CN102125546B - Composition for preventing renal calculi - Google Patents
Composition for preventing renal calculi Download PDFInfo
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Abstract
The invention discloses a composition for preventing kidney stone, comprising the following components in parts by weight: 10-70 parts of daidzin, 3-25 parts of genistin, 5-35 parts of glycitin, 0.1-2 parts of daidzein, 0.005-0.05 part of genistein and 0.01-0.1 part of glycitein. The total amount of the components accounts for above 80w/w% of the total weight of the composition.
Description
Technical field
The present invention relates to the medicine food field of prevention and health care, relate in particular to a kind of compositions that is used to prevent renal calculus.
Background technology
The formation mechanism of calcium oxalate stone is complicated.The supersaturation of urine mesoxalic acid calcium concentration helps crystalline nucleation and growth course.But, after single calcium oxalate crystals forms, only adhere to the surface of renal cells or promptly assemble the bigger crystallization of formation to stop up renal tubules; Otherwise; To be washed away rapidly by urine, (Atmani F, Slimani Y also can not take place in renal calculus; Mimouni M; Et al.Effect of aqueous extract from Herniaria hirsuta L.on experimentally nephrolithiasic rats [J] .J Ethnopharmacol, 2004,95 (1): 87-93).Because the composition in normal person and the calcium oxalate patient urine all is in hypersaturated state for the formation of calcium oxalate, therefore, the urine supersaturation just forms one of condition of calculus, and the damage of renal epithelial cell is very important for promoting lithogenous effect.
Existing discovering, in the forming process of calculus, it is a necessary link that crystallization attaches to renal tubules.Renal cells is impaired can obviously to promote crystalline sticking, and high oxalic acid is the principal element that causes the renal cells damage.If can stop or alleviate of the damage of urine oxalic acid effectively, will help the prevention of kidney calcium oxalate stone to renal cells.Discover soybean isoflavone (soy isoflavones; SIF) has certain cytoprotection; This experiment is through living animal experiment, understand soybean isoflavone effectively antagonism high concentration urine oxalic acid cytotoxicity and reduce the formation of kidney calcium oxalate stone.
Soybean isoflavone is the isoflavones components in the flavone compound, is the general name of one type of material, and their mother nucleus structures and flavone compound are similar.The soybean isoflavone compounds is solid under normal conditions, and most of fusing point is more than 100 ℃, stable in properties under the room temperature; It is Powdered to be white in color, nontoxic, tasteless, is easy to store; Water insoluble, certain dissolubility is arranged in pure and mild ketones solvent, very easily be dissolved in dimethyl sulfoxide.
Up to now; From Semen sojae atricolor, isolate 12 kinds of soybean isoflavone isomers altogether; Be divided into two types in free type aglycon (Anglicans) and conjunction type glucosides (Glucosides), the isoflavone genin structure is shown in general formula I and table 1, and the soybean isoflavone glucoside structure is shown in general formula I I and table 2:
Table 1 isoflavone genin structure
| R 1 | R 2 | Aglycon |
| H | H | Daidzein (Daidzein) |
| OH | H | Genistein (Genistein) |
| H | OCH3 | Glycitein (Glycitein) |
Table 2 soybean isoflavone glucoside structure
Research shows that soybean isoflavone has the various biological activity, but it does not see bibliographical information as yet to the intervention effect that rat calcium oxalate renal calculus generates.Lithangiuria is a frequently-occurring disease, and relapse rate is also very high, does not still have the prevention method of putting things right once and for all at present.Therefore, the prevention of urinary stone is the task of a lifelong participation, and seeking a kind of effective prevention method easy, cheap, that patient's compliance is good of originating has important practical sense.
Summary of the invention
The present invention aims to provide a kind of method of preventing renal calculus.
In the present invention, a kind of purposes of compositions is provided, has been used to prepare the pharmaceutical composition or the food compositions that prevent renal calculus, described compositions contains following composition:
A.10-70 weight portion daidzin (Daidzin),
B.3-25 weight portion genistin (Genistin),
C.5-35 weight portion Glycitein glycosides (Glycitin),
D.0.1-2 weight portion daidzein (Daidzein),
E.0.005-0.05 weight portion genistein (Genistein) and
F.0.01-0.1 weight portion Glycitein (Glycitein);
The total amount of said composition (a)+(b)+(c)+(d)+(e)+(f) accounts for more than the 80w/w% of composition total weight.
Preferably, described compositions contains:
A.25-70 weight portion daidzin (Daidzin),
B.8-20 weight portion genistin (Genistin),
C.12-30 weight portion Glycitein glycosides (Glycitin),
D.0.5-1.5 weight portion daidzein (Daidzein),
E.0.01-0.03 weight portion genistein (Genistein) and
F.0.03-0.08 weight portion Glycitein (Glycitein).
In another preference, also can contain the conjunction type soybean isoflavone glucoside in the described compositions; Described conjunction type soybean isoflavone glucoside is selected from following one or more: Acetyldaidzin (Acetydaidzin), Acetylgenistin 6''-O-Acetylgenistin (Acetygenistin), acetyl group Glycitein glycosides (Acetyglycitin), malonyl daidzin (Malonydaidzin), malonyl genistin (Malonygenistin), malonyl Glycitein glycosides (Malonyglycitin).
In another preference, the total amount of said composition a+b+c+d+e+f accounts for more than the 90w/w% of composition total weight.
In such use, described renal calculus is calcium oxalate renal calculus.
In another preference, the dosage form of described pharmaceutical composition is selected from peroral dosage form, injection or topical dosage form.
In another preference, described prevention renal calculus is to reduce urine concentration of oxalic acid and/or urine oxalic acid excretion.
In another preference, described prevention renal calculus is to increase urine citric acid excretion.
In another preference, described prevention renal calculus is to reduce the adhesion of kidney calcium oxalate crystal, assemble and grow into calculus.
In another preference, described prevention renal calculus is to reduce the nephrocyte apoptotic index.
In view of the above, the invention provides a kind of method of easy, cheap, that patient's compliance the is good effective prevention urinary stone of originating.
Description of drawings
Fig. 1 detects the lithogenous experimental road line chart of compositions prevention kidney of rats of the present invention among the embodiment.
Fig. 2 shows and respectively organizes rat experiment closing day body weight situation in the experimental example; Wherein
A representes the blank group; B representes that simple ethylene glycol group promptly lures the stone group merely, and C representes that ethylene glycol adds 30mg/kgd soybean isoflavone (soy isoflavones, SIF) group; D representes that ethylene glycol adds 60mg/kgd soybean isoflavone (soy isoflavones; SIF) group, E representes that ethylene glycol adds 150mg/kgd soybean isoflavone (soy isoflavones, SIF) group.
Fig. 3 shows and respectively organizes rat urine amount situation in the experimental example; Wherein
A representes the blank group; B representes that simple ethylene glycol group promptly lures the stone group merely, and C representes that ethylene glycol adds 30mg/kgd soybean isoflavone (soy isoflavones, SIF) group; D representes that ethylene glycol adds 60mg/kgd soybean isoflavone (soy isoflavones; SIF) group, E representes that ethylene glycol adds 150mg/kgd soybean isoflavone (soy isoflavones, SIF) group.
Fig. 4 shows experimental example empty control rats nephridial tissue section (HE dyeing * 200).
Fig. 5 shows and lures stone group kidney of rats tissue slice (HE dyeing * 200) in the experimental example merely.
Fig. 6 shows and lures stone+soybean isoflavone 30mg/kgd intervention group kidney of rats tissue slice (HE dyeing * 200) in the experimental example.
Fig. 7 shows and lures stone+soybean isoflavone 60mg/kgd intervention group kidney of rats tissue slice (HE dyeing * 200) in the experimental example.
Fig. 8 shows and lures stone+soybean isoflavone 150mg/kgd intervention group kidney of rats tissue slice (HE dyeing * 200) in the experimental example.
Fig. 9 shows experimental example empty control rats nephridial tissue section (TUNEL dyeing * 200).
Figure 10 shows and lures stone group kidney of rats tissue slice (TUNEL dyeing * 200) in the experimental example merely wherein, black arrow points TUNEL stained positive cell.
Figure 11 show lure stone+soybean isoflavone 30mg/kgd intervention group kidney of rats tissue slice TUNEL dyeing * 200 in the experimental example); Wherein black arrow points TUNEL stained positive cell.
Figure 12 show lure stone+soybean isoflavone 60mg/kgd intervention group kidney of rats tissue slice TUNEL dyeing * 200 in the experimental example); Wherein black arrow points TUNEL stained positive cell.
Figure 13 shows and lures stone+soybean isoflavone 150mg/kgd intervention group kidney of rats tissue to cut (TUNEL dyeing * 200) in the experimental example; Wherein black arrow points TUNEL stained positive cell.
The specific embodiment
The inventor finds that through extensive and deep research several kinds of isoflavone genins and soybean isoflavone glucoside mix the compositions that forms, and can effectively prevent the generation of renal calculus.On this basis, accomplished the present invention.
As used herein, term " contain " or " comprising " comprised " comprising ", " basically by ... constitute " and " by ... constitute ".
As used herein, term " basically by ... constitute " refer in compositions, except containing neccessary composition or necessary component, also can contain a spot of and not influence the submember and/or the impurity of effective ingredient.For example, can contain sweeting agent to improve taste, antioxidant in case oxidation, and other this areas additive commonly used.
As used herein, term " effective dose " is meant and can produces function or amount active and that can be accepted by people and/or animal to people and/or animal.
As used herein, " weight portion " or " parts by weight " interchangeable use, described weight portion can be any one fixed with milligram, the gram number or the kilogram numerical table show weight (like 1mg, 1g, 2g, 5g or 1kg etc.).For example, a compositions that is made up of 1 parts by weight of component a and 9 parts by weight of component b can be 1 gram component a+9 gram components b, also can be the compositions that 10 gram component a+90 gram components b etc. constitute.In said compositions, a certain percentages of ingredients content=(the parts by weight sum of the parts by weight/all components of this component) * 100%.Therefore, in the compositions that is made up of 1 parts by weight of component a and 9 parts by weight of component b, the content of component a is 10%, and components b is 90%.
Compositions
As used herein, " compositions " contains following composition:
A.10-70 weight portion daidzin (Daidzin); B.3-25 weight portion genistin (Genistin); C.5-35 weight portion Glycitein glycosides (Glycitin); D.0.1-2 weight portion daidzein (Daidzein), e.0.005-0.05 weight portion genistein (Genistein) and f.0.01-0.1 weight portion Glycitein (Glycitein); Preferably, also contain 0.003-0.5 weight portion conjunction type soybean isoflavone glucoside; Wherein the total amount of (a)+(b)+(c)+(d)+(e)+(f) accounts for more than the 80w/w% of composition total weight, preferably is more than the 90w/w%.
Pharmaceutical composition and food compositions
The material that As used herein, " pharmaceutical composition " or " food compositions " are meant compositions provided by the invention and acceptable carrier forms pharmaceutically or on the bromatology.Described food compositions can be a dietary supplement.
Described pharmaceutical composition can be pharmaceutically conventional dosage form, such as but not limited to, granule, capsule, tablet, powder agent, oral liquid, suspension or Emulsion.
As used herein, the composition of term " pharmaceutically acceptable " or " acceptable on the bromatology " is applicable to people and/or animal and does not have excessive bad side reaction (like toxicity, stimulation and allergy), the material of rational benefit/risk ratio is promptly arranged.
As used herein, term " pharmaceutically acceptable carrier " refers to be used for the carrier of therapeutic agent administration, comprises various excipient and diluent.This term refers to some medicament carriers like this: they itself are not necessary active component, and do not have undue toxicity after using.Suitable carriers is well known to those of ordinary skill in the art.(Mack Pub.Co. can find discussing fully about pharmaceutically acceptable excipient in N.J.1991) at Remington ' s Pharmaceutical Sciences.Acceptable carrier can contain liquid on combination of Chinese medicine is learned, like water, saline, glycerol and ethanol.In addition, also possibly there is complementary material in these carriers, like filler, disintegrating agent, lubricant, fluidizer, effervescent, wetting agent or emulsifying agent, correctives, pH buffer substance etc.
Described " pharmaceutically acceptable carrier " or " acceptable carrier on the bromatology " also comprise the composition with prevention renal calculus; Such as but not limited to, yoghourt, bean milk, soy milk powder, bean milk, analysis for soybean powder, rich hydrogen water, rich hydrogen beverage, lactobacillus beverage, Chinese wolfberry fruit drink etc.
Purposes
Compositions provided by the invention can be used to prevent renal calculus, especially prevents calcium oxalate renal calculus.Can give of the generation of the compositions provided by the invention of mammal effective dose with prevention renal calculus.Described mammal comprises mice, rat, pig, cattle, sheep, cat, Canis familiaris L., monkey and people.
The using dosage of the present composition and method for using depend on many factors, comprise patient's age, body weight, sex, natural health situation, nutriture, active component intensity, take, metabolic rate, the order of severity of disease and diagnosis and treatment doctor's subjective judgment.When the total amount of each composition accounts for the 80w/w% of composition total weight when above, recommended doses is 10mg/kg every day.
The above-mentioned characteristic that the present invention mentions, or the characteristic that embodiment mentions can combination in any.All characteristics that this case description is disclosed can with any composition forms and usefulness, each characteristic that is disclosed in the description can anyly provide the alternative characteristics of identical, impartial or similar purpose to replace.Therefore removing has special instruction, the characteristic that is disclosed to be merely the general example of equalization or similar features.
Major advantage of the present invention is:
1, compositions of the present invention can reduce the formation that lures stone model kidney of rats calcium oxalate stone, and its effect is dose dependent.
2, compositions of the present invention can reduce urine oxalic acid excretion, the cytotoxicity of the high urine of antagonism oxalic acid, and the apoptosis of minimizing renal cells increases urine citrate concentration, forms the key link in the chain thereby blocked the kidney calcium oxalate stone.
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in the restriction scope of the present invention.The experimental technique of unreceipted actual conditions in the following example is usually according to the normal condition or the condition of advising according to manufacturer.Unless otherwise indicated, otherwise all percent, ratio, ratio or umber by weight.
Unit in the percent weight in volume among the present invention is well-known to those skilled in the art, for example is meant the weight of solute in 100 milliliters solution.
Only if definition separately, 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 with the institute similar content of putting down in writing or the equalization method and material all can be applicable in the inventive method.The usefulness that preferable implementation method described in the literary composition and material only present a demonstration.
Experimental example
Material
Soybean isoflavone powder: available from North China pharmacy joint-stock company; Content 80%, wherein daidzin Daidzin45.9%, genistin Genistin13.36%, Glycitein glycosides Glycitin20.99%, daidzein Daidzein0.96%, genistein Genistein0.02%, Glycitein Glycitein0.05%.Face the soybean isoflavone suspension that is made into variable concentrations with deionized water with preceding.
Animal divides into groups and medication
The health of selecting for use Shanghai Slac Experimental Animal Co., Ltd. (SLAC) to provide cleans 50 of level Thirty male rats; Body weight 180-220g is divided into 5 groups at random, 10 every group; Adaptability fed for 1 week under same environment, handled for 4 weeks by following method subsequently:
A organizes (blank group): the drink deionized water;
B organizes (luring the stone group merely): with 1% ethylene glycol solution is unique drinking water source;
C group-E organizes (luring stone+soybean isoflavone intervention group): with 1% ethylene glycol solution is unique drinking water source, gives soybean isoflavone powder 30,60,150mg/kgd simultaneously respectively, i.e. 30mg SIF group, 60mgSIF group, 150mg SIF group.Referring to Fig. 1.
Detect index and method
1. test and finish preceding 1 day with metabolic cage collection twenty-four-hour urine liquid and metering, after the metering, be divided into three parts: portion is measured calcium, sodium, potassium concn with biochemical instruments; The a concentration of oxalic acid (it is anticorrosion to add concentrated hydrochloric acid) of surveying; The a urine citrate concentration (it is anticorrosion to add thymol) of surveying.4 ℃ of preservations.Put to death rat with 4% pentobarbital sodium anesthesia back dislocation, cut kidney.
2. urine
The red catalysis photometry of mensuration employing Neutral potassium chromate oxidation methyl of urine concentration of oxalic acid (fiber crops give birth to entirely, Yang Wenchu. the red catalytic spectrophotometric trace of Neutral potassium chromate oxidation methyl oxalic acid [J]. and physical and chemical inspection: chemical fascicle, 1998,34 (7): 309-310)
The mensuration employing pentabromoacetone thiourea colorimetry of urine citric acid concentration (Cao Lvcheng, Zhang Shaoshun chief editor. urinary calculus basis and clinical research [M]. Jinan: Shandong science tech publishing house, 1990:60-86)
3. take out two kidneys; Vertically cut left kidney open; Fix with 4% paraformaldehyde, paraffin section HE dyeing, 200 times of light microscopics are observed the little calculus situation of nephridial tissue calcium oxalate down; Press documentation standards (Thamilselvan S; Menon M.Vitamin E therapy prevents hyperoxaluria-induced calcium oxalate crystal deposition in the kidney by improving renal tissue antioxidant status [J] .BJU Int, 2005,96 (1): 117-26) classification:
0 grade: do not have any crystallization bright spot;
The I level: tiny crystallization bright spot extensively but not in heaps;
The II level: the crystallization chap is big, in heaps, does not connect but be dispersed in;
The III level: crystallization in heaps part is interconnection;
The IV level: extensive crystallization in heaps connects in flakes.
4. the breach end-labelling (TUNEL) that adopts the deoxyribonucleotide terminal transferase to mediate is cut into slices to nephridial tissue and is carried out immunohistochemical staining, and 200 times of light microscopics are observed renal tubules down, and sabal color nuclear is apoptotic cell.With image analysis software Imagine-Pro Phs 5.0 counting apoptotic cells, calculate apoptotic index (apoptotic cells number in 100 cells of each visual field counting).
Statistical analysis
With the analysis of SPSS 13.0 statistical softwares, average is relatively used variance analysis between the measurement data group.All data are all according to following method statistic:
(1) at first carries out test of normality;
(2) if data meets normality (P＞0.05), then carry out the homogeneity of variance analysis, if data homogeneity of variance (P＞0.05) is then carried out variance analysis check (F check).If the variance analysis assay is (P＜0.05) significantly, then further carry out the multiple comparisons check with SNK parametric test method; If The results of analysis of variance is remarkable (P＞0.05) not, then statistics finishes.
(3) if data heterogeneity of variance property then carry out Dunett-T3 parametric test method and carry out multiple comparisons check.
(4), then carry out Kruskal-Wallis check (H check) and Median check if data does not meet normality.If the Kruskal-Wallis assay is (P＜0.05) significantly, then further carry out comparison test in twos with the non parametric tests method; If the Kruskal-wallis assay is not remarkable, then statistics finishes.
For ranked data, adopt the Kruskal-Wallis non parametric tests, if result remarkable (P＜0.05) then carries out comparison test in twos with the non parametric tests method; If the Kruskal-Wallis assay is not remarkable, then statistics finishes.
The result
1. respectively organize rat body weight and urine quantitative changeization
The blank group, lure stone group, 30mg SIF group, 60mg SIF group, 150mg SIF group rat body weight to be respectively 296g, 290g, 296g, 295g, 293g merely; But difference not statistically significant (P＞0.05), difference does not have significance meaning (Fig. 2) between three kinds of dosage soybean isoflavone intervention group.Each organizes rat urine amount average difference does not have the significance meaning.
2. the experiment closing day is respectively organized rat urine sodium, calcium, concentration of oxalic acid situation and twenty-four-hour urine sodium, calcium, oxalic acid excretion (seeing table 3)
Each organizes rat urine sodium, urine calcium concentration, twenty-four-hour urine sodium, CaE amount no significant difference (P＞0.05).B group-E group urine concentration of oxalic acid and twenty-four-hour urine oxalic acid excretion all are significantly higher than A group (P＜0.05).C group urine concentration of oxalic acid and twenty-four-hour urine oxalic acid excretion all are lower than the B group, but the difference not statistically significant.Middle and high dosage intervention group (D, E group) urine concentration of oxalic acid and twenty-four-hour urine oxalic acid excretion all significantly are lower than B, two groups of C (P＜0.05).D, E two groups of urine concentration of oxalic acid and twenty-four-hour urine oxalic acid excretion difference not statistically significant (P＞0.05).
Table 3 is respectively organized rat urine biochemical investigation result
* with the blank group than P＜0.05; ▲ with lure the stone group than P＜0.01 merely; ★ and 30mg SIF organize than P＜0.05
3. the experiment closing day is respectively organized rat urine citric acid concentration ratio (seeing table 4)
B group-E group urine citric acid concentration and twenty-four-hour urine citric acid excretion all significantly are lower than A group (P＜0.05).C group urine citric acid concentration and twenty-four-hour urine citric acid excretion all are higher than the B group, but the difference not statistically significant.Middle and high dosage intervention group (D, E group) urine citric acid concentration and twenty-four-hour urine citric acid excretion all are significantly higher than B, two groups of C (P＜0.05).C-E variable concentrations soybean isoflavone group urine citric acid concentration and twenty-four-hour urine citric acid excretion all raise step by step, but D, two groups of no difference of science of statistics of E.
Each group urine citric acid situation of table 4
* with the blank group than P＜0.05; ▲ with lure the stone group than P＜0.01 merely; ★ and 30mg SIF organize than P＜0.05
4. respectively organize kidney of rats tubule calcium oxalate crystal grade scoring
Each is organized, and rat kidney pathological section mesoxalic acid calcium is crystal formation does not see expansion and any calcium oxalate crystals deposition, cell marshalling, rule, clear in structure (see figure 4) with tubular ectasia situation: A group kidney of rats tubule; B organizes most of Ren Mus swollen tissue, the crystallization of surperficial spot distribution yellow-white, and glomerule has out-of-shape more, and obviously there is the transparent calcium oxalate crystal of yellow-white in the tube chamber expansion in most tube chambers, and part tube chamber intercrystalline is assembled agglomerating (see figure 5); C organizes tubular ectasia, has the transparent calcium oxalate crystal (see figure 6) of yellow-white in the tube chamber, and rare slabbing, tube chamber enlarge than the B group and alleviate to some extent; D group and E group renal tubules structure and calcium oxalate crystal deposition conditions occupy (P＜0.05) (seeing Fig. 7-8) between A group (P＜0.05) and the B group, and the accidental point-like of renal tubules intracavity is dispersed in calcium oxalate crystal, and tube chamber enlarges than the B group and obviously alleviates; Along with the increase of soybean isoflavone dosage, the renal tubules crystallization has the trend (r=-0.569, P＜0.05) of minimizing, the calcium oxalate crystal diversity of values not statistically significant between C group and the B group, and D group, E group have statistical significance with B group calcium oxalate crystal diversity of values.D group calcium oxalate crystal score value is higher than the E group, but difference not statistically significant (P＞0.05).
Table 5 is respectively organized distribution of kidney of rats calcium oxalate crystal grade and scoring
5. respectively organize rat renal tubular epithelial cells level of apoptosis situation
Table 6 shows that B organizes to luring the stone group merely, and its nephrocyte apoptotic index is the highest; The C group is low dosage soybean isoflavone intervention group; Compare with the B group; Two groups of renal cells level of apoptosis no significant differences (P＞0.05), but D group and E group show that the soybean isoflavone of middle and high dosage has tangible intervention effect to this, and its effect is dose dependent.In three various dose intervention group, the D of middle and high dosage, two groups of nephrocyte apoptotic indexs of E are compared with the C of low dosage intervention group, and difference has statistical significance, but the group difference not statistically significant (P＞0.05) of two groups of D, E.
Table 6 is respectively organized kidney of rats tubule apoptosis level
| Group | Apoptotic index | The range of decrease (comparing) with the B group |
| A | 2.6±0.97 | / |
| B | 20.1±2.02 ＊ | / |
| C | 18.4±3.83 ＊ | 8.4％ |
| D | 12.2±1.75 ＊▲★ | 39.3％ |
| E | 10.6±1.96 ＊▲★ | 47.3％ |
* with the blank group than P＜0.05; ▲ with lure the stone group than P＜0.01 merely; ★ compares P＜0.05 with 30mg SIF group
Correlation coefficient between concentration of oxalic acid, citric acid concentration and the renal cells apoptotic index is respectively 0.882 and-0.855, all P＜0.01.Correlation coefficient between citric acid concentration, renal cells apoptotic index and the crystallization scoring is respectively 0.690 and 0.714, all P＜0.01.
Discuss
In order to illustrate the renal calculus pathogeny, seek the effectively preventing method, it is very necessary to copy the animal model that meets human renal calculus pathogenic process.At present, bringing out animal renal calculus has several different methods, and distinct methods can produce the calculus and the calcification of heterogeneity and different parts, and the success rate of Cheng Shi and time are also inconsistent.General chronic one-tenth cubic meter of stone method is long experimental period, and gallstone formation rate is low.The most common spent glycol method modeling in the present domestic scientific research, it is easy and simple to handle, and gallstone formation rate is high, good reproducibility; The calculus that forms is distributed in positions such as renal papillae, medullary substance and cortex mostly; And be chronic Cheng Shi, the screening that is applicable to anti-stone medicine and observation of curative effect and become pathological research in the stone process (leaf Zhang Qun, Dong Cheng. urinary system calculus [M]. Beijing: People's Health Publisher; 2003.31), be the animal modeling method of the urinary system calculus of generally acknowledging in the world.
Ethylene glycol is the precursor of oxalic acid; Change into glycolic after getting in the body; The latter both can be converted into oxalic acid under the oxidasic effect of glycolic, also can be through the glyoxalic acid that is catalytically converted into of lactic acid dehydrogenase, and glyoxalic acid can directly finally be converted into oxalic acid again under non-enzyme effect.Give feeding animal ethylene glycol, behind internal metabolism, finally change into oxalic acid, discharge through urine, increase the concentration of urine mesoxalic acid, the calculus formation rate is high in the kidney.
Given this, the inventor has adopted with ethylene glycol and has given the method that rat is drunk, and carries out the modeling in 4 weeks, considers the convenience of freely absorbing and meets rat drinking-water rule, and directly wiring solution-forming gives and drinking.
Oxalic acid is one of most important factor that forms the calcic lithangiuria.The concentration ratio of normal urine mesoxalic acid and calcium is about 1: 5, and is being prone to form in the urine of calcium oxalate crystal, and the ratio of oxalic acid and calcium is 1: 1; In the calcium oxalate crystals; The ratio of oxalic acid and calcium also is 1: 1, during this prompting calcium oxalate stone forms, and the effect that is far longer than calcium that oxalic acid play a part.(Rodgers A.Aspects of calcium oxalate crystallization:theory such as Rodgers; In vitro studies; And in vivo implementation [J] .J Am Soc Nephrol, 1999,10 Suppl 14:S351-4) research shows; Oxalic acid is 23 times of calcium to the contribution of calcium oxalate degree of supersaturation, and calcium is also influential to the secretion of urine oxalic acid.(Sun Xizhao such as Sun Xizhao; Guo Hongqian, Ye Zhangqun. the origin cause of formation of urinary calculi [J]. clinical magazine of urology surgery, 2003; 18 (6): 321-326.) research also shows; Urine mesoxalic acid concentration by day excretion increase by 10%, just equaling to urinate calcium increases by 100%, i.e. the raising of urine mesoxalic acid concentration is 10 times of calcium to the contribution of calcium oxalate saturation.Therefore, to increase be a kind of more dangerous one-tenth stone factor to urine mesoxalic acid excretion.
Result of the present invention shows, no significant difference property (P＞0.05) between each group of rat twenty-four-hour urine amount and body weight in the experimental example of the present invention.Simple ethylene glycol lures stone group urine concentration of oxalic acid to be increased to 3.00mmol/L by 0.99mmol/L, has increased more than 3 times, and twenty-four-hour urine oxalic acid excretion is elevated to 79.05 μ mol/24h by 27.95 μ mol/24h, has increased by 2.82 times.Urine sodium and urine calcium concentration and 24 hours excretions thereof all obviously do not change (P＞0.05).The intervention group of three various dose urine concentration of oxalic acid and 24 hours excretions all are higher than the blank group to some extent, but the rising degree is lower than and lures the stone group merely, especially middle and high dosage intervention group.
Research both at home and abroad shows that oxalic acid can produce damaging action to the renal cells of cultivating, and calcium oxalate crystals is easier to adhere to the renal cells surface of damage, finally possibly bring out the formation of calcium oxalate stone.The research of cell in vitro culture studies and animal model aspect is all found; Be exposed to the oxalic acid of high concentration and/or the renal cells of calcium oxalate crystals and cell membrane damage can occur; The degree of cell injury and crystalline concentration with contact the crystalline time and be directly proportional, be exposed under the oxalic acid, calcium oxalate of high concentration for a long time even apoptosis or necrosis occur.
In the experimental example of the present invention to taking after the rat that lures the stone agent intervenes with soybean isoflavone synchronously; Show when irritate hello soybean isoflavone 30mg/kg to rat every day; This dosage lures the intervention effect of stone agent rat not fairly obvious to drinking, and the kidney crystallization scoring that high urine oxalic acid causes is compared no significant difference with the renal cells apoptotic index with luring the stone group merely; But when dosage reached 60mg/kg, then intervention effect was fairly obvious, and the renal cells apoptotic index amplification that high urine oxalic acid is caused reduces by 40.9% (P＜0.05), and renal tubules calcium oxalate crystal grade scoring reduces by 39.3% (P＜0.05); Along with soybean isoflavone irritate to be fed dosage and is enlarged to 150mg/kg, the renal cells apoptotic index is all than luring the stone group that fine improvement is arranged merely, but compares the difference not statistically significant with the 60mg/kg group.Above results suggest, soybean isoflavone pass through to reduce the damage of high oxalic acid to renal cells, thereby reduce the crystalline adhesion of oxalates, gathering, growth, reach the protective effect to kidney.And soybean isoflavone 60mg/kg can give full play to the protective effect to high oxalic acid kidney.This research proof, soybean isoflavone can be resisted the toxic action of urine oxalic acid to renal cells, have and suppress the effect that the kidney calcium oxalate stone forms, and show good dose-effect relationship.
Citric acid is to suppress to contain the important component that calcium calculus generates in the urine, and epidemiological study confirms that renal calculus patient hypocitruria incidence rate reaches 20-60%, and hypocitruria is the independent hazard factor of renal calculus morbidity and recurrence.In experimental example of the present invention, the urine citric acid concentration level of each calcium oxalate large mouse with renal calculs model group is starkly lower than the blank group, and especially simple ethylene glycol lures the stone group, and it is compared with the blank group, and urine citric acid concentration is reduced to blank group 34.7%.And the SIF intervention group of 3 various dose lures the stone group to compare with simple ethylene glycol, and urine citric acid concentration has then raise 12.2%, 30.7% and 35.7% respectively.Lure the stone group to compare with simple ethylene glycol, the rising not statistically significant of 30mg/kg SIF intervention group urine citric acid concentration, the change of 60mg/kg group, 150mg/kg group urine citric acid concentration then has statistical significance; But the urine citric acid concentration difference not statistically significant between 60mg/kg group and the 150mg/kg group.
From the statistical result of experimental example of the present invention, soybean isoflavone has the cell toxicant of antagonism oxalic acid, the effect of protection renal tubular epithelial, can reduce the apoptosis of renal cells, thereby reduce the deposition of calcium oxalate crystal and grow into stone.
The above is merely preferred embodiment of the present invention; Be not in order to limit essence technology contents scope of the present invention; Essence technology contents of the present invention is broadly to be defined in the claim scope of application, and if any technological entity or method that other people accomplish are defined identical with the claim scope of application; Also or a kind of change of equivalence, all will be regarded as and be covered by among this claim scope.
Claims (9)
1. the purposes of a compositions is used to prepare the pharmaceutical composition or the food compositions that prevent renal calculus, and described compositions contains following composition:
A.10-70 weight portion daidzin (Daidzin),
B.3-25 weight portion genistin (Genistin),
C.5-35 weight portion Glycitein glycosides (Glycitin),
D.0.1-2 weight portion daidzein (Daidzein),
E.0.005-0.05 weight portion genistein (Genistein) and
F.0.01-0.1 weight portion Glycitein (Glycitein);
The total amount of said composition (a)+(b)+(c)+(d)+(e)+(f) accounts for more than the 80w/w% of composition total weight;
Described renal calculus is calcium oxalate renal calculus.
2. purposes as claimed in claim 1 is characterized in that, described compositions contains:
A.25-70 weight portion daidzin (Daidzin),
B.8-20 weight portion genistin (Genistin),
C.12-30 weight portion Glycitein glycosides (Glycitin),
D.0.5-1.5 weight portion daidzein (Daidzein),
E.0.01-0.03 weight portion genistein (Genistein) and
F.0.03-0.08 weight portion Glycitein (Glycitein).
3. like claim 1 or 2 arbitrary described purposes, it is characterized in that, also can contain the conjunction type soybean isoflavone glucoside in the described compositions.
4. purposes as claimed in claim 3, described conjunction type soybean isoflavone glucoside are selected from following one or more: Acetyldaidzin (Acetydaidzin), Acetylgenistin 6''-O-Acetylgenistin (Acetygenistin), acetyl group Glycitein glycosides (Acetyglycitin), malonyl daidzin (Malonydaidzin), malonyl genistin (Malonygenistin), malonyl Glycitein glycosides (Malonyglycitin).
5. purposes as claimed in claim 1 is characterized in that the total amount of said composition a+b+c+d+e+f accounts for more than the 90w/w% of composition total weight.
6. purposes as claimed in claim 1 is characterized in that, described prevention renal calculus is to reduce urine concentration of oxalic acid and/or urine oxalic acid excretion.
7. purposes as claimed in claim 1 is characterized in that, described prevention renal calculus is to increase urine citric acid excretion.
8. purposes as claimed in claim 1 is characterized in that, described prevention renal calculus is to reduce the adhesion of kidney calcium oxalate crystal, assemble and grow into calculus.
9. purposes as claimed in claim 1 is characterized in that, described prevention renal calculus is to reduce the nephrocyte apoptotic index.
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| CN101036725A (en) * | 2006-03-17 | 2007-09-19 | 邵淑艳 | Chinese traditional medicine for treating nephrolithiasis |
| CN101200744A (en) * | 2007-12-07 | 2008-06-18 | 南京师范大学 | High-effective clean method for preparing soybean isoflavone aglycone |
| CN101537079A (en) * | 2008-03-21 | 2009-09-23 | 北京润康普瑞生物技术有限公司 | Pharmaceutical composition or health-care product for improving sleeping and delaying senility and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101036725A (en) * | 2006-03-17 | 2007-09-19 | 邵淑艳 | Chinese traditional medicine for treating nephrolithiasis |
| CN101200744A (en) * | 2007-12-07 | 2008-06-18 | 南京师范大学 | High-effective clean method for preparing soybean isoflavone aglycone |
| CN101537079A (en) * | 2008-03-21 | 2009-09-23 | 北京润康普瑞生物技术有限公司 | Pharmaceutical composition or health-care product for improving sleeping and delaying senility and preparation method thereof |
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