HU198843B - Process for producing veterinary compositions with disinfecting and antiinflammatory action, comprising natural active ingredient and suitable particularly for treating mastitis - Google Patents

Abstract

The invention relates to a method for the production of veterinary products, which are particularly suitable for the treatment of mastitis. According to the invention, the active ingredient is soft propolis in an amount of 0.5 to 10% by volume (prepared by cold process) and one or two emulsifiers of low HLB value (3-8) in an amount of 1 in each case to 6% by volume, in a given case, a high HLB emulsifier (8-18), and further comprising one or more additives which in practice comprise the commercial ointment or emulsion base materials, the viscosity-influencing adjuvants Lubricants, inert hydrophilic solvents and p H-regulating additives are selected.

Description

FIELD OF THE INVENTION The present invention relates to a process for the preparation of veterinary compositions containing a natural disinfectant having anti-inflammatory activity, mainly for the treatment of mastitis, such as tooth infusions, ointments, emulsions and the like. It is known that mastitis is a polyeth therefore, a general defense or treatment procedure for prevention or treatment cannot be given.

Mastitis is mainly a disease of high yielding cows. This is all the more understandable if we know that to produce 1 liter of milk, 300-500 liters of blood must pass through the mammary gland. Its significance is very high, as many authors agree that the economic loss from mastitis is greater than that of all other infectious and parasitic damage combined.

This is substantiated and substantiated by the findings on loss.

In Hungary, annual damage is currently estimated at between $ 720 and $ 750 million, while in the US, annual loss is $ 1294 million, while $ 150 to $ 300 per year is reported for mastitis per cow. In France, the annual loss due to mastitis is estimated at 5 billion francs, in England at 35 million pounds sterling, in the GDR 170 million and in the Federal Republic of Germany 450 million. In general, breeders are burdened with mastitis by 11% of the total cattle yield in each country. The damages can be summarized as follows:

- Reduce milk yield by 10-20%;

- Milk quality is deteriorating;

- The cost of medical treatment is considerable;

- After treatment, the milk should be discarded until the active ingredient is cleared, usually 3-7 days;

- Breeding value decreases to slaughter value;

- There may be more forced slaughter or death;

- Uterine cows should be treated separately;

- The number of years spent in production decreases;

- Healthy animals have a high risk of infection;

- It can also be the cause of human illness. In practice, the incidence and appearance of mastitis is extremely influenced by the current housing technology, nutrition and hygiene conditions, and by the people who move them, so the same conditions and variations in the appearance and severity of mastitis can be expected. Infectious pathogens (bacteria, fungi, viruses, etc.) enter the udder milk and udder parenchyma through galactogenic pathways and cause pathologies of varying severity, depending on their pathogenicity and ability of the body and udder.

Topical drug therapy is usually used for clinical manifestations. The products known so far, whether domestic or foreign, always contain some effective antibiotic or antibiotic or sulfonamide combinations. When used, depending on the product, it is necessary to wait between three and seven days after the last treatment before the milk from the udder or udder is ready for human consumption.

SUMMARY OF THE INVENTION It is an object of the present invention to provide a process for the preparation of a veterinary medicament for the treatment of mastitis to overcome the above disadvantage.

It has now been found that formulations of soft propolis, such as drug infusion, emulsion and ointment, provide at least as good an effect as antibiotic or sulfonamide-containing formulations in treating sick livestock or preventing disease, but without the disadvantages mentioned.

In order to make these formulations, we had to find special emulsifiers for the preparation of the proper quality and stability, and to develop a seemingly. Passive emulsion system that is activated upon contact with the milk in the udder quarter, taking into account the natural emulsifiers of the milk. as well as infected. due to the reduced fat content of milk, the o / v emulsifying capacity conditions.

We have found that our object is achieved by dissolving one, preferably two low HLF (3-8) v / o type emulsifiers in an ideally selected ratio of ointment or emulsion base such as white petrolatum liquid paraffin, 1-6 at 1%. Two emulsifiers are preferably used, with lanaleolum (2 L%) and cetylstearylic alcohol (1-2% by volume) being particularly preferred. At the interface of the phases, the two emulsifiers form a stable, compact film. For the emulsification of 0.5 to 10% by weight of a soft propolis active ingredient with a dilute milk texture, which is more hydrophilic, the above raw material emulsifier system is sufficient.

For the preparation of a drug infusion, given that in both milking cows and dry cows the tooth infusion meets 2 dl to several liters of milk in the milk basin, the soft propolis has a high HhB of 1-6 1%, preferably 3-4 t% (8- Up to 18) with an o / v type emulsifier, preferably sorbylene strain (Polysorbat 20), and thus emulsified in the above stock containing the v / o type emulsifier or emulsifier pair. The resulting - contains a complex emulgent3

GB 198843 The glazing system is activated from the disposable raw material assembly by pressing it into the patient's udder quarter and contacting the milk.

Intensity of o / v emulsifier, sorboxetene derivative (Polysorbat 20) and complex mixed phosphatide - albumin complex in milk as well as o / v emulsifier at the temperature of the udder and biological activity of the cow and the udder This results in a phase inversion which results in a uniform and good release of the dispersed feedstock, which is clearly demonstrated by the clinical results. The choice of emulsifiers used and their proportions was greatly influenced by the basic realization that in case of mastitis the milk fat content is always below average and in this case the excess capacity of the biological emulsifier (mixed phosphatide-albumin complex) can be taken into consideration.

The presence of Polysorbat 20 as an o / v emulsifier seems to be unnecessary for emulsifying the liquid propolis extract, for systemic stability, i.e. for the formulation of the udder infusion. However, it will play an important role in contact with milk if it is then activated.

Special storage conditions

- extreme temperature intervals

- only a negligible amount of liquid paraffin separation (0 to 2% by weight) is obtained from the dense flowable or diluted ointment emulsion when aerosil is added.

Thus, the composition of the present invention is comprised of 0.5 to 10% by weight of soft propolis (prepared by cold extraction) and 1-6% by weight of one or two low (3-8) HLB emulsifiers, optionally, a high emulsifier with a high HLB (8-18) and one or more additives, preferably selected from the group consisting of conventional ointment and emulsion base materials, viscosity modifiers and lubricants, inert hydrophilic solvents, pH adjusters.

The present invention will be further described with reference to the following examples.

Example 1

Propolis-containing udder infusion for the treatment or prevention of acute, semi-acute and chronic mastitis in cattle.

To prepare an udder infusion, follow these steps

materials were used: Standard propolis Concentrate (soft propolis) 15g Polyoxaethene 400 30g Lanalcolum 15g Alc. cetylstearylic. 7.5 g Vaseline album 227.50 g Polysorbatum 24.0 g

Paraffins ·! liquidum 431.00 g

From these components, udder infusion of 2% propolis can be prepared. The following components were used for the 6 1% propolis propellant infusion:

Standard Propolis Concentrate 45.00 g (Soft Propolis)

Lanalcolum 15.00 g

Alcohol. cetylstearylic. 7.50 g

Elin iron. album 227.50 g

Polysorbalum 24.00 g

Paraffinum liquiduin 431.00 g

The total weight of the components used in each case is 750.00 g.

Lanalcol, cetylstearyl alcohol and white petrolatum were melted in a water bath with stirring, then sterilized at 140 ° C for three hours, then stirred under aseptic conditions until cooled. Twenty-four hours later, homogenize. In the resulting base ointment, a homogeneous mixture of Polysorbat and propolis was emulsified in portions, still under aseptic conditions, and liquid paraffin sterilized at 140 ° C for 3 hours was added and homogenized in increasing portions with vigorous stirring. The viscous emulsion was added to the container portion of the special disposable plastic syringe by weighing with agitation and then sealed with the plunger. After the closure has been fitted, it is packaged per unit packet. The syringes made of plastic, the drug storage device, were aseptically cleaned and sterilized.

Example 2

Soft propolis emulsion ointment Composition: Soft propolis 10.0 g Propylenglycol 20.0 g Lanalcolum 50.0 g Alcohol cetylstearyl. 30.0 g Elin iron. album 640.0 g Cork. liquid. 200.0 g 01. ricini 50.0 g

Preparation: The soft propolis powder is mixed with 0.5-10 1%, preferably 6 1%, of a hydrophilic indifferent solvent (propylene glycol - polyoxyethylene 400) - preferably propylene glycol.

In a mixture of white petroleum jelly and 5-30% by weight, preferably 20% by weight, liquid paraffin, a low HLB (3-8) emulsifier soluble in 1 or 2 hydrocarbons was dissolved in a water bath at a rate of 2-6% each. Ideally, we used a well-complemented pair of solid interfacial films at the interface of the phases, such as lanalcolum

HU 198843 3% vol and cetylstearyl alcohol. This base ointment was stirred until cooled, homogenized the next day, and then homogenized in small portions with a blend of soft propolis, propylene glycol, and polysorbate.

Accelerated studies were conducted to determine the stability of the drug infusion.

The tests were carried out on samples stored at 40 and 60 ° C in a thermostat. 5 storage times for samples; 90 days, with weekly and monthly assessments in the first month. The drug content was determined photometrically by total flavonoid determination.

For the assay, 5 replicates were tested (mean values are shown in the table).

Example 3

According to the following composition,

to prepare the preparation in the same way: Starting material: propolis content 3.0 g / 100 g ± 10%. Test substance content of trace material: 2.97 g / g%. As a control, the same sample stored at room temperature: Soft propolis Lanalcolum Vaseline album Polysorbate Paraffin liquid 15g 25g 265g 24g 421 g 15 Example 4 20 Soft propolis 15g Alcohol cetylstearyl 25g Vaseline album 265g Polysorbate 24g 25 Paraffin liquid. 421 g

Period room Temperature 20 ° C drug content accelerated, etc. 40 ° C g / g Exam. 60 ° C startup 2.97 - - 1 week 2965 2.97 2.96 2 weeks 2.97 2.96 2.96 3 weeks 2965 2.95 2.95 4 weeks 2.96 2.95 2.95 2 months 2.96 2.94 2.92 3 months 2.96 2.94 2.92

The formulations of the present invention (such as infusion of ointment, ointment, and the like) have a number of efficacy and economic advantages over the formulations containing the specific active ingredients used to date.

They are: - A very broad range of bactericidal, viricidal and fungicidal active ingredients;

- You do not have a nutritional waiting period because it contains a natural active ingredient;

- Highly anti-inflammatory, local anesthetic, exfoliative and analgesic;

- After using it, the so-called Leukis are released from the treated udder. the content of germicidal material is no longer present in six hours, and so

- the milk does not depreciate.

The described benefits have been clearly demonstrated in the use of the formulation.

Of course, when using it, you should follow the basic principles of maslitis treatment:

- Intervene medically as early as possible.

- Treatment must be carried out in accordance with the rules of the craft (lege artis).

- Treatment should be continued for an appropriate period (until symptoms have resolved or slightly longer).

In keeping with the above, we tested the efficacy of our product in ten dairy farms with different abilities and production levels, and compared the results with previously used antibiotic-containing formulations.

The experience is as follows:

HU 198843 A

All trial farms used the preparation uniformly in cases of peracute, acute, semi-acute and chronic mastitis at any time during lactation. A somewhat earlier survey of the prevalence of mastitis pathogens in one plant was available.

This is:

E. coli 18.9%

Str. Uber 13.9%

Str. Dysgalactiae 12.8%

Str. Agalactiae 2.1%

Staph. aureus 7.5%

Staph. albus 4.3%

Corynebact pyogenes 7.5%

Klebsiella 4.8%

Coliform bacter. 4.3%

Bac. subtle 3.2%

Pseud. aeruginosa 1.6%

Bac. cereue 1.1%

Bac. negative 0.5%

Sprouting mushrooms 4.8%

100.0%

Sporadic bacteriological findings from other farms have shown that similar pathogens are present in mastitis.

- In 32 cases, the product was used in case of inflammatory symptoms (pain, redness of the udder skin, mild fever) in one udder quarter, but no visible changes in the milk had been observed. All udders healed without treatment after one treatment. 14 cases healed after 2 treatments without developing lesions in the Leu, and in 15 cases after the start of treatment, a milky purulent lesion was observed in the milk, especially in the first rays of milk. In these cases, treatment was continued. In 8 cases after the third treatment and in 7 cases after the fourth treatment the condition of the milk and udder normalized. In 3 cases there was a change in the consistency besides purulent flakes and lumps in the milk, it became thinner in serum, in 2 cases healing occurred after the fifth and in one case after the sixth treatment. Each treatment was performed at 24 hour intervals. The previously used, mainly imported, antibiotic-containing udder infusion formulations have also been able to achieve complete cure in cases similar to the above. with the same number of treatments, but the milk had to be destroyed for 3-7 days (or longer).

In the first case, mastitis was observed when there was a change in the milk, especially in the first rays of milk, from a fluffy, clumpy grade to a purulent stage. The pain and flushing of the quarters showing milk changes was not pronounced. Six other animals also had other general symptoms, a slight increase in temperature and anorexia. With the exception of these, the other 3-4 treatments were healed- Of these, four had five complete treatments, one had six treatments, and one had aggravated the lesions in the milk, the milk had become serous and oozing. The quarter of the milk became unfit for secretion. In the case of previously used antibiotic-containing udder infusions, the above-mentioned forms are approximately 50% were cured only if they received parenteral antibiotics and electrolytes in addition to topical, intramuscular treatment.

in the case of animals showing very severe general symptoms (high fever, muscle weakness, proffesional diarrhea). Pneumonia has spread to more than one quarters of the udder, with acute clinical symptoms and severe milk change. The milk was distinctly purulent, yellow and eerie. In 6 cases, parenteral antibiotic, electrolyte, and liver protection were used concurrently with the infusion. 5 cows were fully healed on day 5 after treatment, general symptoms disappeared, milk yield normalized. In 1 case the posterior half was completely paralyzed and the animal had to be sent for emergency slaughter. In 4 cases where muscle weakness was not yet pronounced, toog therapy was repeated twice daily without additional therapy. The udder condition returned to normal by day 5, and the milk showed no visible abnormalities on day 7. In 2 cases, parenteral antibiotic and electrolyte therapy was started on the third day after treatment of the quarters, as general symptoms were not reduced. In these animals, the general symptoms returned to normal on day 7 and milk on day 8 returned to normal. Previously used antibiotic 'I' * containing logyin infusions have always been used in the above clinical cases with complementary parenteral therapy. In general, 80% of the cases were recovered, 20% were due to death or forced slaughter, or due to permanent irreversible changes in several quarters animal has been scrapped.

Summarizing the clinical experience with the propolis-containing udder infusion produced by the method of the present invention, it can be stated:

It was clearly demonstrated to all users that even six hours after the udder treatment, there was no so-called udder milk from the treated udder. Positive inhibitory material, thus suitable for industrial use - at full cost. Therefore, there is no need to destroy the milk from the treated area for 3-7 days after the treatment (the importance of the economy is priceless).

The efficacy of the product is at least as good, but in some cases it is even better than that of domestic or imported antibiotic products available in Hungary.

HU 198843 A

It is also not insignificant that very few imports can be produced domestically, that is, it is extremely foreign currency-saving, which is of great economic importance.

Producer and wholesale 5 prices are expected to remain well below the level of import stocks, thus cost-saving for the producer.

Claims (1)

Patent Claim Point A process for the preparation of a medicament comprising a natural disinfectant and antiinflammatory active ingredient, mainly for the treatment of mastitis, characterized in that the active ingredient is 0.5-10 L% soft propolis (prepared by a cold process) and 1-6 l separately. .% of one or two low (3-8) HLB emulsifiers, optionally 20 high HLB (8-18) emulsifiers, and one or more conventional ointment or emulsion base materials, preferably inert hydrocarbon gels or liquid hydrocarbons, lower molecular weight liquid polyethylene glycol derivatives, glycols, optionally vegetable lubricating oils as a lubricant, and processing them into a pharmaceutical composition in a known manner. 30