TECHNICAL FIELD
[0001] This invention relates to an insert to be inserted into a papillary duct of dairy
cattle.
BACKGROUND ART
[0002] Milking disorders are sometimes caused by thickening or stricture of the opening
or the inner wall of a papilla due to an injury by trample under a hoof, misapplication
of a milking cannula, misuse of a milker, stimulation by a teat cup liner, and the
like. Further, milk leakage is caused by damage of papillary constrictor muscles.
[0003] Such milking disorders have been treated by inserting an insert into the papillary
duct to dilate the duct or to stop a milk leak. Conventional inserts for this use
include a bar-shaped bundle of twisted strands having a diameter of about 3 mm and
a length of about 7 cm with its one end obliquely cut and the other end tied up with
a ring band having a width of about 5 mm, the bundle being impregnated with an antibiotic
and hardened by a binder ("Teat plug B" produced by Denka Seiyaku Co., Ltd. or "TEATOR
POINT" produced by Nihon Eiken Co., Ltd.).
[0004] However, few cases are known where stricture of a papillary duct is healed by application
of the above-mentioned twisted yarn bar except for the very early stage of papillary
duct lesions. Once a cow suffers from papillary duct stricture, no improvement even
for milking once takes place, and one cannot milk without using a cannula, which will
further worthen the papillary lesion. It follows that the papillary duct seriously
thickens, making milking impossible and finally needing cut section or dilation of
the papillary opening. Papillitis caused by postoperative infection cannot be prevented
by the conventional inserts, and papillitis develops into mastitis in most cases.
[0005] While the conventional inserts for treating papillary duct stricture have applied
thereto an antibiotic, the applied antibiotic is gradually diluted with milk while
being kept in the duct between milking and milking, thereby resulting in not only
loss of its antimicrobial activity but contamination of milk. On the contrary, the
support with reduced antimicrobial activity helps invasion of bacteria through a capillary
phenomenon. Besides, long-term use of the antibiotic-impregnated insert induces development
of resistant strains. From all these considerations, use of the conventional inserts
has come into question as a cause inducing iatrogenic mastitis.
[0006] In short, conventionally employed twisted yarn bars or milking cannulae have no effect
in healing papillary duct stricture or wounds or preventing and treating mastitis.
[0007] An object of the present invention is to provide a measure for papillary duct lesions
or for the papillary duct after having a surgical treatment for stricture, consisting
of simple insertion of a bar-shaped insert into the affected papillary duct.
DISCLOSURE OF THE INVENTION
[0008] The present invention relates to a papillary duct insert formed of chitin or a chitin
derivative or a papillary duct insert comprising a support having coated thereon or
impregnated therein chitin or a derivative thereof.
[0009] Chitin is a polysaccharide represented by formula:

comprising N-acetyl-D-glucosamine polycondensed through β(1→4) linkages which is present
in crustaceans (e.g., shrimps and crabs), insects (e.g., grasshoppers and beatles),
a cuttlebone, etc. Chitin which can be used in the present invention can be obtained
by purifying naturally occurring crude chitin from these sources by referring to,
for example, Chitin Chitosan Kenkyukai (ed.),
Chitin Chitosan Jikken Manual, Ch. 1 (Preparation of Chitin), pp. 1-7, Gihodo Shuppan K.K. (1991).
[0010] Chitin derivatives which can be used in the present invention include chemically
modified chitin derivatives, such as deacetylated chitin, Chitosan (especially those
having a degree of deacylation of 80% or more), carboxymethylated chitin, hydroxyethylated
chitin, and sulfonated chitin. Reference can be made to
ibid, Ch. 2 (Preparation of Chitosan and Partially Deacetylated Chitin), pp. 9-17, Ch.
3 (Preparation of Chitin Derivatives), pp. 19-36, Ch. 4 (Preparation of Chitosan Derivatives),
pp. 37-47.
[0011] Supports on or in which chitin or a derivative thereof is coated or impregnated include
yarn, sponge, cloth, etc. made of soft and biologically harmless materials, such as
silk, collagen, cellulose, nylon, polyethylene, polypropylene, polyester, Teflon,
etc.
[0012] If desired, the papillary duct insert according to the present invention formed of
chitin or a derivative thereof or comprising a support coated or impregnated with
chitin or a derivative thereof may further be coated with starch, polyvinyl alcohol,
sodium carboxymethyl cellulose, alginic acid or a salt thereof, and so on as a binder
so as to have increased hardness.
[0013] The insert formed of chitin or a chitin derivative according to the present invention
can be produced, for example, as follows. Yarn, sponge, cloth, etc. made of chitin
or a chitin derivative is shaped into a string or bar having a diameter of from 1
to 5 mm, preferably from 2 to 3 mm. A 1 to 50 w/v%, preferably 1 to 10 w/v%, solution
of a binder is coated thereon and dried to obtain a stock bar of about 3 mm in diameter,
which is then cut to a length of from 1 to 10 cm, preferably from 3 to 7 cm. The tip
of one end of the resulting bar is cut off at right angle or obliquely.
[0014] The insert comprising a support coated or impregnated with chitin or a chitin derivative
according to the present invention can be produced, for example, as follows. A support,
such as a bar, a filament; sponge, cloth, etc. is shaped into a string or bar having
a diameter of from 1 to 5 mm, preferably from 2 to 3 mm, and a solution or dispersion
containing 1 to 50 w/v%, preferably 1 to 10 w/v%, of chitin or a chitin derivative
is coated thereon or impregnated therein. A 1 to 50 w/v%, preferably 10 to 30 w/v%,
binder solution is further coated thereon and dried to prepare a stock bar having
a diameter of 1 to 5 mm, preferably 2 to 3 mm. Alternatively, a support is first coated
with chitin or a chitin derivative and then shaped into a string or bar, and a binder
solution is coated thereon followed by drying. The resulting stock bar is cut at right
angle or obliquely to a length of from 1 to 10 cm, preferably from 3 to 7 cm.
[0015] Chitin and derivatives thereof may be used either individually or in combination
of two or more thereof.
[0016] The support may be prepared by mixing yarn, sponge, cloth, etc. made from the above-described
soft and harmless material (e.g., silk, collagen, cellulose, nylon, polyethylene,
polypropylene, polyester or Teflon) with yarn, sponge, cloth, etc. made from chitin
or a chitin derivative and shaping the mixture to the above-mentioned dimensions.
[0017] The reason why application of the insert according to the present invention to papillary
ducts heals papillary duct stricture or papillary duct lesions after a surgical treatment
of stricture and also prevents mastitis has not yet been made clear. With the insert
inserted into a papillary duct, it seems that various cells participating in healing
mechanism of a wound are made to wander without inducing antixenic reaction to markedly
accelerate vascularization and formation of granulations. Also possessing antimicrobial
properties, the insert of the invention is believed to exert direct accelerating effects
on postoperative treatment after a surgical measure for papillary duct stricture and
to accelerate regeneration of the epithelium while preventing invasion of bacteria.
BEST MODE FOR THE PRESENT INVENTION
[0018] The present invention will now be illustrated in greater detail by way of Examples,
but it should be understood that the present invention is not construed as being limited
thereto.
EXAMPLE 1
[0019] In 1800 mℓ of a 4.2 v/v% acetic acid aqueous solution was dissolved 200 g of chitosan
("FLONAC C" produced by Kyowa Technos Co., Ltd.; degree of deacetylation: 83%), followed
by filtration under pressure of 1 to 2 kg/cm². The solution was allowed to stand for
20 hours to prepare a dope. The dope was spun from a nozzole having 500 orifices of
0.1 mm in diameter into a 1.5 m long first coagulating-bath containing 10 ℓ of ethylene
glycol, 1.5 kg of water, and 1.8 kg of potassium hydroxide and passed through a 0.9
m long second coagulating bath containing a 50 v/v% aqueous solution of methanol at
a speed of 12 m/sec to complete coagulation. The spun filament was drawn at a draw
ratio of 1.17, wound around a bobbin, washed with running water as wound for 12 hours,
immersed in hot water at 70 to 80°C for 4 hours and then in ethanol for 24 hours,
re-wounded around a reel, and spontaneously dried to obtain a hank. The hank was wetted
with water, and 18 filaments out of the hank were intertwined to obtain twisted yarn
having a diameter of 5 mm. The twisted yarn was dipped in a 7 w/v% aqueous solution
of polyvinyl alcohol (a product of Wako Pure Chemical Co., Ltd.; degree of polymerization:
about 1500) to coat 1 mℓ of the polyvinyl alcohol per 10 cm, followed by drying under
reduced pressure to obtain a stock bar having a diameter of 3 mm. The stock bar was
cut to lengths of 6.5 cm, and the tip at one end of each cut bar was cut off at about
45° or at right angle with the longitudinal direction. The other end of the twisted
yarn bar was fitted into a silicone tube of 5 mm in diameter and 5 mm in width to
prepare a papillary duct insert. The resulting insert was designated A.
EXAMPLE 2
[0020] Papillary duct insert B having a diameter of 3 mm and a length of 6.5 m was prepared
in the same manner as in Example 1, except that the twisted yarn was dipped in a 2
w/v% aqueous solution of sodium carboxymethyl cellulose (a first grade reagent produced
by Nakarai Tesuku Co., Ltd.) in place of polyvinyl alcohol to pick up 0.5 mℓ of sodium
carboxymethyl cellulose per 10 cm.
EXAMPLE 3
[0021] In 300 mℓ of a 5 v/v% acetic acid aqueous solution was dissolved 15 g of chitosan
("FLONAC C") followed by filtration under reduced pressure to prepare a homogeneous
chitosan solution. Rayon nonwoven cloth "Bemliese JF601" produced by Asahi Chemical
Industry Co., Ltd.; unit weight: 60 g/m²) 9cm wide and 30 cm long was dipped in the
chitosan solution for 30 minutes. The impregnated nonwoven cloth was squeezed lightly
so as not to drip the liquid and then immersed in a 8 w/v% aqueous solution of sodium
hydroxide for 1 hour. The cloth was washed with running water for 1 hour, soaked in
hot water at 70 to 80°C for 30 minutes, and spontaneously dried to obtain chitosan-impregnated
nonwoven cloth containing 0.2 g of chitosan per gram. After wetted with water, the
cloth was folded in four in the width direction and twisted in the longitudinal direction.
A 2 w/v% aqueous solution of sodium carboxymethyl cellulose (a first grade reagent
produced by Nakarai Tesuku Co., Ltd.) was coated on the resulting bar-shaped twisted
cloth at a spread of 2.0 mℓ/10 cm and dried under reduced pressure to obtain a stock
bar of 3 mm in diameter. The stock bar was cut to lengths of 6.5 cm, and the tip was
cut at an angle of about 45° or at right angles with the longitudinal direction. The
other end of the bar was fitted into a silicone tube of 5 mm in diameter and 5 mm
in width to prepare a papillary duct insert designated C.
[0022] Each of the inserts prepared in Examples 1 to 3 was inserted to the papillary duct
of a female Holstein suffering from papillary duct stricture or a female Holstein
having undergone stricturotomy for dilating the opening of the papillary duct. The
cows were milked twice a day, and a fresh insert was inserted after every milking.
Any change of the papilla was observed everyday. The prognostic symptoms and the state
of mastitis are shown in Table 1 below.

INDUSTRIAL APPLICABILITY
[0023] When the papillary duct insert of the present invention was applied to the papilla
suffering from stricture or having undergone an operation for dilation of the papillary
opening, improvements were observed in 5 out of 6 cases.
[0024] Case 2 showed a sign of improvement on the stricture. While no further effects could
be observed because of shortage of the period of treatment, 7-day application of the
insert of the present invention resulted in healing of mastitis. No influence on other
mammae (any changes of milk of other normal mammae of the same animal) was noted at
all. Development into mastitis due to the use of the insert was not observed.
[0025] Application of insert A caused light swelling of the papilla and light pain but gave
no adverse influences on the therapy and milking.
[0026] No side effect such as swelling of the papilla or pain was recognized in application
of insert B.
[0027] Although the inserts with a crosswise cut encountered slight difficulty in inserting
into the papillary duct as compared with those with an oblique cut, irritation to
the papillary duct was less, and no particular disadvantage resulted when applied
to lightly strictured papillae.
[0028] For comparison, a commercially available insert for a papillary duct ("TEATOR POINT")
was applied to a strictured papillary duct unaffected by mastitis (Case 7) and a papillary
duct after an operation for dilating the opening of a strictured papillary duct (Case
8). Because mastitis occured in 7-day application with no improvement on the stricture,
the experiments were suspended.