MXPA00008161A - New agent - Google Patents

New agent

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MXPA00008161A
MXPA00008161A MXPA/A/2000/008161A MXPA00008161A MXPA00008161A MX PA00008161 A MXPA00008161 A MX PA00008161A MX PA00008161 A MXPA00008161 A MX PA00008161A MX PA00008161 A MXPA00008161 A MX PA00008161A
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strain
deposited
lactobacillus plantarum
pharmaceutical composition
deutsche sammlung
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MXPA/A/2000/008161A
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Spanish (es)
Inventor
Rolf Andersson
Ulla Forsgrenbrusk
Stig E Holm
Grahn Hakansson Eva
Hakansson Stellan
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Essum Ab
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Abstract

A novel strain of Lactobacillus plantarum, referred to as LB931, has now been isolated. The strain has been deposited at Deutsche Sammlung von Mikroorganismen, Braunschweig, DE. It has been assigned accession number DSM11918. Accordingly LB931 can be used for treating and/or preventing urogenital infections. LB931 can advantageously be included in pharmaceutical compositions and in products for personal care, such as feminine hygiene products, diapers and sanitary napkins.

Description

NOVEDOUS AGENT The present invention relates to a novel strain of Lactobacillus that possesses valuable pharmaceutical characteristics. The invention also relates to pharmaceutical compositions and personal care products containing the strain, as well as to the use of the strain for the prevention of urogenital infections.
Technical background (All citations in the following description are incorporated by reference). The normal bacterial flora in the urogenital region is constituted by a complex ecosystem consisting of more than 50 different bacterial species (Hill et al., Scand., J. Urol. Nephrol., 1984; 86 (Suppl.): 23-29). The normal flora is dominated by bacteria belonging to the genus Lactobacillus (LB) which are Gram-positive rods adapted for the environment in the vagina of the fertile woman. These bacteria also contribute to the maintenance of the specific environment and the ecological balance in the vagina. In addition to the complex pattern of interaction of the multitudinous bacterial flora of the vagina and the rest of the urogenital region, it is necessary to consider the variation of physical conditions that can influence bacterial growth and adhesion properties. Some strains of LVS inhibit the growth of potentially pathogenic bacteria by different mechanisms. The metabolism of LB gives rise to the formation of organic acids, especially lactic acid and acetic acid, which contribute to the low pH of the vaginal fluid which is unfavorable for many other species. LB can also produce soluble substances that directly inhibit the growth of potentially pathogenic bacteria and yeasts. They can also produce hydrogen peroxide that is toxic to bacteria lacking the catalase enzyme, such as the gram-negative anaerobic canes and Enterobacteriacae. These inhibition characteristics can vary considerably between different strains of LB (Hooton et al., JAMA 1990; 265: 64-69). Weakness of the natural defense system may allow potentially pathogenic microorganisms to cause clinical infection, for example in connection with medications, poor personal care, or changes in the microflora of the skin or mucous membranes. The normal flora of the vagina is dominated by LB and the surrounding pH is less than 4.5. Yeasts and enterobacteria are scarce or absent (Redondo-Lopez et al., Rev. Inf. Dis. 1987: 12: 856-872). Changes in the vaginal bacterial flora may be related to different pathogenic states. There is an increasing amount of enterobacteria in the vagina and urethral orifice of women who have recrudescent infections in the urinary tract and also have urogenital flora depleted of lactobacilli (Marrie et al., J. Clin Microbiol., 1976, 8, 67-72) . It is known that the frequency of infections increases in connection with the treatment of other infections with antibiotics (Stamey, Rev. Inf. Dis. 1987: 9 (Suppl 2): 195-208; Reid et al., Curr. Opin. Inf. Dis. 1991; 4: 37-41). In addition, it has been shown that children who have a history of frequent episodes of antibiotic treatment are more likely to get urinary tract infections (Márild et al., Ped. Inf. Dis. 1990; 22: 43-47). In bacterial vaginosis, the amount of LB decreases and the pH increases. There is also a domain of the species Bacterioides, Gardnerella vaginalis and Mobil uncus (Redondo-López, supra). Vaginitis, associated with an increased amount of enterobacteria, is usually a tangible problem related to antibiotic treatment. The common oral administration of penicillin gives rise to the accumulation of the substance in the vaginal fluid (Sjórbeg et al., Obstet, Gynecol, 1990; 75: 18-21) followed by colonization by enterobacteria and yeasts (Sjórbeg et al., Gynecol. Obstet, Invest, 1992; 33: 42-46). Research in monkeys (Macaca fascicularis) has shown that vaginal administration of oxycillin impairs the ability of the normal bacterial flora to inhibit the colonization of pathogenic E. coli in the urinary tract (Herthelius et al., Infection 1988: 16: 263-266). During pregnancy, the composition of the vaginal flora can influence the morbidity of the fetus and the child. The presence of group B streptococci (CGBS) in fecal and vaginal flora is common (up to 30% of pregnant women). These bacteria usually do not pose a threat to a woman's health. However, GBS can cause serious infections in the newborn child. In these cases, bacteria are transmitted vertically from mother to child before or during birth. Also, it is possible to transmit other bacteria in this way and cause infections in the child. There is also a strong connection between bacterial vaginosis and premature birth (Marthius et al., Arch. Gynecol.; 247: 1-13). The mechanisms that support this phenomenon are unknown. It has been shown that a change in the vagina flora towards the dominance of gram negative species increases the amount of the enzyme phospholipase A2, which in turn can initiate the synthesis of prostaglandin starting from arachidonic acid (Bejar et al., Obstet. Gynecol, 1981; 57: 479-482). The flora in vaginosis also produces large amounts of endotoxin (Sjóberg et al., Obstet, Gynecol, 1991; 77: 265-266), which can induce the synthesis of endogenous prostaglandin (Romero et al., Obstet. Gynecol. 1989; 73: 31-34), possibly mediated by interleukins. In theory, the positive characteristics of LB have motivated its use in commercial preparations with the proposed use of complementing and reinforcing the vaginal flora. Success has been possible and often the preparations available contain considerably less LB than has been established. Some preparations have also been contaminated (Hughes et al., Obstet.
Gynecol. 1990; 75 (2): 244-248). To complement and improve the normal bacterial flora in the urogenital region by the addition of LB, it is necessary to carefully select the bacterial strains that will be used. An LB strain suitable for this purpose must meet the following criteria: 1. The LB strain must produce large quantities of soluble substances with growth inhibition capacity on enterobacteria, group streptococci B, staphylococci and yeasts. 2. The LB strain must be able to be transferred to the skin and mucosal surfaces of the urogenital region. 3. The LB strain must be able to adhere to the epithelial surfaces in the urogenital region. 4. The LB strain must be able to withstand storage for a prolonged period and it should be possible to induce the strain in different types of preparations.
. The LB strain must be able to preserve its viability and characteristics in an article or preparation during its use. 6. Strain LB must be sensitive to spermicidal preparations containing nonoxynol-9. 7. The LB strain must be isolated from the urogenital tract of women. 8. The LB strain must allow the existence of the human LB urogenite1 flora. Therefore, there is a demand for strains that meet these requirements.
SUMMARY OF THE INVENTION A novel strain of Lactobacillus plantarum, designated LB931, has been isolated, which meets the aforementioned requirements. The strain has been deposited in the Deutsche Sammlung von Mikroorganismen, Braunschweig, DE. With an assigned access number DSM11918. Consequently, LB931 can be used to treat and / or prevent urogenital infections. LB931 can conveniently be included in pharmaceutical compositions and personal hygiene products, such as diapers and sanitary napkins.
Definitions As described herein, the term "LB" refers to bacteria of the genus Lactobacillus. As described herein, the term "urogenital region" refers to the perineum, urethra and vagina. As described herein, the term "absorbent article" refers to products suitable for absorbing a body fluid, such as blood or urine. Examples of these items are feminine hygiene products, incontinence guards and diapers. As described herein, the term "GBS" refers to group B streptococci. As described herein, the term "lactic acid bacteria" refers to the bacteria that produce lactic acid, such as the bacteria belonging thereto. to the genus Lactobacillus and Lactococcus. The term "UFC" is understood as colony forming units.
DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel strain of Lactobacillus plantarum, known as LB931 (DSM11918). This bacterial strain is valuable for the prevention and / or treatment of urogenital infections as it inhibits the growth of a large number of pathogenic microorganisms. The strain is resistant and easily survives prolonged periods of storage at room temperature. Therefore, products containing LB931 have a long shelf life. The strain can be easily transferred to human skin and vaginal epithelium. LB931 is resistant to the therapeutic concentrations of some antibiotic substances and spermicidal compounds. The inhibition characteristics of LB931 have been investigated, examples of the bacterial species that are inhibited successfully are Escherichia, Klebsiella, Proteus, Staphylococcus and Streptococcus group B. LB931 is, therefore, useful for the prevention and / or treatment of infections caused by these microorganisms. As noted in the above, the present invention also provides a variety of pharmaceutical compositions, preferably suitable for topical administration, containing LB931 together with pharmaceutically or physiologically acceptable carriers, excipients and / or diluents. In general, these carriers must be non-toxic to the recipients at the doses and concentrations used. Usually, the preparation of these compositions involves the combination of the therapeutic agent with buffers, thickening agents or gel-forming agents such as glycerin, polyethylene glycol, etc. It is possible to include antioxidants such as ascorbic acid, low molecular weight polypeptides (less than about 10 residues), proteins, carbohydrates including glucose, sucrose and dextrins, and other stabilizers and excipients. Possible pharmaceutical compositions are ointments, creams, liquid solutions, suppositories or capsules. The present invention also relates to absorbent articles containing LB931. Such an article may include a permeable outer sheet that is intended to be in close contact with the wearer's skin, a posterior sheet preferably liquid impervious that is intended to be distant from the wearer during use, and an arranged absorbent structure. on the outer sheet and the back sheet. In some cases, an additional sheet in the form of, for example, wadding or similar material, may be placed between the outer sheet and the absorbent structure. The microorganisms which have antagonistic properties can be arranged in different parts of the absorbent article, for example in the outer sheet, in the absorbent structure of the absorbent article, between two of the layers of the absorbent article, in a loose insert in the absorbent article or in the absorbent article. in some other way. The present invention will now be described with reference to the contained Figures, in which: Figure 1 is a diagram showing the stability of freeze-dried LB931, at room temperature (+ 22 ° C) and at + 6 ° C; Figure 2 is a diagram showing the stability of LB931 impregnated in an absorbent article; Figure 3 and 4 describe the amount of LB931 transferred to the urethral orifice and the perineal skin in young people after using a pantiprotector containing LB931. The present invention will now be described with reference to the following examples: Example Isolation and classification of Lactobacillus plantarum, strain LB931 Bacterial samples were taken from healthy women. From these samples, bacterial strains were isolated and these strains were detected based on their ability to inhibit the growth of enterobacteria (data not shown). The best strain, isolated from a healthy pregnant woman, was classified as Lactobacillus plantarum according to the API 50 CH test kit (API systems, BioMerieux, FR), and was named LB931. The strain was further classified by DNA analysis with SDS-PAGE in BCCM / LMG (Belgium) as Lactobacillus plantarum-pentosus-paraplantarum.
Example 2: Inhibition capacity of strain LB931 The purpose of this experiment was to illustrate the ability of strain LB931 to inhibit the growth of other bacteria. LB931 was grown in MRS broth (Merck, DE) at a temperature of 37 ° C in 5% CO2 overnight. 1 ml, containing 10 bacteria was added to 25 ml of 2% agar melted in MRS broth. The mixture was poured into the petri dish, allowed to solidify and incubated as described above for 24 hours. Another 25 ml of M17 agar (Merck, DE) was poured on top of the first layer and the plates were left at room temperature for four hours. Similar agar plates without LB931 were also prepared and used as control plates. The indicator bacteria were grown separately in TY medium (Holm et al., APMIS 1967; 69, 264) at 37 ° C in air. The cultures were transferred to a Bertani tray with 25 compartments, each compartment containing 0.25 ml (10 bacteria / ml). From each of these trays the bacteria were transferred and fixed on agar plates containing the Lactobacillus, using the Steer steel pin replicator (Steers et al., J. Antibiot, Chemother, 1979, 9, 307). The plates were incubated at 37 ° C overnight. The plates were read and it was established as follows: a) the indicator bacteria had grown; b) the growth of the indicator bacteria had been inhibited, or c) growth of the indicator bacteria had not occurred. The pH of each of the plates was also monitored. The results of the interference tests are shown in Table I.
Table I The results show that Lactobacillus plantarum, LB931 inhibits or prevents the growth of a large number of bacterial strains, and that other strains of Lactobacillus are mostly unaffected.
Example 3: Survival capacities of LB931 in different preparations a) LB931 dissolved in a suspension of equal parts of skimmed milk and 0.9% NaCl. LB931 was dissolved in skim milk containing 0.9% NaCl. The dissolved bacteria were then incubated at different temperatures. The amount of bacteria was monitored continuously by cell counting. The results are described in Table II below.
Table II The results show that LB931 is stable in a mixture of skimmed milk and NaCl for a period of one month at + 4 ° C. b) A skim milk preparation of LB931 was dried by freezing according to the normal methods. The powder obtained was stored in petri dishes at room temperature and at + 6 ° C. The number of bacteria was determined after seven and 25 days, respectively. The results are described in Table III below.
Table III The number of bacteria in the freeze-dried powder was also monitored every fourth week until 68 weeks. These results are presented in Figure 1. It is evident, from the figure, that LB931 is stable at room temperature and at + 6 ° C for 22 weeks. After one year, at + 6 ° C, more than 10 cfu / mg of LB931 is viable. c) The ability of LB931 to survive in synthetic urine, pH 6.6, was reviewed. The synthetic urine contains monovalent and divalent cations and anions as well as urea and was prepared according to the specifications of Geigy, Scientific Tables, vol. 2, 8th ed. 1981, p. 53. A nutrient medium for microorganisms was added to the sterile synthetic urine. The nutrient medium was prepared according to the composition data of the Hook and FSA media. To 1 3 ml of synthetic urine, 10 LB931 bacteria were added, and the samples were incubated for 18 h at 32 ° C. After incubation, the number of bacteria in the sample was > 10 / ml. LB931 can survive and grow in synthetic urine. d) The ability of LB931 to survive on an absorbent article (pantiprotector) was investigated. A suspension of LB931 (150 μl) was added to the absorbent article, and this article was subsequently stored in an airtight container for up to nine months. The results are shown in Figure 2. A large number of bacteria survived for seven months. e) Finally, the characteristics of LB931 were reviewed during a period of growth and storage. LB931 was cultivated in MRS broth and a new step was carried out every third day for three months. After the initial sample of LB931 and the last step were compared in the API, PGFE test and the interference test, the two samples were identical in all tests. This shows that LB931 is very stable after storage and some steps in growth medium.
Example 4: Transfer of LB931 to skin of the perineum and urethral orifice in women To study the transfer of LB931 to the perineum when a pantiprotector is used, the following investigation was carried out. All the people tested were women between 12 and 60 years of age, and the tests were performed between menstrual periods as appropriate. The test products were manufactured from traditional pantiliners containing a liquid permeable outer layer, a liquid-impermeable back side layer and intermediate an absorbent layer of 100-200 g / m cellulose chemical pulp. On the absorbent side of the test product, a suspension of bacteria LB931 was sprayed in an amount of 10 colony-forming units in a product. To determine the presence of LB931 in the perineum of the 13 test persons, a test called rubbing was performed. The bacteria were collected by rubbing a sterile stick containing a cotton tip that had been immersed in a sterile solution of sodium chloride in a defined area of the skin. The presence of LB931 and other LB in the perineal skin and the urethral orifice was determined. The people tested were determined in this way to establish a white sample. Then, the people on trial used the pantiprotector for five hours in the morning. The pantiprotector was removed and again the presence of added lactic acid bacteria and natural lactic acid bacteria, respectively, was determined directly after removing the pantiprotector. This sample was called sample 1.
After another 4-5 hours another sample was taken, and it was named sample 2. The type of lactic acid bacteria was identified using Rogosa-agar with vancomycin for LB931 and Rogosa-agar plates incubated in anaerobic medium for other LB. Another identification was made by means of API (BioMeriux, FR) and PFGE (pulse field electrophoresis). The results are shown in Table IV. LB931 could be found in the skin of the perineum and urethral orifice in all women after using the pantiprotector sprayed with LB931.
Example 5: Transfer of LB931 to the skin of the perineum and urethral trade in girls Thirteen girls between 3 and 12 years were included in the study. Bacterial samples of the perineal skin and urethral orifice were obtained by first immersing a cotton swab in MRS broth, then gently rubbing the swab over the skin or epithelial surface. Finally, the swab was immersed in a sample tube containing MRS broth. The samples were obtained according to the following scheme: Sample 0: A white sample was obtained in the afternoon before entering the study containing LB931 bacteria. Day 1 in the afternoon: a pantiprotector was placed. Sample 1: Day 2 in the morning. A new pantiprotector was used during the day. Sample 2: A sample was taken in the afternoon before an optional bath and before placing a new pantiprotector. Day 2 in the afternoon. Sample 3: the same procedure as for the sample 1. Day 3 in the morning. Sample 4: The same procedure as for the sample 2. Day 3 in the afternoon. Sample 5: The same procedure as for the sample 1. Day 4 in the morning.
Sample 6: A sample is taken in the afternoon before an optional bath. No pantiprotector was used during the night, day 4 in the afternoon. 1 Sample 7: A sample is taken on day 5 in the morning. Pantiprotector is not used during the day. Sample 8: The last sample is taken on day 5 in the afternoon. The results are presented in Figure 3 (urethral orifice) and Figure 4 (perineal skin). The results show that LB931 can be transferred from an absorbent article.
Example Sensitivity antibiotics spermicidal agents The MIC values of Lactobacillus plantarum LB931 were determined using test E (Brown et al., J. Antimicrob Chemother 1991; 27: 185-190). The results are described in Table V below.
Table V Antibiotic substance MIC μg / ml Ampicillin 0.19 Cefotaxime 0.094 Cefuroxy at 0.38 Gentamicin 0.25 Imipenem 0.016 Metronidazole > 32 Erythromycin 0.25 Vancomycin > 256 Piperazine / tazobactam 2 Tetracycline 2 Trimethoprim 0.016 Benzylpenicillin 0.5 Sensitivity to antibiotic substances was also determined using the SIR system. In Table VI below S means sensitivity, and R means resistance.
Table VI Antibiotic substance Area (mm) Indication Cefadroxil 24 S Clindamycin 35 s Tri / sulfamethoazole [sic] 43 s Cefazidime 35 s Amikacin 30 s Aztreonam 0 R Mecilinam 0 R Nalidixin acid 0 R Netilmycin 0 R Nitrofuantin [sic] 36 S Norfloxacin 0 R Tobramycin 32 S Mecillinam / ampicillin 41 S Cefipiro e 47 S Oxacillin 0 R Cefalotin 22 S LB931 is sensitive to some commonly prescribed antibiotics for urinary tract infections, but LB931 is also resistant to, for example, Nalidixin [sic] acid and Norfloxacin. LB931 is also resistant to vancomycin. The MIC tests were also performed for the spermicidal agent Tergitol. LB931 was grown on MRS agar in 5% C02, 37 ° C, for 48 hours. The bacteria were inoculated in 3 ml of MRS broth and incubated for 10 hours under the same conditions indicated above. 14.5% of the culture was reinoculated in 3 ml of MRS broth and incubated under the same conditions for 18 hours. The NP-9 Tergitol (Sigma, US) lot 47F0002 was diluted in MRS broth at a temperature of 37 ° C (reduced viscosity) to a standard solution of 40%. Using this standard solution, 3 ml solutions were prepared with the following concentrations: 0%, 5%, 10%, 20%, 30% and 40%. 10 μl of the bacterial culture were added to each solution. The white solution was mixed and added to MRS agar plates. Plates were grown at 5% C02, 37 ° C for 48 hours to determine cell density. The rest of the solutions were incubated without mixing in 5% C02, 37 ° C for 18 hours. Solutions containing 30% and 40% NP-9 were diluted in MRS broth at 37 ° C (reduced viscosity). All solutions were mixed vigorously, diluted in sterile 0.9% NaCl and added to MRS agar plates. The plates were incubated in 5% C02, 37 ° C for 48 hours to determine the cfu / nl. The results are described in Table VII below.
The amount of LB931 inoculated was 1.0 x 10 ufe Tergitol NP-9 Ufc / ml LB931 1% 2.5 x 10E 5% 2.5 x 10 * 20% 1.4 x 109 30% 1.0 x 109 40% 6.9 x 107 The results show that LB931 can survive well in up to 40% of Tergitol NP-9.
Example 7: Adherence of LB931 to vaginal epithelial cells a) Preparation of a suspension of LB931 LB931 was grown on MRS agar (5% C02, 37 °, 48 h). The culture was inoculated in 3 ml of broth (5% C02, 37 °, 8 h). 2% of the resulting culture was reinoculated in 10 ml of MRS broth (5% C02, 37 °, 18 h). The resulting culture was centrifuged for 8 minutes at 20 ° C and 2000 rpm in a swing-our rotor (820 x g). The cell pack obtained was washed in 5 ml of lactic acid buffer (10 mM lactic acid, pH 4.5, 0.15 M NaCl). The bacteria are diluted in lactic acid buffer until the DO500 e? approximately 1.0 (approximately 10 cfu / ml) b) Preparation of vaginal epithelial cells Vaginal epithelial cells were harvested using a sterile cotton swab, and the cells were transferred to 4 ml of lactic acid buffer or PBS in a small tube. The tube was mixed and the cotton swab was removed. The tube was centrifuged at 700 rpm at 20 ° C for 8 minutes in a Jouan CR-12 rotor ("100 x g) and the obtained pack was washed in 3 ml of lactic acid buffer or PBS. The cells were counted in a hematocyte counter and the concentration was adjusted to 10 -10 cells / ml using lactic acid buffer or PBS. 25 μl of cells were scattered on a microscope slide to control the washing procedure (see below). c) Adhesion tests 0.5 ml of suspension of LB931 and 0.5 ml of cell suspension were mixed for a short time in a 1.5 ml eppendorf tube. A control sample was prepared by mixing 0.5 ml of the cell suspension and 0.5 ml of buffer. The tubes were centrifuged at 20 ° C and 2000 rpm ("720 x g), and subsequently incubated for one hour at 37 ° C. After incubation, the tubes were centrifuged for 8 minutes at 20 ° C at 700 rpm ("90 x g). The packs were washed in 1 ml of lactic acid buffer or PBS. Finally, the package was suspended in 400-500 μl of lactic acid buffer or PBS. d) Analysis 25 μl of the suspended package was allowed to air dry on a microscope slide, followed by fixation and Gram staining. From each sample, 50 epithelial cells were analyzed. The number of LB931 adhered to the cells was counted and the results were divided into five groups (0-10, 11-30, 31-50, 51-100> 100 bacteria / cell). The results are described in Table VIII below: Table VIII Number of people tested: 5 Sampling times: before menstruation (am); ovulation (Ov) epithelial cells LB931 adherent / epithelial cells Samples 0-10 11-30 31-50 51-100 > 100 (a) incubated with LB931, pH 4.5 17.2 * 24.8 14.4 15.6 28.0 (a) incubated control cells, pH 99.6 0.4 4.5 (Ov) incubated with LB931, pH 4.5 8.4 22.8 19.2 20.0 29.6 (Ov) control cells incubated, pH 98.4 1.6 4.5 the figures are given in percent.
The results clearly show that LB931 bacteria adhere well to vaginal epithelial cells regardless of when cells are sampled.

Claims (11)

1. Lactobacillus plantarum, strain LB931 that has been deposited in the Deutsche Sammlung von Mikroorganismen, and assigned with accession number DSM11918.
2. Lactobacillus plantarum, strain LB931 that has been deposited in the Deutsche Sammlung von Mikroorganismen, and assigned with the access number DSM11918, for medical use.
3. A pharmaceutical composition containing Lactobacillus plantarum, strain LB931, which has been deposited in the Deutsche Sammlung von Mikroorganismen, and assigned with accession number DSM11918, together with a pharmaceutically acceptable carrier and / or diluent.
4. The pharmaceutical composition according to claim 3, characterized in that it also contains other lactic acid bacteria.
5. The pharmaceutical composition according to claim 3, which contains 10 4 to 1011 ufe, preferably 105 to 109 ufe of LB931.
6. The pharmaceutical composition according to claim 3, which is a suspension, spray, gel, cream, powder, capsule or vaginal insert.
7. An absorbent product, such as a sanitary product for women, a diaper, a sanitary towel, a panty hose or an incontinence protector, characterized in that it contains Lactobacillus plantarum, strain LB931, which has been deposited in the Deutsche Sammlung von Mikroorganismen, and assigned with the access number DSM1191
8. 8. The absorbent product according to claim 7, which contains 10 to 10 ufe, preferably 10 to 10 ufe of LB931.
9. The pharmaceutical composition according to claim 5, wherein the acceptable pharmaceutical carrier is skimmed milk or the growth factor of Lactobacillus in powder or another form.
10. The use of Lactobacillus plantarum, strain LB931, which has been deposited in the Deutsche Sammlung von Mikroorganismen, with the accession number DSM11918, for preparing a pharmaceutical composition for preventing and / or treating urogenital infections, such as colonization of enterobacteria.
11. The use of Lactobacillus plantarum, strain LB931, which has been deposited in the Deutsche Sammlung von Mikroorganismen, with the accession number DSM11918, to produce an absorbent article, such as a diaper, sanitary napkin, pantyhose or a protective against 'incontinence, convenient to prevent and / or treat urogenital infections, such as the colonization of enterobacteria.
MXPA/A/2000/008161A 1998-03-06 2000-08-21 New agent MXPA00008161A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE9800749-5 1998-03-06
SE9801951-6 1998-06-02

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MXPA00008161A true MXPA00008161A (en) 2001-07-09

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