Halogenated Fullerene Functionalized as a Biocidal and Chemotactic Spermicide to Vaginally Harbor and Neutralize Spermatozoa for Use as a Safe and Effective Contraceptive

Abstract

The present invention provides the methods and composition useful as a contraceptive by preventing motile sperm from reaching a mature ovum, thereby blocking fertilization and preventing pregnancy. The contraceptive is comprised of halogen functionalized fullerene nanoparticles (halo fullerenes) and chemotactic stimulants that act synergistically to divert, incapacitate and ultimately rupture spermatozoa to avert fertilization. When applied vaginally prior to coitus, the suspension is activated by exposure to spermatozoa upon insemination. Notably, non-spermatozoa cells are unaffected by the pH-neutral suspension; however, closer to the same scale, microbes are susceptible to its inherent biocidal properties. Following application and coitus, the contraceptive evacuates naturally, along with seminal and vaginal fluids thereafter.

Claims

1. Composition and use of contraceptive suspension that chemically stimulates, diverts targeting, impedes mobility, ruptures and incapacitates spermatozoa in a neutral pH vehicle and comprising: a. halo fullerenes; b. aromatic aldehyde, bourgeonal; c. cationic peptide, protamine; d. optionally one or more pharmaceutical-grade additives.

2. The composition of claim 1, wherein the concentration of halo fullerenes is between 0.01% and 5.0%, preferably 0.1% and 1.5%, and in particular between 0.5% and 1.0% based on the total weight of the composition.

3. The composition of claim 1, wherein the concentration of bourgeonal is between 0.0001% and 2.0%, preferably 0.001% and 1.0%, and in particular 0.01% and 0.1% based on the total weight of the composition.

4. The composition of claim 1, wherein the concentration of protamine is between 0.0001% and 1.0%, preferably 0.001% and 0.1%, and in particular 0.01% and 0.05% based on the total weight of the composition.

5. The composition of claim 1, wherein the distal flagellum of spermatozoa is structurally damaged and ruptured by halo fullerenes.

6. The composition of claim 1, wherein the composition stimulates hyperactivation of spermatozoa.

7. The composition of claim 1, wherein the composition stimulates competitive behavior between spermatozoa from the same or multiple sources.

8. The composition of claim 1, wherein the composition induces motility impediments, chemotactic stimulation, cellular membrane rupture, and subsequent neutralization of spermatozoa.

9. The composition of claim 1, wherein the composition provides incapacitation of spermatozoa.

10. The composition of claim 1, wherein the composition provides for topical (intravaginal) contraception that is sperm stimulating, attracting, and spermicidal.

11. The composition of claim 1, wherein the composition caustically and physically ruptures the cellular membrane of spermatozoa and irreversibly incapacitates the sperm.

12. The composition of claim 1, wherein the composition causes irreversible damage for incapacitation and immobility of the spermatozoa in the presence of seminal and/or vaginal fluids.

13. A composition of claim 1, wherein the aromatic aldehyde may include an analogue of bourgeonal, such as Helional, or other aliphatic esters, such as n-pentyl acetate.

14. A composition of claim 1, wherein the composition includes a pharmaceutical grade, steroidal hormone, such as progesterone, or other forms and analogues of progesterone, such as dydrogesterone, medroxyprogesterone acetate, cyproterone acetate, nomegestrol acetate, trimegestone, or promegestone at a concentration consistent with spermatozoa stimulation.

15. A composition of claim 1, wherein the composition includes a natural homopolymer, such as poly-1-lysine, between 0.0001% and 1.0%, preferably 0.001% and 0.1%, and in particular 0.01% and 0.05% based on the total weight of the composition.

16. A composition of claim 1, wherein the composition includes biocidal halo fullerenes that neutralize bacterial, fungal and viral pathogens if present in the vaginal or seminal fluids.

17. The composition of claim 1, wherein the composition may be administered as a liquid suspension or in a soluble capsule.

18. The composition of claim 1, wherein the composition and post-coital exudates of incapacitated spermatozoa, cellular and molecular particulates, halo fullerene aggregates, and stimulant analytes remain neutral with respect to vaginal tissues to allow gravitational evacuation and normal vaginal secretions clearance.

19. The composition of claim 1, wherein the composition may be buffered in a suspension that prolongs retention of the contraceptive for continuous efficacy in routine use and administered as a liquid suspension or in a soluble capsule.

Description

BRIEF DESCRIPTION OF THE DRAWING

[0023] FIGS. 1A, 1B, and 1C are molecular representations of prototypical halo fullerenes of 60 carbon atoms functionalized with 4, 8, or 24 halogens (X).

[0024] FIG. 2A is an illustration of a human spermatozoa and major sections of the cell; the distal or end piece 1, the principal piece 2, the mid-piece 3, and the head 4, and FIG. 2B is a representation of the arrangement of halogenated fullerene particles 5 alongside an exploded view of the distal or end tail portion 1 of a spermatozoa cell.

DETAILED DESCRIPTION OF THE INVENTION

[0025] Spermatozoa represent the tiniest cell type in mammalian biology, and proportionately, fullerenes have mass comparable to the smallest aspect of spermatozoa, the distal tail segment 1 that propels them. The primary component of the proposed invention is a halogen modified fullerene 5, as described in parent application U.S. Ser. No. 16/946,892.

[0026] The proposed invention would prevent fertilization following introduction of viable sperm into the vaginal tract and divert its otherwise normal progress through the cervix; whereby, it would have been propelled by chemotactic stimuli and attraction, through the uterine cavity and into a fallopian tube for sperm contact and penetration of a mature ovum, if present. Although the halo fullerenes remain neutral in the absence of spermatozoa introduction, in use, immediate halo fullerene and sperm interactions would occur as a result of unimpeded movement of both masses through the viscous, mucous phase of seminal fluid due to the large space between water molecules (vibrational excitation). The invention formulation would thus prevent fertilization; in the first instance, with substances that stimulate sperm receptors by mimicking the attractant of the mature ovum to divert them from cervical passage, essentially pooling them in the vaginal cul-de-sac. This diversion would then afford yet more agitation from a second mechanism mimicking competitive ejaculate. In turn, the third, yet most lethal, mechanism would result from the magnetic field generated by the spermatozoa flagella excitation that would further intensify velocity and rotation of the halo fullerenes at the atomic scale. This combined, hyperactivation of the sperm would thus propel an overwhelming barrage of halo fullerenes 5 traveling at maximum velocities into the distal flagella 1, thereby rupturing and causing mitochondrial leakage throughout the ejaculate.

[0027] A broad range of carbon shell fullerene modifications have been demonstrated via numerous, well-described chemical reactions [Yan, et al., 2015]. In the parent invention, a halogenated fullerene was comprised of a fullerene shell of C.sub.2n; whereby, n=10, 12, 13, 14, 15, . . . 360, such that multiple side-chain halogens attached to the core carbon cage. The parent invention described three carbon-60 halo fullerenes of C.sub.60X.sub.6; C.sub.60X.sub.8, and C.sub.60X.sub.24; whereby, X=a halogen molecule (e.g. bromine, chlorine, iodine, and fluorine).

[0028] Halogen atoms are hydrophobic and lipophilic, which may be exploited for countless useful applications. Lipophilicity enables halogens to cross and pass through cell membranes. In the parent patent, the halogen functional group applies these highly caustic atomic properties that induce cell rupture and destruction of vulnerable microbes, without a net loss of energy or efficacy, sustaining caustic capabilities at the application or exposure site. Hence, the contraceptive formulation could also prove effective against pathogen transmission.

[0029] The heads 4 of spermatozoa are highly variable (width and length), and the flagella can be divided into four segments: the connecting piece or neck; the mid-piece 3, the principal piece 2 and the distal or end piece 1. The connecting piece is adjacent to the head 4 and contains degenerated centrioles and transitional structures linked with the mid-piece, which is differentiated from the other segments by a cytoskeletal structure surrounded by mitochondria. The mitochondria produce adenosine triphosphate (ATP), which is transported from the mid-piece to the axonemal section, creating the energy required for motility of the sperm. The principal piece has a distinct fibrous sheath that surrounds the cytoskeletal structure. However, unlike the other segments, the end piece 1 is the most exposed region, lacking ancillary structures.

[0030] In this continuation, protruding halogen sidechain(s) of the fullerenes are thus applied so as to compromise spermatozoa cell membrane integrity, which is directly related to motility, viability of attractant receptors, ovum penetration capability (capacitation) and overall osmotic equilibrium. The atomic size of halo fullerenes 5 makes these molecules particularly destructive to flagella end-piece segments 1. Similarly, specific regions of the sperm remain unaffected by the fullerene 5, including the larger head 4 section and the more structurally robust connecting, principal 2, and mid-piece 3 regions of the flagellum. Such scale disparities also prevent fullerene-induced damage to other larger cells. Yet, as noted, membrane damage to the distal flagellum 1 disables spermatozoa by rupture and intracellular fluid loss. Ideal formulation ratios of halo fullerenes in the suspension would thus significantly outnumber total spermatozoa counts, with multiple halogens around each fullerene for numerous contact points. Thus, spermatozoa rupture, structural damage, and immobilization would prevent fertilization before the seminal fluid liquidation phase.

[0031] Notably, spermatozoa cellular membranes are comprised primarily of poly-unsaturated fatty acids (PUFAs); these provide the fluidity and flexibility required for fertilization; but they also make spermatozoa vulnerable to free radical damage and initiation of the lipid peroxidation (LPO) cascade. The LPO cascade is an autocatalytic and self-propagating chain reaction directly associated with degradation. For instance, LPO results in a rapid loss of intracellular ATP, which weakens the axial filament of spermatozoa and diminishes motility. Excessive LPO-based membrane impact can also lead to diminished morphological integrity and apoptosis. These consequences are exacerbated by halo fullerenes.

[0032] As such, spermatozoa cellular membranes are highly susceptible to peroxidation changes, which can directly impair motility and zona pellucida binding, or capacitation. Thus, an abundance of free radicals can cause deleterious cellular oxidation that induces structural and functional changes. Peroxidation-mediated damage to spermatozoa represents a key contributing factor in 30-80% of male infertility [O'Flaherty, 2020]. In particular, halo fullerene induced lipid peroxidation results in a chain reaction that produces reactive oxygen species (ROS).

[0033] The effect on fertility by ROS, as cellular by-products of reactions, is well documented [O'Flaherty, 2020]; whereby, all cellular components are targets for ROS-induced oxidative stress. In spermatozoa, ROS has been shown to trigger hyperactivation, capacitation, and initiation of the acrosome response, which are critical physiological processes necessary for fertilization. Thus, maintaining appropriate ROS equilibrium is essential for adequate spermatozoa functionality. Conversely, ROS excess adversely effects the cell membrane, DNA, and physiological processes of sperm.

[0034] In addition to the caustic properties of the halo fullerenes in the proposed invention, two spermatozoa-specific chemosensory mechanisms are applied. The chemotactic chemistry of the preferred embodiment includes 3-(4-tert-Butylphenyl) propanol (bourgeonal) and protamine. Notably, protamine has been used medically for decades as a heparin antagonist in the blood and is considered as a safe biological substance [Gurses, et al., 2015].

[0035] In the proposed invention, bourgeonal (C.sub.13H.sub.18O), an aromatic aldehyde odorant, is added to the contraceptive suspension to act as a powerful chemo-attractant and stimulant for spermatozoa [Olsson and Laska, 2010]. Bourgeonal is a potent agonist of the human sperm olfactory receptor OR1D2, which governs chemical communication between the sperm and ovum [Olsson and Laska, 2010]. Bourgeonal activation of OR1D2 results in the opening of calcium ion channels in the sperm that both enhance the speed and targeting of sperm motility [Veitinger et al., 2011]. The affinity and activation of bourgeonal and OR1D2 have been associated with species-specific fertilization [Spehr et al., 2006]. Bourgeonal is also linked to calcium-dependent signaling pathways controlled by the plasma membrane Ca.sup.2+-ATPase (PMCA) transport system on the cell membrane [Yoshida et al., 2013]. PMCA is known to regulate calcium concentrations and homeostasis, which are essential for controlling the flagellar whipping, motility regulation, targeting, hyperactivation, zona pellucida binding, and the acrosome reaction. [Yoshida et al., 2013]. In the proposed invention, alternative sperm activating and attracting factors include analogues of bourgeonal, such as Helional, or other aromatic aldehydes, and aliphatic esters, such as n-pentyl acetate.

[0036] The third active component of the proposed invention is protamine. Whereby, human protamine is contained in the sperm head with its structure and size directly related to protamine levels and ratios. Human spermatozoa also have substantial OR1D2 receptors that have appeared to play an evolutionary role associated with exposure to competitive sperm from multiple partners [Eisenbach and Giojalas, 2006]. As such, a uniquely aggressive response has been observed between spermatozoa of two or more different males, reflecting a capacity to recognize self and non-self, which has been characterized in numerous species, including mammals [Andersson and Simmons, 2006]. Thus, the addition of protamine from any other source provides a tertiary contraceptive mechanism as a membrane binding and disruptive agent—and as an antagonist to stimulate the spermatozoa.

[0037] Already primed by the addition of bourgeonal to effect a synthetic chemosensory gradient resembling a proximal mature ovum, this competitive stimulant induces hyperactivation that appears to exhaust sperm motility. These behaviors produce greater ATP levels, which enables further acceleration of the flagella and thereby, increased motility and velocity. Spermatozoa and protamine interactions result in electrostatic membrane binding that coats the sperm and drives an aggressive and confrontational response, including between cells originating from a single source.

[0038] Given the application of the proposed invention suspension at an optimized ratio of halo fullerenes to the upper range of average sperm count levels, the ATP-induced increases in flagella velocity would likewise increase the speed and rotation of the halo fullerenes, exponentially increasing the incidence of halogen collisions and ruptures of the spermatozoa cellular membranes. This mechanism thus enhances the invention contraceptive efficacy by ATP depletion, structural damage, mitochondrial leakage, and lost motility prior to entering the cervix or uterus.

[0039] As spermatozoa mature, their membrane also undergoes surface remodeling that encapsulates the sperm in a glycocalyx layer, which carries a net negative charge [Simon et al., 2016]. About 94% of ejaculated sperm is negatively charged [Simon et al., 2016]. Cationic protamine and anionic sperm contact are governed by electrostatic interactions and upon binding, disrupts the sperm membrane (pore formation that disintegrates the membrane) resulting in mitochondrial and ATP leakage. This electrostatic binding also causes cellular aggregation and creates gloms of multiple-sperm protamine complexes that disrupt targeting and speed.

[0040] Protamine is an arginine-rich, highly cationic peptide with a substantial positive charge throughout the molecule. As such, protamine has also been characterized as a broad-spectrum antimicrobial agent associated with membrane depolarization. Membrane depolarization is characterized by a rapid rise in the membrane potential that results in sodium channels opening on the cellular membrane, causing an influx of sodium ions [Catterall, 1986]. Alterations in the membrane potential affects cellular viability [Aspedon and Groisman, 1996]. As with spermatozoa, bacterial cells also carry a net negative charge, which is highly attractive to cationic peptides.

[0041] All constituents of the preferred embodiment are biocompatible: The atomic size of the halo fullerene derivatives would impart no effect on non-spermatozoa cells; olfactory aldehydes (bourgeonal) are naturally occurring in the female reproductive system; and the cationic peptide (protamine) selectively binds to negatively charged molecules or surfaces (spermatozoa), while not interacting with other neutral eukaryotic cell membranes.

[0042] Alternative embodiments may include the addition of poly-1-lysine (PLL), an FDA approved natural homopolymer, which has been shown to possess antimicrobial activity with low toxicity [Chenicheri et al., 2018]. Like protamine, PLL induces physiological damage to the negatively charged outer membrane of bacteria through potent electrostatic attraction [Chenicheri et al., 2018]. PLL also inhibits specific components of the electron transport system of mitochondria, which compromises cellular integrity through the generation of ROS [Symonds et al., 2005]. PLL is used routinely in sperm microscopy to inhibit motility during imaging; however, its presence is known to induce calcium fluxes in sperm [Wennemuth et al., 1998].

[0043] If included in the present invention, PLL may enhance binding; whereby, the PLL polymer and sperm membrane would impede movement, cause aggregation, disrupt membrane integrity and induce calcium fluxes in the sperm. Calcium fluxes across the membrane of spermatozoa play a critical role in various signal transduction pathways. As such, calcium is a well-known messenger that mediates the fertilization process, including activation of sperm motility, chemotaxis, hyperactivation, capacitation, and the acrosome reaction. Calcium regulates asymmetric movement of flagella, and the concentration of intracellular calcium must be precisely regulated to control targeting. PLL also inhibits electron transport systems that cause ROS production linked to capacitation initiation triggers. In the proposed invention, PLL would thus impede motility, damage structural components, and mimic fertilization cues typically produced when spermatozoa are in the accumulation zone (ovum proximity).

[0044] In another embodiment, hormones may also be added to enhance the contraceptive effect. For example, progesterone or analogues thereof, are well known to stimulate sperm hyperactivation—with a paradoxical reduction in progressive motility (reduced linearity) despite vigorous sperm movement. During fertilization, progesterone stimulates hyperactivation-like motility in the accumulation zone proximal to the ovum, enabling the sperm to dwell in this region.

[0045] The delivery methods for the contraceptive include a simple syringe and plunger or a rapidly dissolving suppository optimized for solubility at a neutral pH of 7, consistent with vaginal homeostasis. Post-coital exudates containing incapacitated spermatozoa, cellular and molecular particulates, halo fullerene aggregates, and stimulant analytes would remain neutral with respect to vaginal tissues to allow gravitational and normal vaginal secretions clearance. The exudate may also remove bacterial, fungal or viral debris, if present in the vagina and/or introduced during coitus and following biocidal rupture by the halo fullerenes.

Preferred Embodiment 1

[0046] a. A caustic halo fullerene (halogenated functionalized fullerenes) between 0.01% and 5.0%, preferably 0.1% and 1.5%, and in particular between 0.5% and 1.0% based on the total weight of the composition; [0047] b. A highly cationic peptide (protamine) between 0.0001% and 1.0%, preferably 0.001% and 0.1%, and in particular 0.01% and 0.05% based on the total weight of the composition; [0048] c. An aromatic aldehyde (bourgeonal) between 0.0001% and 2.0%, preferably 0.001% and 1.0%, and in particular 0.01% and 0.1% based on the total weight of the composition;
in a pH-neutral, buffered suspension that is inserted into the vagina prior to coitus.

Embodiment 2

[0049] a. A caustic halo fullerene (halogenated functionalized fullerenes) between 0.01% and 5.0%, preferably 0.1% and 1.5%, and in particular between 0.5% and 1.0% based on the total weight of the composition; [0050] b. A highly cationic peptide (protamine) between 0.0001% and 1.0%, preferably 0.001% and 0.1%, and in particular 0.01% and 0.05% based on the total weight of the composition; [0051] c. An aromatic aldehyde (bourgeonal) between 0.0001% and 2.0%, preferably 0.001% and 1.0%, and in particular 0.01% and 0.1% based on the total weight of the composition;
in a pH-neutral buffered suspension contained within a dissolvable suppository that is inserted into the vagina prior to coitus.

Embodiment 3

[0052] a. A caustic halo fullerene (halogenated functionalized fullerenes) between 0.01% and 5.0%, preferably 0.1% and 1.5%, and in particular between 0.5% and 1.0% based on the total weight of the composition; [0053] b. A highly cationic peptide (protamine) between 0.0001% and 1.0%, preferably 0.001% and 0.1%, and in particular 0.01% and 0.05% based on the total weight of the composition; [0054] c. An aromatic aldehyde (bourgeonal) between 0.0001% and 2.0%, preferably 0.001% and 1.0%, and in particular 0.01% and 0.1% based on the total weight of the composition; [0055] d. A highly cationic polymer (poly-L-lysine) between 0.0001% and 1.0%, preferably 0.001% and 0.1%, and in particular 0.01% and 0.05% based on the total weight of the composition;
in a pH-neutral, buffered suspension that is inserted into the vagina prior to coitus.

Embodiment 4

[0056] a. A caustic halo fullerene (halogenated functionalized fullerenes) between 0.01% and 5.0%, preferably 0.1% and 1.5%, and in particular between 0.5% and 1.0% based on the total weight of the composition; [0057] b. A highly cationic peptide (protamine) between 0.0001% and 1.0%, preferably 0.001% and 0.1%, and in particular 0.01% and 0.05% based on the total weight of the composition; [0058] c. An aromatic aldehyde (bourgeonal) between 0.0001% and 2.0%, preferably 0.001% and 1.0%, and in particular 0.01% and 0.1% based on the total weight of the composition; [0059] d. A highly cationic polymer (poly-L-lysine) between 0.0001% and 1.0%, preferably 0.001% and 0.1%, and in particular 0.01% and 0.05% based on the total weight of the composition;
in a pH-neutral buffered suspension contained within a dissolvable suppository that is inserted into the vagina prior to coitus.

Embodiment 5

[0060] a. A caustic halo fullerene (halogenated functionalized fullerenes) between 0.01% and 5.0%, preferably 0.1% and 1.5%, and in particular between 0.5% and 1.0% based on the total weight of the composition; [0061] b. A highly cationic peptide (protamine) between 0.0001% and 1.0%, preferably 0.001% and 0.1%, and in particular 0.01% and 0.05% based on the total weight of the composition; [0062] c. An aromatic aldehyde (bourgeonal) between 0.0001% and 2.0%, preferably 0.001% and 1.0%, and in particular 0.01% and 0.1% based on the total weight of the composition; [0063] d. A spermatozoa stimulating hormone (progesterone) between 1 nM and 100 μM, preferably 10 nM and 10 μM, and in particular 0.1 μM and 1 μM;
in a pH-neutral, buffered suspension that is inserted into the vagina prior to coitus.

Embodiment 6

[0064] a. A caustic halo fullerene (halogenated functionalized fullerenes) between 0.01% and 5.0%, preferably 0.1% and 1.5%, and in particular between 0.5% and 1.0% based on the total weight of the composition; [0065] b. A highly cationic peptide (protamine) between 0.0001% and 1.0%, preferably 0.001% and 0.1%, and in particular 0.01% and 0.05% based on the total weight of the composition; [0066] c. An aromatic aldehyde (bourgeonal) between 0.0001% and 2.0%, preferably 0.001% and 1.0%, and in particular 0.01% and 0.1% based on the total weight of the composition; [0067] d. A spermatozoa stimulating hormone (progesterone) between 1 nM and 100 μM, preferably 10 nM and 10 μM, and in particular 0.1 μM and 1 μM;
in a pH-neutral buffered suspension contained within a dissolvable suppository that is inserted into the vagina prior to coitus.

Embodiment 7

[0068] a. A caustic halo fullerene (halogenated functionalized fullerenes) between 0.01% and 5.0%, preferably 0.1% and 1.5%, and in particular between 0.5% and 1.0% based on the total weight of the composition; [0069] b. A highly cationic peptide (protamine) between 0.0001% and 1.0%, preferably 0.001% and 0.1%, and in particular 0.01% and 0.05% based on the total weight of the composition; [0070] c. An aromatic aldehyde (bourgeonal) between 0.0001% and 2.0%, preferably 0.001% and 1.0%, and in particular 0.01% and 0.1% based on the total weight of the composition; [0071] d. A highly cationic polymer (poly-L-lysine) between 0.0001% and 1.0%, preferably 0.001% and 0.1%, and in particular 0.01% and 0.05% based on the total weight of the composition; [0072] e. A spermatozoa stimulating hormone (progesterone) between 1 nM and 100 μM, preferably 10 nM and 10 μM, and in particular 0.1 μM and 1 μM;

[0073] in a pH-neutral, buffered suspension that is inserted into the vagina prior to coitus.

Embodiment 8

[0074] a. A caustic halo fullerene (halogenated functionalized fullerenes) between 0.01% and 5.0%, preferably 0.1% and 1.5%, and in particular between 0.5% and 1.0% based on the total weight of the composition; [0075] b. A highly cationic peptide (protamine) between 0.0001% and 1.0%, preferably 0.001% and 0.1%, and in particular 0.01% and 0.05% based on the total weight of the composition; [0076] c. An aromatic aldehyde (bourgeonal) between 0.0001% and 2.0%, preferably 0.001% and 1.0%, and in particular 0.01% and 0.1% based on the total weight of the composition; [0077] d. A highly cationic polymer (poly-L-lysine) between 0.0001% and 1.0%, preferably 0.001% and 0.1%, and in particular 0.01% and 0.05% based on the total weight of the composition; [0078] e. A spermatozoa stimulating hormone (progesterone) between 1 nM and 100 μM, preferably 10 nM and 10 μM, and in particular 0.1 μM and 1 μM;
in a pH-neutral buffered suspension contained within a dissolvable suppository that is inserted into the vagina prior to coitus.

[0079] Additional embodiments would include obvious combinations of the above-mentioned approaches or complementary molecules to those that have been proposed and as described in the specification of the patent. In particular, existing technology for dissolving capsules and matrices that provide vaginal lubrication for several days would represent another delivery mechanism for this contraceptive invention and would be apparent to those skilled in the art. This knowhow could provide a longer lasting contraceptive approach, as the halo fullerenes and other chemistries are not labile, suggesting routine, discreet administration for continuous efficacy, e.g. semi-weekly application in lieu of a requirement for use immediately before coitus. The various embodiments disclosed in this patent thus provide illustration, not limitations; the intended scope is therefore reflected in the following claims.