Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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BACKGROUND OF THE INVENTION -
Mastitis is an inflammatory condition of the
mammary gland. It may affect any species, but bovine
mastttis is of the greatest economic importance.
Bovine mastitis is usually associated with one
or more microorganisms such às StrePtococcus aaalactiae,
Streptococcus dysqalactTae, Staphlococcus aureus, Aero-
bacter aeroqenes, Escherichia coli, Pseudomonas aeruqi-
nosa, Salmonella enteritidis, C!ostridium Perfinqerls,
and CorYnebacterium Pvoqenes which invade the udder
through the teat canal and produce inflammation of the
miIk-producing tissue causing the formation of scar tis- -
sue which, once formed, may cause a permanent reduction
in the cow's milk production, An infection can also
alter the composition, quantity, appearance and quality
; of the milk,
The etiology of mastTtis makes control of the
problem dependent upon the crltical diagnosis of the spe-
~ ciftc microbial agent involved, the correction of faulty
`~ 20 managerial practlces and the Judicious use of in~ra-
mammary therapy.
BRIEF SUMMARY OF THE INVENTION
~; This Invention relates to new mastitis composi-
tions and to methods of treating mastitis in milk
animals by intramammary infusion of an anti-mastitis
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medicament dispersed in a special vehicle providing a
short anti-mastitis medicament milk-out time.
The vehicle of the present invention comprises
an oil and from 0.5 to 5.0~ by weight of a fatty acid
ester of a member selected from the group consisting of
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~ "~in, propylcne glyc~l J monO- and dihydric alcohol~ of from
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one to twelve carbon atoms, inclusive, and poly~thylene glycols
having a molecular wei~ht of between about 200 and about 6000,
said fatty acid being selected from a group consisting of long
chain saturated and unsaturated monocarboxylic acids having from
twelve to t~enty carbon atoms, inclusive. In addition to a fatty
acid ester as described above, the vehicle of the present invention
may optionally include from 0.02~ to 0.15~ by wei~ht of a fatty
acid salt of a member selected from the group consisting of sodium,
potassium and lithium, said fatty acid being selected from a group
consisting of long chain saturated and unsaturated monocarboxylic
acids having from twelve to twenty carbon atoms, inclusive.
DETAILED DESCRIPTION
The present invention relates to compositions and
methods of treating mastitis in animals, particularly milk animals,
by intramammary infusion. Milk animal is any animal which has
mammary glands and is capable of milk production.
Although bovine mastitis is of the greatest economic
importance and for convenience references herein will be directed
~20 essentially to such situations, it will be understood that the
compositions and methods of the present invention are applicable
to other milk animals as well.
The compositions and methods of the present invention
are particularly advantageous for the treatment of mastitis because
of a surprisingly short anti-mastitis medicament milk-out time,
i.e., the
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105'~697 3240
amount of timc requir~d for an anti-mastitis medicament
to clear the udder after the last intramammal-y infusion.
This property of a short anti-mastitis medicament mil~-
out time is of importance since milk contaminated with
an anti-mastitis medicament cannot be used for human
consumption or marketed for cheese production. -
The nature of the vehicle, on anti-mastitis
medicament milk-out times, has long been considered im-
portant in formulating mastitis infusion compositions.
Heretofore, anti-mastitis medicaments for intra-
mammary infusion have commonly been dispersed in an oil
medlum such as mineral oil or a vegetable oil containing
a trivalent metallic stearate such as aluminurn mono-
stearate, e.g" a peanut oil medium containing 3~ of
alum7num monostearate. A dTsadvantage with intramammary
infusion compositions containing a trivalent metallic
stearate, as described above, is that the anti-mastitis
medicament milk-ollt time for such compositions is quite
long.
It i5 therefore a principal object of this in-
vention to provide compositions and methods for treating
animal masti~is by intramammary infusions affording short
anti-mastitis medicament milk-out times.
The term "anti-mastitis medicament", as used in
the specification and claims, refers to any antimicrobial
effective to treat mastitis. Illustrative of the anti-
mastitis medicaments which can be utilized in the compo-
sitions of the present invention include penicillin,
neomycin, novobiocin~ lincomycin, dihydrostreptoll1ycin,
streptomycin, erythromycir-, polymyxin, tetracycline,
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~o5~69~
oxytetracycllne, chlortetracycline, clindamycin, nitro-
furazonq, cephalosporins, analogs andderlvatives thereof,
and their pharmaceutically acceptable salts. The amount
of anti-rnastitis medicament employed will, of course,
vary depending upon the severity of the mastitis but,
in general~ those amoun-ts which have heretofore bee
used for the treatment of rnastitis are suitable.
In accordance with a sp~cific feature of 1:his
Invention, the oil ot the vehicle may be any vegetabl~
oil which is suitable for carrying an anti-mastitis
medlcament and which has been foun~i fully acceptable for
intramammary Infusion. Vegetable oils may be generally
classlfied as non-drying, semi~drying and drying oils.
Drying vegetable olls include linseed oil and safflower `~
oil. The dry7ng properties of this group of oils is
caused by the presence of unsaturated fatty acids in the
oll, The ~legree of unsatlIrated fatty aclds pr~sellt can
be expressed by the iodine value of the oil. Arranged
according to their lodlne value, t:he afoIemelll:ioned
drying vegetable oils are as follows:
I.inseed oll not less ~har- 170
Safflower oll 140 - 150
; The class of semi-drylng vegetable oils includes
the followlng~ arranged accordlng to their iodine value.
Soybean oil 127 - 138
Cottonseed oil 105 - 114
Sesame oil 103 - 122
Corn oll 109 - 133
The class of non-drying vegetable oils includes
the following, arranged acc~rding to their io~ine value:
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Oli oil 79 - 90
Peanut oil ~ o 5 ~6 9~ 84 - 102
~ s stated, vegetable oils are suitable for the
vehicle, examples being peanut oil, sesame oil, corn oil, cotton-
seed o:il, soybean oil, olive oil, and like vegetable oils or
mixtures thereof. In a broader aspect, it is conceived that
other oils may be employed, in part or in whole, for example,
mineral oil. However, in such compositions, the milk-out
specifications may require that the milk be completely clear -
of such oil in order to be available for human consumption.
The term "mineral oil" as used in the specification
and claims refers to mixtures of liquid hydrocarbons known in
medicine as liquid paraffin and light liquid paraffin or petroleum,
preferably those of the United States or British Pharmacopeias.
An oil, i.e., a vegetable oil or a mineral oil,
is transformed to a gel before being incorporated into the com-
positions of the present invention. This gelling is effected by
treatment of the oil with a atty acid ester of a member selected
. from the group consisting of glycerin, propylene glycol, mono-
. , .
and dihydric alcohols of from one to twelve carbon atoms, inclusive,and polyethylene glycols having a molecular weight of between
about 200 and about 6000, said fatty acid being selected from
a group consisting of long chain saturàted and unsaturated mono-
carboxylic acids having from twelve to twenty carbon atoms,
inclusive. A preferred fatty acid ester of the present invention
is glycerol monos~earate.
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~ 105~'~697
The amount of glycerol monostearate or other
fatty acid ester which can be used in accordance with
this invention is generally within the range of between
about 0.5 and 5.0% by weight, and preferably from 1.0 to
4.0% by weight. A gel formed by gelling peanut oil wi~h
2.0% by weight of glycerol monostearate is a preferred
vehicle for the preparation of compositions of this invention.
Optionally, the vehicle of the present invention
. may also include a fatty acid salt of a member selected from
the group consisting of sodium, potassium and lithium, said '
fatty acid being selected from a group consisting of long --
chain saturated and unsaturated monocarboxylic acids having ''
from twelve to twenty carbon atoms, inclusive. A preferred
fatty acid salt of the present invention is potassium stearate.
'- The amount of potassium stearate or other fatty
acid salt which can be used in accordance with this invention
is generally within the range of between about 0.02% and 0.15%
by weight. ~ gel formed by gelling peanut oil with 2.0% by
weight of glycerol'monostearate and 0.12% by weight'of
20 ' potassium stearate produces an eminently satisfactory vehicle
for the preparation of the compositions of this invention.
To gel a mineral oll or a vegetable oil, the oil
~- is heated to a suitable temperature which may vary somewhat
' with different oils but which will generally `be below 100C.
' ~ Peanut oil, for example,'can be readily gelled by heating it
to 60-90C. and adding 2.0% by weight of glycerol monostearate,
'' and then cooling to
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25 C. wl~h stlrrlng. Thers Is no great danger in over-
heatlng, pr~vlded d~composltion of the oll Is no~ engen-
dered. ~ea~e~ olls are gelled wlth a fatty acid esteru
The method of treatlng mas~itis In accordance
'j wlth the present Inventlon involves admlnlstering to ~he
affect~d mammary gland iy Intramammary Infusion a compo-
sltlo-l as hereln descrlbed.
The followlng sxamples are Illustratlve of the
best mod~ contemplated by the Inventor for carrylng o~t
hls Inventlon and are not to be construed as llmitlng.
EX~nD1~ 1
One hundred grams of e composltlon for the treat-
. ment of mastltls Is prepared ~rom the fol,lowlng types
and amounts ~f Ingredlonts~ ''
Procalne Penlclllln G500,000 Unlts
Sodlum Novoblocln 1.00 gram
Glyc~rol m~nostearate1,00 gram
Peanut oll, q.s. 100 grams
~eat the peanut oll to 60-goc. and add the glyc~
~rol monost~ar~t~, cool to 25~C. wlth s~lrrlng. Ad(l the
sodlum novoblocln and procalne penlc~ltln G wlth stlr-
rlng and pass tho product through a collold mlll. Flll
the mllled product Into dlsposable mastltls syrlnges In
10 gram doses.
The ~oregolng oomposlt!on Is useful for the
treatmen~ of bovlne mastltls by Intramammary,lnfuslon.
One hundred grams of a composltion for the treat-
ment of mas~ltls Is prepared from the followlng types
and amoun~s of Ingredtents:
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IoS~69~ ~
Procalne Peniclllln G1,500,000 Units
Sodium Novobiocln 1.500 gram
Glyceryl monostearate1,425 gram
Potasslum stearate 0.075 gram
Peanut oll, q.s. 100 grams
Heat the peanut oil to 60-90C. and add the
glyceryl monostearate and potasslum stearate, cool to
25 C. wlth stlrrlng. Add the sodlum novobtoc7n and
procalne penlcillIn G with stirring and pass the product
through a collold mlll. Fill the m711ed product into
disposable mastit1s syringes in 10 gram doses.
The foregoing composltion is useful for the
treatment of bovtne mastitls by intramammary infusion.
Exam~le ~
One hundred grams of a composltion for ths treat-
rnent of mastltis Is prepared from the following types
and-amounts of ingredlents: -
Lincomycln hydrochloride 2.0 grams
Glycerol monostearate 2.0 grarns
Peanut oll, q.s~ 100 grams
- Heat the peanut oil to 60-goc. and add the
glycer~l monostearate, cool to 25 C. with stirring. Add
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the lincomycin hydrochloride ~ith stirring and pass the
? product through a colloid mill. Fill the milled product
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2S into disposable mastitls syringes in 10 gram doses.
~-~ The foregoing compositlon Ts useful for the
treatment of bov1ne mastltis by intramammary infusion.
~, Example 4
One hundred grams of a composition for the treat-
30 ment of mastitis is prepared from the following types
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~05'~697
~ ,an(~ am~unts of ingredients:
; Procaine Penicillin G500,000 Units
Sodlum Novobiocin 1.00 gram
Glyceryl monostearate1.00 gram
Mineral oil, q.s. 100 grams
Heat the mineral oil to 60-90C. and add the
glyceryl monostearate, cool to 25C. with stirring. Add
the procaine penicillin G and sodium novobiocin with
s-tirring and pass the product through a colloid mill.
Fill the milled product into disposable mastitis sy-
ringes in 10 gram doses.
The foregoing composition is useful for the
treatment of bovine rnastltis by intramalnmary infusion.
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