CN102151284B - Composition containing fucoidin sulfate and application thereof - Google Patents
Composition containing fucoidin sulfate and application thereof Download PDFInfo
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- CN102151284B CN102151284B CN 201110044905 CN201110044905A CN102151284B CN 102151284 B CN102151284 B CN 102151284B CN 201110044905 CN201110044905 CN 201110044905 CN 201110044905 A CN201110044905 A CN 201110044905A CN 102151284 B CN102151284 B CN 102151284B
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Abstract
The invention relates to a composition containing fucoidin sulfate, and the usage thereof in the preparation of medicament or functional food used for treating or preventing diabetes or diabetic nephropathy. The composition contains the fucoidin sulfate and kelp powder which are extracted from Phaeophyta plants.
Description
Technical field
The present invention relates to a kind of compositions that contains sulfated fucan, and said composition aspect preparation treatment or prevent diabetes or diabetic nephropathy medicine or the purposes of functional food.
Background technology
Sulfated fucan is the natural sulfated polysaccharides of a class, is present in the Brown algae class plant, is called fucoidan according to international nomenclature principle unification, and the Chinese another name is: fucoidan, fucoidin, fucoidan, fucoidin, fucosan.The chemical composition and structure of sulfated fucan is very complicated, in general, mainly formed by fucose and sulfate, its chemical mechanism be (RR ' SO
2OM)
n, R is fucose (C
6H
10O
4), M is single electric charge heavy metal ion, R ' is along with the kind difference of Brown algae may also contain other polysaccharide components such as galactose, xylose, alduronic acid.Polysaccharide part such as the sulfated fucan that extracts in the Thallus Laminariae (Thallus Eckloniae) is comprised of fucose, galactose, mannose etc., take fucose as main.The chemical constitution of Thallus Laminariae (Thallus Eckloniae) fucoidin is (C
6H
10O
3SO
4)
n, namely 1,2-α-fucose, C4 is upper with sulfate, and molecular weight is 226xn, and concrete structure is illustrated as follows:
Various biological function and the pharmaceutical usage of the open sulfated fucan of existing many pieces of documents have antioxidation, anticoagulation, antiproliferative, anti-adhesive, antiviral and the effect such as heavy metal ion adsorbed such as it.For example studies confirm that sulfated fucan can increase the activity of some antioxidase, reduce the generation of free radical, thus the attack that alleviates radical pair liver, renal tissue; Thereby use it for the clinical treatment nephrotic syndrome and early metaphase chronic kidney hypofunction, and for chronic kidney hypofunction the blood urea nitrogen of reduction, serum creatinine are arranged, improve renal function, delay the effect of disease progression.
A small amount of literature research report is also arranged at present, sulfated fucan has positive role for diabetes-alleviating nephrotic's the state of an illness, improves albuminuria significantly as appointing the report sulfated fucan such as an eastern liter, Li Haijian, Tao Ya be non-that the diabetic nephropathy patient that is in azotemia phase is had, corrects hypoproteinemia, improves the renal function effect.Chinese invention patent application Publication Specification CN101306014A discloses the application of low-molecular-weight algal polysaccharide sulfate in medicine for treating diabetic nephropathy after degraded.
Diabetes (diabetes) are to act on body by inherited genetic factors, immunologic function disorder, infected by microbes and toxin thereof, free radical toxin, Nervous and Mental Factors etc. various virulence factors to cause hypoinsulinism, insulin resistant (Insulin Resistance, IR) etc. and a series of metabolism disorder syndromes such as the sugar that causes, protein, fat, power and water Xie Zhi, clinically take hyperglycemia as main feature.
Diabetic nephropathy is the main microvascular complications of diabetes, mainly refers to diabetic glomerulosclerosis, and is a kind of take vascular lesion as main Glomerular lesions.In early days how asymptomatic, blood pressure can be normal or higher.Its incidence rate is along with the course of disease of diabetes prolongs and increases.The early stage kidney volume of diabetes increases, glomerular filtration rate increases, be high filtration state, engender later on space protein urine or microalbuminuria, the lasting albuminuria of prolongation appearance, edema, hypertension, glomerular filtration rate reduction along with the course of disease, and then renal insufficiency, uremia, be one of main cause of death of diabetes.
Only there is at present the open sulfated fucan of a small amount of document to have the drug effect for the treatment of or diabetes-alleviating nephropathy, but, further effective active component analysis and concrete pharmacology pharmacodynamic experimentation also are short of very much, therefore, be badly in need of at present this material is carried out the concrete applied research of medicine further and functional food aspect.
Summary of the invention
One aspect of the present invention provides a kind of compositions that contains sulfated fucan, and wherein, said composition comprises extracts sulfated fucan and the Kelp Powder that obtains from the Phaeophyta plant.
Described sulfated fucan is to extract the sulfated fucan that obtains from any or multiple Brown algae class plant, for example can derive from Thallus Laminariae (Thallus Eckloniae) (Laminaria japonica) (Thallus Laminariae (Thallus Eckloniae) that comprises artificial cultivation), also can derive from the Brown algae class plants such as Alga Sgrgassi Enerves, Thallus Laminariae, Sargassum fusiforme (Harv.) Setch, Thallus Sargassi Kjellmaniani, Thallus Laminariae (Thallus Eckloniae), yellow tang or Fucus Vesiculosus one or more.In a specific embodiments of the present invention, described sulfated fucan derives from Thallus Laminariae (Thallus Eckloniae).
Described sulfated fucan comprises the rear sulfated fucan without degraded of extraction, the low-molecular-weight algal polysaccharide sulfate through degrading, perhaps their modification sulfated fucan through obtaining after chemical modification.Described chemical modification can be modified mode for sulfated fucan well-known to those skilled in the art such as synthetic sulphation, amination, phosphorylation, acetylation and benzoylation modifications.
Described Kelp Powder is the dry powder goods that the step process such as Thallus Laminariae (Thallus Eckloniae) drying, pulverizing make.Those skilled in the art can adopt arbitrarily the method for this area routine to prepare Kelp Powder of the present invention.
Thallus Laminariae (Thallus Eckloniae) is the higher a kind of Sargassum of nutritive value in the sea-plant, its main nutrient composition is that laminarin (is mainly Algin, laminarin, sulfated fucan, dietary fiber, the mixture of mannitol etc.), also contain in addition abundant mineral (calcium for example, potassium, sodium, magnesium) and multivitamin (chlorophyll for example, phylloxanthin, carotene etc.) some active component such as, show after deliberation, Thallus Laminariae (Thallus Eckloniae) and relevant kelp product (for example Kelp Powder) all produce effect in balance the body metabolism many aspects, for example in blood fat reducing, blood pressure lowering, regulate the aspect effects such as immunity and catharsis and toxin expelling particularly evident.
And the inventor is surprised to find, Kelp Powder mixes with sulfated fucan to be taken after composite, on the one hand, can significantly improve sulfated fucan in treatment and improve effect aspect diabetes, the diabetic nephropathy, when improving the diabetic supersession disorder, can further improve the indices (for example further strengthened glomerule filter membrane electrostatic barrier function, reduce the plasma protein filtration, reduced urine protein) of diabetic nephropathy, namely can bring into play the effect that its drug effect plays Synergistic to sulfated fucan; On the other hand, take after composite, to take the sulfated fucan nutritional labeling more comprehensive than single.
In another specific embodiments of the present invention, described sulfated fucan is for extracting rear sulfated fucan without degraded; Preferably, macromolecular sulfated fucan.Preferred, molecular weight is 250,000 dalton～1,000,000 dalton.
In another specific embodiments of the present invention, the sulfated fucan of described sulfated fucan for from the L.Japonica Thallus Laminariae (Thallus Eckloniae), extracting.Preferably, the fucose content in this sulfated fucan accounts for this extract gross weight 15-33.5%wt, sulfate content accounts for this extract gross weight 20-34.7%wt.
Can adopt the existing method of this area to prepare described sulfated fucan.In general the preparation method of sulfated fucan comprises extraction, two key steps of purification, can also carry out staged care according to the difference of molecular weight, dissolubility or charge etc. to the product behind the purification, also can degrade to the product behind the purification.Specifically referring to the clear 46-2248 of Japan Patent, CN1129109A, CN1344565A, CN1517356A, CN1560086A, CN101306014A.
In a specific embodiments of the present invention, described molecular weight is 250,000 dalton～1,000,000 daltonian macromolecule sulfated fucan is to make by the method that comprises at least following three steps, described three steps are followed successively by 1) solvent extraction, 2) filtering and impurity removing, 3) to adopt the mode molecular cut off of ultrafiltration be the above materials of 250,000 dalton.
Preferably, the solvent step 1) adopts water.
Preferably, step 2) adopt diatomite filter to remove physical property impurity.
Preferably, to step 3) liquid held back carries out activated carbon decolorizing; Preferred, the concentrated solution after the decolouring is broken away from son process, remove wherein metal ion and non-sulfuric acid base anion.
Preferably, the liquid that obtains at last concentrates, spray drying obtains solid articles.
In a specific embodiments of the present invention, with kelp soaking pulverize to reduce content of iodine, washing desalination remove impurity, drying and dehydrating, pulverizer, sieving makes Kelp Powder.
Preferably, in the manufacturing process of Kelp Powder, take off iodinate.Preferred, describedly take off iodinate and soak for Thallus Laminariae (Thallus Eckloniae) is put into saturated brine.Preferred, the content of iodine of the Kelp Powder that makes is lower than 1ppm.To take off Kelp Powder after the iodinate and the sulfated fucan product after composite, go for various diabeticss, comprise that hyperthyroid patient all can take.
Preferably, carrying out described microwave drying dehydration is reduced to the moisture of Thallus Laminariae (Thallus Eckloniae) below 5%.In a specific embodiments of the present invention, described drying and dehydrating step adopts the mode of microwave dehydration.
Preferably, the diameter of particle of described Kelp Powder is 40～200 orders.Can be so that the Thallus Laminariae (Thallus Eckloniae) cell wall rupture so that cell between the matter polysaccharide discharge fully, on the one hand, the active component in the Kelp Powder is easier to be absorbed by human body, effect increases; On the other hand, more be conducive to assist described sulfated fucan to bring into play its drug effect.
In a specific embodiments of the present invention, percent meter by weight, said composition comprises 1～99% described sulfated fucan, and 99～1% Kelp Powder.Preferably, said composition comprises 20～80% described sulfated fucan, and 80～20% Kelp Powder.Preferred, said composition comprises 20～40% described sulfated fucan, and 80～60% Kelp Powder.Preferred, said composition comprises 25% described sulfated fucan, and 75% Kelp Powder.
The inventor finds through lot of experiments, and the content of the Thallus Laminariae (Thallus Eckloniae) powder in the compositions that contains sulfated fucan of the present invention is that 60-80% left and right sides synergistic action effect is remarkable.Specifically, replenish dosage according to popular in the world dietary fiber, Coming-of-Age Day is taken the 25g dietary fiber, and just to keep normal metabolism required.It seems accordingly, the upper limit addition of Thallus Laminariae (Thallus Eckloniae) powder does not almost have limit in the sulfated fucan Kelp Powder compound, about lower limit, the inventor thinks by experiment, if taking the Thallus Laminariae (Thallus Eckloniae) dietary fiber amount, Coming-of-Age Day is lower than 800mg, then improve constipation or half congealed Xi, the effect of lowering blood-fat and reducing weight is just not obvious, so just very weak to the synergistic action effect of diabetic nephropathy.So we when design sulfated fucan Kelp Powder composite formulations, its preferred side's Kelp Powder content 60-80%, its synergistic action effect is remarkable.
The present invention also provides the above-mentioned application of the compositions that contains sulfated fucan in the product of preparation treatment or prevent diabetes or diabetic nephropathy on the other hand.This product can be medicine, also can be functional food etc.
Further aspect of the present invention provides a kind of pharmaceutical composition, and this pharmaceutical composition comprises the above-mentioned compositions that contains sulfated fucan, and pharmaceutically acceptable carrier.Preferably, the dosage form of this pharmaceutical composition is selected from tablet, pill, capsule, granule, powder, oral liquid or syrup.
Further aspect of the present invention provides a kind of food, and this food comprises the above-mentioned compositions that contains sulfated fucan, and edible adjuvant and/or additive.
The specific embodiment
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used for explanation the present invention and be not used in and limit the scope of the invention.The experimental technique of unreceipted actual conditions in the following example, or the condition of advising according to manufacturer.Unless otherwise indicated, otherwise percentage ratio and umber calculate by weight.
Unless otherwise defined, the same meaning that employed all specialties and scientific words and one skilled in the art are familiar with in the literary composition.In addition, any method similar or impartial to described content and material all can be applicable among the present invention.The usefulness that better implementation method described in the literary composition and material only present a demonstration.
The preparation of embodiment 1 sulfated fucan
The double centner Thallus Laminariae (Thallus Eckloniae) is added tap water soak, must soak 200 liters in water and collect for subsequent use.The Thallus Laminariae (Thallus Eckloniae) stripping and slicing after soaking and soak, get 200 liters in water, this water is mixed with gained 200 premium on currency last time, obtain 400 liters of immersion water that contain sulfated fucan.This 400 premium on currency through diatomite filtration, is obtained the approximately filtrate of 380 liters of clarifications, these 380 liters of filtrates through the 250000 daltonian ultrafilter ultrafiltration of membrane molecule amount, are obtained approximately 30 liters of ultrafiltrates.These 30 liters of ultrafiltrates are added repeatedly decolouring in activated carbon decolorizing posts, obtain liquid after 28 liters of decolourings.Filtrate injection yin, yang ion exchange resin exchange column carries out obtaining 28 from friendship and lifts away from the rear liquid of friendship.From handing over rear liquid ultrafiltration to obtain 5 liters of ultrafiltrates, then it is carried out sterilization treatment and carries out drying, obtain the approximately dry sulfated fucan of 100 grams.
The sulfated fucan that the method obtains contains fucose 15.5%, sulfate 22.1% etc. in the sulfated fucan extract of the above-mentioned drying of detection confirmation, molecular weight 250, and 000-1,000,000 accounts for more than 95%.
The preparation of embodiment 2 Kelp Powders
Soak 1.5 the kilogram Fresh Laminaria Japonica cleans up rear adding saturated brine, soak time 60 days was changed saturated brine to take off iodinate in per 15 days.Then use tap water flushing desalination, centrifuge dewatering, the microwave dryer oven dry is pulverized, and 120 orders sieve, and get approximately 100 gram Kelp Powders.
The Kelp Powder that the method obtains detects and confirms that amount of iodine is lower than 1ppm.
The composite product of embodiment 3 sulfated fucan and Kelp Powder
The sulfated fucan that 10 gram embodiment 1 obtain fully mixes with the Kelp Powder that 90 gram embodiment 2 obtain, and namely gets sulfated fucan Kelp Powder compound 1.
The sulfated fucan that 20 gram embodiment 1 obtain fully mixes with the Kelp Powder that 80 gram embodiment 2 obtain, and namely gets sulfated fucan Kelp Powder compound 2.
The sulfated fucan that 25 gram embodiment 1 obtain fully mixes with the Kelp Powder that 75 gram embodiment 2 obtain, and namely gets sulfated fucan Kelp Powder compound 3.
The sulfated fucan that 30 gram embodiment 1 obtain fully mix with the Kelp Powder of 70 gram embodiment, 2 acquisitions and namely get sulfated fucan Kelp Powder compound 4.
The sulfated fucan that 40 gram embodiment 1 obtain fully mix with the Kelp Powder of 60 gram embodiment, 2 acquisitions and namely get sulfated fucan Kelp Powder compound 5.
Embodiment 4 implementation result data
In order to confirm that the more single prescription sulfated fucan of sulfated fucan Thallus Laminariae (Thallus Eckloniae) compositions or Kelp Powder improve the more remarkable effect of diabetes and diabetic nephropathy, we have selected 90 above diabetes of 5-year courses or by a definite date 6 months clinical trial has been carried out in the diabetic nephropathy patient grouping;
It is specific as follows that each organizes content of the test:
The sulfated fucan that A: embodiment 1 obtains is randomly drawed the sulfated fucan that the embodiment 1 of 10 oral single prescriptions of patient obtains, and a day dose is 0.6g;
The Kelp Powder that B: embodiment 2 obtains is randomly drawed the Kelp Powder that the embodiment 2 of 10 oral single prescriptions of patient obtains, and a day dose is 1.6g;
The sulfated fucan Thallus Laminariae (Thallus Eckloniae) compound 1,2,3,4,5 that C: embodiment 3 obtains; 70 remaining patients take the sulfated fucan Kelp Powder compound 1-5 that embodiment 3 obtains, and the day dose of compound is 1.6g, wherein takes compound 1,2, each 10 of 4,5 patients, and the patient who takes compound 3 is 30;
In A, B, the C test group, administering mode, each dosage, every day, administration number of times was all identical.
Above-mentioned 90 diabetes and diabetic nephropathy patient were treated 6 months continuously, and to A, B, C test data (before the treatment and treat rear 3 months with 6 months relevant diabetes index and the index of correlation clinical data of diabetic nephropathy) compare.
Each organizes data ginseng following table 1.All data are so that (X ± S) expression uses the SPSS statistical software and analyzes, and P＜0.05 is for there being significant difference.
Table 1 test data analyzer:
A: take the single prescription sulfated fucan 0.6g that embodiment 1 obtains day, only in treatment obvious statistics effect is arranged just in rear 6 months, blood glucose, serum creatinine and urine protein are treated front obvious decline; B: take the Kelp Powder of embodiment 2 acquisitions of the single prescription of 1.6g, except obviously reducing at blood glucose after 6 months, though serum creatinine and urine protein have reduction, not statistically significant, can say does not have effect substantially; And the C group, take the sulfated fucan Thallus Laminariae (Thallus Eckloniae) compound 1-5 that embodiment 3 obtains, its successful is better than A, especially blood glucose, and serum creatinine or urine protein all partly or entirely take an evident turn for the better within 3 months treatment phase, and the statistical data after 6 months also is better than the A group.This proves absolutely that sulfated fucan and Kelp Powder have very strong synergistic action effect aspect treatment or prevent diabetes and the diabetic nephropathy.
Especially, the sulfated fucan Kelp Powder compound 3 that embodiment 3 obtains, (fucoidin content is 0.4g for day dose, Kelp Powder is 1.2g), but it is to the therapeutic effect of diabetes and diabetic nephropathy, obviously be better than compound 1,2,4,5 in the C test group, synergistic function is best.Particularly, behind 30 the above diabetics test-meal of 5-year courses sulfated fucan Kelp Powder compounds 3, blood glucose, the produce effects of serum creatinine and urine protein shortens in 3 months action time, simultaneously, taking this compound can arrive 30 day time enteroception, the urine foam reduces, the legs and feet edema alleviates, and pain in the lumbar region acid is swollen to be improved, and the more important thing is, diabetes constipation or half congealed Xi phenomenon all have clear improvement, while is feeling relaxed from head to foot, and so obvious body sense has given diabetics very strong confidence, can adhere to for a long time taking down.
In addition, as can be seen from Table 1, in the C test group, the day dose of compound 1-4 sulfated fucan compatibility is 0.16-0.48g, be lower than the day dose 0.6g of the sulfated fucan of single prescription in the A test group, but compound 1-4 significantly be better than the A test group in treatment or prevent diabetes and diabetic nephropathy.Therefore, adopt sulfated fucan Kelp Powder compound of the present invention, not only reduced the cost of product, improved simultaneously curative effect, have great importance clinically.
Claims (11)
1. compositions that contains sulfated fucan, it is characterized in that, said composition comprises extracts sulfated fucan and the Kelp Powder that obtains from the Phaeophyta plant, wherein, the preparation method of sulfated fucan comprises: the mode molecular cut off of solvent extraction, filtering and impurity removing, employing ultrafiltration is the above materials of 250,000 dalton.
2. compositions according to claim 1 is characterized in that, described sulfated fucan is the macromolecule sulfated fucan, and its molecular weight is 250,000 dalton～1,000,000 dalton.
3. compositions according to claim 1 is characterized in that, described Kelp Powder takes off the product of iodinate for process.
4. compositions according to claim 3 is characterized in that, the content of iodine in the described Kelp Powder is less than 1ppm.
5. compositions according to claim 1 is characterized in that, the diameter of particle scope of described Kelp Powder is at 40～200 orders.
6. the described compositions of any one is characterized in that according to claim 1-5, percent meter by weight, and said composition comprises 1～99% described sulfated fucan, and 99～1% Kelp Powder.
7. compositions according to claim 6 is characterized in that, percent meter by weight comprises the Kelp Powder of 60%-80% in the said composition, and surplus is sulfated fucan.
8. the application of the described compositions of any one in the product of preparation treatment or prevent diabetes or diabetic nephropathy among the claim 1-5.
9. a pharmaceutical composition is characterized in that, this pharmaceutical composition comprises the described compositions of any one among the claim 1-5, and pharmaceutically acceptable carrier.
10. pharmaceutical composition according to claim 9 is characterized in that, the dosage form of this pharmaceutical composition is selected from tablet, pill, capsule, granule, powder, oral liquid or syrup.
11. a food is characterized in that, this food product packets contains right and requires the described compositions of any one among the 1-5, and edible adjuvant and/or additive.
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|---|---|---|---|
| CN 201110044905 CN102151284B (en) | 2011-02-24 | 2011-02-24 | Composition containing fucoidin sulfate and application thereof |
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103239472B (en) * | 2013-05-10 | 2015-09-02 | 首都医科大学 | The medicinal usage of sulfated fucan |
| CN103804504B (en) * | 2014-01-22 | 2015-12-30 | 山东大学（威海） | Low molecule fucoidan and the effect to diabetic nephropathy thereof |
| CN107899005B (en) * | 2017-11-20 | 2021-02-26 | 北京颐方生物科技有限公司 | Composition containing fucoidan, tablet and application thereof |
| CN109260301A (en) * | 2018-10-23 | 2019-01-25 | 深圳市慧思基因科技有限公司 | Application of the algal polysaccharide in preparation prophylactic treatment Rezulin compositions |
| CN109820013B (en) * | 2019-03-13 | 2022-05-06 | 集美大学 | Flour with low glycemic index, preparation method thereof and wheaten food |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101306014A (en) * | 2008-04-03 | 2008-11-19 | 北京世纪博康医药科技有限公司 | Use of brown algae polysaccharide sulfuric acid ester of low molecular weight in preparing medicine for treating diabetic nephropathy |
| CN101912408A (en) * | 2010-06-24 | 2010-12-15 | 首都医科大学 | Application of alginate sulfuric ester in preparing drugs for preventing and treating diabetes and vascular diseases |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101306014A (en) * | 2008-04-03 | 2008-11-19 | 北京世纪博康医药科技有限公司 | Use of brown algae polysaccharide sulfuric acid ester of low molecular weight in preparing medicine for treating diabetic nephropathy |
| CN101912408A (en) * | 2010-06-24 | 2010-12-15 | 首都医科大学 | Application of alginate sulfuric ester in preparing drugs for preventing and treating diabetes and vascular diseases |
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