Vaccine against urogenital infections on the basis of a vaginal suppository

 

The invention relates to immunobiological industry and relates to vaccines against infections on the basis of a vaginal suppository. The invention includes a suppository for prevention of urogenital infectious diseases, such as urinary tract infections, including inactivated bacteria originating from cultures from 8 to 14 strains uropathogenic bacterial species: E. coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus morganii and Streptococcus faecalis isolated from the urine of people suffering from urinary tract infections, and polietilenglikoli the basis of the suppository, and also a method for prevention of urogenital diseases. The advantage of the invention is to develop a device vaccine delivery based suppository for prevention of urogenital infectious diseases. 6 C. and 23 C. p. F.-ly, 1 Il.

Field of invention the Present invention relates in General to a device and method for the treatment of disease in humans, in particular for prophylactic treatment of urogenital infections in humans. More specifically, the invention relates to a device based suppositories for intravaginal delivery of vaccines for the prevention of urinary tract infections in humans, which is more specifically the present invention relates to a delivery device based on the suppository for prevention of recurrent urinary tract infections in humans, in which the suppository contains vaccine of whole, inactivated bacteria, which come from cultures from 4 to 20 uropathogenic bacterial strains isolated from the urine of persons suffering from infections of the urinary tract, which includes polietilenglikoli the basis of the suppository.

Background of the invention urinary tract Infections are a major problem in medicine. May be affected any part of the urinary tract. The most common diseases are cystitis, urethral syndrome, pyelitis and pyelonephritis. For urinary tract infection characterized by a tendency to recurrent and chronic progression. The disease is ten times more common in women than in men. This difference is due mainly to the fact that the specific anatomy of the female urethra facilitates infection of native bacterial flora of the intestine. The main diagnostic criterion of urinary tract infection bacteriuria is the presence of bacteria in a properly collected urine sample (urine mid stream). For bacteriuria was considered digaudio urinary tract, cause infection or through the blood stream, or by the rising spread from the urethra into the bladder and up the ureter in the kidney. Ascending infection is the most common method and explains its more frequent occurrence in women. Location of the mouth of the urethra and the short urethra in women contribute to infection. Various bacteria originating from the fecal flora, always live in the mouth of the urethra and the distal part of the urethra of women. Urinary tract infections in women begins when one of Enterobacteriaceae, originating from fecal flora colonizes the eve of the vagina.

The most frequent and numerous component of the fecal flora is Escherichia coli, which is also often found in the urine as the causative agent of urinary tract infections. Escherichia coli is also frequently found in periuretralnuu area. This bacterium is able to stick to periuretralnuu epithelial cells. Adhesion of bacteria is a prerequisite for colonization and infection of the urinary tract. Many in vitro studies have shown that the phenomenon of adhesion associated with the presence of fimbriae in Escherichia coli infecting the urinary tract. Bacteria Escherichia coli are the most frequent pathogens sustained fashion cocci, such as Staphylococcus and Streptococcus faecalis (Enterococcus). In the urinary tract also introduced other bacteria, such as Pseudomonas aeruginesa and Haemophilus influenzae. Any bacterial inhabitants of the intestinal tract, which are excreted with feces, can colonize the urinary tract. In addition, the urinary tract can be occupied by Mycoplasma, L-forms of bacteria, chlamydia, fungi, viruses and protozoa.

For urinary tract infection characterized by recurrent and chronic. Relapse can be either due to resume, or due to repeated infections. Despite great advances in the treatment of other bacterial infections over the last 20-25 years, the incidence of and mortality from urinary tract infections remain the same. The reasons for this huge number, and they depend on the host organism and microbial factors.

The recurrence of infections previously infected by a strain of the organism are rare and can occur due to incorrect selection of drug, the emergence of resistant strains, inadequate duration of treatment, insufficient concentrations of antibacterial agents, the existence of bacterial L-forms and survival of organisms in the urinary stones. All recurring infections urea is elshimi higher ability to adhere to epithelial cells of the vagina and urethra. Re-infecting bacteria originate from the intestinal flora. The composition of the intestinal flora may change through preventive and therapeutic use of antibiotics and other antimicrobial materials that are used in the treatment and prevention of urinary tract infections. The intestinal flora often develop resistance to antibiotics and resistant bacteria can then cause re-infection or primary opportunistic infection of the urinary tract. Such primary infections can be caused by opportunistic pathogenic bacteria, which occur due to the destruction of antibiotics normal, harmless flora, such as lactic acid bacteria. In this case, can proliferate and become other pathogenic microbes resistant to antibiotics. Resistance of bacteria to antibiotics, caused by R-plasmids, not only is passed between the same species of bacteria, but also passed almost all Enterobacteriaceae. Often it is also found resistance to many antibiotics.

The main cause of recurrent urinary tract infections in women is an immunological disorder, which facilitates adhesion uropathogenic organisms to perimetralmente immune response of the urinary tract and promotes recurrent ascending urinary tract infections. The most important property of sIgA is that they prevent the interaction of bacterial fimbriae with specific receptors detected in the epithelium of the urinary tract. Mediated by fimbriae ability to adhesion is an important virulence factor involved bacteria. To protect against infection, it is important to reduce the adhesion of pathogens to the epithelium of the urinary tract or to prevent the attachment of bacteria to each other.

Usually the host organism produces specific antibodies against penetrating bacteria and secretes these antibodies in the form of sIgA. In patients with evidence of persistent elevations or frequently recurrent urinary tract infections this natural mechanism of local immunological protection against infection, obviously disturbed. Therefore, the enhancement of immune protection is a rational means of eliminating the causes of recurrent urinary tract infections. Particularly favorable vaccination, which stimulates the production of antibodies against a range of antigens present in several types of Escherichia coli and other common urinary bacteria.

Earlier vaccines against infections of the urinary tract is administered parenterally or orally and led to enhanced us isthe vaccine against urinary tract infections produced by the company Solco Basel AG, Basel, Switzerland, and is described in U.S. patent 4606919, the contents of which are fully incorporated in this description, reduced the severity of urinary tract infections after hysterectomy, reduced the frequency of infections in susceptible women and increased the content of sIgA. However, some patients have experienced side effects such as malaise, fever, and muscle aches. Oral vaccine consisting of immunostimulating fractions extracted from strains of Escherichia coli, reduced bacteriuria, development of sepsis, the need for antibiotics in patients with spinal cord injuries and the frequency of recurrent urinary tract infections in adult women. As and when parenteral, many patients were observed for adverse reactions.

In an attempt to overcome the drawbacks associated with parenteral and oral administration of the vaccine against urinary tract infections, has been proposed intravaginal vaccine against urinary tract infections. The rationale for intravaginal administration of a vaccine against infections of the urinary tract was the fact that there is the immune system of the mucosa, in which the antigens are absorbed through the mucosal surface to Maintain the surface of the mucosa. As discussed above, in the urogenital tracts temporary or partial failure of local antibody production in the vagina or urinary tract is an important factor in the increased susceptibility to urinary tract infection was diagnosed in some women. Immunization via mucosal surfaces within the urinary tract is preferable to parenteral or oral routes of administration, because it was found that vaccination via intravaginal surface creates a secretory immune response in the urinary tracts.

In the past, vaccines against infections of the urinary tract was administered vaginally in the form of liquid vaccine. With intravaginal the introduction of liquid vaccine against urinary tract infection was associated with several problems. The main problem faced was that the liquid vaccine flowed from her vagina soon after injection. This greatly limits the quantitative limits of time during which the liquid antigens are in contact with the mucosal surface of the vagina, reducing the efficacy of the vaccine. In order to cause the reaction of secretory immunoglobulins, antigens requires sufficient contact with the mucous membrane of the vagina. Demanded the back and over an extended period of time after administration of the vaccine. However, often after a period of time spent in the supine position, the vaccine still flowed from her vagina, limiting the efficacy of the vaccine.

In addition, the need to stay in the supine position for an extended period of time after receiving the vaccine is a troublesome condition. During the course of treatment the patient may receive multiple vaccination and after vaccination the patient has a significant amount of time in a stationary state. It is therefore evident that improvements are needed in the prophylaxis against urogenital infectious diseases, such as urinary tract infections, and vaccines against infections of the urinary tract.

The present invention overcomes the above limitations and other drawbacks and describes the device vaccine delivery based suppository for prophylaxis against urogenital infectious diseases, such as urinary tract infections.

Summary of the invention In accordance with the present invention is provided with intravaginal device vaccine delivery based suppository for prevention against infectious diseases of the genitourinary system, such as infections vaccine-based suppository for prophylaxis against urogenital infectious diseases, such as urinary tract infections, in which to enhance the immune response of the vaccine is in contact with the mucous membrane of the vagina for a sufficient period of time.

In addition, in accordance with the present invention, is provided a device for delivery of a vaccine-based suppository for prophylaxis against urogenital infectious diseases, such as urinary tract infections, in which the vaccine is easily inserted, does not require that the patient was in the supine position for a long period of time after receiving the vaccination, and conveniently entered by the patient for the primary immunization and regular needs repeated immunizations.

In addition, in accordance with the present invention, is provided a device for delivery of a vaccine-based suppository for prophylaxis against urogenital infectious diseases, such as urinary tract infections in humans, with the specified suppository includes a vaccine consisting of inactivated bacteria that originate from cultures from 8 to 14 strains uropathogenic bacteria isolated from the urine of persons suffering from urinary tract infection, species Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus morganii and Streptococcus faecalis, and ACA on the suppository, where from half to three quarters of the used strains belong to the species Escherichia coli; and polietilenglikoli the basis of suppositories; in which the suppository is adapted for intravaginal injection in order to ensure the possibility of finding suppository in contact with the mucous membrane of the vagina to facilitate the transmission through it of the material of the suppository.

The advantage of the present invention is to provide a device for the delivery of vaccines based suppository for prophylaxis against urogenital infectious diseases, such as urinary tract infections, in which the vaccine is in contact with the mucous membrane of the vagina over a period of time sufficient to enhance the immune response.

Another advantage of the present invention is to provide a device for the delivery of vaccines based suppository for prophylaxis against urogenital infectious diseases, such as urinary tract infections, in which the vaccine is easily inserted and does not require that the patient was in the supine position for a long period of time after receiving the vaccination.

Another advantage of the present invention is to provide ustreamtv of the present invention is to provide a device of the delivery of the vaccine on the basis of a suppository, in which the vaccine is relatively painless.

Another advantage of the present invention is to provide a device of the delivery of the vaccine on the basis of a suppository, which sIgA-specific stimulation in the vaccination of the mucosa allows immune responses specific to prevent the emergence of bacterial colonization rather than infection after colonization of bacteria.

Another advantage of the present invention is to provide a device of the delivery of the vaccine on the basis of a suppository, in which the patient can independently periodically enter suppositories for revaccination.

Other advantages of the invention will become apparent to experts in this field after reading and comprehending the meaning of the following detailed description, accompanying drawings and appended claims.

A brief description of the drawings the Invention may take physical form in certain parts and locations of parts, a preferred embodiment and method of which will be described in detail in the following description and illustrated in the drawing, which is its integral part, which presents a graph illustrating the percentage patienta implementing This invention is directed to a device for the delivery of vaccines based suppository for immunization against infectious diseases in humans and the way of their treatment. More specifically, this invention is directed to a device for the delivery of vaccines based suppository for prophylaxis against urogenital infectious diseases, such as urinary tract infections. The device vaccine delivery based suppository consists of vaccines, including inactivated bacteria that originate from cultures from 8 to 14 strains uropathogenic bacteria species Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus morganii and Streptococcus faecalis, and polietilenglikoli the basis of suppositories; in which the suppository is adapted for insertion into a hole (passage) of a human body in order to ensure the possibility of finding suppository in contact with the fabric of the orifices of the body to facilitate the transmission through it of the material of the suppository.

Suppository consists of vaccines, including inactivated bacteria that originate from cultures from 8 to 14 strains uropathogenic bacteria species Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus morganii and Streptococcus faecalis. Inactivated bacteria are present in an amount of from about 50 million to about 5 billion bacteria of each strain on the suppository that between half and three quarters of the used strains belong to the species Escherichia coli. irabilis, Proteus morganii and Streptococcus faecalis. In a preferred embodiment, the implementation of inactive bacteria are present in a total amount of from about 1109to approximately 11010bacteria.

Suppository consists of vaccines, which is obtained in accordance with the method described in U.S. patent 4606919, which is fully incorporated here by reference. The vaccine obtained by cultivation in a suitable nutrient medium themselves above from 8 to 14 strains uropathogenic bacteria, which were isolated from the urine of persons suffering from urinary tract infection, and after completion of the cultivation remove formed of biological material in the form of particles and inactivate it by using known methods of mixing quantities of inactivated bacteria obtained from separate cultures with each other and reconstituting the number of sterile isotonic, so in one suppositories is present from about 50 million to about 5 billion bacteria of each strain.

First, in individuals suffering from urinary tract infection, take samples of urine (urine mid flow) and immediately produce depositing seed in the allocate formed colonies and identify with the determination of their biochemical and biological properties.

Selected thus colonies provide the ability to grow on agar plates at 37owithin 24 hours, and then suspended in physiological saline, and examined for purity by gram staining and freeze-drying.

To obtain the vaccine strains are cultivated separately on solid or liquid nutrient medium; preferably uses a solid nutrient medium such as nutrient agar, such as Nutrient Agar Difco. The medium is sterilized at 121oC for 15 minutes, and it has a pH of approximately 7,2.

To obtain in large scale use Roux bottles for laboratory use Petri dishes. The introduction of inoculum spend seeds, a few milliliters of which are distributed uniformly over the entire surface. The Roux bottles closed with cotton plugs and the environment is preserved with seeded surface on the bottom. Seed culture incubated at 37owithin 24 hours.

Bacterial "lawn" washed by the number required (depending on the density of the culture growth in the Cup) salt solution with phosphate buffer with gentle agitation without damaging the surface of the agar.

With each bottle or each h is proved to be contaminated, throw away. The suspension obtained from one strain and in collecting one seeding, merge together through a sterile nylon filter.

Inactivation, as the cultivation takes place individually for each strain. It can be carried out by heating at a temperature of from approximately 55oWith up to approximately 60oC for approximately 1 hour, by treatment with a solution of formaldehyde or with exposure-rays. Because of its simplicity, the preferred inactivation by heat. Amount obtained through cultivation, combine and inactivate in a water bath at 60oC for 1 hour and after inactivation add phenol.

The contents of the container with the source material (inactivated suspension, derived from one strain), centrifuged at 3000 rpm for 1 hour in a refrigerated centrifuge, the supernatant removed and the bacterial sediment suspended in saline solution containing 0.01 percent thimerosal.

The suppository of the present invention consists of any suitable polietilenglikoli basics suppository, known in modern technology. More specifically, polietilenglikol what I base suppository consists of approximately 98 wt.% of polyethylene glycol and about 2 wt.% Polysorbate. Preferably, the polyethylene glycol has an average molecular weight from about 3000 to 5000. In a more preferred embodiment, the implementation polietilenglikolja the basis of the suppository comprises about 39 wt.% polyethylene glycol having a molecular weight of 8000, and 59 wt.% polyethylene glycol having a molecular weight of 400. A suitable commercially available polietilenglikoli the basis of the suppository is POLYBASE manufactured by Paddock Laboratories Inc.

Polietilenglikolja the basis of the suppository is present in the device vaccine delivery on the basis of the suppository in any suitable amount in order to ensure the possibility of contact of the vaccine with the mucous membrane of the vagina for a sufficient period of time to enhance the immune response. Preferably, polietilenglikolja the basis of the suppository ranges from about 80 to 95 wt.% the suppository. Polietilenglikolja the basis of the suppository gives the degree of Miscibility with the surfaces of the mucous membrane of the vagina, in which suspended particles vaccines are in contact with such surfaces of the mucous membrane for sufficient time to cause a reaction secretory immunoglobin. Palmost provide extended contact of the vaccine with the mucous membranes of the vagina, serving as a depot that slowly releases the antigen and using the definition of the localization and delivery of antigens to immunocompetent cells. Polietilenglikolja the basis of a suppository, in addition, serves as a structural necessity that holds the suppository in his press form.

The suppository is inserted into the laminated capsule, suppository, which forms the mold. The suppository is stored in the capsule prior to use. Laminated capsule suppository is any known in modern technology capsule, suitable for packaging of suppositories. Capsule suppository should be capable of withstanding a temperature of 60oS, used in the manufacture of suppositories, and the temperature of the 4oFor long-term storage without compromising the integrity of pressing or reaction with the suppository in an adverse manner. Preferably, laminated capsule suppository is a laminated capsule suppository of polyvinyl chloride-polyethylene. A suitable commercially available laminated capsule suppository is laminated capsule suppository of polyvinyl chloride-polyethylene manufactured by Paddock Laboratories Inc.

tin. Depolarized gelatin represents any suitable depolarized gelatin, known in modern technology. Examples of suitable depolarized gelatin materials include gelatin type a or b from bovine or porcine cartilage, but are not limited to. Preferably, the depolarized gelatin is a gelatin type A. Depolarized gelatin is used to protect components during lyophilization.

Depolarized gelatin is present in suppositories in any suitable amount. More specifically, suppository contains from about 0.01 wt.% to about 0.02 wt.% depolarized gelatin.

In addition, for inclusion in the device of the vaccine on the basis of a suppository suitable thimerosal. Thimerosal is an antimicrobial preservative. Suitable commercially available thimerosal can be purchased from Sigma Chemical Co. Thimerosal is present in suppositories in any suitable amount. More specifically, the suppository comprises from circa 0.0005 wt.% to about 0.005 wt.% thimerosal.

The device vaccine delivery on the basis of the suppository of the present invention receive the boxes under aseptic sterile laminar is, the glycol becomes liquefied. Polietilenglikoli the basis of the suppository is heated for about 1 hour. A vaccine consisting of 8-14 strains inactivated lyophilized uropathogenic bacteria are placed in a flask. Part of the liquefied basis of the suppository is cooled to 60oC and poured into a separate flask containing vaccine. The vaccine and the liquid basis of the suppository is stirred for approximately 10 minutes at a temperature of approximately 60oWith forming a homogeneous suspension, consisting of bases of the suppository and vaccines. A suspension consisting of bases of the suppository and vaccines, are placed in a separate laminated capsule suppository. In the flask, which contains the remainder of the vaccine, add a further quantity of the liquid base of the suppository. The basis of the suppository and the vaccine is stirred for approximately 1 minute at a temperature of 60oFor a homogeneous suspension. This suspension is added to the laminated capsule suppository. On top of the laminated capsule suppository add clean liquid basis of the suppository up until the capsule is filled with. The suppository is cooled at a temperature of approximately 24oWith, giving the opportunity for the sung parts of the suppository, component 67%, where they are protected from cracking and delamination that may occur on the tip of the suppository, when the capsule is opened for use.

Further, the present invention is illustrated by the following example. The example illustrates the effectiveness of the delivery device of the vaccine on the basis of the suppository of the present invention. It is clear that the example only illustrates the preferred options for implementation in accordance with the present invention, which outlines the claims shall define the scope of claims of the present invention.

EXAMPLE Make the device vaccine delivery on the basis of a suppository, comprising a vaccine consisting of inactivated bacteria that originate from cultures from 8 to 14 strains uropathogenic bacteria isolated from the urine of persons suffering from urinary tract infection, species Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus morganii and Streptococcus faecalis, and are present in an amount of from about 50 million to about 5 billion bacteria of each strain on the suppository that between half and three quarters of the used strains belong to the species Escherichia coli; and polietilenglikoli the basis of the suppository.

POLYBASE, polietilenglikoli about the 1 hour to translate the basics of the suppository in the liquid state. The freeze-dried vaccine SOLCOUROVACmade by the company Solco Basel AG, aseptically placed in a sterile Erlenmeyer flask in sufficient quantity to manufacture 50 suppository. Each suppository will contain from about 1109to approximately 11010the bacteria. The liquid base of the suppository is cooled to approximately 60oC and approximately 100 ml of the liquid base of the suppository poured into a separate flask containing vaccine. The flask sterile magnetic bar for mixing, and the vaccine and the base of the suppository is stirred for approximately 10 minutes at approximately the 60oC in a water bath with controlled temperature to form a homogeneous suspension. A suspension consisting of bases of the suppository and vaccines, using a sterile pipette, placed in a separate laminated capsule of polyvinyl chloride-polyethylene for suppository. Each capsule is placed approximately 2.0 ml of the suspension.

In the flask, which contains the remainder of the vaccine, add approximately 25 ml of the liquid base of the suppository. The basis of the suppository and the vaccine paramesh the suspension. Each capsule add approximately 0.5 ml of this suspension. For filling capsules each capsule add clean liquid basis of the suppository. The basis of the suppository is cooled at a temperature of approximately 24oC for approximately 30 minutes for curing the basis of the suppository. Then suppositories stored at 4oC.

In the study of suppository participated 91 the patient aged 18 to 82 years. In all patients within the last year had more than two infections of the urinary tract, and they all were evaluated, consisting of excretory urography or ultrasound of the kidneys and cystoscopy. Before testing suppository in patients undergoing a complete clinical and biochemical analysis of blood, urine and crops from her and vaginal examination with mirrors. Patients are recommended to refrain from conception during the test, and they have before the test was supposed to be a negative result of the examination of the urine for pregnancy. 91 patients were divided into three groups of treatment. the 1st group received suppositories containing approximately 1109bacteria on the suppository. the 2nd group received suppositories containing PR is which did not contain the vaccine. The three groups did not differ in average age, hysterectomy status, sexual activity or preventive receiving antibiotics within 0-4 weeks.

Each patient suppositories were injected 3 times with intervals of 1 week. Suppositories were administered vaginally. For placement of a vaginal suppository patients were placed in supine position, and the suppository was injected high into the vagina. The patient remained in the supine position for approximately 15 minutes. All patients were examined 4 weeks after the first treatment, and then at intervals of 4 weeks to 20 weeks. Every visit was taken to study the serum, urine and vaginal wash liquid. Crops vaginal culture was performed, if during the test there were abnormal vaginal discharge or symptoms.

Of the 91 patients 44, which in the beginning of the study prophylactically received antibiotics, continued the antibiotics until 2 weeks after administration of the third suppository. The remaining 47 throughout the tests did not take preventive antibiotics.

Characteristics of patients were statistically compared using the exact two-sided Fisher's exact test and one-way Crete is a mini-rank criterion. A full explanation of these criteria is given in the guide SAS/STAT Software Changes and Enhancements, Ed. 6.07, Cary, SAS Institute, Inc., p. 620, 1993. The majority of infections were confirmed by culture cultures of urine and study the sensitivity, and they were treated within 3 days of full doses of conventional antibiotics. Episodes of typical symptoms of irritation of the bladder, which is responsive to the public antibiotics, but were not confirmed by culture of urine, also was regarded as a recurrent infection and analyzed in the same way. Changes in antibody levels during treatment were compared using repeated indices ANOVA for unbalanced data.

No patients stopped treatment due to side reactions. One patient complained of slight dizziness upon returning home after the first vaccination, but the second and third vaccination took without complications and scheme. Three other patients noted mild irritation of the vagina after injections, suppositories, but they were able without interruption to complete the treatment regimen three suppositories. There were no other reports of episodes of profuse vaginal discharge, interference with sexual intercourse or signs and symptoms of bacterial vaginosis.

NThis is the lack of treatment effect was due to the fact, that in patients receiving placebo and patients receiving treatment vaccine, within the first 4 weeks of the study had fewer urinary tract infections due to the prophylactic use of antibiotics. In the study of the time of occurrence of re-infection with 0 weeks in 47 women, oseltamivir is not treated with antibiotics in the treatment group were significantly initial lengthening of the period of time until the first occurrence of re-infection. No significant differences in time to first occurrence of infection in groups of low dose and high dose, so these data were combined in the analysis of vaccine efficacy. The results showed that the number of patients who did not have infection within 8 weeks was significantly greater in the group treated with the vaccine than in the placebo group. In addition, the average time to development of first infection has lengthened from 8.7 weeks to 13 weeks in immunized patients. The drawing is a graph illustrating the percentage of patients remaining free from infection during the test. Such patients from the 1st group represented by a dotted line. Patients in the 2nd and 3rd groups represented by a solid line.

The device is letisti membrane of the vagina for a period of time, sufficient to enhance the immune response. In addition, the device vaccine delivery based suppositories in accordance with the present invention is easily inserted, does not require that the patient was in the supine position for an extended period of time after receiving the vaccination, conveniently entered by the patient, painless, suitable for re-vaccination against infections of the urinary tract and is a good way to deliver the antigen to immunocompetent cells through the mucous membrane.

Although there have been disclosed various options for implementation of the delivery device on the basis of a suppository for the treatment of urinary tract infections and treatment of urinary tract infections in humans, it should be understood that the specialists in this field can make changes and adapt to specific situations. Other features and aspects of this invention will be clear to experts in this field upon reading and understanding this description. Obviously, such features, aspects and expected variations and modifications of the presented results and examples are within the range of the claims of the invention, and the invention is limited only by the range of the claims SL is ctice urogenital infections in humans includes (a) a vaccine consisting of inactivated bacteria that originate from cultures from 8 to 14 strains uropathogenic bacteria species scherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus morganii and Streptococcus faecalis isolated from the urine of persons suffering from urinary tract infection, and are present in an amount of from about 50 million to about 5 billion bacteria of each strain, 1 ml, in which one half to three quarters of the strains used are in the form of scherichia coli, and (b) polietilenglikoli the basis of the suppository, in which the suppository is adapted for insertion into the hole of the body in order to ensure the possibility of finding suppository in contact with the fabric of the orifices of the body to facilitate the transmission through it of the material of the suppository.

2. Suppository for prevention of diseases of the urinary tract in humans, including (a) a vaccine consisting of inactivated bacteria that originate from cultures from 8 to 14 strains uropathogenic bacteria species scherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus morganii and Streptococcus faecalis isolated from the urine of persons suffering from urinary tract infection, and are present in an amount of from about 50 million to about 5 billion bacteria of each strain on the suppository in which p is the suppository, in which the suppository is adapted for intravaginal injection in order to ensure the possibility of finding suppository in contact with the mucous membrane of the vagina to facilitate the transmission through it of the material of the suppository.

3. Suppository under item 2, wherein the inactive bacteria come from 6 strains of the species scherichia coli and 1 strain each of the species Klebsiella pneumoniae, Proteus mirabilis, Proteus morganii and Streptococcus faecalis.

4. Suppository under item 2, wherein the inactive bacteria are present in a total amount from about109to approximately 11010bacteria.

5. Suppository under item 2, characterized in that polietilenglikolja the basis of the suppository comprises polyethylene glycol and Polysorbate.

6. Suppository under item 5, characterized in that polietilenglikolja the basis of the suppository comprises about 98 wt.% of polyethylene glycol and about 2 wt.% Polysorbate.

7. Suppository under item 5, wherein the polyethylene glycol has an average molecular weight from about 3000 to about 5000.

8. Suppository under item 2, characterized in that polietilenglikolja the basis of the suppository ranges from some includes depolarized gelatin.

10. Suppository under item 9, characterized in that the depolarized gelatin selected from the group consisting of gelatin type a from bovine collagen, gelatin type a from porcine collagen, gelatin type b from bovine collagen and gelatin type b from porcine collagen.

11. Suppository under item 9, wherein the suppository contains from about 0.01 wt.% to about 0.02 wt.% depolarized gelatin.

12. Suppository under item 2, characterized in that it further includes thimerosal.

13. Suppository under item 12, wherein the suppository comprises from circa 0.0005 wt.% to about 0.005 wt.% thimerosal.

14. Suppository for prevention of urinary tract infections in humans including (a) a vaccine consisting of inactivated bacteria that originate from cultures of 10 strains uropathogenic bacteria species scherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus morganii and Streptococcus faecalis isolated from the urine of persons suffering from urinary tract infection, and are present in an amount of from about 50 million to about 5 billion bacteria of each strain on the suppository that between half and three quarters of the strains used are in the form of scherichia coli in which inactive bacteria prostatron inactive bacteria are present in a total amount from about109to approximately 11010bacteria, and (b) polietilenglikoli the basis of a suppository, which polietilenglikolja the basis of the suppository comprises about 98 wt.% of polyethylene glycol and about 2 wt.% Polysorbate, in which the polyethylene glycol has an average molecular weight from about 3000 to about 5000, and in which polietilenglikolja the basis of the suppository ranges from about 80 wt.% to about 95 wt.% the suppository in which the suppository is adapted for vaginal introduction in order to ensure the possibility of finding suppository in contact with the mucous membrane of the vagina to facilitate the transmission through it of the material of the suppository.

15. Suppository under item 14, characterized in that it further includes depolarized gelatin and thimerosal, which depolarized gelatin selected from the group consisting of gelatin type a from bovine collagen, gelatin type a from porcine collagen, gelatin type b from bovine collagen and gelatin type b from porcine collagen, in which the suppository comprises from about 0.01 wt.% to about 0.02 wt.% depolarized gelatin and in which the suppository included is Pecci urinary tract in humans, obtained by mixing (a) a vaccine consisting of inactivated bacteria that originate from cultures of 10 strains uropathogenic bacteria species scherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus morganii and Streptococcus faecalis isolated from the urine of persons suffering from urinary tract infection, and are present in an amount of from about 50 million to about 5 billion bacteria of each strain on the suppository that between half and three quarters of the strains used are in the form of scherichia coli in which inactive bacteria come from 6 strains of the species scherichia coli and 1 strain each of the species Klebsiella pneumoniae, Proteus mirabilis, Proteus morganii and Streptococcus faecalis, and in which the inactive bacteria are present in a total amount of from about 1109to approximately 11010bacteria, and (b) polietilenglikoli the basis of a suppository, which polietilenglikolja the basis of the suppository comprises about 98 wt.% of polyethylene glycol and about 2 wt.% Polysorbate, in which the polyethylene glycol has an average molecular weight from about 3000 to about 5000, and in which polietilenglikolja the basis of the suppository ranges from about 80 wt.% to probezeit find suppository in contact with the mucous membrane of the vagina to facilitate the transmission through it of the material of the suppository.

17. Method of prevention of urogenital diseases in humans, including the stage of (a) the introduction of the suppository into the hole of the body, including vaccines, including inactivated bacteria that originate from cultures from 8 to 14 strains uropathogenic bacteria species scherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus morganii and Streptococcus faecalis isolated from the urine of persons suffering from urinary tract infection, and are present in an amount of from about 50 million to about 5 billion bacteria of each strain on the suppository that between half and three quarters of the strains used are in the form of scherichia coli and polietilenglikoli the basis of the suppository and (b) ensure contact of the suppository with cloth body orifices to facilitate the transmission through it of the material of the suppository and with the aim to induce an immune response in humans.

18. A method for preventing urinary tract infections in humans, including the stage of (a) the introduction of the suppository into the vagina of a person, including a vaccine comprising inactivated bacteria that originate from cultures from 8 to 14 strains uropathogenic bacteria species scherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus morganii and Streptococcus faecalis isolated from the urine of persons suffering from urinary tract infection, and price, where from half to three quarters of the strains used are in the form of scherichia coli, and polietilenglikoli the basis of the suppository and (b) ensure contact of the suppository with the mucous membrane of the vagina to facilitate the transmission through it of the material of the suppository and with the aim to induce an immune response in humans.

19. The method according to p. 18, wherein the inactive bacteria come from 6 strains of the species scherichia coli and 1 strain each of the species Klebsiella pneumoniae, Proteus mirabilis, Proteus morganii and Streptococcus faecalis.

20. The method according to p. 18, wherein the inactive bacteria are present in a total amount from about109to approximately 11010bacteria.

21. The method according to p. 18, characterized in that polietilenglikolja the basis of the suppository comprises polyethylene glycol and Polysorbate.

22. The method according to p. 21, characterized in that polietilenglikolja the basis of the suppository comprises about 98 wt.% of polyethylene glycol and about 2 wt.% Polysorbate.

23. The method according to p. 21, wherein the polyethylene glycol has an average molecular weight from about 3000 to about 5000.

24. The method according to p. 18, characterized in that polietilenglikolja on p. 18, characterized in that the suppository further includes depolarized gelatin.

26. The method according to p. 25, characterized in that the depolarized gelatin selected from the group consisting of gelatin type a from bovine collagen, gelatin type a from porcine collagen, gelatin type b from bovine collagen and gelatin type b from porcine collagen.

27. The method according to p. 25, wherein the suppository contains from about 0.01 wt.% to about 0.02 wt.% depolarized gelatin.

28. The method according to p. 18, wherein the suppository additionally contains thimerosal.

29. The method according to p. 28, wherein the suppository comprises from circa 0.0005 wt.% to about 0.005 wt.% thimerosal.

 

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