DD293488A5 - PROCESS FOR PREPARING MEDICAMENT FOR RECTAL APPLICATION - Google Patents

PROCESS FOR PREPARING MEDICAMENT FOR RECTAL APPLICATION Download PDF

Info

Publication number
DD293488A5
DD293488A5 DD89325946A DD32594689A DD293488A5 DD 293488 A5 DD293488 A5 DD 293488A5 DD 89325946 A DD89325946 A DD 89325946A DD 32594689 A DD32594689 A DD 32594689A DD 293488 A5 DD293488 A5 DD 293488A5
Authority
DD
German Democratic Republic
Prior art keywords
amino acid
biologically active
condensation product
chloramphenicol
fatty acid
Prior art date
Application number
DD89325946A
Other languages
German (de)
Inventor
Joachim Kossowicz
Karl Milde
Elke Hacker
Vera Gabel-Thaelmann
Diana Krause
Ernst-Josef Straetling
Lothar Till
Original Assignee
Berlin-Chemie Ag,
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 Berlin-Chemie Ag, filed Critical Berlin-Chemie Ag,
Priority to DD89325946A priority Critical patent/DD293488A5/en
Priority to EP19900102872 priority patent/EP0384283A3/en
Priority to JP2038554A priority patent/JPH02264713A/en
Publication of DD293488A5 publication Critical patent/DD293488A5/en

Links

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
    • A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Die Erfindung betrifft ein Verfahren zur Herstellung wirkungsgesteigerter Arzneimittel zur rektalen Applikation, das dadurch gekennzeichnet ist, dasz als resorptionssteigernde Komponente ein Aminosaeure-Fettsaeure-Kondensationsprodukt Verwendung findet. Es findet besonders Anwendung fuer den Wirkstoff Chloramphenicol. Fig. 1 und 2{biologisch aktive Substanzen; Resorption; Aminosaeure-Fettsaeure-Kondensationsprodukt; Suppositorien; Verfahren; Wirkungssteigerung; Arzneimittel, nativ, synthetisch; Hydrolyse; Chloramphenicol}The invention relates to a method for producing Wirkgesteigerter drugs for rectal administration, which is characterized in that as resorption-enhancing component, an amino acid fatty acid condensation product is used. It finds particular application for the active ingredient chloramphenicol. Fig. 1 and 2 {biologically active substances; absorption; An amino acid, fatty acid condensation product; suppositories; Method; Increase in activity; Medicinal, native, synthetic; Hydrolysis; chloramphenicol}

Description

Anwendungsgebiet der ErfindungField of application of the invention

Die Erfindung betrifft die Wirkungssteigerung biologisch aktiver Substanzen, die sich durch schlechte oder langsame Resorption bei rektaler Applikation darstellen und keine Peptidstruktur aufweisen.The invention relates to the increase in activity of biologically active substances, which are represented by poor or slow absorption in rectal administration and have no peptide structure.

Charakteristik des bekannten Standes der TechnikCharacteristic of the known state of the art

Es ist bekannt, daß pharmazeutische Wirkstoffe, insbesondere Analgetika, Antiphlogistika, Antirheumatika wie Propiophenazon, Indomethazin, aber auch Chemotherapeutika in Form von Suppositorien zur Anwendung gelangen, weil die orale Applikation zu nachteiligen Nebenwirkungen für den Patienten führt. Nachteil dieser Verfahrensweise für einige der Substanzen ist jedoch ihre unzureichende bzw. verzögerte Resorbierbarkeit aus dem Rektum. Dem wird dadurch begegnet, daß der Wirkstoff im Suppositorium erheblich höher dosiert wird, um im Vergleich zur per-os-Applikation zu annähernd analogen Ergebnissen zu gelangen. Der Einsatz von resorptionsfördernden Stoffen ist bisher bei der rektalen Anwendung von Peptid-Wirkstoffen beschrieben worden, da diese Wirkstoffe meistens im Darm nicht beständig sind und daher sehr schnell in den Blutkreislauf gelangen müssen.It is known that pharmaceutical active substances, in particular analgesics, anti-inflammatory drugs, anti-inflammatory drugs such as propiophenazone, indomethacin, but also chemotherapeutic agents in the form of suppositories are used because the oral administration leads to adverse side effects for the patient. Disadvantage of this procedure for some of the substances, however, is their insufficient or delayed resorbability from the rectum. This is countered by the fact that the active ingredient in the suppository is dosed considerably higher, in comparison to the per-os application to achieve approximately analogous results. The use of resorption-promoting substances has hitherto been described in the rectal use of peptide active ingredients, since these active ingredients are mostly unstable in the intestine and therefore must reach the bloodstream very quickly.

Z'el der ErfindungZ'el of the invention

Ziel der Erfindung ist es, durch eine Verbesserung der Resorption biologisch aktiver Substanzen aus dem Rektum den Wirkstoffeinsatz zu senken, die rektale Resorption überhaupt zu ermöglichen bzw. die Resorption mit dem Ziel des schnelleren Wirkungseintritts zu beschleunigen.The aim of the invention is to reduce the use of active ingredient by improving the absorption of biologically active substances from the rectum, to allow the rectal absorption at all or to accelerate the absorption with the aim of faster onset of action.

Darlegung des Wesens dor ErfindungExplanation of the nature of the invention

Aufgabe der Erfindung ist das Finden eines Weges, diese Überdosierung des Wirkstoffes herabzusetzen. Als Wirkstoffe werden hier vorzugsweise Chloramphenicol und Propyphena/in genannt. Die Resorptionsverbesserung wird dadurch erzielt, daß als resorptionssteigernde Komponente ein Aminosäure-Fettsäure-Kondensationsprodukt, wobei die Aminosäure auch ein niedermolekulares natives hydrolytisch oder synthetisch gewonnenes Polypeptid sein kann, eingesetzt wird. Die Fettsäurekomponente weist zumeist eine Kettenlänge von Ci0 bis Cw auf, wobei dem Bereich C)2 bis C18 der Vorzug gegeben wird, Die resorptionssteigernde Komponente wird in Konzentrationen von 0,1 bis 20%, auf die Gesamtmasse bezogen, eingesetzt. Als biologisch aktive Substanzen können z.B. Chloramphenicol oder Propyphenazin eingesetzt werden.The object of the invention is to find a way to reduce this overdose of the active ingredient. As active ingredients, chloramphenicol and propyphena / in are preferably mentioned here. The absorption improvement is achieved in that the absorption-enhancing component is an amino acid-fatty acid condensation product, wherein the amino acid may also be a low molecular weight native hydrolytically or synthetically derived polypeptide. The fatty acid component usually has a chain length of Ci 0 to C w , wherein the range C ) 2 to C 18 is preferred, the resorption-increasing component is used in concentrations of 0.1 to 20%, based on the total mass. As biologically active substances, for example chloramphenicol or propyphenazine can be used.

Es war überraschend, daß außer einer positiven Beeinflussung der resorbierbaren Menge der aktiven biologischen Substanz auch in Abhängigkeit von der Konzentration der resorptionssteigernden Komponente die Resorptionsgeschwindigkeit beeinflußt werden konnte.It was surprising that, apart from a positive influence on the absorbable amount of the active biological substance, the absorption rate could also be influenced as a function of the concentration of the absorption-enhancing component.

Ausführungsbeispieleembodiments Beispiel 1example 1 Männlichen Kaninchen {Widderbastarde) mit einem durchschnittlichen Gewicht von 3,8kg, gehalten unter standardisierten,Male rabbits with a weight of 3,8kg, kept under standardized,

konventionellen Umweltbedingungen, wurde 16 Stunden nach Futterentzug ein Chloramphenicol-Zäpfchen eingeführt und der After für 90 Minuten mit einem Gummiband verschlossen.conventional environmental conditions, a Chloramphenicol suppository was introduced 16 hours after food withdrawal and the anus was closed with a rubber band for 90 minutes.

Das Chloramphenicol wurde quantitativ im Blutserum nach der Methode von BESSMANN und STEPHENS (1950) bestimmt. (Lit.:The chloramphenicol was determined quantitatively in the blood serum according to the method of BESSMANN and STEPHENS (1950). (Lit .: BESSMANN und STEPHENS, S., A colorimetric Method for the Determination of chloromycetin in Serum or Plasma, J. Lab. elin. Med.BESSMANN and STEPHENS, S., A Colorimetric Method for the Determination of Chloromycetin in Serum or Plasma, J. Lab. elin. Med.

35,S.129,1950)(Fig.2).35, S.129,1950) (Fig.2).

Beispiel 2Example 2

Klinisch gesunden Kaninchen im Gewicht von 2,5 bis 3,5kg, gehalten unter standardisierten Umweltbedingungen, wurde Pyrecol (gereinigtes Lipopolysaccharid) i.v. injiziert, was zu Fieber führte. Die Temperatursenkung durch Propyphenazinzäpfchen (150mg) mit und ohne Resorptionsbeeinflussung wurde verglichen (Fig. 1).Clinically healthy rabbits weighing 2.5 to 3.5 kg, maintained under standardized environmental conditions, were given Pyrecol (purified lipopolysaccharide) i.v. injected, which led to fever. The decrease in temperature by propyphenazine doses (150 mg) with and without absorption influence was compared (FIG. 1).

Claims (4)

Patentansprüche:claims: 1. Verfahren zur Herstellung von Arzneimitteln zur rektalen Applikation mit gesteigerter Wirkung von biologisch aktiven Substanzen, die keine Peptide darstellen, dadurch gekennzeichnet, daß die biologisch aktive Substanz mit einer resorptionssteigernden Komponente von 0,1 bis 20% aus einem Aminosäure-Fettsäure-Kondensationsprodukt, das aus einfachen oder peptidisch kondensierten Aminosäuren und Fettsäuren der Kettenlänge C10 bis C20 besteht, eingesetzt wird.1. A process for the preparation of medicaments for rectal administration with increased activity of biologically active substances which are not peptides, characterized in that the biologically active substance having a resorption-enhancing component of 0.1 to 20% of an amino acid-fatty acid condensation product, which is composed of simple or peptidically condensed amino acids and fatty acids of chain length C 10 to C 20 is used. 2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß das Aminosäure-Fettsäure-Kondensationsprodukt aus einfachen oder peptidisch kondensierten Aminosäuren und Fettsäuren der Kettenlänge C12 bis C1B besteht.2. The method according to claim 1, characterized in that the amino acid-fatty acid condensation product consists of simple or peptide-fused amino acids and fatty acids of chain length C 12 to C 1 B. 3. Verfahren nach Ansprüchen 1 und 2, dadurch gekennzeichnet, daß die peptidisch kondensierten Aminosäure-Ausgangsprodukte sowohl nativen als auch synthetischen Ursprungs sind bzw. durch Hydrolyse aus nativem Material gewonnen werden.3. Process according to Claims 1 and 2, characterized in that the peptidically condensed starting amino acid products are both native and of synthetic origin or are obtained by hydrolysis from native material. 4. Verfahren nach Ansprüchen 1 bis 3, dadurch gekennzeichnet, daß als biologisch aktive Substanz Chloramphenicol eingesetzt wird.4. Process according to Claims 1 to 3, characterized in that chloramphenicol is used as the biologically active substance.
DD89325946A 1989-02-22 1989-02-22 PROCESS FOR PREPARING MEDICAMENT FOR RECTAL APPLICATION DD293488A5 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
DD89325946A DD293488A5 (en) 1989-02-22 1989-02-22 PROCESS FOR PREPARING MEDICAMENT FOR RECTAL APPLICATION
EP19900102872 EP0384283A3 (en) 1989-02-22 1990-02-14 Pharmaceutical for rectal application and process for its preparation
JP2038554A JPH02264713A (en) 1989-02-22 1990-02-21 Medicine for rectum administration and manufacture thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DD89325946A DD293488A5 (en) 1989-02-22 1989-02-22 PROCESS FOR PREPARING MEDICAMENT FOR RECTAL APPLICATION

Publications (1)

Publication Number Publication Date
DD293488A5 true DD293488A5 (en) 1991-09-05

Family

ID=5607264

Family Applications (1)

Application Number Title Priority Date Filing Date
DD89325946A DD293488A5 (en) 1989-02-22 1989-02-22 PROCESS FOR PREPARING MEDICAMENT FOR RECTAL APPLICATION

Country Status (3)

Country Link
EP (1) EP0384283A3 (en)
JP (1) JPH02264713A (en)
DD (1) DD293488A5 (en)

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1915191A1 (en) * 1968-03-28 1969-10-23 Kyowa Hakko Kogyo Kk Suppositories
GB2051574B (en) * 1979-05-10 1984-01-18 Kyoto Pharma Ind Adjuvant for promoting absorption of pharmacologically active substances through the rectum
US4442090A (en) * 1980-11-09 1984-04-10 Kyoto Yakuhin Kogyo Kabushiki Kaisha Absorption-promoting compounds, compositions thereof with pharmaceuticals and/or bases for rectal administration and method of use
CA1188987A (en) * 1981-03-06 1985-06-18 Masataka Morishita Preparation having excellent absorption property
EP0126348A2 (en) * 1983-05-19 1984-11-28 Kyoto Pharmaceutical Industries, Ltd. Composition for rectal administration and method of promoting rectal drug absorption
US4732892A (en) * 1985-07-12 1988-03-22 American Home Products Corporation L-α-amino acids as transdermal penetration enhancers
DE3532074A1 (en) * 1985-09-09 1987-03-12 Berlin Chemie Veb RESORPTION AGENT FOR BIOLOGICALLY ACTIVE PEPTIDES

Also Published As

Publication number Publication date
JPH02264713A (en) 1990-10-29
EP0384283A3 (en) 1991-07-17
EP0384283A2 (en) 1990-08-29

Similar Documents

Publication Publication Date Title
DE69830582T2 (en) USE OF LACTOFERRINE IN THE TREATMENT OF COMPLAINTS CAUSED BY ALLERGENS
DE3686343T2 (en) PHARMACEUTICAL PREPARATION FOR APPLICATION FOR BONE MEASUREMENT.
DE3486028T2 (en) ADMINISTRATIVE FORM OF MEDICINAL PRODUCTS.
DE68905205T2 (en) USE OF IGF-I FOR PRODUCING A PREPARATION FOR THE TREATMENT AND PREVENTION OF SIDE EFFECTS OF HYPERINSULINEMIA IN DIABETICIANS TREATED WITH INSULIN.
DE68921814T2 (en) VIP conjugates and their active fragments with hydrophobic components and topical preparations for use in the treatment of male impotence.
DE68921546T2 (en) Increase in fetal hemoglobin by treatment with activin and / or inhibin.
DE69101187T2 (en) VIP analogues and their use.
DE69713485T2 (en) Medicines for the treatment or prevention of thrombocytopenia
DE69829254T2 (en) Drug preparation with controlled drug release rate
EP0203580B1 (en) Gamma-ifn as an agent for the inhibition (hindering) of the decay process of bones
DE3781250T2 (en) USE OF "CARTILAGE-INDUCING FACTOR B (CIF-B)" FOR PRODUCING A MEDICINAL AGAINST THE GROWTH OF TUMORS.
LU84546A1 (en) USE OF PEPTIDES AS MEDICINE
EP0346501B1 (en) Pharmaceutical preparation for treating immunodeficiency conditions
DE69420872T2 (en) PHARMACEUTICAL PREPARATIONS CONTAINING HGH
DE69432930T2 (en) IMMUNO-MODULATING COMPOSITIONS FROM GALLE
DE69902127T2 (en) HISTONE CONTAINING COMPOSITION FOR TREATING RHEUMATIC ARTHRITIS
WO1991007187A1 (en) Agent for neutralising the procoagulant activity associated with tumor cells
DE69331465T2 (en) INTRAVENOUS SOLUTION THAT REDUCES PROTEIN AND WATER LOSS IN THE BODY
DE69324812T2 (en) CELL ACTIVATOR OF THE INTEGRAL TRACT
DE3830271A1 (en) MEDIUM WITH IMMUNE SUPPRESSIVE EFFECT
DE69533311T2 (en) METHOD FOR TREATING AUTOIMMUNE DISEASES BY TYPE-1 INTERFERONS
EP0083925B1 (en) Method of treatment to induce ovulation in sheep or heifers
DE3876817T2 (en) APPLICATION OF HUMAN BLOOD COAGULATION FACTOR XIII FOR THE TREATMENT OF COLITIS GRAVIS.
DE1902865A1 (en) Substituted insulin derivatives, processes for their production and their use in pharmaceutical preparations
DD293488A5 (en) PROCESS FOR PREPARING MEDICAMENT FOR RECTAL APPLICATION

Legal Events

Date Code Title Description
RPI Change in the person, name or address of the patentee (searches according to art. 11 and 12 extension act)
RPV Change in the person, the name or the address of the representative (searches according to art. 11 and 12 extension act)
ENJ Ceased due to non-payment of renewal fee