Classifications

• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
  • C08B30/00—Preparation of starch, degraded or non-chemically modified starch, amylose, or amylopectin
  • C08B30/12—Degraded, destructured or non-chemically modified starch, e.g. mechanically, enzymatically or by irradiation; Bleaching of starch
  • C08B30/18—Dextrin, e.g. yellow canari, white dextrin, amylodextrin or maltodextrin; Methods of depolymerisation, e.g. by irradiation or mechanically
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P3/00—Drugs for disorders of the metabolism
• • 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
  • C08B30/00—Preparation of starch, degraded or non-chemically modified starch, amylose, or amylopectin
  • C08B30/12—Degraded, destructured or non-chemically modified starch, e.g. mechanically, enzymatically or by irradiation; Bleaching of starch

Definitions

• the invention relates to a process for the production of starch degradation products with a narrow molecular weight distribution.
• starch products are used today which are used to achieve certain technological or physiological properties, e.g. Solubility, viscosity behavior in solution, swelling and gelatinization behavior, digestibility, are made from native starches by partial degradation.
• the invention is therefore based on the object of providing a process for the production of starch degradation products with a narrow molecular weight distribution with which the disadvantages described above, in particular undesirable low molecular weight fractions, can be largely avoided and with which efficient degradation is achieved the desired products can be carried out in high yields.
• This object is achieved according to the invention by a process for the production of starch degradation products with a narrow molecular weight distribution, which is characterized in that a native starch, a starch derivative, a partially hydrolyzed starch or a partially hydrolyzed starch derivative in aqueous dispersion, suspension or solution subject to the action of ultrasound.
• a suspension is understood to be a dispersion of insoluble solid particles above colloidal dimensions and a solution is a molecularly disperse distribution of the starch starting products in water. Dispersion is also to be understood as a gel.
• the process according to the invention makes it possible to set the desired average molecular weight f ⁇ within wide limits with a very narrow molecular weight distribution by, depending on the other reaction conditions and in particular on the starting product, carrying out the ultrasound action until the desired molecular weight is achieved.
• a partially hydrolyzed starch or partially hydrolyzed starch derivative is preferably a partial hydrolyzate of starch or a starch derivative obtained by acid hydrolysis and / or enzyme hydrolysis, in particular with an average molecular weight W w of greater than 10 6 daltons, which is degraded to such an extent that a 10th up to 40% solution is well pumpable.
• a starch which mainly consists of amylopectin and in particular practically amylose-free amylopectin, which contains not more than 1% by weight of amylose, is preferably used as the native starch.
• Preferred examples of a starch used according to the invention is waxy maize, wax rice and / or wax care starch.
• a partially hydrolyzed starch or a partially hydrolyzed starch derivative can be produced in a manner known per se by means of acid hydrolysis or enzyme hydrolysis.
• Hydrochloric acid is preferably used for acid hydrolysis.
• ⁇ -Amylase is preferred as the enzyme for enzyme hydrolysis.
• Starch derivatives are e.g. Hydroxyalkyl starch or alkoxyalkyl starch and especially hydroxyethyl starch (HES).
• HES hydroxyethyl starch
• reaction mixture obtainable after the partial hydrolysis with acid or enzyme can also be used as the starting mixture, which reaction mixture can then be subjected to the ultrasound treatment without prior isolation of the hydrolyzate.
• the ultrasound treatment can be carried out in a manner known per se and using suitable, commercially available devices.
• the most suitable conditions depend in particular on the starch or starch derivative added as the starting product, the type of reaction mixture (dispersion, suspension or Solution) and the desired average molecular weight of the starch degradation product.
• the process is preferably carried out at room temperature or slightly elevated temperature and in particular in the temperature range from 20 ° C. to 80 ° C., the temperature also being able to be reduced as the degradation progresses.
• the ultrasound treatment can be carried out in batches or continuously. It is preferably carried out with a sound dose in the range from 1 to 20 kWh / 1, depending on the desired degree of degradation.
• the ultrasound treatment is expediently carried out while stirring the reaction mixture.
• the degree of degradation and thus the desired molecular weight of the starch degradation products can easily be checked by measuring the viscosity of a sample diluted with water, in order in this way to determine the desired degradation and the end of the reaction. This also applies to the determination of the degree of hydrolysis of the partial hydrolysates used as the starting product.
• the method according to the invention provides a method for producing starch degradation products with a narrow molecular weight distribution, the desired degree of degradation being able to be obtained by suitable choice and variation of the intensity and / or duration of the sonication.
• degradation products with a very narrow molecular weight distribution can be obtained which, in contrast to previously known degradation methods, contain only very small, undesirable, low molecular weight fractions.
• 1 to 3 show the integral and differential molecular weight distribution of starch breakdown products produced according to the invention (FIG. 1) and of starch breakdown products produced by acid hydrolysis (FIG. 2) and enzymatic hydrolysis (FIG. 3); this clearly shows the much narrower molecular weight distribution obtainable by the process according to the invention.
• the process according to the invention is therefore particularly suitable for the production of starting or end products of starch derivatives, such as e.g. High yield starch ethers (e.g. hydroxyethyl starch) or starch esters (e.g. acetyl starch) which are used medicinally e.g. for clinical, preferably parenteral applications.
• starch derivatives such as e.g. High yield starch ethers (e.g. hydroxyethyl starch) or starch esters (e.g. acetyl starch) which are used medicinally e.g. for clinical, preferably parenteral applications.
• starch degradation products obtainable according to the invention are particularly suitable as starting products for the production of pharmaceutical compositions for peritoneal dialysis, and for the production of blood plasma substitutes in the form of e.g. Starch ethers or starches.
• the invention therefore also relates to the use of starch degradation products obtained by the method according to the invention for pharmaceutical compositions for clinical, preferably parenteral, applications and in particular for the production of pharmaceutical compositions for peritoneal dialysis and for the production of blood plasma substitutes and 18th
• the starch degradation products may also be expedient to remove salts and other low-molecular constituents, such as, for example, still present low-molecular degradation products of the starting starch.
• This can be done, for example, by dialysis and in particular by ultrafiltration (diafiltration), with membranes having an appropriate appropriate exclusion limit can be selected. Expediently, the removal of low molecular weight components takes place together with the removal of salts.
• the products obtained after the treatment with ultrasound into a dried product. This is preferably done by gentle concentration of the solution in vacuo and subsequent drying in vacuo.
• ⁇ means weight average, and ⁇ M ⁇ number average. Temperature information relates to the Celsius scale.
• Example 1 5 g of waxy maize starch were suspended in 100 ml of 0.01 M hydrochloric acid, gelatinized by heating in a boiling water bath with stirring and kept at water bath temperature for a further 5 hours.
• the now thin solution was deacidified by filtration through a weakly basic anion exchanger in the OH "form (LEWATIT AP 49 from BAYER Leverkusen) and the molecular weight distribution was determined as in Example 1 (cf. FIG. 2).
• the proportion ⁇ 50,000 daltons was 51.5%.
• 35 g of waxy maize starch were dissolved in 100 ml of an aqueous solution containing 0.02 g of calcium chloride * 2H 2 0 and 0.02 ml of amylase (TERMAMYL from NOVO, Copenhagen) suspended and heated in a boiling water bath with vigorous stirring. At about 65 ° C solution appeared without the formation of a highly viscous phase. The mixture was kept at water bath temperature for 1 hour, adjusted to pH 3.0 with hydrochloric acid to inactivate the enzyme and cooled. The molecular weight distribution was determined as indicated in Example 1 (see FIG. 3).
• the progress of the degradation was monitored by measuring the relative viscosity n rel of a 20% solution. After the entire sonication time, the molecular weight distribution was determined by gel chromatography (FIG. 6).
• the progress of the degradation over time was monitored by measuring the relative viscosity n ret of a 20% solution. After the entire sonication time, the molecular weight distribution was determined by gel chromatography.
• the share ⁇ 50,000 Daltons was 4.08% b) 150 W.
• 35 g of waxy maize starch were suspended in 100 ml of water in a beaker, 20 ⁇ l -amylase Termamyl (from NOVO, Copenhagen) were added and the mixture was heated in a water bath with stirring until the starch granules had completely dissolved and a viscous solution had formed.
• the enzyme was acidified with about 50 ⁇ l conc. Hydrochloric acid stopped at pH 2.80.
• the partial starch hydrolyzate obtained was sonicated in a 100 ml wide-mouth infusion bottle while cooling with ice water with a switching power of 250 W and the progress of the degradation over time was measured by measuring the relative viscosity n re L of a 20% solution of the molecular weight distribution.

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• Chemical & Material Sciences (AREA)
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• Life Sciences & Earth Sciences (AREA)
• Medicinal Chemistry (AREA)
• Engineering & Computer Science (AREA)
• Organic Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Crystallography & Structural Chemistry (AREA)
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• Polymers & Plastics (AREA)
• Materials Engineering (AREA)
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• General Health & Medical Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Animal Behavior & Ethology (AREA)
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• Polysaccharides And Polysaccharide Derivatives (AREA)
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• 1991
  • 1991-10-01 DE DE4132701A patent/DE4132701A1/de not_active Withdrawn
• 1992
  • 1992-09-28 HU HU9400944A patent/HUT66891A/hu unknown
  • 1992-09-28 AU AU26491/92A patent/AU2649192A/en not_active Abandoned
  • 1992-09-28 JP JP5506588A patent/JPH06511273A/ja active Pending
  • 1992-09-28 EP EP92920694A patent/EP0606332A1/de not_active Withdrawn
  • 1992-09-28 SK SK369-94A patent/SK36994A3/sk unknown
  • 1992-09-28 CA CA002119656A patent/CA2119656A1/en not_active Abandoned
  • 1992-09-28 CZ CS94760A patent/CZ76094A3/cs unknown
  • 1992-09-28 WO PCT/EP1992/002229 patent/WO1993007177A1/de not_active Application Discontinuation
  • 1992-10-01 PT PT100918A patent/PT100918A/pt not_active Application Discontinuation
• 1994
  • 1994-03-21 NO NO941012A patent/NO941012L/no unknown
  • 1994-03-31 FI FI941532A patent/FI941532A/fi not_active Application Discontinuation
  • 1994-03-31 US US08/220,499 patent/US5424302A/en not_active Expired - Fee Related

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