AP105A - Treatment of animals. - Google Patents
Treatment of animals. Download PDFInfo
- Publication number
- AP105A AP105A APAP/P/1988/000111A AP8800111A AP105A AP 105 A AP105 A AP 105A AP 8800111 A AP8800111 A AP 8800111A AP 105 A AP105 A AP 105A
- Authority
- AP
- ARIPO
- Prior art keywords
- animal
- tetracycline
- derivative
- animal body
- released
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- 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
- A61K31/65—Tetracyclines
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Dermatology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a use of an antibiotic
Description
THIS INVENTION relates to the treatment of animals.
According to a first aspect of the invention, there is provided a use of an antibiotic in the treatment of an animal, by administering the antibiotic to the animal through implantation thereof into the animal body.
The antibiotic may be implanted subcutaneously into the animal body, and may be implanted in controlled release form so that a prophylactically effective or immunizing quantity of the antibiotic is released into the animal body over a period of time, eg at least 10 days, to permit the animal body to build up immunity against a disease.
The prophylactically effective quantity of antibiotic which is released may be at a relatively low non-therapeutic dosage level, eg between 0,1 and 2 mg antibiotic per kilogram animal body mass per day. The bloodstream of the animal may simultaneously be challenged, eg by way of injection, with virulent organisms of the disease, thereby
ΑΡ0 0 0 1 0 5
BAD ORIGINAL φ
-3allowing the animal to build up the immunity against the disease.
The Applicant believes that the use of the antibiotic according to the first aspect of the invention will be particularly, but not necessarily exclusively, effective in rendering animals immune to heartwater, anaplasmosis, mastitis, and/or redwater.
The animals.may be ruminants such as cattle, sheep, goats or the like.
In one embodiment of the invention, the antibiotic may be in solid form, eg in tablet, capsule, pellet, rod or the like form. In another embodiment of the invention, it may be in the form of a paste. In both these foims, the antibiotic will hence be in a form in which it is released slowly over a period of time and in controlled fashion into the body.
The antibiotic may be tetracycline or a derivative thereof. For example, it may be a tetracycline derivative, viz doxycycline hydrochloride ie the hemihydrate, hemiethanolate of (4S,4aR,5S,SaR,6R, 12aS)-N-(2-carbamoyl-l,4,4a,5,5a,6,ll, 12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11dioxonaphthacen-4-yl)-dimethylammonium chloride, an
BAD ORIGINAL &
-4antimicrobial substance obtained from oxytetracycline and methacycline and which is long-lasting.
According to a second aspect of the invention, there is provided a use of an antibiotic for the manufacture of a medicament for treating an animal, with the medicament being administrable to the animal body by implantation.
The medicament may be in solid form. Instead, it may be in the form of. a paste.
According to a third aspect of the invention, there is proviced a substance or composition for use in a method of treatment of an animal body by implantation thereof in the animal body, the substance or composition comprising an antibiotic.
According to a fourth aspect of the invention, there is provided a medicament for use in a method of treatment of an animal body by implantation in the animal body, the medicament including an antibiotic as an active ingredient.
The medicament may be in unit dosage form, and may be in solid form, eg in the fonn of a pellet, tablet, or the like. Typically, it may be in the form of a tablet about 1 an long and 2,5 mm in diameter .The medicament may hence include at bad original
AP 0 0 0 1 0 5
-5least one excipient, such as a binder, eg polyvinylpyrrolidone, and/or a lubricant, eg magnesium stearate and/or a mixing agent, eg alcohol, and/or a filler.
According to a fifth aspect of the invention, there is provided a method of treatment of an animal body, which includes inplanting an antibiotic into the animal body such that a prophylactically effective quantity of the antibiotic is released into the animal body in controlled fashion over a period of .time.
The treatment may be effected once during the lifetime of the animal, eg immediately after the birth of the animal or at a time when the animal is introduced into a geographic area in which the predetermined disease is prevalent.
The quantity or dosage rate may be sufficiently high to be prophylactically effective, yet sufficiently low not to inhibit entirely the natural ability of the animal body to build up immunity against the disease. Typically, the dosage rate may, as mentioned hereinbefore, be between 0,1 and 2 mg antibiotic per kilogram bodyweight per day, eg 0,2 to 0,5 mg/kg per day, for a predetermined period of time.
BAD ORIGINAL ft
-6The invention will now be described by way of example, with reference to the following non-limiting tests, formulations and graphs 1 to 10;
TEST 1
To each of six fully grown sheep was initially, on day 0, administered by subcutaneous injection, 1 mg per kg bodyweight per day of LIQUAMYCIN 100 (trade mark), the active ingredient of which is oxytetracycline. Each sheep was also injected intravenously with 5 ml Welgevonden Supply antigen blood containing virulent heartwater organisms, ie Cowdria ruminantium organisms. The daily subcutanoeus administration of the LIQUAMYCIN 10C at the same dosage rate was thereafter continued for a further 25 days, with rectal temperature readings being taken each morning. On day 40, each of the sheep was again injected intravenously, with 5 ml of the Welgevonden Supply antigen blood containing virulent heartwater organisms, ie re-exposed to the disease. All six sheep survived the disease. The sheep were then again, on day 60, injected with 5 ml of the same blood, ie again re-exposed to the disease.
All six sheep survived this re-exposure to the disease, indicating that they had built up immunity to the disease. Temperature readings were ceased after day 90.
AP 0 0 0 1 0 5
BAD original^ ♦
-7Graphs 1 to 4 show the temperature readings versus time for two of the treated sheep (Sheep A and B) as well as two control sheep (Sheep C and D). Sheep C was intravenously injected with the antigen blood on day 0 but was -not pretreated with the tetracycline at the low immunizing dosage rate. Instead, it was treated with a therapeutic dose of the LIQUAMYCIN 100, viz 20 mg per kilogram bodyweight when a temperature rise was noticed, ie on day 11. Temperature readings were ceased in respect of Sheep C on day 18, and recommenced on day 29 after Sheep C had been re-exposed with 5 ml of the antigen blood on day 27. Temperature readings were ceased on day 52, with Sheep C hence also having built up immunity to the disease by being treated with the therapeutic dose of the tetracycline. In sane cases, more than one therapeutic dose will be required.
However, the therapeutic dosage route has risks associated therewith, eg the timing of the dosage is critical. If the therapeutic dosage is administered too early, immunity is not built up; if the therapeutic dosage is administered too late, the animal will die. There is even the risk that an animal will die even when injected with the correct therapeutic dosage at the correct time - see Graph 4 in respect of Control Sheep D. Sheep D was also injected with the antigen blood on day 0; a temperature rise was experienced on day 11; it was injected with a 20 mg/kg
BAD ORIGINAL &
♦
-8therapeutic dose of LIQUAMYCIN LA on day 11; however, Sheep D died on day 12.
TEST 2
Solid tablets having the following formulation were made up (i) doxycycline hydrochloride - 75 parts by mass (ii) polyvinylpyrrolidone - 3,2 parts by mass (iii) magnesium stearate - 1 part by mass.
These solid ingredients, in powdered form, were admixed. Sufficient alcohol, ie ethanol, was added to the powdered admixture to granulate the mixture. After evaporation of the alcohol, the granules were tabletted in known fashion. The tablets were 5 mm in diameter and about 3-5 mm long, with each tablet having a mass of about 100 or about 150 mg.
Three sheep (designated E, F and G) were treated by subcutaneously implanting on day 0 sufficient tablets into the ears of the animals, viz 3x150 mg tablets into the right ear and 2x150 mg tablets into the left ear of Sheep D, 1x150 mg tablet into each ear of Sheep E, and 2x100 mg tablets into each ear of Sheep F, to release a total of 10 mg/kg active ingredient, ie doxycycline hydrochloride, into the animal's body over a period of 25 days. The long-acting tablets released the active ingredient slowly in controlled fashion over the twenty-five days, and were fully dissolved
AP 0 0 0 1 0 5
-9ear, ie 0,4 mg/kg per day. The tablets were implanted in both ears rather than in one only, to minimize reactions in the ears themselves which could adversely influence the absorption of the active ingredient. Reactions were indeed experienced in both ears in each case, but all three animals survived both the initial exposure on day 0 as well as the subsequent exposure on day 35 of 5 ml of antigen blood as described hereinbefore with reference to Test 1, injected intravenously, hence indicating that immunity had been built up. Hence, immunity was achieved by subcutaneously releasing into the body immunizing or prophylactic, ie bacteriostatic, quantities of the antibiotic. It is hence critical that the release rate be below the bacteriocidal or therapeutic dosage rates as this would result in killing off of the organisms without immunity being built up. It is also important that the release rate be sufficient to enable the immunity to build up. If it is too low, the animal will die when subjected to the organisms. The Applicant hence believes that subcutaneous implantation of the antibiotic in solid or paste forms provides a very effective means of obtaining the desired release rate.
Graphs 5 to 7 show temperature profiles versus time for these animals.
BAD ORIGINAL ♦
-10TEST 3
Tablets having a diameter of about 2 mm and a length of about 1 cm, with a mass of about 75 mg, were made up as for the 5 mm diameter tablets and having the same composition. These tablets or pills were easier to implant subcutaneously due to their smaller size. They were implanted in three sheep in the same dosage rates as in Test 2, viz to give a total of 10 mg active ingredient of doxycyclic hydrochloride per kilogram animal body mass over 25 days. Two 75 mg tablets were implanted into each ear of each animal. These sheep, designated Η, I and J, survived an initial exposure to 5 ml of antigen blood as hereinbefore described, injected intravenously, with both the implantations and the exposure being effected on day 0. These sheep have not yet been subjected to re-exposure.
Graphs 8, 9 and 10 show temperature profiles for these sheep.
Applicant believes that, on the basis of the above tests, the prophylactically effective doses could possibly be lowered even further, eg to about 5 mg active ingredient per kg bodyweight or 0,2 mg per kg per day.
Instead of being implanted subcutaneously in the ear, the implantation can be effected in any other suitable body locat i on.
AP 0 0 0 1 0 5 *5
BAD ORIGINAL ♦
-list! 11 further, instead of the controlled release tablets as hereinbefore described, a controlled release gel or paste can be implanted. For example, the gel or paste can then
comprise: | ||
(i) | Doxycycline hydrochloride | 20 mg |
(ii) | Magnesium stearate | 17 mg |
(iii) | Polyvinylpyrrolidone | 15 mg |
(iv) | N-methyl-2-pyrollidone | 55 ml |
(v) | Water to render injectable | 35 ml |
(vi) | Na formaldehyde sulphoxalate | 0,2 mg |
(vii) | Ethanolamine | - to ph 6.6 |
The Applicant also believes that the method and means, ie subcutaneous implantable long-acting tablets and gel as provided by the present invention, provide a quick, easily implementable and effective method and means for prophylactically treating animals for immunity against diseases such as heartwater, anaplasmosis, mastitis and redwater. Hitherto there has been no satisfactory means of building up immunity against these diseases. In addition, by providing the antibiotic in prolonged or slow controlled release form, ie in solid or gel form implanted subcutaneously, the need to treat animals daily while building up immunization, is avoided. This naturally leads to savings in time and labour.
BAD
SHEEP A
0 l 0 0 0 dV
-13SHEEP
-14SHEEP
S ro
APO 0 0 1 0 5
Oo dW31
BAD ORIGINAL
-15TEMP ’C —- TEMP
s 0 I Ο Ο 0 dV
bad omaNMGRAPH <0 m
AP Ο Ο Ο 1 Ο 5
TEMP °C—► TEMP
GRAPH 9
DAYS —GRAPH 10 *
Claims (6)
1.
A use of tetracycline or a derivative thereof in the treatment of an animal, which comprises implanting subcutaneously into the body of an animal a solid implant comprising tetracycline or a derivative thereof;
allowing tetracycline or its derivative to be released into the animal body over a period of time; and challenging the bloodstream of the animal with virulent Cowdria ruminantium organisms, with the amount of tetracycline or its derivative which is released being sufficiently high to be prophylactically effective, but below a therapeutic dosage so as not to inhibit entirely the natural ability of the animal body to build up immunity against heartwater, so that the animal thereby builds up immunity against heartwater.
2. A use according to Claim 1, wherein a tetracycline derivative is used, the tetracycline derivative being doxycycline hydrochloride, with the period of time being about 25 days, and with the doxycycline hydrochloride being released at a controlled rate of between 0.1 and 2 mg/kg animal body mass per day.
3. A use according to Claim 2, wherein the implant is in tablet form, and also comprises polyvinylpyrrolidone as binder and magnesium stearate as lubricant, with the amount of doxycycline hydrochloride released being between 0.2 and 0.5 mg/kg animal body mass per day.
< ' ' r Λ ,
BAD ORIGINAL
S 0 I 0 0 0 dV
A substance or composition for use in a method of treatment of an animal body by implantation thereof in the animal body, the substance or composition comprising powdered tetracycline or a derivative thereof, as active ingredient; a powdered binder and a powdered lubricant, with the active ingredient, binder and lubricant being in compressed solid unitary form.
5. A substance or composition according to Claim 4, wherein the tablet comprises doxycycline hydrochloride, as active ingredient
75 parts by mass polyvinylpyrrolidone, as binder - 3.2 parts by mass magnesium stearate, as lubricant - l part by mass
6.
A method of treating an animal to render it immune against heartwater, which comprises implanting subcutaneously into the body of an animal a solid implant comprising tetracycline or a derivative thereof;
allowing tetracycline or its derivative to be released into the animal body over a period of time; and challenging the bloodstream of the animal with virulent
Cowdria ruminantium organisms, with the amount of tetracycline or its derivative which is released being sufficiently high to be prophylactically effective, but below a therapeutic dosage so as not to inhibit entirely the natural ability of the animal body to build up immunity against heartwater, so that the animal thereby builds up immunity against heartwater.
BAD ORIGINAL
7.
A method according to Claim 6, wherein a tetracycline derivative is used, the tetracycline derivative being doxycycline hydrochloride, with the period of time being about 25 days, and the amount of doxycycline hydrochloride being released at a controlled rate of between 0.1 and 2 mg/kg animal body mass per day.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ZA879347 | 1987-12-11 |
Publications (2)
Publication Number | Publication Date |
---|---|
AP8800111A0 AP8800111A0 (en) | 1989-01-31 |
AP105A true AP105A (en) | 1990-11-07 |
Family
ID=25579098
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
APAP/P/1988/000111A AP105A (en) | 1987-12-11 | 1988-12-07 | Treatment of animals. |
Country Status (3)
Country | Link |
---|---|
AP (1) | AP105A (en) |
AU (1) | AU2671388A (en) |
GB (1) | GB2213375A (en) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4077406A (en) * | 1976-06-24 | 1978-03-07 | American Cyanamid Company | Pellet implanter for animal treatment |
US4159322A (en) * | 1978-06-26 | 1979-06-26 | A. H. Robins Company, Inc. | Anticoccidium implants |
US4374121A (en) * | 1979-09-12 | 1983-02-15 | Seton Company | Macromolecular biologically active collagen articles |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1312918A (en) * | 1969-07-08 | 1973-04-11 | Beecham Group Ltd | Veterinary treatment |
DE2320373B2 (en) * | 1973-04-21 | 1978-04-06 | Merck Patent Gmbh, 6100 Darmstadt | Antibiotic agent and its use as a plastic surgical material |
US4003493A (en) * | 1975-05-27 | 1977-01-18 | Wells Robert A | Easy-open container with nondetachable opening member |
IL58462A0 (en) * | 1978-10-27 | 1980-01-31 | Beecham Group Ltd | Intramammary compositions comprising a penicillin |
DE3007878A1 (en) * | 1980-03-01 | 1981-09-10 | Sigri Elektrographit Gmbh, 8901 Meitingen | CARRIER FOR ANTIBIOTICS |
GB2093348B (en) * | 1981-02-23 | 1984-09-12 | Leo Pharm Prod Ltd | Pharmaceutical composition for implantation |
DE3124981A1 (en) * | 1981-06-25 | 1983-01-13 | Dr. Ruhland Nachfolger GmbH, 8425 Neustadt | ACTIVE INGREDIENT COLLAGEN INSERT FOR INSERTION INTO BONES OR SOFT PARTS AND METHOD FOR THEIR PRODUCTION |
DE3206726A1 (en) * | 1982-02-25 | 1983-09-01 | Merck Patent Gmbh, 6100 Darmstadt | PHARMACADEPOT |
DK119884A (en) * | 1983-03-18 | 1984-09-19 | Lilly Co Eli | FAST, CYLINDRICAL, SUBCUTAN IMPLANTATION AND ITS USE |
FR2559780B1 (en) * | 1984-02-21 | 1990-05-04 | Tech Cuir Centre | IMPLANTABLE BIOCOMPATIBLE COLLAGEN-BASED SYSTEMS FOR CELL STORAGE AND / OR CULTURE AND / OR CONTROLLED RELEASE OF ACTIVE INGREDIENTS |
DE3429038A1 (en) * | 1984-08-07 | 1986-02-20 | B. Braun Melsungen Ag, 3508 Melsungen | ACTIVE SUBSTANCE DEPOT |
GB8514055D0 (en) * | 1985-06-04 | 1985-07-10 | Geistlich Soehne Ag | Chemical substance |
-
1988
- 1988-12-07 AP APAP/P/1988/000111A patent/AP105A/en active
- 1988-12-08 GB GB8828646A patent/GB2213375A/en not_active Withdrawn
- 1988-12-08 AU AU26713/88A patent/AU2671388A/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4077406A (en) * | 1976-06-24 | 1978-03-07 | American Cyanamid Company | Pellet implanter for animal treatment |
US4159322A (en) * | 1978-06-26 | 1979-06-26 | A. H. Robins Company, Inc. | Anticoccidium implants |
US4374121A (en) * | 1979-09-12 | 1983-02-15 | Seton Company | Macromolecular biologically active collagen articles |
Also Published As
Publication number | Publication date |
---|---|
AU2671388A (en) | 1989-06-15 |
GB2213375A (en) | 1989-08-16 |
AP8800111A0 (en) | 1989-01-31 |
GB8828646D0 (en) | 1989-01-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US4650665A (en) | Controlled release of pharmacologically active agents from an absorbable biologically compatible putty-like composition | |
US4568536A (en) | Controlled release of pharmacologically active agents from an absorbable biologically compatible putty-like composition | |
US3507952A (en) | Sustained release bolus for animal husbandry | |
AU783538B2 (en) | Pharmaceutical implant containing immediate-release and sustained-release components and method of administration | |
JP3662942B2 (en) | Sustained release thyroid acting composition | |
EP0009410B1 (en) | Growth promotion method for steers and calves employing an implant | |
EP0139286A2 (en) | Prolonged sustained-release preparations | |
DE2158226A1 (en) | MEDICINAL INGREDIENTS CARRIER MADE OF SILICONE RUBBER | |
JPH07500109A (en) | Biocompatible implant for ovulation control in mares | |
JP4616556B2 (en) | Polytartaric acid ester composition | |
US5550153A (en) | Method for treating heartworm-infected canines | |
SI9300330A (en) | Peroral preparation for gastric antibacterial treatement, process for the preparation thereof and use | |
AP105A (en) | Treatment of animals. | |
ES2734280T3 (en) | Pharmaceutical composition for use in the treatment of sexually transmitted infections | |
WO2001049269A1 (en) | Sustained-releasing anthelmintic compositions comprising praziquantel | |
US4302452A (en) | Use of derivatives of 6α-methylprednisolone as an antiemetic | |
US3758680A (en) | Composition of matter and method of use | |
US3660574A (en) | Method of controlling fertility employing quingestanol acetate | |
JP2586542B2 (en) | A therapeutic agent for cattle abomasum displacement | |
CA2067520A1 (en) | Treatment of mastitis | |
SK68597A3 (en) | Kit for osteoporosis treatment cycle | |
RU2161486C2 (en) | Method of treatment of patients with radiation-thermal damage and agent for its realization | |
US3126319A (en) | Method for the potentiation of anti- | |
JPH04283519A (en) | Composition for suppressing reduction in immunological function with aging | |
MX2011004493A (en) | Veterinary composition and method for treating dental and mouth infections. |