US2968592A - Polyvinylpyrrolidone penicillin treatment of bovine mastitis - Google Patents

Description

United States Patent 2,968,592 POLYVINY-L-PYRROLIDONE PENICILLIN TREATMENT OF BOVINE MASTITIS Clifton Robert Curtis, Hamiiton, NY, assignoljto Hamilton Pharmacal Company, Inc, Hamilton, N.Y.

NoDrawing. Filed Ma s, 1957, SerrNo. 657,735 8 Claims. or. 167-531 This invention :relates to the treatment of bovine mastitis and to a novel composition :for the treatment of bovine mastitis by sintramammary injection.

Polyvinylpyrrolidone, generally referred to as PVP, has in recent years been employed for various .purposes in the fields of pharmaceuticals and cosmetics. Originally resulting as a product of the study of acetylenechemistry, polyvinylpyrrolidone had its first use during World War II as a blood plasma extender or expander and as a blood plasma substitute.

Polyvinylpyrrolidone is a white, amorphous powder which is soluble in water as w'ellas ina Wide variety of organic solvents. In addition to its use "as a plasma extender or substitute, polyvinylpyrrolidone has been variously proposed and to some extent used to retard the absorption of various drugs, including penicillin and insulin; to reduce toxicity and irritating properties of various chemical substances, no'tably'iodineyand as a "solubilizing agent.

Studies of the eifect of polyvinylpyrrolidone on phar macologic activity have led researchers and writers -on the subject to the conclusion that the 'etfectof this material is quite unpredictable, even when applied within a group of related compounds like the barbiturates. The conclusion is that the effect of polyvinylpyrrolidone is specific rather than general and that its action in connection with individual substances or individual pharmacologic uses must'be closely studied in each individual case, even when the individual uses are closely *related chemically. Polyvinylpyrrolidone forms chemical complexes with various substances and does not form complexes in solution with other apparently related substances.

- The treatment of bovine mastitis up to now has been chiefly by intramammary injection'of antibiotics, :notably penicillin and dihydrostreptomycin. -I have found :that remarkable rates of cure are achieved by using combinations of antibiotics and polyvinylpyrrolidone. The outstanding results achieved cannot be due to the usual and expected influences of polyvinylpyrrolidone, such as merely prolonging the action of the antibiotics or by re duction in toxicity or irritation.

Speaking generally, in cases of bovine mastitis and udder infection, the intramammary administration of antibiotics produces cures in a general average of less than eighty percent of cases whereas the treatment with antibiotics plus polyvinylpyrrolidone produces cures in nearly one hundred percent of the cases.

In one example of treatment in accordance with the method of the present invention the dosage comprised 20 cc. of vehicle emulsion containing 1,000,000 units of penicillin, 1 gram of dihydrostreptomycin and 1 gram of poly-vinylpyrrolidone. The amount of vehicle employed in administering a given dosage of active ingredients is not at all critical and may vary widely. In the bovine administration of antibiotics some veterinarians prefer to use relatively large quantities of vehicle in greatly enlarged udders 'to promote dissemination of the antibiotic material.

The vehicles used in treatment according to the present invention are those generally .used in penicillin administration, namely mineral oil or mineral oil emulsion or vegetable oil plus suspending agents. An example is Plastibase which is marketed by E. R. Squibb & Sons. I-LP. vehicle of the Hamilton Pharmacal Company comprises mineral oil emulsion containing cholesterol emulsifiers. .Bristol Laboratories, Inc. provide a patented vehicle comprising aluminum monostearate in either peanut, sesame or mineral oils.

The above dosage was administered to both dry and lactating cows. Dry quarters received only one treatment and lactating quarters received two treatments. In this particular test run .19 of the infected cows were lactatingand 5 were dry. Two months after initial treat ment four of the five dry cows tested entirely negative (cured) and seventeen of the nineteen lactating cows tested entirely negative.

Surveys made under the New York State Mastitis Control Program over a .period of the last ten years indicate that, in the foregoing group of 24 cows, there would be from 6 to 7 post treatment infections following treatment by 'antibotics al'one,without polyvinylpyrrolidone.

Another test and .survey of a herd of 12 cows, '11 lactating and 1 dry, showed no positive quarters whatever after treatment .in the manner set out in the first example. :Inthis herd the normal experience following treatment with antibiotics alone would have been 3 or 4 positive post treatment infections.

The foregoing tests were made throughthe College of Veterinary Medicine of Cornell University, at Ithaca, New York, by field veterinarians of the New York State Mas'titis ControlProgram. 'Theconclusion of the participating veterinarians was that the results were very remarkable andcould not have beenattained without polyvinylpyrrolidone.

In tests conducted by a team-of veterinarians in Turlock, California, similar results were noted, using varying dosages of antibiotics and polyvinylpyrrolidone. These tests involved the treatment of several hundred infected quarters with polyvinylpyrrolidone.

In one instance of a fresh first calf heifer the right rear-quarter was extremely hard and swollen with very little secretion. The affected quarter was infused every 12 hours with 1,000,000 units of penicillin, 1 gram .of dihydrostreptomycin, and 21 :gram of polyvinylpyrrolidone in cc. .of sterile water. This quarter returned to normal in 4 to 5 days. The veterinarians making these tests state that heretofore dozens of similarly infected quarters in first calf heifers have been treated with antibiotics alone without avail, the quarter being destroyed before it began to produce.

In another instance of a four year old cow fresh, with two mastitis quarters, each quarter was treated with 1,000,000 units of penicillin and 1 gram of dihydrostreptomycin in 250 cc. of water. In one of the quarters 1 gram of polyvinylpyrrolidone was added to the dosage and this quarter responded much more quickly than the other.

In a further instance a cow with the left front quarter badly swollen and the right rear quarter only moderately swollen was treated. Both quarters received the same antibiotic treatment but the badly swollen quarter re ceived, in addition, one gram of polyvinylpyrrolidone twice daily. Both quarters returned to normal in the same length of time.

In a further series of tests at Turlock, California, fourteen cows, including Holsteins, Guernseys and Jerseys, in which each cow had about the same degree of mastitis in two or more quarters, were treated. All of the quarters were given one million units of penicillin and one gram of dihydrostreptomycin in 250 cc. of sterile Water, with smaller repeated doses daily for three days. In addition, half the quarters were injected with one gram of polyvinylpyrrolidone twice daily during the treating period. Without exception the quarters receiving the additional polyvinylpyrrolidone treatment responded more quickly and more completely.

In another herd of 125 milking Holsteins, a dozen mastitis cows were treated as above with half of the infected quarters treated with antibiotics alone and half with the same antibiotic treatment plus polyvinylpyrrolidone. The latter quarters came back to milk quicker than the ones receiving antibiotics alone and it was observed that of all of the polyvinylpyrrolidone treated quarters none remained swollen.

Extensive tests indicate that polyvinylpyrrolidone possesses anti-inflammatory properties when infused into the bovine udder, which properties result in opening of the ducts and better drainage of clots. Polyvinylpyrrolidone appears to act synergistically with antibiotics to reduce swelling and congestion quickly and in a manner which cannot be achieved by antibiotics alone, no matter. how the latter may be administered as to amount or frequency of dosage or the particular antibiotics employed.

In testing and practicing the present invention polyvinylpyrrolidone has been combined and used successfully with procaine penicillin G, crystalline potassium penicillin G, dihydrostreptomycin, neomycin and polymyxin B.

Severe and acute inflammatory reaction to infections normally produce after-damage to udder tissues. This after-damage is greatly reduced as the result of the polyvinylpyrrolidone treatment and in most cases no clinical after-damage was found upon examination two weeks after treatment. When polyvinylpyrrolidone is used in conjunction with antibiotics in bovine mastitis and udder infection there is a more complete recovery in swollen quarters and these quarters are left with less permanent scar tissue than when antibiotics are used alone. Polyvinylpyrrolidone is especially effective in treating the very acute hot cases of mastitis where this is extreme hardness, pain and swelling.

In other tests dosages including 500,000 units of penicillin with 1 gram of polyvinylpyrrolidone have been employed successfully and lesser amounts of penicillin, in some cases as low as 100,000 units, may be employed when the question of residual penicillin in the milk is considered to be objectionable.

In tests which were otherwise the same as those specified above two grams of polyvinylpyrrolidone were employed instead of one with substantially the same result. Furthermore, in certain of the tests only 250 mg. of dihydrostreptomycin was used instead of 1 gram, with good result.

I claim:

1. The treatment of bovine mastitis and udder infection which comprises periodic intramammary injection of dosages comprising a vehicle containing penicillin and polyvinylpyrrolidone.

2. The treatment of bovine mastitis and udder infection which comprises periodic intramammary injection of dosages comprising a vehicle containing from 100,000 to 1,000,000 units of penicillin and approximately 1 gram of polyvinylpyrrolidone.

3. The treatment of bovine mastitis and udder infection which comprises periodic intramammary injection of dosages comprising a vehicle containing from 500,000

' to 1,000,000 units of penicillin and approximately 1 gram of polyvinylpyrrolidone.

4. The treatment of bovine mastitis and udder infection which comprises periodic intramammary injection of dosages comprising a vehicle containing from 500,000 to 1,000,000 units of penicillin and approximately 1 to 2 grams of polyvinylpyrrolidone.

5. The treatment of bovine mastitis and udder infection which comprises periodic intramammary injection of dosages comprising a vehicle containing penicillin, dihydrostreptomycin and polyvinylpyrrolidone.

6. The treatment of bovine mastitis and udder infection which comprises periodic intramammary injection of dosages comprising a vehicle containing penicillin, dihydrostreptomycin and approximately 1 gram of polyvinylpyrrolidone.

7. The treatment of bovine mastitis and udder infec tion which comprises periodic intramammary injection of dosages comprising a vehicle containing from 100,000 to 1,000,000 units of penicillin, approximately A to 1 gram of dihydrostreptomycin and approximately 1 gram of polyvinylpyrrolidone.

8. The treatment of bovine mastitis and udder infection which comprises periodic intramammary injection of dosages comprising a vehicle containing penicillin, streptomycin and polyvinylpyrrolidone in the approximate proportions of 1 gram of each of the dihydrostreptomycin and polyvinylpyrrolidone to 1,000,000 units of penicillin.

References Cited in the file of this patent UNITED STATES PATENTS 2,467,583 Cosar Apr. 19, 1949 2,728,704 Edds Dec. 27, 1955 2,745,785 Bruce May 15, 1956 2,792,329 Woodard May 14, 1957 2,793,156 Souler May 21, 1957 OTHER REFERENCES Milberg et al.: Evaluation of Polyvinylpyrrolidone as a Retardant Agent for Penicillin," Antibiotics and Chemotherapy, August 1954, pp. 871-876. V

Claims (1)

1. THE TREATMENT OF BOVINE MASTITIS AND UDDER INFECTION WHICH COMPRISES PERIODIC INTRAMAMMARY INJECTION OF DOSAGES COMPRISING A VEHICLE CONTAINING PENICILLIN AND POLYVINYLPYRROLIDONE.