invention has significantly excellent phosphorus binding ability (phosphorus uptake is 266.5mg/g).
The phosphate binder of the present invention can be prepared with conventional method, and in the present invention, phosphate binder of the invention is used
It is prepared by following method：
(a) carbohydrate of a degraded is provided；
(b) carbohydrate that above-mentioned steps obtain is mixed with the hydroxide of iron, obtains institute of the present invention
The phosphate binder stated.
In a preferred embodiment, methods described can also include step (c), pass through spray drying
Or fluidization and spray-drying separation product, to obtain the phosphate binder of dry powder form.
A kind of preparation method of preferable phosphate binder is as follows：
Hydrolysate and molysite are mixed in water, heated, is reacted 1 to 240 hour, reaction temperature 20
To 100 degrees Celsius；0 to 40 degree Celsius is subsequently cooled to, adds alkali to precipitating, regulation system pH value
To 6 to 13, preferably 7 to 10；Precipitation and separation, obtain product.
The preparation method of another preferable phosphate binder is as follows：
Hydrolysate and alkali are mixed in water, solution temperature is 30 to 100 degrees Celsius；Then drip simultaneously
Adding molysite and alkali, the pH of control system is between 5 to 12, and preferably 7 to 9；Continue to stir 1-24 hours；
Room temperature is cooled to, adds 1-10 times of ethanol, precipitation and separation, obtains product.
In the present invention, molysite is not particularly limited, and a kind of preferable molysite is iron chloride.
Composition and its application
Present invention also offers a kind of composition, it is preferable that is pharmaceutical composition.The composition includes
The phosphate binder of effect amount, in a preference, the composition also includes sodium citrate.In a preference,
Described composition is liquid formulation, solid formulation, semisolid preparations.In a preference, described liquid
State preparation is selected from the group：Solution product or suspension product.
In a preference, the formulation of described composition is selected from the group：Powder agent, powder, tablet, sugar
Clothing agent, capsule, granule, suspending agent, solution, syrup, drops and sublingual lozenge.
Pharmaceutical composition of the present invention can be described with medicinal tablet, any form administration of injection or capsule
The medium and carrier that pharmaceutical preparation includes excipient, medicine allows, these materials can be carried out according to method of administration
Selection.Pharmaceutical formulations of the present invention can further include the active constituent of auxiliary.
Lactose, glucose, sucrose, D-sorbite, mannose, starch, Arabic gum, calcium phosphate, algae
Hydrochlorate, gelatin, calcium silicates, fine crystallization cellulose, polyvinylpyrrolidone (PVP), cellulose, water,
Syrup, methylcellulose, methyl hydroxybenzoate, nipasol, talcum, magnesium stearate or ore deposit
Thing oil etc. is used as the carrier of pharmaceutical composition, excipient or diluent etc. in the present invention.
In addition, the pharmaceutical composition of the present invention can further comprise lubricant, wetting agent, emulsifying agent, suspension
Liquid stabilizer, preservative, sweetener and spices etc..The pharmaceutical composition of the present invention can be by a variety of known
Method is produced with enteric-coated preparations, in order to which the active component of pharmaceutical composition can pass through stomach without by hydrochloric acid in gastric juice
Destroyed.
In specification " medicine effective quantity " refer to that people and/or animal can be produced function or activity and can quilt
The amount that people and/or animal are received.For example in the present invention, can prepare (particularly, can containing 1%-99%
Contain 30% -90%；More particularly, contain 50% -80%) phosphate binder preparation.
When for preparing pharmaceutical composition, the effective dose of phosphate binder used can with administration pattern and treat
The order of severity of the disease for the treatment of and change.Suitable for dosage form for oral administration, comprising with solid-state or liquid pharmacy
Upper acceptable carrier is intimately mixed about (particularly, can to contain 30% -90% containing 1%-99%；Particularly
Ground, contain 50% -80%) phosphate binder.This dosage be can adjust to provide optimal treatment response.Example
Such as, by an urgent demand for the treatment of situation, dosage separated several times can be given daily, or by dosage pari passu
Reduce.
Described phosphate binder can be given by the approach such as oral.Solid-state carrier includes：Starch, lactose, phosphorus
Sour dicalcium, microcrystalline cellulose, sucrose and white bole, and liquid carrier includes：It is culture medium, polyethylene glycol, non-
Ionic surfactant and edible oil (such as corn oil, peanut oil and sesame oil), as long as being adapted to phosphate binder special
Property and required specific administration mode.Also can advantageously it be wrapped preparing adjuvant usually used in pharmaceutical composition
Include, such as flavor enhancement, pigment, preservative and antioxidant such as vitamin E, vitamin C, BHT and BHA.
In terms of easily prepared and administration position, preferable pharmaceutical composition is solid-state composition, especially tablet
The capsule filled with solid-filling or liquid.Oral administration is preferable.
The present composition is administered to the individual, is administered once daily or repeatedly.Dosage unit table
Show that it can be separated and suitable for the mankind or the dosage of other all mammalian subjects in form.Per unit contains
There are the carrier of medicine permission and the phosphate binder of the invention of effective therapeutic dose.Dosage with patient serium inorganic phosphorus water
Flat, included supplement active constituent and used phosphate binder and change.In addition it is such as possible, it can separate
Administration, and if desired for can successive administration.Therefore, the dosage will not cause to limit to the present invention.This
Outside, " composition " in the present invention does not mean only that medicine and expression can be used as functional food and health
Supplement.In a preference, the composition includes：Food, health products, medicine etc..At this
In one preference of invention, a kind of food compositions are additionally provided, it contains the phosphate binder of effective dose, with
And acceptable carrier on the food of surplus, the formulation of described food composition are selected from solid, dairy products, molten
Liquid product, pulverulent product or suspension product.
In a preference, the formula of the composition is as follows：
0.1-90wt% phosphate binder；And on food or pharmaceutically acceptable carrier, and/or excipient.
In another preference, the formula of the composition is as follows：
10-80wt% phosphate binder；And on food or pharmaceutically acceptable carrier, and/or excipient.
The composition containing phosphate binder of the present invention has significantly excellent phosphorus binding ability, therefore can use
Come the hyperphosphatemia treated and/or prevent mammal.The mammal of the present invention can refer to people, can also
Refer to warm-blooded animal, especially cat, dog etc..
Main advantages of the present invention include：
(1) present invention develops a kind of phosphate binder being made up of iron and soluble dietary fiber, and this
Invention reduces the molecular weight of dietary fiber, is absorbed so as to improve it with reference to the ability of iron, the phosphorus of unit iron
Amount etc., the taking dose for reducing patient of high degree.
(2) dietary fiber of the present invention due to its unique structure can not by the hydrochloric acid in gastric juice of alimentary canal and
Enzymic digestion, can go directly large intestine, therefore the phosphate binder is not easy to decompose in the stomach and small intestine of human body,
Therefore a large amount of free irons will not be produced, the iron metabolism to human body will not interfere.And dietary fiber
With specific healthcare function, absorption of the body to sugar will not be increased, be advantageous to chronic renal insufficiency trouble
The diet control of person.
(3) in the present invention, phosphate binder of the invention can also be combined with sodium citrate, can be notable
Increase the absorption efficiency to phosphorus.
With reference to specific embodiment, the present invention is expanded on further.It should be understood that these embodiments are merely to illustrate
The present invention rather than limitation the scope of the present invention.The experiment side of unreceipted actual conditions in the following example
Method, generally according to normal condition, or according to the condition proposed by manufacturer.Unless otherwise indicated, otherwise
Percentage and number are calculated by weight.
Universal method：
Phosphoric acid absorbability method of testing is：Configuration concentration is 2 μ g/mL phosphoric acid solution, with hydrochloric acid hydrogen-oxygen
It is 3.0 to change sodium regulation pH, and samples and be set to standard liquid Control A.Control A 25mL are taken to add system
100 ± the 5mg of phosphate binder (being designated as B) got ready, 24h is reacted at 37 DEG C under stirring at low speed.After 24 hours,
Reaction solution is centrifuged into (14000rpm), takes supernatant liquor, its concentration is C.Use ultraviolet spectrometry light
Degree meter determines A and C concentration respectively.Phosphate binding capacity clicks formula calculating：
Adsorption activity (mg/g) is defined as every gram of adsorbable phosphate radical (PO of API institutes4 3-) quality
Iron content is determined with ICP inductive coupling plasma emission spectrographs.
The measure of molecular weight is determined with GFC gel filtration chromatographies.
Embodiment 1
Experimental method：
100g Arabic gums are dissolved in 1000g water, it is 1 that concentrated sulfuric acid regulation system pH value, which is added dropwise, is added
Heat keeping temperature, stirs 4 hours to 80 DEG C；25g sodium citrates are added, rise temperature is 90 DEG C,
Stir fully to dissolve；The ferric chloride hexahydrate that 20% mass ratio is added dropwise into solution at a temperature of 90 DEG C is water-soluble
Liquid, while it is 8.0-9.0 that the NaOH aqueous solution that 20% mass ratio is added dropwise, which controls the pH of reaction solution, it is bright to having
Aobvious Precipitation, stop being added dropwise, and 5h is stirred at 90 DEG C, obtain red tan solution；It is cooled to room
Wen Hou, the solid being centrifuged off in solution, supernatant add 95% ethanol of 4 times of volumes, and it is heavy to separate out completely
Centrifuged behind shallow lake, and respectively with 70% ethanol and 80% ethanol, washing solid is twice；Products obtained therefrom is sprayed
Dry, receive to obtain 145.6g products altogether, product is in dark reddish brown.
Experimental result：
After hydrolysis 4 hours, Arabic gum molecular weight is 8.5 ten thousand, after product is ground, with above-mentioned general
It is 27.1% that method, which measures iron content, measures phosphorus with above-mentioned universal method and is absorbed as 238.3mg/g.
Embodiment 2
Experimental method：
10g Arabic gums are dissolved in 100g water, it is 1 that concentrated hydrochloric acid regulation system pH value, which is added dropwise, heating
To 70 DEG C, keeping temperature, stirring is added dropwise the six of 20% mass ratio in 20 hours at a temperature of 70 DEG C into solution
Chloride hydrate water solution 150ml, continue stirring 4 hours after being added dropwise, then cool to room temperature；Drop
Add the NaOH aqueous solution of 20% mass ratio, regulation system pH is 8.0, a large amount of Precipitations；Centrifuge
Precipitation, is washed with water precipitation 3 times, and products obtained therefrom is dried, and the common 4.5g of product, product is in bronzing.
Experimental result：
After hydrolysis 20 hours, the number-average molecular weight of Arabic gum is 6.4 ten thousand, after product is ground, is used
It is 31.5% that above-mentioned universal method, which measures iron content, measures phosphorus with above-mentioned universal method and is absorbed as 249.6mg/g.
Embodiment 3
Experimental method：
10g peach gums are dissolved in 200g water, it is 1 that concentrated hydrochloric acid regulation system pH value, which is added dropwise, is heated to 70
DEG C, keeping temperature, stir 40 hours；Six water of 20% mass ratio are added dropwise into solution at a temperature of 70 DEG C
Ferric chloride in aqueous solution 150ml is closed, is sufficiently stirred after being added dropwise 12 hours, then cools to room temperature；It is added dropwise
The NaOH aqueous solution of 20% mass ratio, regulation system pH are 9.0, and flocculent deposit separates out；Centrifuge precipitation,
Precipitation is washed with water 5 times, products obtained therefrom is dried, and the common 14.1g of product, product is in bronzing.
Experimental result：
Peach gum number-average molecular weight after hydrolysis is 8.6 ten thousand, after product is ground, with above-mentioned universal method
It is 28.9% to measure iron content, measures phosphorus with above-mentioned universal method and is absorbed as 223.4mg/g.
Embodiment 4
Experimental method：
50g peach gums are dissolved in 2000g water, it is 1.5 that concentrated sulfuric acid regulation system pH value, which is added dropwise, is heated to
80 DEG C, keeping temperature, stir 24 hours；6g sodium citrates and 4g sodium carbonate are added, rise temperature is
90 DEG C, it is sufficiently stirred；The ferric chloride hexahydrate that 20% mass ratio is added dropwise into solution at a temperature of 90 DEG C is water-soluble
Liquid, while the NaOH aqueous solution that 20% mass ratio is added dropwise controls the pH of reaction solution in the range of 7.5-8.5,
To there is obvious Precipitation, stop being added dropwise, and 10h is stirred at 90 DEG C, obtain red tan solution；It is cold
But to 95% ethanol of 4 times of volumes after room temperature, is added, centrifuged after separating out precipitation completely, and with 80%
Ethanol washing solid is twice；Products obtained therefrom is spray-dried, and receives to obtain 74.6g products altogether, product is in dark reddish brown.
Experimental result：
Peach gum number-average molecular weight after hydrolysis is 3.2 ten thousand, after product is ground, with above-mentioned universal method
It is 32.4% that method, which measures iron content, measures phosphorus with above-mentioned universal method and is absorbed as 266.5mg/g.
Embodiment 5
Experimental method：
10g konjac glucomannans are dissolved in 200g water, it is 1 that concentrated hydrochloric acid regulation system pH value, which is added dropwise, is heated to
70 DEG C, keeping temperature, stir 40 hours；The six of 20% mass ratio is added dropwise into solution at a temperature of 70 DEG C
Chloride hydrate water solution 150ml, it is sufficiently stirred after being added dropwise 6 hours, then cools to 30 DEG C；Drop
Add the NaOH aqueous solution of 20% mass ratio, regulation system pH is 8.5, Precipitation；Centrifuge precipitation,
Precipitation is washed with water 4 times, products obtained therefrom is dried, and the common 7.2g of product, product is in bronzing.
Experimental result：
The number-average molecular weight of konjac glucomannan after hydrolysis is 8.4 ten thousand, after product is ground, with above-mentioned general
It is 27.9% that method, which measures iron content, measures phosphorus with above-mentioned universal method and is absorbed as 182.8mg/g.
Embodiment 6
Experimental method：
By 50g HPGs be dissolved in 2500g be added dropwise concentrated hydrochloric acid regulation pH value be 1 water in,
80 DEG C are heated to, keeping temperature, is stirred 20 hours；Add 10g sodium citrates and 5g sodium carbonate, rise
Temperature is 90 DEG C, is sufficiently stirred；Six chloride hydrates of 20% mass ratio are added dropwise into solution at a temperature of 90 DEG C
Water solution 1000mL, while the pH that the NaOH aqueous solution control reaction solution of 20% mass ratio is added dropwise exists
In the range of 7.5-8.0, rufous suspension is obtained；After being cooled to room temperature, 95% second of 4 times of volumes is added
Alcohol, centrifuge, collect solid, and solid is washed twice with 80% ethanol；Products obtained therefrom is dried, and is received altogether
73.2g products are obtained, product is in dark brown.
Experimental result：
The number-average molecular weight of hydroxypropyl melon glue after hydrolysis is 5.4 ten thousand, after product is ground, is used
It is 30.9% to state universal method and obtain iron content, measures phosphorus with above-mentioned universal method and is absorbed as 226.3mg/g.
Embodiment 7 and influence of the phosphate binder to phosphorus absorption efficiency associated with sodium citrate
Experimental method：
10g Arabic gums are dissolved in 100g water, it is 1 that concentrated hydrochloric acid regulation system pH value, which is added dropwise, heating
To 70 DEG C, keeping temperature, stirring is added dropwise the six of 20% mass ratio in 20 hours at a temperature of 70 DEG C into solution
Chloride hydrate water solution 150ml, continue stirring 4 hours after being added dropwise, then cool to room temperature；Drop
Add the NaOH aqueous solution of 20% mass ratio, regulation system pH is 8.0, a large amount of Precipitations；Centrifuge
Precipitation, is washed with water precipitation 3 times, and products therefrom is dried, the common 4.5g of product, by product and 1g citric acids
Sodium is mixed to get product, and product is in bronzing.
Experimental result：
Gained sugar iron complexes and sodium citrate are mixed with product by the present embodiment, and products therefrom is led to above-mentioned
It is 25.4% to measure iron content with method, measures phosphorus with above-mentioned universal method and is absorbed as 196.4mg/g.As a result
Show that the phosphate binder of the present invention and sodium citrate combination are also had into excellent phosphorus absorbability.
Comparative example 1
Experimental method：
10g Arabic gums (number-average molecular weight 250,000) are dissolved in 100g water, at a temperature of 70 DEG C to
The ferric chloride hexahydrate aqueous solution 150ml of 20% mass ratio is added dropwise in solution, continues stirring 4 after being added dropwise
Hour, room temperature is then cooled to, the NaOH aqueous solution of 20% mass ratio is added dropwise, regulation system pH is 8.0,
A large amount of Precipitations, precipitation being centrifuged, precipitation is washed with water 3 times, products obtained therefrom is dried, the common 9.8g of product,
Product is in bronzing.
Experimental result：
After product is ground, it is 29.5% to measure iron content with above-mentioned universal method, with above-mentioned universal method
Measure phosphorus and be absorbed as 142.9mg/g.
Comparative example 2
Experimental method：
10g Arabic gums are dissolved in 100g water, it is 1 that concentrated hydrochloric acid regulation system pH value, which is added dropwise, heating
To 70 DEG C, keeping temperature, stir 1 hour.The six of 20% mass ratio is added dropwise into solution at a temperature of 70 DEG C
Chloride hydrate water solution 150ml, continue stirring 4 hours after being added dropwise, then cool to room temperature, drip
Add the NaOH aqueous solution of 20% mass ratio, regulation system pH is 8.0, a large amount of Precipitations, is centrifuged
Precipitation, is washed with water precipitation 3 times, and products obtained therefrom is dried, and the common 8.9g of product, product is in bronzing.
Experimental result：
After hydrolysis 1 hour, the number-average molecular weight of Arabic gum is reduced to 210,000, after product is ground, and uses
It is 28.7% that above-mentioned universal method, which measures iron content, measures phosphorus with above-mentioned universal method and is absorbed as 147.8mg/g.
All it is incorporated as referring in this application in all documents that the present invention refers to, just as each document
It is individually recited as with reference to such.In addition, it is to be understood that after the above-mentioned instruction content of the present invention has been read,
Those skilled in the art can make various changes or modifications to the present invention, and these equivalent form of values equally fall within this Shen
Please appended claims limited range.
Claims (10)
- A kind of 1. phosphate binder, it is characterised in that including：The hydroxide of iron；WithThe carbohydrate of degraded；Wherein, with total restatement of the phosphate binder, the mass ratio of iron is 5-45wt%；Also, the degraded The number-average molecular weight of carbohydrate is 1000-300000Da；The number-average molecular weight D1 of the carbohydrate of degraded Ratio (D1/D2) with the carbohydrate number-average molecular weight D2 before degraded is 0.05-0.8.
- 2. phosphate binder as claimed in claim 1, it is characterised in that the mass ratio of the iron is 22-35wt%, It is preferred that 25-31.5wt%, with total restatement of the phosphate binder.
- 3. phosphate binder as claimed in claim 1, it is characterised in that the number of the carbohydrate of the degraded Average molecular weight is 10000-100000Da, it is preferred that 10000-90000Da.
- 4. phosphate binder as claimed in claim 1, it is characterised in that the number of the carbohydrate of the degraded Average molecular weight D1 and the carbohydrate number-average molecular weight D2 before degraded ratio (D1/D2) are 0.1-0.7, It is preferred that 0.2-0.5.
- 5. the purposes of phosphate binder as claimed in claim 1, it is characterised in that suppress serium inorganic phosphorus for preparing The elevated composition of concentration.
- 6. the preparation method of phosphate binder as claimed in claim 1, it is characterised in that including step：(a) carbohydrate of a degraded is provided；(b) carbohydrate that above-mentioned steps obtain is mixed with the hydroxide of iron, obtains claim 1 Described phosphate binder.
- 7. preparation method as claimed in claim 6, it is characterised in that the carbohydrate of the degraded is with such as It is prepared by lower section method：(a1) a undegradable carbohydrate is provided；(b1) in acid condition, the undegradable carbohydrate is degraded, described in acquisition The carbohydrate of degraded.
- 8. preparation method as claimed in claim 6, it is characterised in that methods described also includes step (c), By spray drying or fluidization and spray-drying separation product, to obtain the phosphate binder of dry powder form.
- A kind of 9. composition, it is characterised in that including：Phosphate binder described in claim 1；WithPharmaceutically acceptable carrier.
- 10. composition as claimed in claim 9, it is characterised in that the composition also includes citric acid Sodium.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109331036A (en) * | 2018-10-17 | 2019-02-15 | 上海医药集团青岛国风药业股份有限公司 | Application of the polyferose in the drug of preparation treatment hyperphosphatemia |
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| CN1997596A (en) * | 2004-06-28 | 2007-07-11 | 维福（国际）股份公司 | Iron sulfate-based phosphate adsorbent |
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| CN1997596A (en) * | 2004-06-28 | 2007-07-11 | 维福（国际）股份公司 | Iron sulfate-based phosphate adsorbent |
| CN104688702A (en) * | 2007-11-16 | 2015-06-10 | 维福（国际）股份公司 | Pharmaceutical compositions |
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| CN109331036A (en) * | 2018-10-17 | 2019-02-15 | 上海医药集团青岛国风药业股份有限公司 | Application of the polyferose in the drug of preparation treatment hyperphosphatemia |
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