WO1992015281A1 - Pharmaceutical composition for the treatment of kaposi's sarcoma - Google Patents

Pharmaceutical composition for the treatment of kaposi's sarcoma Download PDF

Info

Publication number
WO1992015281A1
WO1992015281A1 PCT/EP1992/000441 EP9200441W WO9215281A1 WO 1992015281 A1 WO1992015281 A1 WO 1992015281A1 EP 9200441 W EP9200441 W EP 9200441W WO 9215281 A1 WO9215281 A1 WO 9215281A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
pharmaceutical composition
approximately
composition according
solution
Prior art date
Application number
PCT/EP1992/000441
Other languages
French (fr)
Inventor
André Lefesvre
Original Assignee
Lefesvre Andre
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 Lefesvre Andre filed Critical Lefesvre Andre
Publication of WO1992015281A1 publication Critical patent/WO1992015281A1/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
    • A61K9/0012—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
    • 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
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
    • 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
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof

Definitions

  • the present invention relates to a pharmaceutical composition which is preferably injectable intravenously and intended for the treatment of aposi tumors.
  • Kaposi's sarcoma is a common condition in equatorial Africa and also in the countries of the Mediterranean basin, in men aged 40 to 60 years. This cancer can also occur in people with compromised immune systems, for example, patients with AIDS (acquired immunodeficiency syndrome). Kaposi syndrome is characterized by the appearance on the skin of purplish spots or hard nodules, embedded in the dermis.
  • Enkephalin methionine is an opioid pentapeptide which not only has analgesic, anxiolytic,
  • the object of the present invention is to provide a new pharmaceutical composition making it possible to effectively treat Kaposi tumors, without having the drawbacks of the products or techniques of the prior art.
  • the invention relates to a pharmaceutical composition for the treatment of Kaposi tumors.
  • said composition comprises a first compound from the family of products capable of blocking morphine receptors, and a second compound facilitating the penetration of said first compound inside the cells of the human body.
  • the invention therefore consists in associating with a compound of this family of products, a second compound facilitating the penetration of the first compound into the body.
  • the use of the second compound makes it possible to reduce the doses of the first compound while having good clinical results.
  • the invention will be better understood on reading the following description of an embodiment of the invention.
  • the pharmaceutical composition according to the invention therefore comprises a first compound from the family of products capable of blocking morphine receptors and a second compound facilitating the penetration of said first compound inside the cells of the human body.
  • the first compound is chosen, for example, from enkephalins or endorphins and preferably from leucine enkephalin, lysine enkephalin or methionine enkephalin.
  • the second compound is chosen, for example, from carboxymethylcellulose, sodium dioctylsulfosuccinate or preferably dimethylsulfoxide (DMSO).
  • DMSO dimethylsulfoxide
  • This third compound can also add to this composition a third compound trapping free radicals.
  • This third compound is chosen, for example, from vitamin E, vitamin C, gluthation or preferably superoxide dimutase.
  • composition according to the invention comprises: between approximately 0.004 and 2 mg of the first compound, preferably between approximately 0.02 and 0.4 mg or better still approximately 0.1 mg per ml of a solution preferably comprising between 15 and 65% of the second compound and between 85 and 35% of physiological water, or better still approximately 40% of the second compound and approximately 60% of physiological water.
  • composition according to the invention comprises a third compound which traps free radicals, it comprises:
  • Example 1 0.004 mg per ml of a solution preferably comprising between 15 and 65% of the second compound and between 85 and 35% of physiological water or better still approximately 40% of the second compound and approximately 60% of physiological water.
  • a solution preferably comprising between 15 and 65% of the second compound and between 85 and 35% of physiological water or better still approximately 40% of the second compound and approximately 60% of physiological water.
  • REPLACEMENT SHEET The above composition is administered to the patient in the form of a slow intravenous injection or an intravenous infusion in isotonic saline, at a rate of 2.5 ml at the rate of a daily injection for 15 days, then two injections per week. during 2 months.

Abstract

Pharmaceutical composition for the treatment of Kaposi's sarcoma. The aim of the invention is to produce a composition for the effective treatment of tumours without the secondary effects of the other known technics. This aim is achieved with the aid of a pharmaceutical composition to the treatment of Kaposi's sarcoma, characterized in that it comprises a first compound of the family of drugs capable of blocking morphine receptors and a second compound facilitating the penetration of the first compound inside the cells of the human body.

Description

COMPOSITION PHARMACEUTIQUE POUR LE TRAITEMENT DES TUMEURS DE KAPOSI PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF KAPOSI TUMORS
La présente invention concerne une composition pharmaceutique injectable de préférence par voie intraveineuse et destinée au traitement des tumeurs de aposi.The present invention relates to a pharmaceutical composition which is preferably injectable intravenously and intended for the treatment of aposi tumors.
Le sarcome de Kaposi est une affection fréquente en Afrique équatoriale et également dans les pays du bassin méditerranéen, chez les hommes de 40 à 60 ans. Ce cancer peut également survenir chez des personnes dont le système immunitaire est défaillant, par exemple, les malades atteints du SIDA (syndrome d'immuno déficience acquise). Le syndrome de Kaposi se caractérise par l'apparition sur la peau de taches violacées ou de nodules durs, enchâssés dans le derme.Kaposi's sarcoma is a common condition in equatorial Africa and also in the countries of the Mediterranean basin, in men aged 40 to 60 years. This cancer can also occur in people with compromised immune systems, for example, patients with AIDS (acquired immunodeficiency syndrome). Kaposi syndrome is characterized by the appearance on the skin of purplish spots or hard nodules, embedded in the dermis.
Cette éruption s'étend progressivement et entraîne une évolution fatale en quelques mois ou quelques années. Afin de soigner ces tumeurs de Kaposi, on a utilisé jusqu'à présent diverses techniques comme la radiothérapie, la chimiothéra¬ pie anti-cancéreuse et l'emploi d'interférons alpha 2E>. La radiothé¬ rapie donne des résultats intéressants sur le plan esthétique, notamment avec la disparition des taches sur la peau, mais ne soigne pas la maladie proprement dite. La chimiothérapie donne également certains résultats partiels mais entraîne des effets secondaires et une toxicité non négligea¬ ble. Enfin, l'interfëron alpha 2B ne donne pas de très bons résul¬ tats et produit des effets secondaires comme l'apparition de fièvre chez le patient traité. On a également préconisé l'emploi de la mëthionine enképhaline comme principe actif pour tenter de soigner ce type de cancer, (voir notamment l'article de Zunich. K. et Kirkpatrick. CH, Journal of Clin. Immunology, Vol. 8, No 2, 1988).This rash gradually spreads and causes a fatal evolution in a few months or a few years. In order to treat these Kaposi tumors, various techniques have been used until now, such as radiotherapy, anti-cancer chemotherapy and the use of alpha 2E interferons. Radiotherapy gives interesting results from an aesthetic point of view, in particular with the disappearance of spots on the skin, but does not cure the disease itself. Chemotherapy also gives certain partial results but leads to side effects and considerable toxicity. Finally, the interferon alpha 2B does not give very good results and produces side effects such as the appearance of fever in the patient treated. The use of methionine enkephalin has also been recommended as an active ingredient in an attempt to treat this type of cancer, (see in particular the article by Zunich. K. and Kirkpatrick. CH, Journal of Clin. Immunology, Vol. 8, No 2, 1988).
La mëthionine enképhaline est un pentapeptide opioïde qui présente non seulement des propriétés analgésiques, anxiolytiques,Enkephalin methionine is an opioid pentapeptide which not only has analgesic, anxiolytic,
FEUILLE DE REMPLACEMENT et antî-dépressives mais également, des propriétés, i unomodula- trices en particulier au niveau des lymphocytes.REPLACEMENT SHEET and anti-depressive but also, unomodulatory properties, in particular at the level of lymphocytes.
Malgré le grand intérêt thérapeutique théorique de la mëthionine enképhaline, notamment en ce qui concerne ses propriétés immunomodu- latrices, ce produit a été peu utilisé jusqu'à présent. En effet,Despite the great theoretical therapeutic interest of methionine enkephalin, in particular with regard to its immunomodulatory properties, this product has been little used until now. Indeed,
Zunich et Kirkpatrick ont conclu que bien que la mëthionine enképhaline ait des effets in vitro, elle n'entrainaît pas de régression des tumeurs des malades atteints du sarcome de Kaposi.Zunich and Kirkpatrick concluded that although methionine enkephalin has in vitro effects, it did not cause tumor regression in patients with Kaposi's sarcoma.
En conséquence, ce produit a été rejeté par l'homme de l'art qui le considérait comme inefficace pour soigner le sarcome de Kaposi.As a result, this product was rejected by those skilled in the art who considered it ineffective in treating Kaposi's sarcoma.
Le but de la présente invention est de fournir une nouvelle composition pharmaceutique permettant de traiter efficacement les tumeurs de Kaposi, sans présenter les inconvénients des produits ou des techniques de l'art antérieur. A cet effet, l'invention à pour objet une composition pharmaceu¬ tique pour le traitement des tumeurs de Kaposi.The object of the present invention is to provide a new pharmaceutical composition making it possible to effectively treat Kaposi tumors, without having the drawbacks of the products or techniques of the prior art. To this end, the invention relates to a pharmaceutical composition for the treatment of Kaposi tumors.
Selon les caractéristiques de l'invention, ladite composition comprend un premier composé de la famille des produits capables de bloquer les récepteurs à la morphine, et un second composé facili- tant la pénétration dudit premier composé à l'intérieur des cellules du corps humain.According to the characteristics of the invention, said composition comprises a first compound from the family of products capable of blocking morphine receptors, and a second compound facilitating the penetration of said first compound inside the cells of the human body.
En effet, le déposant a constaté par des observations cliniques, que la morphine, utilisée parfois lors de trachéotomies réalisées sur des malades atteints du SIDA, aggravait leur état. En conséquen- ce, il a eu l'idée d'utiliser des produits capables de bloquer les récepteurs à la morphine. Toutefois, comme expliqué ci-dessus, ce type de produit, tel que la mëthionine enképhaline n'est pas effica¬ ce. L'invention consiste donc à associer à un composé de cette famille de produits, un second composé facilitant la pénétration du premier composé dans l'organisme.In fact, the depositor has noted by clinical observations that morphine, sometimes used during tracheostomies performed on patients suffering from AIDS, worsens their condition. Consequently, he had the idea of using products capable of blocking the morphine receptors. However, as explained above, this type of product, such as enkephalin methionine is not effective. The invention therefore consists in associating with a compound of this family of products, a second compound facilitating the penetration of the first compound into the body.
De façon tout à fait inattendue, on a ainsi découvert que les produits bloquant les récepteurs à la morphine pouvaient soigner efficacement le sarcome de Kaposi.Quite unexpectedly, it was discovered that products blocking morphine receptors could effectively treat Kaposi's sarcoma.
De plus, l'utilisation du second composé permet de diminuer les doses du premier composé tout en ayant de bons résultats cliniques. L'invention sera mieux comprise à la lecture de la descrîtpion suivante d'un mode de réalisation de l'invention.In addition, the use of the second compound makes it possible to reduce the doses of the first compound while having good clinical results. The invention will be better understood on reading the following description of an embodiment of the invention.
FEUILLE DE REMPLACEMENT La composition pharmaceutique selon l'invention comprend donc un premier composé de la famille des produits capables de bloquer les récepteurs à la morphine et un second composé facilitant la pénétra¬ tion dudit premier composé à l'intérieur des cellules du corps humain.REPLACEMENT SHEET The pharmaceutical composition according to the invention therefore comprises a first compound from the family of products capable of blocking morphine receptors and a second compound facilitating the penetration of said first compound inside the cells of the human body.
Le premier composé est choisi par exemple parmi les enképhalines ou les endorphines et de préférence parmi la leucine enképhaline, la lysine enképhaline ou la mëthionine enképhaline.The first compound is chosen, for example, from enkephalins or endorphins and preferably from leucine enkephalin, lysine enkephalin or methionine enkephalin.
Le second composé est choisi par exemple, parmi la carboxymé- thylcellulose, le dioctylsulfosuccinate de sodium ou de préférence le diméthylsulfoxyde (DMSO).The second compound is chosen, for example, from carboxymethylcellulose, sodium dioctylsulfosuccinate or preferably dimethylsulfoxide (DMSO).
On peut également ajouter à cette composition un troisième composé piégeant les radicaux libres. Ce troisième composé est choisi par exemple parmi la vitamine E, la vitamine C, le gluthation ou de préférence la superoxyde dimutase.One can also add to this composition a third compound trapping free radicals. This third compound is chosen, for example, from vitamin E, vitamin C, gluthation or preferably superoxide dimutase.
La composition selon l'invention comprend : entre 0,004 et 2 mg environ du premier composé, de préféren¬ ce entre 0,02 et 0,4 mg environ ou mieux environ 0,1 mg par ml d'une solution comprenant de préférence entre 15 et 65% du deuxième composé et entre 85 et 35% d'eau physiologique, ou mieux environ 40% du deuxième composé et environ 60% d'eau physiologique.The composition according to the invention comprises: between approximately 0.004 and 2 mg of the first compound, preferably between approximately 0.02 and 0.4 mg or better still approximately 0.1 mg per ml of a solution preferably comprising between 15 and 65% of the second compound and between 85 and 35% of physiological water, or better still approximately 40% of the second compound and approximately 60% of physiological water.
Lorsque la composition pharmaceutique selon l'invention comprend un troisième composé piégeant les radicaux libres, elle en comprend :When the pharmaceutical composition according to the invention comprises a third compound which traps free radicals, it comprises:
-4 -2 - de préférence entre 8*10 mg et 2 10 mg ou mieux environ-4 -2 - preferably between 8 * 10 mg and 2 10 mg or better approximately
0,004 mg par ml d'une solution comprenant de préférence entre 15 et 65% du deuxième composé et entre 85 et 35% d'eau physiologique ou mieux environ 40% du deuxième composé et environ 60% d'eau physiolo¬ gique. Un exemple de préparation va maintenant être décrit : Exemple 10.004 mg per ml of a solution preferably comprising between 15 and 65% of the second compound and between 85 and 35% of physiological water or better still approximately 40% of the second compound and approximately 60% of physiological water. An example of preparation will now be described: Example 1
On mélange 25 mg de mëthionine en képhaline et éventuellement 1 mg de superoxyde dimutase dans 100 ml de DMSO et 150 ml d'eau physiologique. Le mélange est alors stérilisé à froid, par filtration sur un filtre réalisé en un matériau non sensible aux produits utilisés. Le mode d'administration est le suivant :25 mg of methionine in kephalin are mixed and optionally 1 mg of superoxide dimutase in 100 ml of DMSO and 150 ml of physiological water. The mixture is then sterilized in the cold, by filtration on a filter made of a material not sensitive to the products used. The method of administration is as follows:
FEUILLE DE REMPLACEMENT La composition précédente est administrée au patient sous forme d'une injection intraveineuse lente ou d'une perfusion intraveineuse dans du sérum salé isotonique, à raison de 2,5 ml au rythme d'une injection quotidienne pendant 15 jours, puis deux injections par semaine pendant 2 mois.REPLACEMENT SHEET The above composition is administered to the patient in the form of a slow intravenous injection or an intravenous infusion in isotonic saline, at a rate of 2.5 ml at the rate of a daily injection for 15 days, then two injections per week. during 2 months.
A Tissu d'un mois de traitement, on a observé chez les patients une disparition quasi complète des taches noires des tumeurs cuta¬ nées de Kaposi et des oedèmes qui les accompagnent ainsi qu'une disparition de la dyspnée chez les malades présentant un Kaposi pulmonaire. On a également observé une nette amélioration de l'as¬ thénie et de l'état général des malades. Toutefois, ces améliora¬ tions nécessitent un traitement d'entretien pour que les symptômes ne réapparaissent pas.After a month's treatment, almost complete black spots of Kaposi skin tumors and the edemas that accompany them have been observed, as well as disappearance of dyspnea in patients with pulmonary Kaposi. . There has also been a marked improvement in the asthenia and the general condition of the patients. However, these improvements require maintenance treatment so that the symptoms do not reappear.
Il semble que l'addition de la superoxyde dimutase permette d'obtenir les mêmes résultats cliniques plus rapidement.It seems that the addition of superoxide dimutase makes it possible to obtain the same clinical results more quickly.
FEUILLE DE REMPLACEMENT REPLACEMENT SHEET

Claims

ζ REVENDICATIONS ζ CLAIMS
1. Composition pharmaceutique pour le traitement des tumeurs de Kaposi, caractérisée en ce qu'elle comprend un premier composé de la famille des produits capables de bloquer les récepteurs à la morphi¬ ne, et un deuxième composé facilitant la pénétration dudit premier composé à l'intérieur des cellules du corps humain.1. Pharmaceutical composition for the treatment of Kaposi tumors, characterized in that it comprises a first compound from the family of products capable of blocking morphine receptors, and a second compound facilitating the penetration of said first compound into the inside the cells of the human body.
2. Composition pharmaceutique selon la revendication 1, carac¬ térisée en ce que le premier composé est choisi parmi les enképhali- nes ou les endorphines.2. Pharmaceutical composition according to claim 1, charac¬ terized in that the first compound is chosen from enkephalines or endorphins.
3. Composition pharmaceutique selon la revendication 1, carac- térisée en ce que le premier composé est choisi parmi la leucine enképhaline, la lysine enképhaline ou la mëthionine enképhaline.3. Pharmaceutical composition according to claim 1, characterized in that the first compound is chosen from leucine enkephalin, lysine enkephalin or methionine enkephalin.
4. Composition pharmaceutique selon la revendication 1, carac¬ térisée en ce que le deuxième composé est choisi parmi le dimëthyl- sulfoxyde, la carboxyméthylcellulose de sodium ou le dioctylsulfo- succinate de sodium.4. Pharmaceutical composition according to claim 1, charac¬ terized in that the second compound is chosen from dimethyl sulfoxide, sodium carboxymethylcellulose or sodium dioctylsulfosuccinate.
5. Composition pharmaceutique selon Tune quelconque des revendications précédentes, caractérisée en ce qu'elle comprend entre 0.004 et 2 mg environ du premier composé pour 1 ml d'une solution comprenant entre 15 et 65% du deuxième composé et entre 85 et 35% d'eau physiologique. 5. Pharmaceutical composition according to any one of the preceding claims, characterized in that it comprises between 0.004 and 2 mg approximately of the first compound for 1 ml of a solution comprising between 15 and 65% of the second compound and between 85 and 35% d physiological water.
6. Composition pharmaceutique selon la revendication 5, carac¬ térisée en ce qu'elle comprend entre 0.004 et 2 mg environ du premier composé pour 1 ml d'une solution comprenant environ 40% du deuxième composé et environ 60% d'eau physiologique.6. Pharmaceutical composition according to claim 5, charac¬ terized in that it comprises between 0.004 and 2 mg approximately of the first compound for 1 ml of a solution comprising approximately 40% of the second compound and approximately 60% of physiological water.
7. Composition pharmaceutique selon la revendication 5, carac- térisée en ce qu'elle comprend entre 0,02 et 0,4 mg environ du premier composé pour 1 ml d'une solution comprenant entre 15 et 65% du deuxième composé et entre 85 et 35% d'eau physiologique.7. Pharmaceutical composition according to claim 5, characterized in that it comprises between 0.02 and 0.4 mg approximately of the first compound per 1 ml of a solution comprising between 15 and 65% of the second compound and between 85 and 35% physiological water.
8. Composition pharmaceutique selon la revendication 7, carac¬ térisée en ce qu'elle comprend entre 0,02 et 0,4 mg environ du premier composé pour 1 ml d'une solution comprenant environ 40% du deuxième composé et environ 60% d'eau physiologique.8. Pharmaceutical composition according to claim 7, charac¬ terized in that it comprises between 0.02 and 0.4 mg approximately of the first compound per 1 ml of a solution comprising approximately 40% of the second compound and approximately 60% d physiological water.
9. Composition pharmaceutique selon la revendication 7, carac¬ térisée en ce qu'elle comprend environ 0,1 mg du premier composé pour 1 ml d'une solution comprenant entre 15 et 65% du deuxième composé et entre 85 et 35% d'eau physiologique.9. Pharmaceutical composition according to claim 7, charac¬ terized in that it comprises approximately 0.1 mg of the first compound for 1 ml of a solution comprising between 15 and 65% of the second compound and between 85 and 35% of physiological water.
10. Composition pharmaceutique selon la revendication 9, carac¬ térisée en ce qu'elle comprend environ 0,1 mg du premier composé pour 1 ml d'une solution comprenant environ 40% du deuxième composé et environ 60% d'eau physiologique.10. Pharmaceutical composition according to claim 9, charac¬ terized in that it comprises approximately 0.1 mg of the first compound for 1 ml of a solution comprising approximately 40% of the second compound and approximately 60% of physiological water.
11. Compositon pharmaceutique selon Tune quelconque des reven¬ dications précédentes, caractérisée en ce qu'elle comprend un troi¬ sième composé piégeant les radicaux libres. 11. Pharmaceutical composition according to any one of the preceding claims, characterized in that it comprises a third compound trapping free radicals.
12. Composition pharmaceutique selon la revendication 11, carac¬ térisée en ce que le troisième composé piégeant les radicaux libres est choisi parmi la superoxyde dimutase, la vitamine E, la vitamine C ou le glutathion.12. Pharmaceutical composition according to claim 11, charac¬ terized in that the third compound trapping free radicals is chosen from superoxide dimutase, vitamin E, vitamin C or glutathione.
13. Composition pharmaceutique selon la revendication 5, 7 ou 9,13. Pharmaceutical composition according to claim 5, 7 or 9,
-4 -2 caractérisée en ce qu'elle comprend entre 8*10 mg et 2*10 mg d'un composé piégeant les radicaux libres pour 1 ml d'une solution comprenant entre 15 et 65% du deuxième composé et entre 85 et 35% d'eau physiologique.-4 -2 characterized in that it comprises between 8 * 10 mg and 2 * 10 mg of a compound scavenging free radicals for 1 ml of a solution comprising between 15 and 65% of the second compound and between 85 and 35 % physiological water.
14. Composition pharmaceutique selon la revendication 6, 8 ou 10, caractérisée en ce qu'elle comprend entre 8*10 -4 mg et 2*10-2 mg d'un composé piégeant les radicaux libres pour 1 ml d'une solution comprenant environ 40% du deuxième composé et environ 60% d'eau physiologique.14. Pharmaceutical composition according to claim 6, 8 or 10, characterized in that it comprises between 8 * 10 -4 mg and 2 * 10-2 mg of a compound scavenging free radicals for 1 ml of a solution comprising about 40% of the second compound and about 60% physiological water.
15. Composition pharmaceutique selon la revendication 13, caractérisée en ce qu'elle comprend environ 0,004 mg d'un composé piégeant les radicaux libres pour 1 ml d'une solution comprenant entre 15 et 65% du deuxième composé et entre 85 et 35% d'eau physio¬ logique.15. Pharmaceutical composition according to claim 13, characterized in that it comprises approximately 0.004 mg of a compound scavenging free radicals for 1 ml of a solution comprising between 15 and 65% of the second compound and between 85 and 35% d physio¬ logical water.
16. Composition pharmaceutique selon la revendication 14, caractérisée en ce qu'elle comprend environ 0,004 mg d'un composé piégeant les radicaux libres pour 1 ml d'une solution comprenant environ 40% du deuxième composé et environ 60% d'eau physiologique.16. Pharmaceutical composition according to claim 14, characterized in that it comprises approximately 0.004 mg of a compound scavenging free radicals for 1 ml of a solution comprising approximately 40% of the second compound and approximately 60% of physiological water.
FEUILLE DE REMPLACEMENT REPLACEMENT SHEET
PCT/EP1992/000441 1991-03-01 1992-02-28 Pharmaceutical composition for the treatment of kaposi's sarcoma WO1992015281A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR9102581A FR2673376A1 (en) 1991-03-01 1991-03-01 PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF KAPOSI TUMORS.
FR91/02581 1991-03-01

Publications (1)

Publication Number Publication Date
WO1992015281A1 true WO1992015281A1 (en) 1992-09-17

Family

ID=9410323

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1992/000441 WO1992015281A1 (en) 1991-03-01 1992-02-28 Pharmaceutical composition for the treatment of kaposi's sarcoma

Country Status (2)

Country Link
FR (1) FR2673376A1 (en)
WO (1) WO1992015281A1 (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0181001A2 (en) * 1984-11-09 1986-05-14 Eisai Co., Ltd. Polypeptide, a process for preparing the same, a pharmaceutical composition containing said polypeptide as well as the use thereof
EP0341661A2 (en) * 1988-05-11 1989-11-15 The Du Pont Merck Pharmaceutical Company Peptide-drug compositions containing alpha-aminoboronic acid derivatives
JPH0232028A (en) * 1988-07-19 1990-02-01 Rooman Kogyo:Kk Antitussive agent
US4910021A (en) * 1985-11-29 1990-03-20 R. P. Scherer Corporation Targeted enternal delivery system

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0181001A2 (en) * 1984-11-09 1986-05-14 Eisai Co., Ltd. Polypeptide, a process for preparing the same, a pharmaceutical composition containing said polypeptide as well as the use thereof
US4910021A (en) * 1985-11-29 1990-03-20 R. P. Scherer Corporation Targeted enternal delivery system
EP0341661A2 (en) * 1988-05-11 1989-11-15 The Du Pont Merck Pharmaceutical Company Peptide-drug compositions containing alpha-aminoboronic acid derivatives
JPH0232028A (en) * 1988-07-19 1990-02-01 Rooman Kogyo:Kk Antitussive agent

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Derwent WPIL, numéro d'accès 90-079189 [11], Derwent Publications Ltd, Londres, GB; & JP,A,2032028 (ROMAN KOGYO K.K.) 1 février 1990, voir l'abrégé *

Also Published As

Publication number Publication date
FR2673376A1 (en) 1992-09-04

Similar Documents

Publication Publication Date Title
Berlanga et al. Heberprot-P: a novel product for treating advanced diabetic foot ulcer
CN103327986B (en) Comprising the treatment using magnetic dipole stabilizing solutions or improve disease and enhance the method for performance
RU2070722C1 (en) Method of treatment of mammalian with gastroenteric tract ulcer disease and pharmcomposition for its realization
RU2002127804A (en) MEDICINAL SYSTEM FOR TREATMENT OF COMPLICATIONS CONNECTED WITH DIABETES AND NEUROPATHY, AND THEIR APPLICATION
KR20030034177A (en) Remedies for ischemic diseases
SK137996A3 (en) Cancer treatment and metastasis prevention
IT8922725A1 (en) USE OF IMMUNOMODULANTS AS SYNERGIC AGENTS OF CHEMOTHERAPY IN CANCER THERAPY
CA2018630A1 (en) Use of a polypeptide having human interleukine 2 activity to prepare a pharmaceutical compound for the treatment of primary cancer of the plevra
WO1992015281A1 (en) Pharmaceutical composition for the treatment of kaposi's sarcoma
Thong et al. Immunopotentiation by pyrimethamine in the mouse.
EP0108017B1 (en) Mixture comprising a central analgesic and vitamin b12, or one of its analogs, as active principles
EP1368027B1 (en) Use of tryptophan derivatives for the specific cytostatic treatment of serotonin-producing tumors
KR20210039414A (en) Combination therapy for the treatment of cancer
CA2654956C (en) Peptides with anti-proliferative activity
RU2264815C2 (en) Method for treating localized scleroderma
Mcdonald et al. Treatment of basal cell carcinoma with intralesional interferon alpha: a case report and literature review
DE2740953A1 (en) USE OF PROSTAGLANDINES TO LOWER BLOOD SUGAR LEVELS
EP0402208A1 (en) Mixture of Vitamin A in physiological dosis and different active ingredients having therapeutic effect
CA2333776A1 (en) Composition based on pentoxifylline and anticytokin
JP2019513802A (en) COMBINATION COMPOSITION AND METHOD OF USE THEREOF
JPH0251405B2 (en)
JPH0477436A (en) Cancer metastasis suppressing agent
RU2147440C1 (en) Analgetic and anti-itching agent
JPS60174726A (en) Pharmaceutical composition for injection
RU2140270C1 (en) Method of treatment of patient with kaposi's sarcoma idiopathic type

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): CA US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IT LU MC NL SE

NENP Non-entry into the national phase

Ref country code: CA