MX2014008172A - Pharmaceutical composition comprising isometamidium chloride in solution for the treatment of trypanosomiasis in animals. - Google Patents
Pharmaceutical composition comprising isometamidium chloride in solution for the treatment of trypanosomiasis in animals.Info
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- MX2014008172A MX2014008172A MX2014008172A MX2014008172A MX2014008172A MX 2014008172 A MX2014008172 A MX 2014008172A MX 2014008172 A MX2014008172 A MX 2014008172A MX 2014008172 A MX2014008172 A MX 2014008172A MX 2014008172 A MX2014008172 A MX 2014008172A
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 58
- QNZJTSGALAVCLH-UHFFFAOYSA-N Isometamidium chloride Chemical compound [Cl-].C12=CC(\N=N\NC=3C=C(C=CC=3)C(N)=N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 QNZJTSGALAVCLH-UHFFFAOYSA-N 0.000 title claims abstract description 25
- 229950004591 isometamidium chloride Drugs 0.000 title claims abstract description 25
- 241001465754 Metazoa Species 0.000 title claims abstract description 23
- 201000002311 trypanosomiasis Diseases 0.000 title claims abstract description 19
- AZSNMRSAGSSBNP-UHFFFAOYSA-N 22,23-dihydroavermectin B1a Natural products C1CC(C)C(C(C)CC)OC21OC(CC=C(C)C(OC1OC(C)C(OC3OC(C)C(O)C(OC)C3)C(OC)C1)C(C)C=CC=C1C3(C(C(=O)O4)C=C(C)C(O)C3OC1)O)CC4C2 AZSNMRSAGSSBNP-UHFFFAOYSA-N 0.000 claims abstract description 18
- SPBDXSGPUHCETR-JFUDTMANSA-N 8883yp2r6d Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O[C@@H]([C@@H](C)CC4)C(C)C)O3)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1C[C@H](C)[C@@H]([C@@H](C)CC)O[C@@]21O[C@H](C\C=C(C)\[C@@H](O[C@@H]1O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C1)[C@@H](C)\C=C\C=C/1[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\1)O)C[C@H]4C2 SPBDXSGPUHCETR-JFUDTMANSA-N 0.000 claims abstract description 18
- 229960002418 ivermectin Drugs 0.000 claims abstract description 18
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 15
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 15
- 239000003096 antiparasitic agent Substances 0.000 claims abstract description 13
- 244000045947 parasite Species 0.000 claims abstract description 13
- 229940125687 antiparasitic agent Drugs 0.000 claims abstract description 11
- 229920005862 polyol Polymers 0.000 claims abstract description 11
- 150000003077 polyols Chemical class 0.000 claims abstract description 11
- 230000002496 gastric effect Effects 0.000 claims abstract description 9
- VTDOEFXTVHCAAM-UHFFFAOYSA-N 4-methylpent-3-ene-1,2,3-triol Chemical compound CC(C)=C(O)C(O)CO VTDOEFXTVHCAAM-UHFFFAOYSA-N 0.000 claims abstract description 8
- 230000002685 pulmonary effect Effects 0.000 claims abstract description 8
- 241000282849 Ruminantia Species 0.000 claims abstract description 4
- 230000008030 elimination Effects 0.000 claims abstract description 4
- 238000003379 elimination reaction Methods 0.000 claims abstract description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 18
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 claims description 18
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 15
- BKVAAWMQOQLENB-UHFFFAOYSA-N 15-hydroxy stearic acid Chemical compound CCCC(O)CCCCCCCCCCCCCC(O)=O BKVAAWMQOQLENB-UHFFFAOYSA-N 0.000 claims description 13
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 11
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 11
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 11
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- 229940075579 propyl gallate Drugs 0.000 claims description 9
- 235000010388 propyl gallate Nutrition 0.000 claims description 9
- 239000000473 propyl gallate Substances 0.000 claims description 9
- MNQZXJOMYWMBOU-UHFFFAOYSA-N glyceraldehyde Chemical compound OCC(O)C=O MNQZXJOMYWMBOU-UHFFFAOYSA-N 0.000 claims description 7
- 150000002596 lactones Chemical class 0.000 claims description 6
- UMZCLZPXPCNKML-UHFFFAOYSA-N 2h-imidazo[4,5-d][1,3]thiazole Chemical class C1=NC2=NCSC2=N1 UMZCLZPXPCNKML-UHFFFAOYSA-N 0.000 claims description 3
- 241000283086 Equidae Species 0.000 claims description 3
- 125000006501 nitrophenyl group Chemical group 0.000 claims description 3
- 239000000203 mixture Substances 0.000 abstract description 34
- 229940102223 injectable solution Drugs 0.000 abstract description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 abstract 2
- SHBUUTHKGIVMJT-UHFFFAOYSA-N Hydroxystearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OO SHBUUTHKGIVMJT-UHFFFAOYSA-N 0.000 abstract 1
- 239000003937 drug carrier Substances 0.000 abstract 1
- 235000011187 glycerol Nutrition 0.000 abstract 1
- 229940072106 hydroxystearate Drugs 0.000 abstract 1
- UGKOYGZYLRKTJH-UHFFFAOYSA-O 3-[2-(3-amino-5-ethyl-6-phenylphenanthridin-5-ium-8-yl)iminohydrazinyl]benzenecarboximidamide Chemical compound C12=CC(N=NNC=3C=C(C=CC=3)C(N)=N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 UGKOYGZYLRKTJH-UHFFFAOYSA-O 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 239000003814 drug Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 229940079593 drug Drugs 0.000 description 6
- 208000030852 Parasitic disease Diseases 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000002141 anti-parasite Effects 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 238000009792 diffusion process Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- 238000004497 NIR spectroscopy Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000006184 cosolvent Substances 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 235000013601 eggs Nutrition 0.000 description 2
- 244000144980 herd Species 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 244000144972 livestock Species 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- -1 15-hydroxystearate compound Chemical class 0.000 description 1
- 241000238876 Acari Species 0.000 description 1
- QTANTQQOYSUMLC-UHFFFAOYSA-O Ethidium cation Chemical compound C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 QTANTQQOYSUMLC-UHFFFAOYSA-O 0.000 description 1
- 206010018873 Haemoconcentration Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 208000009182 Parasitemia Diseases 0.000 description 1
- 241001674048 Phthiraptera Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 241000243793 Trichostrongyloidea Species 0.000 description 1
- 241000223104 Trypanosoma Species 0.000 description 1
- 241000223099 Trypanosoma vivax Species 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 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 description 1
- 229950007095 diminazene Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 244000000050 gastrointestinal parasite Species 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 238000005534 hematocrit Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 230000024241 parasitism Effects 0.000 description 1
- 230000003108 parasitologic effect Effects 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000000654 trypanocidal effect Effects 0.000 description 1
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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Communication Control (AREA)
Abstract
The invention relates to a pharmaceutical composition comprising isometamidium chloride with a concentration of 1 % to 4 % (weight/volume), isopropylidene glycerol or glycerine formal with a concentration of 40 % to 95 % (weight/volume), a polyol with a concentration of 0 % to 50 % (weight/volume), 15-polyethylene glycol hydroxystearate with a concentration of 0.5 % to 7 % (weight/volume), in solution together with pharmaceutically acceptable carriers, for the treatment of trypanosomiasis in animals. The pharmaceutical composition is an injectable solution which is ready to use and can be administered intravenously, subcutaneously or intramuscularly to ruminants, equids and camelids. The composition can also include anti-parasitic agents, such as ivermectin, with a concentration of 1 % to 5 % (weight/volume) for the treatment of trypanosomiasis and the elimination of gastrointestinal and pulmonary parasites in animals.
Description
PHARMACEUTICAL COMPOSITION COMPRISING CHLORIDE OF
ISOMETAMIDIUM IN SOLUTION FOR THE TREATMENT OF TRYPANOSOMIASIS IN ANIMALS
FIELD OF THE INVENTION
The present invention is a pharmaceutical composition comprising isometamidium in solution for the treatment of trypanosomiasis in animals. The fields of application of the invention are the veterinary sector, animal health, tropical medicine and livestock production.
BACKGROUND OF THE INVENTION
In the production of animals in tropical areas, parasitic diseases represent one of the greatest challenges for veterinarians and livestock breeders since they cause significant economic losses to farmers, especially when they use selected breeds less adapted to the climate and more sensitive to these diseases.
In Venezuela, the prevalence of trypanosomiasis is 30%, and gastrointestinal parasites account for 100% of the herds. In the other countries of the tropical zone the results are similar. For this reason, strict control of pulmonary, gastrointestinal and trypanosomiasis parasites is necessary.
Ivermectin is one of the medicines used to fight parasitic diseases in tropical areas. Ivermectin is a broad spectrum antiparasitic, capable of effectively controlling gastrointestinal, pulmonary parasites, as well as lice, mites and ticks. This medicine has been used to control parasites or at least to lower parasite loads, thus increasing herd production.
For trypanosomiasis there is a number of limited effective drugs such as isometamidium, diminazene and ethidium.
Isometamidium is an antiparasitic especially active against blood parasites (parasites of the blood) and is one of the drugs that is shown to be most effective against trypanosomiasis. This drug is marketed in the form of tablets for extemporaneous use and no pharmaceutical composition containing isometamidium in solution in which isometamidium is stable and soluble has been described in the state of the art. The low solubility and low stability in aqueous solution of isometamidium causes that the drug has to be dissolved specifically for each preparation and that the surplus has to be eliminated. Isometamidium has to be prepared for each preparation with distilled water or boiled and cooled water
Before its use. With this method of preparation, there is a risk that an incorrect dosage is given or that adequate precautions are not taken and severe reactions occur at the site of the injection.
The present invention is directed to solve the problem posed by the technique, which is to provide a pharmaceutical composition of isometamidium for the treatment of trypanosomiasis and parasitic diseases in animals that prevents the isometamidium from having to be dissolved specifically in each preparation
DESCRIPTION OF THE INVENTION
The present invention is a pharmaceutical composition, comprising:
isometamidium chloride at a concentration between 1 and 4% (weight / volume),
isopropylideneglycerol or glycerinformal at a concentration between 40 and 95% (weight / volume),
a polyol at a concentration between 0 and 50% (weight / volume),
Polyethylene glycol 15-hydroxystearate at a concentration between 0.5 and 7% (weight / volume),
in solution together with pharmaceutically acceptable excipients, for the treatment of trypanosomiasis in animals.
In the present invention all percentages are weight / volume percentages. In the present invention the sum of the amounts of the compounds comprised in the pharmaceutical composition does not exceed the entire composition.
The pharmaceutical composition of the invention is a stable formulation in the form of ready-to-use injectable solution which does not require manipulation by the breeder or veterinarian and which allows the treatment of trypanosomiasis and most parasitic diseases affecting animals in the tropical zones.
The pharmaceutical composition of the invention is completely miscible in water, an important characteristic for isometamidium chloride and other antiparasitics that can be combined even when they are not soluble in water.
The composition of the invention achieves a controlled but effective diffusion of isometamidium chloride and other active ingredients that can be associated. To achieve this, the active ingredients must be kept soluble at the injection point. The composition of the invention comprises a polar organic solvent (isopropylideneglycerol or glycerinformal) and a polyol that create hydrogen bonds with the active ingredients and help keep them soluble and a surfactant (polyethylene glycol 15-hydroxystearate) which
acts as a cosolvent; upon contacting the composition with water, the active ingredients are combined with polyethylene glycol 15-hydroxystearate and do not precipitate.
The concentration of the polyethylene glycol 15-hydroxystearate in the composition determines the solubility of the active ingredients in water. Increasing the concentration of polyethylene glycol 15-hydroxystearate increases the solubility of isometamidium chloride and therefore increases its diffusion from the point of application. By decreasing the concentration of polyethylene glycol 15-hydroxystearate a slower or controlled diffusion of the active ingredients is achieved.
The polyethylene glycol 15-hydroxystearate compound also helps the pharmaceutical composition to be absorbed both subcutaneously and deep intramuscularly.
The polarity of the organic solvents chosen is such that when the water is incorporated into the composition no sudden changes in polarity occur and the solvation of the active principles does not occur; this allows that the active principles do not precipitate and that they do not form crystals.
One embodiment is the composition of the invention, wherein said isometamidium chloride is micronized isometamidium chloride.
Another embodiment is the composition of the invention, wherein the concentration of said isopropylidene glycerol or glycerinformal is 49% (weight / volume).
A further embodiment is the composition of the invention, wherein the concentration of said polyol is 40% (weight / volume). In a preferable embodiment, said polyol is propylene glycol.
One embodiment is the composition of the invention, wherein the concentration of polyethylene glycol 15-hydroxystearate is between 1 and 5% (weight / volume). In a preferable embodiment, said concentration is 2.5% (weight / volume).
One embodiment is the composition of the invention, wherein said excipients are:
propyl gallate between 0.02 and 0.05% (weight / volume),
polyvinylpyrrolidone between 0.5 and 5% (weight / volume),
N-methyl-2-pyrrolidone between 1 and 20% (weight / volume) and
2- (2-ethoxyethoxy) ethanol between 1 and 10% (weight / volume).
In a preferred embodiment, the concentration of said excipients is: propyl gallate 0.02% (weight / volume), polyvinylpyrrolidone 2% (weight / volume), N-methyl-2-pyrrolidone 2.5% (weight / volume) and 2- (2-ethoxyethoxy) ethanol 5% (weight / volume).
Another embodiment is the composition of the invention, wherein said polyvinylpyrrolidone has a K value between 12
and 90.
In the present invention, "K" is understood as the value of the kinematic viscosity.
The polyvinylpyrrolidone behaves as a cosolvent that increases the solubility of the active ingredients (to avoid any precipitation of the active principles) and the viscosity of the composition. By increasing the viscosity, it also acts as a controlled release agent.
One embodiment is the composition of the invention, wherein said animals are selected from the group consisting of ruminants, equidae and camelids.
A further embodiment is the composition of the invention, wherein said pharmaceutical composition is administered parenterally. In a preferred embodiment, said pharmaceutical composition is administered intravenously, subcutaneously or intramuscularly.
A further embodiment is the pharmaceutical composition of the invention, which further comprises one or more antiparasitic agents for the treatment of trypanosomiasis and the elimination of gastrointestinal and pulmonary parasites in animals. A preferred embodiment is the composition of the invention, wherein the concentration of said antiparasitic agent is between 1 and 5% (weight / volume). In a
more preferable embodiment, said concentration is 2% (weight / volume).
Another embodiment is the composition of the invention, wherein said antiparasitic agents are selected from the group consisting of probenzimidazoles, imidazothiazoles, salicylanilides, nitrophenyl substitutes and macrocyclic lactones. In a preferred embodiment, said macrocyclic lactone is ivermectin.
The pharmaceutical composition of the invention that combines in the same product isometamidium chloride and ivermectin is useful both for the treatment of trypanosomiasis and the treatment of gastrointestinal and pulmonary parasites and reduces the handling of the animals and the time of administration. Said composition can be used in the prophylactic plans in the control of trypanosomiasis and gastrointestinal and pulmonary parasites.
PREFERRED EMBODIMENTS
Example 1. Development of different pharmaceutical compositions whose active ingredients are isometamidium chloride and ivermectin.
Composition 1
A pharmaceutical composition was prepared using a
oily vehicle, the lipophilic Labrafac® (C8-C10 glycerides), whose formula was:
Compound Amount in% p / v
Ivermectin 2.00
Isometamidium Chloride 2.40
Labrafac® lipophilic 95,99
Cabosil® (dioxosilane) 2.00
Propyl gallate 0.02
BHT (butylhydroxytoluene) 0.10
BHA (butylhydroxyanisole) 0.10
The results with this composition were not very positive. When this formula was applied to animals subcutaneously and intramuscularly, edema was formed. Blood determinations and PCR studies against
Trypanosoma vivax positive values were observed, indicating that this formula was not properly released from the application site (very slow release).
Composition 2
A pharmaceutical composition with formula was prepared:
Compound Amount in% p / v
Ivermectin 2.00
Isometamidium Chloride 2.40
micronized
Isopropilidenoglicerol 50.00
Propyl gallate 0.02
Polyvinylpyrrolidone (Colidon K - 2.00
30)
2- (2-ethoxyethoxy) ethanol) 5.00
N-methyl-2-pyrrolidone 2.50
(Pharmasolve)
Propylene glycol 40.82
Pharmacist
When elaborating this second formula it was appreciated that the isometamidium chloride was not completely soluble.
Composition 3
A pharmaceutical composition was prepared which included all the components of composition 2 and also polyethylene glycol 15-hydroxystearate (Solutol SH 15), whose formula was:
Compound Amount in% p / v
Ivermectin 2.00
Isometamidium Chloride 2, 0
microni zado
Isopropilidenoglicerol 49.00
Propyl gallate 0.02
Poly inylpyrrolidone (Colidon K 2.00
- 30)
2- (2-ethoxyethoxy) ethanol 5.00
(Transcutol)
N-methyl-2-pyrrolidone 2.50
(Pharmasolve)
Pharmaceutical Propylene Glycol 40.0
15-hydroxystearate of 2.50
polyethylene glycol (Solutol SH 15)
With this formula it was found that ivermectin and isometamidium chloride were completely soluble.
A stability study of the active principles of composition 3 was carried out for 2 years, and it was obtained that ivermectin remains almost unchanged and isometamidium chloride degraded less than 3%, thus remaining within very acceptable ranges of stability , so that composition 3 is stable during all this time.
Example 2. Stability of the active ingredients ivermectin and isometamidium chloride in aqueous solution.
15 ml of composition 3 were measured and placed in a graduated cylinder with a lid and brought to a final volume of 50 ml with distilled water, obtaining a final solution containing 300 mg of ivermectin and 360 mg of isometamidium chloride. The solution was analyzed by NIR (Near-Infrared spectroscopy, near infrared spectroscopy) and quantified, obtaining the following results: 311.3 mg of ivermectin and 358.52 mg of isometamidium chloride.
The previous solution was placed in an oven to evaluate the stability of the mixture subjected to a high stress (50 ° C temperature and relative humidity of 75%). The study was carried out for a period of 5 days taking 1 my cylinder diary and analyzing it by NIR obtaining the following
results:
Table 1. Amount of ivermectin and isometamxdiura chloride present in the solution
The table above shows that ivermectin has a low degradation in the presence of water and that the chloride of isometamidium has a slightly higher degradation.
E p e 3. Efficacy of composition 3 in field studies.
The efficacy of composition 3 was determined by the test on 6 animals. The animals presented high levels of gastrointestinal parasitism evidenced by the coprologias, where eggs of the type of the superfamily of Thichostrongyloidea were mainly appreciated.
After the first 12 days post infection and having confirmed the appearance of parasitemia by parasitological tests of hemoconcentration (oo) for the detection of circulating Trypanosomas in the 4 experimental animals, these were treated with composition 3 and with chloride
isometamidium in the form of tablets for extemporaneous use. The presence of eggs in the feces was confirmed by coprological examinations before and after the treatment. The duration of the study was 50 consecutive days.
Both trial drugs showed trypanocidal action in only 24 hours after treatment. Composition 3 was able to eliminate the parasites, even in extreme conditions of maximum parasitaemia. The animals treated with composition 3 recovered better their hematocrit (Hto) and lowered their parasitic load of Trichostrongyloidea.
Claims (34)
1. A pharmaceutical composition, comprising: isometamidium chloride at a concentration between 1 and 4% (weight / volume), isopropylideneglycerol or glycerinformal at a concentration between 40 and 95% (weight / volume), a polyol at a concentration between 0 and 50% (weight / volume), Polyethylene glycol 15-hydroxystearate at a concentration between 1 and 5% (weight / volume), in solution together with pharmaceutically acceptable excipients, for the treatment of trypanosomiasis in animals, where said excipients are: propyl gallate between 0.02 and 0.05% (weight / volume), polyvinylpyrrolidone between 0.5 and 5% (weight / volume), N-methyl-2-pyrrolidone between 1 and 20% (weight / volume) and 2- (2-ethoxyethoxy) ethanol between 1 and 10% (weight / volume) .
2. Pharmaceutical composition according to claim 1, wherein said isometamidium chloride is micronized isometamidium chloride.
3. Pharmaceutical composition according to one of claims 1 or 2, wherein the concentration of said isopropylidene glycerol or glycerinformal is 49% (weight / volume).
4. Pharmaceutical composition according to any of claims 1 to 3, wherein the concentration of said polyol is 40% (weight / volume).
5. Pharmaceutical composition according to any of claims 1 to 4, wherein said polyol is propylene glycol.
6. Pharmaceutical composition according to any of claims 1 to 5, wherein the concentration of polyethylene glycol 15-hydroxystearate is 2.5% (w / v).
7. Pharmaceutical composition according to any of claims 1 to 6, wherein the concentration of said excipients is: propyl gallate 0.02% (weight / volume), polyvinylpyrrolidone 2% (weight / volume), N-methyl-2-pyrrolidone 2.5 % (weight / volume) and 2- (2-ethoxyethoxy) ethanol 5% (weight / volume).
8. Pharmaceutical composition according to any of claims 1 to 7, wherein said polyvinyl pyrrolidone has a K value between 12 and 90.
9. Pharmaceutical composition according to any of claims 1 to 8, wherein said animals are selected from the group consisting of ruminants, equidae and camelids.
10. Pharmaceutical composition according to any of claims 1 to 9, wherein said pharmaceutical composition is administered parenterally.
11. Pharmaceutical composition according to claim 10, wherein said pharmaceutical composition is administered intravenously, subcutaneously or intramuscularly.
12. A pharmaceutical composition according to any of claims 1 to 11, further comprising one or more antiparasitic agents for the treatment of trypanosomiasis and the elimination of gastrointestinal and pulmonary parasites in animals.
13. Pharmaceutical composition according to the claim 12, where the concentration of said antiparasitic agent is between 1 and 5% (weight / volume).
14. Pharmaceutical composition according to the claim 13, where said concentration is 2% (weight / volume).
15. Pharmaceutical composition according to any of claims 12 to 14, wherein said antiparasitic agents are selected from the group consisting of probenzimidazoles, imidazothiazoles, salicylanilides, nitrophenyl substitutes and macrocyclic lactones.
16. Pharmaceutical composition according to claim 15, wherein said macrocyclic lactone is ivermectin.
17. A pharmaceutical composition, comprising: isometamidium chloride at a concentration between 1 and 4% (weight / volume), isopropylideneglycerol or glycerinformal at a concentration between 40 and 95% (weight / volume), a polyol at a concentration between 0 and 50% (weight / volume), Polyethylene glycol 15-hydroxystearate at a concentration between 0.5 and 7% (weight / volume), in solution together with pharmaceutically acceptable excipients, for the treatment of trypanosomiasis in animals.
18. Pharmaceutical composition according to claim 1, wherein said isometamidium chloride is micronized isometamidium chloride.
19. Pharmaceutical composition according to one of claims 1 or 2, wherein the concentration of said isopropylidene glycerol or glycerinformal is 49% (weight / volume).
20. Pharmaceutical composition according to any of claims 1 to 3, wherein the concentration of said polyol is 40% (weight / volume).
21. Pharmaceutical composition according to any of claims 1 to 4, wherein said polyol is propylene glycol.
22. Pharmaceutical composition according to any of claims 1 to 5, wherein the concentration of polyethylene glycol 15-hydroxystearate is between 1 and 5% (weight / volume).
23. Pharmaceutical composition according to claim 6, wherein said concentration is 2.5% (weight / volume).
24. Pharmaceutical composition according to any of claims 1 to 7, wherein said excipients are: propyl gallate between 0.02 and 0.05% (weight / volume), polyvinylpyrrolidone between 0.5 and 5% (weight / volume), N-methyl-2-pyrrolidone between 1 and 20% (weight / volume) and 2- (2-ethoxyethoxy) ethanol between 1 and 10% (weight / volume) .
25. Pharmaceutical composition according to claim 8, wherein the concentration of said excipients is: propyl gallate 0.02% (weight / volume), polyvinylpyrrolidone 2% (weight / volume), N-methyl-2-pyrrolidone 2.5% (weight / volume) and 2- (2-ethoxyethoxy) ethanol 5% (weight / volume).
26. Pharmaceutical composition according to one of claims 8 or 9, wherein said polyvinylpyrrolidone has a K value between 12 and 90.
27. Pharmaceutical composition according to any of claims 1 to 10, wherein said animals are selected from the group consisting of ruminants, equidae and camelids.
28. Pharmaceutical composition according to any of the claims 1 to 11, wherein said pharmaceutical composition is administered parenterally.
29. Pharmaceutical composition according to claim 12, wherein said pharmaceutical composition is administered intravenously, subcutaneously or intramuscularly.
30. Pharmaceutical composition according to any of claims 1 to 13, further comprising one or more antiparasitic agents for the treatment of trypanosomiasis and the elimination of gastrointestinal and pulmonary parasites in animals.
31. Pharmaceutical composition according to claim 14, wherein the concentration of said antiparasitic agent is between 1 and 5% (weight / volume).
32. Pharmaceutical composition according to claim 15, wherein said concentration is 2% (weight / volume).
33. Pharmaceutical composition according to any of claims 14 to 16, wherein said antiparasitic agents are selected from the group consisting of probenzimidazoles, imidazothiazoles, salicylanilides, nitrophenyl substitutes and macrocyclic lactones.
34. Pharmaceutical composition according to claim 17, wherein said macrocyclic lactone is ivermectin.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES201230092A ES2416004B1 (en) | 2012-01-24 | 2012-01-24 | PHARMACEUTICAL COMPOSITION THAT INCLUDES ISOMETAMIDIUM CHLORIDE IN SOLUTION FOR THE TREATMENT OF TRIPANOSOMIASIS IN ANIMALS. |
| PCT/ES2012/070550 WO2013110830A1 (en) | 2012-01-24 | 2012-07-19 | Pharmaceutical composition comprising isometamidium chloride in solution for the treatment of trypanosomiasis in animals |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2014008172A true MX2014008172A (en) | 2014-10-06 |
Family
ID=46963763
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2014008172A MX2014008172A (en) | 2012-01-24 | 2012-07-19 | Pharmaceutical composition comprising isometamidium chloride in solution for the treatment of trypanosomiasis in animals. |
Country Status (16)
| Country | Link |
|---|---|
| AP (1) | AP2014007798A0 (en) |
| AR (1) | AR089037A1 (en) |
| BR (1) | BR112014016926A8 (en) |
| CL (1) | CL2014001780A1 (en) |
| CO (1) | CO6990714A2 (en) |
| CR (1) | CR20140278A (en) |
| DO (1) | DOP2014000161A (en) |
| EC (1) | ECSP14010152A (en) |
| ES (1) | ES2416004B1 (en) |
| GT (1) | GT201400159A (en) |
| MA (1) | MA35868B1 (en) |
| MX (1) | MX2014008172A (en) |
| NI (1) | NI201400075A (en) |
| PE (1) | PE20141472A1 (en) |
| UY (1) | UY34479A (en) |
| WO (1) | WO2013110830A1 (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2024008B (en) * | 1978-06-28 | 1983-02-16 | Merck & Co Inc | Compositions for treating trypanosomiasis infections |
| GB8805286D0 (en) * | 1988-03-05 | 1988-04-07 | Schering Agrochemicals Ltd | Trypanocides |
| US5496830A (en) * | 1994-09-14 | 1996-03-05 | Johns Hopkins University | Inhibition of hemoflagellates by camptothecin compounds |
| DE19854143A1 (en) * | 1998-11-24 | 2000-05-25 | Chambord Ltd | Antiprotozoal composition useful for treating e.g. piroplasmosis, malaria and sleeping sickness comprises pentamidine and an additional biocide |
| FR2819188B1 (en) * | 2001-01-08 | 2003-03-14 | Virbac Sa | WATER-SOLUBLE PULVERULENT OR GRANULATED COMPOSITIONS BASED ON PHENANTHRIDINES AND USES THEREOF |
| AR060926A1 (en) * | 2007-05-14 | 2008-07-23 | Ciriaco Quiroga | PROPOFOL TRANSPARENT ANESTHETIC SOLUTION, WITH LOW VENOUS IRRITATION. |
| KR20080102010A (en) * | 2007-05-17 | 2008-11-24 | 대원제약주식회사 | Injectable compositions comprising propofol and methods for preparing the same |
| DE102008007381A1 (en) * | 2008-02-01 | 2009-08-13 | Dritte Patentportfolio Beteiligungsgesellschaft Mbh & Co.Kg | Amidines and guanidines and their derivatives for the treatment of diseases |
| WO2011042565A2 (en) * | 2009-10-09 | 2011-04-14 | Instituut Voor Tropische Geneeskunde | Antiprotozoal activity |
-
2012
- 2012-01-24 ES ES201230092A patent/ES2416004B1/en not_active Expired - Fee Related
- 2012-07-19 AP AP2014007798A patent/AP2014007798A0/en unknown
- 2012-07-19 PE PE2014001030A patent/PE20141472A1/en not_active Application Discontinuation
- 2012-07-19 BR BR112014016926A patent/BR112014016926A8/en not_active Application Discontinuation
- 2012-07-19 MX MX2014008172A patent/MX2014008172A/en unknown
- 2012-07-19 WO PCT/ES2012/070550 patent/WO2013110830A1/en not_active Ceased
- 2012-11-29 AR ARP120104496A patent/AR089037A1/en unknown
- 2012-11-29 UY UY0001034479A patent/UY34479A/en not_active Application Discontinuation
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2014
- 2014-06-13 CR CR20140278A patent/CR20140278A/en unknown
- 2014-06-16 CO CO14130085A patent/CO6990714A2/en unknown
- 2014-07-03 CL CL2014001780A patent/CL2014001780A1/en unknown
- 2014-07-14 NI NI201400075A patent/NI201400075A/en unknown
- 2014-07-14 DO DO2014000161A patent/DOP2014000161A/en unknown
- 2014-07-15 MA MA37215A patent/MA35868B1/en unknown
- 2014-07-17 GT GT201400159A patent/GT201400159A/en unknown
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Also Published As
| Publication number | Publication date |
|---|---|
| UY34479A (en) | 2013-07-31 |
| PE20141472A1 (en) | 2014-11-05 |
| MA35868B1 (en) | 2014-12-01 |
| DOP2014000161A (en) | 2014-08-15 |
| GT201400159A (en) | 2015-11-19 |
| AR089037A1 (en) | 2014-07-23 |
| ES2416004B1 (en) | 2014-01-28 |
| CO6990714A2 (en) | 2014-07-10 |
| ES2416004A1 (en) | 2013-07-29 |
| BR112014016926A8 (en) | 2017-07-04 |
| BR112014016926A2 (en) | 2017-06-13 |
| CL2014001780A1 (en) | 2014-10-24 |
| ECSP14010152A (en) | 2015-08-31 |
| WO2013110830A1 (en) | 2013-08-01 |
| CR20140278A (en) | 2014-12-02 |
| NI201400075A (en) | 2015-04-13 |
| AP2014007798A0 (en) | 2014-07-31 |
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