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WO1991018610A1 - Nouvelle utilisation du glucose et nouvelle solution de glucose - Google Patents

Nouvelle utilisation du glucose et nouvelle solution de glucose Download PDF

Info

Publication number
WO1991018610A1
WO1991018610A1 PCT/SE1991/000376 SE9100376W WO9118610A1 WO 1991018610 A1 WO1991018610 A1 WO 1991018610A1 SE 9100376 W SE9100376 W SE 9100376W WO 9118610 A1 WO9118610 A1 WO 9118610A1
Authority
WO
WIPO (PCT)
Prior art keywords
glucose
glutamine
infusion solution
patient
fructose
Prior art date
Application number
PCT/SE1991/000376
Other languages
English (en)
Inventor
Olle Ljungqvist
Original Assignee
Olle Ljungqvist Medical Ab
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Olle Ljungqvist Medical Ab filed Critical Olle Ljungqvist Medical Ab
Publication of WO1991018610A1 publication Critical patent/WO1991018610A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0029—Parenteral nutrition; Parenteral nutrition compositions as drug carriers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/28—Insulins

Definitions

  • the present invention relates to a new use of glucose, fruc ⁇ tose and/or xylose and an infusion solution intended for preoperative administration.
  • the invention also relates to a method of suppressing the negative influence on the metabolism of carbohydrates caused by surgery and improv ⁇ ing the defence capacity of the patient upon bleeding during or after the operation.
  • Elective surgical (i.e. not acute) operations are yearly carried out at a number of approximately 2-300000 in Sweden alone.
  • a routine operation always brings about a relative ⁇ ly long period (weeks) of convalescence for physical re- covery.
  • Routinely all patients planned for surgery undergo a period of fasting before the operation, usually from mid ⁇ night to the day of surgery.
  • the effective period of fast ⁇ ing becomes at least 16-20 h because the last meal of food generally is served around 16.00 h.
  • the obli- gatory fast before surgery has been introduced for reasons of safety related to anaesthesia and has not been consider ⁇ ed to bring about negative effects for the patient.
  • glutamine is supplied by means of the food intake, but during fasting (and to a greater extent after trauma) the glutamine requirements of the bowel is supplied via degradation of glutamine stored in the pro ⁇ teins &£ the muscles.
  • the release of hormones in the body must change. By changes in hormone release, the body thus changes from storage of nutrients (anabolism) to degradation of nutrients (catabolism) . This shift in body metabolism forms a normal part of metabolism and occurs already during normal overnight sleep.
  • specific hormones primarily insulin
  • the present invention is based on the finding that it was possible by preoperative administration of a solution con ⁇ taining glucose not only to improve the body's capacity of the patient to withstand blood loss during or after surgery but also to improve postoperative carbohydrate metabolism by reducing the degree of insulin resistance after the operation.
  • Glucose treated rats had 578 ⁇ dry liver weight (mean ⁇ SE) of glycogen compared to 104 ⁇ 32A/ mol/g, significance p ⁇ 0.01 (Mann Whitney U-test) .
  • G had blood glucose levels of 16.1 ⁇ 0.9 mmol/1 compared to S 5.2 ⁇ 0.1, p ⁇ 0.01.
  • This increase in blood glucose in group G resulted in improved fluid mobilization to the circula ⁇ tion, as indicated by a lower haematocrit in group G (35 ⁇ 1 %) versus group S (40 ⁇ 1 %) , p ⁇ 0.01.
  • Rats pretreated with glucose showed a hor ⁇ mone response with increased insulin levels in the blood in a way which previously has been observed only in not fasted animals and subjected to haemorrhage. This insulin release is not found in 24 h fasted (and untreated) rats, nor could it be reproduced by treatment initiated once the bleeding had been started. 2. Clinical experiments.
  • the present invention relates to the use of at least one carbohydrate selected from •the-group consisting of glucose, fructose and zylose, preferably glucose, for the preparation of an infusion solution intended for preoperative administration in or- - der to suppress the negative influence of the operation -upon postoperative carbohydrate metabolism and to improve the defence capacity of the patient in case of bleeding in connection with or after the operation without anaeste- siological safety being jeopardized.
  • carbohydrate selected from •the-group consisting of glucose, fructose and zylose, preferably glucose
  • the content of qlucose etc. in the infusion solution is suit ⁇ ably within the range which usually is used in nutrient solutions for intravenous supply of nutrients to patients which can not support themselves after surgery, for in ⁇ stance within the range from 50 g/1 to 500 g/1, prefer ⁇ ably 100 g/1 to 200 g/1.
  • the infusion solution in addition to the glucose also contains potassium chloride.
  • the content is also in this case suit ⁇ ably within the range which is usually occurring in solutions for nutrient supply after surgery.
  • the content of potasium chloride may be in the rang from 20 mmol/1 to 100 mmol/1, preferably about 40 rnmol/1.
  • the in ⁇ fusion solution may in addition ' to glucose and possibly potassium chloride also contain at least one of the sub ⁇ stances fructose and xylose.
  • the content of fructose or xylose or mixture thereof is suitably within the range from 50 g/1 to 200 g/1, preferably 50 g/1 to 100 g/1.
  • the in ⁇ fusion solution may in addition to glucose and possibly potassium chloride and/or fructose and/or xylose also contain glutamine and/or ornii ⁇ ine-alfa-ketoglutarate or corresponding glur tamine analogues which in the body are converted to glutamine.
  • the body reserves of glutamine in the body are increased instead of decreased during the period of preoperative fasting.
  • This improvement of availability of body gluta ⁇ mine will reduce the need for muscle protein breakdown for the release of glutamine, which is otherwise en ⁇ countered after surgery. This, in turn, can improve post ⁇ operative muscle function.
  • the content of glutamine etc. is suitably within the range 5 g/1 to 30 g/1, preferably 10 g/1 to 20 g/1.
  • the infusion solution may in addition to glucose and possibly potassium chloride and possibly one or more of the pre ⁇ viously mentioned additional substances also contain.c ⁇ ie or more hormones such as an insulin or insulin derivative which is suitable for administration to man.
  • the content is adjusted so that a suitable dose of insulin is given with the infused amount of solution.
  • suitable insulins and insulin derivatives in this connection is human insulin such as Humilin NPH (Lilly) or A ⁇ trapid ⁇ Human (Novo) .
  • insulin is the most important hormone for the normal storage off nutrients, other hormones and peptides also have anabolic effects on body metabolism.
  • growth hormone, insulin growth factor as well as GLIP have been suggested to have insulin like effects.
  • the infusion solu ⁇ tion may also contain other substances which are occurring in nutrient solutions for intravenous administration, if desired.
  • the infusion solution is drawn into glass bottles or plas ⁇ tics bags of 500 ml - 2000 ml.
  • the patient is given glucose 3-5 mg/kg/min intravenously (corresponding to about 60-100 ml/h 20 mg/ml glucose solution to a pa ⁇ tient weighing 70 kg) .
  • the solutions can be packed up in different sizes in order to correspond to the need of pa ⁇ tients of different weights.
  • this is rela ⁇ ted to an infusion solution, which is characterized in that it in addition to at least one carbohydrate select ⁇ ed from the group consisting of glucose, fructose and xylose, preferably glucose, and potassium chloride also contains ornitnine-alfa-ketoglutarate and/or glutamine and possibly one or more hormones.
  • carbohydrate select ⁇ ed from the group consisting of glucose, fructose and xylose, preferably glucose, and potassium chloride also contains ornitnine-alfa-ketoglutarate and/or glutamine and possibly one or more hormones.
  • this is related to a method f ⁇ tTsuppressing the negative influ ⁇ ence upon the metabolism of carbohydrates caused by an operation of a patient and improving the defence capacity of the patient on bleeding in connection with or after the operation which method comprises preoperative intra ⁇ venous administration of the patient of an infusion solu ⁇ tion containing at least one carbohydrate selected from the group consisting of glucose, fructose and xylose, preferably glucose.
  • infusion solution is prepared in a conventional way for the preparation of infusion solutions, which infusion solution contains glucose (200 mg/ml) and potassium chloride (40 mmol/1) and the solution is d__awn-.iit.tovolumes of 1500 ml.
  • An infusion solution is prepared in a way conventional to the preparation of infusion solutions, which solution con ⁇ tains glucose (200 mg/ml) , potassium chloride (40 mmol/1) and human insulin (Actrapicr ⁇ Human, Novo, Denmark, 20 IE/1) and the solution is drawn into volumes of 1300 ml.
  • An infusion solution is prepared in a way conventional to the preparation of infusion solutions, which solution con- tains glucose (150 mg/ml) , fructose (50 mg/ml) and potas ⁇ sium chloride (40 mmol/1) , and the solution is drawn into volumes of 1200 ml.
  • An infusion solution is prepared in a way conventional to the preparation of infusion solutions, which solution con ⁇ tains glucose (200 mg/ml) , orn__thine- : a-_fa-ketoglutarate (10 mg/ml) and potassium chloride (40 mmol/1) , and the solu- tion is drawn into volumes of 1500 ml.
  • the best mode for carrying out the invention at present comprises the preoperative administration of an infusion solution comprising glucose and potassium chloride dissolv ⁇ ing water.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Endocrinology (AREA)
  • Molecular Biology (AREA)
  • Nutrition Science (AREA)
  • Dermatology (AREA)
  • Diabetes (AREA)
  • Inorganic Chemistry (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention propose d'utiliser du glucose, du fructose et/ou du xylose pour la préparation d'une solution de perfusion destinée à être administrée préalablement à une opération chirurgicale. L'invention décrit une solution de perfusion, qui, à part du glucose, du fructose et/ou du xylose et du chlorure de potassium, contient également de la glutamine et/ou de l'ornithine-alpha-cétoglutarate ou les analogues de glutamine correspondants, qui sont sont transformés en glutamine dans le corps, ainsi qu'éventuellement une ou plusieurs hormones. L'invention décrit en outre un procédé servant à supprimer les effets négatifs d'un acte opératoire sur le métabolisme des hydrates de carbone d'un patient après l'acte chirurgical, et à améliorer la capacité de défense du patient contre le saignement avant ou après l'opération. Ce procédé consiste à administrer au patient par voie intraveineuse préalablement à l'opération une solution de perfusion contenant au moins un hydrate de carbone choisi dans le groupe composé de glucose, de fructose et de xylose.
PCT/SE1991/000376 1990-05-28 1991-05-28 Nouvelle utilisation du glucose et nouvelle solution de glucose WO1991018610A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE9001906-8 1990-05-28
SE9001906A SE502414C2 (sv) 1990-05-28 1990-05-28 Användning av glukos för framställning av lösning för preoperativ administrering samt infusionslösning därför

Publications (1)

Publication Number Publication Date
WO1991018610A1 true WO1991018610A1 (fr) 1991-12-12

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AU (1) AU7957991A (fr)
SE (1) SE502414C2 (fr)
WO (1) WO1991018610A1 (fr)

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992010947A1 (fr) * 1990-12-21 1992-07-09 Olle Ljungqvist Medical Aktiebolag Boisson destinee a un usage preoperatoire
EP0875155A1 (fr) * 1997-05-01 1998-11-04 N.V. Nutricia Boisson périoperatif
US5968896A (en) * 1998-01-16 1999-10-19 Beth Israel Deaconess Medical Center Nutritional supplement for preoperative feeding
WO2001035943A3 (fr) * 1999-11-15 2002-03-21 Hanamaraddi T Gangal Preparation de fluides a base de dextrose et d'insuline destinee a une infusion intraveineuse
US6475529B2 (en) 1999-09-10 2002-11-05 Baxter International Inc. Bicarbonate-based solution in two parts for peritoneal dialysis or substitution in continuous renal replacement therapy
EP1380290A1 (fr) * 2002-07-09 2004-01-14 Universitair Medisch Centrum Utrecht La voie de la structure cross-béta et sa pertinence thérapeutique
WO2004052352A1 (fr) * 2002-12-09 2004-06-24 Fresenius Kabi Deutschland Gmbh Formulation administrable par voie gastro-intestinale, contenant un extrait de the vert et un donneur d'oxyde nitrique (no)
EP1591116A1 (fr) * 2003-02-06 2005-11-02 Otsuka Pharmaceutical Factory, Inc. Inhibiteur de l'augmentation du taux de glycemie peri-operatoire
US7011855B2 (en) 1994-07-01 2006-03-14 Baxter International Inc. Biochemically balanced peritoneal dialysis solutions
US7122210B2 (en) 2002-01-11 2006-10-17 Baxter International Inc. Bicarbonate-based solutions for dialysis therapies
US7445801B2 (en) 2002-06-07 2008-11-04 Baxter International Inc. Stable bicarbonate-based solution in a single container
EP2033623A1 (fr) * 2007-09-07 2009-03-11 Cutech S.R.L. Compositions comportant du cétoglutarate ornithine (OKG)
WO2011069932A1 (fr) * 2009-12-10 2011-06-16 Chiesi Farmaceutici S.P.A. Nouvelles applications therapeutiques d'un complexe d'alpha-cetoglutarate et d'ornithine
US9180069B2 (en) 2005-01-28 2015-11-10 Fresenius Medical Care Holdings, Inc. Systems and methods for delivery of peritoneal dialysis (PD) solutions
US9585810B2 (en) 2010-10-14 2017-03-07 Fresenius Medical Care Holdings, Inc. Systems and methods for delivery of peritoneal dialysis (PD) solutions with integrated inter-chamber diffuser

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
PATENT ABSTRACTS OF JAPAN, Vol. 10, No. 182, C356; & JP,A,61 030 523, 12-02-1986, TERUMO CORP. *
PATENT ABSTRACTS OF JAPAN, Vol. 10, No. 252, C369; & JP,A,61 078 719, 22-04-1986, TANABE SEIYAKU CO LTD. *

Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5438043A (en) * 1990-12-21 1995-08-01 Olle Ljungqvist Medical Ab Beverage for preoperative intake
US5624907A (en) * 1990-12-21 1997-04-29 Olle Ljungqvist Medical Ab Beverage for preoperative intake
WO1992010947A1 (fr) * 1990-12-21 1992-07-09 Olle Ljungqvist Medical Aktiebolag Boisson destinee a un usage preoperatoire
US7011855B2 (en) 1994-07-01 2006-03-14 Baxter International Inc. Biochemically balanced peritoneal dialysis solutions
EP0875155A1 (fr) * 1997-05-01 1998-11-04 N.V. Nutricia Boisson périoperatif
WO1998049906A1 (fr) * 1997-05-01 1998-11-12 N.V. Nutricia Boisson peri-operatoire
US5968896A (en) * 1998-01-16 1999-10-19 Beth Israel Deaconess Medical Center Nutritional supplement for preoperative feeding
US6475529B2 (en) 1999-09-10 2002-11-05 Baxter International Inc. Bicarbonate-based solution in two parts for peritoneal dialysis or substitution in continuous renal replacement therapy
RU2300367C2 (ru) * 1999-11-15 2007-06-10 Ханамарадди Т. ГАНГАЛ Жидкий лечебный состав для внутривенного введения, содержащий декстрозу и инсулин
WO2001035943A3 (fr) * 1999-11-15 2002-03-21 Hanamaraddi T Gangal Preparation de fluides a base de dextrose et d'insuline destinee a une infusion intraveineuse
US7122210B2 (en) 2002-01-11 2006-10-17 Baxter International Inc. Bicarbonate-based solutions for dialysis therapies
US7445801B2 (en) 2002-06-07 2008-11-04 Baxter International Inc. Stable bicarbonate-based solution in a single container
AU2003251233B2 (en) * 2002-07-09 2009-10-29 Crossbeta Biosciences B.V. Proteins binding to cross-beta structure comprising amyloid and methods for detection and modulation of the cross-beta structure, its formation and its associated toxicity
WO2004004698A3 (fr) * 2002-07-09 2004-06-10 Univ Medisch Centrum Utrecht Structure beta-croisee contenant des proteines de liaison amyloide et procedes de detection de la structure beta-croisee en vue de moduler la formation de fibrille dans les structures beta-croisee ainsi que la toxicite induite par la structure beta-croisee
EP1380290A1 (fr) * 2002-07-09 2004-01-14 Universitair Medisch Centrum Utrecht La voie de la structure cross-béta et sa pertinence thérapeutique
HRP20050511B1 (en) * 2002-12-09 2008-01-31 Fresenius Kabi Deutschland Gmbh Formulation, which can be administered gastrointestinally, containing green tea extract and an no donor
WO2004052352A1 (fr) * 2002-12-09 2004-06-24 Fresenius Kabi Deutschland Gmbh Formulation administrable par voie gastro-intestinale, contenant un extrait de the vert et un donneur d'oxyde nitrique (no)
KR101031989B1 (ko) * 2002-12-09 2011-05-02 프레제니우스 카비 도이치란트 게엠베하 녹차 추출물 및 ｎｏ 공여체를 함유하는, 위장관으로투여가능한 제형
EP1591116A4 (fr) * 2003-02-06 2008-05-28 Otsuka Pharma Co Ltd Inhibiteur de l'augmentation du taux de glycemie peri-operatoire
US8273717B2 (en) 2003-02-06 2012-09-25 Otsuka Pharmaceutical Factory, Inc. Inhibitor for perioperative blood sugar elevation
EP1591116A1 (fr) * 2003-02-06 2005-11-02 Otsuka Pharmaceutical Factory, Inc. Inhibiteur de l'augmentation du taux de glycemie peri-operatoire
US9180069B2 (en) 2005-01-28 2015-11-10 Fresenius Medical Care Holdings, Inc. Systems and methods for delivery of peritoneal dialysis (PD) solutions
WO2009030453A1 (fr) * 2007-09-07 2009-03-12 Cutech Srl. Compositions contenant de l'ornithine cétoglutarate (okg)
JP2011514878A (ja) * 2007-09-07 2011-05-12 キューテック・ソシエタ・ア・レスポンサビリタ・リミタータ オルニチンケトグルタレート（ｏｋｇ）含有組成物
US8466112B2 (en) 2007-09-07 2013-06-18 Cutech S.R.L. Compositions comprising Ornithine Ketoglutarate (OKG)
EP2033623A1 (fr) * 2007-09-07 2009-03-11 Cutech S.R.L. Compositions comportant du cétoglutarate ornithine (OKG)
WO2011069932A1 (fr) * 2009-12-10 2011-06-16 Chiesi Farmaceutici S.P.A. Nouvelles applications therapeutiques d'un complexe d'alpha-cetoglutarate et d'ornithine
FR2953719A1 (fr) * 2009-12-10 2011-06-17 Luc Cynober Nouvelles applications therapeutiques d'un complexe d'alpha-cetoglutarate et d'ornithine
US9585810B2 (en) 2010-10-14 2017-03-07 Fresenius Medical Care Holdings, Inc. Systems and methods for delivery of peritoneal dialysis (PD) solutions with integrated inter-chamber diffuser
US10842714B2 (en) 2010-10-14 2020-11-24 Fresenius Medical Care Holdings, Inc. Systems and methods for delivery of peritoneal dialysis (PD) solutions with integrated inter chamber diffuser
US11779519B2 (en) 2010-10-14 2023-10-10 Fresenius Medical Care Holdings, Inc. Systems and methods for delivery of peritoneal dialysis (PD) solutions with integrated inter-chamber diffuser

Also Published As

Publication number Publication date
SE502414C2 (sv) 1995-10-16
SE9001906D0 (sv) 1990-05-28
SE9001906L (sv) 1991-11-29
AU7957991A (en) 1991-12-31

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