DE19654826A1 - Veterinary preparation contains proteolytic enzyme - Google Patents

Abstract

A veterinary preparation (I) contains proteolytic enzymes, optionally in combination with vitamins and antibiotics, an ointment base and a hard fat in the form of a thin rod within a tube.

Description

The invention relates to a largely sterile veterinary dosage form for use of active ingredients, in particular proteolytic enzymes in narrow body cavities, preferably for loading act of mastitis in cows.

Mastitis (inflammation of the udder) occurs during milking, standing dry and after calving from kittens arise as a result of infestation with various infectious agents. This is often a significant proportion of the Herd and the performance of the animals by a reduced milk yield and a reduced quality of the milk is significantly impaired.

It is estimated that a minimum of 1 to 2% of a herd is constantly sick and at least every one second cow develops clinically manifest mastitis during lactation (Wendt, K .; Bostedt, H.; Mielke, H .; Fuchs, H.-W. [Ed.], Udder and udder diseases, Gustav Fischer Verlag, Jena 1994, p. 229).

In addition to prophylactic measures, the goal of effective therapy is therefore not just in the Reduction in the number of new cases, but also in the shortening of the illness time (Hoedemaker, M., Mastitis in first calves: causes, therapy and prophylaxis, collegium veteri narium XXV [1995], pp. 22 to 25; Schulz, J. and Marek, P., The Mastitis of the Cattle, Vet Info - The In information service for the veterinarian).

In the treatment of udder diseases, intramammary treatment is of major importance tion. Mainly antibiotics, steroidal and nonsteroidal anti-inflammatory drugs and vitamin A are used used. This treatment has chronic and subclinical mastitis on all four quarters of the udder (Schulz, J. and Marek, P., ibid).

For the treatment of constrictions and stenoses of the teat canal and the application of active ingredients are usually inserted into the teat teat pins before being inserted into the appropriate Ointment and must be withdrawn after 12 hours at the latest sen. The use of these classic teat pins is associated with disadvantages. The teat pins sol len keep the streak canal wide, but the application and its high instillation is inevitable Overstretching of the teat canal and lesions of the walls associated. Besides, only the lower part of the applied ointment to the intended application site, since when the Pins in the teat canal, most of the ointment is stripped off again. When removing the In addition, teat pins pose a risk of injury to the tissue lining the teat canal large, so that another prerequisite for infections is created. That is a little different Treatment of acute, chronic and subclinical mastitis. Here there is the possibility of high Instillation of ointments or suspensions. Better tolerance and effectiveness is achieved through the short instillation of ointment into the teat canal is achieved (Hamann, J. and Marek, P., On the meaning various instillation methods for the effectiveness of the local antibiotic udder treatment, Der Prakt. Tierarzt 4 [1995] pp. 329 to 336; Schött, S. and Schulz, J., Bacterial colonization of the The streak canal in dairy cows and how they are influenced by various intracisternal antibiotics instillation before drying off taking into account Staphylococcus aureus, TU 5 [1995] p. 335 to 360). In this case, possible sticking of the canal by the ointment occurs as disadvantages the release of the active ingredient occurs spontaneously above the insertion point, which means that there is no uniform distribution treatment of the active ingredient in the treated quarters of the udder is guaranteed.

More recently, he has been used as an active ingredient for treating inflammation of the udder Successfully used enzymes (Weigelt, O., inflammation, enzymes, enzyme therapy; Veterinary Um schau, special edition no. 1,2 [1971]; Product information "Mastitis therapy enzymes", Veyx-Pharma GmbH). These active ingredients are also applied according to the methods described above, the disadvantages described also occur. Furthermore, teatpins or plastic are used cannulas that are immersed in an appropriate ointment after endoscopic treatment used for stenoses and scarring. Heparin and proteo are suitable as active ingredients for this lytic enzymes (Lorenz, H.-L., For the treatment of teat stenoses in lactating cows with He parin and proteolytic enzymes. The practical veterinarian 9 [1969]). This already exists written risk of injury.

In summary, it can be stated that the following treatment methods for mastitis and the follow-up care of surgical interventions in the teat canal are currently available:

• a) Direct instillation of ointments / suspensions into the teat canal. The canal can become clogged with the ointment. In addition, the active substances do not have a uniform and long-term effect.
  Two forms are used:
  • - High instillation up to the teat cistern Here the risk of injuries is extremely high.
  • - Brief instillation only in the lower teat canal
    With this treatment, the risk of injury is lower, but the active ingredient is not evenly released.
• b) Instillation of teat pins, which are usually dipped in ointment before insertion. These Pins will have to be pulled out again later. There is a great deal of injury and death Risk of overstretching.

In the case of the known dosage forms, the question of sterility in the treatment of mastitis is raised no particular importance is attached, but it is of great importance for rapid healing. The invention is based on the object of providing a dosage form for veterinary medicinal products, preferably wise for the treatment of stenoses and scarring as well as various forms of mastitis means proteolytic enzymes and vitamins which do not have the disadvantages described above to show.

The object is achieved according to the invention by a medicinal stick, which consists of the biologically active Active ingredients, an ointment base and hard fat, and that in a ready-to-use Application device, such as a tube made of plastic material, is located, and that by mechanical means Pressure on a stamp that pushes the medicinal stick out of the tube, directly into the body cave can be applied.

These tubes serve as a primary pack and also as an applicator.

Venipuncture caesas are used as tubes that are well suited for the application of the drugs Tubes with a length of approx. 50 to 60 mm and a diameter of approx. 2 mm are considered special proved suitable. The venipuncture cannulas are supplied under sterile conditions, and they can be closed again sterile even after the sterile filling of the drug and so on ensure a largely sterile application of the drug stick in the body cavity.

The drug stick is solid under normal temperature conditions and only melts in the animal body off. This results in a uniform release of the active ingredient. The melt spread well in the body cavities to be treated. When manufacturing under sterile conditions he no antibacterial or preservative additives are required for the drug.

A method for producing the new dosage form for the drugs be wrote.

The individual active ingredients (preferably proteolytic enzymes and vitamins) are micronized Form incorporated into a basic ointment from common ingredients (mixing ratio about 1: 100). This can be done by hand on a laboratory scale by rubbing, whereby the trituration time is at least Must be 10 minutes. In the technical process, this process is preceded by appropriate directions done. This mixture is melted in hard fat (DAB 96), which is under sparing the conditions melted (temperature below 40 ° C) entered, if necessary in small Individual portions, dispersed with stirring until uniformly distributed. Then it is at approx. 37 ° C the melt is sucked into the tube and solidified by cooling. If under steri len conditions are used, the tubes are closed and can be sterile in this form be stored.

The invention is to be explained in more detail below using exemplary embodiments, without the invention to limit it.

example 1 Recipe Approach and weighing

Components Quantity (calculated on 10 g) Micronized papain 2.0 mg Chymotrypsin micronized 4.0 mg Trypsin micronized 4.0 mg Veyx base ointment (without enzymes) ^* ) 990.0 mg Hard fat DAB 96 9000.0 mg

*) Basic ointment Veyxym-M ointment with vitamins A and E (without enzymes) Batch 96F03 manufactured on 05/29/96.

production method

Melting the hard fat in a water bath at a constant 37 ° C
Premix the enzymes
Rub the enzyme mixture with base ointment (at least 10 min)
Enter the trituration in small portions into the hard fat melt and disperse while stirring until it is uniformly distributed
Sucking the melt into the tubes at a constant 37 ° C
After the melt has solidified, cool storage at 3-8 ° C

Physical Properties

AL = L <
15 s

Melting point: 36 ° C, hot Melting time: 15 s Medium filling quantity: 215 +/- 5.6 mg

As ready-to-use primary packaging, plastic tubes were used as part of the venipuncture cannula type: Braunüle MT size 4 / G12 / stitch length 50 mm, item no .: 420645/2, batch 96F252588-0116 from Braun-Petzold GmbH Melsungen.
The tube diameter was 2.1 mm, the length 55 mm.
Application aid: Mandrin Introcan W, type 14 G / 2 (2.1 × 50 mm), Art.-No .: 04214218, lot 96A1888-0119 from the same manufacturer.

Example 2 Approach and weighing

Intended primary packaging:
Plastic tubes as part of the venipuncture cannula for catheter insertion Type: Braunüle MT size 4 / G12 / stitch length 5 cm Art.-No. 420 645/2 Lot 96F2588-0116
Tube diameter: approx. 2 mm
Length of the plastic tube: 55 mm
Stylet: Introcan W
Type 14 G / 2 (2.1 × 50 mm) for long-term closure of intravenous cannulas
Item No. 04214218
Lot 96A1888-0119.

Manufacturing

The enzyme amounts were measured on an analytical balance at various points on a map sheet weighed in. The base ointment was weighed out on a watch glass. Using a spatula, the Transfer enzymes with the base ointment from the card sheet to the watch glass and, if possible, on it rubbed evenly. The hard fat was placed in a 100 ml beaker in a water bath at 38 ° C below Stir with a glass rod until creamy and melted. Then the enzyme was added Amount of base cream stirred into portions. The melt was for the period (approx. 60 min) of the Leave the filling in the Braunülen plastic tube at 38 ° C in a water bath.

With a suction ball with a three-way valve, the melt was drawn into the luer cone onto the ball put plastic tubes open. After pulling up approx. 55 mm (end of the tube on the luer cone) the ball was set down and the filled tube was placed on filter paper to harden. After him rigid, recognizable by its milky appearance, the plastic tube was placed in the refrigerator. The further storage of the filled tubes took place in the refrigerator.

Determination of the tube filling quantity deviation

10 empty and 10 (other) filled tubes were individually weighed on a laboratory balance (100 mg dish).

Approach and weighing

Approach and weighing

Intended primary packaging:
Plastic tubes as part of the Vasocan Braunulen intravenous cannula 2 mm diameter × 50 mm (Art.-No. 425820/7):
The filling quantity in the plastic tube is approx. 100 mg (hard wax)
Tube diameter: approx. 2 mm
Length of the plastic tube: 50 mm.

Manufacturing

The enzyme amounts were measured on an analytical balance at various points on a watch glass weighed. The base ointment was weighed in on another watch glass. Using a spatula was made Transfer the base ointment to the watch glass with the enzymes in portions and, if possible, on it rubbed evenly.

The hard fat was in a 25 ml beaker in a water bath at 38 ° C while stirring with a Glass rod melted creamy. Then the amount of Ba added with the enzymes siscreme in portions.

The melt was for the period (approx. 15 min) of filling into the Braunulen plastic tube Leave 38 ° C in the water bath.

Using a suction ball with a three-way valve, the melt was poured into the plastic placed on a ball tube drawn up. After filling (approx. 48-50 mm) the ball was set down and the filled one Put tubes in the refrigerator. The filled tubes were further stored in a screw jar in the refrigerator.

Checking the melting range

1 string of tubes (4 cm) was long in a water bath (500 ml beaker) starting at 28 ° C Sam (1 ° C / min) heated while swirling. At approx. 34 ° C, the strand becomes glassy, flexible and begins to be glued to the edge of the glass. At approx. 35-36 ° C, the still clearly shaped strand melts quickly (10-15 s) through, with the formation of fat eyes.

1 strand 3 cm long, placed in a water bath at 35 ° C, is as described above, Glassy on the surface, but remains shaped. When increasing to 36 ° C, the strand melts away sharply.

As a result, the strand melted away relatively sharply (approx. 15 s) below the given Determine experimental conditions. With the given measuring accuracy of the thermome used Later this melting point is close to 36 ° C.

Example 4 Recipe

Components quantity Trypsin 4.0 mg Chymotrypsin 4.0 mg Papain 2.0 mg Veyxym-M ointment (without enzymes) 990.0 mg Hard fat DAB 96 9000.0 mg

packaging

Braunulen 250 pcs Mandrins 50 pcs

Manufacturing

Quantity to be weighed: total mass 60.0 g

Trypsin 26.0 mg Chymotrypsin 26.0 mg Papain 12.0 mg Veyxym-M ointment (without enzymes) 5.934 mg Hard fat DAB 96 54.0 mg

Execution:

• - The weighed mass of hard fat is melted on a water bath at 37 ° C in a beaker
• - the enzymes weighed in on the analytical balance are placed on the watch glass with the help of a Kar mixed paper
• - the enzyme mixture is rubbed with the ointment base on the watch glass with a glass rod (10 min)
• - the enzyme-ointment mixture is poured into the melted hard fat base and dispersed
• - The melt is left on the water bath at 37 ° C during the filling into the brown sinks
• - the filling of the mass takes place by suction with a suction ball (peleus ball)
• - The Braunulen are stored at room temperature until the mass solidifies (10 min)
• - then storage in the refrigerator at 8 ° C.

Result: 250 pens were produced.
Uniformity of the mass:

Claims (4)

1. Largely sterile veterinary dosage form for the application of biologically active ingredients, in particular proteolytic enzymes, optionally in combination with vitamins and / or antibiotics, preferably for the treatment of stenoses, scarring, chronic and subclinical mastitis in the form of medicinal sticks, characterized in that that the medicinal active ingredients are mixed with a conventional ointment base and hard fat (DAB 96) at room temperature in solid form as medicinal sticks in a tube, from which they can be applied directly into the body cavity by pressing a stamp, where they melt at body temperature and the Release active ingredient. 2. Veterinary pharmaceutical dosage form according to claim 1, characterized in that it is used as Active ingredients of proteolytic enzymes such as trypsin, chymotrypsin, papain and bromelain are given if in combination with vitamins and / or antibiotics contains. 3. A method for the production of medicaments according to claim 1 and 2, characterized in that the active ingredients preferably proteolytic enzymes in micronized form in a base ointment common ingredients incorporated until evenly distributed and melted in Hard fat (DAB 96) entered and dispersed to a uniform distribution and at approx. 37 ° C the melt is sucked into tubes and solidified by cooling. 4. Tube according to claim 1 and 3, characterized in that it is used as a primary ver pack and applicator can be used.