CS277558B6 - Vaccine for treating chronic yeastlike elytronitis - Google Patents

Abstract

Vaccine for the treatment of protracted yeast Inflammation of the vagina is characterized by 3 strains Candida alblcans, 1 strain Candida krusei, 1 Torulopsls glabrata strain and 3 Propionibacterium strains acnes. It is useful for the treatment of protracted inflammation of mucous membranes and other sites and may be complement to antifungal therapy in organs Forms of Yeast Etlologle Infections.

Description

Field of technology

The invention relates to a polymicrobial vaccine comprising strains of Candida albicans, Candida krusei, Torulopsis glabrata and Propionibacterium acnes. It is determined by its specific and non-specific immunostimulatory activity for the treatment of prolonged and recurrent vaginitis caused by yeast-like microorganisms.

Prior art

Yeast infections of the vagina are undoubtedly one of the most common fungal infections in humans. Their acute forms are well managed with conventional topical antifungals. However, the treatment of recurrent yeast infections with a tendency to a chronic course, the number of which is constantly increasing, remains problematic. They are used with antifungals locally and in general, often for a long time and without effect.

Although mucosal yeast infections are characteristic of patients with endocrinopathy, they can be a serious infection in patients with cellular immune defects, phagocytosis disorders, or humoral immune changes. In these cases, antifungal treatments are also used in combination with transfer factor-type immunostimulatory agents or with immunomodulators such as levamizole. It is an economically and in some cases time-consuming treatment, which usually has only a temporary effect.

The persistence of the problems and the repeated failure of the treatment often lead to a considerable psychological alteration of the patient. Sexual relationships with negative consequences for family life can also be affected.

The essence of the invention

The vaccine according to the invention modulates the specific immune reactivity to the species of yeast-like microorganisms which are most often used as etiological agents in inflammation of the vaginal mucosa. The non-specific component of immunity is influenced by adjuvant strains of Propionibacterium acnes.

The vaccine according to the invention contains as specifically active ingredient 3 strains of Candida albicans (CA 37, CA 91, CA 120), one strain of Candida krusei (CK 9), one strain of Torulopsis glabrata (TG 15) in unlimited proportions and as non-specifically active ingredient 3 strains Propionibacterium acnes (PA 3, PA 17, PA 530) in unlimited proportion. The active ingredients are in a weight ratio of 1: 1. The amount of microbial dry matter in 1 therapeutic dose is 5 mg for oral administration and 7 mg for vaginal administration.

^T 'are both vaccine according to the invention is economically less demanding than the existing methods of treatment. No adverse side effects are observed during vaccination therapy. The relatively fast onset effect of the vaccine is more permanent, especially with simultaneous vaginal and oral administration.

The use of the vaccine in oral form is possible without risk even in childhood, it is suitable for the treatment of yeast infections in endocrinopathies and iminute disorders.

The vaccine of the invention substantially shortens the treatment of chronic forms of the disease and prolongs the intervals between relapses. Indirectly, it increases trust between partners and eliminates the negative consequences of the disease in the family.

The vaccine of the invention can be used in healthcare. In human medicine, it is intended for the treatment of protracted and recurrent yeast infections of the vagina. In its oral form, it can be used to treat lingering mucositis in other locations. It can also be an adjunct to the treatment of antifungals in organ forms, an infection of yeast etiology.

The vaccine according to the invention is preferably administered orally in the form of tablets. Both forms can be administered simultaneously. Dosage forms are prepared so that one oral dose contains 5 mg and one vaginal tablet 7 mg of the microbial mixture.

Example of an embodiment of the invention

Example 1

Candida albicans strains CA 37, CA 91, CA 120, Candida krusei CK 9, Torulopsis glabrata TG 15 were cultured by cellophane technique on glucosopeptone agar at 37 ° C for 48 h, in an air atmosphere containing 10% CO ₂ . The expanded culture was rinsed with distilled water and disintegrated by repeated freezing. The obtained lysate was inactivated with formol (0.1 ml in 4% formula per 1 ml of suspension). After sterility control, all material was lyophilized.

Propionibacterium acnes strains PA 3, PA 17, PA 530 were cultured by cellophane technique on VL agar with 10% blood collection at 37 ° C for 48 h, in a nitrogen atmosphere with 10% CO ₂ . After multiplication, the bacterial bodies were rinsed and extracted with distilled water for 24 h at 4 ° C. The obtained bacterial mass was inactivated by heating at 60 ° C for 1 h, repeatedly at least 3 times in an interval of 24 h. After checking the sterility, all the material was lyophilized.

The final form of the vaccine was prepared:

1.1. By mixing dry matter of Candida albicans strains CA 37, CA 91, CA 120, Candida krusei CK 9, Torulopsis glabrata TG 15 in mass, ratio 1: 1: 1: 1: 1 for individual strains

2. By mixing dry matter of Propionibacterium acnes strains PA 3, PA 17, PA 530 in mass, ratio 1: 1: 1 for individual strains.

II. By mixing the 1st and 2nd dryers in a weight ratio of 1: 1.

Example 2

Candida albicans strains CA 37, CA 91, CA 120, Candida krusei CK 9, Torulopsis glabrata TG 15 were cultured by fermentor technique in liquid glucosopeptone medium at 37 ° C for 48 h. After propagation, the yeast culture was separated from the culture medium by repeated washing in distilled water and centrifuged at 2,000 to

500 G. Isolated yeast bodies were disintegrated by freezing and inactivated with a mold (0.1 ml of 4% formol per 1 ml of suspension). After sterility control, all material was lyophilized.

Propionibacterium acnes strains PA 3, PA 17, PA 530 were cultured by fermentor technique in VL broth at 37 ° C for 48 h. After multiplication, the bacterial bodies were separated from the nutrient medium by repeated washing in distilled water and centrifugation at 2,000 to 2,500 G Isolated bacterial bodies were extracted with distilled water for 24 h at 4 ° C and inactivated by heating at 60 ° C for 1 h, at least 3 times at 24 h intervals. After sterility control, all material was lyophilized.

The final form of the vaccine was prepared:

1.1. By mixing the dry matter of Candida albicans strains CA 37, CA 91, CA 120, Candida krusei CK 9, Torulopsis glabrata TG 15 in a weight ratio of 1: 1: 1: 1: 1 for the individual strains.

2. By mixing dry matter of Propionibacterium acnes strains PA 3, PA 17, PA 530 in mass, ratio 1: 1: 1 for individual strains.

II. By mixing solids 1. and 2, in a weight ratio of 1: 1.

Pharmacological tests

The effect of the vaccine on the reticuloendothelial system of SPF mice was verified. A single dose of 1.5 mg was administered intraperitoneally to a group of 20 mice. Ten days after vaccination, the animals were sacrificed and histological examinations of the spleen and springs were performed. The obtained results showed strong stimulation of the reticuloendothelial system.

A group of mice was infected with Candida albicans at a dose of LD ₅₀ intravenously into the tail vein on day 14 after vaccination. The infection killed 3 mice on the 4th day of infection, during the 8th to 10th day another 9 of the total number of 15 mice died. In the same control group, 14 mice died on the 2nd to 3rd day of infection.

Due to non-specific vaccine prevention, the animals were much more resistant to lethal infections and viral origin. Mice were infected with EMC virus at a dose of LD- ₁₀ at intervals of 24 h, 4 and 8 days after vaccination with the vaccine. Of the group of mice infected with the EMC virus 24 h after vaccination, 60% died on day 11, of the mice infected no days after vaccination only 20%, while of the mice infected 8 days after vaccination 40%. Mice in the control group died 100%.

Clinical trials in patients with vaginal mycosis:

Total number of patients (women) 175

Method of application% of successful applications

Oral (99 patients) 72.7 (72 patients)

Local (54 patients) 68.5 (37 patients)

Combination of oral and topical 77.3 (17 patients) (22 patients)

Claims (3)

PATENT CLAIMS A vaccine for the treatment of prolonged yeast inflammation of the vagina, characterized in that it contains as specifically active ingredient 3 strains of Candida albinans, one strain of Candida krusei, one strain of Torulopsis glabrata in unlimited proportions and as non-specifically active ingredient 3 strains of Propionibacterium acnes in that the active ingredients are in a weight ratio of 1: 1, the proportion of the individual ingredients differing by at most 10% and the total amount of microbial dry matter in 1 therapeutic dose is 4.5 to 5.5 mg for oral administration or 6.5 up to 7.5 mg for vaginal administration. 2. The vaccine according to item 1, characterized in that it comprises strains of Candida albinacs CA 37, CA 91, CA 120, Candida krusei CK 9, Torulopsis glabrata TG 15 and strains of Propionibacterium acnes PA 3, PA 17, PA 530.