WO2014020613A1

WO2014020613A1 - Probiotic layered condom

Info

Publication number: WO2014020613A1
Application number: PCT/IN2013/000004
Authority: WO
Inventors: Venkatsatyasurya Subrahmanya Prasad KOMPELLA; Laxman Jay SOMAN
Original assignee: PLANTUS HEALTH SUPPLEMENTS PRIVATE Ltd
Current assignee: PLANTUS HEALTH SUPPLEMENTS PRIVATE Ltd
Priority date: 2012-07-30
Filing date: 2013-01-03
Publication date: 2014-02-06
Anticipated expiration: 2015-01-30

Description

"PROBIOTIC LAYERED CONDOM" TECHNICAL FILED OF THE INVENTION:

The present invention relates to probiotic layered condom, for both male and female, which offers a method to treat and maintain eubiotic state of vaginal health with respect to lactic acid producing bacteria and control of vaginal pH in bacterial vaginosis.

BACKGROUND AND PRIOR ART:

During the childbearing age of a female, various physiological changes occur that alter the Urogenital environment also, One amongst which is the alteration of vaginal pH. This deviation from normalcy occurs due to infections, drugs such as clomifene, cycle regulators, contraceptives. Vaginitis (infection of the vagina) is the most common gynecologic condition encountered in the working women, with symptoms of abnormal discharge, vulvovaginal discomfort, or both. Cervicitis may also cause a discharge and sometimes occur with vaginitis. The most common causes of vaginitis in symptomatic women are bacterial vaginosis (40-45%), vaginal candidiasis (20-25%), and trichomoniasis (15-20%). Treatment to all these groups occurs only when they are presented clinically. Bacterial vaginosis (BV) is a condition in which the normal, laetobacillus-predominant vaginal flora is replaced with anaerobic bacteria, gardnerella vaginalis, and mycoplasma hominis. Eighty-five percent of those with bacterial vaginosis are asymptomatic. From as low as 7% to as high as 72% of the cases remain undiagnosed. Overall a large amount of population is left untreated even by conventional means.

BV results in several changes in the vaginal flora that provide biological plausibility for an increased risk of HIV acquisition in BV positive women. BV is associated with a depletion of hydrogen peroxide-producing lactobacilli that may reduce vaginal defense against microorganisms including HIV. An analysis of HIV incidence studies indicates that BV increases the risk of HIV acquisition by approximately 60 percent. Higher vaginal pH (>4.5) that occurs with BV may also increase the availability of vaginal HIV target cells and also increase the adherence and survival of HIV. A meta-analysis of 23 eligible publications involving 30,739 women on BACTERIAL VAGINOSIS & HIV ACQUISITION concludes that increase in the prevalence of Bacterial vaginosis was consistently associated with increased risk of HIV. Many other factors such as intercourse, douching, medications (contraceptives, antihistamines) or hormonal changes during pregnancy, menopause or during the menstrual cycle increases the vaginal pH.

Apart from pH, lactobacilli count is also important. Studies of sex workers in Thailand and Mombassa have demonstrated that women with a low prevalence of lactobacilli are at significantly higher risk of acquiring disease. Several new studies link the loss of vaginal flora with an increased risk of sexually transmitted diseases. The meta-analysis of available literature resulted in a positive association between BV and uterine cervical HPV infection.

Overall BV prevalence was high in several populations of women studied, with prevalence rates as high as 70 percent. All age groups are affected. The highest incidence is noted among young, sexually active women and also pregnant women. Vaginitis affects all races. The highest incidence of bacterial vaginosis is in blacks (23%), and the lowest is in Asians (6%). Prevalence increases with age among non-Hispanic black women. The incidence is 9% in whites and 16% in Hispanics.

Treatment of vaginal infections happens conventionally with antibiotics such as metronidazole, clindamycin and tinidazole for bacterial vaginosis, through either-oral or vaginal route based on the choice of antibiotic. Certain limitations exist to conventional approach such as -

1. During pregnancy, women who are high-risk for preterm labor are advised to avoid vaginal application of any treatment, by some doctors.

2. Sexual activity may sometimes be advocated to be refrained for the vaginal usage of any such treatment of bacterial vaginosis. 3. Medicines inserted into the vagina cause fewer side effects than oral medicines, although they can make the environment vulnerable to vaginal yeast infection.

On the other hand, while the purpose of condom is to prevent HIV, in case of women with Bacterial vaginosis, undiagnosed/asymptomatic, who participate in sexual intercourse a mere condom tends to be incomplete as the same prevents physical transmission of virus. The gap lies in the fact that it doesn't attempt to ensure the recolonization of natural micro-flora or restore the eubiotic vaginal environment or pH abnormality.

US5623945 deals with a two layer prophylactic condom having spiral path filled into pharmacological liquid to kill sperms as an additional family planning aid.

Vaginal pH buffering for prevention of miscarriage and premature labor and for preventing bacterial vaginosis is reported in US6479045.

Also, with bacterial vaginosis being associated with premature rupture of membranes preterm delivery infection of the chorion and amnion, histologic chorioamnionitis, infection of amniotic fluid, intrauterine death, the invention gains relevance for a bigger cause.

Use of drug-impregnated loose gauze tampon into vagina for inducing selective effect on pathogenic microflora with minimum suppression of lactobacilli is disclosed in RU2124890, titled Method of Treating Bacterial Vaginosis and Inflammatory Processes of Genitalia.

RU2113183 also describes a tampon based method of treatment of bacterial vaginosis.

Use of suppository based treatment of vagina for eliminating Atopobium vaginae bacteria in bacterial vaginosis is claimed in RU20101 12734. However, none of the reported methods of treatment of vaginal bacteriosis employs use of condoms to provide probiotics to maintain vaginal health.

SUMMARY OF THE INVENTION;

With a large prevalence and increasing incidence of Vaginitis, symptomatic-treated and an equal prevalence & incidence trend for asymptomatic and undiagnosed, the risk of secondary infections such as HIV is no more just by physical means. Latest research opines that the unfavorable vaginal environment is by itself an independent trigger to HIV colonization. While condoms protect women from physical transmission of HIV, there still exists a gap that can actually correct conditions such as Bacterial vaginosis (BV) which presents an alkaline vaginal environment, favorable for the growth of HIV. This is due to the depletion of lactic acid producing bacteria and increase in vaginal pH. The proposed invention attempts to recolonize the lactic acid producing bacteria by a novel method to decrease the risk of HIV / HPV in women affected primarily with bacterial vaginosis, by use of probiotic layered condom (both male and/or female wearable type) that offers the method/process to maintain eubiotic state of vaginal health with respect to presence of lactic acid producing bacteria and vaginal pH in Bacterial vaginosis.

DETAILED DESCRIPTION OF THE INVENTION:

The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated. However, any skilled person will appreciate the extent to which such embodiments could be extrapolated in practice.

In the context of vagina being incessantly subjected to cyclic changes as well as behavioural exposures that may challenge the perpetuation of the Lactobacillus microflora, the intrinsic stability of the resident microflora is paramount to women's health. The method enlists the means by which the device of a condom offers the benefit either by a direct microbistatic / microbicidal action, or by proliferation of beneficial microflora, or by generating lactic acid environment (eubiotic) detrimental to pathogens or by a combination of all these benefits.

The invention offers to benefit in asymptomatic / undiagnosed cases or both by physiological recolonization, to prevent the incidence of secondary complications such as HIV, HPV. In all such conditions, which are not presented for treatment, the novelty of the concept is that it benefits the woman during the intravaginal ejaculation latency time by the physiological recolonization of Lactic acid bacillus in the dysbiotic environment by a device which is otherwise very popular in most parts of the world for its use to prevent STI. The invention facilitates the phsyiological range of vaginal pH (3.8 to 4.5). The device offers the method of correction of the local environment to eubiotic state and consequentially be helpful to treat BV / prevent HIV / HPV which by itself a novelty compared to conventional means of treatment such as oral or vaginal antibiotics.

While any condom can prevent physical transmission of HIV, the invention (probiotic layered condom) stands out to be first one to address complete prevention of HIV transmission in case of women affected with bacterial vaginosis, by use of the condom during intercourse.

In a preferred embodiment, the present invention describes a condom, whose outer layer is coated or layered with lactic acid producing probiotic and or its formulations has been introduced which would spread in the vaginal cavity and proliferate to release lactic acid which in turn maintains the health and hygiene of vaginal environment which is essential in case the couple opt for conception in the near future.

In another preferred embodiment, the present invention describes a condom, wherein the probiotic and or its formulations are mixed with any surfactants such as "SILICONE OIL" or any such carrier and growth and survival enhancer of probiotic and or its formulations whilst the said surfactant works as lubricant during the intercourse.

Lactic acid producing probiotic formulation of the present invention comprising of a probiotic is present in the range of 100 million CFU /g to 500 million CFU/g, preferably 200 million CFU /g, but not limiting to the same, silicone oil is present in the range of 350 mg to 450 mg, preferably 400 mg and sodium lauryl sulphate is present in the range of 0.001 % to 1 %, preferably 0.01%.

The probiotics used in the present invention are selected from Lactic acid bacillus (LAB) such as Lactobacillus acidophilus, Bacillus coagulans, Lactobacillus rhamnosus, or any of such lactic acid producing probiotic species either individually or as combination. Possibility of probiotic species that ensure the modulation of vaginal pH, by inducing either butyric acid rich environment or an environment that presents a mixture of acetic & butyric acid to normalcy either individually or as combination.

The composition of lactic acid bacillus or probiotic species that ensure to correct the vaginal pH to normalcy presented in silicone oil which serves both as lubricant for the host and also growth promoting media for lactic acid bacillus. The composition may comprise of Bifidobacterium species such as B.adoloscentis, B. breve, B.bifidum either singly or as a combination with lactic acid bacilli with or without traces of prebiotic presence such as glycogen coexisting with probiotic coating.

In another preferred embodiment, the present invention describes the process for preparation of probiotic formulation includes the following steps:- a) Adding Probiotic (crude) to silicone oil and mixing for 30 min with stirrer;

b) adding 0.01% of SLS (Sodium Lauryl Sulphate) to the mixture of step (a) and sonicating for 30 min followed by serial dilution and heating for 30 min at 75°C; c) transferring the mixture of step (b) in PNY medium, to perform the assay with regular analytical procedure.

The composition of PNY medium containing the ingredients such as Yeast extract, Bacto- casitone, Dextrose, ΚΗ₂Ρ0_4> K₂HP0_4; Magnesium Sulphate, Agar along with Mineral Salt Solution (M.S.S.).

The composition of Mineral Salt Solution (M.S.S.) containing the ingredients such as NaCl, MnS0₄.5H₂0, FeS0₄.7H₂0, CuS0₄.5H₂0, ZnS0₄.7H₂0 and CoS0₄.7H₂0; wherein the said ingredients are dissolve in 50ml of distilled water and acidify with sulphuric acid to get a clear solution.

The present invention describes the process for preparation of PNY Medium includes the following steps :- a) Dissolving the composition of PNY medium in about 700 ml of distilled water; b) adding 1 ml of mineral salt solution to step (a);

c) making the volume to 1000 ml and adjusting the pH between 5.8 to 6.0 followed by adding 15 gm of agar to obtain a medium; and

d) autoclave the medium obtained in step (c) to maintain pH 6 followed by further autoclave at 121°C for 15 minutes.

In one preferred embodiment, the Probiotics of the present invention is premixed in Silicone oil and before striping into sachet metered dose of silicone oil is dropped/sprayed on the preformed, folded condom then is sealed. As the oil spreads on the outer layer of the condom the probiotic also spreads.

The present invention discloses a method of preventing the growth of opportunistic pathogenic microbes such as bacteria, fungi, yeast either manifested single or as concomitant presentations by providing a condom whose outer layer is coated or layered with lactic acid producing probiotic and or its formulations.

The present invention discloses a method of controlling the existing pathogens by physiological recolonization of micro-flora by a probiotic film or layer or any of such presentation on the lubricating surface of the condom.

The present invention discloses a method of destroying the existing pathogens in human vagina by creating an environment that provides for the favorable vaginal pH range (3.8 - 4.5) due to lactic acid producing bacteria. Condom of the present invention is wearable by both man and woman designed for vaginal health during intercourse is also described herein. The present invention provides a method of decreasing the risk of HIV colonisation by providing a eubiotic environment incongenial to HIV, by using condom whose outer layer is coated or layered with lactic acid producing probiotic and or its formulations, during intercourse. A method of preventing the risk of HPV by providing a condom whose outer layer is coated or layered with lactic acid producing probiotic and or its formulations to alter the pH to the normal range is provided herein.

The condom of the present invention can be used in intercourse by various groups such as premarital groups, married women, pregnant women and in all those women of reproductive age who are prone to local urogenital infections such as Bacterial vaginosis, though asymptomatic /undiagnosed.

The following examples, which include preferred embodiments, will serve to illustrate the practice of this invention, it being understood that the particulars shown are by way of example and for purpose of illustrative discussion of preferred embodiments of the invention.

EXAMPLES:

Example 1: Probiotic formulation

Example 2: Preparation of Probiotic formulation

a) Adding Probiotic (crude) to silicone oil and mixing for 30 min with stirrer;

b) adding 0.01% of SLS (Sodium Lauryl Sulphate) to the mixture of step (a) and sonicating for 30 min followed by serial dilution and heating for 30 min at 75°C; c) transferring the sample of step (b) in PNY medium, to performed the assay with regular analytical procedure.

Results:

Conclusion:

From the above result (Silicone oil + LAB + 0.01% SLS) recovery is 86.85 % and loss is 13.15 %.

Example 3: Composition of PNY Medium

Example 4: Composition of Mineral Salt Solution (M.S.S.)

Ingredients Grams / 50 ml

NaCl 0.5

MnS0₄. 5H₂0 0.8 FeS0₄. 7H₂0 0.9

CuS0₄. 5H₂0 0.08

ZnS0₄. 7H₂0 0.08

CoS0₄. 7H₂0 0.08

Dissolve the above ingredients in 50ml of distilled water

and acidify with sulphuric acid to get a clear solution.

Example 5: Preparation of PNY Medium a) Dissolving the ingredients of Example 1 in about 700 ml of distilled water;

b) adding 1 ml of Mineral salt solution of Example 2;

d) autoclave the medium obtained in step (c) to maintain pH 6 followed by further autoclave at 121 °C for 15 minutes.

Example 6: Composition for coating the condom

Example 7: Coating of the condom with the composition

Coating of the condom is done by incorporating the active ingredient along with lubricant such as silicone oil and before striping into sachet metered dose of silicone oil is dropped/sprayed on the preformed, folded condom then is sealed. As the oil spreads on the outer layer of the condom the probiotic also spreads. Example 8

Silicon oil + LAB experiment Experiment analysis procedure a) Adding LAB Probiotic (crude) to silicone oil and mixing for 30 min with stirrer; b) taking lgram of (silicon oil + lab) as sample 1

c) taking another lgram of sample 1 which is mixed with SLS (0.01%) based on initial dilution factor to obtain sample 2.

d) sonicating both the samples for 30 min followed by serial dilution and heat shock for 30 min at 75°C;

c) transferring the samples of step (d) in PNY medium, to perform the assay with regular analytical procedure.

The results experiment is demonstrated in below table.

Conclusion:

From the above results

sample-1 ( Silicon oil + Lab) recovery is 76.06 % and loss is 23.94 %

sample-2 ( Silicon oil + Lab + 0.01% SLS) recovery is 86.96 % and loss is 13.04 %

Claims

We Claim,

1. A probiotic layered condom comprising an outer layer coated with lactic acid producing probiotic and/or its formulation capable of maintaining the eubiotic state of vaginal health and controlling the vaginal pH in bacterial vaginosis; wherein the said condom is used during intercourse.

2. A probiotic layered condom according to claim 1, wherein said probiotic formulation comprising of probiotic in an amount ranges from 100 million CFU /g to 500 million CFU /g, silicon oil in an amount ranges from 350 mg to 450 mg and sodium lauryl sulphate in an amount ranges from 0.001 to 1 %.

3. A probiotic layered condom according to claim 1 and 2, wherein said probiotic formulation is prepared by the process comprising of;

a) Adding Probiotic to silicon oil and mixing for 30 min with stirrer; b) adding 0.01% of SLS (Sodium Lauryl Sulphate) to the mixture of step (a) and sonicating for 30 min followed by serial dilution and heating for 30 min at 75°C;

c) transferring the mixture of step (b) in PNY medium, and assay is performed with regular analytical procedure.

4. A probiotic layered condom according to any of the preceding claims, wherein said condom is wearable by both man and woman, during intercourse.

5. A method of preventing the growth of opportunistic pathogenic microbes such as bacteria, fungi, yeast either manifested single or as concomitant presentations comprising use of a probiotic layered condom during intercourse according to claim 1.

6. A method of controlling the existing pathogens by physiological recolonization of micro-flora by a probiotic film or layer or any of such presentation on the lubricating surface of a probiotic layered condom according to claim 1, used during intercourse.

7. A method of destroying the existing pathogens comprising the use of a probiotic layered condom during intercourse according to claim 1, to create an environment that provides for the favorable vaginal pH range 3.8 - 4.5 due to lactic acid producing bacteria.

8. A method of decreasing the risk of HIV colonisation comprising use of a probiotic layered condom during intercourse according to claim 1, to maintain eubiotic environment incongenial to HIV.

9. A method of preventing the risk of HPV comprising use of a probiotic layered condom during intercourse according to claim 1, to alter the pH to the normal range.

10. Use of probiotic layered condom during intercourse according to any of the preceding claims, in the treatment of local urogenital infections such as Bacterial vaginosis, though asymptomatic / undiagnosed.