CN100389741C - A method for preparing a medical solution for the manufacture of a medicament for peritoneal dialysis - Google Patents
A method for preparing a medical solution for the manufacture of a medicament for peritoneal dialysis Download PDFInfo
- Publication number
- CN100389741C CN100389741C CNB2003801057810A CN200380105781A CN100389741C CN 100389741 C CN100389741 C CN 100389741C CN B2003801057810 A CNB2003801057810 A CN B2003801057810A CN 200380105781 A CN200380105781 A CN 200380105781A CN 100389741 C CN100389741 C CN 100389741C
- Authority
- CN
- China
- Prior art keywords
- solution
- compartment
- sterilization
- acetylglucosamine
- eventually
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
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Images
Classifications
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- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
- A61M1/28—Peritoneal dialysis ; Other peritoneal treatment, e.g. oxygenation
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
- A61M1/28—Peritoneal dialysis ; Other peritoneal treatment, e.g. oxygenation
- A61M1/287—Dialysates therefor
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- Medical Preparation Storing Or Oral Administration Devices (AREA)
- Apparatus For Disinfection Or Sterilisation (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention provides a method for preparing a medical solution, comprising the steps of a) providing a solution comprising one or more acetylated or deacetylated amino sugar/sugars in at least one compartment of a container in a concentration from 15% by weight to 40% by weight, with the basis of the solution in said at least one compartments, and b) terminal sterilisation of said at least one compartment and the contents therein, is disclosed, as well as a solution used for preparing the medical solution, a container containing said solution, and use of said solution for the manufacture of a medicament for peritoneal dialysis.
Description
Background of invention
The present invention relates to be used to prepare medical solution method, be used to prepare this medical solution solution, hold the container of described solution, and the purposes of described solution in producing medicament for peritoneal dialysis.
Technical background
N-acetyl-glucosamine (NAG) and glycosamine are classified as amino sugar on biochemistry.Amino sugar forms from blood glucose by series of biochemical reactions in nearly all cell.Hyaluronic acid (hyaluronan) is a kind of polymer of being made up of the dimer that contains N-acetyl-glucosamine and glucuronic acid.Show, in the rat of using the solution that is supplemented with exogenous hyaluronic acid to dialyse for a long time, its peritoneum can better be kept (referring to people such as Wieczorowska K, Breborowicz A as the function of dialyzer, " hyaluronic acid is to the protective effect of peritoneal injury ", Perit Dial Int 1995; 15:81-83).
People such as Breborowicz A, Kuzlan-Pawlaczyk M (" N-acetyl-glucosamine is as the effect that is used for by the substrate of people's peritoneal mesothelium cell and the external synthetic glucosaminoglycan of fibroblast ", Advances in Peritoneal Dialysis, 1998; But 14:31-35) instructed NAG rapid stimulation peritoneal mesothelium cell and fibroblast to generate hyaluronic acid and sulphation glucosaminoglycan.
People (" N-acetyl-glucosamine can change the permeability of peritoneum in the rat chronic peritoneal dialysis process ", Perit Dial Int, 1998 such as Wu G, Wieczorowska-Tobis K; 18:217-224) make summary: use the dialysis solution that is supplemented with N-acetyl-glucosamine to carry out the accumulation that peritoneal dialysis can produce glucosaminoglycan in the peritoneal spaces, the result causes the good change of peritoneum permeability.
Breborowicz, people such as M have disclosed and have used N-acetyl-glucosamine to replace glucose in peritoneal dialysis solution.
U.S. patent No.5,536,469 have disclosed the system of the sterile medical of the chemical compound that a kind of employing contains glucose or similar glucose, and the solution that is used for described system.
Because its advantageous feature, NAG has been introduced into as a kind of composition in the peritoneal dialysis solution, replaces part or all of glucose composition, is intended to obtain a kind of more biocompatible peritoneal dialysis solution (referring to WO97/06810).
Peritoneal dialysis is that a kind of hypertonic solution that uses also is fed into this hypertonic solution in the peritoneal cavity with the solute in the exchange patient peritoneum blood capillary and the method for moisture content.The principle of the method is according to the solute diffusion of Concentraton gradient transhipment and because the migration of water of permeable pressure head.This method has many advantages, does not for example need special equipment usually.Because blood samples of patients do not need to carry out extracorporeal circulation, so method is less to hemodynamic influence, and peritoneal dialysis is a kind of lasting treatment, so it is more similar to renal function.
Peritoneal dialysis is divided into continuous ambulatory peritoneal dialysis (CAPD), intermittent peritoneal dialysis (IPD), continuous cycling peritoneal dialysis (CCPD) or automated peritoneal dialysis (APD) usually.
In CAPD, implanted a conduit by standing in patient's stomach wall, and in peritoneal cavity, introduce about dialysis solution of 1.5 to 2.5L usually by conduit.To be full of dialysis solution in the peritoneal cavity, wait until, and then it is drained through one suitable period.The removing of solute and moisture content is undertaken by peritoneum, and at this moment, peritoneum is just as a kind of half penetrating film.
The dialysis solution that is generally used for peritoneal dialysis is the aqueous solution that contains penetrating agent such as glucose etc., electrolyte such as sodium, potassium, calcium, magnesium and acylate such as sodium lactate, sodium bicarbonate or Sodium Pyruvate.The composition of selecting these peritoneal dialysis solutions in order to the level of control electrolyte or acid-base balance, remove waste material and effectively carry out ultrafiltration.
In the known multicell packaging bag that medical solution can be packaged in WO 99/27855 (Gambro Lundia AB) for example, wherein different solutes can be stored in the compartment that separates of packaging bag, especially is intended to regulate the concentration of active ingredient in the final prepared solution.
Medical solution is sterilized by heating usually.In many countries, medical authoritative institution also requires medical product to sterilize behind final packaging again.Therefore unlikely solution is carried out aseptic filtration usually.
But, for multiple medical solution, especially in field of dialysis,, there is the problem of the cytotoxicity product that formation is not expected in heat sterilization and the storage process for example for peritoneal dialysis solution.For example known by EP-B1-0668785 (Gambro Lundia AB), can reduce the amount of the toxic decomposition products of glucose in the medication solution or similar glucose substance.
Have now found that cytotoxicity increased after the amino sugar in conventional medical solution, for example NAG were also shown in heat sterilization.This kind cytotoxicity depends on the formation of the toxic decomposition products of described amino sugar.Opposite with glucose, in the NAG of heat sterilization solution, do not find any known glucose degradation product.This fact is not known as yet before this, and has constituted basis of the present invention.
NAG and other amino sugars all have an amino, and have an acetyl group that is coupled to glucose ring, and this is the main difference with glucose and similar glucosylation compound.About degradation process, have been found that in sterilization process the pH of NAG solution raises, and the pH of glucose solution reduces in sterilization process.This shows that NAG is opposite with glucose, and it forms acetate by hydrolysis and degrades, and this pH that can raise.
Therefore, need to solve problem discussed above, and a kind of amino sugar, particularly NAG and derivant thereof and simultaneously can heat sterilization and can not form the medical solution of above-mentioned cytotoxicity product of containing need be provided.
Summary of the invention
The object of the invention is for addressing the above problem.
According to the present invention, by a kind ofly prepare medical solution, preferred improving one's methods of peritoneal dialysis solution reaches this purpose, it may further comprise the steps:
A) provide the solution that comprises one or more acetylations or deacetylation amino sugar at least one compartment of container, concentration is 20-40% by weight based on the solution in described at least one compartment, and
B) to described at least one compartment with and content carry out end Mo sterilization.
In addition, the invention still further relates to the solution that is used to prepare this medical solution, and relate to the container that holds described solution.
The invention still further relates to the purposes of described solution in producing medicament for peritoneal dialysis.
On the other hand, the present invention relates to carry out the method for peritoneal dialysis, wherein said method comprises to be introduced described medicament for peritoneal dialysis in patient's the peritoneal cavity.
With reference to accompanying drawing and appended claim, from following detailed description of the present invention, the further content of purpose of the present invention, problem, solution and attribute will be apparent.
The accompanying drawing summary
Fig. 1 is for being presented in the sterilization process cell growth inhibited (ICG) and containing the chart that concerns between the NAG concentration in the NAG solution.
Fig. 2 is for showing for three kinds of different pH value the bar diagram of the NAG mass action of 1.5% to 30% increase.
Fig. 3 for when different pH value through the fluorescence chart that contains NAG solution of heat sterilization.
Fig. 4 is presented in the solution that contains 1.5%NAG, the chart of relation between pH and the cell growth inhibited (ICG).
Fig. 5 a-5d for show through the NAG of heat sterilization solution and between the glucose solution of heat sterilization the HPLC chromatogram of different degradation models.
Detailed description of preferred embodiments
The present invention is the above-mentioned development of proposing instruction, and relates to the method that is used to prepare sterile medical, preferred peritoneal dialysis solution.
Illustrate among Fig. 1-4 and carrying out cell growth inhibited (ICG) percent and fluorimetric experiment with different NAG concentration and different pH value in the last heat sterilization process eventually.Experimental result is pointed out, and should determine the concentration of one or more best amino sugars.Experimental result shows that also in a preferred embodiment of the present invention, the pH value that contains amino sugar solution also should be low from the neutral water pancake.
Cytotoxic a kind of simple, the reliable and familiar method of research material or medical solution suppresses (ICG) for detecting the propagation in the cultured cell as in-vitro cell growth.The another kind of method of the amino sugar quantity of readjusting being carried out rough estimate is for measuring its fluorescence.
More accurately, as seen, to containing the 5%NAG solution sterilization of having an appointment, it is maximum that the cell growth inhibited reaches from the chart of Fig. 1, and along with the increase of NAG concentration, the cell growth inhibited reduces.
Bar diagram among Fig. 2 shown in whole last heat sterilization process, the effect that NAG concentration increases during different pH value.As can be seen, cell growth inhibited percent behind end last of pH3.0 heat sterilization will be lower than the cell growth inhibited of pH5.5 and at 7.2 o'clock, and, for all three kinds of pH value, NAG concentration be 30% o'clock eventually the cell growth inhibited behind the last heat sterilization to be lower than NAG concentration be 1.5% cell growth inhibited.
Fig. 3 has shown the pH that contains NAG solution of whole last heat sterilization and the relation between the fluorescence, and fluorescence is measured in excitation wavelength 350nm and emission wavelength 430nm place.At the visible minimum fluorescence in about pH4 place.
Fig. 4 is presented at the cell growth inhibited that contains in the 1.5%NAG solution.
Find that also from external toxicology viewpoint, the NAG solution that contains of sterilizing in the best pH of about 2.5-3.5 has the higher compatibility than the solution that has higher growth inhibited percent when higher or lower pH value is sterilized to the mankind.
Term used herein " eventually end " sterilization mean product in its final packaging by a kind of relate to increase energy, for example heating and/or radiating sterilizing methods are sterilized (for the detailed description of this term and for looking back different sterilization technologies, also can be referring to European Pharmacopoeia 1977,283 pages, first section on the 1st hurdle final stage to the 2 hurdles; And 284 pages, the 2nd hurdle " filtration ").Aseptic filtration relates to the solution that will contain in the filtering product, and this solution is aseptically filled in the container.This can not guarantee needed aseptic herein, if can sterilize to medicine by the sterilization of whole end, therefore aseptic filtration also can not be used as the sterilizing methods of this medicine.
Eventually last sterilization can comprise heat sterilization and/or radiation sterilization, but the heat sterilization that preferably under at least 100 ℃, preferred 121 ℃ temperature, in autoclave, is carried out.Sterilization time can be depending on sterilising temp, Container Type and content wherein subject to sterilization and is different.Radiation sterilization can be ionization sterilization or unionized sterilization.Examples of ionising sterilisation is γ and β radiation.The example of Non-ionizing radiation sterilization is a ultraviolet radiation.
The method according to this invention preferred pin is to carrying out as the multichamber vessel that is disclosed among the WO 99/27885 (Gambro AB).In the present invention, this container comprises that compartment that at least one accommodates physiological compatibility pH regulator and dilute solution and at least one accommodate the compartment that comprises one or more acetylations or deacetylation amino sugar (being referred to as amino sugar hereinafter for simplicity) solution.Amino sugar solution can exist only in the compartment.But the solution in the different compartments is heat sterilization all, and entire container also can be carried out heat sterilization in autoclave when each solution is arranged in described compartment.Be arranged in the solution of compartment separately, in sterilization and storage process subsequently, demarcated mutually, after sterilization, can mix the final prepared sterile medical of formation, be preferably peritoneal dialysis solution.Its also can with at least one other pH regulator and dilution liquid-phase mixing in end sterilization compartment eventually in this container through end sterilization eventually, thereby finally prepare this medical solution.With before the pH regulator of eventually end sterilization and diluent mix, this kind medical solution can be stored to the longer time period at end eventually after sterilizing.But, also can carry out end Mo sterilization by interconnected container to what separate, described container comprises solution subject to sterilization and has connecting device, and this connecting device has the aseptic connection valve that is used for aseptic connection.The described container that separates also can be in process of production by dividing the sealer that unloads, the pin that easily unloads for example commonly used to connect.
In a preferred embodiment of the present invention, be present in and contain that amino sugar is N-acetyl-glucosamine (NAG) in the amino sugar solution in one or more described compartments, concentration is 15-40% by weight based on the solution in each described compartment, for example by weight 15,20,25,30,35 and 40%.
In another embodiment of the present invention; comprise concentration for 15-40% by weight, preferred 20-40% by weight, most preferably the pH of the medical solution of at least 30% one or more acetylations or deacetylation amino sugar is 2.0-5.0, preferred 2.5-3.5, most preferably 3.0 by weight, wherein the formation of cytotoxic substance is prevented from basically in last sterilization steps eventually.
The upper limit of each amino sugar concentration is determined in dissolubility wherein by it in the solution.
Also can contain any organic acid or other pH stabilizing agents for further in sterilization process, stablizing pH value, comprise the compartment that contains amino sugar solution.Solution in the different compartments has pH value, concentration and volume separately, so that mix behind each compartment solution the pH of medical solution of final preparation be neutrality substantially, be pH between 6.0 and 8.0, preferred about 7.4, and amino sugar concentration is 0.2-15.0% by weight, preferably 0.5-6.0%, for example 0.5-2.0% based on final prepared solution.
The volume and the ratio between the compartment of each compartment are in fact unimportant.The volume of each compartment depends on the volume that wherein will contain component.In the most preferred embodiment, the compartment that holds pH regulator and diluent is greater than and holds the compartment that contains amino sugar solution, and it simultaneously also is one or more solution of other compartments and pH regulator and diluent in blended compartment wherein.
In a preferred embodiment, the medicine of institute's desire preparation is that to contain N-acetyl-glucosamine and pH be 7.4 peritoneal dialysis solution.
Should be noted that the degradation model of amino sugar solution in the heat sterilization process follow special Maillard reaction, produce several different toxic decomposition products.For example for the glucose solution in the heat sterilization process, the degradation model difference wherein forms different catabolites.This species diversity is illustrated in Fig. 5 a-5d, and it has shown the 3-DG (3-deoxyglucosone) and 3 that analyzes NAG solution and glucose solution, the chromatogram of 4-DGE (3,4-dideoxy glucosone-3-alkene) respectively.The difference of degraded may be because the NAG molecule contains the group that allows to take place the Maillard reaction, and has therefore generated a large amount of catabolites of never being seen in the glucose solution.
Term used herein " solution that contains amino sugar " means and comprises the solution that is selected from following acetylation or deacetylation amino sugar related among one or more the present invention: the monomer of N-acetyl-glucosamine (NAG), galactosamine, N-acetylgalactosamine, mannosamine and N-acetylmannosamine, its oligomer and/or polymer form; comprise chitin; and people's glucosaminoglycan, with and derivant.Most preferred amino sugar is N-acetyl-glucosamine (NAG).Therefore, acetylation or deacetylation amino sugar can be only by listed a kind of amino sugar or by its combination with and derivant represent.
Term used herein " its derivant " is meant the derivant with identical or substantially the same described amino sugar that forms cytotoxicity catabolite ability in sterilization process.
Term used herein " pH regulator and diluent " be meant be used for and contain amino sugar solution mix, for example as containing the solution of the receiver media of amino sugar solution, simultaneously its also be regulate with the pH that contains the mixed solution of amino sugar solution to basic neutrality be pH for example between 6.0 to 8.0, preferred about 7.4 solution.
Term used herein " low-level cytotoxicity catabolite " is meant that the amount of amino sugar catabolite in the medical solution prepared according to the present invention is so low, to such an extent as to its toxicity to cultured cell is no more than the toxicity of prior art dialysis solution.
In preferred embodiments, pH regulator and diluent contain the pH regulator agent in the pharmaceutically stable scope, as the salt of mineral acid, organic acid, alkaline matter etc.Mineral acid comprises hydrochloric acid etc., and organic acid comprises lactic acid, malic acid, acetic acid, succinic acid, maleic acid, acetone acid, citric acid, gluconic acid etc., and alkaline matter comprises sodium hydroxide, sodium bicarbonate etc.And each seed amino acid also can be used as the pH regulator agent.
After sterilization, by the solution that will contain amino sugar mix with pH regulator and diluent, solution optional and in other compartments of container mixes, and is used for use finally to make.So the medical solution that obtains, preferred peritoneal dialysis solution also can contain different electrolyte ions with the concentration that bio-compatible and basic etc. is opened, for example sodium, potassium, calcium, magnesium, chlorine, lactic acid and bicarbonate ion.Electrolyte can be contained among the another kind of solution in one or more other compartments of pH regulator and diluent, the solution that contains amino sugar and/or container at first, and this depends on its compatibility in sterilization and storage process, is generally the form of pharmaceutically acceptable salt.In the peritoneal dialysis solution that is ready to use, cationic amount is generally 110-140mEq/ml sodium ion, 0-0.05mEq/ml potassium ion, 0-3mEq/l magnesium ion and 0-6mEq/l calcium ion.The amount of preferred chloride ion is 80-144mEq/l.
Peritoneal dialysis solution as a preferred embodiment of medical solution of the present invention also can comprise other physiological compatibility compositions, other penetrating agent for example, as carbohydrate, preferred glucose, protein and polypeptide, preferred albumin, and antioxidant such as bisulfites.
Above-mentioned peritoneal dialysis solution of the present invention not only can be applied to continuous ambulatory peritoneal dialysis (CAPD), also can be used for intermittent peritoneal dialysis (IPD), continuous cycling peritoneal dialysis (CCPD) and automated peritoneal dialysis (APD).In addition, it contains low-level amino sugar cytotoxicity catabolite.
The invention still further relates to solution itself with above-mentioned institute defined property.
The present invention also relates to a kind of container, it accommodates at least one compartment and contains amino sugar solution, and wherein, described solution is optional through sterilizing and containing low-level cytotoxicity catabolite.
In addition, the present invention relates to according to the purposes of solution of the present invention in producing medicament for peritoneal dialysis, wherein this solution mixes with pH regulator and diluent through sterilizing.
As mentioned above, the invention still further relates to a kind of method of carrying out peritoneal dialysis, wherein said method comprises to be introduced described medicament for peritoneal dialysis in patient's the peritoneal cavity.
For illustrating different embodiments of the present invention, following examples have explanation different compartment structures, contain the container that is useful on each composition of preparation peritoneal dialysis solution, and the composition of solution in each compartment.In an embodiment, in one or two compartment of container, N-acetyl-glucosamine (NAG) all is used as amino sugar.Before mixing, the pH that contains NAG solution in each compartment changes between 2.0 and 5.0, and in the medical solution that finally makes, its pH changes between 6.0 and 8.0.
Embodiment
Embodiment 1
Compartment A volume 100ml
Sodium 0-140mM
NAG 300g/l
Compartment B volume 180ml
Sodium 0-140mM
NAG 300g/l
Compartment C volume 1900ml
Sodium 0-140mM
Lactate 40mM
Magnesium 0.25-0.75mM
Calcium 0.9-2.0mM
Final composition when mixing content among the compartment A+C:
Volume 2000ml
Sodium 0-140mM
NAG 15g/l
Lactate 38mM
Magnesium 0.24-0.71mM
Calcium 0.85-1.9mM
Final composition when mixing content among the compartment B+C:
Volume 2080ml
Sodium 0-140mM
NAG 26g/l
Lactate 36.5mM
Magnesium 0.22-0.68mM
Calcium 0.82-1.8mM
Final composition when mixing content among the compartment A+B+C:
Volume 2180ml
Sodium 0-140mM
NAG 38.5g/l
Lactate 34.9mM
Magnesium 0.21-0.65mM
Calcium 0.78-1.7mM
Compartment A volume 100ml
Sodium 0-140mM
NAG 300g/l
Compartment B volume 180ml
Sodium 0-140mM
Glucose 500g/l
Compartment C volume 1900ml
Sodium 0-140mM
Lactate 40mM
Magnesium 0.25-0.75mM
Calcium 0.9-2.0mM
Final composition when mixing content among the compartment A+C:
Volume 2000ml
Sodium 0-140mM
NAG 15g/l
Glucose 0g/l
Lactate 38mM
Magnesium 0.24-0.71mM
Calcium 0.86-1.9mM
Final composition when mixing content among the compartment A+B+C:
Volume 2100ml
Sodium 0-140mM
NAG 14.3g/l
Glucose 23.8g/l
Lactate 36mM
Magnesium 0.23-0.68mM
Calcium 0.81-1.8mM
Embodiment 3
Compartment A volume 60ml
Sodium 0-140mM
NAG 200g/l
Glucose 330g/l
Compartment B volume 100ml
Sodium 0-140mM
NAG 200g/l
Glucose 330g/l
Compartment C volume 1900ml
Sodium 0-140mM
Lactate 40mM
Magnesium 0.25-0.75mM
Calcium 0.9-2.0mM
Final composition when mixing content among the compartment A+C:
Volume 1960ml
Sodium 0-140mM
NAG 6.2g/l
Glucose 10.1g/l
Lactate 38.8mM
Magnesium 0.24-0.73mM
Calcium 0.87-1.9mM
Final composition when mixing content among the compartment B+C:
Volume 2000ml
Sodium 0-140mM
NAG 10.0g/l
Glucose 16.5g/l
Lactate 38.0mM
Magnesium 0.24-0.71mM
Calcium 0.86-1.9mM
Final composition when mixing content among the compartment A+B+C:
Volume 2060ml
Sodium 0-140mM
NAG 15.5g/l
Glucose 25.6g/l
Lactate 37mM
Magnesium 0.23-0.69mM
Calcium 0.83-1.8mM
With reference to the preferred embodiments of the invention, above describe the present invention.It will be appreciated by those skilled in the art that other combinations also are possible.The change that it will be apparent to those skilled in the art all should be included among the scope of the invention, and only be subjected to the restriction of claims.
Claims (18)
1. method for preparing medical solution, it comprises the steps:
A) provide the solution that comprises the N-acetylglucosamine at least one compartment of container, concentration is with weight 15-40% based on the solution in described at least one compartment, and
B) to described at least one compartment with and content carry out end Mo sterilization.
According to the process of claim 1 wherein in described at least one compartment of described container described N-acetylglucosamine with based on the solution in described at least one compartment by weight the concentration of 20-40% provide.
3. according to the method for claim 2, wherein the described N-acetylglucosamine in described at least one compartment of described container with based on the solution in described at least one compartment by weight at least 30% concentration provide.
4. according to the process of claim 1 wherein that eventually end sterilization is the heat sterilization when at least 100 ℃ the temperature, and/or radiation sterilization.
5. according to the method for claim 4, wherein the end sterilization is the heat sterilization when 121 ℃ the temperature eventually.
6. according to each method in the claim 1,4 and 5, wherein each compartment of container is being demarcated with other one or more compartments in the last sterilization process eventually, and the solution through end sterilization eventually that wherein contains the N-acetylglucosamine mixes with at least one other pH regulator and diluent through end sterilization eventually in the compartment of end sterilization eventually in the container, thereby finally prepares this medical solution.
7. according to the method for claim 6, wherein finally the pH of the medical solution of preparation is 6.0-8.0.
8. according to the method for claim 7, wherein finally the pH of the medical solution of preparation is 7.4.
9. according to the method for claim 7, wherein the concentration of N-acetylglucosamine is 0.2-15.0% by weight in final preparation solution.
10. according to the method for claim 9, wherein the concentration of N-acetylglucosamine is 0.5-6.0% by weight in final preparation solution.
11. according to the process of claim 1 wherein that the physiological compatibility composition and the antioxidant of carbohydrate form are present in one or more described compartments.
12. according to the method for claim 11, wherein carbohydrate is glucose, protein, peptide.
13. according to each method among the claim 1-5,11 and 12, this wherein prepared medical solution is a peritoneal dialysis solution.
14. comprise the solution of the N-acetylglucosamine of the amount of 15-40% by weight, wherein said solution is through the sterilization of whole end and contain low-level cytotoxicity catabolite.
15. the described solution of claim 14, it comprises the N-acetylglucosamine of the amount of 20-40% by weight, and wherein said solution is through the sterilization of whole end and contain low-level cytotoxicity catabolite.
16. the described solution of claim 15, it comprises by weight the N-acetylglucosamine of at least 30% amount, and wherein said solution is through end sterilization eventually and contain low-level cytotoxicity catabolite.
17. a container, it comprises that at least one contains the compartment of each solution in the with good grounds claim 14 to 16.
18. according to each the purposes of solution in producing medicament for peritoneal dialysis in the claim 14 to 16, wherein this solution mixes with the pH regulator and the diluent of sterilizing through end eventually.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE02036721 | 2002-12-10 | ||
| US60/432,581 | 2002-12-10 | ||
| SE0203672A SE524531C2 (en) | 2002-12-10 | 2002-12-10 | Solution useful in the manufacture of medicament for peritoneal dialysis e.g. continuous ambulatory peritoneal dialysis comprises acetylated or deacetylated amino sugar in specified amount |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1725997A CN1725997A (en) | 2006-01-25 |
| CN100389741C true CN100389741C (en) | 2008-05-28 |
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|---|---|---|---|
| CNB2003801057810A Expired - Lifetime CN100389741C (en) | 2002-12-10 | 2003-12-10 | A method for preparing a medical solution for the manufacture of a medicament for peritoneal dialysis |
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| Country | Link |
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| SE (1) | SE524531C2 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE524530C2 (en) * | 2002-12-10 | 2004-08-24 | Gambro Lundia Ab | Solution useful in the manufacture of medicament for peritoneal dialysis e.g. continuous ambulatory peritoneal dialysis comprises acetylated or deacetylated amino sugar having specified pH |
| CN102973600B (en) * | 2012-12-13 | 2014-11-26 | 天津金耀集团有限公司 | Peritoneal dialysis solution (lactate) (low calcium) composition |
Citations (4)
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|---|---|---|---|---|
| US5536469A (en) * | 1991-11-18 | 1996-07-16 | Gambro Ab | System employing a sterile medical solution containing glucose or glucose-like compounds and a solution intended for said system |
| CN1195291A (en) * | 1995-08-11 | 1998-10-07 | G·武 | Biocompatible aqueous solution for use in continuous ambulatory peritoneal dialysis |
| CN1280481A (en) * | 1997-11-28 | 2001-01-17 | 甘布罗股份公司 | Multiple compartment container for medical solution |
| CN1725996A (en) * | 2002-12-10 | 2006-01-25 | 甘布罗伦迪亚股份有限公司 | A method for preparing a medical solution for the manufacture of a medicament for peritoneal dialysis |
-
2002
- 2002-12-10 SE SE0203672A patent/SE524531C2/en not_active IP Right Cessation
-
2003
- 2003-12-10 CN CNB2003801057810A patent/CN100389741C/en not_active Expired - Lifetime
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5536469A (en) * | 1991-11-18 | 1996-07-16 | Gambro Ab | System employing a sterile medical solution containing glucose or glucose-like compounds and a solution intended for said system |
| CN1195291A (en) * | 1995-08-11 | 1998-10-07 | G·武 | Biocompatible aqueous solution for use in continuous ambulatory peritoneal dialysis |
| CN1280481A (en) * | 1997-11-28 | 2001-01-17 | 甘布罗股份公司 | Multiple compartment container for medical solution |
| CN1725996A (en) * | 2002-12-10 | 2006-01-25 | 甘布罗伦迪亚股份有限公司 | A method for preparing a medical solution for the manufacture of a medicament for peritoneal dialysis |
Non-Patent Citations (2)
| Title |
|---|
| Replacement of glucose with N-acetylglucosamine inperitoneal dialysis fluid-experimental study in rats. Andrezj Breborowicz et al.Peritoneal Dialysis International,Vol.21 . 2001 |
| Replacement of glucose with N-acetylglucosamine inperitoneal dialysis fluid-experimental study in rats. Andrezj Breborowicz et al.Peritoneal Dialysis International,Vol.21 . 2001 * |
Also Published As
| Publication number | Publication date |
|---|---|
| SE0203672L (en) | 2004-06-11 |
| SE0203672D0 (en) | 2002-12-10 |
| SE524531C2 (en) | 2004-08-24 |
| CN1725997A (en) | 2006-01-25 |
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