CN102973597A - Peritoneal dialysis solution (containing lactate and low calcium) combination and preparation method thereof - Google Patents

Abstract

The invention discloses a peritoneal dialysis solution (containing lactate and low calcium) combination and a preparation method thereof. The peritoneal dialysis solution combination comprises the following components: 1.5%-4.0% of C6H12O6.H2O, 0.5%-0.6% of Cl2Na, 0.0001%-0.0002% of CaCl2, 0.00004%-0.00006% of MgCl2 and 0.4%-0.5% of C3H5NaO3. The preparation method is characterized in that the sterilization of a sub-packaged peritoneal dialysis solution is implemented by a method comprising the following steps of: firstly, heating the sub-packaged peritoneal dialysis solution to 115 DEG C by virtue of a hot-press sterilization method, and maintaining the sub-packaged peritoneal dialysis solution at 115 DEG C for 5 minutes; secondly, performing ultrasonic treatment on the peritoneal dialysis solution at a frequency of 20-50 kHz and an intensity of 5-20 W/cm<2> while the heating of the peritoneal dialysis solution begins; and thirdly, after the peritoneal dialysis solution is maintained at 115 DEG C for 5 minutes, stopping the heating and the ultrasonic treatment on the peritoneal dialysis solution, and cooling the peritoneal dialysis solution.

Description

Peritoneal dialysis solution (lactate) (low calcium) composition and method of making the same

Technical field

Peritoneal dialysis solution of the present invention and preparation method thereof.

Background technology

Peritoneal dialysis owing to compare with hemodialysis, have applied widely, dialytic efficiency is high, residual renal function is kept, the patients ' life quality advantages of higher, occupies more and more consequence in the alternative medicine of chronic renal failure.The key of successful peritoneal dialysis is the peritoneum that ultrafiltration function is good.Yet because the chronicity of peritoneal dialysis treatment, the ultrafiltration performance of peritoneum tends to be subjected to various factors to affect to change in therapeutic process, and this change is irreversible, finally can cause the forfeiture of patient's peritoneum ultrafiltration function, can't carry out abdomen again and thoroughly treat.Traditional peritoneal dialysis solution is mainly the GES of variable concentrations, produce peritoneal dialysis solution (lactate) and peritoneal dialysis solution (lactate) (low calcium) etc. such as Tianjin TianAn Medicine Industry Co., Ltd, when high temperature sterilize and storage, can decompose impurity such as producing 5 hydroxymethyl furfural (5-HMF) owing to contain the peritoneal dialysis solution of glucose, and existing studies show that, the glucose degradation products take 5-HMF as representative in the peritoneal dialysis solution (glucose degradation products, GDP) be that peritoneum is produced one of dysgenic key factor, in view of the chronicity of dialysis patient treatment, reducing as far as possible the GDP content take 5-HMF as representative in the peritoneal dialysis becomes and mainly needs the problem that solves in the prior art.

The ultrasonic sterilization technology is a kind of cold sterilization technology of sterilizing new that developed recently gets up, the fields such as food, drinking water and wastewater treatment have been applied to, China's document " ultrasound wave is inquired into several frequently seen pathogenic entero becteria killing effect and the mechanism of action thereof " (Fang Xiang etc., acoustic technique, the 4th phase of the 28th volume August in 2009, disclose in 491-494) when adopting ultrasonic sterilization technology and the collaborative sterilization of heating for some heat resistanceheat resistant effect preferably antibacterial do not produce synergy.

Summary of the invention

We find unexpectedly through research, select ultrasound wave in conjunction with the preparation technology of high temperature sterilize, can obtain the significantly reduced peritoneal dialysis solution of a kind of 5-HMF content.

The percentage ratio of the following stated all refers to percent weight in volume if no special instructions among the present invention.Wherein glucose is with C ₆H ₁₂O ₆H ₂The O meter, calcium chloride is with CaCl ₂2H ₂The O meter, magnesium chloride is with MgCl ₂6H ₂The O meter.

The invention provides a kind of peritoneal dialysis solution, the glucose that contains 1.5-4.0%, the sodium chloride of 0.5-0.6%, the calcium chloride of 0.0001-0.0002%, the magnesium chloride of 0.00004-0.00006%, and the sodium lactate of 0.4-0.5%, it is characterized in that adopting when described peritoneal dialysis solution is sterilized following method after packing:

1) adopts autoclaving, the peritoneal dialysis solution after the packing is warming up to 115 ℃, keep 5min;

2) beginning the while of heating up, peritoneal dialysis solution is imposed frequency 20-50kHz, intensity is 5-20W/cm ²Ultrasonic Treatment;

3) stopped heating and ultrasonic Treatment after step 1) is held time and arrived cool.

Described peritoneal dialysis solution, optimization formula are by 0.5377% sodium chloride, 0.000147% calcium chloride, and 0.0000508% magnesium chloride, 0.4483% sodium lactate, and 1.5% or 4.0% glucose, and the water for injection of surplus forms.

Described peritoneal dialysis solution, preferably adopt the following methods preparation:

1. dope preparation: get the water for injection of recipe quantity 10%, other compositions that enter recipe quantity are stirred to whole dissolvings.After, then add after medicinal charcoal 0.1 ~ 1% stirs, place to filter after 10 ~ 20 minutes and obtain dope.

2. medicinal liquid dilution: to dilute preparing tank, the supplementary injection water is to full dose with dope pressure filtration.Through 0.22 μ m ultimate filter be filtered to visible foreign matters qualified after embedding.

Preferably adopt inert gas shielding when preparation and embedding, described noble gas is selected from one or more in nitrogen or the carbon dioxide.

Described percent weight in volume is the ratio of adding active carbon weight with the prescription volume of the injection of preparing.

The specific embodiment

The transformation of sterilizing installation,

Sterilizing installation in the present invention, adopt the transformation of existing high temperature sterilize pot, the JT01-01-computer full-automatic fountain High Temperature High Pressure conditioning retorts that adopts the Jin Tai Zhucheng safe food machinery company limited of gold to produce, arrange ultrasonic oscillator around in autoclave, make the maximum ultrasonic intensity in the autoclave can reach 20w/cm ², ultrasound wave adopts and the 40kHz specification.

Prescription described in the present embodiment is the inventory in 1000 bottles of injection.High temperature sterilize among the embodiment adopts the moist hear heat test sterilization under 115 ℃ of conditions without exception, adopt (the comparisons of several temperature indicators of steam sterilization such as Chen Jinqiu, China's Disinfection magazine, the 3rd phase of the 9th volume in 1992,186-187) disclosed content, (every bacterial content is 5 * 10 for culture presevation numbering ATCC7953, the production of Hangzhou Fu Jie Bioisystech Co., Ltd to select damp and hot pimelobacter sp sporeformer sheet ⁵～5 * 10 ⁶Cfu, under 121 ℃ of saturated vapors sterilization testing conditions, D value is 1.3～1.9min) as the biological indicator, verifies the reliability of the compound moist heat sterilization method of ultrasound wave.

Example of formulations

Prescription is such as following table, and the packing specification is the 2000ml/ bag, and data are to amount to the prescription of every bag of dialysis solution in the table

1. dope preparation: get the water for injection of recipe quantity 10%, other compositions that add recipe quantity are stirred to whole dissolvings.After, then add after medicinal charcoal 0.1 ~ 1% stirs, place to filter after 10 ~ 20 minutes and obtain dope.

2. medicinal liquid dilution: to dilute preparing tank, the supplementary injection water is to full dose with dope pressure filtration.Through 0.22 μ m ultimate filter be filtered to visible foreign matters qualified after embedding.

When preparation and embedding, adopt nitrogen protection.

The sterilization effect confirmatory experiment

Get and respectively organize peritoneal dialysis solution by example of formulations method preparation, after filtration sterilization, before the packing, add bacillus stearothermophilus bacterium sheet biological indicator, add after the bacterium sheet broken up in sterile water for injection, addition is every 2000ml/ sheet, and each embodiment sterilising temp unification fixes on 115 ℃, and experiment grouping batch sees the following form

The experimental group numbering	1	2	3	4	5	6	7	8	9	10
											115 ℃ of persistent period/min	3	3	5	5	7	7	10	10	10	15
Ultrasonic intensity/(W/cm 2）	5	20	5	20	5	20	5	20	0	0

Each experimental group is all got 20 bags of injection, is respectively according to example of formulations 1-2 prescription preparation, 10 bags of each example of formulations.Stopped heating and ultrasonic after arriving heat time heating time is reduced to the injection temperature below 75 ℃ in 10min, takes out sample, base sampling under aseptic condition, cultivated 7 days with the cultivation that contains coeruleum bromocresolis, for being positive, detect sterilization effect with the culture medium flavescence, simultaneously, see the following form according to embodiment

The experimental group numbering	1	2	3	4	5	6	7	8	9	10
											Positive rate	5	0	0	0	0	0	0	0	5	0

Can find out by sterilization experiment, when adopting the sterilization of ultrasound wave assisted with high-temperature, when being heated to 115 ℃ of 5min, can all kill thermoduric bacteria among the biological indicator, and when adopting high temperature sterilize separately, be heated at least the sterilization that 15min could be good.Illustrate that sterilizing methods provided by the invention can be on the basis that reduces high-temperature duration, the collaborative killing effect of the hot antibacterial that creates antagonism realizes reducing the effect that high-temperature duration can well be sterilized simultaneously.

The glucose degradation products contrast experiment

The grouping situation sees the following form

The experimental group numbering	1	3	5
				The example of formulations numbering	2	2	2
The bag number	10	10	10

Wherein, wherein, experimental group 1 adopts the sterilization process of experimental group 4 in the sterilization effect confirmatory experiment, and experimental group 2 adopts the sterilization process of experimental group 10 in the sterilization effect confirmatory experiments, and experimental group 3 does not heat for matched group.

After experiment finishes, get respectively the sample detection 5-HMF content of experimental group 1-6.

Detection method is carried out absorbance detection according to the detection method under the Mannitol sodium chloride injection item in 2010 editions second one 94 pages of the Chinese Pharmacopoeias.

Testing result sees the following form

Numbering	1	3	5
				Absorbance	0.108±0.012	0.215±0.018	0.079±0.010

Testing result shows, adopted the peritoneal dialysis solution of ultrasound wave in conjunction with the high-temperature sterilizing process preparation, can reduce significantly the glucose degradation products take 5-HMF as representative in the product, thereby reduce the saturating dialysis solution of abdomen to the toxicity of human body peritoneum, avoid causing the forfeiture of peritoneum ultrafiltration function, improve the safety of its life-time service.

Claims (2)

1. peritoneal dialysis solution, the glucose that contains 1.5-4.0%, the sodium chloride of 0.5-0.6%, the calcium chloride of 0.0001-0.0002%, the magnesium chloride of 0.00004-0.00006%, and the sodium lactate of 0.4-0.5%, it is characterized in that adopting when described peritoneal dialysis solution is sterilized following method after packing:

1) adopts autoclaving, the peritoneal dialysis solution after the packing is warming up to 115 ℃, keep 5min;

2) beginning the while of heating up, peritoneal dialysis solution is imposed frequency 20-50kHz, intensity is 5-20W/cm ²Ultrasonic Treatment;

3) stopped heating and ultrasonic Treatment after step 1) is held time and arrived cool.

2. peritoneal dialysis solution as claimed in claim 1, it is characterized in that filling a prescription is 0.5377% sodium chloride, 0.000147% calcium chloride, 0.0000508% magnesium chloride, 0.4483% sodium lactate, and 1.5% or 4.0% glucose, and the water for injection of surplus forms.