WO1997006769A2 - Pharmaceutical composition with trypanocidal properties - Google Patents
Pharmaceutical composition with trypanocidal properties Download PDFInfo
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- WO1997006769A2 WO1997006769A2 PCT/EP1996/003657 EP9603657W WO9706769A2 WO 1997006769 A2 WO1997006769 A2 WO 1997006769A2 EP 9603657 W EP9603657 W EP 9603657W WO 9706769 A2 WO9706769 A2 WO 9706769A2
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- Prior art keywords
- pharmaceutical preparation
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Links
- 239000008194 pharmaceutical composition Substances 0.000 title abstract 2
- 230000000654 trypanocidal effect Effects 0.000 title abstract 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 22
- XDRYMKDFEDOLFX-UHFFFAOYSA-N pentamidine Chemical compound C1=CC(C(=N)N)=CC=C1OCCCCCOC1=CC=C(C(N)=N)C=C1 XDRYMKDFEDOLFX-UHFFFAOYSA-N 0.000 claims abstract description 12
- VEQOALNAAJBPNY-UHFFFAOYSA-N antipyrine Chemical compound CN1C(C)=CC(=O)N1C1=CC=CC=C1 VEQOALNAAJBPNY-UHFFFAOYSA-N 0.000 claims abstract description 10
- 235000011187 glycerol Nutrition 0.000 claims abstract description 10
- 229960004448 pentamidine Drugs 0.000 claims abstract description 10
- 229960005222 phenazone Drugs 0.000 claims abstract description 9
- 239000007864 aqueous solution Substances 0.000 claims abstract description 7
- 229920003086 cellulose ether Polymers 0.000 claims abstract description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 17
- 239000004480 active ingredient Substances 0.000 claims description 10
- XNYZHCFCZNMTFY-UHFFFAOYSA-N diminazene Chemical compound C1=CC(C(=N)N)=CC=C1N\N=N\C1=CC=C(C(N)=N)C=C1 XNYZHCFCZNMTFY-UHFFFAOYSA-N 0.000 claims description 9
- 229950007095 diminazene Drugs 0.000 claims description 9
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 claims description 7
- 229960004194 lidocaine Drugs 0.000 claims description 6
- 229920000609 methyl cellulose Polymers 0.000 claims description 5
- 239000001923 methylcellulose Substances 0.000 claims description 5
- 235000010981 methylcellulose Nutrition 0.000 claims description 5
- 230000001754 anti-pyretic effect Effects 0.000 claims description 4
- 239000002221 antipyretic Substances 0.000 claims description 4
- 230000000202 analgesic effect Effects 0.000 claims description 3
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 2
- 230000007935 neutral effect Effects 0.000 claims description 2
- 229960004919 procaine Drugs 0.000 claims description 2
- 239000003589 local anesthetic agent Substances 0.000 claims 3
- 239000001913 cellulose Substances 0.000 claims 2
- 229920002678 cellulose Polymers 0.000 claims 2
- 229920000642 polymer Polymers 0.000 claims 2
- 238000010411 cooking Methods 0.000 claims 1
- JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 5
- 229960005150 glycerol Drugs 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 description 21
- 239000000243 solution Substances 0.000 description 9
- 239000007924 injection Substances 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 208000015181 infectious disease Diseases 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 239000003995 emulsifying agent Substances 0.000 description 4
- 229960002900 methylcellulose Drugs 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 229950010741 aceturate Drugs 0.000 description 3
- 201000008680 babesiosis Diseases 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 208000035473 Communicable disease Diseases 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- 229910052785 arsenic Inorganic materials 0.000 description 2
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229940124641 pain reliever Drugs 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 208000000230 African Trypanosomiasis Diseases 0.000 description 1
- 241000223836 Babesia Species 0.000 description 1
- 241000223840 Babesia bigemina Species 0.000 description 1
- 241000223846 Babesia canis Species 0.000 description 1
- 241000675161 Babesia motasi Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010007269 Carcinogenicity Diseases 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 208000010362 Protozoan Infections Diseases 0.000 description 1
- 208000035415 Reinfection Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000489254 Tetranychus takafujii Species 0.000 description 1
- 241000223778 Theileria annulata Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000007670 carcinogenicity Effects 0.000 description 1
- 231100000260 carcinogenicity Toxicity 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 208000021760 high fever Diseases 0.000 description 1
- 208000029080 human African trypanosomiasis Diseases 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229940071826 hydroxyethyl cellulose Drugs 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 201000002612 sleeping sickness Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 201000002311 trypanosomiasis Diseases 0.000 description 1
Classifications
-
- 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
- A61K31/655—Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds
Definitions
- the invention relates to a pharmaceutical preparation with trypanozid properties for the veterinary field, in the form of an aqueous solution, the diminazenediacetate (4,4'-diamidinodiazobenzenediacetamidoacetate) and pentamidine (4,4 '- (pentamethylendioxy) ) -dibenzamidine) as trypanozide active ingredients, phenazone (1,2-dihydro-l, 5-dimethyl-2-phenyl-3H-pyrazol-3-one) as antipyretic and analgesic component as well as glycerin.
- Arsenic preparations and trypan dyes are known as chemotherapeutic agents, but due to their arsenic
- a preparation for the treatment of such infections in animals is a trypanozide based on diminazen powder.
- Other commercially available trypanozides are also only available in powder form.
- the powdered form of the medicament is extremely disadvantageous, since the powdered preparations cannot be added to the feed and they therefore have to be mixed with water in order to prepare an injection solution. It is not possible to prepare a sterile solution from the powdery preparations, since the active substances crystallize out of the solution after a short time, so that the effectiveness of the preparation is quickly lost. Such solutions are therefore not adequately storable and transportable.
- the injection solution must therefore be prepared shortly before the injection, but this is very dangerous due to the generally available water, since it can generally contain bacteria, viruses and germs which cause additional infections in the animals, so that the animals are very heavily burdened by an additional infection.
- a complete solution of the solids is not achieved, so that the solution for injection has a poor effectiveness.
- the currently known powdery trypanozides thus represent a risk of additional infections or contamination, at the same time that There is a risk of underdosing of the therapeutic agent, so that the chemotherapy may have to be repeated, which naturally increases the risk potential for infections or the like.
- aqueous solutions of diminazene diacetate which contain castor oil as a solubilizer.
- the invention is therefore based on the object of providing a solution of a pharmaceutical preparation of the type mentioned at the outset which is stable even at high temperatures.
- the invention provides to create a pharmaceutical preparation with trypanozid properties in the form of an aqueous solution which contains the following substances: - Diminazene di-aceturate
- Diminazene diacetate and pentamidine are trypanoicidal active ingredients which have a different spectrum of activity and thus complement one another in their action, so that almost all types of blood parasites are detected. In addition, resistances are advantageously avoided by the combination.
- the poor water solubility of diminazene diacetate is compensated for by the combination of the two trypanozidic active substances according to the invention, since pentamidine, which is water soluble, acts as a solubilizer.
- the phenazone also brings about better solubility of the diminazene di-aceturate, in addition to its action as an analgesic, which advantageously alleviates pain and fever conditions in the animals which are caused by the injection or the infection.
- Glycerin and the water-soluble cellulose ether serve as emulsifiers.
- a stable aqueous solution can be obtained according to the combination of all of the aforementioned substances.
- the stability of the preparation according to the invention is advantageously so great that it can also be heated to 70 ° C. over a long period of time without any signs of decomposition occurring.
- Methyl-cellulose is preferably used as the water-soluble cellulose ether, although other cellulose ethers, such as, for. B. hydroxy-ethyl cellulose or hydroxypropyl cellulose or their mixed forms are suitable.
- the water used is preferably water which is physiologically, ie. H. in terms of pH and osmolality.
- the water is pH neutral and isotonic. It also has a saline content of 0.9 + 0.3%.
- aqueous solution is obtained as a preparation which can be stored without any problems since the active ingredient cannot crystallize out. In addition, there is no risk of an additional infection since it can be produced under sterile conditions.
- Babesiosis (Babesia bigemina, Babesia motasi, Babesia canis and other Babesia) Theileria annulata.
- the preparation according to the invention is combined with a further antipyretic substance and / or a pain reliever.
- a further antipyretic substance and / or a pain reliever.
- Lidocaine, procaine or their derivatives are preferably used. If necessary, acetylsalicylic acid can also be used as a fever and pain reliever.
- the preparation according to the invention contains isometadium hydrochloride from the group of the phenathridines as a further biocidal active ingredient.
- Methyl cellulose physiologically adjusted water 66.5 vol.-3
- composition in% by weight of the active ingredients is preferably:
- Methyl cellulose 1.6% physiologically adjusted water 78.4%.
- the preparation according to the invention has the advantage that, based on the volume, the active substance content can be doubled compared to the prior art.
- a particular advantage is that a single injection, which is necessary for chemotherapy, also provides three-month protection against reinfections.
- a preferred embodiment of the pharmaceutical preparation is produced by the biocidal active ingredients, the intended activity-reducing agents.
- water Emulsifier mixture can be mixed.
- the emulsifier / water mixture which is composed of glycerol 20% by volume, methyl cellulose 1.6% by volume and physiological water 78.4% by volume, is then added to the active substances.
- the ready-to-use preparation can be filled sterile filtered.
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- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Abstract
Description
Pharmazeutisches Präparat mit trypanoziden Eiqen- schaften Pharmaceutical preparation with trypanozid properties
Anwendungsgebietfield of use
Die Erfindung betrifft ein pharmazeutisches Präparat mit trypanoziden Eigenschaften für den veterinärmedi¬ zinischen Bereich, in Form einer wässrigen Lösung, die Diminazen-di-aceturat (4,4'-Diamidinodiazobenzen- diacetamidoacetat) und Pentamidin (4,4'-(Pentamethyl- endioxy)-dibenzamidin) als trypanozide Wirkstoffe, Phenazon (1,2-Dihydro-l,5-dimethyl-2-phenyl-3H-pyrazol- 3-on) als fiebersenkende und schmerzstillende Komponente sowie Glycerin enthält.The invention relates to a pharmaceutical preparation with trypanozid properties for the veterinary field, in the form of an aqueous solution, the diminazenediacetate (4,4'-diamidinodiazobenzenediacetamidoacetate) and pentamidine (4,4 '- (pentamethylendioxy) ) -dibenzamidine) as trypanozide active ingredients, phenazone (1,2-dihydro-l, 5-dimethyl-2-phenyl-3H-pyrazol-3-one) as antipyretic and analgesic component as well as glycerin.
In Ländern mit tropischem Klima sind Infektionskrank¬ heiten, die durch Protozoen hervorgerufen werden, weit verbreitet, wie z. B. die sogenannte Schlafkrankheit (Trypanosomiasis) , die das zentrale Nervensystem schädigt und bei Nichtbehandlung zum Tode führt. Die Krankheit betrifft Mensch und Tier gleichermaßen und muß chemotherapeutisch behandelt werden.In countries with a tropical climate, infectious diseases caused by protozoa are widespread, such as: B. the so-called sleeping sickness (trypanosomiasis), which damages the central nervous system and leads to death if not treated. The disease affects humans and animals alike and must be treated with chemotherapy.
Im landwirtschaftlichen Bereich besteht für die Vete¬ rinärmedizin ein großer Bedarf an wirksamen Präparaten zur Bekämpfung derartiger Infektionskrankheiten, wo¬ bei stets zu berücksichtigen ist, daß die Bedingungen in hygienischer Hinsicht, die z. B. in Afrika ange¬ troffen werden, oftmals schlecht sind.In the agricultural field, there is a great need for veterinary medicine for effective preparations for combating such infectious diseases, although it must always be taken into account that the conditions in terms of hygiene, which, for. B. encountered in Africa, are often bad.
,* Stand der Technik, * State of the art
((
Als Chemotherapeutika sind Arsenpräparate und Trypan- Farbstoffe bekannt, die jedoch aufgrund ihres Arsen-Arsenic preparations and trypan dyes are known as chemotherapeutic agents, but due to their arsenic
ORIGINAL UNTERLAGEN gehaltes bzw. ihrer Karzinogenität nachteilhaft sind. ,ORIGINAL DOCUMENTS content or their carcinogenicity are disadvantageous. .
Ein bekanntes und seit langem vielfach eingesetztes {A well-known and widely used {
Präparat zur Behandlung solcher Infektionen bei Tieren ist ein Trypanozid auf Diminazen-Pulver-Basis. Auch andere handelsübliche Trypanozide sind ausschließlich in Pulverform erhältlich. Doch gerade die Pulverform des Medikaments ist äußerst nachteilhaft, da die pulverförmigen Präparate nicht dem Futter beigemengt werden können und sie daher zur Bereitung einer Injek¬ tionslösung mit Wasser vermischt werden müssen. Die Herstellung einer sterilen Lösung aus den pulver¬ förmigen Präparaten ist nicht möglich, da die Wirk¬ stoffe nach kurzer Zeit aus der Lösung auskristalli¬ sieren, so daß die Wirksamkeit des Präparates rasch verlorengeht. Derartige Lösungen sind demnach nicht ausreichend lager- und transportfähig. Die Injektions¬ lösung muß daher kurz vor der Injektion hergestellt werden, was jedoch aufgrund des im allgemeinen zur Verfügung stehenden Wassers sehr gefährlich ist, da in der Regel Bakterien, Viren und Keime enthalten sein können, die zusätzliche Infektionen bei den Tieren hervorrufen, so daß die Tiere durch eine zu¬ sätzliche Infektion sehr stark belastet werden. Außerdem wird aufgrund der schlechten Löslichkeit derartiger pulverförmiger Medikamente keine voll¬ ständige Lösung der Feststoffe erzielt, so daß die Injektionslösung eine mangelhafte Wirksamkeit auf¬ weist.A preparation for the treatment of such infections in animals is a trypanozide based on diminazen powder. Other commercially available trypanozides are also only available in powder form. However, the powdered form of the medicament is extremely disadvantageous, since the powdered preparations cannot be added to the feed and they therefore have to be mixed with water in order to prepare an injection solution. It is not possible to prepare a sterile solution from the powdery preparations, since the active substances crystallize out of the solution after a short time, so that the effectiveness of the preparation is quickly lost. Such solutions are therefore not adequately storable and transportable. The injection solution must therefore be prepared shortly before the injection, but this is very dangerous due to the generally available water, since it can generally contain bacteria, viruses and germs which cause additional infections in the animals, so that the animals are very heavily burdened by an additional infection. In addition, due to the poor solubility of such powdered medicaments, a complete solution of the solids is not achieved, so that the solution for injection has a poor effectiveness.
Die derzeit bekannten pulverförmigen Trypanozide stellen somit eine Gefahr zusätzlicher Infektionen ' bzw. von Verseuchungen dar, wobei gleichzeitig das Risiko einer Unterdosierung des Therapeutikums be¬ steht, so daß gegebenenfalls die Chemotherapie wiederholt werden muß, wobei sich naturgemäß das Gefahrenpotential für Infektionen o. dgl. vergrößert,The currently known powdery trypanozides thus represent a risk of additional infections or contamination, at the same time that There is a risk of underdosing of the therapeutic agent, so that the chemotherapy may have to be repeated, which naturally increases the risk potential for infections or the like.
Um die Nachteile der pulverförmigen Trypanozide zu vermeiden, sind wässrige Lösungen von Diminazendi- aceturat entwickelt worden, die Rhizinusöl als Lösungsvermittlelr enthalten.In order to avoid the disadvantages of powdered trypanozides, aqueous solutions of diminazene diacetate have been developed which contain castor oil as a solubilizer.
Das Herstellungsverfahren ist jedoch relativ zeit¬ aufwendig und die Stabilität der erhaltenen Lösung des Präparats ist lediglich bis zu einer Temperatur von ca. 25 Grad C gewährleistet.However, the production process is relatively time-consuming and the stability of the solution of the preparation obtained is only guaranteed up to a temperature of approximately 25 degrees C.
Dies mag unter normalen Umständen ausreichen, je¬ doch können diese Lagerungsbedingungen in tropischen Ländern oftmals nicht eingehalten werden, so daß das Präparat verdirbt.This may be sufficient under normal circumstances, but these storage conditions can often not be maintained in tropical countries, so that the preparation spoils.
Aufgabe, Lösung, VorteileTask, solution, advantages
Der Erfindung liegt daher die Aufgabe zugrunde eine Lösung eines pharmazeutischen Präparates der eingangs genannten Art zu schaffen, die auch bei hohen Tempe¬ raturen stabil ist.The invention is therefore based on the object of providing a solution of a pharmaceutical preparation of the type mentioned at the outset which is stable even at high temperatures.
Zur Lösung der Aufgabe ist erfindungsgemäß vorgesehen, ein pharmazeutisches Präparat mit trypanoziden Eigen¬ schaften in Form einer wässrigen Lösung zu schaffen, die folgende Stoffe enthält: - Diminazen-di-aceturatTo achieve the object, the invention provides to create a pharmaceutical preparation with trypanozid properties in the form of an aqueous solution which contains the following substances: - Diminazene di-aceturate
(4,4'-Diamidino-diazoaminobenzen-diacetamido- acetat)(4,4'-diamidino-diazoaminobenzen-diacetamido-acetate)
- Pentamidin (4,4'-(Pentamethylendioxy)- dibenzamidin)- pentamidine (4,4 '- (pentamethylenedioxy) - dibenzamidine)
- Phenazon (l,2-Dihydro-l,5-dimethyl-2-phenyl- 3H-pyrazol-3-on)Phenazone (1,2-dihydro-1,5-dimethyl-2-phenyl-3H-pyrazol-3-one)
- Glycerin- glycerin
- wasserlöslichen Celluloseether.- water-soluble cellulose ether.
Diminazen-di-aceturat und Pentamidin sind trypano¬ zide Wirkstoffe, die ein unterschiedliches Wirkungs¬ spektrum haben und sich somit in ihrer Wirkung er¬ gänzen, so daß nahezu alle Arten von Blutparasiten erfaßt werden. Zudem werden vorteilhafterweise durch die Kombination Resistenzen vermieden.Diminazene diacetate and pentamidine are trypanoicidal active ingredients which have a different spectrum of activity and thus complement one another in their action, so that almost all types of blood parasites are detected. In addition, resistances are advantageously avoided by the combination.
Vorteilhafterweise wird durch die erfindungsgemäße Kombination beider trypanozider Wirkstoffe die schlechte Wasserlöslichkeit von Diminazen-di-aceturat kompensiert, da Pentamidin, das wasserlöslich ist, als Lösungsvermittler wirkt.Advantageously, the poor water solubility of diminazene diacetate is compensated for by the combination of the two trypanozidic active substances according to the invention, since pentamidine, which is water soluble, acts as a solubilizer.
Auch das Phenazon bewirkt eine bessere Löslichkeit des Diminazen-di-aceturats, neben seiner Wirkung als Analgetikum, wodurch vorteilhafterweise Schmerz- und Fieberzustände bei den Tieren, die durch die Injektion bzw. die Infektion bedingt sind, gelindert werden.The phenazone also brings about better solubility of the diminazene di-aceturate, in addition to its action as an analgesic, which advantageously alleviates pain and fever conditions in the animals which are caused by the injection or the infection.
Glycerin und der wasserlösliche Celluloseether dienen als Emulgatoren, wobei erst durch die erfindungsge- mäße Kombination aller vorgenannter Stoffe eine stabile wässrige Lösung erhalten werden kann.Glycerin and the water-soluble cellulose ether serve as emulsifiers. a stable aqueous solution can be obtained according to the combination of all of the aforementioned substances.
Die Stabilität des erfindungsgemäßen Präparates ist vorteilhafterweise derart groß, daß es auch über längere Zeit bis 70 Grad C erhitzt werden kann, ohne daß Zersetzungserscheinungen auftreten.The stability of the preparation according to the invention is advantageously so great that it can also be heated to 70 ° C. over a long period of time without any signs of decomposition occurring.
Als wasserlöslicher Celluloseether wird vorzugsweise Methyl-Cellulose eingesetzt, wobei jedoch auch andere Celluloseether, wie z. B. Hydroxy-Ethyl-Cellulose oder Hydroxy-Propyl-Cellulose oder deren Mischformen geeignet sind.Methyl-cellulose is preferably used as the water-soluble cellulose ether, although other cellulose ethers, such as, for. B. hydroxy-ethyl cellulose or hydroxypropyl cellulose or their mixed forms are suitable.
Als Wasser wird vorzugsweise Wasser eingesetzt, das physiologisch, d. h. hinsichtlich des pH-Wertes und der Osmolalität, angeglichen ist. Das Wasser ist pH-neutral und isotonisch. Dazu weist es einen Kochsalzgehalt von 0,9 + 0,3 % auf.The water used is preferably water which is physiologically, ie. H. in terms of pH and osmolality. The water is pH neutral and isotonic. It also has a saline content of 0.9 + 0.3%.
Es wird eine wässrige Lösung als Präparat erhalten, die problemlos zu lagern ist, da der Wirkstoff nicht auskristallisieren kann. Zudem ist keine Gefahr einer zusätzlichen Infektion gegeben, da es unter sterilen Bedingungen hergestellt werden kann.An aqueous solution is obtained as a preparation which can be stored without any problems since the active ingredient cannot crystallize out. In addition, there is no risk of an additional infection since it can be produced under sterile conditions.
Durch das erfindungsgemäße Präparat wird die Wirksamkeit des Präparates gegenüber folgenden Protozoen sichergestellt:The preparation according to the invention ensures the effectiveness of the preparation against the following protozoa:
- Trypanosomes congolense, Tryp. vivax, Tryp. Bruccei und T. Evansi- Trypanosomes congolense, Tryp. vivax, tryp. Bruccei and T. Evansi
- Piroplasmose (Piroplasma motasi, Piroplasma caballi)- Piroplasmosis (Piroplasma motasi, Piroplasma caballi)
Babesiose (Babesia bigemina, Babesia motasi, Babesia canis und andere Babesien) Theileria annulata.Babesiosis (Babesia bigemina, Babesia motasi, Babesia canis and other Babesia) Theileria annulata.
Nach einer weiteren bevorzugten Ausführungsform ist das erfindungsgemäße Präparat mit einer weiteren fiebersenkenden Substanz und/oder einem Schmerzmittel kombiniert. Diese Kombination hat den o. g. Vorteil, daß die Sterblichkeit der zu behandelnden Tiere stark verringert wird, da das mit der Protozoeninfektion auftretende hohe Fieber abgesenkt wird, bzw. die mit der Injektion verbundenen starken Schmerzen vermieden werden, die zu tödlichen Schockzuständen führen können.According to a further preferred embodiment, the preparation according to the invention is combined with a further antipyretic substance and / or a pain reliever. This combination has the above. Advantage that the mortality of the animals to be treated is greatly reduced, since the high fever occurring with the protozoan infection is reduced, or the severe pain associated with the injection is avoided, which can lead to fatal shock states.
Es wird vorzugsweise Lidocain, Procain oder deren Deri¬ vate verwandt. Als Fieber- und Schmerzmittel kann zu¬ sätzlich auch Acetylsalicylsäure bei Bedarf verwandt werden.Lidocaine, procaine or their derivatives are preferably used. If necessary, acetylsalicylic acid can also be used as a fever and pain reliever.
Nach einer weiteren Ausführungsform beinhaltet das er¬ findungsgemäße Präparat Isometadium-Hydrochlorid aus der Gruppe der Phenathridine als weiteren bioziden Wirkstoff.According to a further embodiment, the preparation according to the invention contains isometadium hydrochloride from the group of the phenathridines as a further biocidal active ingredient.
Eine bevorzugte Ausführungsform des erfindungsgemäßen Präparates weist folgende Zusammensetzung auf:A preferred embodiment of the preparation according to the invention has the following composition:
Wirkstoffe: Diminazen-di-aceturat,Active ingredients: diminazene di-aceturate,
PentamidinPentamidine
Phenazon Lidocain 33 , 5 Vol . -%Phenazone Lidocaine 33.5 vol. -%
Emulgator-Wasser-Emulsifier water
Gemisch: GlycerinMixture: glycerin
Methyl-Cellulose physiologisch angeglichenes Wasser 66,5 Vol.-3Methyl cellulose physiologically adjusted water 66.5 vol.-3
Die Zusammensetzung in Gew.-% der Wirkstoffe ist vorzugsweise:The composition in% by weight of the active ingredients is preferably:
Diminazen-di-aceturat 20,9 %Diminazene di-acetate 20.9%
Pentamidin 11,9 %Pentamidine 11.9%
Phenazon 37,3 %Phenazone 37.3%
Lidocain 29,9 %Lidocaine 29.9%
und die des Emulgator-Wasser-Gemisches in Vol.-%and that of the emulsifier-water mixture in vol .-%
Glycerin 20,0 %Glycerin 20.0%
Methyl-Cellulose 1,6 % physiologisch angeglichenes Wasser 78,4 %.Methyl cellulose 1.6% physiologically adjusted water 78.4%.
Das erfindungsgemäße Präparat bietet den Vorzug, daß bezogen auf das Volumen, der Wirkstoffgehalt gegenüber dem Stand der Technik verdoppelt werden kann.The preparation according to the invention has the advantage that, based on the volume, the active substance content can be doubled compared to the prior art.
Weitere Vorteile können darin gesehen werden, daß mit dem erfindungsgemäßen Präparat eine extremFurther advantages can be seen in the fact that an extreme with the preparation according to the invention
schnelle vollständige Heilung in 8 bis 12 Stunden erreicht wird, wobei eine erhöhte Effizienz gegen¬ über anderen Präparaten besteht, da alle Protozoen wirksam bekämpft werden können. Zudem erfolgt die Applikation mühelos, da die vorgeschriebenen Dosen kleiner sind als bei anderen trypanoziden Präparaten, so daß seltenere Behandlungen, d.h. mitunter eine einzige Injektion von 15 ml ausreichen.quick complete healing in 8 to 12 hours is achieved, with an increased efficiency compared to other preparations, since all protozoa can be effectively combated. In addition, the application is effortless, since the prescribed doses are smaller than with other trypanozid preparations, so that rarer treatments, ie sometimes a single injection of 15 ml are sufficient.
Als besonderer Vorteil ist anzusehen, daß mit einer einzigen Injektion, die zur Chemotherapie notwendig ist, auch ein dreimonatiger Schutz gegen Reinfektionen gegeben ist.A particular advantage is that a single injection, which is necessary for chemotherapy, also provides three-month protection against reinfections.
Als wesentlicher Vorteil ist es auch anzusehen, daß die Herstellungszeit gegenüber anderen Präparaten drastisch verringert werden kann, da die Komponenten einfach ohne Erhitzen durch Rühren vermischt werden können.It is also to be regarded as an essential advantage that the production time can be drastically reduced compared to other preparations, since the components can be easily mixed by heating without heating.
Weitere vorteilhafte Ausgestaltungen werden in den Unteransprüchen gekennzeichnet.Further advantageous refinements are characterized in the subclaims.
Detailierte Beschreibung der Erfindung und bester Weg zur Durchführung der ErfindungDetailed description of the invention and best way to practice the invention
Nachstehend wird die Erfindung anhand eines Bei¬ spiels näher erläutert.The invention is explained in more detail below with the aid of an example.
Eine bevorzugte Ausführungsform des pharmazeu¬ tischen Präparates wird hergestellt, indem die bioziden Wirkstoffe, die vorgesehenen wirkungsver-A preferred embodiment of the pharmaceutical preparation is produced by the biocidal active ingredients, the intended activity-reducing agents.
bessernden weiteren Komponenten und das Wasser- Emulgator-Gemisch gemischt werden.improving other components and the water Emulsifier mixture can be mixed.
Um 3,35 g einer Mischung aus biozidem Wirkstoff und wirkungsverbessernden Komponenten zu schaffen, werdenIn order to create 3.35 g of a mixture of biocidal active ingredient and effect-enhancing components
0,7 g Diminazen-di-aceturat,0.7 g diminazene di-acetate,
0,4 g Pentamidin,0.4 g pentamidine,
1,25 g Phenazon und1.25 g phenazone and
1,0 g Lidocain1.0 g lidocaine
miteinander vermischt.mixed together.
Anschließend wird das Emulgator-Wasser-Gemisch, das sich aus Glycerin 20 Vol.-%, Methyl-Cellulose 1,6 Vol.-% und physiologischem Wasser 78,4 Vol.-% zusammensetzt, den Aktivsubstanzen hinzugefügt. Das gebrauchsfertige Präparat kann steril filtriert abgefüllt werden.The emulsifier / water mixture, which is composed of glycerol 20% by volume, methyl cellulose 1.6% by volume and physiological water 78.4% by volume, is then added to the active substances. The ready-to-use preparation can be filled sterile filtered.
Voranstehend angeführte Mengenverhältnisse haben sich als am geeignetsten erwiesen, wobei für die erfindungsgemäße Stoffkombination auch andere Mengenverhältnisse möglich sind, so daß eine An¬ passung an jeweilige Verhältnisse möglich ist. The quantitative ratios mentioned above have proven to be the most suitable, although other quantitative ratios are also possible for the combination of substances according to the invention, so that an adaptation to the respective ratios is possible.
Claims
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EA199800218A EA199800218A1 (en) | 1995-08-21 | 1996-08-20 | PHARMACEUTICAL PREPARATION WITH TRIPANOSIDE PROPERTIES |
| APAP/P/1998/001196A AP827A (en) | 1995-08-21 | 1996-08-20 | Pharmaceutical preparation with trypanocidal qualities for veterinary use. |
| EP96929285A EP0845983A2 (en) | 1995-08-21 | 1996-08-20 | Pharmaceutical composition with trypanocidal properties |
| AU68750/96A AU6875096A (en) | 1995-08-21 | 1996-08-20 | Pharmaceutical composition with trypanocidal properties |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE1995130708 DE19530708C2 (en) | 1995-08-21 | 1995-08-21 | Pharmaceutical preparation with trypanocidal properties |
| DE19530708.9 | 1995-08-21 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1997006769A2 true WO1997006769A2 (en) | 1997-02-27 |
| WO1997006769A3 WO1997006769A3 (en) | 1997-05-09 |
Family
ID=7769997
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP1996/003657 WO1997006769A2 (en) | 1995-08-21 | 1996-08-20 | Pharmaceutical composition with trypanocidal properties |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0845983A2 (en) |
| AP (1) | AP827A (en) |
| AU (1) | AU6875096A (en) |
| DE (1) | DE19530708C2 (en) |
| EA (1) | EA199800218A1 (en) |
| OA (1) | OA10665A (en) |
| WO (1) | WO1997006769A2 (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998017266A3 (en) * | 1996-10-18 | 1998-06-25 | Alain Jacques Bourdichon | Pharmaceutical preparation |
| WO2000030611A3 (en) * | 1998-11-24 | 2000-08-31 | Chambord Ltd | Pharmaceutical preparation |
| WO2004105772A1 (en) * | 2003-06-03 | 2004-12-09 | Tropmed Gmbh | Pharmaceutical preparation for treating tropical parasitic diseases containing diaminazen-diaceturate and/or pentamidine |
| CN105168121A (en) * | 2015-08-28 | 2015-12-23 | 重庆布尔动物药业有限公司 | Diminazene compound for veterinary use and preparation method of diminazene compound |
| RU2638444C1 (en) * | 2016-12-15 | 2017-12-13 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Горский государственный аграрный университет" | Method of increasing medical efficiency for cattle pyroplasmosis with neozidin-m in association with laserpuncture |
| RU2638433C1 (en) * | 2016-12-15 | 2017-12-13 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Горский государственный аграрный университет" | Method for increast of therapeutic efficiency of diminasin-70 in case of cattle pyroplasmosis |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4309415C2 (en) * | 1993-03-19 | 1996-11-07 | Alain Jaques Bourdichon | Pharmaceutical preparation |
-
1995
- 1995-08-21 DE DE1995130708 patent/DE19530708C2/en not_active Expired - Fee Related
-
1996
- 1996-08-20 AP APAP/P/1998/001196A patent/AP827A/en active
- 1996-08-20 AU AU68750/96A patent/AU6875096A/en not_active Abandoned
- 1996-08-20 WO PCT/EP1996/003657 patent/WO1997006769A2/en not_active Application Discontinuation
- 1996-08-20 EP EP96929285A patent/EP0845983A2/en not_active Ceased
- 1996-08-20 EA EA199800218A patent/EA199800218A1/en unknown
-
1998
- 1998-02-20 OA OA9800022A patent/OA10665A/en unknown
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998017266A3 (en) * | 1996-10-18 | 1998-06-25 | Alain Jacques Bourdichon | Pharmaceutical preparation |
| WO2000030611A3 (en) * | 1998-11-24 | 2000-08-31 | Chambord Ltd | Pharmaceutical preparation |
| WO2004105772A1 (en) * | 2003-06-03 | 2004-12-09 | Tropmed Gmbh | Pharmaceutical preparation for treating tropical parasitic diseases containing diaminazen-diaceturate and/or pentamidine |
| CN105168121A (en) * | 2015-08-28 | 2015-12-23 | 重庆布尔动物药业有限公司 | Diminazene compound for veterinary use and preparation method of diminazene compound |
| RU2638444C1 (en) * | 2016-12-15 | 2017-12-13 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Горский государственный аграрный университет" | Method of increasing medical efficiency for cattle pyroplasmosis with neozidin-m in association with laserpuncture |
| RU2638433C1 (en) * | 2016-12-15 | 2017-12-13 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Горский государственный аграрный университет" | Method for increast of therapeutic efficiency of diminasin-70 in case of cattle pyroplasmosis |
Also Published As
| Publication number | Publication date |
|---|---|
| EA199800218A1 (en) | 1998-12-24 |
| AP827A (en) | 2000-04-28 |
| AP9801196A0 (en) | 1998-03-31 |
| AU6875096A (en) | 1997-03-12 |
| EP0845983A2 (en) | 1998-06-10 |
| DE19530708C2 (en) | 1999-01-07 |
| DE19530708A1 (en) | 1997-02-27 |
| WO1997006769A3 (en) | 1997-05-09 |
| OA10665A (en) | 2002-09-25 |
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