DE19845285A1 - Treatment or prophylaxis of feline infectious peritonitis, using glyoxal or derivative, preferably in combination with immunostimulant - Google Patents

Abstract

The use of glyoxal and/or its derivative for the treatment and/or prophylaxis of feline infectious peritonitis (FIP) is new. An Independent claim is included for a kit containing glyoxal (and/or its derivative) and an immunostimulant, in a suitable dosage form.

Description

The present invention relates to agents for treatment and / or prophylaxis xe of feline infectious peritonitis.

Feline infectious peritonitis (FIP) is one of the major infectious diseases Feuds for which there is currently no suitable therapy option and which therefore ei ne mortality rate of 100%. The causative agent of feline infectious peritonitis is a Corona virus (FIPV), which is distributed worldwide. Virus strains with under Different virulence occur in the field and cause infections in the most cases are asymptomatic. The transmission of the corona virus can intrauterine or postnatally orally. The virus is either via the Leu mother's cocytes are transferred to the fetus or orally ingested FIPV colonize the intestinal epithelium and possibly epithelia of the upper respiratory tract animal, where virus replication occurs and then in a few cases cease mild symptoms of illness. In some cases, the virus becomes affini for monocytes and can spread through these cells in the body. The sick outbreak depends on the general condition of the animal, e.g. B. the age of Immune competence, stress factors, taking immunosuppressants, e.g. B. Glucocorti koiden. If the cellular immune response is weak, there is an exudative Form of FIP. Infected macrophages accumulate especially around blood vessels and in the Interstitium of the serous surfaces. The infected cells express antigens and are increasingly synthesizing complement factors and other inflammatory mediators. This leads to the activation of lymphocytes with appropriate systemic fol conditions such as fever and increased antibody production. Because of the participation neutrophic granulocytes, the perivascular infiltrates are often called pyogranulo called matous. When infected macrophages disintegrate, viruses become antibodies per bound, and an immune complex is created. This activates the complement factor ren, which increases the local inflammation. The resulting Im mu complexes are in turn phagocytosed by macrophages, in which the Virus can multiply. This leads to a vicious circle, which in a ver utility coagulophathy with vascular damage and conversion of a protein-rich Fluid culminates in the abdomen and / or chest. This ascites is an ex  sudat with a specific weight above 1030 g / l, a protein concentration above 50 g / l and a cell content of over 25,000 leukocytes / l.

If the cell-mediated immune response to the virus is strong, one occurs "dry" course of the disease without the passage of liquid into the abdominal and / or chest cavity. This course is due to a less strong macropha gene response and lower virus production. In rare cases with a good overall constitution of the animal, the virus replication by the body your own immune system.

During the course of the disease there is an increasing deterioration of space of cats' common health. You lose weight and life action and her coat appears dull and ruffled. The patient almost always gets sick The course of the disease is accompanied by a relatively high fever, which is usually continuous. Typically, the circumference of the abdomen increases with the exudative course to what is on the influence of the protein-containing liquid in the chest and the Abdominal cavity. Hepatomegaly is also common. Wei Other diseased organs include the spleen, pancreas, kidneys, brain and the internal organs of the eye. Accordingly, the other symptoms are the sick chronic hepatitis, indigestion, uremia, breathing difficulties, disturbances Central nervous system disorders and impaired vision. The same symptoms are observed in the "dry" clinical picture mentioned above respects, but the swelling of the abdomen or chest is missing in the sick animals.

The severity of the disease stage can be determined by "FIP screening" in combination with the occurrence of the above-mentioned disease symptoms. "FIP screening" is understood in specialist circles to determine the following blood parameters: total bilirubin, large blood count (including determination of the values for Hb, Hb _E , erythrocytes, differential blood count, MCV (mean corpuscular volume), hematocrit, leukocytes), electrophoretogram and GPT (glutamate pyruvate transaminase).

Titer examinations in healthy cats are not sensible, since an increased titer in healthy animals also an infection with the harmless enteral coronavi rus can be attributed. Over 50% of cats in Germany are serological Coronavirus positive. With acute FIP symptoms, the antibody titer is often on values increased over 1: 400, which can be taken as an indication of FIP disease. Furthermore, approximately 75% of the animals have an increased plasma protein concentration tration. This results particularly from a shortly after infection with FIP respectful increase in γ-immunoglobulins in the blood, on which in the course of the sick an increase in the α and β globulin values follows. Furthermore, you can continue stage of the exudative course with a consumption coagulopathy observe prolonged bleeding times.

Previously used therapy methods are limited to the symptoms, not however, to treat the cause of the disease, and overall have only a minor Success rate on. So with the exudative form of the disease, a lavage of the Abdominal cavity performed with a physiological saline solution and then dexamethasone in a high dose, but it is quickly reduced enough. This therapy is supported by the administration of azathioprine. Al Alternatively, the antibiotic chloramphenicol is prescribed. Because of this so far unsatisfactory therapy procedures, characterized by a mortality rate of 100% Are characterized, there is a great need for an effective The therapy for feline infectious peritonitis.

An effective prophylaxis for FIP is also not yet known. So z. B. a recently developed vaccine is currently controversial in its effectiveness However, since there is a greatly increased risk that z. B. after the disease Animal in a herd also get other animals, there is definitely a problem after preventive treatment, e.g. B. in animal homes, zoos, animal parks, etc.

It is therefore an object of the present invention to provide means for a successful loading to provide treatment or / and prophylaxis of feline peritonitis.

The task is accomplished through the use of glyoxal and / or at least one Derivative thereof for the treatment and / or prophylaxis of feline infectious peritonitis solved.

The task is further accomplished by a kit comprising glyoxal and / or at least a derivative thereof and a means of strengthening the immune system in a suitable one Dosage form, solved.

The substance glyoxal is often used as an additive in disinfectant liquids used, but can also be used in homeopathic dilutions in pediatrics Combating infections and their late effects and generally for treatment used by malignancies. The present invention first sees the Use of glyoxal and / or derivatives thereof, such as. B. methylglyoxal, for loading treatment of a virus-related disease and / or prophylaxis thereof Animals.

In a preferred embodiment, glyoxal is used along with its derivative Methylglyoxal used. In this case a ratio of 1: 1 is particularly advantageous arrested.

Furthermore, an agent can be used together with glyoxal and / or a derivative thereof used to strengthen the immune system. Examples of such Immunsti mulants are thymopentine acetate or dimepranol-4-acetamidobenzoate and be agreed herbal extracts.

In a preferred embodiment, the immunostimulating agent is echinacin, an extract from above and / or underground parts of plants from plants of the Gat tung Echinacea, used. The genus Echinacea includes 9 species, the predominant can be found on the North American continent. The ingredients of this plant zen have been studied extensively. It was shown that the root organs have a rela tively high proportion of essential oils (up to over 2%) and a relatively high proportion  on polyacetylenes and alkamides. Furthermore, caffeic acid Derivatives such as B. echinacoside and cynarin, which is characteristic of echinacin is proven. The immune-stimulating we of Echinacea extracts, especially from the root organ. So leads oral administration of 10 ml / kg body weight / day of a solution of 0.5 ml of a Echinacea ethanol extract in 30 ml of physiological saline over 2 Days to a significantly increased phagocytosis rate in mice (factor 1.7). The per oral administration of mother tincture from Echinacea angustifolia (coneflower) also showed IgG and IgA levels increased by up to 32% after 7 and 9 days of treatment, respectively. In contrast, the IgM value on the 7th day was only about 8% compared to the control elevated. In Plaque inhibition tests were also able to demonstrate that aqueous extracts (1:10) from the root of Echinacea angustifolium an antibacterial and virussta show a table effect. So for the ingredient echinacoside a schwa inhibitory effect against Staphylococcus aureus can be measured. For the Polyacetylene trideca-1-en-3,5,7,9,11-pentain was in a concentration of 50 µg / ml observed a total growth inhibition against Escherichia coli and against a strong growth inhibition at a concentration of 1 mg / ml Pseudomonas aeruginosa detected. Furthermore, in the carrageenan Rat paw edema model showed that the polysaccharide fraction was made up Echinacea anpustifolia roots in an IV applied dose of 0.1 mg / kg body weight has a 65% inhibitory effect on edema. In addition, the etheri The oil of the plant genus confirmed as a tumor-inhibiting composition. A Effect on corona viruses has not been established so far.

In addition, for the treatment and or prophylaxis of FIP, vitamin B Be used complex. This complex is structurally very subordinate various water-soluble vitamins, such as thiamine, riboflavin, vitamin B6, vitamin B12, folic acid, niacin, biotin and pantothenic acid. In general, these vitamins work as co-factors for metabolic enzymes and regular intake of vitamin B- Complexities can prevent deficiency symptoms.  

Furthermore, at least one substance, selected from the group consisting of orotic acid, aneurine, PP factor (nicotine acid amide), choline citrate, i-inositol, cytochrome C and glucose.

Tea tree oil can be used as a further effective component. The oil will extracted from the deciduous tree Melaleuca alternifolia, which is only natural in Australia occurs. The oil shows a strong antiseptic effect without being toxic or being irritant. Furthermore, a virucidal and fungal strain could also be found fighting effect can be demonstrated. Because of these properties, Oil nowadays often as an additive for skin care products such as shampoos, soaps, deodorants, Body lotions and toothpaste used. However, it can also be used orally because no toxic effects could be determined.

Treatment of enemies with FIP can also include the administration of Milk thistle (Silybum marianum) and / or active ingredients thereof sen. The milk thistle belongs to the genus Asteraceae and is also under the common name fever thistle, female thistle, savory thistle, Christikrone and Marien- or prickly grains known. The plants are one or two years old, 60 to 150 cm high and rich in hairy leaves with thorny edges. The milk thistle is be especially in southern Europe, but sometimes also in northern countries such as England and Denmark, as well as in Asia Minor, North Africa and the Canaries. As a drug the ripe fruits freed from the pappus are usually used. Main ver the flavos contained in it are responsible for the healing properties of the plant seeds nolignane, with the three most common flavonolignans being Silybin, Silycri stin and silydianin are summarized under the term silymarin.

Furthermore, star hyacinth (Scilla bifiolia) or effective components of it Plant used to treat and / or prevent FIP. The star hyacinth belongs to the genus of the lily family and is mainly in the sub spread to tropical regions of the old world. In homeopathic dilutions Extracts of this plant are used for mild forms of heart failure  also given reduced kidney output at the same time, since they drive water de effect, which relieves the circulatory system.

The present invention further provides a kit, the glyoxal and / or at least one derivative thereof and an agent for strengthening the immune system systems in a suitable dosage form.

In a preferred embodiment, the agent contained in this kit is for Strengthening the immune system an extract from Echinacea, e.g. B. Echinacin.

The kit can also contain a vitamin B complex and / or substances chooses from the group consisting of orotic acid, aneurine, PP factor, choline citrate, i- Inositol and cytochrome C include.

In a preferred embodiment, the kit contains, in addition to substances The group described above continues to have dextrose.

In addition, the kit can also use tea tree oil, milk thistle and / or sternhya contain tin or active ingredients of these plants. All of the above Agents and substances can be given to the patient at the same time or at intervals administered from each other.

To treat FlP-related feuds, one should be at the disease stage adapted treatment method can be selected. For mild illnesses, with de slight to marginal changes in the blood count can be observed without that however liver damage or other clinical symptoms are present or Prophylaxis of FIP, e.g. B. if other animals already fall ill from the same husbandry are successful with the following treatment regimen:  

Table 1

Treatment schedule I

The administration of the glyoxal-containing drug carbonyl groups (1 ampoule à 2 ml contains: 1 ml methylglyoxal D6 aquos., 1 ml glyoxal D6 aquos.) 1 to 2 subcutaneous administration of immunostimulants, e.g. B. Echinacin and Vit accompanied amine B complex. The use of echinacin in the form of a Solution, e.g. B. Echinacea Miniplex® (1-2 ml / day / cat; active ingredients / 100 ml: 9.70 g Echinacea angustifolia D5, 38.80 g Lachesis D8, 38.80 g Pyrogenium D18, 9.70 g Belladonna D4, potentiated with 20% alcohol) or Echinacea compositum S. (1-2.2 ml / day / cat; active ingredients / 2.2 ml: Echinacea angustifolia D3, Aconitum D3, Sanguinaria D4, Sulfur D8, Baptisia D4, Lachesis D10, Bryonia D6, Hipalorium perloliatum D6, Pulsatilla D8, Hydrargyrum bichloral D8, Ihuja D8, flu Nosode D13, phosphorus D8, cortisone acetate D13, streptococcinum D18, staphylo coccinum D18, Phylolacca D6, Pyrogenium D198, Zincum metallicum D10, Colseni around D6, Hepar sullaris D10, Rhus toxicodendron D4, Arnica D4, Acidum arsenicosum D8, Argentum nitricum D8, Euphorbium D6 each 22 µl) and of vitamin B complex as brachiopas (active ingredients / 2 ml: 2 mg cyanocobalamin, 40 mg Nicoti namid, rutoside-sulfuric acid ester, 50 mg sodium salts, 40 mg procaine hydrochloro rid) determined in a dose of 1-4 ml as particularly suitable.

In FIP patients who already have mild to moderate electrical changes phorese and other blood count values (see Example 2: normal values), but otherwise a general condition that can still be described as good without disturbance of the liver the following treatment scheme II is used:  

Table 2

Treatment schedule II

With this therapy, the sick patient gets an additional one every day Orocid® tablet (active ingredients / tablet: 100 mg orotic acid, 4 mg aneurine, 25 mg PP factor, 10 mg choline citrate, 10 mg i-inositol, 1 µg cytochrome C, 100 mg Dextrose) as well as commercially available tea tree oil and one or twice a week Solution containing the immune stimulants and vitamin B complex as described above holds, administered subcutaneously.

With a severe clinical picture, which can be seen in a strongly changed blood picture, especially with regard to the electrophoresis values, as well as liver dysfunction and If other clinical symptoms mentioned above are manifested, the following treatment is performed Scheme III successfully used:  

Table 3

Treatment regimen III

Accompanying seriously ill FIP patients will receive a mixture once or twice a week from immune stimulants and vitamin B complex in soluble form, as described above ben, injected subcutaneously. If increased liver enzyme values were found in the blood count, also milk thistle extract administered. The gift of milk thistle in Form of Heparano N® coated tablets (active ingredients / coated tablets: 133.6-203.7 mg native dry extract from milk thistle fruits (20-33.3 = 1), corresponding to 84 mg Silymann, calculated as silibin; Extracting agent: 1. acetone, 2. ethanol 94% (v / v)) or Silibene®140 tablets (active ingredients / tablet: 233-280 mg dryex tract of milk thistle fruits (25-35: 1), corresponding to 140 mg Silymann, calculated as silibinin (extracting agent: acetone)) in a dosage of one dragee or one Tablet per day proved to be particularly effective. In the case of the exudative sick A homeopathic dilution of star is also carried out daily administered hyacinth. A dosage of one tablet (effective Components / tablet: Star hyacinth D1), possibly administered several times a day is enough to prove effective. To support FIP therapy or -Prophylaxis are the drinking water of all patients 3-5 drops of the immune  stimulant Viruvetsan® (active ingredients / 100 g: 1 g Echinacea angustifolia D1, 1 g of Bufo D10, 5 g of Coffea tosta D1) are added.

Treatment regimens I-III are intended as guidelines for treatment and prophylaxis xe serve the various stages of FIP disease; however, they should relate on the duration of use and concentrations of the individual components The patient's needs can be varied accordingly.

The following figures and examples serve to explain the invention.

Fig. 1 physiological electrophoretogram of a cat for immunoglobulin determination;

Fig. 2 is a diseased electrophoretogram with FIP after 4 weeks of treatment according to the treatment scheme III (patient no. 21);

Fig. 3 electrophoretogram a diseased cat FIP after 6 weeks of treatment according to the treatment scheme III.

EXAMPLE 1

Table 4 shows the course of treatment of 27 test cats, which were treated according to the treatment regimens I-III mentioned above.  

Test cats No. 1 to 8, in which no FIP symptoms were shown, were per treated phylactically according to treatment schedule I. After 4-6 weeks of treatment wa no FIP symptoms. In patients with mild symptoms (Patients nos. 9 to 18) the treatment according to treatment schedule II was successful be performed richly, with the result that the patients have no FIP symptoms had more. Treatment scheme III was applied to patients who were were already seriously ill with FIP (patients nos. 19 to 27). In all cases len a significant improvement in general condition and the absence of FIP symptoms can be diagnosed.

EXAMPLE 2

The laboratory results for patient 21 (see Table 4) are shown in Table 5a-5c. This shows that the measured values for α-, β- and γ-immunoglobulins in the blood have largely adjusted to values in the normal range after four weeks of treatment. Furthermore, the value for serum glutamate pyruvate trans aminase (SGPT) as well as the value for the hemoglobin content of the erythrocytes (Hb _E ) and the haematocrit value have also reached a normal level.

TABLE 5a

TABLE 5b

TABLE 5c

EXAMPLE 3

The laboratory results for another patient who was treated according to treatment schedule III treated are shown in Table 6a-6c. It follows that the patient had an unusually high titer of <1: 1 600. The blood measurements have changed after six weeks of treatment largely adjusted to values in the normal range. In addition, the general condition of the patient has significantly improved sert.

TABLE 6a

TABLE 6b

TABLE 6c

Claims (19)

1. Use of glyoxal and / or at least one derivative thereof for treatment treatment and / or prophylaxis of feline infectious peritonitis. 2. Use according to claim 1, characterized in that the glyoxal derivative Is methylglyoxal. 3. Use according to claim 2, characterized in that glyoxal and Me thylglyoxal in a ratio of 1: 1 can be used. 4. Use according to one of claims 1 to 3, characterized in that a means of strengthening the immune system continues to be used. 5. Use according to claim 4, characterized in that the agent for starch immune system echinacin. 6. Use according to at least one of claims 1 to 5, characterized records that a vitamin B complex is still used. 7. Use according to at least one of claims 1 to 6, characterized records that at least one substance selected from the group, consisting of orotic acid, aneurine, PP factor, choline citrate, i-inositol and cytochrome C, is used. 8. Use according to at least one of claims 1 to 7, characterized indicates that dextrose is still used. 9. Use according to at least one of claims 1 to 8, characterized records that tea tree oil (Oleum melaleucae alternifoliae) continues to be used becomes. 10. Use according to at least one of claims 1 to 9, characterized indicates that milk thistle (Silybum marianum) and / or effective Be parts of it are used.   11. Use according to at least one of claims 1 to 10, characterized records that star hyacinth (Scilla bifolia) and / or effective stock continues parts of it are used. 12. Kit comprising glyoxal and / or at least one derivative thereof and an agent for Strengthening the immune system in a suitable dosage form. 13. Kit according to claim 12, characterized in that the means for strengthening the Echinacin's immune system. 14. Kit according to one of claims 12 or 13, characterized in that the kit further comprises a vitamin B complex. 15. Kit according to at least one of claims 12 to 14, characterized in that that the kit further be at least one substance selected from the group consisting of: orotic acid, aneurine, PP factor, choline citrate, i-inositol and cytochrome C, includes. 16. Kit according to at least one of claims 12 to 15, characterized in that that the kit continues to contain glucose. 17. Kit according to at least one of claims 13 to 16, characterized in that that the kit also includes tea tree oil (Oleum melaleuca alternifolia). 18. Kit according to at least one of claims 13 to 17, characterized in that that the kit continues milk thistle (Silybum marianum) and / or effective stock parts thereof. 19. Kit according to at least one of claims 13 to 18, characterized in that that the kit also contains star hyacinth (Scilla bifolia) and / or active ingredients of which includes.