JP2023538798A - Personal lubricants containing lambda-carrageenan - Google Patents

Abstract

An injectable non-toxic lubricating composition comprising lambda-carrageenan as an antiviral agent to protect against viruses including, but not limited to sexually transmitted viruses and respiratory viruses, and a non-oily lubricating composition. A method of administering carrageenan for use as a pseudoplastic lubricant product to reduce the proliferation of sexually transmitted viruses, including HPV, during sexual activity. [Selection diagram] Figure 1

Description

The present invention relates to a method for making a personal lubricant composition useful for reducing or inhibiting the transmission of human papillomavirus between partners during sexual activity.

Background of the invention

According to the World Health Organization (WHO), human papillomavirus (HPV) is the most common sexually transmitted infection (STI) in the world, with more than 14 million new infections occurring each year. In the United States alone, more than 42% of people between the ages of 18 and 59 are infected with HPV, and one in nine men is infected with oral HPV. Furthermore, HPV is the root cause of essentially all cervical cancers and is the second most common cancer in women worldwide by age-standardized incidence, leading to approximately 500,000 deaths annually. . More than 85% of deaths from cervical cancer occur in developing countries, and it accounts for 13% of all cancers in women. The WHO also estimates that HPV causes 90% of anal cancers. In another study on HPV and throat cancer, AECOM found that the presence of HPV types in the mouth made a person 22 times more likely to develop head and neck cancer. HPV is also the root cause of all genital warts.

HPV is spread through skin-to-skin contact and is most commonly transmitted to the genitals, anus, and mouth during sex. As a result, condoms are only marginally effective in preventing HPV transmission. Although there are several treatment options for HPV, there are actually more than 150 strains of HPV, of which approximately 30 have been shown to cause cancer and genital warts. Vaccines are being developed and may be useful, but the best HPV vaccine currently available in the United States has antiviral activity against only 9 out of more than 150 HPV strains, and only a small number of It only works for people. In 2015, the CDC reported that the HPV vaccine has only a 40% uptake rate among adolescents and is generally not effective for people over the age of 26, as well as for African American women of all ages. Additionally, the CDC reports that the vaccine is also ineffective if you have previously been exposed to HPV. Additionally, HPV vaccines are generally expensive, require multiple treatments and injections, and are largely unavailable to people in developing countries. As a result, many people are not vaccinated and rely on condoms as their only protection against HPV.

in vitro (see Buck, CB, et al., (2006) PLoS Pathogens 2(7):671-680)) and in vivo in mice (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). Some promising research has been conducted on the use of carrageenan formulations, particularly those containing the lambda form of carrageenan. Several other patents and patent publications also discuss the use of carrageenan in pharmaceuticals as antimicrobial or antiviral compounds (U.S. Pat. Nos. 5,208,031 and 8,367,098, and U.S. Pat. See 2005/0171053, 2005/0239742, 2005/0261240, 2006/0127340, 2008/0227749, 2009/0088405 and 2011/0229446. (Incorporated by reference in its entirety).

More recently, in vivo studies in humans have shown that lambda-carrageenan formulations can be utilized to inhibit HPV transmission during sexual activity (Magnan, S., et al., (2019) Clin. Microbiol. Infect. 25(2):210-216, the disclosure of which is incorporated by reference in its entirety). However, there are very few commercially available personal lubricants that contain carrageenan because carrageenan is very difficult to process into a form suitable for use during sex. Carrageenan is a large, flexible polysaccharide that mostly occurs as a complex mixture of at least two and usually three different forms: kappa-carrageenan, iota-carrageenan, and lambda-carrageenan, which vary in degree of sulfation. different. The kappa and iota forms of carrageenan have the lowest number of sulfate ester groups per molecule, dominate most carrageenan mixtures, and are commonly used as gelling or thickening agents in the food or cosmetic industry. On the other hand, lambda-carrageenan has the highest number of sulfate groups per polysaccharide and cannot form any gel. In the case of lambda-carrageenan, increasing sulfate ester levels generally decrease the dissolution temperature in water, which is closely associated with a decrease in gel strength or inhibition of gel formation. When present, all combinations of the kappa, iota, and lambda forms of carrageenan, as a function of the total concentration of carrageenan in the composition, have an exponential effect on the viscosity of the composition. This can result in a 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. Furthermore, the viscosity of a particular carrageenan-containing composition is very sensitive to the exact proportions of kappa, iota, and lambda forms within the composition. Thus, a composition containing 50% lambda-carrageenan and 50% kappa-carrageenan will be different from a composition containing 70% lambda-carrageenan and 30% kappa-carrageenan, even if the total concentration of carrageenan in both compositions is the same. even will have different viscosities. This effect is exacerbated in compositions containing all three forms of carrageenan. As a result, the viscosity of carrageenan-containing compositions is generally unpredictable from composition to composition when the total concentration of carrageenan is the same but the proportions of kappa, iota, and lambda forms are different.

Additionally, the processing steps used to produce carrageenan-containing compositions can themselves affect viscosity and performance as sexual lubricants. For example, the temperature at which the ingredients are mixed has a dramatic effect on the viscosity of carrageenan-containing products, particularly as a function of the ratio of each form of carrageenan in the mixture. When an untreated carrageenan mixture is heated in an aqueous solvent, the individual polysaccharides within the mixture begin to hydrate and begin intermolecular interactions with other polysaccharides, increasing the viscosity of the composition. Further increasing the temperature breaks the intermolecular interactions, homogenizes the carrageenan, and brings it into the aqueous phase, reducing the overall viscosity to near the starting level. However, the proportion of each type of carrageenan included within the composition can influence what happens upon cooling. If the predominant type is kappa- or iota-carrageenan, the cooled composition will form a gel, but if the predominant type is lambda-carrageenan, the cooled composition will not form a gel. Nevertheless, the relative proportions of kappa-carrageenan and iota-carrageenan within the composition influence the viscosity of non-gelling lambda-carrageenan-containing compositions.

On the other hand, excessive heating of carrageenan-containing compositions has the effect of breaking intramolecular bonds within adjacent sugar units, effectively causing significant changes in carrageenan molecules and reducing their average molecular weight. This may further reduce the viscosity of the resulting composition, but with the trade-off that the composition dries more rapidly once it is applied. Similarly, mixing carrageenan-containing mixtures for extended periods of time under high speed or high shear conditions can disrupt the intra- and intermolecular relationships of carrageenan molecules within the composition.

Therefore, there remains a need for a formulation containing lambda-carrageenan that also functions well as a sexual lubricant, allowing both men and women to protect themselves from HPV infection in a comfortable and discreet manner. . Lubricant formulations must balance effectiveness against HPV while maintaining the viscosity, tactility, and performance enhancements obtained by using personal lubricants during sexual activity. There also remains a need for products that can be used in conjunction with condoms or other sexual accessories to reduce the risk of contracting HPV, HIV, and herpes during sexual activity, especially when two or more men are involved. ing.

The present invention includes lambda-carrageenan and reduces transmission, persistence, or symptoms caused by viruses, including but not limited to sexually transmitted viruses and other pathogenic viruses from taxonomic families; A method of making a low viscosity antiviral lubricating composition useful for inhibiting or improving antiviral properties is provided. Other pathogenic viruses from the taxonomic families are Orthomyxoviridae, Paramyxoviridae, Pneumoviridae, Coronaviridae, and Retroviridae. , Herpesviridae, Papillomaviridae, Picornaviridae, Reoviridae, Adenoviridae, and combinations thereof. or can be selected from the group consisting of: Antiviral lubricant compositions made in accordance with the disclosed process may contain viruses, including tissue in or on the cervix, vulva, vagina, clitoris, penis, anus, mouth, nose, nasal cavity, or throat. It can be applied to epithelial or skin tissue that is present or may spread.

In various embodiments, antiviral lubricant compositions made by the methods of the invention can be used in conjunction with sexual activity. As used herein, the term "sexual intercourse" includes touching the cervix, vulva, vagina, clitoris, penis, anus, mouth, or throat of one, two, or more sexual partners. includes intimate or sexual contact with the skin or epithelial tissue in or on the skin. In certain embodiments, application of the antiviral lubricant compositions of the present invention is effective in reducing transmission of sexually transmitted viruses in humans compared to a placebo composition that does not contain lambda-carrageenan, and Limited examples include human papillomavirus (HPV), human immunodeficiency virus (HIV), and herpes simplex virus (HSV). In further embodiments, the antiviral lubricating composition is capable of causing cancer, which can occur during male-female sexual encounters, male-male sexual encounters, and female-female sexual encounters. Provides protection against HPV infection, including but not limited to known HPV strains. In an even further aspect, the antiviral lubricant composition can provide protection against transmission of HPV among high-risk sexual partners, including those who are already infected with at least one strain of HPV. .

In various embodiments, any of the antiviral lubricant compositions described herein are administered to one or more people prior to sexual activity to preventively inhibit the transmission of HPV from one sexual partner to another. of a sexual partner, particularly skin or epithelial tissue located on or within at least one of the vagina, anus, mouth, or penis. In such embodiments, the antiviral lubricating composition is applied to the skin of one or more sexual partners less than 8 hours, such as less than 4 hours, less than 2 hours, less than 1 hour, 30 hours before sexual activity. Contact can be made for less than a minute, less than 15 minutes, less than 5 minutes, less than 1 minute, or 30 seconds up to less than 1 second. In other embodiments, the antiviral lubricant composition is applied to the skin or epithelial tissues of one or more sexual partners, particularly the vagina, after sexual activity to reduce the spread of HPV from cell to cell after HPV is transmitted. , the skin or epithelial tissue located on or within at least one of the anus, mouth, or penis. In such embodiments, the antiviral lubricating composition is administered within 8 hours after sexual activity, such as less than 4 hours, less than 2 hours, less than 1 hour, less than 30 minutes, less than 15 minutes, less than 5 minutes, less than 1 minute after sexual activity. or less than 1 second after sexual activity, such as less than 30 seconds, with the skin or epithelial tissue of one or more sexual partners.

In various embodiments, antiviral lubricant compositions made by the methods of the invention can be applied to a person's skin or epithelial tissue independent of sexual activity. In some embodiments, the antiviral lubricant composition may contain viruses such as coronaviruses, reoviruses, adenoviruses, orthomyxoviruses, paramyxoviruses, pneumoviruses, picornaviruses, and non-sexually transmitted retroviruses and herpesviruses. It can be applied to reduce, inhibit, or ameliorate the transmission or effects of non-sexually transmitted viruses, including but not limited to. Non-limiting examples of diseases caused by such viruses include Severe Acute Respiratory Disease (SARS), COVID-19, influenza, measles, mumps, varicella, enterovirus, rhinovirus, polio, adenovirus, and rotavirus. These include, but are not limited to. In certain embodiments, the antiviral lubricant composition can be applied to an animal having an infection from a disease caused by a virus caused by any of the virus families or types listed above. Methods and substrates for applying antiviral lubricant compositions to help treat or lessen the effects of such conditions in humans or animals are described in further detail below.

In other embodiments, the antiviral lubricating compositions can be utilized in conjunction with sanitary products for purposes including, but not limited to, as vaginal moisturizers, vaginal deodorizers, and vaginal odor removers.

In another embodiment, the antiviral lubricating composition is a non-Newtonian pseudoplastic fluid that undergoes thixotropic shear thinning that further reduces the viscosity of the composition in response to mechanical strain. By way of non-limiting example, such mechanical distortions may be caused by one, two or more persons, male and female sexual partners, two or more male sexual partners, two or more female sexual partners, can occur when engaging in sexual activity, including sexual activity with sexual partners and combinations thereof.

In another embodiment, the antiviral lubricant composition maintains the lubricity of the dry antiviral lubricant composition on the skin upon adding water or other body fluid to the dry antiviral lubricant composition. It has a rheological profile that can Non-limiting examples of body fluids include saliva and vaginal secretions or discharge. In a further embodiment, upon adding water or body fluid to the dry antiviral lubricant composition, the antiviral lubricant composition retains its antiviral activity, including against HPV.

In various embodiments, the antiviral lubricating compositions of the present invention are typical of commercially available personal lubricants, including, but not limited to, oils, particularly silicone oils; cellulose; and polyquaternium. It can be prepared substantially free of components that are commonly used. In various embodiments, antiviral lubricant compositions can be prepared substantially free of spermicides, such as nonoxynol-9, which are also often present in commercially available personal lubricants. However, in other embodiments, antiviral lubricant compositions can be prepared that include oil, cellulose, polyquaternium, and/or nonoxynol-9.

In another embodiment, a method of forming an antiviral lubricating composition of the present invention includes the steps of: (a) providing a carrageenan powder having carrageenan, the carrageenan comprising at least 80% by weight of lambda-carrageenan and iota-carrageenan. having up to 10% by weight of secondary carrageenan, preferably 10% by weight of kappa-carrageenan, selected from the group consisting of carrageenan and kappa-carrageenan and combinations thereof; (b) while mixing, carrageenan powder; (c) heating the carrageenan aqueous suspension to a temperature of at least 60°C; (d) heating the carrageenan aqueous suspension to a temperature of at least 60°C; (e) cooling the homogeneous aqueous solution to a temperature below 50°C; and (f) making one or more pH adjustments to the cooled homogeneous aqueous solution. the antiviral lubricating composition.

In various embodiments, the carrageenan suspension is cloudy. Once substantially all the polysaccharides in the carrageenan suspension are homogenized by heating and mixing, the carrageenan suspension becomes clear and the resulting homogeneous solution becomes translucent. In another embodiment, the antiviral carrageenan suspension becomes clear upon formation of a homogeneous solution and remains clear. In another embodiment, there are substantially no visible particulates, aggregates, or agglomerates within the antiviral lubricating composition.

In various embodiments, the turbidity of any of the mixtures, suspensions, or antiviral lubricant compositions disclosed herein is in the range of Formazin Nephelometric Units (FNU), Jackson Turbidity Units (Jackson Turbidity Units (JTU), and Nephelometric Turbidity Units (NTU) can be quantitatively described based on methods of measuring the concentration of suspended particles in a sample, including but not limited to. In another aspect, the turbidity of any of the mixtures, suspensions, or antiviral lubricant compositions described herein is characterized as a function of NTU. In another aspect, the turbidity of the carrageenan suspension when the carrageenan is added to the aqueous solution is at least 100 NTU, at least 200 NTU, 300 NTU, 400 NTU, 500 NTU, 600 NTU, 700 NTU, 800 NTU, 900 NTU, 1000 NTU, 2000 NTU, or 3000 NTU up to at least 4000 NTU. In another aspect, the turbidity of the homogenized antiviral lubricating composition is less than 25 NTU, less than 20 NTU, less than 15 NTU, less than 10 NTU, less than 8 NTU, less than 6 NTU, less than 5 NTU, less than 4 NTU, less than 3 NTU, or less than 2 NTU. The turbidity should be less than 1 NTU, preferably 5 NTU or less, and more preferably about the same as the turbidity of drinking water.

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

In various embodiments, mixing the wet carrageenan mixture with the aqueous solution comprises dispersing the carrageenan included in the wet carrageenan mixture within the aqueous solution. In a further embodiment, the dispersion step comprises thoroughly shear mixing the carrageenan powder with the polyol using a dispersion mixer for a time sufficient to homogenize the carrageenan into the aqueous solution, while simultaneously dispersing the carrageenan powder within each carrageenan polysaccharide. Minimize cleavage of intramolecular bonds between sugar residues.

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

In various embodiments, mixing the other powder, solid, or liquid adjuvant into the aqueous solution includes mixing the adjuvant in the aqueous solution under sufficient shear mixing and for a sufficient time to form a compositionally uniform solution. Have stirring.

In various embodiments, the carrageenan powder comprising lambda-carrageenan is a dry extract from seaweed, particularly the red alga Chondrus crispus. In various embodiments, the lambda-carrageenan comprises at least 80%, such as at least 85%, 90%, or 95% by weight of the seaweed extract. In various embodiments, the lambda-carrageenan comprises up to 100%, such as up to 95%, 90%, or 85% by weight of the seaweed extract. In various embodiments, lambda-carrageenan comprises 90% by weight of the seaweed extract.

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

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

In various embodiments, within the carrageenan powder having lambda-carrageenan, the remaining carrageenan species can have kappa-carrageenan, iota-carrageenan, or a combination of kappa-carrageenan and iota-carrageenan. In various embodiments, either or both of kappa-carrageenan and iota-carrageenan comprises up to 20% by weight of the carrageenan powder, such as up to 15% by weight, 10% by weight, 8% by weight, 6% by weight of the carrageenan powder, It can have 4%, 2%, or 1% by weight. In various embodiments, when present, kappa-carrageenan and iota-carrageenan together comprise 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 various 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 various embodiments, lambda-carrageenan can comprise 90% by weight of the carrageenan powder and kappa-carrageenan can comprise 10% by weight of the carrageenan powder. In various embodiments, the lambda-carrageenan can comprise 90% by weight of the carrageenan powder, and the lambda-carrageenan can comprise 10% by weight of the carrageenan powder.

In various embodiments, the antiviral lubricating composition comprises at least 0.001% carrageenan, such as at least 0.01%, 0.1%, 0.5%, 0.75%, 1.0% by weight. Weight%, 1.2% by weight, 1.4% by weight, 1.6% by weight, 1.8% by weight, 2.0% by weight, 2.2% by weight, 2.4% by weight, 2.5% by weight , or 3% by weight, optionally up to at least 5% by weight. In other embodiments, the antiviral lubricating composition comprises less than 5% carrageenan, such as less than 3%, less than 2.5%, less than 2.4%, less than 2.2%, less than 2% by weight. , less than 1.8% by weight, less than 1.6% by weight, less than 1.4% by weight, less than 1.2% by weight, less than 1.0% by weight, less than 0.75% by weight, less than 0.5% by weight, less than 0.1%, less than 0.01%, or less than 0.001% by weight. In a further embodiment, the antiviral lubricating composition has from 0.2% to 2.3% by weight carrageenan. In an even further embodiment, the antiviral lubricating composition has from 0.8% to 2% by weight carrageenan. In yet a further embodiment, the antiviral lubricating composition has 1.5% to 1.7% by weight carrageenan.

In various embodiments, the addition of one or more polyols to the carrageenan powder partially loosens the carrageenan polysaccharides within the powder, making additional polarizable contacts available for interaction upon addition of the aqueous solution. Make it. In other embodiments, the presence of a polyol within the antiviral lubricant composition enhances the sensation, tactility, and/or lubricity experienced by the wearer or his partner during sexual activity. In a further embodiment, the at least one polyol is 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; and combinations thereof. In still further embodiments, the antiviral lubricating composition comprises less than 50%, such as less than 25%, less than 15%, less than 10%, less than 9%, 8% by weight of the polyol of the antiviral lubricating composition. less than 7% by weight, less than 6% by weight, less than 5% by weight, less than 4% by weight, less than 3% by weight, less than 2% by weight, less than 1% by weight, less than 0.5% by weight, or 0.1 It has less than % by weight. In other embodiments, 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% by weight of a polyol. , 6%, 7%, 8%, 9%, 10%, 15%, 25%, or 35% by weight. In yet a further embodiment, the antiviral lubricating composition has less than 10% by weight polyol. In yet a further embodiment, the antiviral lubricating composition has from 0.5% to 5% by weight polyol. In other still further embodiments, the antiviral lubricating composition has 4% to 4.5% by weight 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 has a viscosity of less than 10,000 cP, such as less than 8,000 cP, less than 6,000 cP, less than 5,000 cP, less than 4,000 cP, less than 3,000 cP, less than 2,000 cP, or The injectable composition is less than 1,000 cP. In other embodiments, the antiviral lubricating composition has a viscosity of at least 500 cP, such as at least 1,000 cP, 2,000 cP, 3,000 cP, 4,000 cP, 5,000 cP, 6,0000 cP, or 8,000 cP. In a further embodiment, the antiviral lubricating composition has a viscosity of 500 cP to 8,000 cP, more particularly 1,000 cP to 4,000 cP, even more particularly 2,000 cP to 3,000 cP. In certain embodiments, the antiviral lubricating composition has a viscosity of 1,500 cP to 2,500 cP. In certain embodiments, the antiviral lubricating composition has a viscosity of 2,000 cP.

In various embodiments, the antiviral lubricating composition has a viscosity that allows it to be poured from an open container, but remains on an inclined, inclined, curved, or countercurved surface upon application. Non-limiting examples of surfaces may 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 antiviral lubricating compositions can be applied include sex toys, vibrators, sexual accessories or devices such as rings, or beads, or swabs; elongated sticks. or internal applicators such as elongate sticks or rods, wearable inserts, injectors, syringes, cannulas, pipettes, etc.

In various embodiments, applying one or more shear forces to or using a surface containing an applied antiviral lubricant composition, as commonly applied during sexual activity, causes the antiviral lubricant composition to The viscosity of a substance decreases in a non-Newtonian manner. In a further aspect, the viscosity is less than 5,000 cP, such as less than 4,000 cP, less than 3,000 cP, less than 2,500 cP, less than 2,000 cP, less than 1,500 cP, less than 1,000 cP, less than 800 cP, less than 600 cP, 500 cP less than 400 cP, or less than 300 cP, and optionally less than 200 cP. In other embodiments, the lubricity of the antiviral lubricating composition is 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, optionally under continuous application of shear for up to at least 1 hour.

In various embodiments, increasing the total concentration of carrageenan within an antiviral lubricating composition exponentially increases the viscosity of the composition. In a further aspect, the relative concentrations of the kappa, iota, and lambda forms of carrageenan have different effects on the exponential growth rate of viscosity of the antiviral lubricant composition. In an even further embodiment, the antiviral lubricating composition has 90% lambda-carrageenan and 10% one or both of kappa-carrageenan or iota-carrageenan. In yet another embodiment, the antiviral lubricating composition has 90% lambda-carrageenan and 10% kappa-carrageenan. In yet a further embodiment, the antiviral lubricating composition has 90% lambda-carrageenan and 10% iota-carrageenan.

In various embodiments, the type of mixing rotor and mixing speed can be optimized to control the viscosity of the resulting antiviral lubricating composition. In some embodiments, the mixing is performed under sufficient shear conditions to homogenize the carrageenan-containing composition while maintaining the length of each carrageenan polysaccharide, and prior to applying the composition to the skin or epithelial tissue. Particularly before or at the same time as sexual activity, the lubricity can be maintained.

In various embodiments, the apparatus for carrying out the mixing steps of the present invention, including stirring or dispersing steps, can include any conventional mixing device for the intended use. One non-limiting example of a mixing device is a paddle mixer. An example of a paddle mixer is a mixer comprising at least one folded impeller blade. One particular example of a paddle mixer is the Mixer Direct R-AD665 industrial gallon paddle mixer with two folding impeller blades. In an even further embodiment, a paddle mixer is used for each of the mixing steps to form the antiviral lubricating composition. In other even further embodiments, each mixing step is performed in a low speed mixer operating at a rotational speed of 500 revolutions per minute (RPM) or less. In yet a further embodiment, mixing of the antiviral lubricating composition after homogenizing the carrageenan in the aqueous solution can be performed at a speed of 250 RPM or less.

In various embodiments, the antiviral lubricant composition formed by the methods of the invention has a molar mass that enables the skin or epithelial tissue, particularly within the vagina or rectum, to maintain a healthy plasma water electrolyte balance. It has an osmotic concentration. In a further aspect, the antiviral lubricating composition has an osmolarity of less than 1200 mOsmol/kg, such as less than 1000 mOsmol/kg, less than 900 mOsmol/kg, less than 800 mOsmol/kg, less than 700 mOsmol/kg, less than 600 mOsmol/kg, 500 mOsmol/kg. /kg, less than 400 mOsmol/kg, less than 300 mOsmol/kg, or less than 200 mOsmol/kg, and optionally less than 100 mOsmol/kg. In an even further embodiment, the antiviral lubricating composition has an osmolality of between 650 mOsmol/kg and 800 mOsmol/kg. In other even further embodiments, the osmolarity of the antiviral lubricant composition is isotonic with the normal osmolarity of human semen, and is between 250 mOsmol/kg and 380 mOsmol/kg. In yet a further embodiment, the osmolarity of the antiviral lubricant composition is isotonic with the normal osmolarity of vaginal secretions and is between 260 mOsmol/kg and 290 mOsmol/kg.

In various embodiments, the antiviral lubricating compositions of the present invention can further have one or more pH adjusting agents with acids, especially organic acids, and more particularly citric acid. In other embodiments, the one or more pH adjusting agents can include a weak acid and its conjugate base to create a buffer. As a non-limiting example, adding citrate to an antiviral lubricating composition can be accomplished by adding both citric acid and a citrate salt, such as sodium citrate or magnesium citrate.

In various embodiments, the pH of the antiviral lubricating composition is less than 9.0, such as less than 8.0, less than 7.0, less than 6.5, less than 6.0, less than 5.5, less than 5.0. , less than 4.5, or less than 4.0, and optionally less than 3.5. In other further embodiments, the pH of the antiviral lubricating composition is 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 antiviral lubricating composition has a pH of 5.5 to 7.0. In yet a further embodiment, the pH of the antiviral lubricant composition can be optimized for direct application to the vagina or for contacting the vagina during sexual activity. In such embodiments, the pH of the antiviral lubricating composition is between 3.5 and 5.5, particularly 4.5.

In various embodiments, the pH of the antiviral lubricant composition is adjusted after the carrageenan is homogenized and the resulting antiviral lubricant composition is cooled. In further embodiments, the antiviral lubricating composition can be cooled to less than 50°C, such as less than 45°C, less than 40°C, less than 35°C, less than 30°C, or less than 25°C, optionally less than 20°C. In an even further embodiment, the antiviral lubricating composition is cooled to less than 30° C. before adjusting the pH of the composition.

In various embodiments, the concentration of the one or more pH adjusting agents in the pH-adjusted antiviral lubricant composition is less than 1% by weight of the antiviral lubricant composition, e.g. less than 0.5%, less than 0.25%, less than 0.1%, or less than 0.05%, 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 0.1% by weight or less. In an even further embodiment, the weight of the one or more pH adjusting agents in the pH adjusted antiviral lubricating composition is 0.05% by weight or less. The pH adjusting agent can be added to the composition as a component of the carrageenan powder to which the polyol is added, to the carrageenan suspension, or to the antiviral lubricating composition after the carrageenan has been homogenized.

In various embodiments, a method of forming an antiviral lubricating composition includes adding one or more sweeteners and/or one or more preservatives to a carrageenan powder, a carrageenan aqueous suspension, or a chilled homogeneous aqueous solution. It may further include the step of mixing either of the above. In various embodiments, one or more sweeteners are added to the carrageenan aqueous suspension. In various embodiments, one or more preservatives are added to the homogeneous aqueous solution along with one or more pH adjusting agents. In various embodiments, each of the sweeteners and preservatives described above, as well as additional ingredients such as salts and/or flavoring agents, are included within the antiviral lubricant composition to supplement its antiviral activity and to the skin or epithelial tissue. application and/or enhance its performance during sexual activity.

In various embodiments, the antiviral lubricant compositions of the present invention contain from 0.01% to 1% by weight of one or more sweeteners, particularly saccharin, of the antiviral lubricant composition, particularly of the antiviral lubricant composition. It can further contain 0.1% to 0.5% by weight. In another embodiment, the concentration of saccharin in the antiviral lubricant composition is up to 0.5% by weight. In another embodiment, the concentration of saccharin in the antiviral lubricant composition is 0.125% by weight.

In various embodiments, saccharin can be added to the carrageenan mixture or carrageenan suspension as an aliquot from a concentrated stock solution. In a further embodiment, the total weight of the carrageenan mixture or saccharin stock solution added to the antiviral lubricant composition has from 1% to 10% by weight of the finished antiviral lubricant composition. In an even further embodiment, the saccharin stock solution is 2.5% by weight saccharin in water. In yet a further embodiment, the amount of the 2.5% by weight saccharin stock solution added to the carrageenan mixture is equal to 5% by weight of the antiviral lubricating composition, and the final concentration of saccharin in the antiviral lubricating composition is 0.125% by weight. %. In yet a further embodiment, saccharin is provided as saccharin sodium.

In various embodiments, the antiviral lubricating compositions of the present invention contain one or more preservatives, particularly one selected from the group consisting of 2-phenoxylethanol, chlorphenesin, and sodium dehydroacetate, and combinations thereof. It may further contain 0.01% to 1.0% by weight of the above preservatives.

In various embodiments, the antiviral lubricating compositions of the present invention can optionally further include one or more fragrances designed to impart a pleasant aromatic effect to the composition. Fragrances can include essential oils or component compounds within essential oils that can impart an odor. Non-limiting examples of aromas that may be provided by such fragrances include citrus, lemon, berry, or peppermint aromas. In certain embodiments, the fragrance can 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 compositions of the present invention can further comprise a salt, particularly a sodium salt or a zinc salt, more particularly a zinc salt, which can be used to increase the ionic strength of the composition. while supporting or complementing either or both the rheological properties or antiviral activity of the composition. The salt can be added to the composition as a component of the carrageenan powder to which the polyol is added, to the carrageenan suspension, or to the antiviral lubricant composition after the carrageenan has been homogenized.

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

In another aspect, a method of forming an antiviral lubricating composition includes (a) providing a carrageenan powder having carrageenan, the carrageenan comprising 90% by weight lambda-carrageenan and 10% by weight kappa-carrageenan. (b) combining the carrageenan powder with an aqueous solution comprising propylene glycol while mixing to form an aqueous carrageenan suspension; (c) adding one or more sweeteners to the aqueous carrageenan suspension. (d) heating the aqueous carrageenan suspension to a temperature of at least 70°C to 75°C; (e) mixing the heated aqueous carrageenan suspension for a sufficient time to form a homogeneous aqueous solution. (f) cooling the homogeneous aqueous solution to a temperature below 30° C.; (g) one or more pH values sufficient to adjust the antiviral lubricating composition to a pH of 3.5 to 7.0; mixing the modifier and one or more preservatives into the cooled homogeneous aqueous solution, thereby forming an antiviral lubricating composition. In another embodiment, the antiviral lubricating composition formed by the above method comprises: 1.5% to 1.7% by weight carrageenan and 4.0% to 4.5% by weight propylene glycol. up to 0.5% by weight of sweeteners, up to 1% by weight of one or more preservatives, and from 0.01% to 1% by weight of one or more pH regulators, essentially from water as balance. can become. In a further aspect, the antiviral lubricating composition formed by the above method may be translucent, have a viscosity of at least 2,000 cP, at most 3,000 cP, and a turbidity of 25 NTU or less, preferably 5 NTU. It can be as follows. In a further aspect, the antiviral lubricating composition formed by the above method can have an osmolality ranging from at least 650 mOsmol/kg to 850 mOsmol/kg. In yet a further embodiment, the antiviral lubricating composition formed by the above method has a pH of 3.5 to 5.5. In other yet further embodiments, the antiviral lubricating composition formed by the above method has a pH of 5.5 to 7.0. In yet a further aspect, the antiviral lubricant composition formed by the above method is effective in reducing, inhibiting, or ameliorating transmission of HPV. In other still further embodiments, the antiviral lubricant composition formed by the above method is effective in reducing, inhibiting, or ameliorating the transmission of COVID-19.

In another embodiment, a method of forming an antiviral lubricating composition of the present invention includes (a) providing a carrageenan powder having carrageenan, the carrageenan comprising 90% by weight of lambda-carrageenan and kappa-carrageenan. (b) mixing carrageenan powder with a polyol, the process comprising stirring or agitating the carrageenan powder and polyol for a sufficient period of time to form a wet carrageenan mixture; (c) dispersing the wet carrageenan mixture in the aqueous solution under shear mixing for a sufficient time to form a cloudy carrageenan suspension; (d) adding one or more sweeteners to the cloudy carrageenan suspension while stirring the cloudy carrageenan suspension; adding, the sweetener having up to 0.5% by weight of the finished antiviral lubricant composition; (e) shearing the cloudy carrageenan suspension for a sufficient period of time, including up to 100 minutes; heating under mixing to a temperature of 70° C. to convert the cloudy carrageenan suspension into a clarified homogeneous solution, thereby forming an antiviral lubricating composition; (f) antiviral lubricating composition; (g) a weight sufficient to adjust the antiviral lubricating composition to a pH of 3.5 to 7.0; (h) adding up to 1% by weight of the antiviral lubricating composition of one or more preservatives to the cooled antiviral lubricant composition under stirring; adding to the carrageenan suspension or cooled antiviral lubricating composition under stirring; (i) the antiviral lubricating composition comprises 0.2% to 2.3% by weight carrageenan; (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 The composition is effective to reduce, inhibit, or ameliorate transmission of human papillomavirus (HPV). In a further embodiment, the antiviral lubricating composition has 1.5% to 1.7% by weight carrageenan; 4% to 4.5% by weight 1,2-propanediol; and a viscosity of 2,000 cP. ˜3,000 cP; osmolality between 650 mOsmol/kg and 850 mOsmol/kg; pH between 6.25 and 6.75. In an even further embodiment, the carrageenan has 90% by weight lambda-carrageenan and about 10% by weight kappa-carrageenan. In yet a further aspect, the antiviral lubricant composition formed by the above method is effective in reducing, inhibiting, or ameliorating transmission of HPV. In other still further embodiments, the antiviral lubricant composition formed by the above method is effective in reducing, inhibiting, or ameliorating the transmission of COVID-19.

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

In various embodiments, a method of reducing, inhibiting, or ameliorating the transmission, symptoms, or effects of a viral infection comprises: (a) providing a substrate having one or more skin-contacting surfaces; , the substrate is configured to contact skin or epithelial tissue and/or to be inserted into one or more body cavities; (b) coating one or more skin-contacting surfaces of the substrate with an antiviral agent; (c) contacting the lubricated substrate with skin or epithelial tissue; and (d) applying the antiviral lubricating composition to the lubricating base. from the material to the skin or epithelial tissue.

In various aspects, a method of reducing, inhibiting, or ameliorating the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV between two or more partners engaged in sexual activity comprises (a) ) providing any of the antiviral lubricant compositions described above; and (b) contacting the antiviral lubricant composition with the skin or epithelial tissue of one or more partners, the skin or epithelial tissue comprising: The tissue may be at least one of vagina, anus, mouth, and penis. In further embodiments, at least one partner is male and at least one partner is female. In other further embodiments, at least two partners are male. In yet another further embodiment, at least two partners are female. In yet another embodiment, three or more sexual partners consisting of any combination of men or women.

In various aspects, a method of reducing, inhibiting, ameliorating, or preventing the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV between sexually active partners comprises: a) providing a substrate comprising one or more skin-contacting surfaces, the substrate being configured for insertion into one or more body cavities selected from the group consisting of the vagina, mouth, or anus; (b) lubricating one or more skin-contacting surfaces of the substrate with an antiviral lubricating composition, thereby producing a lubricated substrate; (c) lubricating the lubricated substrate with an antiviral lubricating composition; contacting the skin or epithelial tissue located on or within at least one of the vagina, anus, mouth, or penis of one or more human partners; and (d) transferring the antiviral lubricating composition from the lubricated substrate to the skin or transferring to epithelial tissue;

In various embodiments, the substrate is a condom. In further embodiments, the condom has latex. In other further embodiments, the condom comprises polyurethane and/or other synthetic materials. In yet other further embodiments, the condom is not compatible with oil-based personal lubricants. In yet another embodiment, the condom is selected from the group consisting of male condoms and female condoms.

In various condom-based embodiments, reducing, inhibiting, ameliorating, or preventing the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV, between sexual partners. The method includes the steps of: lubricating the skin-contacting surface of the condom; contacting skin or epithelial tissue within the mouth, vagina, or anus of one or more partners with the lubricated skin-contacting surface of the condom; The method further includes transferring the antiviral lubricating composition from the lubricated skin-contacting surface to the skin or epithelial tissue.

In various condom-based embodiments, reducing, inhibiting, ameliorating, or preventing the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV, between sexual partners. The method includes placing a condom on the fingers or penis of one partner; lubricating the outer surface of the condom with an antiviral lubricating composition; and using the lubricated outer surface of the condom to place a condom on one or more additional partners contacting the skin or epithelial tissue within the mouth, vagina, or anus of the condom; and transferring the antiviral lubricating composition from the lubricated outer surface of the condom to the skin or epithelial tissue.

In various condom-based embodiments, the method reduces, inhibits, or ameliorates the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV, between sexual partners; Methods to prevent this include: lubricating the condom; sealing the lubricated condom in a package; storing the lubricated condom in the package; removing the lubricated condom from the package; applying a lubricated condom to a person's finger or penis; contacting the skin or epithelial tissue within the mouth, vagina, or anus of one or more additional partners with the lubricated condom; and antiviral properties. The method further includes transferring the lubricating composition from the lubricated condom to the skin or epithelial tissue.

In various embodiments, the substrate is a sexual accessory device, including, but not limited to, a sex toy, dildo, vibrator, ring, or beads. In a further aspect, the method includes the steps of: sealing the sexual accessory device within a package; storing the lubricated sexual accessory device within the packaging; and contacting the skin or epithelial tissue of one or more partners. The method further includes the step of removing the lubricated sexual accessory device from the package prior to the step of removing the lubricated sexual accessory device from the package. The antiviral lubricant composition is typically applied to any skin-contacting surface of a sexual accessory device prior to contact with the skin of one or more sexual partners, particularly prior to insertion into the vagina, anus, or mouth. It can be applied to

In various embodiments, a condom lubricated with any of the antiviral lubricant compositions of the present invention is applied to an unlubricated sexual accessory device to provide lubricity for use during sexual activity. Can be done. In other embodiments, an unlubricated condom can be applied to a sexual accessory device lubricated with any of the antiviral lubricating compositions of the present invention. In yet other embodiments, an unlubricated condom can be applied to an unlubricated sexual accessory device and then 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, and the internal applicator can be a swab, an elongated stick or rod, a wearable device, an injector, a syringe, a cannula. , or a pipette. In a further embodiment, the internal applicator comprises a skin-contacting surface configured to contact epithelial tissue within a body cavity of a person, particularly within the vagina, nose, mouth, or rectum. In other further embodiments, the internal applicator is configured to house or contain the antiviral lubricant composition prior to transferring the antiviral lubricant composition to epithelial tissue within a human body cavity, particularly the vagina, nose, mouth, or rectum. It has a container configured to.

In various embodiments, the substrate is a swab of sufficient length to be inserted into the mouth or nose to contact epithelial tissue within the nasal cavity, including the throat, or the oral cavity. In various embodiments, a lubricated swab is inserted into the nose or mouth to contact epithelial tissue within the nasal cavity or oral cavity, and the lubricated swab is inserted into the nose or mouth to contact the epithelial tissue within the nasal cavity or oral cavity, and the The transmission, symptoms, or effects of viral respiratory infections such as adenovirus can be reduced, inhibited, or ameliorated.

The present invention also provides kits for reducing, inhibiting, or ameliorating the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV between sexually active partners, and has an antiviral lubricant composition as described above and instructions describing any of the above disclosed methods of contacting the antiviral lubricant composition with the skin of one or more partners. The kit can further include any of the substrates described above, including a condom, a sexual accessory device, and/or an internal applicator.
These and other aspects of the invention will be apparent to those skilled in the art from the following detailed description.

FIG. 1 shows a plot of the viscosity of an antiviral lubricant composition as a function of carrageenan concentration. FIG. 2 shows a plot of osmolarity of antiviral lubricant compositions as a function of 1,2-propanediol concentration.

Detailed description of the invention

It will be understood that although reference has been made to exemplary embodiments and specific language has been used to describe the same, it is not intended to limit the scope of the invention. Further modifications of the methods described herein, as well as additional applications of the principles of the invention described, will occur to those skilled in the relevant art and in possession of this disclosure; should be considered within the scope of the invention. Furthermore, unless otherwise defined, 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 aspect of the invention pertains. The terminology used is for the purpose of describing these aspects only and, unless specified as such, the terminology is not limiting. Headings are provided for convenience only and should not be construed as limiting the invention in any way. Furthermore, throughout the specification and claims, a given chemical formula or name is intended to encompass all optical isomers and stereoisomers, as well as racemic mixtures in which such isomers and mixtures exist.

The present disclosure provides antiviral activity against several different taxonomic families, including but not limited to one or both of the Coronaviridae and Papillomaviridae families, and the use of antiviral agents during sexual activity. Contains aqueous compositions that can be used as lubricants. The antiviral lubricating composition is suitable for use on skin or epithelial tissues where viral infections are known to reside inside or outside the body, or on the cervix, vulva, vagina, which are commonly lubricated during sexual activity. Areas can be touched including, but not limited to, the clitoris, penis, anus, nose, nasal cavity, mouth, and throat. The antiviral lubricating composition may be used to prevent human papillomavirus (HPV), human immunodeficiency virus (HIV), or herpes simplex virus (HSV) between sexual partners, including male-female, male-male, female-female sexual partnerships. ) can reduce, inhibit, ameliorate, or prevent the transmission and/or persistence of sexually transmitted disease viruses, including:

Lambda-Carrageenan-Containing Compositions The antiviral activity of the antiviral lubricating compositions of the present invention is due to the presence of carrageenan, particularly lambda-carrageenan. Carrageenan is a broad family of naturally occurring sulfated polysaccharides extracted from a wide variety of seaweeds, particularly Chondrus crispus, a red seaweed found along the Atlantic coast of the United States. Extracted carrageenan is typically available in any of ten forms that differ in sulfation content, sulfation position within each polysaccharide, and acid/base properties. Three types are particularly common in compositions used in the food and pharmaceutical industries: kappa-carrageenan, iota-carrageenan, and lambda-carrageenan. The structures of kappa-carrageenan, iota-carrageenan, and lambda-carrageenan are shown below.

As mentioned above, kappa-carrageenan, iota-carrageenan, and lambda-carrageenan contain repeating galactose units. In particular, kappa-carrageenan and iota-carrageenan have alternating units of D-galactose and 3,6-anhydro-galactose (3,6-AG), whereas lambda-carrageenan does not have 3,6-AG. Each type differs in the number of sulfate groups per disaccharide, with kappa-carrageenan, iota-carrageenan, and lambda-carrageenan having one, two, or three sulfate groups, respectively, per alternating unit. As the number of sulfate groups within the polysaccharide increases, certain types of carrageenan become less capable of producing gels. Similarly, the kappa, iota, and lambda forms of carrageenan all have the ability to solubilize in aqueous solutions. However, the temperature at which a particular form becomes solubilized is also a function of relative sulfate content. Therefore, a pure sample of lambda-carrageenan can be solubilized in water at a lower temperature than a pure sample of kappa-carrageenan.

Carrageenan is commonly used in the food and pharmaceutical industries as a thickening and/or gelling agent. When carrageenans are hydrated within an aqueous composition, they begin to swell, increasing the viscosity of the composition exponentially as a function of total carrageenan concentration. However, because the exponential rate of increase is inversely proportional to the sulfate content within each form of carrageenan, kappa-carrageenan has a higher viscosity than iota-carrageenan, which itself has a greater impact on viscosity than lambda-carrageenan. Causes exponential growth. It should be noted that heated compositions with kappa-carrageenan and iota-carrageenan can form a gel network upon cooling, since the polysaccharides form a double helix quasicrystalline network, especially in the presence of cations. However, the presence of lambda-carrageenan in the composition partially inhibits gel formation, and in compositions richest in lambda-carrageenan, gel formation is completely prevented. Without wishing to be bound by any particular theory, it is believed that the lack of 3,6-AG groups within lambda-carrageenan promotes gel inhibition.

Although the relative effects of the kappa, iota, and lambda forms of carrageenan on the viscosity of a composition are known, the exponential growth rate of viscosity generally cannot be predicted from one composition to another. . Particularly when the ratios of kappa, iota, and lambda-carrageenan vary depending on the composition, they are unpredictable. The method by which carrageenan and other ingredients are processed also dramatically affects the viscosity of the resulting composition. Factors related to the viscosity of the final product may include, but are not limited to, heating temperature, shear conditions, rotor type, mixing speed, mixing time, and additional ingredients that are also added to the composition. As a result, viscosity as a function of total carrageenan concentration can only be modeled if the proportions of each type of carrageenan are constant and the other processing steps are the same.

While carrageenan compositions containing primarily kappa and iota types of carrageenan are useful for thickening compositions or gels, they are inactive against HPV. On the other hand, the lambda-carrageenan type has been shown to be active against HPV both in vitro (see Buck, et al., supra) and in vivo. Similarly, several patents and patent publications discuss the use of carrageenan in pharmaceuticals as antimicrobial or antiviral compounds (U.S. Patent Nos. 5,208,031 and 8,367,098, and U.S. Patent Publications No. See 2005/0171053, 2005/0239742, 2005/0261240, 2006/0127340, 2008/0227749, 2009/0088405, and 2011/0229446. (these disclosures are incorporated by reference in their entirety). Without wishing to be bound by any particular theory, lambda-carrageenan is believed to act as a "lock" in which the polysaccharide attracts the virus, interacts with the viral capsid, halts or prevents viral replication, and further inhibits viral activity. Utilizes a "key" type mechanism. This will greatly reduce the transmission and persistence of the virus, especially HPV in sexually active men and women.

In one study, sexually active women at high risk of contracting and/or transmitting HPV during sex were given a gel containing lambda-carrageenan (Marais, D., et al., (2011) Antiviral Therapy 16: 1219-1226, and US Pat. No. 8,367,098, the disclosures of which are incorporated by reference in their entirety). The tested composition Carraguard® has a 3% by weight mixture of kappa-carrageenan and lambda-carrageenan and has a viscosity of 30,000-40,000 cP. Study participants were instructed to apply the gel in conjunction with vaginal intercourse. Over a three-year study, the authors found that among women with "relatively high compliance rates for gel use," those given the lambda-carrageenan-containing gel were only 62% more likely to be classified as HPV positive. It was determined that

However, as mentioned above, carrageenan (of any type) has been historically used as a thickener because it exponentially increases the viscosity of the composition, but is generally not used in personal lubricant formulations. Undesirable. In particular, gel compositions containing large amounts of kappa-carrageenan and/or iota-carrageenan are typically very viscous and tend to dry quickly when applied to skin or epithelial tissue, leaving a sticky residue. It forms particles and causes loss of lubricity. As a result, most topical carrageenan-containing compositions are typically gels or creams, including those studied by Marais, et al., along with the related compositions of US Pat. No. 8,367,098. To put the viscosity of these carrageenan-containing compositions into context, the viscosity of Carraguard® compared to some common compositions is shown in Table 1 below.

As shown in Table 1, the viscosity of the Carraguard® gel utilized in the Marais study ranges between the viscosity of chocolate and that of ketchup. Both chocolate and ketchup have shear-thinning properties, and while chocolate in particular can have an edible composition that can be utilized during sexual intercourse, the high viscosity of both compositions makes it difficult to use as a personal and sexual lubricant. reduce the functionality of

In contrast, carrageenan-free compositions commonly used as personal lubricants 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 would have a viscosity such that it can be poured from a container or lightly squeezed, remains on the skin after application, and produces shear thinning in response to stress, such as during sexual activity. should have. Materials commonly found in personal lubricants include, but are not limited to, oils, especially silicone oils, gums, cellulose, glycerin, polyols, glycols, glycans, polyquathemiums, and other polymers. Not done. However, while these lubricants provide pleasurable results during sexual activity, they do not provide protection against HPV.

Another human in vivo study (see Magnan, et al., supra) investigated the use of a low viscosity personal composition containing lambda-carrageenan for anti-HPV activity. Similar to the Marais study above, women were randomly assigned a commercially available composition, Divine 9®, with either a placebo or lambda-carrageenan, and were told to apply the composition in conjunction with sexual activity. The test composition had 1.4% by weight of a carrageenan mixture with lambda-carrageenan and iota-carrageenan, 37% by weight of propylene glycol, and had a viscosity of 1,000 to 4,000 cP (Example 1 below). checking). The Magnan study showed similar reductions in HPV incidence as the Marais study, but due to the presence of such high concentrations of propylene glycol, the osmolarity of the composition exceeded 5,000 mOsm/kg, and the levels poses a potential risk to people using the composition, and may increase the likelihood of contracting HPV for some people.

According to the findings presented in the World Health Organization (WHO) report on sexual health (“Use and procurement of additional lubricants for male and female condoms: WHO/UNFPA/FHI360 Advisory Note”), World Health Research shows that high osmolality lubricants cause damage to the vaginal and anal epithelium and are associated with HPV, HIV, and May increase risk of infection with other sexually transmitted diseases. The WHO has also found that the primary factor determining the osmolality of a particular personal lubricant is the presence of glycol within the composition. Glycols, also commonly known as "polyols," most commonly include glycerol, 1,2-propanediol, and 1,3-propanediol, and can disrupt the water-electrolyte balance within epithelial cells. . The WHO states that most commercially available lubricants have an osmolarity far exceeding that of normal vaginal secretions (260-290 mOsmol/kg) and semen (250-380 mOsmol/kg). The osmolarity of commercially available personal lubricant compositions is determined by the company to be as osmolal as possible with vaginal secretions and/or semen (between 250 and 400 mOsmol/kg). It is recommended that the amount be adjusted to 1,200 mOsmol/kg or less, with the aim of achieving this.

Antiviral Lubricant Compositions of the Invention The present invention describes several novel antiviral lubricant compositions that contain lambda-carrageenan, are active against viruses, including HPV, and have a viscosity similar to commercially available lubricants that do not contain carrageenan. A viral lubricating composition is provided. In another embodiment, the antiviral lubricating composition has a rheological profile that allows the composition to retain its moisture and lubricity for several hours upon application, providing a pleasant experience for those 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 strain, particularly during sexual activity. In an even further embodiment, the antiviral lubricant compositions of the present invention can be poured directly from the container without the need for squeezing or manual removal. In other even further embodiments, the antiviral lubricating composition is substantially free of gel network.

As mentioned above, all types of carrageenan can be obtained from seaweed extracts, typically as a mixture of two, three or more types of carrageenan. Carrageenan mixtures are available as raw extracts or as powders. In a further embodiment, the carrageenan utilized within the antiviral lubricant composition is obtained as a carrageenan powder. Non-limiting examples of commercially available carrageenan powders include Viscarin® PC109, Viscarin® PC209, Viscarin® PC515, Gelcarin® PC379, and Gelcarin® PC911. It will be done. In an even further embodiment, the carrageenan powder is Viscarin® PC209.

In another embodiment, the carrageenan powder has at least about 85% by weight lambda-carrageenan, including at least about 90% by weight lambda-carrageenan.
In another embodiment, the kappa-carrageenan and iota-carrageenan together account for about 20% by weight of the carrageenan powder, including up to about 15%, 10%, 8%, 6%, 4%, 2%. or up to about 1% by weight of the carrageenan powder. In other embodiments, when present, kappa-carrageenan and iota-carrageenan together comprise at least about 1% by weight of the carrageenan powder, and at least about 2%, 4%, 6%, 8% by weight of the carrageenan powder. %, or up to 10%, at least about 15% by weight.

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

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

In another embodiment, the carrageenan mixture with lambda-carrageenan is substantially homogenized within the antiviral lubricating composition, and the majority of the carrageenan polysaccharides within the composition are present as free molecules within the aqueous solvent. . In a further embodiment, the carrageenan mixture is fully homogenized within the antiviral lubricating composition. In certain further embodiments, the uniform antiviral lubricating composition has a substantially uniform appearance and density. In other even further embodiments, the antiviral lubricating composition is a solution in which the ratio of carrageenan to solvent is substantially uniform. In still other even further embodiments, the antiviral lubricant composition is substantially free of particles, aggregates, lumps, or other solids visible to the naked eye and/or under a microscope at 10x magnification. In yet a further embodiment, the antiviral lubricant composition is translucent. In yet a further embodiment, the antiviral lubricant composition is transparent.

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

Similarly, the viscosity, rheology, feel, and overall performance of antiviral lubricating compositions containing lambda-carrageenan can be controlled by adding small amounts of polymers, particularly polyols, to the antiviral lubricating composition. As mentioned above, polyols are commonly used in commercial products as fillers, flavor preservers/masking agents, humectants, stabilizers, anti-crystallization agents, and for systemic and oral health benefits. is one type of compound found in Although polyols are typically added to enhance the solubility of other polymers that may be present in commercially available personal lubricant products, polyols are added in small amounts to the antiviral lubricant compositions of the present invention; Reduce viscosity, reduce irritation, provide a secondary source of lubrication, and/or provide the stimulating "warmth" or "tingling" sensation often enjoyed by users during sexual activity. Can be done.

Non-limiting examples of polyols that can be added include glycerol; propylene glycol (1,2-propanediol); 1,3-propanediol; 1,3-butanediol; 1,4-butanediol; Mention may be made of butanediol; xylitol; sorbitol; erythritol; isomalt; lactitol; maltitol; mannitol; polyethylene glycol; and polypropylene glycol; and combinations thereof. Generally, the identity and concentration of polyol(s) included in antiviral lubricant compositions can be controlled to obtain desired properties. For example, mannitol and xylitol are regulated as food additives for special dietary needs, while polyols are otherwise "generally considered safe" (GRAS). Xylitol is also used for oral prophylaxis, and mannitol is also used to prevent urinary tract infections. 1,3-butanediol, 1,4-butanediol, 2,3-butanediol have been shown to reduce irritation in topical application of ointments, creams, and gel compositions. Sugar-based polyols can provide some sweetness, while maltitol can mimic the texture of fats in edible products.

In another embodiment, the polyol can have less than about 50%, less than about 25%, less than 15%, less than 10%, 9% by weight of the antiviral lubricating composition, by weight of the antiviral lubricating composition. less than 8%, less than 7%, less than 6%, less than 5%, less than 4%, less than 3%, or less than 2%, by weight of the antiviral lubricating composition. %. In other further embodiments, the antiviral lubricating composition comprises at least about 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10% by weight of a polyol. %, including 15%, or 25%, and including at least about 35%, and at least about 1% by weight. In an even further embodiment, the polyol has from about to about 10% 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 has up to 8% propylene glycol by weight. In an even further embodiment, the antiviral lubricating composition has from 0.5% to about 5% propylene glycol by weight. In yet a further embodiment, the antiviral lubricating composition has from about 4% to about 5% by weight propylene glycol. In some embodiments, the antiviral lubricating composition has about 4.0% to about 4.5% propylene glycol by weight. In yet a further embodiment, the antiviral lubricating composition has from about 2.0% to about 2.5% propylene glycol by weight.

In another aspect, the presence of the polyol provides an antiviral lubricant composition that is superior to known personal lubricant compositions while retaining all of the sexual performance benefits of commercially available personal lubricants. , has the ability to inhibit HPV transmission and/or persistence. Additionally, the antiviral lubricant composition is thin enough to provide the tactile benefits of a personal lubricant composition, while at the same time being able to penetrate the skin or epithelial tissues, particularly the vagina, before initiating sexual contact. It is also thick enough to stay in the anus, penis, or mouth. In certain embodiments, the personal lubricant composition has a viscosity of less than about 10,000 cP, less than about 8,000 cP, less than 6,000 cP, less than 4,000 cP, or from less than 2,000 cP to less than about 1,000 cP. . In other embodiments, the antiviral lubricating composition has a viscosity of at least about 500 cP, from at least about 1,000 cP, 2,000 cP, 4,000 cP, or 6,000 cP to at least about 8,000 cP. 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, more particularly about 2,000 cP to about 3,000 cP. In certain embodiments, the antiviral lubricating composition has a viscosity of about 1,500 cP to 2,500 cP. In certain embodiments, the antiviral lubricating composition has a viscosity of about 2,000 cP.

In another embodiment, the amount of polyol within the antiviral lubricating composition is limited to provide an osmolarity within the WHO recommended levels. In other embodiments, the antiviral lubricating composition has an osmolality of less than about 1,200 mOsm/kg, less than about 1,000 mOsm/kg, less than 900 mOsm/kg, less than 800 mOsm/kg, less than 700 mOsm/kg. less than 600 mOsm/kg, less than 500 mOsm/kg, less than 400 mOsm/kg, less than 300 mOsm/kg, or less than 200 mOsmol/kg, up to less than about 100 mOsmol/kg. In further embodiments, the antiviral lubricant composition has an osmolality of about 250 to about 800 mOsmol/kg. In other further embodiments, the antiviral lubricant composition has an osmolality of about 650 to about 850 mOsmol/kg.

In another embodiment, the osmolarity of the antiviral lubricant composition is isotonic with the osmolality of human plasma. In further embodiments, the antiviral lubricant composition is isotonic with semen. In other further embodiments, the antiviral lubricant composition is isotonic with vaginal secretions. In still other further embodiments, the antiviral lubricating composition has an osmolality of about 250 mOsmol/kg to about 400 mOsmol/kg.

Also, in another embodiment, some supplemental ingredients can be added to the antiviral lubricant composition to complement the antiviral activity of the composition and/or enhance the performance of the composition during sex. In some embodiments, the pH of the antiviral lubricant composition can be controlled by adding a pH adjusting agent. Once the carrageenan is solubilized in water, the pH of the composition is typically about 7-9. However, the effectiveness of antiviral lubricant compositions can be supplemented by controlling the pH of the composition to match or resemble 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, while the pH of other epithelial cells, including those located within the rectum, is closer to neutral pH. Accordingly, in some embodiments, the pH adjusting agent is in a range complementary to the intended epithelial surface, particularly less than about 7.0, less than 6.5, less than 6.0, less than 5.5, less than 5.0, An acid that can lower the pH to a pH of less than about 8.0, including less than 4.5, and up to and including less than about 3.5. In other embodiments, the pH of the antiviral lubricant composition is at least about 3.5, and at least about 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, or 7. up to at least about 8.0. In a further embodiment, the antiviral lubricating composition has a pH of about 3.5 to about 5.5, especially about 4.5. In other further embodiments, the antiviral lubricant composition has a pH of about 5.5 to about 7.0. In still other further embodiments, the antiviral lubricant composition has a pH of about 6.25 to about 6.75.

In some embodiments, the pH adjusting agent is a strong acid including, 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. Weak acids can be selected based on buffering capacity, pKa, and availability. Non-limiting examples of weak acids that can be used as pH adjusting agents include citric acid, lactic acid, and acetic acid. In a further embodiment, the antiviral lubricating composition has from about 0.01% to about 1.0%, particularly from about 0.04% to about 0.06%, by weight of a pH adjusting agent. In an even further embodiment, the pH adjusting agent is citric acid.

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

In some embodiments, the antiviral lubricant composition can optionally further include one or more sweeteners that enhance the flavor of the composition upon contact with a person's mouth. In some embodiments, the sweetener is an artificial sweetener, the presence of which can also inhibit bacterial growth within the antiviral lubricant composition during storage. Non-limiting examples of artificial sweeteners may include, but are not limited to, aspartame, saccharin, sucralose, neotame, and acesulfame potassium. In further embodiments, the sweetener is saccharin. In an even further embodiment, the antiviral lubricating composition further comprises up to about 0.005% by weight of saccharin. In yet a further embodiment, the antiviral lubricant composition has about 0.125% saccharin.

In addition to or in place of sweeteners, the antiviral lubricant compositions may mask the odor of the composition itself, or other agents that may mask either the skin or epithelial tissue to which the antiviral lubricant compositions are applied. It can optionally further include an aromatic agent or fragrance. Non-limiting examples of such fragrances include, but are not limited to, any essential oil-based fragrance, including vanilla, lavender, oregano, thyme, lemongrass, lemons, oranges, anise, cloves, aniseed, cinnamon, Mention may be made of geraniums, roses, mint, peppermint, citronella, eucalyptus, sandalwood, cedar, rosmarine, pine, vervain fleagrass, or rattan millet, or combinations thereof. In other embodiments, the antiviral lubricant composition can optionally further include one or more chemical, aroma-generating compounds that contribute to the odor or fragrance contained in the essential oil-based fragrance. Non-limiting examples of chemical aroma-generating compounds that can be included in any of the antiviral lubricant compositions include carvacrol, eugenol, linalool, thymol, p-cymene, myrcene, borneol, camphor, caryophyllin, cinnamaldehyde. , geraniol, nerol, citronellol, and menthol, and combinations thereof.

In some embodiments, the antiviral lubricating composition can optionally further include one or more metal salts. Addition of metal salts can have several effects, including controlling the ionic strength of the composition, enhancing its antibacterial or antiviral activity, or adding to the solubilization of one or more components. . Metal salts that can be added include, but are not limited to, zinc, silver, copper, alkali metal salts, or alkaline earth metal salts. In further embodiments, the metal salt is a zinc salt or a sodium salt.

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

The present invention also provides for the use of antiviral lubricant compositions produced by the methods described below to prevent the transmission of HPV, HIV, and HSV between two or more partners engaged in sexual activity. Several methods are provided for reducing, inhibiting, or ameliorating the transmission of sexually transmitted viruses. In a first aspect, the method includes contacting the antiviral lubricating composition with the skin or epithelial tissue of one or more partners, the skin or epithelial tissue being vaginal, anal, oral, or penile. a step located on or within at least one of the two. As used herein, the term "vagina" includes the vagina itself and/or the skin or epithelial tissue surrounding the vagina, including, but not limited to, the vulva, labia, clitoris, vaginal opening, and cervix. . In further embodiments, at least one partner is male and at least one partner is female. In other further embodiments, at least two partners are male. In yet another embodiment, at least two partners are female.

In another embodiment, the antiviral lubricant composition is placed on or within the skin of one or more of the sexual partners, particularly at least one of the vagina, anus, mouth, or penis, prior to sexual activity. In contact with the skin, the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV, from one sexual partner to another can be prophylactically inhibited. In such embodiments, the antiviral lubricant composition is administered for less than about 8 hours, less than 4 hours, less than 2 hours, less than 1 hour, less than 30 minutes, less than 15 minutes, less than 5 minutes, less than 1 minute, or less than about 1 minute before sexual activity. Contact can be made with the skin of one or more sexual partners for less than about 30 seconds and up to less than about 1 second prior to sexual activity. In other embodiments, the antiviral lubricating composition is administered at least 1 hour, at least about 30 seconds, 1 minute, 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, or about 8 hours before sexual activity. Can be brought into contact with the skin of more than one sexual partner.

In another embodiment, the antiviral lubricating composition is applied to the skin of one or more of the sexual partners after sexual activity, particularly the skin located on or within at least one of the vagina, anus, mouth, or penis. The cell-to-cell spread of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV, can be reduced after HPV is infected by skin-to-skin contact. In such embodiments, the antiviral lubricant composition is administered for less than about 8 hours, less than 4 hours, less than 2 hours, less than 1 hour, less than 30 minutes, less than 15 minutes, less than 5 minutes, less than 1 minute, or less than about 1 minute after sexual activity. Contact can be made with the skin of one or more of the sexual partners for less than about 30 seconds, even less than about 1 second. In other embodiments, the antiviral lubricating composition is administered to one person 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. Can be brought into contact with the skin of a sexual partner.

In another aspect, a method of reducing, inhibiting, or ameliorating the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV between two or more partners engaged in sexual activity comprises: providing a substrate having one or more skin-contacting surfaces, the substrate being configured for insertion into one or more body cavities selected from the group consisting of a vagina, a mouth, or an anus; lubricating one or more skin-contacting surfaces of the substrate with an antiviral lubricating composition, thereby producing a lubricated substrate; applying the lubricated substrate to the vagina, anus, or mouth of one or more partners; or the skin or epithelial tissue located on or within at least one of the penis; and further comprising the step of transferring the antiviral lubricating composition from the lubricated substrate to the skin or epithelial tissue. In some further embodiments, only one person, either a man or a woman, uses the substrate during sexual activity. In other further embodiments, there is more than one partner using the substrate, and any of the sexual partners may be either male or female.

Any object, device, or material that can be used to contact internal or external surfaces on or within the vagina, anus, mouth, or penis during sexual activity may be used as a suitable substrate for use in conjunction with the method of the present invention. Accessories can be mentioned. Non-limiting examples of substrates that can be utilized according to the method of the invention include condoms having materials including, but not limited to, rubber, latex, plastic, wood, and/or metal; sex toys, dildos, vibrators, rings; , sexual accessories such as beads; and internal applicators. Such examples are described in US 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. Those skilled in the art will appreciate the commercially available and improvised, sexual-themed or not, base materials that can be utilized during sexual activity and to which the antiviral lubricant compositions of the present invention can be applied. It will be appreciated that there are countless other examples of materials.

In another embodiment, the substrate is a condom. As used herein, the term "condom" includes devices designed to be worn in or on the penis, vagina, anus, or fingers by a man or a woman. Condoms can also be worn over the sexual accessories described below. The antiviral lubricating composition may be applied to the inner surface of the condom or the outer surface of the condom before or after the condom is placed on or into the penis, finger, vagina, anus, mouth, or other body part or object. It can be applied to the skin-contacting surface located on at least one of the following: In a further embodiment, a condom pre-lubricated with any of the antiviral lubricating compounds of the present invention can be provided in a package that encloses the lubricated condom and seals it from the external environment outside the package. In an even further embodiment, the package includes a watertight seal, such that the antiviral lubricating composition is removed before opening the package, applying a pre-lubricated condom over the penis or similar sexual accessory device, and engaging in sexual activity. Prevent property loss. Methods of lubricating condoms and packaging them to protect them from the external environment prior to use during sexual activity are well known in the art.

In some embodiments where the condom is a base material, the method reduces, inhibits, or ameliorates the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV, between sexual partners. or the method of preventing includes: lubricating the skin-contacting surface of the condom; contacting skin or epithelial tissue within the mouth, vagina, or anus of one or more partners with the lubricated skin-contacting surface of the condom; and transferring the antiviral lubricating composition from the lubricated skin-contacting surface of the condom to the skin or epithelial tissue.

In further embodiments where the substrate is a condom, the method reduces or inhibits the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV, between two or more partners engaged in sexual activity; The method includes placing a condom on the fingers or penis of one partner; lubricating the outer surface of the condom with an antiviral lubricating composition; The method further comprises contacting the skin or epithelial tissue within the partner's mouth, vagina, or anus; and transferring the antiviral lubricating composition from the lubricated outer surface of the condom to the skin or epithelial tissue.

In other further embodiments where the substrate is a condom, the method reduces or inhibits the transmission of sexually transmitted viruses, including but not limited to HPV, HIV, and HSV, between two or more partners engaged in sexual activity. , or a method for improving the process of lubricating a condom; sealing a lubricated condom in a package; storing a lubricated condom in a package; removing a lubricated condom from a package; applying a lubricated condom to the finger or penis of a partner; contacting the skin or epithelial tissue within the mouth, vagina, or anus of one or more additional partners with the lubricated condom; and the lubricated condom transferring the antiviral lubricating composition from the skin or epithelial tissue to the skin or epithelial tissue.

In another embodiment, the substrate is an internal applicator. Internal applicators suitable for use in conjunction with the methods of the invention can be configured to be inserted into a body cavity of a person and are capable of transferring the antiviral lubricant composition to epithelial tissue within the body cavity of a person. can include any object, device, or accessory that can Non-limiting examples of internal applicators that can be utilized in accordance with the methods of the present invention include syringes, pipettes, swabs, cannulas having materials including, but not limited to, rubber, latex, plastic, wood, and/or metal. , elongated sticks or rods, and wearable inserts. Such examples include US Patent No. 2,546,754, 4,557,720, 4,808,166, No. 6,503,220, No. 6,537,260, No. 7,442,179, No. 7,591,808, No. 9,290,551, the same. No. 9,757,549 No. 9,884,173, the disclosures of which are incorporated by reference in their entirety. Those skilled in the art will appreciate that the antiviral lubricating composition of the present invention can be applied to and contacted with the skin or inserted into a body cavity to transfer the antiviral lubricant composition to the epithelial tissue within the body cavity. It will be appreciated that there are countless other examples of applicators.

In another embodiment, the internal applicator comprises a skin-contacting surface configured to contact epithelial tissue within a body cavity of a person, particularly within the vagina or rectum. In other embodiments, the internal applicator has a container that houses or is configured to contain the antiviral lubricant composition prior to transferring the antiviral lubricant composition to epithelial tissue within a human body cavity. In either case, the internal applicator can be provided in a package with or without the antiviral lubricating composition. In a further embodiment, the internal applicator is pre-lubricated with an antiviral lubricant composition and sealed within the package to protect the lubricated internal applicator from the external environment and to apply the antiviral lubricant prior to transfer to epithelial tissue within a human body cavity. Prevents loss of composition. Methods of applying lubricants or therapeutic substances to internal applicators and packaging them are well known in the art.

In another aspect, the invention also provides methods of reducing, inhibiting, or ameliorating the transmission, symptoms, or effects of non-sexually related viruses. The method comprises the steps of: (a) providing any of the antiviral lubricant compositions described above; and (b) administering the antiviral lubricant composition to a skin or epithelial tissue in which a viral infection is known or suspected to be present, inside or outside the body. contacting on either the outside. The antiviral lubricant composition can be applied to the skin or epithelial tissue using the fingers or any of the applicators described above. In another embodiment, a lubricated swab, stick, or rod can be inserted into any of the above body cavities, including the mouth and nose, and contacted with the epithelial tissue lining the nasal cavity or throat.

Non-limiting examples of viral taxonomic families that can be treated with any of the antiviral lubricating compositions of the present invention include Orthomyxoviridae, Paramyxoviridae, Pneumoviridae, Coronaviridae, Retroviridae, Included are Viridae, Herpesviridae, Padromaviridae, Picornaviridae, Reoviridae, and Adenoviridae, and combinations thereof. Such viruses within these taxonomic families include severe acute respiratory disease (SARS) strains 1 and 2 (COVID-19); influenza A, B, and C; enteroviruses, rhinoviruses, polioviruses, and adenoviruses. Viruses include, but are not limited to, rotavirus, and the viruses that cause measles, mumps, and chickenpox. In another embodiment, the antiviral lubricant composition can be applied to the skin or epithelium of a human having a viral infection or as a prophylactic to prevent receiving a viral infection. In another embodiment, the antiviral lubricant composition can be applied to the skin or epithelium of an animal that has a viral infection or as a prophylactic to prevent receiving a viral infection.

Treatment of Antiviral Lubricating Compositions Antiviral lubricating compositions produced by the methods of the present invention have the ability to inhibit viral activity, including the viral activity of sexually transmitted viruses such as HPV, HIV, and HSV; It is unique in having optimized viscosity, lubricity, and feel that enhance its performance as a lubricant during sexual activity, while at the same time minimizing the osmolarity of the composition. In some embodiments of the invention, a method of forming an antiviral lubricating composition of the invention includes (a) providing a carrageenan powder having carrageenan, the carrageenan comprising at least about 90% by weight lambda-carrageenan. and iota-carrageenan up to about 10% by weight; (b) combining the carrageenan powder with an aqueous solution having a polyol while mixing to form a cloudy carrageenan suspension; and (c) cloudy carrageenan suspension. heating the liquid to a temperature of at least 60°C and mixing for a sufficient time to convert the cloudy carrageenan suspension into a clear homogeneous solution, thereby forming an antiviral lubricating composition; (i) the antiviral lubricating composition has from about 0.5% to about 2.3% by weight carrageenan and up to about 10% polyol; (ii) the antiviral lubricating composition has (iii) the antiviral lubricating composition is translucent; (iv) the antiviral lubricating composition has a turbidity of less than 25 nephelometric turbidity units (NTU); .

In another embodiment, the method of forming an antiviral lubricating composition of the present invention can further include a premixing step of first combining carrageenan powder and polyol to form a wet carrageenan mixture having carrageenan and polyol. Without wishing to be bound by any particular theory, it is believed that premixing and dispersing the carrageenan powder in the polyol before adding water may partially loosen the carrageenan polysaccharides and free up additional fractions to interact upon addition of the aqueous solution. It is believed that polar contacts will be available. Premixing includes mixing under low speed and low shear conditions; heating at low temperatures to homogenize the carrageenan in the aqueous solution; enhancing the efficiency of each mixing step, especially mixing to homogenize the carrageenan in the aqueous solution; Protecting the carrageenan polysaccharide from breaking down into smaller segments, which could adversely affect the viscosity and performance of the composition as a personal lubricant; (see below). In a further embodiment, a method of forming an antiviral lubricating composition of the present invention includes the steps of: (a) providing a carrageenan powder having carrageenan, the carrageenan comprising about 90% by weight of lambda-carrageenan and 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) combining the wet carrageenan mixture with an aqueous solution while mixing to form a cloudy carrageenan suspension, the volume ratio of the aqueous solution to carrageenan being from about 45:1 to about 8:1; a step; (d) heating the cloudy carrageenan suspension to a temperature of at least 60°C and mixing for a sufficient time to convert the cloudy carrageenan suspension into a clear homogeneous solution, thereby forming an antiviral lubricant composition; (i) the antiviral lubricating composition has 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 NTU. be.

In particular, the viscosity of an antiviral lubricant composition is an important factor in its performance as a personal lubricant that can be used in conjunction with sexual activity. Ideally, a personal lubricant would have sufficient viscosity to be applied to the skin or epithelial tissue and remain there until sexual activity begins, while at the same time providing lubrication and moisture from the composition for the entire duration of sexual activity. It also has a rheological profile that is maintained throughout. The presence of carrageenan in the composition is diametrically opposed to the performance of a sexual lubricant since the viscosity of the composition increases exponentially as a function of carrageenan concentration (see Example 3 below) .

Similarly, the viscosity of antiviral lubricating compositions depends on the total carrageenan concentration, as well as the identity and relative concentrations of the kappa, iota, and lambda forms of carrageenan; the concentration and identity of additional components, particularly polyols; and the weight ratio of carrageenan to polyol, if present. The viscosity also depends on the heating of one or more of the wet carrageenan mixture, carrageenan suspension, and/or antiviral lubricating composition; the rate of addition of any components of the composition; the speed and duration of the mixing process; It also depends on the process itself, including but not limited to the type of rotor used. In short, all of the above factors need to be adjusted to optimize the performance of antiviral lubricant compositions during sexual activity.

In another aspect, the viscosity of the antiviral lubricating composition is determined by the kappa, iota, and lambda forms of carrageenan, which differentially affect not only the total carrageenan concentration, but also the exponential rate of increase in the viscosity of the antiviral lubricating composition. It also depends on the relative concentration of As an example, the presence and increasing concentration of kappa-carrageenan causes a rapid increase in the viscosity of the composition, whereas the exponential growth rate caused by the presence and increasing concentration of iota-carrageenan less than the rate of The exponential growth rate caused by the presence and increasing concentration of lambda-carrageenan is smaller than both kappa-carrageenan and iota-carrageenan. Therefore, a composition that is primarily lambda-carrageenan has a lower viscosity than a composition that is primarily kappa-carrageenan and/or iota-carrageenan. As a result, as discussed above, the antiviral lubricating compositions of the present invention can have about 90% or more lambda-carrageenan and up to about 10% kappa-carrageenan or iota-carrageenan or both. In an even further embodiment, the antiviral lubricating composition has about 90% lambda-carrageenan and about 10% kappa-carrageenan. In other even further embodiments, the antiviral lubricating composition has about 90% lambda-carrageenan and about 10% lambda-carrageenan.

The physical form in which carrageenan mixtures are obtained also influences how they must be processed. When carrageenans are obtained as raw extracts, they are already primarily liquid. However, raw carrageenan extracts typically have a shorter shelf life than solid powders, and carrageenan extracts may contain undesirable or harmful components. As a result, it is common to obtain dry carrageenan in powdered form for use in the food or pharmaceutical industry, but with the trade-off that the carrageenan must be resolubilized for use in liquid compositions. .

In applications where carrageenan is ultimately used as a thickening agent, carrageenan powder can be easily solubilized by high shear and high speed mixing conditions over extended periods of time, often even under aggressive heating conditions. However, carrageenan powder cannot be processed in the same manner to produce the antiviral lubricating compositions of the present invention. This is because such conditions cause the resulting composition to lose its lubricity over time, especially when subjected to shear thinning stresses that occur during sexual activity. Without wishing to be bound by any particular theory, it is believed that the length of the carrageenan polysaccharide is directly correlated to the lubricity and moisture content of the resulting composition. As the average length of the polysaccharide increases, the lubricity of the composition also improves. On the other hand, solubilizing carrageenan powder under high shear and stress conditions results in premature drying of the resulting composition.

In another embodiment, solubilization of carrageenan powder can be assisted by adding the powder to a polyol. As mentioned above, polyols are commonly included in personal lubricant compositions because of the pleasurable properties their presence provides during sexual activity. The multiple hydroxyl groups on each polyol molecule have an additional advantage because they provide intermolecular contacts that allow individual sugars within the larger carrageenan polysaccharide to interact in solution. Without being limited to alternative theories, as the amount of polyol that is mixed with carrageenan powder to form a wet carrageenan mixture increases, it becomes available to interact with and solubilize the aqueous solvent. The number of polar functional groups within each carrageenan polysaccharide also increases, causing a concomitant increase in the viscosity of the antiviral lubricant composition.

Conventional antiviral lubricant compositions containing polyols with lambda-carrageenan lubricant compositions have been synthesized by simply adding carrageenan powder to a bulk solvent containing greater than 37% by weight propylene glycol (as described in the following implementation). (see Example 1). At this concentration, the propylene glycol concentration causes a dangerous increase in the osmolality of the composition. However, it was found that by simply lowering the polyol concentration in the solvent, it was not possible to completely homogenize the carrageenan powder even when heated to 75°C. Instead, multiple "hydro-sealed" masses were formed containing dried carrageenan powder surrounded by semi-hydrated carrageenan molecules that were impermeable to the addition of water. The same is true for dry powders that are only exposed to atmospheric conditions containing water, and a similar phenomenon was observed in the '098 patent (supra).

In some embodiments, the method of forming an antiviral lubricating composition of the present invention includes first mixing carrageenan powder with at least one polyol to form a wet carrageenan mixture prior to adding the carrageenan. Can be done. In a further embodiment, complete homogenization of the carrageenan polysaccharide within the antiviral lubricant composition is facilitated by first solubilizing the carrageenan powder in a polyol.

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 about 50 times more viscous than water, while glycerol is about 23 times more viscous than 1,2-propanediol. Thus, an antiviral lubricating composition can have a much higher concentration of 1,2-propanediol than a second composition containing glycerol while having the same viscosity. Consequently, in another embodiment, the weight ratio of polyol to carrageenan in the wet carrageenan mixture is at least 1:10, 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 50:1. In further embodiments, the weight ratio of polyol to carrageenan is from about 1:1 to about 10:1. In an even 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, the viscosity of the antiviral lubricating composition decreases as the weight ratio of aqueous solution to wet carrageenan mixture increases. 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 an even 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 one or more of the wet carrageenan mixture, carrageenan suspension, and/or antiviral lubricant composition allows solubilization and homogenization of the carrageenan in water. Without being bound by any particular theory, heating carrageenan causes at least partial unfolding of each carrageenan polysaccharide and disruption of intermolecular interactions between the polysaccharides, both of which affect the viscosity of the composition. is expected to increase. As heating continues, the carrageenan polysaccharide begins to solubilize within 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 oligosaccharides with smaller molecular weights and chain lengths. There is sex. In a further embodiment, the carrageenan suspension is heated until an antiviral lubricant composition is formed that has a viscosity of less than about 5,000 cP. In an even further embodiment, the carrageenan suspension is heated until an antiviral lubricating composition is formed that has a viscosity of about 1,000 cP to about 4,000 cP.

Compositions containing carrageenan, such as non-homogenized carrageenan suspensions, are typically cloudy, hazy, or cloudy and have a large number of macroscopically visible carrageenan particles. Without wishing to be bound by any particular theory, it is believed that the turbidity of carrageenan suspensions results from two or more carrageenan polysaccharides being completely unwound and forming aggregates before being exposed to the aqueous solvent. It will be done. In another embodiment, the carrageenan suspension is heated until a translucent antiviral lubricant composition is formed. In a further embodiment, the carrageenan suspension is heated until a clear antiviral lubricant composition is formed. In such embodiments, the translucent and/or transparent properties of the antiviral lubricating composition are maintained even after extended packaging and/or storage. In an even further embodiment, there are substantially no particles, aggregates, or aggregates visible within the antiviral lubricating composition. In yet a further embodiment, the substantially homogeneous antiviral lubricating composition is a solution.

Turbidity of any of the mixtures, suspensions, or antiviral lubricant compositions disclosed herein can be quantitatively described based on methods for determining the concentration of suspended particles in a sample. This includes, but is not limited to, formazin nephelometric units (FNU), Jackson turbidity units (JTU), NTU, optical density, Helm units, parts per million (PPM), etc. . FNU and NTU are widely used to describe the turbidity of compositions with a uniform distribution of small particles and are measured by measuring the amount of light scattered at 90 degrees to the incident light beam. In particular, NTU is typically measured using visible light from about 400 nm to about 680 nm as the incident light beam, whereas FNU is typically measured using infrared light from about 780 nm to about 900 nm as the incident light beam.

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

In other embodiments, antiviral lubricant compositions made by the methods of the invention, particularly antiviral lubricant compositions that may come into contact with the mouth during sexual activity, have a turbidity that is approximately equivalent to the turbidity of drinking water. It can be homogenized to a certain degree. Governments, health agencies, and other regulatory bodies are concerned with the potential risk of turbidity caused by agents that increase solution turbidity, including, but not limited to, polymers and other macromolecules; insoluble small molecules; and bacteria and other microorganisms; Describe safety standards to protect people and animals from hazardous health conditions. WHO has determined that drinking water should not exceed 5 NTU, and ideally should be less than 1 NTU. In the United States, systems that utilize conventional or direct filtration methods are required to reduce drinking water turbidity to less than 1 NTU, and some regions strive to achieve turbidity levels of less than 0.1 NTU. There is.

In another embodiment, the type of mixing equipment, rotation speed, and mixing time can be optimized to control the viscosity of the resulting antiviral lubricating composition to disperse and homogenize the carrageenan in the aqueous solution. In some embodiments, prior to applying the composition to the skin or epithelial tissue, particularly before or in connection with sexual activity, maintaining the length of each carrageenan polysaccharide and maintaining their lubricity, Mixing can be carried out under low shear conditions for a sufficient time to homogenize the composition. In contrast, and in other embodiments, mixing can be conducted under high shear conditions for a minimum amount of time; however, mixing for more than the minimum amount of time irreversibly destroys the carrageenan polysaccharide and destroys the composition. It can reduce viscosity and reduce the composition's performance as a lubricant during sexual activity. Non-limiting examples of mixers include, but are not limited to, screw mixers, tumble mixers, ribbon mixers, and paddle mixers. In an even further embodiment, a paddle mixer can be used for each of the mixing steps to form the antiviral lubricating composition. Similarly, mixing at relatively low speeds preserves the structural integrity of each polysaccharide. In other even further embodiments, each mixing step is performed at a mixing speed of about 500 RPM or less. In still further embodiments, mixing of the antiviral lubricating composition after homogenizing the carrageenan in the aqueous solution can be performed at a speed of about 250 RPM or less.

In another aspect, a method of forming an antiviral lubricating composition includes the steps of: (e) cooling the homogenized antiviral lubricating composition until the temperature of the antiviral lubricating composition is less than about 30°C; (f ) mixing one or more pH adjusting agents into the cooled antiviral lubricant composition in a weight sufficient to adjust the antiviral lubricant composition to a pH of about 3.5 to about 7.0; (g) optionally mixing one or more sweeteners into the carrageenan suspension or the cooled antiviral lubricant composition at up to 0.5% by weight of the antiviral lubricant composition; (h) optionally , into the carrageenan suspension or the cooled antiviral lubricant composition, one or more preservatives at up to 1% by weight of the antiviral lubricant composition; . In further embodiments, each of the pH adjusting agents, sweeteners, and preservatives described above, and additional ingredients such as salts and/or fragrances are included within the antiviral lubricant composition to supplement its anti-HPV activity; and/or can improve performance during sexual activity. Composition properties as a result of adding pH modifiers, sweeteners, and preservatives are described above.

In another embodiment, the above method can be utilized to homogenize carrageenan mixtures having different lambda, kappa, and iota-carrageenan ratios into an aqueous solvent at any desired viscosity. In some embodiments, the lambda-carrageenan has at least about 50% by weight of the carrageenan powder, including at least about 60 or 70% by weight and up to about 80% by weight of the carrageenan powder. In other embodiments, the lambda-carrageenan has less than about 85%, less than 80%, or less than 70% to less than about 60% by weight of the carrageenan powder. In such embodiments, the amount of kappa and iota-carrageenan, if present, is up to about 50%, such as up to 40%, up to 30%, by weight of the combined carrageenan powder; It can be increased to have up to 20% by weight.

While particular aspects of the invention have been described, the invention can be further modified within the spirit and scope of this disclosure. Those skilled in the art will recognize, or be able to ascertain, using no more than routine experimentation, many equivalents to the specific procedures, embodiments, claims, and examples described herein. Such equivalents are therefore deemed to be within the scope of this invention, and this application is therefore intended to cover any variations, uses, or adaptations of this invention, using its general principles. There is. In addition, the present invention is intended to cover such departures from this disclosure as are within the scope of those known or practiced in the art to which the present invention pertains and which fall within the scope of the appended claims. .

It is understood that certain features of the invention that are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention that are, for brevity, described in the context of a single embodiment, may be used separately or in any suitable subcombination or in any other described embodiment of the invention. It may be suitably provided in a different manner. Certain features described in the context of various embodiments should not be considered essential features of those embodiments, unless the embodiments are not functional without those elements.

The contents of all references, patents, and patent applications mentioned herein are hereby incorporated by reference, and there is an acknowledgment that such references are available as prior art to the present invention. It should not be interpreted as such. All publications and patent applications incorporated herein are indicative of the level of those skilled in the art to which this invention pertains, and are indicative of the level of those skilled in the art to which this invention pertains, as if each individual publication or patent application were specifically indicated and individually indicated by reference. It is incorporated to the same extent as if it were.

The invention is further illustrated by the following examples and prophetic examples, none of which should be construed as limiting the invention. Further, to the extent section headings are used, they should not necessarily be construed as limiting. The use of the past tense to describe examples shown to be constructive or prophetic is not intended to reflect that the constructive or prophetic examples were actually carried out.

The following examples and prophetic examples illustrate the aspects of the invention that are currently best known. However, it is to be understood that the following is merely an illustration or explanation of the application of the principles of the 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 invention. Thus, having described the invention in detail, the following examples provide further details regarding what are presently considered to be the most practical and preferred embodiments of the invention.

EXAMPLES Example 1: Preparation of High Osmolality Personal Lubricant Compositions The following antiviral lubricant compositions were prepared from the commercially available Lambda-Carrageenan-based personal lubricant Divine 9®. Prepared according to the procedure used for its preparation.
component
55.70% (w/w) Deionized water 37.40% (w/w) Propylene glycol 5.00% (w/w) 2.5% (w/v) Sodium saccharin in deionized water 1.40% (w/w) Viscarin® PC209 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® PC209 carrageenan powder were combined and mixed thoroughly together. The composition was gradually heated to 75° C. with constant mixing. When the composition reached 50° C., Viscarin® PC209 carrageenan powder was gradually mixed in until all of the carrageenan powder was added. The composition was continued to be mixed at 75° C. for approximately 2 hours until all of the Viscarin® PC209 carrageenan powder was dissolved. Once the carrageenan powder was dissolved, mixing was stopped and the composition was rapidly cooled. Once 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 a Low Osmolarity Antiviral Lubricating Composition The following antiviral lubricating composition was prepared according to embodiments of the invention and the following procedure.
component
88.49% (w/w) deionized water 4.40% (w/w) 1,2-propanediol 5% (w/w) 2.5% (w/v) Sodium saccharin 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) Chlorphene 0.03% (w/w) GeoGard 111-Dehydroacetate Sodium Preservative (Lonza Consumer Care)

Mix Viscarin® PC 209 carrageenan powder and 1,2-propanediol for approximately 10 minutes using a Mixer Direct R-AD665 industrial gallon paddle mixer with two folding impeller blades operating at 500 RPM. A wet carrageenan mixture was formed. After 10 minutes, no agglomerated particles of powder were observed in the wet carrageenan mixture. While mixing continued, approximately 90% by volume water and total saccharin were 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 mixed under the same mixing conditions until the carrageenan powder was completely homogenized in water. After about 90 minutes, homogenization was achieved with a transition from a cloudy suspension to a clear solution. After homogenization, mixing was continued for an additional 10 minutes. The mixer was paused and the composition was cooled to below 30°C. Once cooled, the preservative, citric acid, and remaining water were added to the composition and mixed for 20 minutes at 250 RPM. The resulting antiviral lubricant composition was translucent and had a pH of approximately 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 with various carrageenan concentrations. The first sample, Sample VI, was prepared according to the same ingredient specifications and procedure as the composition of Example 1. Additional antiviral lubricant compositions containing different concentrations of carrageenan (Samples V2-V5) were prepared using the procedure of Example 2. The amount of water added was adjusted as necessary. Final volume of 200 mL for each sample composition. The concentration of carrageenan and the viscosity of each sample are shown in Table 2 below.

Each of the viscosity measurements were made using a Brookfield LVF Dial Reading Viscometer using a #2 spindle at 12 revolutions per minute according to the instructions provided with the instrument. The relationship of viscosity of antiviral lubricant compositions as a function of carrageenan concentration is shown in FIG. By fitting the data to an exponential model using Microsoft Excel, a fitted curve with an ^R2 value of 0.994 was obtained, indicating a strong correlation between the data and the model.

Example 4: Linear Effect of 1,2-Propanediol on the Osmolality of the Composition To evaluate the effect of 1,2-propanediol on the osmolarity of the antiviral lubricating composition, 1, Several compositions were formulated with varying concentrations of 2-propanediol. The first sample, Sample O1, was prepared according to the same ingredient specifications and procedure as the composition of Example 1. Additional antiviral lubricant compositions (Samples O2-O5) with different concentrations of 1,2-propanediol were prepared using the procedure of Example 2. The amount of water added was adjusted as necessary. Final volume for each sample composition: 50 mL. The concentration of 1,2-propanediol and the osmolarity of each sample are shown in Table 3 below.

Each of the osmolarity measurements was performed with an osmometer capable of measuring freezing point depression according to the United States Pharmacopeial Convention Standard Protocol (USP <785>, see Osmolarity and Osmolarity, 2017). The relationship of osmolarity of antiviral lubricating compositions as a function of 1,2-propanediol concentration is shown in FIG. 2. Fitting the data to a linear model using Microsoft Excel yields a fitted line with an ^R2 value of 0.9974, indicating a strong correlation between the data and the model.

Prophetic Examples Example 5: Disaccharide Content Characterization of Antiviral Lubricating Compositions Each primary form of carrageenan has a different repeating disaccharide structure - iota-carrageenan contains D-galactose-4-sulfate and 2 - has alternating disaccharides of sulfo-3,6-anhydro-D-galactose; Kappa-carrageenan has alternating disaccharides of D-galactose-4-sulfate and 3,6-anhydro-D-galactose; Lambda-carrageenan has alternating disaccharides of D-galactose-2-sulfate (1-3 linkages) and D-galactose-2,6-disulfate (1,4 linkages). As a result, lambda-carrageenan typically contains more sulfate groups per polymer and substantially fewer anhydrogalactose residues commonly found in iota-carrageenan and kappa-carrageenan. Therefore, the relative ratios of lambda, iota and kappa carrageenan in antiviral lubricating compositions can be determined using infrared spectroscopy (IR), nuclear magnetic resonance (NMR) spectroscopy (de Araujo, CA, et al., (2013) Carbohydrate Polymers 91:483-491) and liquid chromatography coupled to mass spectrometry (LC-MS) (Internet http://abstracts.aaps.org/Verify/AAPS2017/PosterSubmissions/M8109. Diez, F., et al., (2017) “Development of an Analytical Method to Determine the amount of e Carrageenan in HPMC Capsules by LCMS,” American Association of Pharmaceutical Scientists Poster Submission, available as pdf on May 3, 2018. It can be measured by a number of analytical techniques, including but not limited to (see ).

In particular, the IR spectra of antiviral lubricating compositions can be used to determine the profile of the composition, which can be compared to other lambda-carrageenan-containing compositions, and the lambda-, iota-, and kappa-carrageenan types within the composition. (See Volery, P., et al., (2004) J. Agric. Food Chem. 52 (25):7457-7463). Within the fingerprint region of a typical IR spectrum (about 800 cm ^-1 to about 1250 cm ^-1 ), carrageenan exhibits several strong and broad absorptions for commonly found residues or functional groups within each polymer. It has a strong absorption maximum at about 1065 cm ⁻¹ to about 1020 cm ⁻¹ , especially about 1050 cm ⁻¹ . Determine the relative abundance of specific forms of carrageenan in the IR sample by comparing the intensities of the main absorption bands at 1050 cm ⁻¹ and using the absorbance intensities of specific bands corresponding to residues or functional groups. be able to. The characteristic absorption bands and their intensity relative to the main absorption band at 1050 cm ⁻¹ are shown in Table 4 below.

A study was conducted in accordance with the principles of the present invention to characterize carrageenan within a sample of an antiviral lubricating composition. Samples of antiviral lubricant compositions were submitted to the Food and Agriculture Organization of the United Nations/World Health Organization Joint Compendium of Food Additive Specifications (“Carrageenan, Compendium of Food Additive Specifications FAO JEFCA Monographs 16; FAO/WHO Publications; Rome, Italy). ; pp. 7-12).The antiviral lubricating composition of the present invention can be compared with other compositions containing lambda-carrageenan. The IR spectrum of the antiviral lubricant composition is expected to have peaks at 810 cm ^-1 to 820 cm ^-1 and 825 cm ^-1 to 830 cm ^-1 . This indicates the presence of lambda-carrageenan in the antiviral lubricating composition. Furthermore, the molar ratio of lambda-carrageenan in the antiviral lubricating composition is lower than the molar ratio of kappa-carrageenan and iota-carrageenan. is also expected to be large.

Example 6: Antiviral Effects of Antiviral Lubricant Compositions Against Respiratory Viruses in Human Subjects Research was conducted in accordance with the principles of the present invention to treat human subjects with active viral respiratory infections, such as COVID-19, or The effectiveness of an antiviral lubricant composition in human subjects who are in close contact with a person with a sexually transmitted viral respiratory infection is determined. Participants will be asked to apply the antiviral lubricant composition of Example 2 to the tip of the swab and insert the swab through the nose until it makes contact with the epithelial tissue within the nose and nasal cavity. Alternatively, participants are asked to dispense an amount of the antiviral lubricant composition into their mouth and sip, swirl, or gargle the composition in their mouth before swallowing. The volume of the composition administered by either method is between 0.1 mL and 5 mL. The antiviral lubricant composition of Example 2 can be administered in neat form or diluted before administration. Participants will be asked to administer the antiviral lubricant composition into their nasal cavity 1 to 4 times per day. Participants may also be asked to administer the composition before and/or after coming into close contact with another person or going out in public. In the case of an active infection, the progression of symptoms is expected to be attenuated or attenuated in a dose-dependent manner until complete elimination. Also, the viral load of the virus transmitted to subjects who are not sick but are in close contact with sick patients is expected to be delayed, reduced, or eliminated.

Claims (20)

(a) 0.1% to 3% by weight carrageenan having about 90% by weight of lambda-carrageenan and about 10% by weight of kappa-carrageenan;
(b) polyol 0.1% to 8% by weight;
(c) one or more pH adjusters from 0.01% to 1% by weight; 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;
An antiviral lubricating composition having
(i) the antiviral lubricating composition is a homogeneous aqueous solution having a turbidity of about 25 nephelometric turbidity units (NTU) or less;
(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 3.5 to 7.0.
Antiviral lubricating composition. 1. The antiviral lubricating composition comprises 1.5 to 1.7% by weight of carrageenan and 4.0 to 4.5% by weight of propylene glycol, and has a viscosity of 2,000 cP to 3,000 cP. The antiviral lubricating composition described in . The antiviral lubricating composition according to claim 1, wherein the antiviral lubricating composition has an osmolality of 200 mOsmol/kg to 1400 mOsmol/kg. The antiviral lubricant composition comprises 1.5% to 1.7% by weight of carrageenan; 4.0% to 4.5% by weight of propylene glycol; and 0.01% by weight of one or more pH adjusters. % to 1% by weight; one or more sweeteners up to 0.5% by weight; and one or more preservatives up to 1% by weight; ~7.0; the viscosity of the antiviral lubricating composition is 2,000 cP ~ 3,000 cP; and the osmolarity of the antiviral lubricating composition is 650 mOsmol/kg ~ 850 mOsmol/kg. Antiviral lubricating composition according to any one of claims 1 to 3. The composition may include Orthomyxoviridae, Paramyxoviridae, Pneumoviridae, Coronaviridae, Retroviridae, Herpesviridae, Papillomaviridae. Reduces the transmission of viruses from a taxonomic family selected from the group consisting of papillomaviridae, picornaviridae, reoviridae, and adenoviridae, and combinations thereof. 2. The antiviral lubricating composition of claim 1, wherein the antiviral lubricating composition is effective to inhibit, inhibit, or ameliorate. 6. The antiviral lubricating composition of claim 5, wherein the composition is effective to reduce, inhibit, or ameliorate transmission of human papillomavirus (HPV). 6. The composition of claim 5, wherein the composition is effective to reduce, inhibit, or ameliorate transmission of a virus selected from the group consisting of Severe Acute Respiratory Syndrome (SARS) virus 1 strain and SARS strain 2. Antiviral lubricating composition. A lubricated substrate having at least one skin contacting surface lubricated with an injectable antiviral lubricating composition according to any one of claims 1 to 7, wherein the antiviral lubricating composition is applied to the skin contacting surface. A lubricated substrate useful for transfer from skin to human skin or epithelial tissue. 9. The lubricated substrate of claim 8, wherein the lubricated substrate is a condom. 9. The lubricated substrate of claim 8, wherein the lubricated substrate is a sexual accessory device selected from the group consisting of sex toys, dildos, vibrators, rings, and beads. the lubricated substrate is an internal applicator having a skin-contacting surface configured to contact epithelial tissue within a human body cavity, the internal applicator comprising: a swab; an elongated stick or rod; a wearable insert; an injector. 10. The lubricated substrate of claim 9, wherein the lubricated substrate is selected from the group consisting of; a syringe; a cannula; and a pipette. 12. The lubricated substrate of claim 11, wherein the lubricated substrate is a swab. A method of forming any of the antiviral lubricating compositions according to any one of claims 1 to 7, comprising:
(a) providing a carrageenan powder having carrageenan, the carrageenan having 90% by weight lambda-carrageenan and 10% by weight kappa-carrageenan;
(b) mixing carrageenan powder with a solution having a polyol to form an aqueous carrageenan suspension;
(c) heating the carrageenan aqueous suspension to a temperature of at least 70°C to 75°C;
(d) mixing the heated carrageenan aqueous suspension for a sufficient time to form a homogeneous aqueous solution having a turbidity of about 25 nephelometric turbidity units (NTU) or less;
(e) cooling the homogeneous aqueous solution to a temperature of less than about 30°C; and (f) one or more in an amount sufficient to adjust the antiviral lubricating composition to a pH in the range of 3.5 to 7.0. mixing a pH adjusting agent thereby forming an antiviral lubricating composition;
The above method, comprising: Carrageenan comprises 0.1% to 3% by weight of the antiviral lubricating composition;
the polyol is propylene glycol, and the propylene glycol comprises 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;
14. The method according to claim 13, wherein the antiviral lubricating composition has an osmolality of 200 mOsmol/kg to 1400 mOsmol/kg. Carrageenan comprises 1.5% to 1.7% by weight of the antiviral lubricating composition;
Propylene glycol comprises 4.0% to 4.5% by weight of the antiviral lubricating composition;
the antiviral lubricating composition has a pH in the range of 5.5 to 7.0;
The antiviral lubricating composition has a viscosity of 2,000 cP to 3,000 cP;
15. The method of claim 14, wherein the antiviral lubricating composition has an osmolarity of 650 mOsmol/kg to 850 mOsmol/kg. A method according to any one of claims 13 to 15, wherein one or more pH adjusters are added and mixed into the cooled homogeneous aqueous solution. 13. The method further comprises adding with mixing up to about 0.5% by weight of one or more sweeteners; and adding with mixing up to about 1% by weight of one or more preservatives. 15. The method according to any one of items 15 to 15. 18. The method of claim 17, wherein one or more sweeteners are added to the carrageenan aqueous suspension and one or more preservatives are added to the cooled homogeneous aqueous solution. Step (b) is
(A) a substep of mixing carrageenan powder with an amount of propylene glycol for a sufficient time to form a wet carrageenan mixture, the weight ratio of the amount of propylene glycol to the carrageenan powder being from about 1:1 to about and (B) combining the wet carrageenan mixture with an aqueous solution while mixing for a sufficient time to form an aqueous suspension of carrageenan, the substep of combining the aqueous solution and the wet carrageenan mixture. a sub-step in which the volume ratio is from about 45:1 to about 8:1;
The method according to any one of claims 13 to 15, comprising: 20. The total mixing time for forming the wet carrageenan mixture, forming the carrageenan aqueous suspension, forming the homogeneous aqueous solution, and forming the antiviral lubricating composition is about 3 hours or less. Method.

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