GB2329125A - Warfarin compositions - Google Patents

Warfarin compositions Download PDF

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Publication number
GB2329125A
GB2329125A GB9719315A GB9719315A GB2329125A GB 2329125 A GB2329125 A GB 2329125A GB 9719315 A GB9719315 A GB 9719315A GB 9719315 A GB9719315 A GB 9719315A GB 2329125 A GB2329125 A GB 2329125A
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GB
United Kingdom
Prior art keywords
antibiotic
warfarin
tetracycline
salt
composition
Prior art date
Legal status (The legal status 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 status listed.)
Granted
Application number
GB9719315A
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GB9719315D0 (en
GB2329125B (en
Inventor
Richard M Poch
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Reckitt Benckiser LLC
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Reckitt Benckiser LLC
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Publication date
Application filed by Reckitt Benckiser LLC filed Critical Reckitt Benckiser LLC
Priority to GB9719315A priority Critical patent/GB2329125B/en
Publication of GB9719315D0 publication Critical patent/GB9719315D0/en
Publication of GB2329125A publication Critical patent/GB2329125A/en
Application granted granted Critical
Publication of GB2329125B publication Critical patent/GB2329125B/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Classifications

    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES, AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/002Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing a foodstuff as carrier or diluent, i.e. baits
    • A01N25/004Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing a foodstuff as carrier or diluent, i.e. baits rodenticidal
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES, AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/14Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings
    • A01N43/16Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings with oxygen as the ring hetero atom

Abstract

The presence of a small amount of an antibiotic, such as tetracycline, in warfarin-containing rodent baits enhances the toxicity of warfarin against rodents which have heretofore shown apparent resistance to warfarin.

Description

IMPROVEMENTS IN PESTICIDES This invention relates to methods for enhancing the toxicity of warfarin in rodenticidal compositions and to warfarin-containing rodenticidal compositions which are effective against warfarin-resistant rodents.

Warfarin, 3-a-phenyl-ss-acetylethyl-4-hydroxy coumarin, which has the chemical structure <img class="EMIRef" id="026495163-00010001" />

has, since the 1950s been in use as an active ingredient in rodenticidal compositions. In addition to its use as a rodenticide, warfarin is also used, in generally smaller amounts, in humans to provide similar anti-coagulating effects.

The basis for the effectiveness of warfarin as a rodenticide lies in the fact that it is effective in small, multiple doses. One or two doses of the compound are seldom fatal if taken at the recommended concentration: thus the hazard of acute toxicity to man, domestic animals, and wildlife is greatly reduced. In practical use, warfarin has been sold as a "concentrate" containing 0.5 percent of the active ingredient. This is diluted for use with a suitable bait, to a concentration of about 0.025 percent. Baits commonly used are cereal products, corn meal, rolled oats, mixed animal feeds, and similar products.

Baits containing warfarin can be placed in stations and left there for considerable periods of time, so that the rodent populations may partake of several doses in sequence. Usually the rodents begin to die after four or five daily doses of the materials, and the population is greatly reduced or eradicated in approximately three weeks. Death is caused by hemorrhages, brought about by the action of the warfarin in reducing the clotting power of the blood. These hemorrhages may be external or internal and can be initiated by very slight injury or capillary damage. One of the other advantages of warfarin is that, because multiple ingestions are required to kill the rodents, they do not develop bait shyness.

Beginning in the early 1970s, rodents -- particularly rats -- began showing resistance to warfarin baits. The general assumption was that such resistance had a genetic basis. Similar resistance was found regarding the use of warfarin as an anti-coagulant in treating humans and, to a certain extent, a possible genetic, or at least familial, basis for the decrease in effectiveness of warfarin in treating humans has been substantiated.

As far as warfarin in rodenticides is concerned, the development of resistance has spawned the search for other rodenticidal compounds, including particularly other coumarin derivatives such as flocoumafen, difenacoum and brodifacoum. Brodifacoum currently appears to be the compound of choice in rodenticidal compositions, although others are used. Unfortunately, many of these other compounds also exhibit toxicity toward household pets and therefore use of brodifacoum-containing rodenticidal compositions has to be carefully controlled in a household environment.

As noted above, warfarin, which is often referred to as a "first generation anti-coagulant rodenticide", has the advantage of very low toxicity toward household pets and wildlife and its use does not involve the need to take special precaution to avoid contact with household pets or wildlife. Since warfarin has been available for over 40 years and there have been extensive studies of its effectiveness and toxicological properties, it would be extremely advantageous to be able to use warfarin in commercial rodenticide formulations.

It has now been discovered that the efficacy of warfarin in rodenticidal compositions can be enhanced by adding an antibiotic to the warfarin-containing composition. An example of an appropriate antibiotic is tetracycline, or one of its salts or one of its derivatives, and the antibiotic should be added in sufficient amount to inhibit the action of bacteria present in the gastrointestinal tract of the rodent.

Accordingly, this invention also provides a rodenticidal composition which comprises a rodenticidally effective amount of warfarin and an antibiotic in sufficient amount to inhibit the action of bacteria present in the gastrointestinal tract of the rodent. The antibiotic may be tetracycline, or one of its salts or a derivative thereof. In these compositions, only a relatively small amount of antibiotic is required, generally ranging from about 0.05% to 1.0% based on the weight of the bait.

The invention further provides a method for killing rodents by causing the rodents to ingest a composition containing a rodenticidally effective amount of warfarin and an antibiotic in an amount sufficient to inhibit the action of bacteria present in the gastrointestinal tract of said rodent. The antibiotic may be tetracycline, or one of its salts or derivatives, or others such as cotrimoxazole, metronidazole, erythromycin fluconazole, isoniazid, miconazole, ciprofloxacin, and itraconazole.

Without wishing to be bound by any scientific theory, it is believed that warfarin "resistance" in rodents may not be true resistance, but rather the result of bacterial action which rapidly metabolizes the warfarin so that the substance no longer acts against the rodents in its customary manner. The addition of a small amount of an antibiotic agent to the rodenticidal composition has the effect of substantially inhibiting the action of such bacteria, thereby allowing warfarin to metabolize in its usual manner and act as an effective rodenticide. It is therefore not necessary to kill off all of the bacteria which act against warfarin, but only to inhibit such action for sufficient time to enable the warfarin to metabolize normally. Thus, the amount of antibiotic required in the bait composition need only be in the range of, for example, from about 0.05% to 1.0% by weight of the bait compositions. Warfarin used at a level of 0.005-0.05% in said bait compositions is sufficiently effective in controlling rodents.

Any antibiotic which acts against the warfarin-inhibiting bacteria is suitable for use in the practice of this invention. These include the well known tricyclic and tetracyclic antibiotics such as tetracycline, its salts and derivatives, for example, tetracycline hydrochloride. Other usable antibiotics include cotrimoxazole, metronidazole, erythromycin, fluconazole, isoniazid, miconazole, itraconazole and ciprofloxacin, as well as their salts and derivatives. The choice of the antibiotic to be used will depend on various factors, including compatibility with other ingredients in the rodenticidal composition, stability, cost, palatability toward the target species, etc. The choice of the particular antibiotic to be employed is well within the knowledge of persons skilled in the art.

Warfarin-containing rodenticidal compositions are typically formulated as granular bait compositions containing from 50-300 ppm, preferably about 250 ppm, of warfarin. The amount of antibiotic to be added to such composition should be from about 0.005 to 0.05% by weight of the warfarin. The bait is typically formulated with from 0.5% to 2.5% of warfarin concentrate in a suitable binder such as corn oil. If corn oil is used as a binder, it can be present in an amount of from about 0.5% to about 2% of the total composition. The binder and warfarin are then mixed in with a grain-based bait composition of the type known in the art. Prior to mixing the composition, an appropriate amount of an antibiotic, such as tetracycline hydrochloride, is added. In addition, an antioxidant may be added to the composition as a preservative for both the warfarin and the antibiotic.

The compositions of this invention may be used for a variety of rodent control products to reduce the population of house mice, rats, field mice, ground squirrels, and other rodents which may be of concern to public health.

Example I A typical formulation has the following constituents: Ingredient Grain carrier 93.9 Corn oil 1.0 Warfarin Concentrate (0.5%) 5.0 Tetracycline hydrochloride 0.1 Total 100.0 Example II A formulation similar to Example I containing only 50 ppm warfarin was tested on groups of warfarin-resistant Norway rats from Chicago, Illinois, and compared against similar formulations without antibiotic. Each group tested had 10 animals. The results are shown in the following table, which contains mortality figures after 5 days of feeding.

Group Antibiotic Mortalitv T-l Yes 9/10 T-2 No 5/10 The presence of the antibiotic tetracycline hydrochloride appears to enhance the toxicity of warfarin.

Claims (16)

We claim:
1. A method of enhancing the efficacy of warfarin in a rodenticide which comprises adding an antibiotic to a warfarin-containing rodenticidal composition.
2. A method according to claim 1 wherein the antibiotic is added in sufficient amount to inhibit the action of bacteria present in the gastrointestinal tract of a rodent.
3. A method according to claims 1 or 2 wherein the antibiotic is tetracycline, cotrimoxazole, metronidazole, erythromycin, fluconazole, isoniazid, miconazole, ciprofloxacin, itraconazole, or a salt or derivative thereof.
4. A method according to claim 3 wherein the antibiotic is tetracycline or a salt or a derivative thereof.
5. A method according to claim 4 in which the antibiotic is tetracycline or a salt thereof.
6. A method for killing rodents which comprises causing the rodents to ingest a composition comprising a rodenticidally effective amount of warfarin and an antibiotic in an amount sufficient to inhibit the action of bacteria present in the gastrointestinal tract of said rodents.
7. A method according to claim 6 in which the antibiotic is tetracycline, cotrimoxazole, metronidazole, erythromycin, fluconazole, isoniazid, miconazole, ciprofloxacin, itraconazole, or a salt or derivative thereof.
8. A method according to claim 7 in which the antibiotic is tetracycline or a salt or a derivative thereof.
9. A method according to claim 8 in which the antibiotic is tetracycline or a salt thereof.
10. A composition for killing rodents comprising a rodenticidally effective amount of warfarin and an antibiotic in sufficient amount to inhibit the action of bacteria present in the gastrointestinal tract of the rodent.
11. A composition according to claim 10 in which the antibiotic is tetracycline, cotrimoxazole, metronidazole, erythromycin, fluconazole, isoniazid, miconazole, ciprofloxacin, itraconazole, or a salt or derivative thereof.
12. A composition according to claim 11 in which the antibiotic is tetracycline or a salt or derivative thereof.
13. A composition according to claim 12 in which the antibiotic is tetracycline or a salt thereof.
14. A composition according to claim 13 in which said composition comprises warfarin and tetracycline or a salt thereof suspended in a solid carrier.
15. A composition according to claim 11 in which the antibiotic is present in an amount of from about 0.05 to 1.0% based on the weight of the composition.
16. A composition according to claim 15 in which warfarin is present in an amount of from about 50 to about 300 ppm.
GB9719315A 1997-09-12 1997-09-12 Enhancing warfarin efficacy Expired - Fee Related GB2329125B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
GB9719315A GB2329125B (en) 1997-09-12 1997-09-12 Enhancing warfarin efficacy

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9719315A GB2329125B (en) 1997-09-12 1997-09-12 Enhancing warfarin efficacy
GBGB9804867.1A GB9804867D0 (en) 1997-09-12 1998-03-09 Improvements in pesticides

Publications (3)

Publication Number Publication Date
GB9719315D0 GB9719315D0 (en) 1997-11-12
GB2329125A true GB2329125A (en) 1999-03-17
GB2329125B GB2329125B (en) 2002-03-20

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GB9719315A Expired - Fee Related GB2329125B (en) 1997-09-12 1997-09-12 Enhancing warfarin efficacy
GBGB9804867.1A Ceased GB9804867D0 (en) 1997-09-12 1998-03-09 Improvements in pesticides

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999045778A1 (en) * 1998-03-09 1999-09-16 Reckitt Benckiser Inc. Enhancing the toxicity of warfarin in rodents
CN103329901A (en) * 2013-07-18 2013-10-02 广东省农业科学院植物保护研究所 Anticoagulative rodenticide enhancer and preparation method and application thereof

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7814702B2 (en) 2007-12-14 2010-10-19 Smg Brands, Inc. Rodent trap having a pivoting platform
US7886479B2 (en) 2007-12-14 2011-02-15 Smg Brands, Inc. Rodent trap having compressive trapping members
US8490323B2 (en) 2007-12-14 2013-07-23 Oms Investments, Inc. Rodent trap having a pivoting platform
US7921593B2 (en) 2007-12-14 2011-04-12 Smg Brands, Inc. Rodent trap having a snare

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE623572A (en) * 1961-10-13

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Chemical Abstracts 85:187800 and DE002515639 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999045778A1 (en) * 1998-03-09 1999-09-16 Reckitt Benckiser Inc. Enhancing the toxicity of warfarin in rodents
CN103329901A (en) * 2013-07-18 2013-10-02 广东省农业科学院植物保护研究所 Anticoagulative rodenticide enhancer and preparation method and application thereof

Also Published As

Publication number Publication date
GB9804867D0 (en) 1998-04-29
GB2329125B (en) 2002-03-20
GB9719315D0 (en) 1997-11-12

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Date Code Title Description
732E Amendments to the register in respect of changes of name or changes affecting rights (sect. 32/1977)
PCNP Patent ceased through non-payment of renewal fee

Effective date: 20060912