NOVEL SPERMICIDAL AND ANTI-INFECTIVE CONTRACEPTIVE DEVICE

FIELD OF THE INVENTION

The present invention relates to novel spermicidal and anti-infective devices which are highly useful as a contraceptive method for prevention of unwanted pregnancy besides providing effective protection against microbes. The present invention also describes process for preparation of such novel devices and method of using them. The novel devices of the present invention can be used by males or females or both. Also, the devices are safe and easy to formulate and provides effective protection particularly against sexually transmitted diseases (STDs) and human immunodeficiency virus

(HIV) and optionally against fungal infections.

BACKGROUND OF THE INVENTION

HIV infection is a worldwide epidemic affecting people everywhere. The spread of HIV infection has occurred on such a scale, and the impact of the disease is potentially so devastating to world health, that only a concerted, global response is appropriate. There are approximately 16,000 new HIV-I infections per day, 90% of which occur in developing countries. At the end of 2004, it was estimated that nearly 40 million people were currently living with HIV infection. HIV is transmitted through direct contact of a mucus membrane with a bodily fluid such as blood, semen, vaginal fluid or breast milk. This transmission can come in the form of: penetrative (anal or vaginal) sex; oral sex; blood transfusion; contaminated needles; exchange between mother and infant, during pregnancy, childbirth and breastfeeding; or other exposure to one of the above bodily fluids. The majority of HIV infections are acquired through unprotected sexual relations. Sexual transmission occur when there is contact between sexual secretions of one partner with the rectal, genital or mouth mucous membranes of another. Results of multiple studies suggest that the presence of other STDs can greatly increase transmission of HIV. From a public health perspective, the need for contraception has never been greater. Although the existing male-specific methods such as withdrawal, condoms, and vasectomy are safe and effective, increasing male options for fertility control could improve family planning. For new male contraceptive methods to have an impact, they must be acceptable to both men and women, as well as effective. Other

strategies such as contraceptive vaccines, and inhibitors of spermatogenesis and sperm motility, provide a potential for nonhormonal male contraceptives.

Methods such as 'Coitus interruptus' (withdrawal) does not require any devices, chemicals, or hormonal treatments, but the same provides no protection from lesions on skin or mucus membranes, and fluid from the pre-ejaculate that may contain pathogens such as gonorrhea and HIV. Vasectomy involves the surgical isolation and division, electrocauterization, or occlusion (with clips) of the paired vas deferentia and provides long-lasting benefit, but initial costs are high and there are concerns about possible elevated risk of heart disease and prostate cancer. Contraceptive methods for female includes herbal methods such as consumption of wild yam and application of neem oil on the cervix, inserting a film or a sponge or jellies or foam containing a spermicide into vagina and depositing over the cervix or use of an inter uterine device (IUD). However such methods often cause lower abdominal pain, allergic reactions such as vaginal burning, itching, redness and rashes, etc. and do not offer any protection from STDs or HIV and instead may increase opportunity for infections.

Condoms are by far the best available methods for contraception. A condom can be described as a protective sheath used as a contraceptive or to protect against sexually transmitted diseases. They are primarily of three types: (i) 'Latex condoms' are by far the most abundant on the market. They are relatively inexpensive, thin, flexible, and extremely effective against pregnancy and STDs including AIDS. The only drawbacks include possible allergies to latex and bad odour of the latex rubber. Oil based lubricants such as petroleum jelly and cold cream will break down latex rubber, hence water based lubricant needs to be used, (ii) 'Polyurethane condoms' are made from polyurethane which is a plastic-like material. It is extremely thin, durable, has no taste or odour, causes no known allergic reactions, and can be used with both oil and water based lubricants. They cost a little more than latex condoms, and aren't quite as flexible as latex, but they make a great alternative, (iii) Natural or Sheepskin condoms are made from animal intestines. They are just as effective against pregnancy as polyurethane or latex, however they do not offer good protection against STDs. They cost two to three times as much as latex and are not as widely available. Oil and water based lubricants can be used with them.

Male condoms cover the penis with a thin sheath of material designed to prevent the release of semen into the vagina. This protects the skin and prevents the exchange of sperm or infectious material. Substantial evidence links the use of latex and/or plastic condoms to a reduction in the risk of STDs, including HIV. Condoms are inexpensive, portable, and widely available, and permit men to actively participate in protecting their partners. Although all condoms protect against pregnancy, the pore size of natural membrane condoms is large enough to allow hepatitis B and HIV viruses to pass easily through the material. Some natural membrane condoms even allow leakage of the herpes simplex virus, which is larger than either hepatitis B or HIV particles (120-150 nm). Although there are no comparative clinical trials of STD transmission, natural membrane condoms are not indicated for the prevention of STDs. Plastic (polyurethane) condoms provide an alternative in cases in which allergy or other factors prevent the use of latex. Although in one randomized crossover trial a majority of male subjects preferred the sensitivity of plastic over latex condoms, the clinical failure rates (breakage or slippage) were significantly increased for polyurethane models. Another randomized trial found a lower condom-related dropout rate and greater overall satisfaction among men assigned to the latex condom group. Perfect use of male condoms is associated with a 3% probability of pregnancy, whereas typical use increases the risk to 14%. The addition of spermicidal lubricants to condoms may further reduce the risk of pregnancy for all types of condoms. However, such lubricants do not affect the transmission of STDs, and may increase the risk of urinary tract infections in female partners. Oil-based lubricants such as petroleum jelly should never be used with latex condoms because they degrade the latex and therefore increase the risk of breakage. One of the cornerstones of safer sex programs is correct condom use to prevent both unplanned pregnancies and the spread of sexually transmissible infections, including HI V/ AID S. However, many people are unaware that commonly used products may have an adverse effect on the protective properties of barrier contraceptives made of latex. The products most likely to come into contact with condoms or diaphragms are lubricants, spermicidal preparations, personal hygiene products, hormonal preparations, acidifying agents, and preparations used for treatment of common vaginal infections, especially Candida. It is possible that any dermatological product used on the genital area in both sexes, may have an effect on latex rubber. Research strategies on hormonal methods of male contraception include weekly or

long-acting intramuscular injections, and implantable, oral, or transdermal testosterone delivery systems. In an effort to boost the rates of azoospermia, combination regimens involving gonadotropin-releasing hormone analogues and progestins have also been studied. The efficacy of male hormonal methods depends on the degree of suppression of spermatogenesis. Concerns regarding hepatotoxicity and short half-life limit the potential use of currently available oral testosterone as a contraceptive.

Worldwide, the predominant mode of human immunodeficiency virus (HIV) transmission is heterosexual intercourse, but the risk of heterosexual transmission and the effectiveness of measures to prevent it are not well defined. A study has revealed that consistent use of condoms for heterosexual intercourse is highly effective in preventing the transmission of HIV. The only nonsurgical method of male contraception marketed worldwide, the condom is also known to be highly effective against the sexual transmission of HIV and other diseases. Condoms, however, are underutilized compared to other methods. A review study conducted by d'Oro et al (Genitourin Med. 1994 Dec; 70(6):410-7) reported evidence that barrier methods of contraception (BMC) reduce the risk of gonorrhoea and HIV transmission. Use of chemical compound as spermicide increases the risk of urinary tract infection (UTI). A study was conducted by Fihn et al (Am J Epidemiol. 1996 Sep 1; 144(5):512-20) to determine whether spermicide-coated condoms are also associated with an increased risk of UTI. Condoms coated with spermicide such as nonoxynol-9 were responsible for 42% of the UTIs among women who were exposed to these products. The association confirmed in this study supported by research indicating that nonoxynol-9 induces changes in the normal vaginal flora that facilitate colonization with coliform bacteria. Roddy et al (Sex Transm Infect. 1998 Apr; 74(2): 116-9) tested the effect of nonoxynol-9 (N-9) in condom lubrication on the risk of acquiring STD and genital discomfort. They concluded that plain silicone lubricated condoms are as effective as N-9 lubricated condoms, cost effective, have longer expected shelf life, and therefore may be the better condom to provide. Currently, nonoxynol-9 (N-9) is the most widely used lubricant along with condoms that claims protection from transmission of STDs. While the effectiveness of nonoxynol-9 as a spermicide is well known, its usefulness as a microbicide has been questioned, and in fact recent data indicate that nonoxynol-9 may actually increase the risk of HIV transmission. The frequent use of nonoxynol-9

can induce lesions and ulcerations to genital mucosa, thereby increasing the probability of transmitting infectious agents. Studies have also indicated that these adverse effects of N-9 are dose related, supporting the notion that a potentially narrow margin of safety may exist for N-9. A recent report from WHO concluded that spermicides containing nonoxynol-9 do not protect against gonorrhoea and chlamydia. Clinical surveys have suggested that use of spermicides with antiviral activity, e.g. nonoxynol-9, will not satisfactorily restrict the spread of HIV (Cates et al. Family Planning Perspective, 24:75-84, 1992), as the frequent use of nonoxynol-9 leads to the creation of vaginal lesions (genital ulcers and vulvitis), which provide entry ports for HIV particles to pass through the protective barrier of the skin and reach the bloodstream (Kreiss et al. The Journal of The American Medical Association, 268: 477-482, 1992). US5624675 discloses a method of using a topical genital lubricant with a non-toxic, non-irritating zinc salt during sexual intercourse for the reduction of HIV infection. US5552382 discloses the use of gramicidin as an active ingredient of spermicide with virucidal activity against HIV. US5778886 discloses the use of nonoxynol-9 and hydrogen peroxide in vaginal compositions for the prevention of conception and the transmission of STD. US6624198 discloses a spermicidal lubricant composition, which includes chlorhexidine salt as an active ingredient against HIV and other viruses.

Several patents have been granted for coating of condoms with a lubricant, with additional anti-microbial property. Patents have been granted for anti-microbial preparations of trioxolane or diperoxide derivatives [US5364879], antiviral protein preparation of a particular sequence [US6420336], Lactic acid bacteria containing compositions [US 6,892,732], beta-cyclodextrin containing compositions [US6835717], chlorhexidine and paraben containing compositions [US6624198] and butylurea in combination with Nonoxynol-9 and benzalkonium chloride, which may be incorporated into condom lubricants. Further, several patents or publications disclose the devices used for protecting from unwanted pregnancy and the spread of sexually transmitted diseases such as US20060048784, US5623945, US6796311, US6458346, US20060048784 and US20040176748. There are also a number of patents or publications that disclose the method of preventing or treating a STD and compositions used for prevention of STDs such as US5466714, US20050241645, US20050143461, US6302108, US 6192887, US6458346 and US 20030108509. PCT publication no. WO

200682596 describes a stable non-synthetic herbal anti-fertility composition having high spermicidal activity for intra vaginal administration comprising neem oil and pharmaceutically acceptable excipients in suitably formulated dosage form for vaginal administration; however no disclosure is provided on making a spermicidal device with herbal product which is also effective against microbes and STDs. US Patent no. 6333058 describes a process for preparing a spermicidal agent from neem oil. European patent no. EP472791 discloses the use of neem oil or its components in the manufacture of a medicament for the reversible blocking of fertility in a female. US Patent no. 5196197 describes an antifertility agent comprising neem oil and a reetha extract wherein the neem oil is present in a concentration of about 10%-25% w/w and the concentration of the reetha extract is about 0.5-1% w/w. But none of them disclose a device along with plant derived substance for use as spermicidal and anti-infective. Since the work of Henshaw in 1953, there has been a steady accumulation of information regarding the screening of plants having antifertility efficacy (Chopra et al, 1956, 1958; Casey, 1960; Choudhury, 1966; Bhakuni et al, 1969; Farnsworth et ctl., 1975). Various reviews, such as those by Orzechowski (1972), Brondegaard (1973), Kholkute et al. (1976), Bingel and Farnsworth (1980), Woo et α/.(1981), Zhu (1982), Kamboj and Dhawan (1982), Xie et al. (1986) and Wong (1987) have been given on medicinal plants and their active principles for fertility regulation.

An ideal male contraceptive should be safe, effective and reversible, and not have an effect on the libido. Suppression of spermatogenesis by sex steroids has been considered as a reversible chemical method of male contraception for a long time despite the side effects associated with hormonal methods. Androgens alone, or progestogens combined with androgens, were effective in inducing azoospermia in Caucasian men (Schearer et al, 1978). These were found to be effective in suppression of spermatogenesis but their treatment caused unacceptable side effects with long-term use, hence the search for alternatives preferably natural/herbal products.

Neem (Azadirachta indicd), an esteemed evergreen plant, is native to the Indian subcontinent. Neem seed oil is a traditionally known anti-microbial agent with documented potent anti-bacterial, anti-fungal and anti-viral activities along with spermicidal properties. Several diverse chemical compounds and their derivatives like

azadirachtin and nimbicidin have been isolated from neem products. Such compounds possess varied biological properties and impart bitterness to neem. Bitter compounds exhibit repellent, sterilising, and antifertility effects in insects, and are hence employed in the manufacture of pesticides. Hypoglycaemic, anti-inflammatory, anti-infective, and antinematodal effects of neem derivatives are well documented. Aqueous extracts of neem seeds, bark, or leaves exhibit potent immunostimulant activity through both humoral and cell-mediated response. Nimbin and Nimbidin which have been shown to be potent anti-viral agents along with other triterpenoids present in neem, occur predominantly in the oil extracted from the kernels [Verma, Acta Microbiol Pol B. 1974; 6(1): 9-13]. The volatile, odourous fraction of neem oil coded as NIM-76 obtained by steam distillation was investigated for in-vitro spermicidal activity and was found to inhibit spermatozoal motility at minimum concentrations of 0.25 mg/ml for rat and 25 mg/ml for human spermatozoa [Riar et al. Contraception. 1990 Oct; 42(4): 479- 87]. The NIM-76 preparation inhibited growth of various pathogens including Escherichia coli and Klebsiella pneumoniae, which were not affected by the whole neem oil. NIM-76 also exhibited antifungal activity against Candida albicans and antiviral activity against Poliovirus replication in vero cell lines. It also protected mice from systemic candidiasis as revealed by enhanced % survival and reduced colony forming units of C. albicans in various tissues. This shows that NIM-76 has a potent broad-spectrum anti-microbial activity [Sairam et al., J Ethnopharmacol. 2000 Aug; 71(3): 377-82]. A polyherbal pessary formulated with purified ingredients from Neem, Sapindus mukorossi and Mentha citrata oil was tested for spermicidal action on human sperm by Sander-Cramer slide test in-vitro and by post coital tests in-vivo in rabbits. When applied in the vagina before mating, it prevented rabbits from becoming pregnant [Raghuvanshi et al., Indian J Med Res. 2001 Apr; 113:135-41]. Patents have been granted for the intra- vas application of Neem oil for long-term male contraception [e.g. US5501855]. Administration of Azadirachta indica (leaf extract) affects the structure and function of testis and spermatozoa in male rats (Shaikh et al., 1993). Kasturi et al. (1995) have reported antiandrogenic properties of A. indica leaves in male rats. The ethanol extract of neem bark and flowers induced reversible infertility in male rats. Extract interfered with spermiogenesis at Stage XII of late spermatids. Bioassay studies showed antiandrogenic nature of crude extracts (Dixit et al., 1992).

Several studies on neem have been conducted to demonstrate its spermicidal activity. Garg et al (J. Ethnopharmacol. 1994 oct;44(2): 87-92) has reported that Azadirachta indica (neem) seed extracts are known to activate the local cell-mediated immune reactions after a single intrauterine administration, leading to a long term reversible block of fertility. In order to identify and characterize the active fraction responsible for this activity, neem seeds were extracted by both mechanical expression and solvent extraction using a range of polar to non-polar solvents which yielded three broad fractions. The mechanically expressed oil was fractionated using different approaches and studied for antifertility activity. The hexane extract and a corresponding column fraction showed potent and reproducible antifertility activity. Other fractions were less stable with regard to reproducibility of effects and composition. It was concluded that for subsequent fractionation to reach the last active fraction, the hexane extract is the most useful starting material. Parida et al (J. Ethnopharmacol. 2002 Feb; 79(2):273-8) have reported in-vitro and in-vivo inhibitory potential of crude aqueous extract of neem leaves and pure neem compound (Azadirachtin) on the replication of Dengue virus type-2. The aqueous extract of neem leaves at its maximum non-toxic concentration of 1.897 mg/ml completely inhibited 100-10,000 TCID (50) of virus as indicated by the absence of cytopathic effects. The in-vivo protection studies with neem leaves extract at its maximum non-toxic concentrations 120-130 mg/ml resulted in inhibition of the virus replication. Zeitlin et al (Contraception. 1997 Nov; 56(5):329-35) have studied several microbicide candidates including neem that demonstrated activity against sperm or sexually transmitted disease pathogens in vitro, and the efficacy of these agents for preventing vaginal transmission of genital herpes infection was evaluated in the progestin-treated mouse.

Gossypol is a natural polyphenols compound, derived mainly from cottonseed oil, that causes antifertility and antisteroidogenic activities in both males and females. It reportedly induces disturbances of the hypothalamic-pituitary axis, disruption of spermatogenesis in the testes, and inhibition of post ejaculatory spermatozoa motility. A study conducted by Gu et al (Asian J. Androl. 2000 Dec; 2(4):283-7) to ascertain whether the side effects of gossypol, hypokalemia and irreversibility, could be avoided on dose reduction. A regimen with 10 or 12.5 mg of gossypol as the daily loading dose

and 35 or 43.75 mg as the weekly maintenance dose could induce infertility in male volunteers without developing hypokalemia or irreversibility.

Papaya (Carica papaya) seed has been traditionally known as an orally active contraceptive. Several animal studies have confirmed that purified fractions of Papaya seed extract are effective oral male contraceptives [Lohiya et al, Reprod Toxicol. 2005 May-Jun; 20(l):135-48; Asian J Androl. 2002 Mar; 4(l):17-26]. A complete loss of fertility has been reported in male rabbits, rats and monkeys fed an chloroform extract of papaya seeds (Lohiya et al. 1999; Pathak et al. 2000; Lohiya et al. 2002), suggesting that ingestion of papaya seeds may adversely affect the fertility of human males or other male mammals. Papaya seed extract purified fraction showed a dose-dependent spermicidal effect showing an instant fall in the sperm motility to less than 20% at 2% concentration when applied in-vitro on human sperms. Only 250 microliters of the 2% solution of the extract was able to cause total immobilization of human sperms within 20-25 minutes [Lohiya et al. Asian J Androl. 2000 Jun; 2(2): 103-9]. An oral dose of crude ripe pawpaw {Carica papaya) seeds in male albino rats caused degeneration of the germinal epithelium and germ cells, reduction in the number of Leydig cells and vacuoles in the tubules (Udoh and Kehinde, 1999). Lohiya et al (Asian J. Androl. 2002 Mar; 4(1): 17-26) evaluated the antifertility activity of the chloroform extract of Carica papaya seeds by oral administration in langur monkey. It was concluded that Carica papaya seed extract may selectively act on the developing germ cells, possibly mediated via Sertoli cells, leading to azoospermia. Manivannan et al (Phytother. Res. 2004 Apr;18(4):285-9) has shown that the benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya at a dose of 10 mg/rat/day for 150 days provides a total inhibition of motility and reduced sperm count and infertility.

A multiglycoside extract of the plant Tripterygium wilfordii, long used in Chinese traditional medicine for the treatment of psoriasis, was shown to cause a reduction in sperm motility and concentration in male patients (Qian, 1987). A collaborative programme between Chinese, Thai and British research centres succeeded in isolating a series of diterpene epoxides from extracts of the root bark of the plant. One triptolide was chosen for further pharmacological studies and was found to induce complete infertility in male rats acting primarily on epididymal sperm with minimal effects on

the testis (Lue et al, 1998). Coconut oil is unusually rich in short and medium chain fatty acids. Laurie acid, the major fatty acid from the fat of the coconut, has been recognized for its unique properties in foods which are related to its antibacterial, antiviral and antiprotozoal functions. Laurie acid is a medium-chain fatty acid, which has the additional beneficial function of being transformed into a substance called "monolaurin" in the human body. Monolaurin is an antibacterial, antiviral and antiprotozoal substance used by the human body to destroy lipid-coated viruses such as HIV, herpes, influenza, various pathogenic bacteria and protozoa such as Giardia lamblia. Capric acid, another one of coconut's medium-chain fatty acids has been added to the list of coconut's antimicrobial components. Capric acid is found in large amounts in coconuts and it has a similar beneficial function when it is transformed into "monocaprin" in the human body. Monocaprin has been shown to have antiviral effects against HIV and is being tested for its antiviral effects against herpes simplex and antibacterial effects against chlamydia and other sexually transmitted diseases. Embelin (2,5-dihydroxy-3-undicyl-l,4-benzoquinone) isolated from Embelia ribes berries showed spermicidal activity by inhibition of sperm count and activity of enzymes of energy metabolism. Purandare et al. (1979) studied the spermicidal activity of berries of E. ribes in male bonnet monkeys {Macaca radiatd). Agarwal et al. (1986) found that embelin altered testicular histology in male rats. The compound is suggested to possess antiandrogenic properties.

It has long been claimed by Ayurvedic physicians in Sri Lanka that the powdered seeds of Abrus precatorius (Linn) when taken orally inhibit conception in humans (Jayaweera, 1981). Dose dependent reduction in testicular weight, sperm count and degeneration in later stages of spermatogenesis were found in the testis of rats treated with steroidal fraction of A. precatorius seeds (Kulshreshtha and Mathur, 1990). Ratnasooriya et al. (1991) found that the seeds extract of A. precatorius caused concentration related impairment of sperm motility with the EC50 concentration being 2.29 mg/mL. Solasodine, a steroidal alkaloid of Solarium xanthocarpum caused disruptive changes in the acrosomal membrane of sperm and arrest of spermatozoal motility (Kanwar et ah, 1988). Oral administration of solasodine to intact dogs significantly decreased the epithelial cell height of the cauda epididymides. Concurrent treatment of solasodine along with testosterone propionate was unable to restore the

normal epithelial lumen parameters (Gupta and Dixit, 2002). A peculiar antispermatogenic effect oϊEchallium ellaterum has been reported in the US Patent No. 4148892 (Nassar, 1979). Administration of 1 mg of the extract of leaves and stem of the plant by gastric intubation produced a steep drop in the sperm motility and pH of semen of rabbit and human within 1 hr post treatment. Complete motility inhibition was reported in rabbits after 2 hours of treatment and in men, it dropped to 5%. A pharmacologically active ingredient isolated from this plant has been marketed as a male oral contraceptive pill known as Contrasperm®. Vinca rosea leaf extract has shown to be antispermatogenic as well as antiandrogenic in male rats (Murugavel and Akbarsha, 1991). Vincristine an indole-indoline dimeric alkaloid obtained from Vinca rosea caused regression of seminal vesicle and prostate gland and decreased secretary activity in male rats.

The closest known prior arts relating to a contraceptive device describe condoms with antispermzoidal coatings, medicated suppository for penal erection, vaginal shields and vaginal birth control medications. Particularly the spermicidal agents are chemical compounds possessing varied quantum of side effects. In case of a contraceptive device such as a condom, a major problem is that in case if the condom slips down during a decreased erection then the pathogens of STDs can cause an infection either by getting into the inner part of the condom or by getting out of it. Also, a frequent cause for tearing the condoms is that they are hurt by the nails of users trying to retain them on their place when they are felt slipping down. Another problem associated particularly with latex condoms are the chances of leakage of sperm and/or pathogens through pinholes present on such devices which might lead to pregnancy and/or infection. Hence up to now no contraceptive device is available which would provide an effective protection against both unwanted pregnancy and infections during the whole coitus and that too without any side effects. A prime factor in the development of contraceptives is the global HIV epidemic, which continues to expand at an alarming rate. The current epidemics of AIDS and other sexually transmitted diseases (STDs) have created an urgent need for a new type of contraceptive, one that is not only effective both as a spermicide and as anti-infective, but also safe and devoid of side effects. However, currently available methods of fertility regulation cannot yet meet the practical

demands for fertility regulation and prevention of infection in a safe manner. The novel spermicidal and anti -infective devices of the present invention address this unmet need.

SUMMARY OF THE INVENTION It is an objective of the present invention to provide novel spermicidal and anti- infective contraceptive device comprising at least one plant derived substance(s) possessing spermicidal and/or anti-infective properties, which is effective as a contraceptive method for prevention of unwanted pregnancy besides providing effective protection against microbes and optionally against fungal infections.

It is an objective of the present invention to provide novel spermicidal and anti- infective contraceptive devices comprising at least one plant derived substance which are effective as a contraceptive method for prevention of unwanted pregnancy besides providing effective protection against microbes particularly against sexually transmitted diseases (STDs) and human immunodeficiency virus (HIV), and optionally against fungal infections.

It is a further objective of the present invention to provide a condom as the contraceptive device to which at least one spermicidal and anti-infective plant derived substance is applied either inside or outside or on both sides, which is effective as a contraceptive method for prevention of unwanted pregnancy besides providing effective protection against microbes and optionally against fungal infections.

It is a still further objective of the present invention to provide a condom to which the applied spermicidal and anti-infective plant derived substance is an extract obtained from the plant Azadirachta indica optionally comprising another spermicidal and/or anti-infective plant derived substance, which is effective as a contraceptive method for prevention of unwanted pregnancy besides providing effective protection against microbes and optionally against fungal infections.

It is a still further objective of the present invention to provide a condom to which the applied spermicidal and anti-infective plant derived substance is an extract obtained from the plant Azadirachta indica and another spermicidal plant derived substance

which is an extract obtained from the plant Carica papaya, optionally with one or more carrier(s) or excipient(s).

It is also an objective of the present invention to provide a composition comprising one or more spermicidal and anti-infective plant derived substance in the form of spray coat, gel, lubricant cream or the like intended for application on a contraceptive device such as a condom by at least one of the individuals involved in intercourse.

It is also an objective of the present invention to provide process for preparation of such novel devices and methods of using them.

It is a further objective of the present invention to provide process for preparation of such novel devices comprising the following steps: i) obtaining the spermicidal and anti-infective extract from plant source(s), ii) applying the extract either inside or outside or on both sides of the contraceptive device.

It is a still further objective of the present invention to provide process for preparation of such novel devices comprising the following steps: i) obtaining the spermicidal and anti-infective extract from plant source(s), ii) formulating the said extract into a suitable composition along with one or more carrier(s) or excipient(s). iii) providing the said composition along with a contraceptive device either as a single pack or separately, wherein the composition is applied either inside or outside or on both sides of the contraceptive device.

It is a still further objective of the present invention to provide novel devices that can be used by males or females or both, wherein the devices are safe, easy to formulate, convenient to use and provides protection particularly against sexually transmitted diseases (STDs) and human immunodeficiency virus (HIV) and optionally against fungal infections.

It is a still further objective of the present invention to provide a method of using the novel contraceptive device for alleviating or reducing the risk of contracting HIV infection and/or any other sexually transmitted disease and/or fungal infection during sexual intercourse.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides novel spermicidal and anti-infective contraceptive devices comprising at least one plant derived substance which are effective as a contraceptive method for prevention of unwanted pregnancy besides providing effective protection against microbes and optionally against fungal infections. The device particularly provides effective protection against microbes particularly against sexually transmitted diseases (STDs) and human immunodeficiency virus (HIV), and/or against fungal infections.

In an embodiment, the contraceptive device of the present invention to which at least one spermicidal and anti-infective plant derived substance is applied either inside or outside or on both sides, is a condom. Such device is effective as a contraceptive method for prevention of unwanted pregnancy besides providing effective protection against microbes and optionally against fungal infections.

In an embodiment, the spermicidal and anti-infective plant derived substance or composition comprising such substance formulated optionally with one or more carrier(s) or excipient(s), applied to the condom is an extract obtained from the plant Azadirachta indica optionally comprising another spermicidal and/or anti-infective plant derived substance, which is effective as a contraceptive method for prevention of unwanted pregnancy besides providing effective protection against microbes and optionally against fungal infections. In an embodiment, another spermicidal plant derived substance is an extract obtained from the plant Carica papaya,

In an embodiment of the present invention is provided a composition comprising one or more spermicidal and anti-infective plant derived substance in the form of spray coat, gel, lubricant cream or the like intended for application on a contraceptive device such as a condom by at least one of the individuals involved in intercourse.

In an embodiment of the present invention is provided a novel spermicidal and anti- infective contraceptive devices comprising at least one plant derived substance, wherein the plant derived substance is applied either inside or outside or on both sides.

In an embodiment, the contraceptive device of the present invention comprises of at least one plant derived spermicidal and at least one anti-infective substance alongwith acceptable carriers or excipients which are useful in preventing bacterial, viral and fungal infections.

In an embodiment of the present invention, the anti-infective substance(s) is obtained from a plant selected from but not limited to a group comprising Azadirachta indica, reetha saponins, quinine hydrochloride (obtained from Cinchona), gossypol, coconut oil, and the like or mixtures thereof.

In an embodiment of the present invention, the plant derived spermicidal substance(s) is obtained from the plant selected from but not limited to a group comprising Aristolochia indica; Neem {Azadirachta indica); Balanites roxburghii; Calotropis procera; Papaya {Carica papaya); Catharanthus roseus; Dieffenbachia seguine; Ecballium elaterium; Gossypium species; Hibiscus rosa-sinensis; Hippophae salicifolia; Leucaena glauca; Lonicera ciliosa; Lupinus tennis; Malvaviscus conzattii; Momordica charantia; Ocimum sanctum; Prunus emarginata; Withania somnifera; Embelia ribes; Solanum xanthocarpum; Vinca rosea; Karanj {Pongamia pinnata), carrageenan, reetha saponins, quinine hydrochloride (obtained from Cinchona) or any other plant extract known to exhibit spermicidal activity, used either alone or in combination thereof. The plant derived spermicidal substance(s) incapacitate or kill the sperm on contact if used alongwith the male contraceptive device or applied topically in the vagina by the female.

In an embodiment, the spermicidal and anti-infective plant derived substance applied to the condom is an extract obtained from the plant Azadirachta indica. In a further embodiment, the device comprises another spermicidal and/or anti-infective plant derived substance which is preferably an extract obtained from the plant Carica papaya, optionally with one or more acceptable carriers.

The plant based spermicidal or anti-infective substance(s) of the present invention may be extracted by using any one or combination of the following techniques:

1. Solvent extraction, filtration and distillation,

2. Expression of fixed oil(s), 3. Extraction of Volatile oil(s) by steam distillation,

4. Purification by solvent partitioning,

5. Purification by pH regulated precipitation,

6. Purification by crystallization,

7. Purification by column chromatography (including preparative HPLC), 8. Purification by Planar chromatography (TLC), and

9. Purification by molecular distillation.

In an embodiment of the present invention, the process of extraction of the spermicidal agent generally comprises the following steps: i) Extraction of dried and powdered plant or part(s) of plant with either medium polar solvents selected from but not limited to dichloromethane, chloroform, ethyl acetate and like used either alone or in combination thereof, or, polar solvents selected from but not limited to isopropanol, ethanol, methanol and like used either alone or in combination thereof, ii) Filtration of extract optionally using a filter aid, iii) Distillation of the extract to remove the solvent, iv) Optionally, fractionation of the residue obtained, after extraction with medium polar solvent, with a polar solvent selected from but not limited to isopropanol, ethanol, methanol and like used either alone or in combination thereof, v) Optionally, fractionation of the residue obtained, after extraction with polar solvent, with a medium polar solvent selected from but not limited to dichloromethane, chloroform, ethyl acetate, acetone and like used either alone or in combination thereof.

In an embodiment of the present invention, the process of extraction of the spermicidal agent from Azadirachta indica comprises the following steps:

i) Extraction of oil with polar solvents selected from but not limited to a group comprising acetone, isopropanol, ethanol, methanol, water, and the like, used either alone or in combination thereof, ii) Distillation of the extract to remove the solvent partly or completely, iii) Optionally, washing the residue obtained with a non-polar solvent selected from but not limited to a group comprising heptane, hexane, petroleum ether, benzene, toluene, and like, used either alone or in combination thereof.

In an embodiment of the present invention, the process of extraction from Azadirachta indica can be carried out by any of the following methods:

1. Neem oil (5 kg) was extracted by stirring at room temperature four times with methanol (4 ^χ 20L) for 1 hour each time. The mixture was allowed to stand every time in a separating funnel for 1 hour so that the oil and methanol layers get separated. The methanol extracts obtained were pooled and dried under vacuum in a distillation assembly (10OL capacity). The waxy material (Yield - 1.5 kg) was obtained.

2. Neem oil (5 kg) was extracted by stirring at room temperature four times with 80% ethanol (4 ^χ 20L) for 1 hour each time. The mixture was allowed to stand every time in a separating funnel for 1 hour so that the oil and ethanol layers get separated. The aqueous ethanolic extracts obtained were pooled and dried under vacuum in a distillation assembly (10OL capacity). The waxy material (Yield - 1.1 kg) was obtained.

3. Neem oil (5 kg) was extracted by stirring at room temperature four times with 80% methanol (4*20L) for 1 hour each time. The mixture was allowed to stand every time in a separating funnel for 1 hour so that the oil and methanol layers get separated. Aqueous niethanolic extracts obtained were pooled and concentrated to half of its volume under vacuum in a distillation assembly (10OL capacity). This was washed by stirring twice with hexane (2><20L) for 15 minutes each time in extraction assembly (10OL capacity) attached with stirrer. Aqueous methanolic layer was collected and concentrated to semisolid under vacuum in a distillation assembly (10OL capacity). The residue was finally dried under vacuum on a rotavapour to get dried solid material (Yield - 500 g).

4. Dried powdered neem leaves (5 kg) were extracted by refluxing four times with methanol (4 ^χ 30L) for 1 hour each time. The methanolic extracts obtained were pooled and concentrated to semisolid mass under vacuum in a distillation assembly (10OL capacity). The residue obtained was suspended in 2L water and was washed by stirring four times with hexane (4x5L) at room temperature for 15 minutes each time in extraction assembly (2OL capacity) attached with stirrer. Aqueous layer was collected and dried under vacuum on a rotavapour to get dried solid material (Yield - 735 g).

5. Dried powdered neem barks (5 kg) were extracted by refluxing four times with methanol (4x3 OL) for 1 hour each time. The methanolic extracts obtained were pooled and concentrated to semisolid mass under vacuum in a distillation assembly (10OL capacity). The residue obtained was suspended in 2L water and was washed by stirring four times with hexane (4><5L) at room temperature for 15 minutes each time in extraction assembly (2OL capacity) attached with stirrer. Aqueous layer was collected and dried under vacuum on a rotavapour to get dried solid material (Yield - 395 g).

In an embodiment, 4 kg neem seeds were expressed in a roller mill and filtered to obtain about 850 g neem oil. The neem oil was optionally further extracted with a polar solvent selected from but not limited to 2-propanol, ethanol, methanol, water, and the like, used either alone or in combination thereof. The polar solvent extract was distilled to remove the solvent and to yield an oily extract (280 g). In another embodiment, 5 kg neem seeds were powdered and extracted with a medium polar to polar solvent selected from but not limited to chloroform, dichloromethane, ethyl acetate, acetone, methanol, ethanol, water and the like, used either alone or in combination thereof. The solvent extract was distilled to remove solvent yielding an oily extract (365 g). In another embodiment, 3 kg neem seeds were powdered and steam distilled along with 1OL of water. The volatile oil (3 ml) obtained was collected in a Clavenger Apparatus. In another embodiment, 4 kg neem seeds were expressed in a roller mill and filtered to obtain about 850 g neem oil. The neem oil was optionally steam distilled along with 5 L of water. The volatile oil (4 ml) obtained was collected in a Clavenger Apparatus.

In an embodiment of the present invention, the process of extraction from Carica papaya can be carried out by any of the following methods:

1. Powdered seeds of Carica papaya (5 kg) were extracted by refluxing four times with methanol (4 ^χ 30L) for 2 hours each time. Methanol extracts obtained were pooled and filtered through buchner's funnel using celite as filter aid. The methanol was removed under vacuum in a distillation assembly (10OL capacity). The oily material (Yield - 848 g) obtained was shaken with 2.5L chloroform in a

5 L separating funnel. The chloroform layer was collected and dried under vacuum on a rotavapour to get desired waxy substance (Yield - 378 g).

2. Powdered seeds of Carica papaya (5 kg) were extracted by refluxing four times with chloroform (4x30 L) for 2 hours each time. Chloroform extracts obtained were pooled and filtered through buchner's funnel using celite as filter aid. The chloroform was removed under vacuum in a distillation assembly (10OL capacity). The oily material (Yield - 1.3 kg) obtained was stirred four times with methanol (4 x 3 L) in a round bottom flask (1OL capacity). The methanol layers were separated in a 5L separating funnel, pooled and dried under vacuum on a rotavapour to get desired waxy substance (Yield - 260 g).

3. Powdered seeds of Carica papaya (5 kg) were extracted by refluxing four times with 95% ethanol (4><30L) for 2 hours each time. Ethanol extracts obtained were pooled and filtered through buchner's funnel using celite as filter aid. The ethanol was removed under vacuum in a distillation assembly (10OL capacity). The oily material (Yield - 410 g) obtained was shaken with 2.5L chloroform in a 5L separating funnel. The chloroform layer was collected and dried under vacuum on a rotavapour to get desired waxy substance (Yield - 165 g).

In another embodiment, 5 kg Papaya seeds were powdered and extracted with a medium polar to polar solvent selected from but not limited to chloroform, dichloromethane, ethyl acetate, acetone, methanol, ethanol, water and the like, used either alone or in combination thereof. The solvent extract was distilled to remove the solvent and to yield an oily extract (365 g). In a further optional embodiment, the papaya seed extract was loaded on a column packed with a polar stationary phase selected from but not limited to silica gel, kieselgurh, aluminium oxide, magnesium silicate and the like, used either alone or in combination thereof. The column was washed with a non-polar solvent selected from but not limited to petroleum ether, hexane, pentane, cyclohexane and the like, used either alone or in combination thereof.

Then the column was eluted with a medium polar solvent selected from but not limited to chloroform, dichloromethane, ethyl acetate, acetone, methanol, ethanol, and the like, used either alone or in combination thereof. The solvent elute was then dried to yield an oily substance (650 mg).

In an embodiment of the present invention, the plant derived spermicidal substance(s) are selected such that preferably a positive synergistic effect in the spermicidal activity is obtained which implies the use of reduced concentrations of each agent to bring about the desired action.

The spermicidal and anti-infective contraceptive device of the present invention may be in the form of a condom spray coated with an aqueous or oily extract of one or more plant derived spermicidal and anti-infective substance(s), or in the form of a cream, gel or a pessary intended to be applied to the contraceptive device such as condom prior to use. In an aspect of the present invention, the condom may be made synthetically from plastics, polymers, nitrile, latex or polyurethane or a natural membrane obtained from a natural source such as sheep skin or lamb cecum. In another embodiment, the condoms are either for male or female use.

In an embodiment of the present invention, the addition of one or more plant derived spermicidal and anti-infective substance(s) to condoms further reduces the risk of pregnancy and/or alleviates or reduces genital discomfort and/or prevents lesions and ulcerations to genital mucosa, thereby minimizing the probability of transmitting infectious agents. In a further embodiment, the contraceptive device is a male contraceptive that is safe, effective and reversible, and does not have an effect on the libido.

In an embodiment, the plant derived substance useful in the present invention obtained from Azadirachta indica may be the neem oil or fraction thereof that inhibits human spermatozoal motility in at minimum concentrations of about 25 mg/ml. The oil extract obtained from Azadirachta indica in the present invention inhibited growth of various pathogens including Escherichia coli and Klebsiella pneumoniae, and also exhibited antifungal activity against Candida albicans and Chlamydia, and antiviral activity

against Poliovirus. Also it reduces the risk of gonorrhoea and HIV transmission. Further the aqueous/alcoholic extract of neem leaves or seeds and pure neem compound (Azadirachtin) are highly effective in inhibiting viral infection. In another embodiment, plant derived substance useful in the present invention obtained from Carica papaya in the form of aqueous or alcoholic seed extract are effective is highly effective as spermicidal. Papaya seed extract showed a dose-dependent spermicidal effect showing an instant fall in the sperm motility to less than 20% at about 2% concentration when applied in-vitro on human sperms. In another embodiment, the plant derived substance may be combined with one or more other spermicidal or anti-infective agents known to the art such as hormones e.g. danazol, depot medroxy progesterone acetate (DMPA), cyproterone acetate, melatonin, levonorgestrel, Ru-486, testosterone buciclate and other androgen esters.

Plant derived substance such as an extract obtained from the plant Azadirachta indica although safe and effective had not been disclosed in the prior art for use as spermicidal and/or anti-infective along with a contraceptive device probably due to the unacceptable colour and/or odour of such product. However, the device of the present invention removes such limitations of the art by providing extracts/compositions which have an acceptable colour and/or odour.

The acceptable carriers or excipients useful in formulating the devices of the present invention are preferably lubricants such as KY jelly (a lubricant produced by Johnson & Johnson), carboxymethyl cellulose, sodium alginate, EDTA, natural vegetable oils, propylene glycol, glycerin, low melting temperature triglyceride, mineral oil, aqueous solutions of high molecular weight polyethylene oxides, and the like or mixtures thereof. Polymers such as water soluble cellulose derivative (e.g. methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose) or other water soluble polymers such as sodium alginate, polyvinyl pyrrolidone, polyvinyl alcohol or polymer of ethylene oxide, and the like can be used in the present invention. Other optional substances that can be used in the present invention include anti- infectives such as methylparaben, chlorhexidine and the like. The novel spermicidal and anti-infective contraceptive device of the present invention provide protection from transmission of STDs and HIV by virtue of the anti-infective substance(s), undesired

pregnancy by virtue of spermicidal substance(s) and adequate lubrication for enhanced pleasure and ease of use. The devices of the present invention optionally comprise natural sensation enhancers.

In a preferred embodiment of the present invention, the contraceptive device is a condom and the effective preparation to be coated inside and/or outside the condom comprises a spermicidal and anti-infective substance(s) along with a carrier such as vegetable oil. In an embodiment, the vegetable oil useful in the present invention is selected from but not limited to a group comprising sunflower oil, soyabean oil, linseed oil, cottonseed oil, olive oil, palm oil, coconut oil and the like or mixtures thereof. In another embodiment, the hydrocarbon base comprises paraffins, waxes, petroleum jelly, lanolin, and the like or mixtures thereof. Although vegetable oils are compatible with latex condoms, polyurethane condoms are the preferred. Additional substances such as yohimbine (selective competitive alpha2-adrenergic receptor antagonist for penile vasodilation), clove oil (mild stimulant and local anaesthetic), arginine (capillary blood circulation enhancer), and the like, or mixtures thereof can be added to the preparation.

In an embodiment, the Azadirachta indica extract is present in the range of about 20 to 60% w/v and the Carica papaya extract is present in the range of about 1 to 5% w/v in the novel device of the present invention. A volume of about 0.25 to 0.50 ml of the preparation is preferably used to make the coating inside and/or outside the condom.

In another embodiment of the present invention is provided a process for preparation of such novel devices comprising the following steps: i) obtaining the spermicidal and anti-infective extract from plant source(s), ii) applying the extract either inside or outside or on both sides of the contraceptive device.

In another embodiment of the present invention is provided a process for preparation of such novel devices comprising the following steps: i) obtaining the spermicidal and anti-infective extract from plant source(s),

ii) formulating the said extract into a suitable composition along with one or more carrier(s) or excipient(s). iii) providing the said composition along with a contraceptive device either as a single pack or separately, wherein the composition is applied either inside or outside or on 5 both sides of the contraceptive device. i)

The novel devices of the present invention preferably do not use lubricants such as nonoxynol-9 that is commonly used in most of the marketed condoms. Nonoxynol-9 has been shown in several recent studies to actually increase the risk of HIV

10 transmission rather than preventing such infection. Instead safer and non-toxic lubricants such as silicone and/or vegetable oils are used in the present invention. In an embodiment, the extract or composition of the plant derived substance used along with the contraceptive device, besides acting as spermicidal and anti-infective, also functions as a lubricant. The spermicidal and anti-infective contraceptive device is easy to

15 manufacture; effective against multiple STDs including HIV, gonorrhea, syphilis, and chlamydia and fungal infections; safe to use several times daily; fast acting; acceptable to users; affordable; cosmetically acceptable and easy to store and to use.

In an embodiment of the present invention is provided a method of using the novel

20 contraceptive device for alleviating or reducing the risk of contracting HIV infection and/or any other sexually transmitted disease and/or fungal infection during sexual intercourse. In an embodiment, the plant derived extract or composition as active agent according to the present invention is useful for the prevention of STDs wherein said

STD virus is selected from the group consisting of HIV viruses, herpesviruses, hepatitis

25 viruses, influenza A viruses, parainfluenza viruses, and human papilloma viruses.

Pharmacological study was carried out to evaluate the in-vitro spermicidal activity of water miscible Neem-Papaya Extract gels in healthy human semen samples. The gel composition was prepared as described hereinafter in Example-3. Good quality human 30 semen samples were used for the study. Semen samples with sperm count 30-50 million/ml semen, rapid, linear and progressive motility, and sperm viability 45-50%, was considered for the in vitro testing. Following in-house preparations were tested: B.No. 0580/090C (Placebo); B.No. 0580/086C (0.2% Papaya extract); B.No.

0580/090B (Placebo); B.No. 0580/086B (0.5% Papaya extract); B.No. 0580/090A (Placebo) and B.No. 0580/086A (2% Papaya extract). The apparatus used for testing was Sperm Quality analyzer (SQA II C-P). The parameters studied included the Concentration (number of spermatozoa/mL); Progressive motility (percent of spermatozoa with progressive motility); Motile Sperm Concentration [MSC] (number of spermatozoa that are progressively motile/mL); Morphology (Percentage spermatozoa with normal morphology); Functional Sperm Concentration[FSC] (Number of spermatozoa that are both progressive motile and morphologically normal per mL) and Sperm Motility Index [SMI] ('sperm concentration' multiplied by 'average progressive velocity'). Prior to testing, the actual quality of semen was determined using SQA. Thereafter, 250μL of liquefied semen was mixed with 500μL of gel sample at room temperature and the above mentioned parameters were determined at time intervals of 0.25, 1, 2, 4, 6, and 10 minutes of incubation. The result is presented in table- 1.

Table 1: Average values over a period of 10 minutes after treatment of 50 ml of semen with 100 ml of spermicidal agent

The results of the study indicated that the plant derived extract composition of the present invention is effective as spermicidal agent. The safe gel comprising 2% papaya extract (B.No. 0580/086 A) exhibited highly significant spermicidal activity comparable to Saline (control) as well as placebo.

In an embodiment of the present invention where certain spermicidal, antimicrobial, cytocidal, or antibacterial usage is intended, a spermicidal, antimicrobial, cytocidal, or antibacterial effective amount of a natural or plant derived substance is applied with or

without a carrier to the inner, outer or both surfaces of an appropriate contraceptive device such as a condom. For example, a condom or diaphram could be coated wholly or partially with dry or semisolid or liquid coating material containing an effective amount of the plant derived substance for spermicidal and anti-infective use according to the invention. In addition, an effective amount of the natural substance of the invention can be applied in admixture with other antimicrobially, cytocidally, antibacterially, and/or spermicidally active ingredients prior to or during application to a condom or diaphram. Further, in some instances the natural substances of the invention could be applied, alone or in admixture with another spermicide, topically or vaginally.

In an embodiment of the present invention, while reference is made to the anti-infective use of the contraceptive device, such use is intended as antimicrobial, cytocidal, antifungal, antiviral or antibacterial activity, particularly activity against sexually transmitted diseases and HIV. Such sexually transmitted diseases include, but are not limited to, herpes, chlamydia, syphilis, gonorrhea, HIV, and other retroviruses, such as HTLV-I and HTLV-II. Treatment or prevention could consist of topical or vaginal application of an effective amount of plant derived substance according to the invention, in or on a suitable carrier, for example, a condom, a diaphram, sponge, IUD, or other suitable device or substrate containing or having thereon an effective amount of the active ingredient, may be positioned intravaginally.

In an embodiment, the spermicidal and anti-infective gel composition of the present invention may further contain a preservative, such as one or more members of parabens. The gel can maintain its antiviral activity in dilutions of not less than 100 times. The methods for preventing the transmission of HIV and other sexually transmitted viruses comprise applying the gel composition onto the contraceptive device such as a condom or a diaphragm before sexual intercourse. In a preferred embodiment, when a condom is used in conjunction with the gel, the gel is capable of enhancing the risk-reducing effectiveness of condom and providing maximum protection for users. Such an increase in the anti-viral protection offered by a condom assumes significance in several situations, such as when a condom breaks or if the male loses his erection prior to withdrawal and spillage or leakage of fluid occurs from the

inside of the condom into the vagina. The gel composition comprising the plant derived active substance(s) can be coated onto condoms during manufacture, and enclosed within conventional watertight plastic or foil packages that contain one condom per package, or it can be manually applied by a user to the inside and/or the outside of a condom, immediately before use.

In an embodiment of the present invention, during sexual intercourse, the plant derived substance as active agent in the gel deactivates the viruses and prevents the infected person from transmitting the STD viruses to the non-infected person. The coated extract or composition on the contraceptive device maintains its efficacy against secretion of bodily fluids thus providing the intended protection during sexual intercourse. The coated extract or composition provides lubricity which further helps reduce the likelihood of transmitting the diseases by reducing the rupture of skins and/or blood vessels during sexual relationships. When the plant derived extract is formulated as a composition such as a gel or cream, the same may be packaged in any of the known forms, such in tubes, in bottles, in sachets or in capsules. To the composition, a preservative such as paraben(s) may be added. Further, in accordance with the invention, the device coated with a plant derived extract per se or formulated into a composition is provided that can be used in acidic conditions that exist in the vagina and surrounding area without destabilization.

In an embodiment, the present invention provides a kit for preventing sexually transmitted disease and infection and killing male sperm essentially comprising at least one preferably two plant derived active components, that can individually or collectively be loaded and/or preloaded into the contraceptive device such as condom. One of the major advantages of the spermicidal and anti-infective contraceptive device of the present invention is that it offers a unique method of protection against HIV, STDs and other microbial or fungal infection by using plant derived substance(s) as active agents which are highly effective, coupled with enhanced safety.

The examples given below serve to illustrate embodiments of the present invention. However they do not intend to limit the scope of present invention.

EXAMPLES

Example 1: Latex Condom

S. No. Ingredient Quantity (%w/v)

1. Azadirachta indica extract 30 2. Carica papaya extract 3

3. Vegetable oil base q.s.

Procedure: i) Azadirachta indica extract, Carica papaya extract were prepared and mixed with the vegetable oil base. ii) A volume of 0.25 ml of the preparation was used to make the coating inside and/or outside the latex condom.

Example 2: Polyurethane Condom

S. No. Ingredient Quantity (%w/v) 1. Azadirachta indica extract 20

2. Carica papaya extract 5

3. Hydrocarbon base q.s. Procedure: i) Azadirachta indica extract, Carica papaya extract were prepared and mixed with the vegetable oil base. ii) A volume of 0.25 ml of the preparation was used to make the coating inside and/or outside the polyurethane condom.

Example-3: Emulgel S. No. Ingredients Qry./100 gms

1. Neem Extract 10.000

2. Glyceryl Monostearate 4.000

3. PEG 100 stearate 6.000

4. Methyl Paraben 0.200 5 5.. P Prrooppyyll pPaarraabbeenn 0.100

6. Carbomer 940 0.100

7. Polyethylene oxide (301) 0.125

8. Propylene glycol 10.00

9. Glycerine 10.00

10. Water q.s. to 100 ml Procedure: i) Carbomer 940 and Polyethylene oxide were added to sufficient quantity of water under stirring. ii) Propylene glycol was heated to 75 °C. iii) The Methyl paraben and Propyl paraben were added to propylene glycol of step

(ii) and cooled it to 25° C. iv) Glycerine was added to the mixture of step (iii) and stirred to dissolve. v) Glyceryl Monostearate and PEG 100 stearate were heated on heating mantle, vi) Neem Extract was added to the mixture of step (v) and heated to 75°C. vii) The mixture of step (i) was heated to 75 ⁰ C and the mixture of step (vi) was added to it under high stirring to form emulsion. viii) Mixture of step (iv) was added to the emulsion of step (vii) and pH was adjusted between 4.5-5.0 with triethanolamine.

The gel is applied on the outer side or inner side or on both sides of condom.

Example-4: Emulgel

S. No. Ingredients Qty./lOO gms 1. Neem Extract 10.000

2. Tween® 80 5.000

3. Span® 80 5.000

4. Methyl Paraben 0.200

5. Propyl paraben 0.100 6. Carbomer 940 0.275

7. Polyethylene oxide 0.125

8. Propylene glycol 10.00

9. Glycerine 10.00

10. Water q.s. to 100 ml Procedure: i) Carbomer 940 and Polyethylene oxide were added to sufficient quantity of water under stirring, ii) Propylene glycol was heated to 75°C.

iii) The Methyl paraben and Propyl paraben were added to propylene glycol of step

(ii) and cooled it to 25° C. iv) Glycerine and Tween® 80 were added to the mixture of step (iii) and stirred to dissolve. v) Neem Extract and Span® 80 were mixed together. vi) The mixture of step (i) was heated to 75 ⁰ C and the mixture of step (v) was added to it under high stirring to form emulsion, vii) Mixture of step (iv) was added to the emulsion of step (vi) and pH was adjusted between 4.5-5.0 with triethanolamine. The gel is applied on the outer side or inner side or on both sides of condom.

Example 5: Cream

S. No. Ingredient mg/gm

1. Azadirachta indica extract 5.0 2 2.. C Caarr iiccaa p paappaayyaa eexxttrraacctt 5.0

3. Propylene glycol 50.0

4. Titanium dioxide 10.0

5. Stearic acid 130.0

6. Cetyl alcohol 10.0 7 7.. I Issoopprrooppyyll mmyyrriissttaattee 60.0

8. Sorbitan stearate 20.0

9. Methyl paraben 1.5

10. Propyl paraben 0.3

11. Corn oil 50.0 1 122.. G Gllyycceerriinn 50.0

13. Sorbitol solution 30.0

14. Veegum HV 10.0

15. Sodium CMC 3.0

16. Tween® 80 15.0 1 177.. P Puurriiffiieedd wwaatteerr q.s.

Procedure:

i) Azadirachta indica extract, Carica papaya extract, Methyl paraben and Propyl paraben were dissolved in propylene glycol; the mixture was heated to 55-60°C; titanium dioxide was added to it and stirred well. ii) Stearic acid, Cetyl alcohol, Isopropyl myristate, Sorbitan stearate and Corn oil were heated to 70°-75°C. iii) In another vessel, Sorbitol solution and Tween® 80 were taken. iv) Veegum HV was separately hydrated in the Purified water. v) Sodium carboxymethyl cellulose (sodium CMC) was separately hydrated in

Glycerin. vi) The materials of step (iv) and step (v) were added to the material of step (iii) and heated to 70°-75°C. vii) The materials of step (ii) and step 6 were mixed and cooled. viiϊ) When the material of step (vii) attains a temperature of 50°-55°C, the material of step (i) was added to it. ix) The mixture was allowed to cool to room temperature to obtain the cream.

The mixture is applied on the cervix by inserting a film/sponge containing said mixture.

Example 6: Vaginal cream

S. No. Ingredient mg/gm 1 1.. A Azzaaddiirraacchhttaa iinnddiiccaa eexxttrraacctt 7.0

2. Carica papaya extract 5.0

3. Pongamia pinnata 6.0

4. Propylene glycol 50.0

5. Titanium dioxide 10.0 6 6.. H Haarrdd p paarraaffffiinn 60.0

7. Liquid paraffin 10.0

8. Isopropyl myristate 30.0

9. Span® 60 20.0

10. Methyl paraben 1.5 1 111.. P Prrooppvyll υ paarraabbeenn 0.3

12. Corn Oil 20.0

13. Glycerin 80.0

14. Sorbitol solution 50.0

15. Veegum HV 20.0

16. Tween® 80 15.0

17. Purified water . q.s. Procedure: i) Azadirachta indica extract, Carica papaya extract, Pongamia pinnata, methyl paraben and propyl paraben were dissolved in propylene glycol; the mixture heated to 55-60 ⁰ C; titanium dioxide was added to it and stirred well, ii) Hard paraffin, liquid paraffin, isopropyl myristate, Span® 60, and Corn Oil were heated to 70°-75°C. iii) Veegum HV was hydrated in purified water; Glycerin, Tween® 80 and sorbitol were added to it; and the mixture was heated to 70°-75°C. iv) The material of step (ii) was added to the material of step (iii) with stirring and the mixture was allowed to cool to 55°-60°C. v) The material of step (i) was added to the material of step (iv), stirred, and allowed to cool to room temperature to obtain the cream.

The cream is applied on to the vagina preferably by using a sponge.

Example 7: Vaginal pessary

S. No. Ingredient gm/10 units 1. Azadirachta indica extract 0.7

2. Carica papaya extract 0.5

3. Polyethylene glycol 4000 (PEG 4000) 3.56

4. Polyethylene glycol 1000 (PEG 1000) 12.46

5. Polyethylene glycol 400 (PEG 400) 1.78 6. Propylene glycol 1.50

7. . Glycerin 0.20

Procedure: i) PEG 4000, PEG 1000 and PEG 400 were melted together and mixed well, ii) Azadirachta indica extract and Carica papaya extract were dissolved in propylene glycol at 40-45 °C with stirring and Glycerin was added. iii) The material of step (ii) was added to the material of step (i) and mixed well, iv) The material of step (iii) was poured into suppository moulds and cooled, v) Pessaries thus formed were removed from moulds and packed suitably.