CN109528760A - A kind of Icodextrin peritoneal dialysis solution and preparation method thereof - Google Patents
A kind of Icodextrin peritoneal dialysis solution and preparation method thereof Download PDFInfo
- Publication number
- CN109528760A CN109528760A CN201811348914.1A CN201811348914A CN109528760A CN 109528760 A CN109528760 A CN 109528760A CN 201811348914 A CN201811348914 A CN 201811348914A CN 109528760 A CN109528760 A CN 109528760A
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- CN
- China
- Prior art keywords
- peritoneal dialysis
- dialysis solution
- icodextrin
- cysteine
- acetyl
- Prior art date
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- Pending
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- 239000000385 dialysis solution Substances 0.000 title claims abstract description 93
- 229920002177 Icodextrin Polymers 0.000 title claims abstract description 75
- 229940016836 icodextrin Drugs 0.000 title claims abstract description 75
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 claims abstract description 49
- 239000007853 buffer solution Substances 0.000 claims abstract description 38
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- 238000004659 sterilization and disinfection Methods 0.000 claims abstract description 22
- 239000003792 electrolyte Substances 0.000 claims abstract description 20
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 60
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 36
- 239000011780 sodium chloride Substances 0.000 claims description 30
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 24
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 20
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 claims description 19
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- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 claims description 8
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- 229940001447 lactate Drugs 0.000 claims description 8
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- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 5
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- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 3
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Classifications
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- A61K31/19—Carboxylic acids, e.g. valproic acid
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- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
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- A—HUMAN NECESSITIES
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Abstract
The invention proposes a kind of Icodextrin peritoneal dialysis solutions and preparation method thereof, are related to the technical field of peritoneal dialysis.Peritoneal dialysis solution of the invention includes Icodextrin, buffer base (BB) and electrolyte, further includes N-acetyl-L-cysteine；The concentration of N-acetyl-L-cysteine is 10-25mmol/L.The present invention gives the preparation method of above-mentioned peritoneal dialysis solution, forms by ingredient, adjusting pH value and moist heat sterilization.Peritoneal dialysis solution of the invention contains N-acetyl-L-cysteine, on the one hand the addition of N-acetyl-L-cysteine has anti-oxidative stress, can further suppress the formation of homocysteine after on the other hand entering body；Resulting peritoneal dialysis solution has good Dialysis, it can be achieved that good ultrafiltration, reduces oxidativestress damage, avoids relevant adverse reaction, reduces the formation of internal homocysteine, has positive prevention effect to cardiovascular complication.
Description
Technical field
The present invention relates to the technical field of peritoneal dialysis, a kind of Icodextrin peritoneal dialysis solution and its preparation side are particularly related to
Method.
Background technique
Currently, peritoneal dialysis is a kind of common terminal phase renal replacement therapies mode.Compared with haemodialysis, advantage
Show as medical expense relative moderate, it is easy to operate, independent of large-scale dialysis machine, may be implemented to treat at home, to patient
The free less-restrictive of life.Therefore, it promotes peritoneal dialysis therapy and especially meets the national conditions of China at this stage.But China is most
For common lactate peritoneal dialysat with the glucose of high concentration for main bleeding agent, this peritoneal dialysis solution has pH low, seeps
The features such as pressure is high thoroughly, easily formation advanced glycation end products (AGE), is easy to cause peritoneal fibrosiss, and induce hyperlipidemia, high pancreas
The general metabolisms disorder such as island element mass formed by blood stasis and obesity, to limit the application of peritoneal dialysis therapy.
The peritoneal dialysis solution containing Icodextrin is listed in successful foreign at present, and the clinical use of many years confirms the peritoneal dialysis liquid
Peritonaeum ultrafiltration volume can not only be obviously increased, but also metabolism can be improved, protection residual renal function maintains blood pressure and body fluid control etc.
Curative effect.Although there are some superiorities for the clinical application of this peritoneal dialysis liquid containing Icodextrin, there is also adverse reactions, such as
It may cause oxidativestress damage etc..The research of Ueda et al. points out, fresh (unused) peritoneal dialysis containing Icodextrin
The AGE of active carbonyl compound and less concentration of the liquid compared with the glucose peritoneal dialysis liquid of G1.5% with lower loading is generated
Object；But Icodextrin, after patient's abdomen is treated thoroughly, active carbonyl compound concentration obviously increases in the saturating efflux of abdomen.With
Peritoneal dialysis liquid sets the extension stayed, in above two peritoneal dialysis liquid efflux the content difference of active carbonyl compound and AGE product by
It is decrescence few.In addition, nearest research also indicates that, the Icodextrin abdomen that normal rat receives 7.5% treats 4 hours, abdomen thoroughly
Products of oxidative stress malonaldehyde (MDA) concentration in saturating efflux shows as linearly increasing.These are research shows that Icodextrin
Bleeding agent as macromolecule is possible to induction mesothelial cell's film and lipid peroxidation occurs.
For End-stage Renal Disease Patients, the metabolic toxicities accumulated in vivo make oxygen radical generation horizontal significantly raised,
Easily lead to all kinds of oxidative damages；Such as the oxidative stress of uremic patient takes part in cardiovascular pathology damage process, is to cause
One of major incentive of cardiovascular event.Therefore the oxidative stress for reducing patient, for reducing uremia related complication
With positive therapeutic potential.The existing peritoneal dialysis solution containing Icodextrin can not effectively reduce the oxidation of uremic patient
Stress damage.
Summary of the invention
The present invention proposes a kind of Icodextrin peritoneal dialysis solution and preparation method thereof, solves in the prior art containing Chinese mugwort
The peritoneal dialysis solution for examining dextrin is easy to cause the problem of oxidativestress damage is so as to cause related complication.
A kind of Icodextrin peritoneal dialysis solution of the invention, technical solution are achieved in that the peritoneal dialysis solution
It further include N-acetyl-L-cysteine including Icodextrin, buffer base (BB) and electrolyte；In the peritoneal dialysis solution, the Chinese mugwort
The concentration for examining dextrin is 70-80g/L, and the concentration of the buffer base (BB) is 32-40mmol/L, and the concentration of the electrolyte is 80-
105mmol/L, the concentration of the N-acetyl-L-cysteine are 10-25mmol/L.
Peritoneal dialysis solution of the invention includes Icodextrin, buffer base (BB), electrolyte and N-acetyl-L-cysteine, is one
Kind includes the Icodextrin peritoneal dialysis solution of N-acetyl-L-cysteine, this is a kind of novel Icodextrin peritoneal dialysis solution, is fitted
In the peritoneal dialysis solution that Renal Failure Patients use, including continuous bedside peritoneal dialysis (CAPD) and automated peritoneal dialysis
(APD), with the novel Icodextrin peritoneal dialysis solution of good drug effect and anti-oxidative stress.Peritoneal dialysis solution of the invention
It can be achieved to maintain good ultrafiltration, newly increased N-acetyl-L-cysteine ingredient, on the one hand enhanced the antioxygen of peritoneal dialysis liquid
Change stress ability, has good protective effect to oxidativestress damage etc.；On the other hand, N-acetyl-L-cysteine can be with
The formation for inhibiting homocysteine, strengthens the prevention effect to cardiovascular event.Therefore, novel Icodextrin of the invention
Peritoneal dialysis solution has good Dialysis, it can be achieved that good ultrafiltration, reduces oxidativestress damage, avoids related concurrent
The generation of disease reduces the formation of internal homocysteine, has prevention effect to cardiovascular complication.
Embodiment as one preferred, the pH value of the peritoneal dialysis solution are 5.5-7.0.Peritoneal dialysis of the invention
The pH value of liquid approaches with the physiological ph of human body close to neutrality, alleviates the discomfort of patient in use, increase patient
Compliance.Here pH value is the pH value of peritoneal dialysis liquid product.
Embodiment as one preferred, the pH value of the peritoneal dialysis solution are 6.4-6.8.Peritoneal dialysis of the invention
The pH value of liquid can further be adjusted to 6.4-6.8, be more nearly the physiological ph of itself and human body, further improve its life
Object compatibility.Peritoneal dialysis solution of the invention is generally loaded on plastic containers, and this plastic containers are usually by polypropylene, poly- second
Alkene, polyvinyl chloride, polyester, ethylene/vinyl acetate copolymer, styrene-ethylene-butadiene (SEB polymer), nylon or more
What the materials such as the mixture of component were prepared, preferably it is loaded into three layers of infusion co-extrusion film bag.
Embodiment as one preferred, the concentration of the N-acetyl-L-cysteine are 20-25mmol/L.N- second
Acyl-L-cysteine is white crystalline powder, there is the smell of similar garlic, sour, there is a hygroscopicity, soluble easily in water or ethyl alcohol, no
It is dissolved in ether and chloroform, in aqueous solution in acidity；N-acetyl-L-cysteine addition after Icodextrin, buffer base (BB) and
Under the synergistic effect of electrolyte, the anti-oxidation stress ability of peritoneal dialysis solution is enhanced, it is suppressed that the formation of homocysteine,
Improve the dialysis curative effect of peritoneal dialysis solution.
Embodiment as one preferred, the buffer base (BB) are lactate, citrate, isocitrate, pyruvic acid
Salt, succinate, fumarate, malate, any one or a few in oxaloacetate.Buffer base (BB) of the invention has
Many kinds selection, is chosen according to the actual situation；Preferably lactate, especially sodium lactate.
Embodiment as one preferred, the electrolyte be sodium chloride, calcium chloride, in magnesium chloride any one or
It is several.The addition of electrolyte is the electrolyte balance disorder phenomenon in order to correct patient's body, and the intracorporal dominant cation of people is
Sodium ion, potassium ion, calcium ion and magnesium ion, electrolyte of the present invention include sodium ion, calcium ion, magnesium ion, chloride ion, preferably
Exist in the form of sodium chloride, calcium chloride, magnesium chloride.
Embodiment as one preferred, the peritoneal dialysis solution include Icodextrin 70-80g/L, sodium chloride 82-
102mmol/L, calcium chloride 1.50-1.75mmol/L, magnesium chloride 0.20-0.25mmol/L, lactate 32-40mmol/L, N- second
Acyl-L-cysteine 10-25mmol/L.Peritoneal dialysis solution of the invention has adjusted the ingredient and concentration of each component well, respectively
Science matching, while maintaining good ultrafiltration, reduces oxidativestress damage between component, avoids related concurrent
The generation of disease reduces the formation of internal homocysteine, has prevention effect to cardiovascular complication.
Embodiment as one preferred, the peritoneal dialysis solution include Icodextrin 75g/L, sodium chloride 92mmol/
L, calcium chloride 1.75mmol/L, magnesium chloride 0.25mmol/L, sodium lactate 40mmol/L, N-acetyl-L-cysteine 20-
25mmol/L.The effect of peritoneal dialysis solution of the invention in Icodextrin, buffer base (BB), electrolyte and N-acetyl-L-cysteine
Under, each component passes through scientific compatibility, mutually cooperates with, complements each other, and has reached anti-oxidation stress and has inhibited internal half Guang ammonia of homotype
The purpose that acid is formed has certain prevention effect to the cardiovascular complication of the saturating patient of abdomen.Icodextrin of the invention, buffering
Alkali, electrolyte and N-acetyl-L-cysteine concentration are the concentration in prescription.
A kind of preparation method for examining dextrin peritoneal dialysis solution of the invention, technical solution be achieved in that including with
Lower step: 1) taking Icodextrin, N-acetyl-L-cysteine, buffer base (BB) and electrolyte, and mixing adds water for injection, keeps its molten
Solution, obtains mixed liquor；2) into the resulting mixed liquor of step 1), acidity regulator is added, adjusting pH value is 5.7-6.8, and filtering is wet
Heat sterilization, sterilising temp are 115 DEG C, and sterilization time 30min obtains peritoneal dialysis solution.
The preparation method of peritoneal dialysis solution of the invention be will first weigh bulk pharmaceutical chemicals add be dissolved in water for injection after pass through
It crosses pH value adjusting, filtering and moist heat sterilization and obtains, easy to operate, process flow is short, and easy to control, reaction condition is mild,
There is no particular/special requirement to equipment, low energy consumption, and high production efficiency, cost is small, industrialization easy to accomplish.Filter operation of the invention is logical
It is often to be fitted into after filtering in three layers of infusion co-extrusion film bag using filtering with microporous membrane, it is saturating up to peritonaeum by moist heat sterilization
Analyse liquid.
Embodiment as one preferred, the acidity regulator in the step 2) be dilute hydrochloric acid, citric acid, lactic acid,
Phosphoric acid, citric acid, tartaric acid, malic acid, metatartaric acid, acetic acid, adipic acid, any one or a few in fumaric acid.This hair
Bright to be adjusted using pH value of the acidity regulator to peritoneal dialysis solution, there are many type of acidity regulator, can be according to reality
It being selected, source is wide, and it is cheap and easy to get, it is easy to use.
Compared with prior art, the beneficial effects of the present invention are: peritoneal dialysis solution of the invention is in Icodextrin, buffer base (BB)
With N-acetyl-L-cysteine is added on the basis of electrolyte, this is that a kind of Chinese mugwort comprising N-acetyl-L-cysteine examines paste
Smart peritoneal dialysis solution is a kind of novel Icodextrin peritoneal dialysis solution；On the one hand the addition of N-acetyl-L-cysteine enhances
The anti-oxidation stress ability of peritoneal dialysis solution has good protective effect to oxidativestress damage；On the other hand also inhibit
The formation of homocysteine, strengthens the prevention effect to cardiovascular complication.Therefore, novel Icodextrin of the invention
Peritoneal dialysis solution has good Dialysis, it can be achieved that good ultrafiltration, reduces oxidativestress damage, avoids related concurrent
The generation of disease reduces the formation of internal homocysteine, has prevention effect to cardiovascular complication, it is saturating to improve peritonaeum
The curative effect of analysis.The preparation method of peritoneal dialysis solution of the invention is easy to operate, and process flow is short, easy to control, reaction condition temperature
With there is no particular/special requirement to equipment, low energy consumption, and high production efficiency, cost is small, industrialization easy to accomplish.
Specific embodiment
Technical solution of the present invention is clearly and completely described below in conjunction with specific embodiments of the present invention, is shown
So, described embodiment is only a part of the embodiments of the present invention, instead of all the embodiments.Based in the present invention
Embodiment, every other embodiment obtained by those of ordinary skill in the art without making creative efforts, all
Belong to the scope of protection of the invention.
A kind of Icodextrin peritoneal dialysis solution of the invention, the peritoneal dialysis solution include Icodextrin, buffer base (BB) and electricity
Xie Zhi further includes N-acetyl-L-cysteine；In the peritoneal dialysis solution, the concentration of the Icodextrin is 70-80g/L,
The concentration of the buffer base (BB) is 32-40mmol/L, and the concentration of the electrolyte is 80-105mmol/L, the N- acetyl-L- half
The concentration of cystine is 10-25mmol/L.
Preferably, the pH value of the peritoneal dialysis solution is 5.5-7.0.
Further, the pH value of the peritoneal dialysis solution is 6.4-6.8.
Specifically, the concentration of the N-acetyl-L-cysteine is 20-25mmol/L.
Further, the buffer base (BB) be lactate, citrate, isocitrate, acetonate, succinate,
Fumarate, malate, any one or a few in oxaloacetate.
More specifically, the electrolyte is sodium chloride, calcium chloride, any one or a few in magnesium chloride.
It is highly preferred that the peritoneal dialysis solution includes Icodextrin 70-80g/L, sodium chloride 82-102mmol/L, calcium chloride
1.50-1.75mmol/L, magnesium chloride 0.20-0.25mmol/L, lactate 32-40mmol/L, N-acetyl-L-cysteine 10-
25mmol/L。
Again less preferably, the peritoneal dialysis solution includes Icodextrin 75g/L, sodium chloride 92mmol/L, calcium chloride
1.75mmol/L, magnesium chloride 0.25mmol/L, sodium lactate 40mmol/L, N-acetyl-L-cysteine 20-25mmol/L.
A kind of preparation method for examining dextrin peritoneal dialysis solution of the invention, comprising the following steps:
1) Icodextrin, N-acetyl-L-cysteine, buffer base (BB) and electrolyte are taken, is mixed, water for injection is added, makes it
Dissolution, obtains mixed liquor；
2) into the resulting mixed liquor of step 1), acidity regulator is added, adjusting pH value is 5.7-6.8, and filtering is damp and hot to go out
Bacterium, sterilising temp are 115 DEG C, and sterilization time 30min obtains peritoneal dialysis solution.
Preferably, the acidity regulator in the step 2) is dilute hydrochloric acid, citric acid, lactic acid, phosphoric acid, citric acid, winestone
Acid, malic acid, metatartaric acid, acetic acid, adipic acid, any one or a few in fumaric acid.
Embodiment one
A kind of preparation method for examining dextrin peritoneal dialysis solution of the invention, comprising the following steps:
1) according to prescription: Icodextrin 70g/L, N-acetyl-L-cysteine 22mmol/L, fumaric acid sodium 32mmol/
L, calcium chloride 1.50mmol/L and sodium chloride 78.5mmol/L successively weighs bulk pharmaceutical chemicals Icodextrin, half Guang ammonia of N- acetyl-L-
Acid, fumaric acid sodium, CALCIUM CHLORIDE DIHYDRATE and sodium chloride；
2) by the Icodextrin of step 1), N-acetyl-L-cysteine, fumaric acid sodium, CALCIUM CHLORIDE DIHYDRATE and chlorination
Sodium, mixing add water for injection, make it dissolve, obtain mixed liquor；
3) into the resulting mixed liquor of step 2), addition dilute hydrochloric acid is as acidity regulator, and adjusting pH value is 5.8, filtering,
Moist heat sterilization, sterilising temp are 115 DEG C, and sterilization time 30min obtains peritoneal dialysis solution, i.e. experiment sample one.
Embodiment two
A kind of preparation method for examining dextrin peritoneal dialysis solution of the invention, comprising the following steps:
1) according to prescription: Icodextrin 80g/L, N-acetyl-L-cysteine 24mmol/L, sodium citrate 40mmol/L and
Sodium chloride 106mmol/L successively weighs bulk pharmaceutical chemicals Icodextrin, N-acetyl-L-cysteine, sodium citrate and sodium chloride；
2) by the Icodextrin of step 1), N-acetyl-L-cysteine, sodium citrate and sodium chloride, mixing, addition injection
It with water, makes it dissolve, obtains mixed liquor；
3) into the resulting mixed liquor of step 2), addition citric acid is as acidity regulator, and adjusting pH value is 6.2, filtering,
Moist heat sterilization, sterilising temp are 115 DEG C, and sterilization time 30min obtains peritoneal dialysis solution, i.e. experiment sample two.
Embodiment three
A kind of preparation method for examining dextrin peritoneal dialysis solution of the invention, comprising the following steps:
1) according to prescription: Icodextrin 75g/L, N-acetyl-L-cysteine 25mmol/L, sodium lactate 40mmol/L, chlorine
Change calcium 1.75mmol/L, magnesium chloride 0.25mmol/L and sodium chloride 92mmol/L, successively weighs bulk pharmaceutical chemicals Icodextrin, N- second
Acyl-L-cysteine, sodium lactate, CALCIUM CHLORIDE DIHYDRATE, Magnesium dichloride hexahydrate and sodium chloride；
2) by the Icodextrin of step 1), N-acetyl-L-cysteine, sodium lactate, CALCIUM CHLORIDE DIHYDRATE, six chloride hydrates
Magnesium and sodium chloride, mixing add water for injection, make it dissolve, obtain mixed liquor；
3) into the resulting mixed liquor of step 2), addition lactic acid is as acidity regulator, and adjusting pH value is 5.7, and constant volume is micro-
Hole membrane filtration, moist heat sterilization, sterilising temp are 115 DEG C, and sterilization time 30min obtains peritoneal dialysis solution, i.e. experiment sample three.
Example IV
A kind of preparation method for examining dextrin peritoneal dialysis solution of the invention, comprising the following steps:
1) according to prescription: Icodextrin 75g/L, N-acetyl-L-cysteine 20mmol/L, sodium lactate 40mmol/L, chlorine
Change calcium 1.75mmol/L, magnesium chloride 0.25mmol/L and sodium chloride 92mmol/L, successively weighs bulk pharmaceutical chemicals Icodextrin, N- second
Acyl-L-cysteine, sodium lactate, CALCIUM CHLORIDE DIHYDRATE, Magnesium dichloride hexahydrate and sodium chloride；
2) by the Icodextrin of step 1), N-acetyl-L-cysteine, sodium lactate, CALCIUM CHLORIDE DIHYDRATE, six chloride hydrates
Magnesium and sodium chloride, mixing add water for injection, make it dissolve, obtain mixed liquor；
3) into the resulting mixed liquor of step 2), addition citric acid is as acidity regulator, and adjusting pH value is 6.8, constant volume,
Filtering with microporous membrane, moist heat sterilization, sterilising temp are 115 DEG C, and sterilization time 30min obtains peritoneal dialysis solution, i.e. experiment sample
Four.
Embodiment five
A kind of preparation method for examining dextrin peritoneal dialysis solution of the invention, comprising the following steps:
1) according to prescription: Icodextrin 75g/L, N-acetyl-L-cysteine 15mmol/L, sodium lactate 40mmol/L, chlorine
Change calcium 1.75mmol/L, magnesium chloride 0.25mmol/L and sodium chloride 92mmol/L, successively weighs bulk pharmaceutical chemicals Icodextrin, N- second
Acyl-L-cysteine, sodium lactate, CALCIUM CHLORIDE DIHYDRATE, Magnesium dichloride hexahydrate and sodium chloride；
2) by the Icodextrin of step 1), N-acetyl-L-cysteine, sodium lactate, CALCIUM CHLORIDE DIHYDRATE, six chloride hydrates
Magnesium and sodium chloride, mixing add water for injection, make it dissolve, obtain mixed liquor；
3) into the resulting mixed liquor of step 2), addition adipic acid is as acidity regulator, and adjusting pH value is 6.5, constant volume,
Filtering with microporous membrane, moist heat sterilization, sterilising temp are 115 DEG C, and sterilization time 30min obtains peritoneal dialysis solution, i.e. experiment sample
Five.
Embodiment six
A kind of preparation method for examining dextrin peritoneal dialysis solution of the invention, comprising the following steps:
1) according to prescription: Icodextrin 75g/L, N-acetyl-L-cysteine 10mmol/L, sodium lactate 40mmol/L, chlorine
Change calcium 1.75mmol/L, magnesium chloride 0.25mmol/L and sodium chloride 92mmol/L, successively weighs bulk pharmaceutical chemicals Icodextrin, N- second
Acyl-L-cysteine, sodium lactate, CALCIUM CHLORIDE DIHYDRATE, Magnesium dichloride hexahydrate and sodium chloride；
2) by the Icodextrin of step 1), N-acetyl-L-cysteine, sodium lactate, CALCIUM CHLORIDE DIHYDRATE, six chloride hydrates
Magnesium and sodium chloride, mixing add water for injection, make it dissolve, obtain mixed liquor；
3) into the resulting mixed liquor of step 2), addition tartaric acid is as acidity regulator, and adjusting pH value is 6.3, constant volume,
Filtering with microporous membrane, moist heat sterilization, sterilising temp are 115 DEG C, and sterilization time 30min obtains peritoneal dialysis solution, i.e. experiment sample
Six.
Embodiment seven
A kind of preparation method for examining dextrin peritoneal dialysis solution, comprising the following steps:
1) according to prescription: Icodextrin 75g/L, sodium lactate 40mmol/L, calcium chloride 1.75mmol/L, magnesium chloride
0.25mmol/L and sodium chloride 92mmol/L successively weighs bulk pharmaceutical chemicals Icodextrin, sodium lactate, CALCIUM CHLORIDE DIHYDRATE, six hydrations
Magnesium chloride and sodium chloride；
2) by the Icodextrin of step 1), sodium lactate, CALCIUM CHLORIDE DIHYDRATE, Magnesium dichloride hexahydrate and sodium chloride, mixing adds
Add water for injection, make it dissolve, obtains mixed liquor；
3) into the resulting mixed liquor of step 2), addition tartaric acid is as acidity regulator, and adjusting pH value is 6.3, filtering,
Moist heat sterilization, sterilising temp are 115 DEG C, sterilization time 30min, obtain peritoneal dialysis solution, i.e. control sample one.
By seven gained of the embodiment of the present invention one to the resulting experiment sample one of embodiment six to experiment sample six and embodiment
Control sample one carries out pharmacodynamic experiment respectively.
1, the preparation of rabbit Uremia Dialysis model
New Zealand White Rabbit 90 of selection health, half male and half female, weight about 1.5-2Kg.Normal diet and drinking-water are given,
Adaptive feeding one week.Random selection wherein 10 is only used as Normal group, remaining 80 is only used as preparing Uremia Dialysis model.
The first step prepares uremia model.80 New Zealand White Rabbit make 5/6 nephrectomy uremia model, by New Zealand
White rabbit anesthesia, fixed, row left side abdominal incision removes scrotum portion, and dissociate left kidney, cuts off left kidney up and down at extremely each 1/3, and weigh weight
Amount, result are equal to 2/3 weight of single kidney that calculates previously according to weight, and penicillin anti-infective 3 days；After 1 week, ligation excision is right
Kidney, penicillin anti-infective 3 days；After 4 weeks, renal function is detected, uremia is diagnosed as, then uremia model modeling success.
Second step prepares the saturating model of abdomen.Uremic New Zealand White Rabbit will be diagnosed as to anaesthetize, abdomen is placed in abdominal cavity
Pipe, rest 7-10 days after operation obtain Uremia Dialysis model until wound healing is complete thoroughly.
The successful New Zealand White Rabbit of above-mentioned Uremia Dialysis model modeling 64 is chosen, completely random is divided into 8 groups, i.e. uremic
Disease is without dialysis control group, one group of control sample and extremely six groups of sample of the experiment of one group of experiment sample, every group of 8 animals.1 abdomen is carried out daily
Thoroughly treatment, inject each group peritoneal dialysis solution of 40mL/Kg, in dialyse 240min when terminate.Continuous peritoneal dialysis treatment 8 weeks, in
At the end of last is dialysed, blood and dialysis efflux sample are collected.
2, Ultrafiltration experiment and result
The different group animal net ultrafiltration amount test results of table 1
| Test group name | Size of animal (only) | Net ultrafiltration amount (mL) |
| One group of sample of experiment | 8 | 51±2 |
| Two groups of sample of experiment | 8 | 53±5 |
| Three groups of sample of experiment | 8 | 56±4 |
| Four groups of sample of experiment | 8 | 52±6 |
| Five groups of sample of experiment | 8 | 48±3 |
| Six groups of sample of experiment | 8 | 46±3 |
| One group of control sample | 8 | 40±5 |
When abdomen 240min is set in last dialysis, dialysis efflux is collected, and measure volume.Calculate the flat of dialysis groups of animals
Equal net ultrafiltration amount, experimental result are as shown in table 1.
As can be seen from Table 1, the embodiment of the present invention one to six resulting six experiment sample groups of embodiment (test sample one
Group to experiment six groups of sample) ultrafiltration effect it is very good, net ultrafiltration amount is all larger than one group of control sample.Therefore, the present invention is resulting
The ultrafiltration drug effect of peritoneal dialysis solution is better than the Icodextrin peritoneal dialysis solution without N-acetyl-L-cysteine.
3, malonaldehyde (MDA) Concentration Testing in blood plasma
Mda content measurement result in the different group animal blood plasmas of table 2
| Test group name | Size of animal (only) | Contents of mda (concentration μm ol/L) |
| One group of sample of experiment | 8 | 3.14±0.67 |
| Two groups of sample of experiment | 8 | 3.07±0.42 |
| Three groups of sample of experiment | 8 | 2.67±0.58 |
| Four groups of sample of experiment | 8 | 3.22±0.81 |
| Five groups of sample of experiment | 8 | 3.29±1.13 |
| Six groups of sample of experiment | 8 | 3.76±0.86 |
| One group of control sample | 8 | 5.18±1.24 |
| Uremia is without dialysis control group | 8 | 5.22±1.21 |
| Normal group | 10 | 2.32±0.36 |
After last peritoneal dialysis, the ear vein blood of New Zealand White Rabbit is extracted, with anticoagulant heparin, 3000 revs/min are centrifuged,
Isolate blood plasma.Using the MDA content in thiobarbituricacidα- plasma by colorimetic method, experimental result is as shown in table 2.
As can be seen from Table 2, in one group of experiment sample extremely six groups of sample of experiment and one group of control sample of New Zealand White Rabbit blood plasma
Mda content be below uremia without the mda content in dialysis control group in New Zealand White Rabbit blood plasma, one group of control sample
New Zealand White Rabbit blood plasma in mda content compared with uremia without dialysis control group New Zealand White Rabbit blood plasma in malonaldehyde
The degree that content reduces is smaller, and tests one group of the sample mda content into the New Zealand White Rabbit blood plasma for testing six groups of sample and relatively urinate
Toxication has apparent reduction without the mda content in New Zealand White Rabbit blood plasma in dialysis control group, and one group of experiment sample is extremely tested
Malonaldehyde in mda content and blank control group in six groups of sample of New Zealand White Rabbit blood plasma in New Zealand White Rabbit blood plasma contains
Amount is more nearly.Therefore, the resulting peritoneal dialysis solution of the present invention can significantly reduce the mda content in blood plasma, this illustrates N-
The addition of acetyl-L-cysteine has good antioxidation.
4, homocysteine in blood plasma Concentration Testing
Content of homocysteine measurement result in the different group animal blood plasmas of table 3
| Test group name | Size of animal (only) | Plasma Hcy content (μm ol/L) |
| One group of sample of experiment | 8 | 34.01±8.24 |
| Two groups of sample of experiment | 8 | 33.68±6.45 |
| Three groups of sample of experiment | 8 | 33.47±7.79 |
| Four groups of sample of experiment | 8 | 34.15±5.37 |
| Five groups of sample of experiment | 8 | 37.12±6.42 |
| Six groups of sample of experiment | 8 | 38.35±6.23 |
| One group of control sample | 8 | 47.28±16.14 |
| Uremia is without dialysis control group | 8 | 42.13±11.54 |
| Normal group | 10 | 10.12±0.68 |
After last peritoneal dialysis, the ear vein blood of New Zealand White Rabbit is extracted, with anticoagulant heparin, 3000 revs/min are centrifuged,
Isolate blood plasma.With the concentration of the homocysteine in Syrups by HPLC blood plasma, experimental result is as shown in table 3.
As can be seen from Table 3, the content highest of the homocysteine in one group of control sample of new zealand rabbit blood plasma is big
In content of the uremia without the homocysteine in New Zealand White Rabbit blood plasma in dialysis control group；One group of sample of experiment is to testing sample
Content of homocysteine in six groups of New Zealand White Rabbit blood plasma is significantly lower than New Zealand White Rabbit blood plasma in one group of control sample
In content of homocysteine, meanwhile, be also below uremia without same in New Zealand White Rabbit blood plasma in dialysis control group
Type cysteine content.Therefore, the homocysteine that the resulting peritoneal dialysis solution of the present invention can significantly reduce in blood plasma contains
Amount, this illustrates that the addition of N-acetyl-L-cysteine has the function of inhibiting homocysteine formation.
Compared with prior art, the beneficial effects of the present invention are: peritoneal dialysis solution of the invention is in Icodextrin, buffer base (BB)
With N-acetyl-L-cysteine is added on the basis of electrolyte, this is that a kind of Chinese mugwort comprising N-acetyl-L-cysteine examines paste
Smart peritoneal dialysis solution is a kind of novel Icodextrin peritoneal dialysis solution；On the one hand the addition of N-acetyl-L-cysteine enhances
The anti-oxidation stress ability of peritoneal dialysis solution has good protective effect to oxidativestress damage；On the other hand also inhibit
The formation of homocysteine, strengthens the prevention effect to cardiovascular complication.Therefore, novel Icodextrin of the invention
Peritoneal dialysis solution has good Dialysis, it can be achieved that good ultrafiltration, reduces oxidativestress damage, avoids related concurrent
The generation of disease reduces the formation of internal homocysteine, has prevention effect to cardiovascular complication, it is saturating to improve peritonaeum
The curative effect of analysis.The preparation method of peritoneal dialysis solution of the invention is easy to operate, and process flow is short, easy to control, reaction condition temperature
With there is no particular/special requirement to equipment, low energy consumption, and high production efficiency, cost is small, industrialization easy to accomplish.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all in essence of the invention
Within mind and principle, any modification, equivalent replacement, improvement and so on be should all be included in the protection scope of the present invention.
Claims (10)
1. a kind of Icodextrin peritoneal dialysis solution, it is characterised in that: the peritoneal dialysis solution includes Icodextrin, buffer base (BB) and electricity
Xie Zhi further includes N-acetyl-L-cysteine；
In the peritoneal dialysis solution, the concentration of the Icodextrin is 70-80g/L, and the concentration of the buffer base (BB) is 32-
40mmol/L, the concentration of the electrolyte are 80-105mmol/L, and the concentration of the N-acetyl-L-cysteine is 10-
25mmol/L。
2. Icodextrin peritoneal dialysis solution according to claim 1, it is characterised in that:
The pH value of the peritoneal dialysis solution is 5.5-7.0.
3. Icodextrin peritoneal dialysis solution according to claim 2, it is characterised in that:
The pH value of the peritoneal dialysis solution is 6.4-6.8.
4. Icodextrin peritoneal dialysis solution according to claim 1, it is characterised in that:
The concentration of the N-acetyl-L-cysteine is 20-25mmol/L.
5. Icodextrin peritoneal dialysis solution according to claim 1, it is characterised in that:
The buffer base (BB) is lactate, citrate, isocitrate, acetonate, succinate, fumarate, apple
Any one or a few in hydrochlorate, oxaloacetate.
6. Icodextrin peritoneal dialysis solution according to claim 1, it is characterised in that:
The electrolyte is sodium chloride, calcium chloride, any one or a few in magnesium chloride.
7. Icodextrin peritoneal dialysis solution according to claim 1, it is characterised in that:
The peritoneal dialysis solution includes Icodextrin 70-80g/L, sodium chloride 82-102mmol/L, calcium chloride 1.50-
1.75mmol/L, magnesium chloride 0.20-0.25mmol/L, lactate 32-40mmol/L, N-acetyl-L-cysteine 10-
25mmol/L。
8. Icodextrin peritoneal dialysis solution according to claim 7, it is characterised in that:
The peritoneal dialysis solution includes Icodextrin 75g/L, sodium chloride 92mmol/L, calcium chloride 1.75mmol/L, magnesium chloride
0.25mmol/L, sodium lactate 40mmol/L, N-acetyl-L-cysteine 20-25mmol/L.
9. the preparation method of Icodextrin peritoneal dialysis solution described in any one of -8 according to claim 1, it is characterised in that:
The following steps are included:
1) Icodextrin, N-acetyl-L-cysteine, buffer base (BB) and electrolyte are taken, is mixed, water for injection is added, makes it dissolve,
Obtain mixed liquor；
2) into the resulting mixed liquor of step 1), acidity regulator is added, adjusting pH value is 5.7-6.8, it filters, moist heat sterilization,
Sterilising temp is 115 DEG C, and sterilization time 30min obtains peritoneal dialysis solution.
10. the preparation method of Icodextrin peritoneal dialysis solution according to claim 9, it is characterised in that:
Acidity regulator in the step 2) is dilute hydrochloric acid, citric acid, lactic acid, phosphoric acid, citric acid, tartaric acid, malic acid, partially
Tartaric acid, acetic acid, adipic acid, any one or a few in fumaric acid.
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Cited By (1)
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