CN105640985A - Peritoneal dialysis fluid (lactate) (low-calcium) medicinal composition - Google Patents
Peritoneal dialysis fluid (lactate) (low-calcium) medicinal composition Download PDFInfo
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Abstract
The invention relates to a peritoneal dialysis fluid (lactate) (low-calcium) medicinal composition. The peritoneal dialysis fluid (lactate) (low-calcium) medicinal composition contains 1.5-4.0% of glucose, 0.5-0.6% of sodium chloride, 0.01-0.02% of calcium chloride, 0.004-0.006% of magnesium chloride, and 0.4-0.5% of sodium lactate. The peritoneal dialysis fluid (lactate) (low-calcium) medicinal composition is characterized in that the pH is adjusted to be 7.3-7.7 by adopting trihydroxymethyl aminomethane.
Description
Technical field
The present invention relates to a kind of with trishydroxymethylaminomethane adjustment weakly alkaline peritoneal dialysis solution (lactate) (low calcium) pharmaceutical composition.
Background technology
Peritoneal dialysis (peritonealdialysis, PD) it is the important renal replacement therapy (CRRT) of end stage renal failure patient, due to compared with hemodialysis, have applied widely, dialytic efficiency is high, residual renal function is kept, patients ' life quality advantages of higher, occupies more and more consequence in the alternative medicine of chronic renal failure. Successful peritoneal dialysis it is critical only that the peritoneum and peritoneal dialysis solution that ultrafiltration function is good. Due to the chronicity of peritoneal dialysis treatment, the ultrafiltration performance of peritoneum is often affected by various factors over the course for the treatment of changes, and this change is irreversible, will ultimately result in patient's peritoneum ultrafiltration function and loses, it is impossible to carries out abdomen again and thoroughly treat. Wherein peritoneal fibrosis caused by the poor biocompatibility of peritoneal dialysis solution (peritonealdialysisfluid, PDF) and ultrafiltration unsuccessfully become the major issue that current peritoneal dialysis is badly in need of and must be solved. Abdomen abdomen dialysis solution (peritonealdialysisfluid, PDF) it is core link in PD, the ultimate principle of peritoneal dialysis, be exactly utilize different the formed electrochemistry potential energy difference of the concentration of each composition between patients serum from peritoneal dialysis liquid in peritoneal cavity, by disperse and Ultrafiltration correct in uremic patient blood physically different. The setting of each composition of peritoneal dialysis liquid and compatibility are based primarily upon this principle. Desirable peritoneal dialysis liquid not only can fully remove toxin, ultrafiltration moisture, moreover it is possible to protection peritoneal membrane function, reduces the generation of ultrafiltration exhaustion (UFF). The lactate dialysate that traditional peritoneal dialysis liquid is is penetrating agent with the glucose of variable concentrations, clinical practice for many years shows, although PD has played highly important effect in the treatment of chronic kidney hypofunction, but from human physiology's angle, current conventional use of dialysis solution is still prominent there is problems in that (1) dialysis solution is with glucose for main penetrating agent, because it can be absorbed by peritoneum, therefore its osmosis is held time very short, it is difficult to reach desirable liquid and Solute removal; (2) in dialysis solution, some composition (glucose and base etc.) can activate inflammatory cytokine (somatomedin, nitric oxide synthetase), life-time service can cause peritoneum chronic inflammatory to change, and promotes peritoneal fibrosis and thickens; (3) after the glucose in dialysis solution is decomposed in vivo, the non-product of substantial amounts of advanced glycosylation endproduct (AGEs) can be produced, the latter can extensively deposit in vivo, especially interstitial can be caused to thicken after blood vessel wall and peritoneum interstitial deposit, cause that ultrafiltration function declines; (4) glucose degradable in high-temperature sterilization forms a series of glucose degradation products (GDPs), GDPs can coup injury peritoneal cell, and promote that AGE is formed;(5) in dialysis solution, buffer base adopts lactate mostly, and they must first pass through the metabolic conversion of liver is after bicarbonate, can play the acidosic effect of correction, therefore the patient that a part is associated with hepatic disease often has certain limitation.
Glucose is as traditional peritoneal dialysis solution penetrating agent, although itself is without direct biology toxicity, but a large amount of virose glucose degradation products (glucosedegradationproducts.GDPs) can be produced in the process of high temperature sterilize and single bag of long term storage, research finds that in heating disinfection process, tradition pH value condition (5.5��6.5) residing for PDF can dramatically increase acetaldehyde, formaldehyde, methylglyoxal, 3-deoxyfructose (3-deoxy-glucosone, 3-DG), 3, the double, two deoxyglucose keto-aldehyde-3-alkene (3 of 4-, 4-dideoxyglucosone-3-ene, 3, 4-DGE), the generation of the GDPs such as 5 hydroxymethyl furfural. when GDPs enters abdominal cavity, damaging Peritoneal Mesothelial Cells function, and cause a large amount of cytokine such as IL-6, TGF-��, VEGF etc. produces. therefore can induce and increase the weight of Peritoneal Mesothelial Cells transdifferentiation and new vessels formation as peritoneal tissues is exposed in the peritoneal dialysis solution of high GDPs for a long time, additionally, non-enzyme material can also be attached to albumen and lipid by GDPs, and then form advanced glycation end products (advancedglycationendproducts, AGE), AGE is attached to the Peritoneal Mesothelial Cells layer containing AGE receptor (RAGE), increase the weight of peritoneal injury, and AGE can enter blood circulation, increase the weight of atherosclerosis and amyloidosis etc., therefore the prolonged application of conventional peritoneal dialysis liquid can cause peritoneum ultrafiltration function and the failure of PD technology, owing to generally believing the representative that 5 hydroxymethyl furfural (5-HMF) is glucose degradation products (GDPs), so general 5 hydroxymethyl furfural (5-HMF) is as evaluation index in Glucose Liquid body preparation. although glucose has above-mentioned deficiency, but at present owing to other penetrating agent are also immature, document " Development outline of peritoneal dialysis solution " (Zhu Hong, Journal of Chinese Hospital Pharmacy, 2000,5th phase) point out that up to the present aminoacid, glucose polimer, small molecule crystals glycerol, Sorbitol, xylitol and fructose, macromolecular colloid gelatin, polycation, dextran and polypeptide all as penetrating agent, but still can not find the penetrating agent of alternative glucose.
Generally believe that glucose solution is stable in acid condition at present, and the bibliographical information (pH value impact on five kinds of infusion solutions stability, practical medical technologies magazine, 2007, 8, 3236) glucose solution semi-finished product pH value is more high, finished product pH value fall is more big, it is more big that content declines, it is more many that 5 hydroxymethyl furfural (5-HMF) produces, medicinal liquid variable color is more deep, other documents also have (the pH value impact on glucose injection stability of similar report simultaneously, modern combination of Chinese and Western medicine magazine, 1999, 8, 1221), Chinese Pharmacopoeia (2010 editions) is 3.2-6.5 for glucose injection PH claimed range, it is 3.5-5.5 for Dextrose and Sodium Chloride Inj. PH claimed range, also illustrate that above-mentioned viewpoint. just because of peritoneal dialysis solution pH value all��7, peritoneal dialysis solution in use occurs in that some problems, first the body fluid of normal person lies substantially in alkalescence, such as pH value of blood 7.35��7.45, the pH value 7.20��7.45 of the pH value 7.0��7.5 of tissue fluid, Cell sap, pH value peritoneal dialysis solution all��7 causes bigger zest with body fluid gap compared with conference, peritoneum is caused damage, secondly end stage renal failure patient often all has acidosic problem, and the conventional peritoneal dialysis liquid of life-time service acidity can increase the weight of this point undoubtedly.
Additionally in peritoneal dialysis solution possibly together with substantial amounts of divalent calcium, magnesium ion as buffer salt, it is considered that the calcium salt in dialysis solution, magnesium salt meeting and base in the basic conditions, as hydroxyl, carbonate react and cause precipitation.
Just because of glucose, divalent calcium, magnesium ion the requirement of buffer salt stability, research worker is always puzzled can not get both between the effect of medicine, stability, zest, untoward reaction, cannot accept or reject, so in order to ensure that current peritoneal dialysis solution is still with glucose for penetrating agent, with valency calcium, magnesium ion for buffer salt, so peritoneal dialysis solution pH value still��7.
So the pH value of current peritoneal dialysis solution is all��7, even adding base is also solved by the method for dual-chamber bag system, deposit in dual-chamber bag respectively by base and other divalent calcium, magnesium ion, in use base is mixed mutually with divalent ion, but this kind of method is relatively costly, easily there is local supersaturation in mixing in bicarbonate and divalent calcium, magnesium ion simultaneously, increase the possibility that insoluble microparticle produces, but also cannot detect, add the risk of patient.
Summary of the invention
In the present invention, " peritoneal dialysis solution (lactate) (low calcium) " name is called the title that State Food and Drug Administration is such dialysis solution Uniform provisions, it is specifically shown in State Food and Drug Administration standard YBH00232007, below can by peritoneal dialysis solution (lactate) (low calcium) referred to as peritoneal dialysis solution.
Through Literature Consult and research, we have found that actually no matter glucose after acid condition or alkali condition store certain time, degradation reaction all can occur, relatively small in acid condition (especially under high temperature) 5 hydroxymethyl furfural degradation reaction, past is in order to emphasize the stability of product, so the PH of the peritoneal dialysis solution of glucose is controlled in acid condition always, but the peritoneum that acid meeting is to human body, body fluid has undesirable effect, the glucose degradation products simultaneously affecting peritoneum also includes formaldehyde, the material that the toxicity such as acetaldehyde are higher, 5 hydroxymethyl furfural is the one in glucose degradation products, glucose degradation products only measures 5 hydroxymethyl furfural and there is certain one-sidedness using this material as the index of product quality, actually formaldehyde, the far super 5 hydroxymethyl furfural of the toxicity of the materials such as acetaldehyde. relatively many by the 5 hydroxymethyl furfural compared with acid of alkalescence peritoneal dialysis solution (lactate) (low calcium) in the stability experiment accelerated test of known 4 months, but the formaldehyde that toxicity is bigger, acetaldehyde is less, the toxicity gap generally that catabolite produces is little, and the 5 hydroxymethyl furfural compared with acid of the alkalescence peritoneal dialysis solution after the ordinary temperature stability test of 12 months, the formaldehyde that toxicity is bigger, it is less that acetaldehyde increases, the toxicity that catabolite produces is less generally, so in peritoneum infringement experiment, we are by finding that pH value is less than on the impact of peritoneum at the alkalescence peritoneal dialysis solution of 7.3-7.7 and the acid peritoneal dialysis solution of PH��7 of same prescription. and pH value can also improve, at the alkalescence peritoneal dialysis solution of 7.3-7.7, the problem that the blood pH that life-time service acidity peritoneal dialysis solution causes declines, be conducive to alleviating the accumulation of internal acidity.
By being alkalescence for using trishydroxymethylaminomethane to regulate peritoneal dialysis solution, under other divalent calcium, the simultaneous condition of magnesium ion, it is formed without precipitation.
In preparation, invention before is then after peritoneal dialysis solution is configured, liquid high temperature sterilize respectively is regulated with alkalescence, the method that then mixes is thus avoiding the problem that the catabolite that high temperature sterilize under alkali condition causes increases, and adopt low concentration, the method being slowly added to can avoid base and divalent calcium, magnesium ion forms precipitation, but mixed process ensures there is air pollution and be mixed into the possibility of insoluble granule, operation in mixing simultaneously needs extremely fine, flow velocity, temperature and mixing speed must control extremely fine, otherwise there is the situation that insoluble granule exceeds standard. and the present invention adopts trishydroxymethylaminomethane to regulate pH value to alkalescence, then can adopt the mode of sterilizing after mixing, it is to avoid above-mentioned problem.
A kind of peritoneal dialysis solution (lactate) (low calcium) compositions, glucose containing 1.5-4.0%, the sodium chloride of 0.5-0.6%, the calcium chloride of 0.01-0.02%, the magnesium chloride of 0.004-0.006%, and the sodium lactate of 0.4-0.5%, it is characterised in that described trishydroxymethylaminomethane used for peritoneal dialysate regulates pH value to 7.2-7.7. Above-mentioned peritoneal dialysis solution, is characterized in that the content of sodium chloride is 0.5377%, and the content of calcium chloride is 0.0147%, and the content of magnesium chloride is 0.00508%, and the content of sodium lactate is 0.4483%, and the content of sodium pyrosulfite is 0.005%.
Above-mentioned peritoneal dialysis solution, is characterized in that compositions is by the glucose of 1.5-4.0%, the sodium chloride of 0.5-0.6%, the calcium chloride of 0.01-0.02%, the magnesium chloride of 0.004-0.006%, and the sodium lactate of 0.4-0.5%, trishydroxymethylaminomethane and water lower than 5% form. Above-mentioned peritoneal dialysis solution, is characterized in that the content of sodium chloride is 0.5377%, and the content of calcium chloride is 0.0147%, and the content of magnesium chloride is 0.00508%, and the content of sodium lactate is 0.4483%.
Above-mentioned peritoneal dialysis solution, it is characterized in that compositions is by the glucose of 1.5-4.0%, the sodium chloride of 0.5-0.6%, the calcium chloride of 0.01-0.02%, the magnesium chloride of 0.004-0.006%, and the sodium lactate of 0.4-0.5%, the sodium pyrosulfite of 0.001%��0.01%, sodium sulfite or sodium sulfite, trishydroxymethylaminomethane lower than 5% and water composition. On peritoneal dialysis solution, it is characterized in that the content of sodium chloride is 0.5377%, the content of calcium chloride is 0.0147%, and the content of magnesium chloride is 0.00508%, and the content of sodium lactate is 0.4483%, and the content of sodium pyrosulfite is 0.005%.
Above-mentioned peritoneal dialysis solution, is characterized in that pH value is 7.3-7.5.
Above-mentioned peritoneal dialysis solution, is characterized in that pH value is 7.3-7.4.
Above-mentioned peritoneal dialysis solution, is characterized in that the content of trishydroxymethylaminomethane is lower than 5%.
Above-mentioned peritoneal dialysis solution, is characterized in that the sodium pyrosulfite possibly together with 0.001%��0.01%, sodium sulfite or sodium sulfite.
The preparation method of above-mentioned peritoneal dialysis solution, it is characterized in that step one is by the glucose of 1.5-4.0%, the sodium chloride of 0.5-0.6%, the calcium chloride of 0.01-0.02%, the magnesium chloride of 0.004-0.006%, and the sodium lactate of 0.4-0.5% and part water mix, step 2 is that the pH value that trishydroxymethylaminomethane, water for injection regulating step one obtain liquid at 7.3-7.7 and regulates total amount to 100%.
The preparation method of above-mentioned peritoneal dialysis solution, it is characterised in that the sterilization of liquids that before step 2, step one can be obtained, it is also possible to sterilizing after step 2 completes. The preparation method of above-mentioned peritoneal dialysis solution, it is characterised in that sterilizing methods is high temperature or High Temperature High Pressure.
A kind of peritoneal dialysis solution described above reduces the application in peritoneal fibrosis medicine in preparation.
In case of no particular description, in the present invention, the content of compositions is w/v, for instance the sodium chloride of 0.4-0.7% is the sodium chloride having 0.4-0.7g in 100ml water.
Glucose in the present invention, calcium chloride, magnesium chloride content calculate with Dextrose monohydrate, calcium chloride dihydrate, magnesium chloride hexahydrate respectively, the glucose of such as 1.5-4% is actually 1.5-4% Dextrose monohydrate, the glucose of such as 1.5-4% be 100ml water containing in have a Dextrose monohydrate of 1.5-4g, rather than 100ml water containing in have the glucose of 1.5-4g.
Embodiment
In case of no particular description, the glucose in embodiment, calcium chloride, magnesium chloride refer respectively to Dextrose monohydrate, calcium chloride dihydrate, magnesium chloride hexahydrate.
Example of formulations 1
Formula is following table such as, and subpackage specification is 1000ml/ bag, and in table, data are amount to the formula of every bag of dialysis solution
1. dope preparation: take the water for injection of recipe quantity 10%, add other compositions stirring of recipe quantity to all dissolvings, be subsequently adding after medicinal charcoal 0.1��1% stirs, after placing 10��20 minutes after 0.22 ��m of end-filtration 115 DEG C of steam sterilizations 15 minutes, obtain standby dope.
2. by trishydroxymethylaminomethane, water for injection, dope, alkali liquor at the uniform velocity being mixed, regulate solution to 1000ml, pH value is the numerical value in upper table, by embedding after 0.22 ��m of end-filtration (every bag of 1000ml or 2000ml). Wherein the content of trishydroxymethylaminomethane is less than 5%.
Nitrogen protection is adopted when preparation and embedding.
3, sterilizing: 115 DEG C of constant temperature 10 minutes
Nitrogen protection is adopted when preparation and embedding.
Example of formulations 2
Formula is following table such as, and subpackage specification is 1000ml/ bag, and in table, data are amount to the formula of every bag of dialysis solution
Preparation method is with embodiment 1.
Example of formulations 3
Formula is following table such as, and subpackage specification is 1000ml/ bag, and in table, data are amount to the formula of every bag of dialysis solution
Preparation method is with embodiment 1.
Example of formulations 4
Formula is following table such as, and subpackage specification is 1000ml/ bag, and in table, data are amount to the formula of every bag of dialysis solution
Preparation method is with embodiment 1.
Comparative examples 1
Formula is following table such as, and subpackage specification is 1000ml/ bag, and in table, data are amount to the formula of every bag of dialysis solution
| Embodiment is numbered | 1-1 | 1-2 |
| Glucose (g) | 15 | 15 |
| Sodium chloride (g) | 5 | 6 |
| Calcium chloride (g) | 0.1 | 0.2 |
| Magnesium chloride (g) | 0.05 | 0.06 |
| Sodium lactate (g) | 4 | 5 |
| PH | 3.5 | 6.5 |
1. dope preparation: take 20% water for injection, puts into the glucose that weighs up, sodium chloride, calcium chloride, magnesium chloride, sodium lactate are stirred to dissolve, and heating is to after all dissolving, regulating pH value as above table with 5%HCl solution, water for injection and be settled to full dose. Be subsequently adding after medicinal charcoal 0.1��1% (g/ml) stirs, medicinal liquid through 0.22 ��m of ultimate filter filter to visible foreign matters qualified after embedding (every bag of 1000ml or 2000ml)
2. sterilizing: 115 DEG C of constant temperature 20 minutes
Nitrogen protection is adopted when preparation and embedding.
Comparative examples 2
Formula is following table such as, and subpackage specification is 1000ml/ bag, and in table, data are amount to the formula of every bag of dialysis solution
| Embodiment is numbered | 2-1 | 2-2 | 2-3 |
| Glucose (g) | 40 | 40 | 40 |
| Sodium chloride (g) | 5 | 5.377 | 6 |
| Calcium chloride (g) | 0.1 | 0.147 | 0.2 |
| Magnesium chloride (g) | 0.05 | 0.0508 | 0.06 |
| Sodium lactate (g) | 4 | 4.483 | 5 |
| PH | 7.7 | 7.4 | 7.2 |
1. dope preparation: take the water for injection of recipe quantity 10%, add other compositions stirring of recipe quantity to all dissolvings, be subsequently adding after medicinal charcoal 0.1��1% stirs, after placing 10��20 minutes after 0.22 ��m of end-filtration 115 DEG C of steam sterilizations 15 minutes, obtain standby dope.
2. Alkali liquid compounding: configuration content, lower than 0.05% sodium bicarbonate solution, is subsequently adding after medicinal charcoal 0.1��1% stirs, after placing 10��20 minutes after 0.22 ��m of end-filtration, 115 DEG C of steam sterilizations 10 minutes, obtain alkali liquor standby.
3, dope, alkali liquor at the uniform velocity being mixed, by alkali liquor, water for injection, regulate solution to 1000ml, pH value is the numerical value in upper table, by embedding after 0.22 ��m of end-filtration (every bag of 1000ml or 2000ml).
Preparation process step 3 notes mixing velocity, precipitation must not occur.
Nitrogen protection is adopted when preparation and embedding.
4, sterilizing: 115 DEG C of constant temperature 10 minutes
Nitrogen protection is adopted when preparation and embedding.
Comparative examples 3
Formula is following table such as, and subpackage specification is 1000ml/ bag, and in table, data are amount to the formula of every bag of dialysis solution
| Embodiment is numbered | 3-1 | 3-2 | 3-3 |
| Glucose (g) | 15 | 15 | 15 |
| Sodium chloride (g) | 5 | 5.377 | 6 |
| Calcium chloride (g) | 0.1 | 0.147 | 0.2 |
| Magnesium chloride (g) | 0.05 | 0.0508 | 0.06 |
| Sodium lactate (g) | 4 | 4.483 | 5 |
| PH | 7.7 | 7.4 | 7.2 |
Preparation method is with comparative examples 2.
Stability test 1
Peritoneal dialysis solution that embodiment, comparative examples are obtained (use same batch crude drug, adjuvant, water for injection) be grouped according to group number, often group 10 bags, every bag of 100ml, stores respectively when thermostatic accelerated experiment, room temperature long term test, detects in the stipulated time.
1, the amount of 5 hydroxymethyl furfural, acetaldehyde, formaldehyde is measured.
Thermostatic accelerated experiment (abbreviation accelerated test) condition: by commercially available back, in temperature 50 C �� 2 DEG C, places when relative humidity 75% �� 5%.
Room temperature long term test (abbreviation long term test) condition: commercially available back, temperature 25 DEG C �� 2 DEG C, places when relative humidity 60% �� 10%.
Acetaldehyde, formaldehyde content adopt external standard method vapor phase method measure, actual conditions is as follows:
Chromatograph: Hewlett-Packard 5890 type gas chromatograph, fid detector.
Chromatographic column: chromatographic column internal diameter 2mm, long 1.5mm glass column, carrier: silanization 102 white monomer (60-80 order), fixative: SE-30
Operating condition: column temperature 190 DEG C, detector: 250 DEG C, vaporizer: 200 DEG C
Sample size: 1 �� l
(unit is for acetaldehyde and the formaldehyde (both are added) content meansigma methods in embodiment, comparative examples peritoneal dialysis solution), 5 hydroxymethyl furfural content assaying method is according to national drug standards WS1The method of-XG-002-2007 measures, and measurement result is absorbance, and absorbance is more high, and 5 hydroxymethyl furfural content is more high.
5 hydroxymethyl furfural measures absorbance (n=10, meansigma methods):
Adopt the light blockage method detection particulate matter quantity in Chinese Pharmacopoeia (2005 editions) annex IXC particulate matter method of inspection
By above-mentioned inspection, alkalescence peritoneal dialysis solution (lactate) (low calcium) in the accelerated test embodiment of the present invention of 4 months 5 hydroxymethyl furfural compared with peritoneal dialysis solution that is acid and that use inorganic base is relatively many, but the formaldehyde that toxicity is bigger, acetaldehyde is less, the toxicity gap generally that catabolite produces is little, and the 5 hydroxymethyl furfural compared with peritoneal dialysis solution that is acid and that use inorganic base of the alkalescence peritoneal dialysis solution (lactate) (low calcium) after the ordinary temperature stability test of 12 months, the formaldehyde that toxicity is bigger, it is less that acetaldehyde increases, the toxicity that catabolite produces is likely to less generally.
In the accelerated test of 4 months, alkalescence peritoneal dialysis solution (lactate) (low calcium) is compared with the peritoneal dialysis solution using inorganic base, and particulate matter is decreased obviously, and compared with acid peritoneal dialysis solution, particulate matter is similar to.
Be simultaneously introduced the materials such as sodium pyrosulfite for peritoneal dialysis solution stability have have certain effect, wherein add sodium pyrosulfite effect best.
Use national drug standards WS1Analysis method in-XG-002-2007 measures the calcium chloride in example of formulations 1-1 to 8-3, content of magnesium chloride, calcium chloride, magnesium chloride content all between the 90-110% of recipe quantity.
The peritoneal dialysis solution of the embodiment of use, comparative examples in effect example, is all temperature 25 DEG C �� 2 DEG C, places the product of 12 months when relative humidity 60% �� 10%.
The impact test of effect example 1 peritoneum
Laboratory animal: SD rat, male, body weight 200 �� 10g
Test method: by rat random packet, often group 10, blank group accepts normal saline 2Oml lumbar injection every day, rat is given the peritoneal dialysis solution lumbar injection of the corresponding group number of embodiment group by embodiment 1-1 to 6-3 group, every day 100ml/Kg, rat is given the peritoneal dialysis solution lumbar injection in the corresponding group number of comparative examples group by matched group 1-1 to 6-3 group, and every day, 100ml/Kg, injected 28 days continuously. Within 29th, 30 days, stop injection, within 31st day, measuring animal peritoneal function, every rat is injected 4.25% glucose peritoneal dialysis solution 25ml, 4h tailing edge hunter's line with 10% chloral hydrate anesthesia pneumoretroperitoneum and cuts off stomach wall, accurately measure intraperitoneal liquid, leave and take 0 and 4h peritoneal dialysis liquid and blood preparation simultaneously. Blood preparation is centrifuged 10 minutes with 5000 revs/min, and peritoneal dialysis liquid specimen is centrifuged 5 minutes with 1500 revs/min, measures concentration of glucose with automatic clinical chemistry analyzer.
Ultrafiltration volume (ultrafiltration, UF)=(last water yield-25);
Glucose transport amount (masstransferofglucose, MTG)=(dialysis solution initial glucose concentration �� injection dialysis liquid measure)-(dialysis last dialysis solution output at last concentration of glucose �� end).
Put to death animal afterwards, parietal peritoneum tissue is carried out HE (hematoxylin-eosin staining method), Masson dyeing, measures peritoneum thickness. Masson staining procedure: paraffin-embedded tissue is cut into 3m section, dewaxes to water, celestite orchid dye liquor dye 6��10min, running water, WeigerShi Garapa element liquid dye 5��10min, running water, Ponceaux acid fuchsin liquid (2:1) contaminates l5��20min, 1% phosphomolybdic acid aqueous solution and 1% glacial acetic acid quickly break up, viride nitens solution-dyed 2��10min, again quickly break up with phosphomolybdic acid aqueous solution and glacial acetic acid, 95% dehydration of alcohol, drying, dimethylbenzene is transparent, neutral gum mounting. Take 12 high power fields and measure peritoneum thickness, average as the standard judging peritoneum thickness.
Result:
Each group rat 4 weeks posterior peritoneum thickness, glucose transport amount, ultrafiltration volumes compare (n=10, mean �� SD)
| Group number | Peritoneum thickness (��m) | Ultrafiltration volume (ml) | Glucose transport amount (mmol/kg) |
| Blank group | 13.71��1.41 | 7.97��0.89 | 12.98��0.42 |
| Embodiment 1-1 | 20.13��1.28 | 5.21��0.44 | 14.03��0.42 |
| Embodiment 1-2 | 19.80��1.32 | 5.28��0.38 | 13.96��0.41 |
| Embodiment 1-3 | 19.21��1.25 | 5.74��0.41 | 13.52��0.42 |
| Embodiment 1-4 | 19.13��1.29 | 5.78��0.39 | 13.61��0.40 |
| Embodiment 1-5 | 19.56��1.49 | 5.51��0.37 | 13.85��0.38 |
| Embodiment 2-1 | 20.89��1.20 | 4.92��0.42 | 14.82��0.40 |
| Embodiment 2-2 | 20.80��1.37 | 5.02��0.37 | 14.76��0.41 |
| Embodiment 2-3 | 20.14��1.26 | 5.56��0.39 | 14.21��0.39 |
| Embodiment 2-4 | 20.20��1.38 | 5.59��0.40 | 14.14��0.40 |
| Embodiment 2-5 | 20.72��1.29 | 5.21��0.43 | 14.57��0.37 |
| Embodiment 3-1 | 22.15��1.26 | 4.51��0.35 | 15.07��0.45 |
| Embodiment 3-2 | 21.98��1.39 | 4.71��0.39 | 14.92��0.43 |
| Embodiment 3-3 | 21.25��1.25 | 5.01��0.42 | 14.53��0.41 |
| Embodiment 3-4 | 21.16��1.34 | 5.06��0.43 | 14.60��0.39 |
| Embodiment 3-5 | 21.59��1.37 | 4.82��0.39 | 14.79��0.39 |
| Comparative examples 1-1 | 25.72��1.39 | 3.54��0.38 | 15.97��0.59 |
| Comparative examples 1-2 | 24.86��1.42 | 3.78��0.44 | 15.54��0.51 |
| Comparative examples 2-1 | 25.83��1.43 | 3.73��0.38 | 15.90��0.47 |
| Comparative examples 2-2 | 25.06��1.45 | 3.93��0.37 | 15.60��0.46 |
| Comparative examples 2-3 | 25.49��1.46 | 3.86��0.37 | 15.71��0.52 |
| Comparative examples 3-1 | 20.95��1.45 | 4.52��0.35 | 14.40��0.48 |
| Comparative examples 3-2 | 20.23��1.52 | 4.73��0.40 | 14.29��0.49 |
| Comparative examples 3-3 | 20.56��1.21 | 4.53��0.42 | 14.30��0.51 |
Proved by above-mentioned experiment, alkalescence peritoneal dialysis solution is less than the impact that peritoneum is thickened compared with peritoneal dialysis solution that is acid and that use inorganic base, simultaneously ultrafiltration volume, glucose transport amount closer to normal physiological condition, PH relatively 7.7,7.2 better effects if when 7.3-7.4 generally simultaneously. Additionally this experimental result may infer that 5 hydroxymethyl furfural index is not the key index causing peritoneum to affect, and other high toxicity glucose degradation products such as pH value, formaldehyde, acetaldehyde have bigger power of influence.
Effect example 2 blood PH recovers test
Laboratory animal: SD rat, male, body weight 200 �� 10g
Peritoneal dialysis causes peritoneum injured rats model preparation method: to rats by intraperitoneal injection control formulation embodiment 5-1 group peritoneal dialysis solution, and every day, 100ml/Kg, injected 28 days continuously, within the 29th, 30 days, stopped injection, and within the 31st day, survival rats is considered as modeling success.
Test method: peritoneal dialysis is caused peritoneum impaired modeling success rat random packet, often group 10, base set directly measures the pH value of modeling success later group rats with left strength arterial blood, blank group accepts normal saline 2Oml lumbar injection every day, embodiment 1-1 to the 6-3 group peritoneal dialysis solution to the rats by intraperitoneal injection corresponding group number of embodiment group, every day 100ml/Kg, rat is given the peritoneal dialysis solution lumbar injection in the corresponding group number of comparative examples group by matched group 1-1 to 6-3 group, every day 100ml/Kg, injection 14 days continuously, the pH value of each group of rats with left strength arterial blood is measured after stopping injection 1 day. take the healthy rat before modeling 10 and be only set to healthy group, measure the pH value of rats with left strength arterial blood.
The pH value of rats with left strength arterial blood uses blood gas analyzer analysis.
Experimental result (n=10, mean �� SD)
| Group number | PH |
| Healthy group | 7.40��0.09 |
| Base set | 7.26��0.09 |
| Blank group | 7.29��0.08 |
| Embodiment 1-1 | 7.38��0.05 |
| Embodiment 1-2 | 7.38��0.06 |
| Embodiment 1-3 | 7.36��0.08 |
| Embodiment 1-4 | 7.36��0.09 |
| Embodiment 1-5 | 7.34��0.08 |
| Embodiment 2-1 | 7.37��0.07 |
| Embodiment 2-2 | 7.36��0.09 |
| Embodiment 2-3 | 7.35��0.07 |
| Embodiment 2-4 | 7.35��0.08 |
| Embodiment 2-5 | 7.34��0.05 |
| Embodiment 3-1 | 7.37��0.09 |
| Embodiment 3-2 | 7.37��0.08 |
| Embodiment 3-3 | 7.34��0.07 |
| Embodiment 3-4 | 7.35��0.06 |
| Embodiment 3-5 | 7.35��0.09 |
| Comparative examples 1-1 | 7.20��0.07 |
| Comparative examples 1-2 | 7.23��0.09 |
| Comparative examples 2-1 | 7.35��0.07 |
| Comparative examples 2-2 | 7.34��0.10 |
| Comparative examples 2-3 | 7.30��0.07 |
| Comparative examples 3-1 | 7.37��0.07 |
| Comparative examples 3-2 | 7.35��0.06 |
| Comparative examples 3-3 | 7.32��0.09 |
By above-mentioned inspection, the work that blood pH is regulated by the alkalescence peritoneal dialysis solution (lactate) (low calcium) in the embodiment of the present invention, significantly better than the peritoneal dialysis solution with acidity, compare approximate with the peritoneal dialysis solution using inorganic base.
Claims (10)
1. peritoneal dialysis solution (lactate) (low calcium) compositions, glucose containing 1.5-4.0%, the sodium chloride of 0.5-0.6%, the calcium chloride of 0.01-0.02%, the magnesium chloride of 0.004-0.006%, and the sodium lactate of 0.4-0.5%, it is characterised in that described trishydroxymethylaminomethane used for peritoneal dialysate regulates pH value to 7.2-7.7.
2. peritoneal dialysis solution as claimed in claim 1, it is characterized in that compositions is by the glucose of 1.5-4.0%, the sodium chloride of 0.5-0.6%, the calcium chloride of 0.01-0.02%, the magnesium chloride of 0.004-0.006%, and the sodium lactate of 0.4-0.5%, trishydroxymethylaminomethane and water lower than 5% form.
3. peritoneal dialysis solution as claimed in claim 1, it is characterized in that compositions is by the glucose of 1.5-4.0%, the sodium chloride of 0.5-0.6%, the calcium chloride of 0.01-0.02%, the magnesium chloride of 0.004-0.006%, and the sodium lactate of 0.4-0.5%, the sodium pyrosulfite of 0.001%��0.01%, sodium sulfite or sodium sulfite, trishydroxymethylaminomethane lower than 5% and water composition.
4. peritoneal dialysis solution as claimed in claim 1, is characterized in that pH value is 7.3-7.5.
5. peritoneal dialysis solution as claimed in claim 1, is characterized in that the content of trishydroxymethylaminomethane is lower than 5%.
6. peritoneal dialysis solution as claimed in claim 1, is characterized in that the sodium pyrosulfite possibly together with 0.001%��0.01%, sodium sulfite or sodium sulfite.
7. peritoneal dialysis solution as claimed in claim 1, is characterized in that the content of sodium chloride is 0.5377%, and the content of calcium chloride is 0.0147%, and the content of magnesium chloride is 0.00508%, and the content of sodium lactate is 0.4483%, and the content of sodium pyrosulfite is 0.005%.
8. peritoneal dialysis solution as claimed in claim 2, is characterized in that the content of sodium chloride is 0.5377%, and the content of calcium chloride is 0.0147%, and the content of magnesium chloride is 0.00508%, and the content of sodium lactate is 0.4483%.
9. peritoneal dialysis solution as claimed in claim 3, is characterized in that the content of sodium chloride is 0.5377%, and the content of calcium chloride is 0.0147%, and the content of magnesium chloride is 0.00508%, and the content of sodium lactate is 0.4483%, and the content of sodium pyrosulfite is 0.005%.
10. a peritoneal dialysis solution as claimed in claim 1 reduces the application in peritoneal fibrosis medicine in preparation.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107281219A (en) * | 2017-06-30 | 2017-10-24 | 华仁药业股份有限公司 | A kind of anti-peritoneal fibrosiss and the peritoneal dialysis solution of infection and preparation method thereof |
| CN113304132A (en) * | 2021-06-11 | 2021-08-27 | 北京畅盛医药科技有限公司 | Special dialysate for treating cardiovascular and cerebrovascular diseases of renal dialysis patients |
| CN115624557A (en) * | 2022-12-22 | 2023-01-20 | 广东省人民医院 | Peritoneal dialysis solution for preventing peritoneal infection and preparation method and application thereof |
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| CN102973600A (en) * | 2012-12-13 | 2013-03-20 | 天津金耀集团有限公司 | Peritoneal dialysis solution (lactate) (low calcium) composition |
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| CN102973600A (en) * | 2012-12-13 | 2013-03-20 | 天津金耀集团有限公司 | Peritoneal dialysis solution (lactate) (low calcium) composition |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107281219A (en) * | 2017-06-30 | 2017-10-24 | 华仁药业股份有限公司 | A kind of anti-peritoneal fibrosiss and the peritoneal dialysis solution of infection and preparation method thereof |
| CN107281219B (en) * | 2017-06-30 | 2020-08-04 | 华仁药业股份有限公司 | Peritoneal dialysis solution for resisting peritoneal fibrosis and infection and preparation method thereof |
| CN113304132A (en) * | 2021-06-11 | 2021-08-27 | 北京畅盛医药科技有限公司 | Special dialysate for treating cardiovascular and cerebrovascular diseases of renal dialysis patients |
| CN115624557A (en) * | 2022-12-22 | 2023-01-20 | 广东省人民医院 | Peritoneal dialysis solution for preventing peritoneal infection and preparation method and application thereof |
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Application publication date: 20160608 |