KR20230042020A - Personal lubricants containing lambda-carrageenan - Google Patents

Abstract

A pourable, non-toxic lubricating composition and non-greasy, pseudoplastic composition comprising lambda carrageenan as an antiviral agent for protection against viruses including but not limited to sexually-transmitted viruses and respiratory viruses A method of using a lubricating composition as a lubricating product and administering carrageenan to reduce transmission of sexually-transmitted viruses, including HPV, during sexual activity is disclosed.

Description

Personal lubricants containing lambda-carrageenan

The present invention relates to personal lubricant compositions useful for reducing or inhibiting transmission of human papillomavirus between partners during sexual activity.

According to the World Health Organization (WHO), human papillomavirus (HPV) is the world's most common sexually transmitted infection (STI), infecting 14 million new people each year. In the United States alone, more than 42% of people between the ages of 18 and 59 are infected with HPV, and 1 in every 9 men is infected with oral HPV. Additionally, HPV is the root cause of essentially all cervical cancers, and is the second most common cancer in women worldwide by age-standardized incidence rate, causing approximately 500,000 deaths each year. More than 85% of cervical cancer deaths occur in developing countries, where it accounts for 13% of all cancers in women. The WHO also estimates that HPV causes 90% of anal cancers. In a separate study on HPV and throat cancer, AECOM found that the presence of HPV forms in the oral cavity increased the odds of developing head and neck cancer up to 22-fold. HPV is also the underlying cause of all genital warts.

HPV is spread from skin-to-skin contact, transmitted most commonly during sexual activity to the genitals, anus, and oral cavity. As a result, condoms are only marginally effective in preventing transmission of HPV. Although some treatment options exist for HPV, in practice there are more than 150 HPV strains, of which approximately 30 have been shown to cause cancer and genital warts. Although vaccines have been developed and can be useful, the best HPV vaccines available in the United States today provide antiviral activity against only 9 of the 150+ HPV strains and they are effective in only a small subset of humans. In 2015, the CDC reported that only HPV vaccines have a 40% absorption rate among adolescents, and that they are generally not effective for black American women of any age, as well as those over 26 years of age. Additionally, the CDC also reported that the vaccine is also not effective if the person has already been exposed to HPV. Additionally, HPV vaccines are typically expensive, require multiple treatments or injections, and are largely unavailable to humans in developing countries. As a result, a large percentage of people are unvaccinated and rely on condoms as their only protection against HPV.

In vitro (Ref. Buck, C.B., et al., (2006) PLoS Pathogens 2 (7):671-680) and in vivo in mice (Ref. Roberts, J.N., et al., (2007) Nature Medicine 13 ( 7):857-861, and Maguire, R.A., et al., (1998) Sexually Transmitted Diseases 25 (9):494-500) Carrageenan formulations for reducing or inhibiting transmission of viruses, particularly lambda- of carrageenan There is some promising research into the use of formulations containing the mold. Several other patents and patent publications similarly discuss the use of carrageenan in medicine as an antimicrobial or antiviral compound (see U.S. Pat. Nos. 5,208,031 and 8,367,098, and U.S. Patent Publication Nos. 2005/0171053, No. 2005/0239742, 2005/0261240, 2006/0127340, 2008/0227749, 2009/0088405, and 2011/0229446, the disclosures of which are incorporated by reference in their entirety).

Recently, in vivo studies in humans have shown that lambda-carrageenan formulations can be utilized to inhibit transmission of HPV during sexual activity (Magnan, S., et al., (2019) Clin. Microbiol. 25 (2):210-216, the details of which are incorporated by reference in their entirety). However, there are few commercially-obtainable personal lubricants containing carrageenan because carrageenan is very difficult to process into a form suitable for use during sexual activity. Carrageenans are large, highly flexible polysaccharides obtained as complex mixtures of at least two and typically three different forms, almost absolutely differing in their degree of sulfurization: kappa-carrageenan, iota-carrageenan and lambda-carrageenan. The kappa- and iota-forms of carrageenan, which contain the fewest number of estersulfate groups per molecule, predominate in most carrageenan mixtures and are typically used as gelling or thickening agents in the food or cosmetic industry. On the other hand, lambda-carrageenan has the most estersulfate groups per polysaccharide and cannot form gels at all. For lambda-carrageenan, increasing estersulfate levels generally result in lower dissolution temperatures in water and are associated with reduced gel strength or inhibition of gel formation. When present, all combinations of the kappa-form, iota-form and lambda-form of carrageenan have an exponential effect on the viscosity of the composition, as a function of the total concentration of carrageenan in the composition. This can result in loss of rheological, tactile and performance benefits when the composition is used as a sexual lubricant. In particular, carrageenan-based formulations tend to dry quickly after application, resulting in a sticky, non-lubricating residue that defeats the purpose of using a personal lubricant in the first place. Additionally, the viscosity of a particular carrageenan-containing composition is very sensitive to the exact ratio of kappa-form, iota-form and lambda-form in the composition. Thus, even when the total concentration of carrageenan in both compositions is the same, a composition comprising 50% lambda-carrageenan and 50% kappa-carrageenan is a composition comprising 70% lambda-carrageenan and 30% kappa-carrageenan. may have different viscosities. These effects are exacerbated in compositions containing all three forms of carrageenan. As a result, even when the total carrageenan concentration is the same, the viscosity of a carrageenan-containing composition is generally unpredictable from one composition to the next when the ratios of kappa-type, iota-type and lambda-type are different.

Furthermore, the processing steps used to prepare the carrageenan-containing composition itself can affect its viscosity and performance as a sexual lubricant. For example, the temperature at which the ingredients are mixed has a dramatic effect on the viscosity of the carrageenan-containing product, particularly as a function of each type of carrageenan in the mixture. When a raw carrageenan mixture is placed in an aqueous-based solvent and heated, the individual polysaccharides in the mixture begin to hydrate and interact intermolecularly with other polysaccharides to increase the viscosity of the composition. As the temperature is further increased, intermolecular interactions are disrupted and the carrageenan is homogenized and incorporated into the aqueous solution, reducing the overall viscosity to near starting levels. However, the proportion of each type of carrageenan included in the composition may affect what occurs upon cooling. When the dominant form is kappa-carrageenan or iota-carrageenan, the cooled composition may form a gel, whereas when the dominant form is lambda-carrageenan, the cooled composition may not form a gel. Nevertheless, the relative proportions of kappa-carrageenan and iota-carrageenan in the composition affect the viscosity in non-gelling lambda-carrageenan containing compositions.

On the other hand, excessive heating of the carrageenan-containing composition can break intramolecular bonds in adjacent sugar units, effectively causing significant changes in the carrageenan molecule and reducing the average molecular weight. This can further reduce the viscosity of the resulting composition, but comes with a trade-off that allows the composition to dry more quickly once applied. Similarly, mixing a carrageenan-containing mixture under high speed or high-shear conditions for an extended period of time may also disrupt the intermolecular relationships of the carrageenan molecules in the composition.

Therefore, there is still a need for formulations containing lambda-carrageenan and which also perform satisfactorily as sexual lubricants in which both men and women can protect themselves from HPV transmission in a pleasant and unobtrusive manner. . Lubricant formulations must balance efficacy against HPV while maintaining the viscosity, feel and performance enhancements obtained by using personal lubricants during sexual activity. There is also a need for a product that can be used with a condom or other sexual accessory device that reduces the risk of transmission of HPV, HIV and herpes during sexual activity, particularly in encounters involving two or more men.

The present invention includes lambda-carrageenan, Orthomyxoviridae ( Orthomyxoviridae ), Paramyxoviridae ( paramyxoviridae ), Pneumoviridae ( pneumoviridae ), Coronaviridae ( coronaviridae ), Retroviridae ( Retroviridae ), Herpesviridae ( Herpesviridae ), Papilloma Viridae ( papillomaviridae ), picornaviridae ( picornaviridae ), reoviridae ( reoviridae ) and adenoviridae ( adenoviridae ), and combinations thereof, which may include any one of the groups and may alternatively be selected from this group Useful for reducing, suppressing or ameliorating transmission, persistence or symptoms caused by viruses, including but not limited to transmissible viruses and other disease-causing viruses from taxonomic families. A method for preparing a low-viscosity, antiviral lubricating composition is provided. The antiviral lubricating composition prepared according to the described method may contain tissues in or on the cervix, vulva, vagina, clitoris, penis, anus, mouth, nose, nasal cavity or throat, where viruses may reside or spread. It can be applied to any epithelial or skin tissue that can be applied.

In various embodiments, antiviral lubricating compositions prepared by the methods of the present invention may be used in conjunction with sexual activity. As used herein, the term "sexual activity" means contact with the skin or epithelial tissue in or on the cervix, vulva, vagina, clitoris, penis, anus, mouth, or throat of one, two, or more sexual partners. Includes intimate or sexual contact. In some embodiments, the application of the antiviral lubricating composition of the present invention comprises human papillomavirus (HPV), human immunodeficiency virus (HIV) and herpes simplex virus (HSV) compared to a placebo composition that does not contain lambda-carrageenan. It is effective in reducing transmission of sexually-transmitted viruses in humans, including non-limiting examples of In a further embodiment, the antiviral lubricating composition includes, but is not limited to, HPV strains known to cause cancer during male-female sexual encounters, male-male sexual encounters, and female-female sexual encounters. It provides protection against transmission of HPV. In a further embodiment, the antiviral lubricating composition can provide protection against transmission of HPV among high-risk sexual partners, eg, partners already infected with at least one strain of HPV.

In various embodiments, any of the antiviral lubricating compositions described herein are used to prophylactically inhibit transmission of HPV from one sexual partner to another, to the skin or epithelial tissue, particularly prior to sexual activity. It may come into contact with skin or epithelial tissue located on or within at least one of the vagina, anus, mouth, or penis of one or more of the sexual partners. In such embodiments, the antiviral lubricating composition is administered less than 8 hours prior to sexual activity, such as less than 4 hours, 2 hours, 1 hour, 30 minutes, 15 minutes, 5 minutes, 1 minute or 30 seconds prior to sexual activity. May be in contact with the skin of one or more of the sexual partners for less than 1 second. In another embodiment, the antiviral lubricating composition is used to reduce the spread of HPV from cell to cell after transmission of HPV, in skin or epithelial tissue, particularly in at least one of the vagina, anus, mouth, or penis of one or more of the sexual partners. It may be in contact with skin or epithelial tissue located on or within one. In such embodiments, the antiviral lubricating composition is administered less than 8 hours after sexual activity, such as less than 4 hours, 2 hours, 1 hour, 30 minutes, 15 minutes, 5 minutes, 1 minute or 30 seconds after sexual activity. May come into contact with the skin or epithelial tissue of one or more of the sexual partners for less than 1 second.

In various embodiments, the antiviral lubricating composition prepared by the method of the present invention can be applied to the skin or epithelial tissue of a person regardless of whether or not they are involved in sexual activity. In some embodiments, the antiviral lubricating composition is a non-sexually transmitted virus, including but not limited to coronavirus, reovirus, adenovirus, orthomyxovirus, paramyxovirus, pneumovirus, picornavirus and to reduce, inhibit or ameliorate the transmission or effects of non-sexually transmitted retroviruses and herpes viruses. Non-limiting examples of diseases caused by these viruses include severe respiratory disease (SARS), COVID-19, influenza, measles, mumps, varicella, enterovirus, rhinovirus, polio, adenovirus and rotavirus. but is not limited to these. In some embodiments, the antiviral lubricating composition can be applied to animals suffering from infections from diseases caused by viruses caused by any of the virus families or types described above. Methods and substrates for applying antiviral lubricating compositions to humans or animals to aid in the treatment or reduction of the effects of these conditions are described in further detail below.

In another embodiment, the antiviral lubricating composition can be used in conjunction with feminine hygiene products for this purpose including but not limited to: as a vaginal moisturizer, as a vaginal deodorant and as a vaginal deodorant.

In another embodiment, the antiviral lubricating composition is a non-Newtonian, pseudoplastic fluid that undergoes thixotropic shear thinning that reduces the viscosity of the composition even further in response to mechanical deformation. By way of non-limiting example, such mechanical transformation may include sexual activity between male and female sexual partners, two or more male sexual partners, two or more female sexual partners, and combinations thereof, whereby one, two or more persons are sexually active. This can happen when participating in an activity.

In another embodiment, the antiviral lubricating composition has a rheological profile such that the lubricity of the dried antiviral lubricating composition can be maintained on the skin by adding water or other bodily fluid to the dried antiviral lubricating composition. . Non-limiting examples of bodily fluids include saliva and vaginal secretions or secretions. In a further embodiment, by adding water or bodily fluid to the dried antiviral lubricating composition, the antiviral lubricating composition retains antiviral activity, including against HPV.

In some embodiments, an oil, particularly a silicone oil; cellulose; and polyquaternium, but is substantially free of components typically used in commercially available personal lubricants, including but not limited to polyquaternium. there is. In another embodiment, the antiviral lubricating composition can also be formulated to be substantially free of spermicides, such as nonoxinol-9, which are commonly present in commercially available personal lubricants. However, in other embodiments, the antiviral lubricating composition can be formulated to include oil, cellulose, polyquaternium and/or nonoxynol-9.

In another embodiment, the method for forming the antiviral lubricating compositions of the present invention comprises the steps of: (a) providing a carrageenan powder comprising carrageenan, wherein the carrageenan is at least 80% by weight of lambda-carrageenan and up to 10% by weight of a secondary carrageenan selected from the group consisting of iota-carrageenan and kappa-carrageenan (including combinations thereof), preferably 10% by weight of kappa-carrageenan; (b) while mixing, mixing an aqueous solution containing an amount of a polyol with carrageenan powder to form an aqueous carrageenan suspension; (c) heating the aqueous carrageenan suspension to a temperature of 60°C; (d) mixing for a period of time sufficient to transform the heated aqueous carrageenan suspension into an aqueous homogeneous solution; (e) cooling the aqueous homogeneous solution to a temperature of less than 50°C; and (f) mixing one or more pH-adjusting agents into the chilled aqueous homogeneous solution, thereby forming an antiviral lubricating composition.

In some embodiments, the carrageenan suspension is turbid. When substantially all of the polysaccharides in the carrageenan suspension are homogenized by heating and mixing, the carrageenan suspension is clarified and the resulting homogeneous solution is translucent. In another embodiment, the antiviral carrageenan suspension is clarified and remains clear by formation of a homogeneous solution. In another embodiment, there are substantially zero visible particles, agglomerates or agglomerates in the antiviral lubricating composition.

In various embodiments, the turbidity of any of the mixtures, suspensions, or antiviral lubricating compositions described herein is formed in Formazin Nephelometric Units (FNU), Jackson Turbidity Units (JTU), and ratio Turbidity can be described quantitatively based on a method for determining the concentration of suspended particles in a sample, including but not limited to Nephelometric Turbidity Units (NTU). In another embodiment, the turbidity of any of the mixtures, suspensions or antiviral lubricating compositions described herein is characterized as a function of NTU. In another embodiment, the turbidity of the carrageenan suspension resulting from the addition of carrageenan to the aqueous solution is at least 100 NTU, at least 200, 300, 400, 500, 600, 700, 800, 900, 1000, 2000 or 3000 NTU, up to at least at least 4000 NTU. In another embodiment, the homogenized antiviral lubricating composition has a turbidity of less than 20, 15, 10, 8, 6, 5, 4, 3 or 2 NTU, up to and including less than 1 NTU, less than 25 NTU, preferably 5 NTU or less, more preferably approximately equal to the turbidity of drinking water.

In various embodiments, mixing the aqueous solution and carrageenan powder while mixing includes the following sub-steps: (A) mixing the carrageenan powder with the polyol for a time sufficient to form a wet carrageenan mixture, and ( B) while mixing, combining the wet carrageenan mixture with the aqueous solution for a time sufficient to form an aqueous carrageenan suspension. In some embodiments, the weight ratio of polyol to carrageenan in the wet carrageenan mixture is at least 1:5, 1:1, 2:1, 4:1, 6:1, 8:1, 10:1, 20:1, 30: 1 or 40:1, up to at least 1:10, including up to at least 50:1. In a further embodiment, the weight ratio of polyol to carrageenan is from 1:1 to 10:1. In some embodiments, the weight ratio of the aqueous solution mixed with the wet carrageenan mixture to form the carrageenan suspension is from 3:1 to 60:1. In yet a further embodiment, the weight ratio of the aqueous solution mixed with the wet carrageenan mixture to form the carrageenan suspension is from 8:1 to 45:1.

In various embodiments, mixing the wet carrageenan mixture with the aqueous solution includes dispersing the carrageenan included in the wet carrageenan mixture in the aqueous solution. In a further embodiment, the dispersing step includes sufficiently shear mixing the carrageenan powder with a dispersing mixer for a time sufficient to homogenize the carrageenan into the aqueous solution while also breaking the intramolecular bonds between the sugar moieties within each carrageenan polysaccharide. including minimizing

In various embodiments, heating the wet carrageenan mixture, aqueous carrageenan suspension, and/or one or more of the antiviral lubricating compositions enables dissolution and homogenization of the carrageenan in the water. In various embodiments, one or more of the wet carrageenan mixture, aqueous carrageenan suspension and/or antiviral lubricating composition is at least 60°C, such as at least 65°C, 70°C, 75°C, 80°C, 85°C or 90°C. and optionally heated to a temperature of up to at least 95°C. In some embodiments, the aqueous carrageenan suspension is heated to at least 70°C and up to 75°C.

In various embodiments, mixing another powdered or solid or liquid adjuvant into the aqueous solution comprises agitating the adjuvant in the aqueous solution under sufficient shear mixing and for a sufficient time to form a compositionally uniform solution. .

In several embodiments, the carrageenan powder comprising lambda-carrageenan is a dried extract from seaweed, particularly from the red algae Irishmos ( Chondrus crispus ). In some embodiments, the lambda-carrageenan comprises at least 80%, such as at least 85%, 90% or 95% by weight of the seaweed extract. In some embodiments, lambda-carrageenan comprises up to 100%, such as up to 95%, 90% or 85% by weight of the seaweed extract. In some embodiments, lambda-carrageenan comprises 90% by weight of the algae extract.

In various embodiments, the carrageenan powder consists of carrageenan in powder form. In another embodiment, the carrageenan powder consists essentially of carrageenan in powder form.

In various embodiments, the carrageenan powder may include carrageenan in powder form and additional powder ingredients. Non-limiting examples of additional powder ingredients include pH-adjusting agents, bactericides, preservatives, sweeteners and salts, all of which are described in further detail below.

In various embodiments, in a carrageenan powder comprising lambda-carrageenan, the residual carrageenan species may include kappa-carrageenan, iota-carrageenan, or a combination of kappa-carrageenan and iota-carrageenan. In some embodiments, either or both kappa-carrageenan and iota-carrageenan can be present in up to 20% by weight of the carrageenan powder, such as up to 15%, 10%, 8%, 6% by weight of the carrageenan powder. %, 4%, 2% or 1% by weight. In various embodiments, when present, the kappa-carrageenan and iota-carrageenan together constitute at least 1%, such as 2%, 4%, 6%, 8% or 10% by weight of the carrageenan powder. and up to at least 15% by weight. In some embodiments, lambda-carrageenan can comprise 90% by weight of the carrageenan powder, and kappa-carrageenan and iota-carrageenan together comprise 10% by weight of the carrageenan powder. In some embodiments, the lambda-carrageenan can comprise 90% by weight of the carrageenan powder and the kappa-carrageenan comprises 10% of the carrageenan powder. In some embodiments, the lambda-carrageenan can comprise 90% by weight of the carrageenan powder, the lambda-carrageenan can comprise 90% by weight of the carrageenan powder, and the lambda-carrageenan comprises 10% by weight of the carrageenan powder.

In various embodiments, the antiviral lubricating composition contains, by weight, at least 0.001% carrageenan, for example at least 0.01, 0.1, 0.5, 0.75, 1.0, 1.2, 1.4, 1.6, 1.8, 2.0, 2.2, 2.4, 2.5 or 3% carrageenan, and optionally up to at least 5% carrageenan. In another embodiment, the antiviral lubricating composition is less than 5% by weight, for example 3, 2.5, 2.4, 2.2, 2, 1.8, 1.6, 1.4, 1.2, 1.0, 0.75, 0.5, 0.1, 0.01 or 0.001 by weight. % carrageenan. In a further embodiment, the antiviral lubricating composition comprises 0.2% to 2.3% by weight of carrageenan. In yet a further embodiment, the antiviral lubricating composition comprises 0.8% to 2% by weight of carrageenan. In a still further embodiment, the antiviral lubricating composition comprises 1.5% to 1.7% by weight of carrageenan.

In various embodiments, addition of one or more polyols to the carrageenan powder partially loosens the carrageenan polysaccharides in the powder, allowing additional polarizable contacts to be interacted with by the addition of an aqueous solution. In another embodiment, the presence of a polyol in the antiviral lubricating composition enhances the sensory, tactile and/or lubricity experienced by the user or his partners during sexual activity. In a further embodiment, the at least one polyol may be selected from the group consisting of: glycerol; propylene glycol (1,2-propanediol); 1,3-propanediol; 1,3-butanediol; 1,4-butanediol; 2,3-butanediol; xylitol; sorbitol; erythritol; isomalt; lactitol; maltitol; mannitol; polyethylene glycol; and polypropylene glycol; combination of them. In yet further embodiments, the antiviral lubricating composition is less than 50% by weight of the antiviral lubricating composition, for example 25, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2, less than 1, 0.5 or 0.1% by weight polyol. In another embodiment, the antiviral lubricating composition comprises at least 0.1% by weight of a polyol, such as at least 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 25 or 35 % polyol by weight. In a still further embodiment, the antiviral lubricating composition comprises less than 10% by weight of a polyol. In a still further embodiment, the antiviral lubricating composition comprises 0.5% to 5% by weight of a polyol. In a still further embodiment, the antiviral lubricating composition comprises 4% to 4.5% by weight of a polyol. In some embodiments, the polyol is propylene glycol. In some embodiments, the polyol is 1,3-propanediol.

In various embodiments, the antiviral lubricating composition is a pourable composition having a viscosity of less than 10,000 cP, eg, less than 8,000, 6,000, 5,000, 4,000, 3,000, 2,000 or 1,000 cP. In another embodiment, the antiviral lubricating composition has a viscosity of at least 500 cP, such as at least 1,000, 2,000, 3,000, 4,000, 5,000, 6,0000 cP or 8,000 cP. In a further embodiment, the antiviral lubricating composition has a viscosity from 500 cP to 8,000 cP, more specifically from 1,000 cP to 4,000 cP, and even more specifically from 2,000 cP to 3,000 cP. In some embodiments, the antiviral lubricating composition has a viscosity of 1,500 cP to 2,500 cP. In some embodiments, the antiviral lubricating composition has a viscosity of 2,000 cP.

In various embodiments, the antiviral lubricating composition can be poured from an open container, but has a viscosity that allows it to remain on a sloped, beveled, curved or inverted surface by application. Non-limiting examples of surfaces include skin or epithelial tissue such as the cervix, vulva, vagina, clitoris, penis, anus, nose, nasal cavity, mouth, and throat. Other non-limiting examples of surfaces to which the antiviral lubricating composition may be applied include masturbation devices, vibrators, sexual aids such as rings or beads, or cotton swabs, extension rods or rods, wearable inserts, injectors, syringes, catheters, or the like. Internal applicators such as pipettes and the like may be included.

In various embodiments, by exerting or using one or more shear forces on a surface comprising the applied antiviral lubricating composition, as is commonly applied during sexual activity, the viscosity of the antiviral lubricating composition is reduced in a non-Newtonian manner. decreases to In a further embodiment, the viscosity is reduced to less than 5,000 cP, e.g., less than 4,000, 3,000, 2,500, 2,000, 1,500, 1,000, 800, 600, 500, 400 or 300 cP, and optionally less than 200 cP. . In another embodiment, the antiviral lubricating composition has a lubricity of at least 15 seconds, such as at least 30 seconds, 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes. or 45 minutes and optionally up to at least 1 hour by continuously applying the shearing force.

In various embodiments, the viscosity of the composition increases exponentially as the total concentration of carrageenan in the antiviral lubricating composition increases. In a further embodiment, the relative concentrations of the kappa-, iota- and lambda-forms of carrageenan differentially affect the rate of exponential increase in viscosity of the antiviral lubricating composition. In yet further embodiments, the antiviral lubricating composition comprises 90% lambda-carrageenan and 10% either or both kappa-carrageenan or iota-carrageenan. In a still further embodiment, the antiviral lubricating composition comprises 90% lambda-carrageenan and 10% kappa-carrageenan. In a still further embodiment, the antiviral lubricating composition comprises 90% lambda-carrageenan and 10% iota-carrageenan.

In various embodiments, the mixing rotor geometry and mixing speed may be optimized to control the viscosity of the antiviral lubricating composition resulting from mixing. In some embodiments, mixing is sufficient to homogenize the carrageenan-containing composition while preserving the length of each carrageenan polysaccharide and maintaining the lubricity of the composition, particularly prior to application of the composition to the skin or epithelial tissue prior to or in conjunction with sexual activity. It can be performed under shear conditions sufficient to do so.

In various embodiments, the apparatus for carrying out the mixing step of the present invention, including the step of stirring or the step of dispersing, may include any conventional mixing device for the intended use. One non-limiting example of a mixing device is a paddle mixer. One example of a paddle mixer is a mixer that includes at least one collapsible impeller blade. One specific example of a paddle mixer is the Mixer Direct R-AD665 Industrial Gallon Paddle Mixer with two collapsible impeller blades. In yet a further embodiment, a paddle mixer is used for each of the mixing steps to form the antiviral lubricating composition. In yet further embodiments, each of the mixing steps is performed with a low speed mixer operating at a rotational speed of 500 revolutions per minute (RPM) or less. In another embodiment, mixing of the antiviral lubricating composition after homogenizing the carrageenan in the aqueous solution may occur at a speed of 250 RPM or less.

In various embodiments, the antiviral lubricating composition formed by the method of the present invention has an osmolality such that skin or epithelial tissue, particularly epithelial tissue in the vagina or rectum, maintains a healthy plasma-electrolyte balance. In a further embodiment, the antiviral lubricating composition has an osmolality less than 1200 mOsmol/kg, such as less than 1000, 900, 800, 700, 600, 500, 400, 300 or 200 mOsmol/kg, optionally optionally less than 100 mOsmol/kg. In yet a further embodiment, the osmolality of the antiviral lubricating composition is between 650 mOsmol/kg and 800 mOsmol/kg. In a still further embodiment, the osmolality of the antiviral lubricating composition is isosmolar to the normal osmolality of human semen between 250 mOsmol/kg and 380 mOsmol/kg. In yet a further embodiment, the osmolality of the antiviral lubricating composition is iso-osmolar to the normal osmolality of vaginal secretion between 260 mOsmol/kg and 290 mOsmol/kg.

In various embodiments, the antiviral lubricating composition of the present invention may further comprise one or more pH-adjusting agents comprising acids, particularly organic acids, and more particularly citric acid. In another embodiment, the one or more pH-adjusting agents may include a weak acid and its conjugate base to form a buffer. In one non-limiting example, the addition of citrate salt to the antiviral lubricating composition can be accomplished by adding both citric acid and a citrate salt such as sodium or magnesium citrate.

In various embodiments, the pH of the antiviral lubricating composition is less than 9.0, eg, 8.0, 7.0, 6.5, 6.0, 5.5, 5.0, 4.5, or less than 4.0, optionally less than 3.5. In yet further embodiments, the antiviral lubricating composition has a pH of at least 3.5, such as at least 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0 or 8.0, and optionally at least 9.0. In an even further embodiment, the pH of the antiviral lubricating composition is between 5.5 and 7.0. In a still further embodiment, the pH of the antiviral lubricating composition can be applied directly to the vagina or optimized for contact with the vagina during sexual activity. In this embodiment, the pH of the antiviral lubricating composition is between 3.5 and 5.5, particularly about 4.5.

In various embodiments, the pH of the antiviral lubricating composition is adjusted after the carrageenan has been homogenized and the resulting antiviral lubricating composition has cooled. In a further embodiment, the antiviral lubricating composition may be cooled to less than 50°C, such as less than 45°C, 40°C, 35°C, 30°C or 25°C, and optionally less than 20°C. In yet a further embodiment, the antiviral lubricating composition is cooled to less than 30° C. and then the pH of the composition is adjusted.

In various embodiments, the concentration of one or more pH-adjusting agents in the pH-adjusted antiviral lubricating composition is less than 1% by weight of the antiviral lubricating composition, such as 0.5%, 0.25% by weight of the antiviral lubricating composition. %, less than 0.1% or 0.05%, and optionally less than 0.01%. In a further embodiment, the concentration of one or more pH-adjusting agents in the pH-adjusted antiviral lubricating composition is less than or equal to 0.1% by weight. In yet a further embodiment, the weight of one or more pH-adjusting agents in the pH-adjusted antiviral lubricating composition is less than or equal to 0.05% by weight. The pH-adjusting agents can be added into the composition as a component of the carrageenan powder to which the polyol is added, into the carrageenan suspension or into the antiviral lubricating composition after the carrageenan has been homogenized.

In various embodiments, the method for forming the antiviral lubricating composition further comprises admixing one or more sweeteners and/or one or more preservatives to any one of carrageenan powder, aqueous carrageenan suspension or chilled aqueous homogeneous solution. can include In various embodiments, one or more sweeteners are added to the aqueous carrageenan suspension. In various embodiments, one or more preservatives are added to the aqueous homogeneous solution along with one or more pH-adjusting agents. In various embodiments, each of the additional ingredients such as salts and/or flavoring agents as well as the sweeteners and preservatives described above are included in the antiviral lubricating composition to supplement the antiviral activity of the composition and facilitate application to the skin or epithelial tissue. assist and/or enhance the performance of the composition during sexual activity.

In various embodiments, the antiviral lubricating composition of the present invention comprises from 0.01% to 1% by weight of the antiviral lubricating composition, in particular from 0.1% to 0.5% by weight of the antiviral lubricating composition comprising one or more sweeteners, in particular Saccharin may additionally be included. In another embodiment, the concentration of saccharin in the antiviral lubricating composition is at most 0.5% by weight. In another embodiment, the concentration of saccharin in the antiviral lubricating composition is 0.125% by weight.

In various embodiments, saccharin may be added to the carrageenan mixture or carrageenan suspension as an aliquot from the concentrated stock solution. In a further embodiment, the total weight of the carrageenan mixture or saccharin stock solution added to the antiviral lubricating composition comprises from 1% to 10% by weight of the finished antiviral lubricating composition. In yet a further embodiment, the saccharin stock solution is 2.5% by weight saccharin in water. In a still further embodiment, the amount of 2.5% by weight saccharin stock solution added to the carrageenan mixture equals 5% by weight of the antiviral lubricating composition, wherein the final concentration of saccharin in the antiviral lubricating composition is 0.125% by weight. %am. In yet a further embodiment, the saccharin is provided as saccharin sodium.

In various embodiments, the antiviral lubricating composition of the present invention comprises 0.01% to 1.0% by weight of one or more preservatives, particularly 2-phenoxylethanol, chlorphenesin, and sodium dehydroacetate ( sodium dehydroacetate), and one or more preservatives selected from the group consisting of combinations thereof.

In various embodiments, the antiviral lubricating composition of the present invention may optionally further include one or more fragrances designed to provide a pleasant fragrance effect to the composition. Fragrances can include essential oils or constituent compounds within essential oils that can provide odor. Non-limiting examples of flavors that can be provided by such fragrances include citrus, lemon, berry, or peppermint flavors. In some embodiments, the fragrance may comprise from 0.01% to 5% by weight of the antiviral lubricating composition, particularly from 0.1% to 2.5% by weight of the antiviral lubricating composition.

In various embodiments, the antiviral lubricating composition of the present invention is a salt, particularly a salt, which may be utilized to increase the ionic strength of the composition while also supporting or supplementing either or both of the rheological properties or antiviral activity of the composition. sodium salts or subsalts, more particularly zinc salts. The salt may be added into the composition as one component of the polyol-added carrageenan powder, into the carrageenan suspension or into the antiviral lubricating composition after the carrageenan has been homogenized.

In various embodiments, the method for forming the homogenized antiviral lubricating composition of the present invention is performed in less than 12 hours, such as less than 10, 8, 6, 4 or 3 hours, and optionally, less than 2.5 hours. can be completed In a further embodiment, the method for forming the homogenized antiviral lubricating compositions of the present invention is completed within 2 to 3 hours.

In another embodiment, a method for forming an antiviral lubricating composition may include the steps of: (a) providing a carrageenan powder comprising carrageenan, wherein the carrageenan is 90% by weight lambda-carrageenan and 10 contains kappa-carrageenan in weight percent; (b) while mixing, mixing an aqueous solution comprising propylene glycol and carrageenan powder to form an aqueous carrageenan suspension; (c) adding one or more sweetening agents to the aqueous carrageenan suspension; (d) heating the aqueous carrageenan suspension to a temperature of at least 70° C. and at most 75° C.; (e) mixing the heated aqueous carrageenan suspension for a time sufficient to form an aqueous homogeneous solution; (f) cooling the aqueous homogeneous solution to a temperature of less than 30°C; and (g) mixing into a chilled aqueous homogeneous solution at least one pH-adjusting agent and at least one preservative sufficient to adjust the antiviral lubricating composition to a pH of 3.5 to 7.0, thereby forming the antiviral lubricating composition. step to do. In another embodiment, the antiviral lubricating composition formed by the above method may consist essentially of: 1.5% to 1.7% by weight of carrageenan, 4.0% to 4.5% by weight of propylene glycol, up to 0.5% by weight. % of one or more sweeteners, up to 1% by weight of one or more preservatives and from 0.01% to 1% by weight of one or more pH-adjusting agents, the balance being water. In a further embodiment, the antiviral lubricating composition formed by the above method may be translucent and has a viscosity of at least 2,000 cP and at most 3,000 cP and a turbidity of less than 25 NTU, preferably less than 5 NTU. In yet a further embodiment, the antiviral lubricating composition formed by the above method may have an osmolality within the range of at least 650 mOsmol/kg and at most 850 mOsmol/kg. In a still further embodiment, the antiviral lubricating composition formed by the above method has a pH of 3.5 to 5.5. In a still further embodiment, the antiviral lubricating composition formed by the above method has a pH of 5.5 to 7.0. In yet a further embodiment, the antiviral lubricating composition formed by the above method is effective to reduce, inhibit or ameliorate the transmission of HPV. In yet a further embodiment, the antiviral lubricating composition formed by the above method is effective to reduce, inhibit or ameliorate transmission of COVID-19.

In another embodiment, a method for forming an antiviral lubricating composition of the present invention may include the following steps: (a) providing a carrageenan powder comprising carrageenan, wherein the carrageenan is at least 90% by weight lambda -contains carrageenan and up to 10% by weight of kappa-carrageenan; (b) mixing the carrageenan powder and the polyol, including stirring or scrambling, for a time sufficient to form a wet carrageenan mixture with the carrageenan powder, wherein the weight ratio of glycol to carrageenan is from 1:1 to 10:1. ; (c) dispersing the wet carrageenan mixture into an aqueous solution under shear mixing for a time sufficient to form a turbid carrageenan suspension, wherein the weight ratio of aqueous solution to carrageenan is from 45:1 to 8:1; (d) while stirring the turbid carrageenan suspension, adding one or more sweeteners into the turbid carrageenan suspension, wherein the sweetener comprises up to 0.5% by weight of the finished antiviral lubricating composition; (e) heating to a temperature of 70° C. under shear mixing for a time sufficient to transform the cloudy carrageenan suspension into a clarified homogeneous solution, including 100 minutes, thereby forming an antiviral lubricating composition; (f) cooling the homogenized antiviral lubricating composition until the temperature of the antiviral lubricating composition is less than 30°C; (g) adding one or more pH-adjusting agents into the cooled antiviral lubricating composition in a weight sufficient to adjust the antiviral lubricating composition to a pH of 3.5 to 7.0, under agitation, and (h) under agitation, adding one or more preservatives in up to 1% by weight of the viral lubricating composition into the turbid carrageenan suspension or cooled antiviral lubricating composition; wherein (i) the antiviral lubricating composition comprises from 0.2% to 2.3% by weight of carrageenan and up to 10% by weight of a polyol; (ii) the antiviral lubricating composition has a viscosity of less than 5,000 cP; (iii) the antiviral lubricating composition is translucent; and (iv) the antiviral lubricating composition is effective in reducing, inhibiting or ameliorating transmission of human papillomavirus (HPV). In a further embodiment, the antiviral lubricating composition comprises: 1.5% to 1.7% by weight of carrageenan; 4% to 4.5% by weight of 1,2-propanediol; a viscosity of 2,000 cP to 3,000 cP; an osmolality of 650 mOsmol/kg to 850 mOsmol/kg; and a pH of 6.25 to 6.75. In yet a further embodiment, the carrageenan comprises 90% lambda-carrageenan and about 10% kappa-carrageenan by weight. In yet a further embodiment, the antiviral lubricating composition formed by the above method is effective to reduce, inhibit or ameliorate the transmission of HPV. In yet a further embodiment, the antiviral lubricating composition formed by the above method is effective to reduce, inhibit or ameliorate transmission of COVID-19.

In another aspect, the present invention also describes a method for reducing, inhibiting or ameliorating the transmission, symptoms or effects of a viral infection comprising the steps of: (a) one of the above-described antiviral lubricating compositions; providing any; and (b) contacting the antiviral lubricating composition with the skin or epithelial tissue of one or more of the partners. Non-limiting examples of skin or epithelial tissues to which the antiviral lubricating composition may be applied include skin, cervix, vulva, vagina, clitoris, penis, anus, nose, nasal cavity, mouth, and throat. In another embodiment, the antiviral lubricating composition can be applied to any internal or external skin or epithelial tissue known to have a viral infection.

In various embodiments, a method for reducing, inhibiting, or ameliorating the transmission, symptoms, or effects of a viral infection may include the steps of: (a) providing a substrate comprising one or more skin-contacting surfaces, wherein wherein the substrate is configured to contact skin or epithelial tissue and/or to be inserted into one or more body cavities; (b) lubricating at least one skin-contacting surface of the substrate with an antiviral lubricating composition, thereby forming a lubricated substrate; (c) contacting the lubricated substrate with skin or epithelial tissue; and (d) delivering the antiviral lubricating composition from the lubricated substrate to the skin or epithelial tissue.

In various embodiments, a method for reducing, inhibiting or ameliorating transmission of a sexually-transmitted virus including but not limited to HPV, HIV and HSV between two or more partners engaging in sexual activity comprises the following steps: (a) providing any of the above-described antiviral lubricating compositions; and (b) contacting the antiviral lubricating composition with the skin or epithelial tissue of at least one of the partners, wherein the skin or epithelial tissue is placed on or within at least one of the vagina, anus, mouth, or penis. In a further embodiment, at least one partner is male and at least one partner is female. In still further embodiments, at least two partners are male. In still further embodiments, at least two partners are female. In yet a further embodiment, there are three or more sexual partners including any combination of male or female.

In various embodiments, a method for reducing, inhibiting, ameliorating or preventing transmission of sexually-transmitted viruses, including but not limited to HPV, HIV and HSV, between partners engaging in sexual activity comprises the following steps: (a) providing a substrate comprising one or more skin-contacting surfaces, wherein the substrate is configured to be inserted into one or more body cavities selected from the group consisting of the vagina, mouth, or anus; (b) lubricating at least one skin-contacting surface of the substrate with an antiviral lubricating composition, thereby forming a lubricated substrate; (c) contacting the lubricated substrate with skin or epithelial tissue located on or within at least one of the vagina, anus, mouth, or penis of one or more of the partners; and (d) delivering the antiviral lubricating composition from the lubricated substrate to the skin or epithelial tissue.

In several embodiments, the substrate is a condom. In a further embodiment, the condom comprises latex. In yet further embodiments, the condom comprises polyurethane and/or other synthetic materials. In yet a further embodiment, the condom does not coexist with oil-based personal lubricants. In a still further embodiment, the condom is selected from the group consisting of a male condom and a female condom.

Methods for reducing, inhibiting, ameliorating or preventing transmission of sexually-transmitted viruses, including but not limited to HPV, HIV and HSV, between partners engaging in sexual activity, in several embodiments in which condoms are described The method may further include: lubricating the surface-contacting surface of the condom; contacting skin or epithelial tissue within the mouth, vagina or anus of one or more of the partners with the lubricated skin-contacting surface of the condom; and delivering the antiviral lubricating composition from the lubricated skin-contacting surface of the condom to the skin or epithelial tissue.

Methods for reducing, inhibiting, ameliorating or preventing transmission of sexually-transmitted viruses, including but not limited to HPV, HIV and HSV, between partners engaging in sexual activity, in several embodiments in which condoms are described may further include the following steps: placing the condom on one's partner's finger or penis; lubricating the outer surface of the condom with an antiviral lubricating composition; contacting skin or epithelial tissue within the mouth, vagina, or anus of one or more additional partners using the lubricated outer surface of the condom; and delivering the antiviral lubricating composition from the lubricated outer surface of the condom to the skin or epithelial tissue.

Methods for reducing, inhibiting, ameliorating or preventing transmission of sexually-transmitted viruses, including but not limited to HPV, HIV and HSV, between partners engaging in sexual activity, in several embodiments in which condoms are described further comprises the following steps: lubricating the condom; sealing the lubricated condom within the package; storing the lubricated condom within the package; removing the lubricated condom from the packaging; applying the lubricated condom to the finger or penis of one of the sexual partners; contacting the skin or epithelial tissue in the mouth, vagina or anus of one or more additional partners using a lubricated condom; and delivering the antiviral lubricating composition from the lubricated condom to the skin or epithelial tissue.

In various embodiments, the substrate is a sexual aid device including but not limited to a sex toy, penis substitute, vibrator, ring, or bead. In a further embodiment, the method comprises sealing the lubricated sexual aid device within packaging, storing the lubricated sexual aid device within the packaging, and prior to contacting the lubricated sexual aid device with the skin or epithelial tissue of one or more partners. including, but not limited to, removing the device from packaging. The antiviral lubricating composition may be applied to any skin-contacting surface of a sexual assistive device, typically prior to contact with the skin of one or more sexual partners, particularly prior to insertion into the vagina, anus, or oral cavity.

In various embodiments, condoms lubricated with any of the antiviral lubricating compositions of the present invention can be applied to unlubricated sexual aids to provide lubrication for use during sexual activity. In another embodiment, an unlubricated condom may be applied to a sexual aid device lubricated by any of the antiviral lubricating compositions of the present invention. In yet another embodiment, an unlubricated condom may be applied to an unlubricated sexual aid device and subsequently lubricated with any of the antiviral lubricating compositions of the present invention.

In various embodiments, the substrate is an internal applicator configured to be inserted into the vagina, rectum, mouth, or nose, wherein the internal applicator is a group consisting of a cotton swab, an extension rod or rod, a wearable insert, an injector, a syringe, a catheter, or a pipette. is selected from In a further embodiment, the internal applicator comprises a skin-contacting surface configured to contact epithelial tissue within a body cavity of an individual, particularly within the vagina, nose, mouth, or rectum. In yet a further embodiment, the internal applicator is a container configured to contain or contain the antiviral lubricating composition prior to delivery of the antiviral lubricating composition onto an epithelial tissue within a body cavity of an individual, particularly the vagina, nose, mouth or rectum. includes

In various embodiments, the substrate is a cotton swab of sufficient length to be inserted into the mouth or nose and contact epithelial tissue in the nasal or oral cavity, including the throat. In various embodiments, a lubricated swab is inserted into the nose or mouth to contact epithelial tissue within the nasal or oral cavity, including but not limited to viruses such as SARS, COVID-19, Middle East Respiratory Syndrome (MERS), and adenovirus. Reduce, suppress or ameliorate the transmission, symptoms or effects of a respiratory infection.

The present invention also provides kits for reducing, inhibiting or mitigating the transmission of sexually-transmitted viruses, including but not limited to HPV, HIV and HSV, between partners engaged in sexual activity, comprising such The kit includes any of the foregoing antiviral lubricating compositions and instructions describing any of the methods disclosed above for contacting the antiviral lubricating compositions with the skin of one or more partners. The kit may further include any of the above-described materials including condoms, sexual aids and/or internal applicators.

These and other embodiments of the invention will be apparent to those skilled in the art from the detailed description that follows.

Figure 1 shows a plot of the viscosity of an antiviral lubricating composition as a function of the concentration of carrageenan.
Figure 2 shows a plot of osmolality of an antiviral lubricating composition as a function of 1,2-propanediol concentration.

Although references are made to exemplary implementations and specific language is used to describe them, it should be understood that they are not intended to limit the scope of the invention. Further modifications of the methods described herein, as well as further applications of the principles of the present invention as described, which may occur to those skilled in the art and having this disclosure, are to be considered within the scope of the present invention. do. Also, unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this particular embodiment of the invention pertains. The terminology used is for the purpose of describing these implementations only, and the terminology is not intended to be limiting unless specified on its own. Headings are provided for convenience only and should not be construed as limiting the invention in any way. Also, throughout the specification and claims, formulas or chemical names given include all optical and stereoisomers, as well as racemic mixtures in which such isomers and mixtures exist.

This specification describes an aqueous composition that has antiviral activity against several different taxonomic families, including but not limited to one or both of the Coronaviridae and Papillomaviridae, and which can be utilized as a personal lubricant during sexual activity. include The antiviral lubricating composition can be used for viral infections inside or outside the body or areas commonly lubricated during sexual activity including but not limited to the cervix, vulva, vagina, clitoris, penis, anus, nose, nasal cavity, mouth and throat. It can come into contact with skin or epithelial tissue anywhere known to be present in the body. The antiviral lubricating composition protects against human papillomavirus (HPV), human immunodeficiency virus (HIV) or herpes simplex virus (HSV) between sexual partners, including male-female, male-male and female-female sexual partnerships. to reduce, inhibit, ameliorate or prevent transmission and/or persistence of sexually-transmitted viruses.

Lambda-carrageenan-containing composition

The antiviral activity of the antiviral lubricating composition of the present invention results from the presence of carrageenan, particularly lambda carrageenan. Carrageenan is a general term for a broad family of naturally occurring sulfated polysaccharides derived from a wide variety of seaweed species, particularly Chondrus crispus , a red algae found on the Atlantic coast of the United States. Extracted carrageenan can typically be obtained in one of ten different forms in terms of sulfurization content, sulfurization position within each polysaccharide and acid/base properties. The three forms of kappa-carrageenan, iota-carrageenan and lambda-carrageenan are particularly common in compositions used in the food and pharmaceutical industries. The structures of kappa-carrageenan, iota-carrageenan and lambda-carrageenan are shown below:

As indicated above, kappa-carrageenan, iota-carrageenan and lambda-carrageenan contain repeating galactose units. In particular, kappa-carrageenan and iota-carrageenan contain alternating units of D-galactose and 3,6-anhydro-galactose (3,6-AG), whereas lambda-carrageenan does not contain any 3,6-AG also does not include Each form differs in the number of sulfate groups per disaccharide, wherein kappa-carrageenan, iota-carrageenan and lambda-carrageenan each contain one, two or three sulfate groups per alternating unit. As the number of sulfate groups in the polysaccharide increases, the ability of certain types of carrageenan to create a gel decreases. Similarly, all of the kappa-, iota- and lambda-forms of carrageenan have the ability to dissolve in aqueous solution, although the temperature at which a particular form can dissolve is also a function of the relative sulfate content. Thus, a pure sample of lambda-carrageenan can be soluble in water at a lower temperature than a pure sample of kappa-carrageenan.

Carrageenan is commonly used as a thickening and/or gelling agent in the food and pharmaceutical industries. As the carrageenan hydrates within the aqueous composition, the carrageenan begins to swell, exponentially increasing the composition's viscosity as a function of the total carrageenan concentration. However, the rate of exponential growth is inversely proportional to the sulfate content within each form of carrageenan, so kappa-carrageenan has a greater effect on viscosity than iota-carrageenan itself, which has a greater effect on viscosity than lambda-carrageenan. cause exponential growth. Moreover, since polysaccharides form a double-helical, semi-crystalline network, especially in the presence of cations, a heated composition comprising kappa-carrageenan and iota-carrageenan can form a gel network upon cooling. there is. However, the presence of lambda-carrageenan in the composition partially inhibits the formation of gels, and in the most lambda-carrageenan-rich compositions, gel formation is completely pre-excluded. Without being limited to any particular theory, it is believed that the lack of 3,6-AG groups in lambda-carrageenan drives gel inhibition.

Although the relative influence of the kappa-, iota- and lambda-types of carrageenan on the viscosity of the composition is not known, in particular when the ratio of kappa-carrageenan, iota-carrageenan and lambda-carrageenan is different between the compositions , the rate of exponential growth of viscosity is generally not predictable from one composition to another. Additionally, the way the carrageenan and other ingredients are processed also has a dramatic effect on the viscosity of the resulting composition. Factors associated with the viscosity of the final product include, but are not limited to: heating temperature(s), shear conditions, rotor type, mixing speed, mixing time, and also any additional ingredients added to the composition. Consequently, viscosity as a function of total carrageenan concentration can only be modeled if the proportion of each form of carrageenan is constant and the processing steps are otherwise identical.

Although carrageenan compositions comprising primarily the kappa- and iota-forms of carrageenan are useful for thickening compositions or gels, they are inactive against HPV. On the other hand, the lambda-carrageenan form has been shown to be active against HPV both in vitro (see Buck, et al., supra) and in vivo. Several patents and publications similarly describe the use of carrageenan in drugs as an antibacterial or antimicrobial compound (U.S. Pat. Nos. 5,208,031 and 8,367,098, and U.S. Pat. Pubs. 2005/0171053, 2005/0239742, 2005 /0261240, 2006/0127340, 2008/0227749, 2009/0088405 and 2011/0229446, the details of which are incorporated by reference in their entirety). Without being bound by any particular theory, lambda-carrageenan is believed to be a “lock and key” type mechanism by which the polysaccharide attracts the virus, interacts with the viral capsid, arrests or prevents viral replication, and further inhibits viral activity. make use of This results in a significant reduction in transmission and persistence of the virus, particularly HPV in sexually active men and women.

In one study, lambda-carrageenan-containing gel was administered to sexually active women at high risk of contracting and/or transmitting HPV during sexual activity (Marais, D., et al., (2011) Antiviral Therapy 16 : 1219-1226, see also US Patent 8,367,098, the details of which are incorporated by reference in their entirety). The tested composition Carraguard® comprises a mixture of kappa-carrageenan and lambda-carrageenan at 3% by weight and has a viscosity of 30,000 to 40,000 cP. Study participants were instructed to apply the gel along with vaginal intercourse. Over a three-year study, the authors found that among women with "a relatively high attachment to using the gel," women who received the lambda-carrageenan-containing gel had only a 62% chance of being classified as HPV-positive compared to the placebo group. decided.

However, as described above, carrageenan (in any form) has historically been used as a thickening agent and is generally not preferred in personal lubricant formulations because it increases the viscosity of the composition exponentially. In particular, gel compositions comprising kappa-carrageenan and/or large amounts of iota-carrageenan are typically very viscous and, once applied to the skin or epithelial tissue, tend to dry quickly to form a sticky residue and lose lubricity. . As a result, like the compositions studied in the paper by Marais and colleagues, U.S. Patent No. 8,367,098 topical carrageenan-containing compositions are typically gels or creams. To put into context the viscosities of these carrageenan-containing compositions, the viscosities of Carraguard® compared to several conventional compositions are shown in Table 1 below.

As shown in Table 1, the viscosity of the Carraguard® gel utilized in the Marais study is in the range between that of chocolate and that of ketchup. Although both chocolate and ketchup have shear-thinning properties, and chocolate can contain edible compositions that can be utilized especially during sexual activity, the high viscosity of both compositions makes these compositions a personal and sexual lubricant. as it does not perform well.

In contrast, compositions that are commonly used as personal lubricants and do not contain carrageenan are typically 5 to 10 times less viscous than the gels used in the Marais study and described in the '098 patent. Ideally, a personal lubricant composition should have a viscosity such that it can be poured or lightly squeezed from a container, remain on the skin after application, and undergo shear thinning in response to stress, such as during sexual activity. Materials commonly found in personal lubricants include, but are not limited to: oils, particularly silicone oils, gums, celluloses, glycerin, polyols, glycols, glycans, polyquaterniums, and other polymers. However, although these lubricants provide satisfactory results during sexual activity, they do not provide any protection against HPV.

Other human in vivo studies (see Magnan and colleagues, above) explored the use of less viscous personal compositions containing lambda-carrageenan for anti-HPV activity. Similar to the Marais study above, women were randomly assigned either a placebo or Divine 9®, a commercial composition containing lambda-carrageenan, and instructed to apply the composition in conjunction with sexual activity. The test composition contained 1.4% by weight of a carrageenan mixture comprising lambda-carrageenan and iota-carrageenan, 37% by weight of propylene glycol and a viscosity of 1,000 to 4,000 cP (see Example 1 below). Although the Magnan study showed a decrease in HPV incidence similar to the Marais study, the presence of these high concentrations of propylene glycol is potentially dangerous to people using the composition and may increase the chances of getting HPV in some people. An osmolality of more than 5,000 mOsm/kg, which is a level, was induced.

According to findings provided by the World Health Organization (WHO) report on sexual health (see “Use and Procurement of Additional Lubricants for Male and Female Condoms: WHO/UNFPA/FHI360 Advisory Note” World Health Organization, Geneva Switzerland, (2012), incorporated by reference in its entirety), studies have shown that lubricants with high osmolality can cause vaginal and anal epithelial damage, which in turn can increase the risk of infection with HPV, HIV and other sexually transmitted infections. there is. WHO has also found that the main factor determining the osmolality of a given personal lubricant is the presence of glycols in the composition. Glycols, also commonly known as “polyols,” include glycerol, 1,2-propanediol and 1,3-propanediol, and can disrupt the water-electrolyte balance within epithelial cells. WHO has demonstrated that most commercially available lubricants have osmolality far exceeding that of normal vaginal secretion (260 to 290 mOsmol/kg) and semen (250 to 380 mOsmol/kg), and Aiming to be isosmotic with vaginal secretion and/or semen (250 to 400 mOsmol/kg), we recommend that companies tailor their commercial personal lubricant compositions to be less than 1,200 mOsmol/kg.

Antiviral lubricating composition of the present invention

The present invention provides several novel antiviral lubricating compositions comprising lambda-carrageenan, active against viruses, including HPV, and having similar viscosities to commonly-obtainable lubricants that do not contain carrageenan. In another embodiment, the antiviral lubricating composition possesses a rheological profile that allows the composition to retain moisture and lubricity for several hours upon application and provides a satisfactory experience to a person engaging in sexual activity. . In a further embodiment, the antiviral lubricant composition is a pseudoplastic, non-Newtonian fluid composition that undergoes shear thinning in response to mechanical stress, particularly during sexual activity. In yet a further embodiment, the antiviral lubricant composition of the present invention can be poured directly from a container without having to be squeezed or otherwise manually extracted from the container. In yet a further embodiment, the antiviral lubricating composition is substantially free of a gel network.

As described above, all forms of carrageenan can be obtained from seaweed extracts, typically as mixtures of two, three or more forms of carrageenan. The carrageenan mixture can be obtained as a crude extract or as a powder. In a further embodiment, the carrageenan utilized in the antiviral lubricating composition is obtained as carrageenan powder. Non-limiting examples of commercially-obtainable carrageenan powders include Viscarin® PC 109, Viscarin® PC 209, Viscarin® PC 515, Gelcarin® PC 379 and Gelcarin® PC 911. In yet a further embodiment, the carrageenan powder is Viscarin® PC 209.

In another embodiment, the carrageenan powder comprises at least about 85% by weight lambda-carrageenan, including at least about 90% by weight lambda-carrageenan.

In other embodiments, the kappa-carrageenan and iota-carrageenan together constitute up to about 15%, 10%, 8%, 6%, 4%, 2%, or up to about 1% by weight of the carrageenan powder. Including, it may contain up to about 20% by weight of carrageenan powder. In other embodiments, when present, kappa-carrageenan and iota-carrageenan together constitute at least about 2%, 4%, 6%, 8% or 10%, up to at least about 15% by weight of the carrageenan powder. It includes at least about 1% by weight of carrageenan powder, including.

In another embodiment, the carrageenan powder comprises at least about 90 weight percent lambda-carrageenan and up to about 10 weight percent iota-carrageenan. In a further embodiment, the carrageenan powder comprises about 90% lambda-carrageenan and about 10% iota-carrageenan by weight.

In another embodiment, the carrageenan powder comprises at least about 90% by weight of lambda-carrageenan and up to about 10% by weight of kappa-carrageenan. In a further embodiment, the carrageenan powder comprises about 90% lambda-carrageenan and about 10% kappa-carrageenan by weight.

In another embodiment, carrageenan mixtures comprising lambda-carrageenan are rendered substantially homogeneous in the antiviral lubricating composition, wherein a majority of the carrageenan polysaccharides in the composition exist as free molecules in an aqueous solvent. In a further embodiment, the carrageenan mixture is completely homogeneous within the antiviral lubricating composition. In some other further embodiments, the homogeneous antiviral lubricating composition has a substantially uniform appearance and density. In a still further embodiment, the antiviral lubricating composition is a solution having a substantially uniform ratio of carrageenan to solvent. In yet a further embodiment, the antiviral lubricating composition is substantially free of particles, agglomerates, lumps or other solids visible to the naked eye and/or under a microscope at 10X magnification. In a still further embodiment, the antiviral lubricating composition is translucent. In a still further embodiment, the antiviral lubricating composition is clear.

In another embodiment, the carrageenan is at least about 0.001% by weight of the antiviral lubricating composition, including at least about 0.01, 0.1, 0.5, 1, 2, 2.5 or 3%, up to at least about 5% by weight of the antiviral lubricating composition. contains %. In a further embodiment, carrageenan comprises from 0.5% to about 2.3% by weight of the antiviral lubricating composition. In yet a further embodiment, carrageenan comprises from 0.8% to about 2.0% by weight of the antiviral composition. In a still further embodiment, carrageenan comprises from 1.5% to about 1.7% by weight of the antiviral lubricating composition.

Similarly, the viscosity, rheology, sensation, and overall performance of lambda-carrageenan-containing, antiviral lubricating compositions can be adjusted by adding low concentrations of polymers, particularly polyols, to the antiviral lubricating compositions. As described above, polyols are a class of compounds commonly found in commercially-obtainable products as bulking agents, flavor-retaining/flavoring agents, humectants, stabilizers, anti-crystallizers, and systemic and oral health convenience agents. Although polyols are typically added to enhance the solubility of other polymers that may be present in commercial personal lubricant products, polyols can also be added in small amounts to the antiviral lubricating compositions of the present invention to reduce viscosity, reduce itching, and act as an agent of lubricity. 2 supply and/or provide a stimulating "warm" or "tingling" feeling that often delights the user during sexual activity.

Non-limiting examples of polyols that may be added may include: glycerol; propylene glycol (1,3-propanediol); 1,3-propanediol; 1,3-butanediol; 1,4-butanediol; 2,3-butanediol; xylitol; sorbitol; erythritol; isomalt; lactitol; maltitol; mannitol; polyethylene glycol; and polypropylene glycol; combination of them. In general, the identity and concentration of the polyol(s) included in the antiviral lubricating composition can be adjusted to obtain the desired properties. For example, mannitol and xylitol are regulated as food additives with special dietary requirements, whereas polyols are otherwise 'Generally Regarded as Safe' (GRAS). Xylitol is also used to prevent oral infections, and mannitol is used as a preventive measure against urinary tract infections. 1,3-butanediol, 1,4-butanediol, 2,3-butanediol have been shown to reduce irritation in topical application in ointments, creams and gel compositions. Sugar-based polyols can provide some sweetness, while maltitol can mimic the fat texture of edible products.

In other embodiments, the polyol is present in less than about 50% by weight of the antiviral lubricating composition, for example less than about 25, 15, 10, 9, 8, 7, 6, 5, 4, 3, or 2% by weight, about down to less than 1% by weight may be included in the antiviral lubricating composition. In still further embodiments, the antiviral lubricating composition comprises at least about 1% by weight, for example at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, or 25% by weight, e.g. for example, at least about 35% by weight of propylene glycol polyol. In an even further embodiment, the polyol comprises about 10.0% by weight of the antiviral lubricating composition.

In another embodiment, the polyol is propylene glycol (1,2-propanediol). In a further embodiment, the antiviral lubricating composition comprises up to 8% by weight of propylene glycol. In yet a further embodiment, the antiviral lubricating composition comprises from 0.5% to about 5% by weight of propylene glycol. In another embodiment, the antiviral lubricating composition comprises about 4% to about 5% by weight of propylene glycol. In another embodiment, the antiviral lubricating composition comprises about 4.0% to about 4.5% by weight of propylene glycol. In a further embodiment, the antiviral lubricating composition comprises about 2.0% to about 2.5% by weight of propylene glycol.

In another embodiment, the presence of a polyol results in an antiviral lubricating composition superior to known personal lubricating compositions, wherein such compositions also have the ability to inhibit the transmission and/or persistence of HPV, while still being comparable to those of commercially available personal lubricating agents. Because it retains all of its sexual performance advantages. Further, the antiviral lubricating composition is thin enough to provide the tactile benefits of a personal lubricant composition, but also thick enough to remain on the skin or epithelial tissue, particularly the vagina, anus, penis, or oral cavity, prior to initiating sexual contact. In some embodiments, the personal lubricant composition has a viscosity of less than about 10,000 cP, eg, less than about 8,000, 6,000, 4,000, or 2,000 cP, less than about 1,000 cP. In another embodiment, the antiviral lubricating composition has a viscosity of at least about 500 cP, eg, at least about 1,000, 2,000, 4,000, or 6,000 cP, and at least about 8,000 cP or less. In a further embodiment, the antiviral lubricating composition has a viscosity of about 500 cP to about 8,000 cP, particularly about 1,000 cP to about 4,000 cP, particularly about 2,000 cP to about 3,000 cP. In some embodiments, the antiviral lubricating composition has a viscosity of about 1,500 cP to about 2,500 cP. In some embodiments, the antiviral lubricating composition has a viscosity of about 2,000 cP.

In another embodiment, the amount of polyol in the antiviral lubricating composition is limited to provide an osmolality that is within WHO-recommended levels. In another embodiment, the antiviral lubricating composition is about 1,200 mOsmol/kg, including less than about 1000, 900, 800, 700, 600, 500, 400, 300 or 200 mOsmol/kg, including less than about 100 mOsmol/kg. It has an osmolality less than In a further embodiment, the antiviral lubricating composition has an osmolality of about 250 to about 800 mOsmol/kg. In yet a further embodiment, the antiviral lubricating composition has an osmolality of about 650 to about 850 mOsmol/kg.

In another embodiment, the osmolality of the antiviral lubricating composition is isosmolality with that of human plasma. In a further embodiment, the antiviral lubricating composition is iso-osmotic with seminal fluid. In yet a further embodiment, the antiviral lubricating composition is iso-osmotic with vaginal secretions. In a still further embodiment, the antiviral lubricating composition has an osmolality of about 250 mOsmol/kg to about 400 mOsmol/kg.

Additionally, in other embodiments, several supplemental ingredients may be added to the antiviral lubricating composition to supplement the antiviral activity of the composition and/or to enhance the performance of the composition during sexual intercourse. In some embodiments, the pH of the antiviral lubricating composition can be adjusted by adding a pH-adjusting agent. Typically, once the carrageenan is dissolved into the water, the pH of the composition is approximately 7 to 9. However, the efficacy of an antiviral lubricating composition can be compensated for by adjusting the pH of the composition to match or approximate the target surface to which the composition is applied. For example, the pH of a healthy vagina typically ranges from about 3.5 to about 5.5, whereas the pH of other epithelial cells, such as those located in the rectum, is closer to neutral pH. Thus, in some embodiments, the pH-adjusting agent adjusts the pH to a range that is complementary to the intended epithelial surface, particularly below about 8.0, such as about 7.0, 6.5, 6.0, 5.5, 5.0, 4.5, or less than 4.0, about It is an acid that can reduce the pH to less than 3.5. In other embodiments, the antiviral lubricating composition has a pH of at least about 3.5, such as at least about 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, or 7.0, at least about 8.0 or less. In a further embodiment, the pH of the antiviral lubricating composition is from about 3.5 to about 5.5, particularly about 4.5. In yet a further embodiment, the pH of the antiviral lubricating composition is from about 5.5 to about 7.0. In yet a further embodiment, the pH of the antiviral lubricating composition is from about 6.25 to about 6.75.

In some embodiments, the pH-adjusting agent is a strong acid, such as, but not limited to, hydrochloric acid or sulfuric acid. However, in other embodiments, the pH-adjusting agent is a weak acid, to create a buffered antiviral lubricating composition. A weak acid can be selected based on its buffering capacity, pKa, and availability. Non-limiting examples of weak acids that can be utilized as pH-adjusting agents may include citric acid, lactic acid, and acetic acid. In a further embodiment, the antiviral lubricating composition comprises from about 0.01% to about 1.0% by weight of a pH-adjusting agent, in particular from about 0.04% to about 0.06% by weight of a pH-adjusting agent. In a further embodiment, the pH-adjusting agent is citric acid.

In some embodiments, the antiviral lubricating composition may optionally further include one or more preservatives, which may be added to prevent microbial growth within the antiviral lubricating composition during storage. Any one or more of several preservatives may be selected from preservatives known to those skilled in the art, such as, but not limited to, one or more of the following: methylparaben, benzoic acid, salicylic acid, sorbic acid, propylparaben, and sodium dehydroacetate and combinations thereof. Preservatives may be present in the compositions of the present invention in an amount of up to about 1% by weight of the composition.

In some embodiments, the antiviral lubricating composition may optionally further include one or more sweetening agents that enhance the flavor of the composition when it comes into contact with the oral cavity of an individual. In some embodiments, the sweetener is an artificial sweetener, the presence of which may also inhibit bacterial growth in the antiviral lubricating composition during storage. Non-limiting examples of artificial sweeteners include, but are not limited to, aspartame, saccharin, sucralose, neotame, and acesulfame potassium. In a further embodiment, the sweetening agent is saccharin. In a further embodiment, the antiviral lubricating composition further comprises up to about 0.005% by weight of saccharin. In a further embodiment, the antiviral lubricating composition comprises about 0.125% by weight of saccharin.

In addition to or instead of a sweetener, the antiviral lubricating composition may optionally further contain other flavoring agents or flavoring agents capable of masking the odor of the composition itself or of the skin or epithelial tissue to which the antiviral lubricating composition is applied. Any essential oil-based flavor may be selected, but non-limiting examples of such flavors include vanilla, lavender, oregano, thyme, lemongrass, lemon, orange, anise, clove, fennel seed. ), cinnamon, geranium, rose, mint, peppermint, citronella, eucalyptus, sandalwood, cedar, rosmarin, pine, vervain flaregrass ( vervain fleagrass), or ratanhiae, and combinations thereof. In another embodiment, the antiviral lubricating composition may optionally further include one or more chemical, aroma-inducing compounds that impart an odor or aroma within the essential oil-based perfume. Non-limiting examples of chemical, aroma-inducing compounds that can be included in any antiviral lubricating composition are carvacrol, eugenol, linalool, thymol, p-cymene ( cymene), myrcene, borneol, camphor, caryophillin, cinnamaldehyde, geraniol, nerol, citronellol, and menthol, and and combinations thereof.

In some embodiments, the antiviral lubricating composition may optionally further include one or more metal salts. Addition of a metal salt can have several effects, such as control of the ionic strength of the composition, enhancement of its antimicrobial or antiviral activity, or addition of one or more components upon solubilization. Metal salts that may be added include, but are not limited to, zinc, silver, copper, alkali, or alkaline earth metal salts. In a further embodiment, the metal salt is a zinc salt or sodium salt.

In some embodiments, the antiviral lubricating composition may optionally further include one or more pharmaceutical antiviral, antifungal, or antimicrobial compounds.

Additionally, the present invention also relates to the sexually transmitted, including but not limited to, HPV, HIV and HSV between two or more partners engaging in sexual activity using antiviral lubricating compositions made by the methods described below. -Provides several methods to reduce, suppress or ameliorate the transmission of contagious viruses. In a first embodiment, the method comprises contacting the antiviral lubricating composition with the skin or epithelial tissue of one or more of the partners, wherein the skin or epithelial tissue is on or in at least one of the vagina, anus, mouth, or penis. located inside it As used herein, the term “vagina” includes the skin or epithelial tissue located within and/or around the vagina, including but not limited to the vulva, labia, clitoris, vaginal opening, and cervix. In a further embodiment, at least one partner is male and at least one partner is female. In yet further implementations, at least two of the partners are male. In a still further embodiment, at least two partners are female.

In another embodiment, the antiviral lubricating composition is applied to the skin prior to sexual activity, particularly to one or more sexual partners, to prophylactically inhibit transmission of HPV, HIV, and HSV, including but not limited to, from one sexual partner to another. It may be contacted with the partner's skin, in particular the skin on or within at least one of the vagina, anus, globe, or penis. In such embodiments, the antiviral lubricating composition is applied to the skin of one or more sexual partners for about 8 hours, 4 hours, 2 hours, 1 hour, 30 minutes, 15 minutes, 5 minutes, 1 minute, or about 30 seconds prior to sexual activity. Less than 1 second prior to sexual activity. In other embodiments, the antiviral lubricating composition is applied to the skin of one or more sexual partners for at least about 30 seconds, 1 minute, 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, or about 8 hours prior to sexual activity. time can be contacted.

In another embodiment, the antiviral lubricating composition is used to prevent cell-to-cell spread of sexually-transmitted viruses, including but not limited to HPV, HIV and HSV, after HPV is transmitted through skin-to-skin contact. skin, in particular located on or inside at least one of the vagina, anus, mouth or penis of one or more of the sexual partners after sexual activity to reduce In such embodiments, the antiviral lubricating composition is administered less than about 8 hours, 4 hours, 2 hours, 1 hour, 30 minutes, 15 minutes, 5 minutes, 1 minute, or about 30 seconds after sexual activity, or less than about 1 second after sexual activity. May come into contact with the skin of one or more of the sexual partners. In other embodiments, the antiviral lubricating composition is applied to one of the sexual partners at least about 30 seconds, 1 minute, 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours or about 8 hours after sexual activity. It may come in contact with more than one skin.

In another embodiment, methods for reducing, inhibiting or ameliorating the transmission of sexually-transmitted viruses, including but not limited to HPV, HIV and HSV between two or more partners engaging in sexual activity, include one or more cutaneous - providing a substrate comprising contact surfaces, wherein the substrate is configured to be inserted into one or more body cavities selected from the group consisting of the vagina, mouth or anus; lubricating one or more of the skin-contacting surfaces of the substrate with an antiviral lubricating composition, thereby creating a lubricated substrate; contacting the lubricated substrate with skin or epithelial tissue located on or within at least one of the vagina, anus, mouth, or penis of one or more of the partners; and delivering the antiviral lubricating composition from the lubricated substrate to the skin or epithelial tissue. In some further embodiments, only one person, male or female, uses the device during sexual activity. In yet further embodiments, two or more partners use the substrate, wherein any one of the sexual partners may be male or female.

Substrates suitable for use with the methods of the present invention include any object, device, or accessory that can be used to contact an internal or external surface on or within the vagina, anus, oral cavity, or penis during sexual activity. Non-limiting examples of substrates that may be utilized in accordance with the methods of the present invention include, but are not limited to, condoms; rubber, latex, plastic, wood, and/or metal; sexual accessory devices such as masturbation devices, penis substitutes, vibrators, rings, and beads; and internal applicators. Examples of this include U.S. Patent Nos. 6,983,751 and 9,119,763; US Design Patent No. D599486, and US Patent Publication No. 2006/0178602, the disclosures of which are incorporated by reference in their entirety. One of ordinary skill in the art can appreciate that there are countless other examples of substrates, both commercially available and extemporaneous, sexually themed or otherwise, that can be utilized during sexual activity and to which the antiviral lubricating composition of the present invention can be applied.

In another embodiment, the substrate is a condom. As used herein, the term “condom” includes devices designed to be worn by a man or woman in or over the penis, vagina, anus, or fingers. Condoms can also be applied over the sexual aids described below. The antiviral lubricating composition is placed on at least one of the inner surface of the condom or the outer surface of the condom prior to or after placement of the condom on or within the penis, finger(s), vagina, anus, oral cavity, or other body part or object. It can be applied to any skin contact surface. In a further embodiment, a condom pre-lubricated with any of the antiviral lubricating compounds of the present invention may be provided in packaging that surrounds the lubricated condom and seals it from the external environment outside the packaging. In an even further embodiment, the packaging includes a watertight seal, such that the packaging is opened and a pre-lubricated condom or similar sexual accessory device is applied over the penis and loss of the antiviral lubricating composition prior to engaging in sexual activity. to prevent Methods of lubricating and packaging a condom so that it is protected from the external environment prior to use during sexual activity are well known in the art.

In some embodiments in which condoms are described, methods for reducing, inhibiting, improving or preventing the transmission of sexually-transmitted viruses, including but not limited to HPV, HIV and HSV, between partners engaging in sexual activity include: It further comprises the following steps: lubricating the skin-contacting surface of the condom; contacting skin or epithelial tissue within the mouth, vagina or anus of one or more of the partners with the lubricated skin-contacting surface of the condom; and delivering the antiviral lubricating composition from the lubricated skin-contacting surface of the condom to the skin or epithelial tissue.

In a further embodiment wherein the substrate is a condom, for reducing, inhibiting or ameliorating transmission of sexually-transmitted viruses including but not limited to HPV, HIV and HSV between two or more partners engaging in sexual activity. The methods further include the steps of: placing the condom over one partner's finger or penis; lubricating the outer surface of the condom with an antiviral lubricating composition; contacting skin or epithelial tissue within the mouth, vagina, or anus of one or more additional partners using the lubricated outer surface of the condom; and delivering the antiviral lubricating composition from the lubricated outer surface of the condom to the skin or epithelial tissue.

In yet further embodiments wherein the substrate is a condom, reducing, inhibiting or ameliorating transmission of sexually-transmitted viruses including but not limited to HPV, HIV and HSV between two or more partners engaging in sexual activity. The methods for doing this further include: lubricating the condom; sealing the lubricated condom within the package; storing the lubricated condom within the package; removing the lubricated condom from the packaging; applying the lubricated condom to the finger or penis of one of the sexual partners; contacting the skin or epithelial tissue in the mouth, vagina or anus of one or more additional partners using a lubricated condom; and delivering the antiviral lubricating composition from the lubricated condom to the skin or epithelial tissue.

In another embodiment, the substrate is an internal applicator. Internal applicators suitable for use with the methods of the present invention include any object, appliance, or accessory that can be configured to be inserted into a body cavity of an individual and capable of delivering an antiviral lubricating composition to epithelial tissue within the body cavity of an individual. may be included. Non-limiting examples of internal applicators that may be utilized in accordance with the method of the present invention include materials including but not limited to rubber, latex, plastic, wood and/or metal, including syringes, pipettes, Swabs, conduits, elongated rods or rods and wearable inserts are included. These examples are U.S. Patent No. 2,546,754, 4,557,720, 4,808,166, 6,503,220, 6,537,260, 7,442,179, 7,591,808, 9,290,551, 9,757,549 and 9,884,173, the details of which are incorporated by reference in their entirety. For those of ordinary skill in the art, the antiviral lubricating composition of the present invention can be applied and commercially available, which can be brought into contact with the skin or inserted into a body cavity to deliver the antiviral lubricating composition to the epithelial tissue within the body cavity. It can be appreciated that there are countless other examples of internal applicators designed for this purpose.

In another embodiment, the internal applicator comprises a skin-contacting surface configured to contact epithelial tissue within a body cavity of an individual, particularly within the vagina or rectum. In another embodiment, the internal applicator comprises a container configured to contain or contain the antiviral lubricating composition prior to delivery of the antiviral lubricating composition onto epithelial tissue within a body cavity of an individual. In either case, the internal applicator may be provided in a package with or without the antiviral lubricating composition. In a further embodiment, the internal applicator is pre-lubricated with the antiviral lubricating composition and sealed within the package, protecting the lubricated internal applicator from the external environment and loss of the antiviral lubricating composition prior to delivery to the epithelial tissue in the body cavity of the individual. this is prevented Methods for applying lubricants or curative substances to internal applicators and for packaging internal applicators are known to those skilled in the art.

In another embodiment, the present invention also provides methods for reducing, inhibiting or ameliorating transmission, symptoms or effects of a virus not associated with sexual activity. The methods include the following steps: (a) providing any of the above antiviral lubricating compositions and (b) skin where a viral infection is known or suspected to exist inside or outside the body. or contacting epithelial tissue. The antiviral lubricating composition may be applied to the skin or epithelial tissue using a human finger or any of the applicators described above. In another embodiment, a lubricated swab, rod or wand can be inserted into any of the body cavities described above, including the mouth and nose as well, and brought into contact with epithelial tissue in the nasal cavity or throat.

Non-limiting examples of taxonomic families of viruses that can be treated with any of the antiviral lubricating compositions of the present invention include Orthomyxoviridae, Paramyxoviridae, Pneumoviridae, Coronaviridae, Retroviridae, Herpesviridae, Papilloma Viridae, Picornaviridae, Reoviridae and Adenoviridae and combinations thereof are included. Such viruses within these taxonomic families include, but are not limited to: severe acute respiratory disease (SARS) strains 1 and 2 (COVID-19); influenza A, B and C; Enterovirus, rhinovirus, poliovirus, adenovirus, rotavirus and the viruses that cause measles, mumps and chickenpox. In another embodiment, the antiviral lubricating composition can be applied to the skin or epithelium of a person suffering from a viral infection or as a prophylactic to prevent viral infection. In another embodiment, the antiviral lubricating composition can be applied to the skin or epithelium of an animal suffering from a viral infection or as a prophylactic to prevent viral infection.

Processing of antiviral lubricating compositions

Antiviral lubricating compositions made by the method of the present invention are such that these compositions have the ability to inhibit viral activity, including the viral activity of sexually-transmitted viruses such as HPV, HIV and HSV, and that these compositions during sexual activity They are unique in that they have optimized viscosity, lubricity and feel that improve their performance as lubricants while at the same time minimizing the osmolality of the composition. In one embodiment of the present invention, the methods for forming the antiviral lubricating compositions of the present invention may include the following steps: (a) providing a carrageenan powder comprising carrageenan, wherein the carrageenan is at least about comprising 90% by weight lambda carrageenan and up to about 10% by weight iota carrageenan; (b) while mixing, combining the carrageenan powder with an aqueous solution comprising a polyol to form a turbid carrageenan suspension; and (c) heating the turbid carrageenan suspension to a temperature of at least 60° C. and mixing for a time sufficient to transform the turbid carrageenan suspension into a clarified homogeneous solution, thereby forming an antiviral lubricating composition; wherein (i) the antiviral lubricating composition comprises from about 0.5% to about 2.3% by weight carrageenan and up to about 10% polyol; (ii) the antiviral lubricating composition has a viscosity of less than about 5,000 cP; (iii) the antiviral lubricating composition is translucent; and (iv) the antiviral lubricating composition has a turbidity of less than 25 turbidimetric turbidity units (NTU).

In another embodiment, the method for forming the antiviral lubricating compositions of the present invention may further include a pre-mixing step wherein the carrageenan powder and polyol are first combined to form a wet carrageenan mixture comprising carrageenan and polyol. . Without being bound by any particular theory, pre-mixing and dispersing the carrageenan powder in the polyol prior to adding the water causes the carrageenan polysaccharides to partially dissolve, allowing further polarizable contacts to interact with the addition of the aqueous solution. It is considered to be Pre-mixing is believed to have several advantages including, but not limited to: mixing under low speed and lower shear conditions; homogenizing the carrageenan in an aqueous solution by heating at lower temperatures; accelerating each mixing step, especially mixing to homogenize the carrageenan in the aqueous solution; and preventing carrageenan polysaccharides from breaking down into smaller fragments that can negatively affect the viscosity and performance of the composition as a personal lubricant (see below). In a further embodiment, the method for forming the antiviral lubricating compositions of the present invention may include the following steps: (a) providing a carrageenan powder comprising carrageenan, wherein the carrageenan is at least about 90% lambda-carrageenan % by weight and up to about 10% iota-carrageenan; (b) mixing carrageenan powder with a polyol to form a wet carrageenan mixture, wherein the weight ratio of glycol to carrageenan is from about 1:1 to about 10:1; (c) while mixing, combining the wet carrageenan mixture with the aqueous solution to form a cloudy carrageenan suspension, wherein the volume ratio of the aqueous solution to carrageenan is from about 45:1 to about 8:1; (d) heating the turbid carrageenan suspension to a temperature of at least 60° C. and mixing for a time sufficient to transform the turbid carrageenan suspension into a clarified and homogeneous solution, thereby forming an antiviral lubricating composition; wherein (i) the antiviral lubricating composition comprises from about 0.5% to about 2.3% carrageenan and up to about 10% polyol by weight; (ii) the antiviral lubricating composition has a viscosity of less than about 5,000 cP; (iii) the antiviral lubricating composition is translucent; and (iv) the antiviral lubricating composition has a turbidity of less than 25 NTU.

In particular, the viscosity of an antiviral lubricating composition is an important factor in the composition's performance as a personal lubricant that can be used in conjunction with sexual activity. Ideally, personal lubricants have a viscosity thick enough to be applied onto the skin or epithelial tissue and remain where applied until sexual activity is initiated, while also providing lubricity and moisture from the composition over the duration of the entire sexual activity. It has a rheological profile that can be maintained over The presence of carrageenan in the composition typically contradicts sexual lubricant performance as the viscosity of the composition increases exponentially as a function of carrageenan concentration (see Example 3 below).

Similarly, the viscosity of an antiviral lubricating composition is sensitive to the balance of several factors in addition to the total carrageenan concentration, including but not limited to: the identity of the kappa-, iota- and lambda-forms of carrageenan; relative concentration; concentration and identity of further components, in particular polyols; and, if present, a weight ratio of carrageenan to polyol. Additionally, the viscosity also depends on the processing steps themselves including but not limited to: heating one or more of the carrageenan mixture, carrageenan suspension and/or antiviral lubricating composition; rate of addition of any of the composition ingredients; speed and duration of any of the mixing steps; and the type of rotor used for mixing. In summary, all of the above factors must be adjusted to optimize the performance of antiviral lubricant compositions during sexual activity.

In another embodiment, not only is the viscosity of the antiviral lubricating composition not dependent on the total carrageenan concentration, but also the relative concentrations of the kappa-type, iota-type and lambda-types of carrageenan are dependent on the geometry of the viscosity of the antiviral lubricating composition. Differentially affects the rate of exponential growth. As an example, the presence and increasing concentration of kappa-carrageenan increases the viscosity of the composition most rapidly, while the rate of exponential growth due to the presence and increasing concentration of iota-carrageenan is greater than that of kappa-carrageenan. The low, exponential rate of growth due to the increase in the presence and concentration of lambda-carrageenan is lower than both kappa-carrageenan and iota-carrageenan. Thus, a lambda-carrageenan-dominant composition will have a lower viscosity than a kappa-carrageenan and/or iota-carrageenan-dominant composition. As a result, and as described above, the antiviral lubricating composition of the present invention may comprise at least about 90% lambda-carrageenan and up to about 10% either or both kappa-carrageenan or iota-carrageenan. . In yet a further embodiment, the antiviral lubricating composition comprises about 90% lambda-carrageenan and about 10% kappa-carrageenan. In a still further embodiment, the antiviral lubricating composition comprises about 90% lambda-carrageenan and about 10% lambda-carrageenan.

Additionally, the physical form from which the carrageenan mixtures are obtained also influences how the carrageenan mixtures are to be processed. When carrageenan is obtained as crude extracts, the carrageenan is already present mainly in a liquid state. However, the shelf life of crude carrageenan extracts is typically reduced compared to solid powders, and carrageenan extracts can contain unwanted or even harmful ingredients. Thus, while it is common to obtain dried carrageenan in powder form for use in the food or pharmaceutical industry, there is a trade-off that the carrageenan must be re-dissolved in order to be available as a liquid composition.

In applications where carrageenan is ultimately used as a thickening agent, carrageenan powders can often simply be dissolved by high-shear and high-speed mixing conditions for long periods of time under intense heating conditions. However, carrageenan powder is an antiviral lubricating composition of the present invention, as these conditions cause the resulting composition to lose its lubricity over time, particularly as it undergoes the shear-thinning stress that occurs during sexual activity. They cannot be processed in the same way to make them. Without being bound by any particular theory, it is believed that the length of the carrageenan polysaccharide directly correlates to the lubrication and moisture of the resulting composition. As the average length of the polysaccharide increases, the lubricity of the composition also increases. On the other hand, dissolving carrageenan powder under high-shear and high-stress conditions results in premature drying of the resulting composition.

In another embodiment, dissolution of the carrageenan powder may be assisted by the addition of a polyol to the powder. As described above, polyols are commonly included in personal lubricant compositions because the presence of polyols has satisfactory properties during sexual activity. The multiple hydroxyl groups within each polyol molecule have additional advantages because they provide intermolecular contacts with individual sugars within the larger carrageenan polysaccharide with which these hydroxyl groups can interact in solution. Without being limited by any other theory, as the amount of polyol mixed with the carrageenan powder to form the wet carrageenan mixture increases, the number of polar functional groups within each carrageenan polysaccharide that is capable of interacting and dissolving in the aqueous solvent also increases. increase, leading to a simultaneous increase in the viscosity of the antiviral lubricating composition.

Conventional antiviral lubricant compositions comprising polyols with lambda-carrageenan lubricant compositions were synthesized by simply adding carrageenan powder to a bulk solvent containing greater than 37% by weight of propylene glycol (see Example 1 below). At these concentrations, the propylene glycol concentration causes an unsafe increase in the osmolality of the composition. However, it was determined that simply reducing the polyol concentration in the solvent did not achieve complete homogenization of the carrageenan powder even when heated to a maximum of 75°C. Instead, a plurality of “watertight” masses were formed comprising dry carrageenan powder surrounded by semi-hydrated carrageenan molecules that could not penetrate with the addition of water. In the '098 patent (described above), a similar phenomenon was observed for dry powders even simply exposed to water-containing atmospheric conditions.

In some embodiments, methods for forming antiviral lubricating compositions of the present invention may include a first step of mixing carrageenan powder with at least one polyol to form a wet carrageenan mixture prior to addition of carrageenan. In a further embodiment, first dissolving the carrageenan powder in a polyol facilitates complete homogenization of the carrageenan polysaccharides in the antiviral lubricating composition.

Additionally, the identity of the polyol and the weight ratio of polyol to carrageenan also affect the viscosity of the antiviral lubricating composition. As a non-limiting example, 1,2-propanediol is approximately 50 times more viscous than water, while glycerol is approximately 23 times more viscous than 1,2-propanediol. Thus, the antiviral lubricating composition may contain a greater concentration of 1,2-propanediol than the second composition comprising glycerol, while having the same viscosity. As a result and in other embodiments, the weight ratio of polyol to carrageenan in the wet carrageenan mixture is at least 1:5, 1:1, 2:1, 4:1, 6:1, 8:1, 10:1, 20: 1, 30:1 or 40:1, up to at least 1:10, including at least 50:1. In a further embodiment, the weight ratio of polyol to carrageenan is from about 1:1 to about 10:1. In yet a further embodiment, the polyol is 1,2-propanediol.

Similarly, the weight ratio of the aqueous solution mixed with the wet carrageenan mixture to form the carrageenan suspension also affects the viscosity of the antiviral lubricating composition. In some embodiments, as the weight ratio of aqueous solution to wet carrageenan mixture increases, the viscosity of the antiviral lubricating composition decreases. In a further embodiment, the weight ratio of the aqueous solution mixed with the wet carrageenan mixture to form the carrageenan suspension is from about 3:1 to about 60:1. In yet a further embodiment, the weight ratio of the aqueous solution mixed with the wet carrageenan mixture to form the carrageenan suspension is from about 8:1 to about 45:1.

In another embodiment, heating of one or more of the wet carrageenan mixture, carrageenan suspension and/or antiviral lubricating composition enables dissolution and homogenization of the carrageenan in water. Without being limited by any particular theory, it is believed that heating the carrageenan causes at least partial loosening of each carrageenan polysaccharide as well as disruption of the intermolecular interactions between the polysaccharides, both of which increase the viscosity of the composition. As heating continues, the carrageenan polysaccharides begin to dissolve in the aqueous solution, reducing the viscosity and forming a homogeneous antiviral lubricating composition. However, if the composition continues to be heated after all the carrageenan has been homogenized, the viscosity of the composition may continue to decrease and the polysaccharide itself may dissociate into smaller oligosaccharides with lower molecular weight and chain length. In a further embodiment, the carrageenan suspension is heated until an antiviral lubricating composition having a viscosity of less than about 5,000 cP is formed. In yet a further embodiment, the carrageenan suspension is heated until an antiviral lubricating composition having a viscosity of about 1,000 cP to about 4,000 cP is formed.

Compositions comprising unhomogenized carrageenan, such as carrageenan suspensions, are typically hazy, hazy or turbid and contain numerous carrageenan particles visible to the naked eye. Without being limited by any particular theory, it is believed that the turbidity of a carrageenan suspension is the result of aggregate formation between two or more carrageenan polysaccharides before the carrageenan polysaccharides are completely dissolved and exposed to an aqueous solvent. In another embodiment, the carrageenan suspension is heated until a translucent antiviral lubricating composition is formed. In a further embodiment, the carrageenan suspension is heated until a clear antiviral lubricating composition is formed. Within this embodiment, the translucent and/or transparent properties of the antiviral lubricating composition are maintained even after packaging and/or storage for extended periods of time. In yet a further embodiment, there are substantially zero particles, agglomerates or agglomerates visible in the antiviral lubricating composition. In another embodiment, the fully homogenized antiviral lubricating composition is a solution.

The turbidity of any of the mixtures, suspensions or antiviral lubricating compositions described herein can be described quantitatively based on a method for determining the concentration of suspended particles in a sample, including but not limited to: Formazine turbidity units (FNU), Jackson turbidity units (JTU), NTU, optical density, Helms Units, parts per million (PPM), etc. FNU and NTU are widely used to describe the haze of a composition with uniformly distributed small particles and is determined by measuring the amount of light scattered at 90° relative to the incident light flux. In particular, NTU is measured using visible light, typically from about 400 nm to about 680 nm, as the incident luminous flux, whereas FNU is measured using infrared light, typically from about 780 nm to about 900 nm, as the incident luminous flux.

In another embodiment, the turbidity of any of the mixtures, suspensions or antiviral lubricating compositions described herein is characterized as a function of NTU. In a still further embodiment, the turbidity of the carrageenan suspension resulting from the addition of carrageenan to the aqueous solution is at least about 200, 300, 400, 500, 600, 700, 800, 900, 1000, 2000 or 3000 NTU, up to at least about at least about 100 NTU, including 4000 NTU. In still further embodiments, the homogenized antiviral lubricating composition has a turbidity of about 25 NTU, including less than about 20, 15, 10, 8, 6, 5, 4, 3 or 2 NTU, including less than about 1 NTU. is less than In a still further embodiment, the homogenized antiviral lubricating composition has a turbidity of about 5 NTU or less.

In another embodiment, an antiviral lubricating composition prepared by the method of the present invention, particularly an antiviral lubricating composition that may come in contact with the mouth during sexual activity, is homogenized until the composition has a turbidity approximately equal to that of drinking water. can Governments, health organizations, and other regulatory agencies have outlined safety standards for protecting humans and animals from potentially dangerous health conditions caused by agents that increase the turbidity of solutions, including but not limited to: polymers and other macromolecules; insoluble small molecules; and bacteria and other microorganisms. WHO has determined that drinking water should not exceed 5 NTU, ideally less than 1 NTU. In the United States, systems utilizing conventional or direct filtration are required to reduce drinking water turbidity to less than 1 NTU, and some jurisdictions are working to achieve turbidity levels of less than 0.1 NTU.

In another embodiment, the type of mixing device, rotation speed and mixing time can be optimized to control the viscosity of the resulting antiviral lubricating composition and to disperse and homogenize the carrageenan into the aqueous solution. In some embodiments, the mixing is prolonged and sufficient to homogenize the composition while preserving the length of each carrageenan polysaccharide and to maintain lubricity of the composition, particularly prior to application of the composition to the skin or epithelial tissue prior to or in conjunction with sexual activity. It may be performed under low-shear conditions for a period of time. In contrast, and in other embodiments, mixing can be performed under high-shear conditions for a minimum amount of time, however, mixing that exceeds the minimum amount of time irreversibly destroys the carrageenan polysaccharides, reduces the viscosity of the composition, and It can reduce the performance of the composition as a lubricant during activity. Non-limiting examples of mixers include, but are not limited to, screw mixers, tumble mixers, ribbon mixers, and paddle mixers. In yet a further embodiment, a paddle mixer may be used for each of the mixing steps to form the antiviral lubricating composition. Similarly, mixing at relatively low speeds also maintains the structural integrity of each polysaccharide. In yet further embodiments, each of the mixing steps is performed at a mixing speed of about 500 RPM or less. In yet a further embodiment, mixing of the antiviral lubricating composition after homogenizing the carrageenan in the aqueous solution may occur at a rate of about 250 RPM or less.

In other embodiments, the method for forming the antiviral lubricating composition may further include several steps, including the steps of: (e) until the temperature of the antiviral lubricating composition is less than about 30°C. cooling the homogenized antiviral lubricating composition; (f) mixing into the cooled antiviral lubricating composition one or more pH-adjusting agents by weight sufficient to adjust the pH of the antiviral lubricating composition from about 3.5 to about 7.0; (g) optionally mixing one or more sweeteners into the carrageenan suspension or cooled antiviral lubricating composition, optionally up to 0.5% by weight of the antiviral lubricating composition; and (h) optionally mixing one or more preservatives into the carrageenan suspension or cooled antiviral lubricating composition, optionally up to 1% by weight of the antiviral lubricating composition. In a further embodiment, each of the additional ingredients such as salts and/or flavoring agents as well as the pH-adjusting agents, sweeteners and preservatives described above are included in the antiviral lubricating composition to supplement the anti-HPV activity of the composition and/or It can enhance the performance of the composition during sexual activity. The composition properties as a result of the addition of pH-adjusting agents, sweetening agents and preservatives are described above.

In another embodiment, the methods described above can be utilized to homogenize carrageenan mixtures having different lambda-carrageenan, kappa-carrageenan and iota-carrageenan ratios to any desired viscosity into an aqueous solvent. In some embodiments, the lambda-carrageenan comprises at least about 50% by weight of the carrageenan powder, including at least about 60 or 70%, up to about 80% by weight of the carrageenan powder. In other embodiments, lambda-carrageenan may comprise less than about 85, 80 or 70%, up to less than about 60% by weight of the carrageenan powder. In this embodiment, the amounts of kappa-carrageenan and iota-carrageenan, if present, together comprise up to 40%, up to 30%, or up to 20% by weight of the carrageenan powder. This can be increased to include up to about 50% by weight of the carrageenan powder.

While specific embodiments of the invention have been described, the invention may be further modified within the spirit and scope of its disclosure. Those skilled in the art will recognize, or be able to ascertain using no more than routine examination, many equivalents to the specific procedures, embodiments, claims, and examples described herein. Accordingly, such equivalents are considered to be within the scope of this invention, and therefore this application is intended to cover any variations, uses or adaptations of this invention using its general principles. Further, it is intended that the present invention cover such departures from the present disclosure as come within known or customary practice in the art to which this invention pertains and which fall within the scope of the appended claims.

For clarity, it is recognized that certain features of the invention that are described in the context of separate embodiments may also be provided in conjunction with a single embodiment. Conversely, for brevity, various features of the invention that have been described in the context of a single embodiment can also be provided separately or in any suitable sub-combination or as suitable in any other described embodiment of the invention. Certain features that are described in the context of various implementations should not be considered essential features of such implementations unless the implementation operates without those elements.

The contents of all references, patents, and patent applications mentioned herein are incorporated herein by reference and are not to be construed as an admission that such references are available as prior art to the present invention. All of the publications and patent applications included herein are indicative of the level of skill in the art to which this invention pertains and are incorporated to the same extent as if each individual publication or patent application had been specifically indicated and individually indicated by reference.

The present invention is further illustrated by the following working and predictive examples, none of which are to be construed as limiting the present invention. Also, to the extent paragraph headings are used, they should not be construed as necessarily limiting. Any use of the past tense to describe an embodiment otherwise indicated as constructive or predictive is not intended to reflect that the constructive or predictive embodiment has actually been performed.

Example

The following working and predictive examples represent the presently best known implementations of the present invention. However, it should be understood that the following is merely illustrative or explanatory of the application of the principles of the present invention. Numerous modifications and alternative compositions, methods, and systems can be devised by those skilled in the art without departing from the spirit and scope of the present invention. Thus, while the present invention has been described above in particular, the following examples provide additional detail in relation to what is presently considered to be the most practical and preferred embodiment of the present invention.

working example

Example 1: Preparation of high-osmolality personal lubricant composition

The following antiviral lubricating composition was prepared according to the process used to manufacture the commercially available product of lambda-carrageenan-based personal lubricant, Divine 9®:

ingredient

55.70% (w/w) deionized water

37.40% (w/w) propylene glycol

2.5% (w/v) sodium saccharin solution in 5.00% (w/w) deionized water

1.40% (w/w) Viscarin® PC 209 carrageenan powder

0.04% (w/w) citric acid

0.01% (w/w) sodium hydroxide

0.95% (w/w) GeoGard ECT Preservative (Lonza Consumer Care)

0.03% (w/w) GeoGard 111 - Sodium Dehydroacetate Preservative (Lonza Consumer Care)

All ingredients except Viscarin® PC 209 carrageenan powder were combined and thoroughly mixed together. With constant mixing, the composition was then gradually heated to 75°C. When the composition reached 50° C., the Viscarin® PC 209 carrageenan powder was gradually mixed until all of the carrageenan powder was added. The composition was continuously mixed at 75° C. for about 2 hours until all of the Viscarin®-PC 209 carrageenan powder was dissolved. Upon dissolution of the carrageenan powder, mixing was stopped and the composition cooled rapidly. When the temperature of the composition reached 30°C, citric acid was added to bring the pH to about 6.5, +/- 0.25.

Example 2: Preparation of low-osmolality antiviral lubricating composition

The following antiviral lubricating composition was prepared according to an embodiment of the present invention and the following procedure:

ingredient

88.49% (w/w) deionized water

4.40% (w/w) 1,2-propanediol

5% (w/w), 2.5% (w/v) sodium saccharin solution in deionized water

1.60% (w/w) Viscarin® PC 209 carrageenan powder

0.05% (w/w) citric acid

0.32% (w/w) 2-phenoxyethanol

0.11% (w/w) chlorphenesin

0.03% (w/w) GeoGard 111 - Sodium Dehydroacetate Preservative (Lonza Consumer Care)

Viscarin® PC 209 carrageenan powder and 1,2-propanediol were mixed for approximately 10 minutes using a Mixer Direct R-AD665 industrial gallon paddle mixer with two collapsible impeller blades operating at 500 RPM to form a wet carrageenan mixture. did After 10 minutes, no agglomerated particles of powder were observed in the wet carrageenan mixture. With continued mixing, approximately 90% by volume of water and all of the saccharin was added to the wet carrageenan mixture over an additional 5 minutes to form a cloudy carrageenan suspension. The carrageenan suspension was heated to 70° C. and allowed to mix under the same mixing conditions until the carrageenan powder was completely homogenized in water. After about 90 minutes, homogenization was achieved by switching from a turbid suspension to a clarified solution. Mixing was continued for another 10 minutes after homogenization had occurred. The mixer was paused and the composition cooled to less than 30°C. Once cooled, preservatives, citric acid and remaining water were added to the composition while mixing at 250 RPM for 20 minutes. The resulting antiviral lubricating composition was translucent and had a pH of about 6.5±0.25.

Example 3: Exponential Effect of Carrageenan Concentration on Composition Viscosity

To evaluate the effect of carrageenan on the viscosity of antiviral lubricating compositions, several compositions were formulated at various concentrations of carrageenan. The first sample, Sample V1, was prepared according to the same component specifications and procedures as the composition of Example 1. Using the procedure of Example 2, additional antiviral lubricating compositions (Samples V2-Samples V5) having different concentrations of carrageenan were prepared. The volume of water added was adjusted as needed. The final volume of each sample composition was 200 ml. The carrageenan concentrations and viscosities of each sample are provided in Table 2 below.

Each viscosity measurement was made using a Brookfield LVF Dial Reading Viscometer using the #2 shaft at 12 revolutions per minute, according to the instructions provided with the instrument. The relationship between the viscosity of an antiviral lubricating composition as a function of carrageenan concentration is shown in FIG. 1 . Fitting the data to an exponential model using Microsoft Excel gives a trend line with an R ² value of 0.994, indicating a strong correlation between the data and the model.

Example 4: Linear effect of 1,2-propanediol on composition osmolality

To evaluate the effect of 1,2-propanediol on the osmolality of antiviral lubricating compositions, several compositions were formulated at various concentrations of 1,2-propanediol. The first sample, Sample 01, was prepared according to the same ingredient specifications and procedures as the composition of Example 1. Using the procedure of Example 2, additional antiviral lubricating compositions (Samples O2 to O5) with different concentrations of 1,2-propanediol were prepared. The volume of water added was adjusted as needed. The final volume of each sample composition was 50 ml. The concentrations and osmolality of 1,2-propanediol of each sample are provided in Table 3 below.

Each osmotic pressure measurement was performed with an osmometer capable of measuring freezing point depression according to the standard protocol of the United States Pharmacopeial Convention (see USP <785>, Osmolality and Osmolarity , 2017). The relationship between osmolality of an antiviral lubricating composition as a function of 1,2-propanediol concentration is shown in FIG. 2 . Fitting the data to a linear model using Microsoft Excel produced a trend line with an R ² value of 0.9974, indicating a strong correlation between the data and the model.

Predictive Examples

Example 5: Characterization of disaccharide content of antiviral lubricating compositions

Carrageenan in HPMC Capsules by LCMS," American Association of Pharmaceutical Scientists Poster Submission, 2018년 5월 3일자 http://abstracts.aaps.org/Verify/AAPS2017/PosterSubmissions/M8109.pdf에서 인터넷으로부터 수득함)을 포함하나, 이에 한정되지 않는, 수개의 분석 기술에 의해 측정될 수 있다.Each initial form of carrageenan has a different repeating disaccharide structure, and iota-carageenan is an alternative to D-galactaose-4-sulfate and 2-sulfo-3,6-anhydro-D-galactose. contains a disaccharide of; Kappa-carrageenan includes alternative disaccharides of D-galactose-4-sulfate and 3,6-anhydro-D-galactose; Lambda-carrageenan includes alternative disaccharides of D-galactose-2-sulfate (1-3 linked) and D-galactose-2,6-disulfate (1,4 linked). As a result, lambda-carrageenan typically contains more sulfate groups per polymer and substantially less anhydrogalactose residues, which are generally found in iota-carrageenan and kappa-carrageenan. Consequently, the relative ratio of lambda- to iota- to kappa-carrageenan in antiviral lubricating compositions can be determined by infrared spectroscopy (IR), nuclear magnetic resonance (NMR) spectroscopy (ref: de Araujo, CA, et al., (2013) Carbohydrate Polymers 91:483-491), and liquid chromatography coupled to mass spectrometry (LC-MS) (see Diez, F., et al., (2017) "Development of an Analytical Method to Determine the amount of

Carrageenan in HPMC Capsules by LCMS," American Association of Pharmaceutical Scientists Poster Submission, obtained from the Internet at http://abstracts.aaps.org/Verify/AAPS2017/PosterSubmissions/M8109.pdf, May 3, 2018; , can be measured by several analytical techniques, including but not limited to.

In particular, the IR spectrum of an antiviral lubricating composition can be utilized to determine the relative molar ratios of lambda-, iota-, and kappa-carrageenan forms in the composition, as well as a profile of the composition comparable to other lambda-carrageenan-containing compositions. (Reference: Volery, P., et al., (2004) J. Agric. Food Chem. 52 (25): 7457-7463). Within the fingerprint region (about 800 cm ^-1 to about 1250 cm ^-1 ) of the representative IR spectrum, carrageenan has several strong, broad absorption bands for residues or functional groups commonly found in each polymer. as well as strong absorption maxima from about 1065 cm ^-1 to about 1020 cm ^-1 , especially about 1050 cm ^-1 . With respect to the intensity of the main absorption band at 1050 cm ⁻¹ , the intensity of the absorbance of a specific band corresponding to a residue or functional group can be used to determine the relative abundance of a specific form of carrageenan using an IR sample. The characteristic absorption band and its intensity for the main absorption band at 1050 cm ^-1 are shown in Table 4 below.

A study was conducted according to the principles of the present invention to characterize carrageenan in a sample of an antiviral lubricating composition. Samples of antiviral lubricating compositions were prepared from the Food and Agricultural Organization of the United Nations/World Health Organization joint compendium of food additive specifications (see "Carrageenan, Compendium of Food Additive Specifications FAO JEFCA Monographs 16 ; FAO/WHO Publications; Rome, Italy; pp. 7-12) and applied to IR spectroscopy analysis The antiviral lubricating composition of the present invention is applied to other products containing lambda-carrageenan. It is predicted that the composition has a unique and characteristic IR spectrum comparable to it.In addition, the IR spectrum for the antiviral lubricating composition has peaks between 810 cm ^-1 and 820 cm ^-1 as well as between 825 cm ^-1 and 830 cm ^-1 , which indicates the presence of lambda-carrageenan in the antiviral lubricating composition It is also predicted that the molar ratio of lambda-carrageenan in the antiviral lubricating composition is greater than that of kappa-carrageenan and iota-carrageenan.

Example 6: Antiviral Efficacy of Antiviral Lubricating Compositions Against Respiratory Viruses in Human Subjects

Principles of the present invention can be applied to determine the efficacy of an antiviral lubricating composition in a human subject suffering from an active viral respiratory infection, such as COVID-19, or in close contact with a person suffering from an active viral respiratory infection. A study was conducted according to Participants were asked to apply the antiviral lubricating composition of Example 2 to the tip of a swab and insert the swab through the nose until contact was made with the nose and the epithelial tissue within the nasal cavity. Alternatively, participants were asked to dispense a volume of an antiviral lubricating composition into the mouth and to swirl, swirl or gargle the composition in the mouth before swallowing. The volume of the composition administered by either method is 0.1 ml to 5 ml. The antiviral lubricating composition of Example 2 may be administered in the form of a stock solution or diluted before administration. Participants were asked to administer the antiviral lubricating composition to the nasal cavity 1 to 4 times per day. Additionally, participants may be asked to administer the composition before and/or after close contact with others or going out into public places. For those with an active infection, on a dose-dependent basis, the progression of symptoms is expected to be attenuated or reduced until complete clearance. It is also expected that the viral load of a virus transmitted to a subject who is not ill but has close contact with a sick patient is delayed, reduced or eliminated.

Claims (20)

An antiviral lubricating composition comprising:
(a) 0.1% to 3% by weight carrageenan, the carrageenan comprising about 90% lambda-carrageenan and about 10% kappa-carrageenan;
(b) 0.1% to 8% by weight of a polyol;
(c) 0.01% to 1% by weight of one or more pH-adjusting agents; and
(d) optionally up to 0.5% by weight of one or more sweeteners and up to 1% by weight of one or more preservatives;
From here:
(i) the antiviral lubricating composition is an aqueous, homogeneous solution having a turbidity of less than about 25 turbidimetric turbidity units (NTU);
(ii) the antiviral lubricating composition is translucent;
(iii) the antiviral lubricating composition has a viscosity of 500 cP to 10,000 cP; and
(iv) the pH of the antiviral lubricating composition is between 3.5 and 7.0. According to claim 1,
An antiviral lubricating composition comprising 1.5% to 1.7% by weight of carrageenan and 4.0% to 4.5% by weight of propylene glycol and having a viscosity of 2,000 cP to 3,000 cP. According to claim 1,
An antiviral lubricating composition, wherein the antiviral lubricating composition has an osmolality of 200 mOsmol/kg to 1400 mOsmol/kg. According to any one of claims 1 to 3,
An antiviral lubricating composition, 1.5% to 1.7% by weight of carrageenan; 4.0% to 4.5% by weight of propylene glycol; 0.01% to 1% by weight of one or more pH-adjusting agents; up to 0.5% by weight of one or more sweeteners; and at most 1% by weight of one or more preservatives;
From here:
The antiviral lubricating composition has a pH of 5.5 to 7.0;
The antiviral lubricating composition has a viscosity of 2,000 cP to 3,000 cP; and
An antiviral lubricating composition, wherein the osmolality of the antiviral lubricating composition is 650 mOsmol/kg to 850 mOsmol/kg. According to claim 1,
An antiviral lubricating composition, wherein the composition is effective for reducing, inhibiting or ameliorating transmission of a virus from a taxonomic family selected from the group consisting of:
Orthomyxoviridae ( Orthomyxoviridae ) , Paramyxoviridae ( paramyxoviridae ) , Pneumoviridae ( pneumoviridae ) , Coronaviridae ( coronaviridae ) , Retroviridae ( retroviridae ) , Herpesviridae ( herpesviridae ) , Papillomaviridae ( papillomaviridae ) , Picornaviridae ( picornaviridae) , reoviridae and adenoviridae and combinations thereof. According to claim 5,
An antiviral lubricating composition, wherein the composition is effective for reducing, inhibiting or ameliorating transmission of human papillomavirus (HPV). According to claim 5,
An antiviral lubricating composition, wherein the composition is effective for reducing, inhibiting or improving transmission of a virus selected from the group consisting of Severe Acute Respiratory Syndrome (SARS) virus strain 1 and SARS strain 2. A lubricated substrate comprising at least one skin-contacting surface lubricated with a pourable antiviral lubricating composition of any one of claims 1 to 7, comprising: A lubricated substrate useful for transfer from a skin-contacting surface to the skin or epithelial tissue of an individual. According to claim 8,
A lubricated substrate wherein the lubricated substrate is a condom. According to claim 8,
A lubricated substrate wherein the lubricated substrate is a sexual aid selected from the group consisting of a sex toy, a dildo, a vibrator, a ring, and a bead. According to claim 9,
The lubricated substrate is an internal applicator having a skin-contacting surface configured to contact epithelial tissue within a body cavity of an individual, the internal applicator comprising: a swab; extension rods or rods; wearable implants; injector; syringe; conduit; and a lubricated substrate selected from the group consisting of pipettes. According to claim 11,
A lubricated substrate wherein the lubricated substrate is a cotton swab. A method for forming the antiviral lubricating composition of any one of claims 1 to 7 comprising the following steps:
(a) providing a carrageenan powder comprising carrageenan, wherein the carrageenan comprises 90% lambda-carrageenan and 10% kappa-carrageenan by weight;
(b) mixing a solution containing a polyol with carrageenan powder to form an aqueous carrageenan suspension;
(c) heating the aqueous carrageenan suspension to a temperature of at least 70° C. and at most 75° C.;
(d) mixing the heated aqueous carrageenan suspension for a time sufficient to form an aqueous homogeneous solution having a turbidity of less than about 25 nephelometry turbidity units (NTU);
(e) cooling the aqueous homogeneous solution to a temperature of less than about 30°C; and
(f) forming an antiviral lubricating composition by mixing one or more pH-adjusting agents in an amount sufficient to adjust the antiviral lubricating composition to a pH within the range of 3.5 to 7.0. According to claim 13,
Carrageenan comprises 0.1% to 3% by weight of the antiviral lubricating composition;
the polyol is propylene glycol, and the propylene glycol comprises from 0.1% to 8% by weight of the antiviral lubricating composition;
The antiviral lubricating composition has a viscosity of 500 cP to 10,000 cP; and
The method wherein the osmolality of the antiviral lubricating composition is 200 mOsmol/kg to 1400 mOsmol/kg. According to claim 14,
1.5% to 1.7% by weight of the antiviral lubricating composition of carrageenan;
4.0% to 4.5% by weight of the antiviral lubricating composition of propylene glycol;
The pH of the antiviral lubricating composition is within the range of 5.5 to 7.0;
The antiviral lubricating composition has a viscosity of 2,000 cP to 3,000 cP; and
The method wherein the osmolality of the antiviral lubricating composition is 650 mOsmol/kg to 850 mOsmol/kg. According to any one of claims 13 to 15,
A method in which one or more pH-adjusting agents are added and mixed into a chilled aqueous homogeneous solution. According to any one of claims 13 to 15,
adding up to about 0.5% by weight of one or more sweeteners while mixing; and
adding up to about 1% by weight of one or more preservatives while mixing
How to further include. According to claim 17,
A process in which one or more sweetening agents are added to an aqueous carrageenan suspension and one or more preservatives are added to a chilled aqueous homogeneous solution. According to any one of claims 13 to 15,
Step (b) is
(A) mixing carrageenan powder with an amount of propylene glycol for a time sufficient to form a wet carrageenan mixture, wherein the weight ratio of propylene glycol to carrageenan powder is from about 1:1 to about 10:1; and
(B) while mixing, combining the wet carrageenan mixture with the aqueous solution for a time sufficient to form an aqueous carrageenan suspension, wherein the volume ratio of the aqueous solution to the wet carrageenan mixture is from about 45:1 to about 8:1;
A method comprising the sub-steps of According to claim 19,
A process wherein the total mixing time for forming the wet carrageenan mixture, forming the aqueous carrageenan suspension, forming the aqueous homogeneous solution, and forming the antiviral lubricating composition is about 3 hours or less.

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