EP1530593A1 - Hochverzweigte, nicht oder niedrig substituierte stärkeprodukte, dialyselösung und plasmaexpander enthaltend diese und deren verwendung - Google Patents
Hochverzweigte, nicht oder niedrig substituierte stärkeprodukte, dialyselösung und plasmaexpander enthaltend diese und deren verwendungInfo
- Publication number
- EP1530593A1 EP1530593A1 EP03793660A EP03793660A EP1530593A1 EP 1530593 A1 EP1530593 A1 EP 1530593A1 EP 03793660 A EP03793660 A EP 03793660A EP 03793660 A EP03793660 A EP 03793660A EP 1530593 A1 EP1530593 A1 EP 1530593A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- degree
- substitution
- starch
- branching
- starch product
- 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.)
- Withdrawn
Links
- 229920002472 Starch Polymers 0.000 title claims abstract description 63
- 235000019698 starch Nutrition 0.000 title claims abstract description 62
- 239000008107 starch Substances 0.000 title claims abstract description 59
- 239000003058 plasma substitute Substances 0.000 title claims abstract description 8
- 239000000385 dialysis solution Substances 0.000 title claims description 12
- 239000000047 product Substances 0.000 title description 39
- 238000006467 substitution reaction Methods 0.000 claims abstract description 26
- 238000000502 dialysis Methods 0.000 claims abstract description 15
- -1 hydroxyethyl groups Chemical group 0.000 claims abstract description 10
- 230000002016 colloidosmotic effect Effects 0.000 claims abstract description 8
- 239000002357 osmotic agent Substances 0.000 claims abstract description 7
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 239000000654 additive Substances 0.000 claims description 4
- 230000003647 oxidation Effects 0.000 claims 1
- 238000007254 oxidation reaction Methods 0.000 claims 1
- 102000013142 Amylases Human genes 0.000 abstract description 8
- 108010065511 Amylases Proteins 0.000 abstract description 8
- 235000019418 amylase Nutrition 0.000 abstract description 8
- 239000004382 Amylase Substances 0.000 abstract description 7
- 229920002527 Glycogen Polymers 0.000 abstract description 7
- 239000012634 fragment Substances 0.000 abstract description 7
- 229940096919 glycogen Drugs 0.000 abstract description 7
- 230000015556 catabolic process Effects 0.000 abstract description 5
- 210000000056 organ Anatomy 0.000 abstract description 5
- 230000007774 longterm Effects 0.000 abstract 1
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 20
- 229940050526 hydroxyethylstarch Drugs 0.000 description 18
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 11
- 239000008103 glucose Substances 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 9
- 229920000945 Amylopectin Polymers 0.000 description 8
- 238000003860 storage Methods 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 229920000856 Amylose Polymers 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 230000002255 enzymatic effect Effects 0.000 description 4
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 238000005227 gel permeation chromatography Methods 0.000 description 3
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical group O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 210000000952 spleen Anatomy 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 239000003792 electrolyte Substances 0.000 description 2
- 238000006266 etherification reaction Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 210000004303 peritoneum Anatomy 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 208000002513 Flank pain Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920002177 Icodextrin Polymers 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010061373 Sudden Hearing Loss Diseases 0.000 description 1
- 230000009102 absorption Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 229940025131 amylases Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 1
- 230000002727 hyperosmolar Effects 0.000 description 1
- 229940016836 icodextrin Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 206010034674 peritonitis Diseases 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000006098 transglycosylation Effects 0.000 description 1
- 238000005918 transglycosylation reaction Methods 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B31/00—Preparation of derivatives of starch
- C08B31/08—Ethers
- C08B31/12—Ethers having alkyl or cycloalkyl radicals substituted by heteroatoms, e.g. hydroxyalkyl or carboxyalkyl starch
Definitions
- the present invention relates to highly branched, unsubstituted or low-substituted starch products which are particularly suitable for use as a colloid-osmotic agent in peritoneal dialysis and as a volume replacement agent (plasma expander).
- glucose has mainly been used as an osmotic agent in peritoneal dialysis. This has proven itself, especially in the case of brief intermittent use (residence time approx. 2 to 3 hours), is not toxic, is compatible with the other ingredients of the dialysis solution and can be steam sterilized under non-alkaline conditions. In addition, glucose is relatively inexpensive. Nevertheless, glucose is not an ideal agent because undesirable side effects can occur during peritoneal dialysis. Unphysiologically low pH values and hyperosmolar solutions necessarily lead to irritation. Due to rapid reabsorption into the blood, high blood sugar and blood lipid levels occur. Therefore, the ultrafiltration performance can only be maintained over relatively short periods of time.
- continuous outpatient peritoneal dialysis (also called CAPD below) indicated that glucose should be replaced by an agent that causes a allows a longer residence time of the dialysis solution in the peritoneal space and thus reduces the burden on the patient.
- a sufficient ultrafiltration performance and depletion (“clearance”) of solutions is not only achieved by setting an osmotic pressure, but also by that of Macromolecules called colloid osmotic pressure.
- dialysis solutions could also be used in the isoosmolar or hypoosmolar range.
- Glucose polymers are used, which are obtained by hydrolysis of unmodified grain starch and have molecular weights of approx. 20,000 (icodextrin).
- a major disadvantage of such hydrolyzed starch fractions is that the molecular weight is limited by the water solubility which decreases with increasing molecular weight and is therefore not in the optimal range for the intended application.
- slightly branched or unbranched starch fragments tend to retrogradate - generally known for the amylose content of starch - and can lead to undesirable precipitations. This is all the more true when starches rich in amylose are chosen as the starting point for the hydrolysates.
- maltodextrin-like starch products under autoclaving conditions, tend to form undesirable and possibly harmful by-products such as formaldehyde and aldonic acids.
- HES hydroxyethyl starch
- HES is currently the most modern and most widespread volume substitute.
- the active ingredient is used in different variants, which differ in their molecular weight and their degree and pattern of substitution.
- Hydroxyethyl starches are generally distinguished from other volume substitutes, such as gelatin, dextrans or artificial colloids, by a high level of tolerance, which is based on the fact that wax starch is used as the starting material for HES, a special type of starch that consists of over 98% amylopectin, which in its chemical structure is similar to the body's own reserve substance glycogen. The remaining approx. 2% consist of little or hardly branched amylose.
- amylopectin is made up of glucose units which are connected to one another in the basic structure via ⁇ -1, 4 linkages and at the branching sites via ⁇ -1, 6 linkages.
- amylopectin with approx. 5% ⁇ -1, 6-linkages is significantly less branched than glycogen with 10 to 16% ⁇ -1, 6-linkages (every 6th to 10th glucose unit)
- Amylopectin is not water soluble. If this were the case, it would be broken down quickly by the body's own amylases and remain ineffective.
- the amylopectin becomes water-soluble, and in addition - depending on the degree of substitution (degree of etherification) - the degradation by amylase is slowed down, which then together with the set molecular weight the desired duration of action in use, e.g. determined as a volume substitute by HES.
- a serious disadvantage of all known hydroxyethylated or hydroxypropylated starch types is therefore that the more or less substitution by hydroxyethyl or hydroxypropyl groups makes complete degradation by amylase difficult or impossible.
- residual fragments remain in the organism, which are eliminated very slowly or are stored in various organs / tissues, such as the spleen, liver and lungs. This can be particularly critical with higher and / or longer-term dosing. It is believed that the known side effects, such as flank pain or itching, are due to this.
- HES types in the molecular weight range from 40,000 to 450,000 and degrees of substitution from 0.5 and 0.7 for use in peritoneal dialysis showed that reabsorbed HES and fragments thereof in spleen, Lungs and liver are stored, so that the use of HES as a colloid osmotic agent can be classified as not unproblematic.
- This undesirable storage of HES is due to the fact that due to the high substitution, the body's own amylase does not completely break down HES.
- the invention was therefore based on the object of providing an agent which has the advantageous properties of the hydroxyethyl or hydroxypropyl starches known in the prior art, but in addition no longer has the disadvantageous properties of storing residual fragments in organs and tissues ,
- the object can be achieved with a highly branched, unsubstituted or low-substituted starch product, i.e. with a starch which has a significantly higher degree of branching than amylopectin or which has or even exceeds the ⁇ -1,6 degree of branching of glycogen and - if substituted - a degree of substitution MS of only up to 0.3, preferably of 0 , 05 to 0.3.
- MS molecular substitution
- the MS is understood to mean the average number of hydroxyethyl or hydroxypropyl groups per anhydroglucose unit.
- the MS is usually determined by determining the content of hydroxyethyl or hydroxypropyl groups in a sample and the arithmetic Allocation to the anhydroglucose units contained therein.
- the MS can also be determined by gas chromatography.
- the degree of branching can be determined via a gas chromatographic methylation analysis as mol% of the ⁇ -1,4,6-glycosidically linked anhydroglucoses in the polymer.
- the degree of branching is in any case an average since the starch products according to the invention are polydisperse compounds.
- the glucose units in starch and glycogen or in the product according to the invention are linked via ⁇ -1, 4 and ⁇ -1, 6 bonds.
- the degree of branching is understood to mean the proportion of the ⁇ -1,4,6-linked glucose units in mol% of the total of all anhyroglucoses.
- the C 2 / C 6 ratio expresses the ratio or substitution at C-2 to that at C-6.
- the starch products according to the invention have a degree of branching of 8% to 20%, which can be achieved by a transglucosidation step with the aid of branching enzymes.
- any starch can be used as the starting material for this, but preferably wax starches with a high proportion of amylopectin or the amylopectin fraction itself.
- the degree of branching of the starch products required for the use according to the invention is in the range from 8% to 20%, expressed as mol% the anhydroglucose. This means that the starch products useful in the context of the invention have on average every 12.5 to 5 glucose units an ⁇ -1,6 bond and thus a branch point.
- Starch products with a degree of branching of more than 10% to 20% and in particular of 11 to 18% are preferred.
- the starch products according to the invention can be prepared by targeted enzymatic construction using so-called branching or transfer enzymes, optionally followed by a partial derivatization of free hydroxyl groups with hydroxyethyl or hydroxypropyl groups.
- branching or transfer enzymes instead of this, a hydroxyethylated or hydroxypropylated starch can be converted into a starch product according to the invention by enzymatic construction using so-called branching or transfer enzymes.
- branching or transfer enzymes so-called branching or transfer enzymes.
- Suitable branching or transfer enzymes and their extraction are known from WO-A-00 / 18,893, US-A-4,454,161, EP-A-418,945, JP-A-2001 / 294,601 or US-A-2002 / 65,410 known. This latter document describes unmodified starch products with degrees of branching from more than 4% to over 10%.
- the enzymatic transglycosylation can be carried out in a manner known per se, for example by incubating waxy maize starch with the corresponding enzymes under mild conditions at pH values between 6 and 8 and temperatures between 25 and 40 ° C. in aqueous solution.
- the average molecular weight (M w ) - depending on the application - is preferably in the range from 10,000 to 450,000 and, if appropriate, the C 2 / C 6 ratio in the range from 4 to 20.
- M w average molecular weight
- Molecular weights in the range from 10,000 to 200,000, in particular 20,000 to 40,000, and molecular weights in the range from 40,000 to 450,000 for use in the plasma expander are used.
- Molecular weight M w in the sense of this description is understood to mean the weight average of the molecular weight. This can be done in a manner known per se Different methods can be determined, for example by gel permeation chromatography (GPC) or high pressure liquid chromatography (HPLC) in connection with light scattering and Rl detection.
- GPC gel permeation chromatography
- HPLC high pressure liquid chromatography
- the preferred C 2 / C 6 ratio is in the range from 5 to 9.
- undesired by-products such as, for example, aldonic acids and formaldehyde, can be avoided by methods known to those skilled in the art for reducing or oxidizing the aldehyde groups at the reducing end.
- the high degree of branching of the starch products according to the invention increases their water solubility in such a way that a hydroxyethyl or hydroxypropyl substitution can be completely or largely dispensed with in order to keep the starch product in solution.
- a major advantage is that the average molecular weight can be raised appropriately above the permeability limit of the peritoneum.
- the GPC value of the so-called BF90% soil fraction (molecular weight at 90% of the peak area as a measure of the proportion of smaller molecular fractions) can also serve as a parameter. By increasing the molecular weight accordingly, a higher UF performance can be achieved with a drastically reduced absorption over the peritoneal membrane.
- a colloid-osmotic agent suitable for peritoneal dialysis can be produced with minimal effort by methods known per se in the prior art, which agent can also be readily mixed with various electrolytes, amino acids, lactate, acetate, bicarbonate and others in a known manner osmotically active agents, such as glucose, can be combined.
- osmotically active agents such as glucose
- a suitable choice of molecular weight can be used to obtain a product for use as a volume substitute, the volume effect of which is further favored by the spatial expansion of such a highly branched starch product.
- the residence time in the body can be adjusted by the choice of the molecular weight distribution.
- the products according to the invention are distinguished in that they have the advantages, known in the prior art, of hydroxyethyl starches used in volume therapy, but no longer have their typical disadvantages. This makes them particularly interesting for use in peritoneal dialysis. Their advantages are particularly advantageous in areas of application where volume substitutes in large quantities in a short time or, e.g. in the event of sudden hearing loss, must be administered intravenously over long periods. Because, when used in peritoneal dialysis, only fractions that can pass through the peritoneum or are absorbed by the lymphatic route can get into the blood, HES is given directly into the bloodstream in volume therapy. For example, while the upper limit for administration for an HES of specification 130 / 0.4 is currently 3 g per kg of body weight and day, larger amounts of the products according to the invention can be applied without problems.
- the products according to the invention are furthermore distinguished by the fact that they show the advantages of known colloid-osmotic agents for peritoneal dialysis, without having the disadvantages of the formation of harmful by-products or the tendency towards retrogradation.
- the products according to the invention can be used both in volume therapy and in peritoneal dialysis.
- the invention also relates to dialysis solutions containing water, the starch products according to the invention and other additives customary for dialysis solutions.
- the latter are, for example, electrolytes, amino acids, lactate, acetate or bicarbonate, as well as other osmotically active agents, such as e.g. Glucose.
- the starch product according to the invention is usually present in a concentration of 2 to 10, preferably 4 to 7.5% by weight, based on the dialysis solution.
- the invention further relates to volume substitutes (plasma expanders) containing water, the starch products according to the invention and other additives customary for plasma expanders.
- the latter is, for example, sodium chloride for producing a physiologically acceptable infusion solution.
- the starch product according to the invention is usually present in the plasma expanders according to the invention in a concentration of 2 to 12, preferably 4 to 10% by weight, based on the plasma expander.
- the invention further relates to the use of the starch products according to the invention in dialysis, preferably in peritoneal dialysis.
- the invention further relates to the use of the starch products according to the invention as a plasma expander.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Anesthesiology (AREA)
- Polymers & Plastics (AREA)
- Materials Engineering (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Vascular Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Medicinal Preparation (AREA)
- External Artificial Organs (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10237442 | 2002-08-16 | ||
DE10237442A DE10237442B4 (de) | 2002-08-16 | 2002-08-16 | Hochverzweigte, niedrig substituierte Stärkeprodukte |
PCT/EP2003/008411 WO2004022602A1 (de) | 2002-08-16 | 2003-07-30 | Hochverzweigte, nicht oder niedrig substituierte stärkeprodukte, dialyselösung und plasmaexpander enthaltend diese und deren verwendung |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1530593A1 true EP1530593A1 (de) | 2005-05-18 |
Family
ID=31501768
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP03793660A Withdrawn EP1530593A1 (de) | 2002-08-16 | 2003-07-30 | Hochverzweigte, nicht oder niedrig substituierte stärkeprodukte, dialyselösung und plasmaexpander enthaltend diese und deren verwendung |
Country Status (7)
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE540996T1 (de) | 2005-06-06 | 2012-01-15 | Univ British Columbia | Polymerbasierter serumalbumin-ersatzstoff |
EP1943908A1 (en) * | 2006-12-29 | 2008-07-16 | Nederlandse Organisatie voor toegepast-natuurwetenschappelijk Onderzoek TNO | Novel slowly digestible storage carbohydrate |
US7736328B2 (en) | 2007-07-05 | 2010-06-15 | Baxter International Inc. | Dialysis system having supply container autoconnection |
FR2955861B1 (fr) | 2010-02-02 | 2013-03-22 | Roquette Freres | Polymeres solubles de glucose branches pour la dialyse peritoneale |
CN102906157B (zh) | 2010-03-01 | 2016-08-24 | 不列颠哥伦比亚大学 | 衍生的超支化聚丙三醇 |
AR095937A1 (es) * | 2013-04-05 | 2015-11-25 | Acraf | Potenciador de la solubilidad en agua a base de glucógeno |
WO2014172786A1 (en) | 2013-04-26 | 2014-10-30 | Mirexus Biotechnologies Inc | Phytoglycogen nanoparticles and methods of manufacture thereof |
DE102015014699A1 (de) * | 2015-11-13 | 2017-05-18 | Fresenius Medical Care Deutschland Gmbh | Dialyselösung mit wenigstens einem Osmotikum |
JP6783875B2 (ja) | 2016-05-06 | 2020-11-11 | ガンブロ ルンディア アー・ベー | 貯水器および使い捨てセットを用いる使用場所での透析流体調製を有する腹膜透析のためのシステムおよび方法 |
FR3055898B1 (fr) * | 2016-09-15 | 2018-11-02 | Roquette Freres | Nouveaux polymeres de glucose pour dialyse peritoneale |
US10837142B2 (en) * | 2018-12-14 | 2020-11-17 | Sappi North America, Inc. | Paper coating composition with highly modified starches |
US20200190222A1 (en) * | 2018-12-14 | 2020-06-18 | Kansas State University Research Foundation | Degraded hydroxyalkylated starches and methods of preparation |
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CA1055932A (en) * | 1975-10-22 | 1979-06-05 | Hematech Inc. | Blood substitute based on hemoglobin |
US4454161A (en) | 1981-02-07 | 1984-06-12 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | Process for the production of branching enzyme, and a method for improving the qualities of food products therewith |
DE19975071I2 (de) * | 1989-06-16 | 2000-02-03 | Fresenius Ag | Hydroxyethylstaerke als Plasmaexpander Verfahren zu ihrer Herstellung und Verwendung als kolloidales Plasmaersatzmittel |
NL8902128A (nl) | 1989-08-23 | 1991-03-18 | Avebe Coop Verkoop Prod | Vertakkingsenzym en gebruik daarvan. |
DE4123001A1 (de) * | 1991-07-11 | 1993-01-14 | Laevosan Gmbh & Co Kg | Pharmazeutische zusammensetzung fuer die peritonealdialyse |
DE4242926C2 (de) | 1992-12-18 | 1994-12-15 | Fresenius Ag | Dialyselösung für die Peritonealdialyse |
FR2783838B1 (fr) | 1998-09-25 | 2000-12-01 | Roquette Freres | Procede de preparation d'un melange d'enzymes de branchement de l'amidon extraites d'algues |
GB2342656B (en) | 1998-10-10 | 2003-03-19 | Ml Lab Plc | Production of glucose polymer mixture by starch hydrolysis |
US6770148B1 (en) | 1998-12-04 | 2004-08-03 | Baxter International Inc. | Peritoneal dialysis solution containing modified icodextrins |
FR2792941B1 (fr) * | 1999-04-30 | 2001-07-27 | Roquette Freres | Polymeres solubles de glucose branches et leur procede d'obtention |
AT409928B (de) | 1999-08-10 | 2002-12-27 | Tulln Zuckerforschung Gmbh | Plasmaexpander, blutverdünnungsmittel und kryoprotektor, hergestellt unter verwendung von amylopektin-kartoffelstärke |
US20020065410A1 (en) * | 1999-12-02 | 2002-05-30 | Antrim Richard L. | Branched starches and branched starch hydrolyzates |
JP2001294601A (ja) | 2000-04-11 | 2001-10-23 | Akita Prefecture | 高度分岐澱粉と該高度分岐澱粉の製造方法 |
DE10140594A1 (de) * | 2001-08-18 | 2003-03-06 | Supramol Parenteral Colloids | Verfahren zur Herstellung von Polymeren mit hydrolytisch eingestelltem Molekulargewicht |
DE10235954A1 (de) * | 2001-08-22 | 2003-03-06 | Supramol Parenteral Colloids | Hyperverzweigtes Amylopektin zum Einsatz in Verfahren zur chirurgischen oder therapeutischen Behandlung von Säugern oder in Diagnostizierverfahren, insbesondere zur Verwendung als Plasmavolumenexpander |
FR2840612B1 (fr) * | 2002-06-06 | 2005-05-06 | Roquette Freres | Polymeres solubles de glucose hautement branches et leur procede d'obtention |
-
2002
- 2002-08-16 DE DE10237442A patent/DE10237442B4/de not_active Expired - Fee Related
-
2003
- 2003-07-30 CN CNB038193566A patent/CN100340578C/zh not_active Expired - Fee Related
- 2003-07-30 WO PCT/EP2003/008411 patent/WO2004022602A1/de active Application Filing
- 2003-07-30 EP EP03793660A patent/EP1530593A1/de not_active Withdrawn
- 2003-07-30 US US10/524,424 patent/US7550446B2/en not_active Expired - Fee Related
- 2003-07-30 AU AU2003251668A patent/AU2003251668A1/en not_active Abandoned
- 2003-07-30 JP JP2004533291A patent/JP4594729B2/ja not_active Expired - Fee Related
-
2010
- 2010-05-21 JP JP2010117591A patent/JP2010209349A/ja active Pending
Non-Patent Citations (1)
Title |
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See references of WO2004022602A1 * |
Also Published As
Publication number | Publication date |
---|---|
CN100340578C (zh) | 2007-10-03 |
JP2010209349A (ja) | 2010-09-24 |
JP4594729B2 (ja) | 2010-12-08 |
US7550446B2 (en) | 2009-06-23 |
DE10237442B4 (de) | 2004-08-19 |
CN1675248A (zh) | 2005-09-28 |
AU2003251668A1 (en) | 2004-03-29 |
JP2005539107A (ja) | 2005-12-22 |
WO2004022602A1 (de) | 2004-03-18 |
DE10237442A1 (de) | 2004-03-11 |
US20060032400A1 (en) | 2006-02-16 |
HK1080872A1 (zh) | 2006-05-04 |
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