Protective bioresponsive polymer seal

Abstract

In some aspects, this disclosure is directed toward polymer coatings that may be used in medical devices such as tampons or intravaginal contraceptives to generate a seal that prevents the transmission of sperm or infectious particles. In some embodiments, a seal may be formed when the polymer coating is exposed to a physiological fluid such as semen.

Description

[Technical Field]

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 453,454 dated March 20, 2023, the entire contents of which are incorporated herein by reference.

[0002] 1. Field This disclosure relates to the fields of medicine, pharmacology, and chemistry. In particular, novel compositions and methods for preventing unwanted pregnancies and sexually transmitted infections are disclosed. [Background technology]

[0003] 2. Related Technologies Sexually transmitted infections (STIs) and unwanted pregnancies continue to threaten the lives of millions of women worldwide. Currently, an estimated 17 million women are infected with the HIV / AIDS virus, with over 50% living in sub-Saharan Africa (Njororai & Njororai, 2010). Despite significant advances in contraception, women in developing countries face a greater risk of STIs and unwanted pregnancies due to limited access to socially acceptable and economically affordable preventative products (Ross et al., 2002).

[0004] For decades, topical inventions for contraception and STI prevention via the vaginal route have remained underutilized and untapped, partly due to outdated delivery systems that do not meet the needs of modern society. Vaginal drug delivery has been demonstrated to effectively reduce systemic side effects with limited systemic exposure (e.g., progesterone) and to enable convenient self-administration (de Araujo Pereira et al., 2012). The majority of vaginal drug delivery systems are designed for topical administration of antifungal, microbiotid, and spermicidal agents, despite the potential for disrupting vaginal equilibrium, which can increase the likelihood of subsequent infection. In recent years, systemic delivery of drugs via the vaginal route has been studied. Therapeutic applications involving systemic delivery include hormone replacement therapy and contraceptives. However, periodic fluctuations in mucosal barrier properties can interfere with consistent drug delivery (de Araujo Pereira et al., 2012; Vermani et al., 2000).

[0005] Legal, commercially available vaginal products for female-initiated localized vaginal infection prevention and contraception are administered as semi-solid gels, polymer films, tablets, creams, vaginal rings, foams, or suppositories. Disadvantages of these approaches include irritation, lack of retention within the vaginal cavity, and variability in efficacy (Vermani et al., 2000). Crucial to the future development of these female-initiated, on-demand technologies for preventing unintended pregnancies and STIs is the development of novel compositions that enhance the natural barrier properties of the cervix and vaginal region. Previous studies have shown that sperm motility and viability, as well as the infectivity of HIV / AIDS virions, are significantly impaired under acidic conditions (Garg et al., 2001; Jay et al., 2009). Furthermore, the viscosity of cervical mucus prevents spermatids from entering the uterus and advancing towards the fallopian tubes (Clift & Hart, 1953). Therefore, the combination of increased viscosity after exposure to semen and the maintenance of an acidic vaginal environment is predicted to establish an effective barrier as a first line of defense against unwanted pregnancy and STIs.

[0006] Therefore, there is still a need to develop new compositions that can be used in the preparation of devices and materials to achieve this objective. [Overview of the project]

[0007] overview In some aspects, this disclosure relates to the preparation of compositions and medical devices that may be used to prevent pregnancy or infections such as sexually transmitted infections. In particular, these medical devices and compositions may be used transvaginally. [Brief explanation of the drawing]

[0008] The accompanying drawings form part of this specification and are included to further demonstrate certain aspects of this disclosure. This disclosure may be better understood by referring to one or more of these drawings in conjunction with the detailed description of the particular aspects presented herein. [Figure 1] Figures 1A to 1C show polymer compositions that form a protective, bioresponsive seal upon contact with physiological fluids (Figure 1A = hydrogel, Figure 1B = rod-shaped xerogel, Figure 1C = nonwoven fiber mat). [Figure 2] The diagram shows a bioresponsive seal formed upon contact between a claimed drug-added polymer composition and a physiological fluid, for enhancing natural contraceptive mechanisms and prevention of sexually transmitted infections. [Figure 3] Figures 3A and 3B show the spreadability of a bioresponsive polymer seal formed after exposure of a hydrated Carbopol® 974P / PVP (CP / PVP) polymer blend to a pH 7.6 semen-like substance (SFS). Experimental setup (Figure 3A). Concentration-dependent shear work of the hydrogel (Figure 3B). [Figure 4] This demonstrates the spreadability of a bioresponsive polymer seal formed after exposure of a partially hydrated xerogel composed of a Carbopol® 974P / PVP (CP / PVP) polymer blend to a pH 7.6 semen-like substance (SFS). [Figure 5] Figures 5A and 5B show the spreadability of the bioresponsive polymer seal formed on a nonwoven fiber mat composed of Carbopol® 974P / PVP (CP / PVP) polymer blend after exposure to pH 8.0 phosphate buffer. Experimental setup (Figure 5A). Concentration-dependent shear work of hydrated nonwoven fiber mats composed of different acidic / nonionic polymer blends (Figure 5B). [Figure 6] This exhibits the ductility of a bioresponsive polymer seal formed on a nonwoven fiber mat composed of Carbopol® 974P / PVP (CP / PVP) polymer blend (50:50, w / w) after exposure to a vaginal fluid simulated substance (VFS) at pH 4.3 and a semen simulated substance (SFS) at pH 7.6, respectively. [Figure 7] Figures 7A and 7B show the in vitro contraceptive effect of a bioresponsive polymer seal formed after combining a Carbopol® 974P / PVP (CP / PVP) polymer blend with liquid human semen at pH 7.8–8.5. Experimental setup (Figure 7A). Composition-dependent barrier properties of the hydrated CP / PVP polymer blend (Figure 7B). Results are expressed as mean + SD (n=3) and compared to filters only, 1% (w / v) methylcellulose gel (MC gel), and spermicidal VCF® gel products containing 4% (w / v) nonoxynol-9. Compositions were evaluated using liquid human semen at pH 7.8–8.5 at the indicated volume dilutions. [Figure 8] This study demonstrates in vivo contraceptive efficacy. Pregnancy rates in rabbits after artificial insemination were observed in the presence and absence of a bioresponsive polymer seal formed in the vagina using a Carbopol® 974P / PVP (CP / PVP) polymer blend. Results are expressed as mean ± SD (n=10) and compared to animals treated with an empty vaginal applicator only (i.e., sham treatment) or with a spermicidal VCF® gel product containing 4% (w / v) nonoxynol-9 as a positive control. CP = Carbopol® 974P, PVP = poly(N-vinylpyrrolidone). [Figure 9]This shows the drug release profile from a metronidazole-containing bioresponsive polymer seal in vitro. Cumulative metronidazole (MTZ) was released within 24 hours at 37°C into a vaginal fluid simulator (VFS) at pH 4.3 from a 0.5% (w / v) MTZ-containing hydrated Carbopol® 974P / PVP (CP / PVP) polymer blend. Data are reported as mean ± SD (n≧6). [Figure 10] This study demonstrates the pharmacodynamic activity of metronidazole (MTZ) released from a drug-added bioresponsive polymer seal in vitro. Prevotella bivia growth patterns after 6-hour incubation with a hydrated Carbopol® 974P / PVP (CP / PVP) polymer blend containing 0.5% (w / v) MTZ were compared to a medium control, a drug-free CP / PVP hydrogel, a drug-free CP / PVP fiber mat, and a positive control, an antimicrobial intravaginal NUVESSA® gel product containing 1.3% (w / v) MTZ. Data are reported as mean ± SD (n≧4). [Modes for carrying out the invention]

[0009] Exemplary Description The present disclosure is directed, in part, to a polymer composition that forms a bioresponsive seal upon contact with a physiological fluid having a pH value of 4.0 to 8.9 for preventing, alleviating, or curing a medical condition in a mammal. The bioresponsive polymer seal can be formed in a number of ways, but is preferably formed at the site of administration after interaction of the polymer composition, which is at least composed of a blend of one acidic polymer and one nonionic polymer, with the physiological fluid. The polymer seal can be effective in using its chemical and physical barrier properties to protect the underlying tissue and organs from exposure to unwanted external molecules and unicellular and multicellular organisms. The polymer compositions, biocompatible composites, and devices incorporating them of the present invention can contain at least one pharmacologically active ingredient suitable for preventing, alleviating, or curing a medical condition in a mammal.

[0010] In some embodiments, the motility of sperm and the movement of infectious particles such as HIV / AIDS virions can be blocked by this polymer coating, thereby increasing the contact time with contraceptives and / or anti-infective agents. In some embodiments, the present disclosure provides for the successful manufacture of a tampon-like xerogel structure that can reduce the pregnancy rate in rabbits by at least 40%. In some embodiments, the bioresponsive properties of the reconstituted polymer coating can lead to an increase of more than 100% in the shear work done after exposure to a semen stimulant (SFS), and can limit the pH of the gel phase to less than pH 7 after dilution with an equal volume of a pH 7.6 semen simulant.

[0011] In some embodiments, the present disclosure may provide hydrated crosslinked polymer networks that have the ability to retain water in their porous structure, primarily due to the presence of polar functional groups, and are intended for prophylactic and therapeutic applications in women's health. The inventors intended to create a bioresponsive system that generates a high-viscosity barrier after exposure to alkaline semen at pH 7.0–8.9 by utilizing the pH-dependent change in viscoelastic properties associated with selected acidic polymers (e.g., polyacrylic acid derivatives). As a result, the movement of infectious particles such as spermatids and HIV / AIDS virions is expected to be hindered by this physical barrier, thus creating a polymer seal that protects against unwanted pregnancies and mucosal infections. Crucial to the future development of these bioresponsive polymer seals is the use of acidic polymers, such as Carbopol® 974P NF, an acrylic acid-based polymer, which effectively improves the buffering capacity of the reconstituted hydrogel in the acidic range of pH less than 5.0. Previous studies have shown that sperm motility and viability, as well as the infectivity of HIV / AIDS virions, are significantly impaired under acidic conditions. Following topical administration, such bioresponsive polymer seals can also serve as carriers or delivery systems for a wide variety of pharmacologically active chemicals exhibiting anti-infective efficacy, and / or negatively affect spermatocyte motility / viability. The combination of increased viscoelasticity after exposure to semen and maintenance of an acidic vaginal environment is predicted to establish an effective polymer seal as a first-line defense against unwanted pregnancies and sexually transmitted infections.

[0012] In some aspects, the present disclosure may provide a novel tampon-like xerogel structure that, in some aspects, can be administered without the use of an applicator and can function as a bioreactive vaginal device for prophylactic and therapeutic uses in women's health. In contrast to conventional vaginal gels and creams, this tampon-like device may be administered with a finger without an applicator and can convert to a bioadhesive hydrogel upon exposure to vaginal fluid. In some aspects, the bioreactive tampon-like device can serve as a carrier or delivery system for a wide variety of pharmacologically active chemicals that exhibit contraceptive or anti-infective efficacy. A bioreactive device that generates a high-viscosity barrier covering the vaginal mucosa after exposure to semen was fabricated using the pH-dependent change in viscosity associated with a selected polymeric excipient (e.g., Carbopol). As demonstrated by the significantly reduced percentage of sperm cells recovered in the receiver compartment of a Transwell™ system (Figure 7), a semi-solid bioreactive polymer seal composed of a hydrated Carbopol® 974P / PVP (CP / PVP) polymer blend (50:50, w / w) can effectively limit the penetration of single-celled organisms.

[0013] I. Vaginal Drug Delivery Systems The therapeutic efficacy of vaginally administered drugs depends on a properly designed intravaginal device that not only promotes local deposition of the pharmacologically active agent within the vaginal cavity but also affects the pharmacokinetic properties of these agents as a result of the selected excipients (Valenta, 2005). In general, drugs administered into the vaginal cavity can affect either local or systemic targets. To date, the majority of commercially available products have focused on local action mainly for managing bacterial and antifungal infections as well as spermicides (de Araujo Pereira et al., 2012; Vermani et al., 2000).

[0014] Conventional delivery systems for these locally acting drugs include solutions, foams, gels, and creams, which are primarily designed to allow uniform spread across the mucosal surface. In contrast, intravaginal administration of drugs designed for systemic treatment requires penetration of the active ingredient beyond the vaginal epithelium. Among the several products approved for this purpose, controlled-release systems such as vaginal rings made of silicone elastomers and polystyrene are highly promising because they significantly improve patient compliance by reducing the frequency of medication (Ndesendo et al., 2008).

[0015] To achieve desirable efficacy and overall tolerability, the majority of vaginal gel formulations are generally empirically designed to mimic the mechanistic characteristics of other commercially accepted products (Mahalingam et al., 2010). The most commonly used methods for managing local conditions such as infections are the administration of creams and gels via the vaginal route. These delivery systems have the ability to physically interact with the mucosal surface, thereby extending the contact time between the pharmacological agent and the desired therapeutic target due to their mucosal adhesion properties. Semi-solid formulations such as creams and gels are widely accepted due to their low cost and reasonable therapeutic efficacy (De Araujo Pereira et al., 2012). Examples include metronidazole and itraconazole products, which are approved for the treatment and management of bacterial vaginosis and vaginal candidiasis. Polyacrylic acid-based progesterone gel formulations (e.g., Noveon® AA1) are used for the treatment of hormonal imbalances (Hussain & Ahsan, 2005). As a result, vaginal gel formulations for delivering antiviral agents such as tenofovir and pyrimidinedione analog IQP-0528 for the purpose of preventing HIV-1 / AIDS transmission have also been studied (Mahalingam et al., 2010; Mahalingam et al., 2011). The main drawbacks associated with these preparations are the need to administer them using disposable plastic applicators, and the limited retention within the vaginal cavity due to reduced bioadhesion properties when diluted with vaginal fluid and / or semen, which can lead to leakage and subsequent loss of therapeutic efficacy (Vermani et al., 2000).

[0016] Compression tablets and suppositories are also used as delivery systems for vaginal intervention. Mucosal adhesive tablets are primarily designed for sustained delivery of drugs over long periods using conventional manufacturing techniques established for oral solid dosage forms (Hussain & Ahsan, 2005). The main advantages associated with these systems are that they are easy to produce and easy to insert. Metronidazole and clotrimazole tablets are widely used for the treatment of bacterial and antifungal infections (Alam et al., 2007). The composition of vaginal tablets, e.g., the incorporation of excipients such as disintegrants and binders, is similar to that of conventional oral tablets (Hussain & Ahsan, 2005). Prescriptions of vaginal suppositories in clinical use are decreasing and are mainly limited to the induction of cervical ripening and hormone replacement therapy with progesterone (Vukovich et al., 1977; Abrams & Weintraub, 1983). Due to its short residue time and the need for precise placement within the vaginal cavity, this dosage form is becoming less desirable among all commercially available options for vaginal products.

[0017] Vaginal rings represent a prime example of a modern class of drug delivery systems specifically designed for women's health applications. Vaginal rings are currently marketed primarily for systemic or topical contraception and for hormone replacement therapy (e.g., NuvaRing®) (Harwood & Mishell, 2001; Dezarnaulds & Fraser, 2003). However, various preclinical and clinical trials have focused on the study evaluation of vaginal rings for controlled-release applications using microbiotids (e.g., TMC 120 - dapivine) (Romano et al., 2009; Malcolm et al., 2005). Microbiotids are generally dispersed in elastomer or thermoplastic materials (e.g., silicon) that allow for easy molding and facilitate continuous release by diffusion (Kelly & Shattock, 2011). Johnson and his collaborators recently published a novel polyurethane-based vaginal ring design that has been demonstrated to facilitate the sustained release of two hydrophilic antiretroviral agents, dapivine and tenofovir, over 30 days (Johnson et al., 2010). The same research group fabricated a polyurethane vaginal ring using a hot-melt extrusion process that sustained the diffusion-controlled release of the potent non-nucleoside reverse transcriptase inhibitor UC781 (Clark et al., 2012). The circular shape of the device facilitates easy, user-controlled positioning towards the posterior end of the vaginal cavity. Because the thin, flexible design does not interfere with intercourse and offers the potential for sustained drug release for up to one month, the vaginal ring is expected to offer unique advantages over conventional intravaginal drug delivery systems (Hussain & Ahsan, 2005). Nevertheless, vaginal irritation, the need for cold-chain storage, and limited dosing flexibility appear to be limiting the rapid market expansion of this innovative vaginal dosage form. Furthermore, accurate placement of the vaginal ring inside the vaginal cavity requires appropriate instruction and training, which may not be readily available in developing countries where healthcare infrastructure is not well-developed.

[0018] To improve patient compliance and enhance the vaginal retention of conventional dosage forms after administration, bioadhesive polymers have been studied as suitable excipients in vaginal drug delivery systems. Among the most commonly used bioadhesive polymers are polycarbophil, Carbopol®, sodium alginate, and various cellulose derivatives such as sodium carboxymethylcellulose, hydroxypropylcellulose, and hydroxypropylmethylcellulose (Hussain & Ahsan, 2005). The incorporation of these excipients into vaginal formulations has been demonstrated to induce desirable bioadhesive properties, swelling upon interaction with biological fluids, and, in some cases, pH-responsive behavior, providing greater selectivity in therapeutic interventions (Ferguson & Rohan, 2011). Bioadhesive polymers extend vaginal retention time by forming intermolecular interactions, such as hydrogen bonds and ionic forces, between the epithelial layer and the formulation. Furthermore, hydration of these polymers establishes a three-dimensional network that can generate a diffusion layer effective in controlling drug release (Das Neves & Bahia, 2006). Recent in vitro and in vivo studies using a combination product containing UC781 and tenofovir prepared in hydroxyethylcellulose / Carbopol 974P gel demonstrated effective topical deposition of the microbial agent on vaginal tissue (Kiser et al., 2012). However, a clinical study conducted in South Africa using tenofovir-containing hydroxyethylcellulose gel (CAPRISA 004) revealed only a disappointing 39% reduction in HIV-1 transmission (Karim et al., 2010). The incorporation of ionizable polymers such as Carbopol® offers an opportunity to control the pH level in the vaginal cavity, which can positively impact infection management by enhancing the natural acidic protective barrier produced by lactic acid bacteria. More importantly, it has been scientifically established that an acidic pH environment in the vaginal cavity reduces sperm motility and viability, thereby contributing to contraceptive protection (Garg et al., 2001).This concept has commercially led to the carboxymethylcellulose-based contraceptive gel Gynol II®.

[0019] II. Human Immunodeficiency Virus More than 30 years after its initial discovery, modern medicine is still searching for effective strategies to prevent HIV infection. However, it has been established that exposure of the vaginal mucosa to semen containing HIV virions during sexual intercourse significantly increases the risk of contracting HIV / AIDS. More than 50% of the global female population infected with HIV / AIDS lives in sub-Saharan Africa, where poor genital hygiene and multiple partner sexual activity are thought to contribute to the increased risk of HIV infection (Ferguson & Rohan, 2011). Since heterosexual male-to-female transmission accounts for the majority of HIV infections, short-term prevention strategies focusing on woman-controlled barriers to minimize exposure of vulnerable cervical-vaginal mucosa to HIV-infected semen appear to be more advantageous. However, the most effective approach to preventing HIV infection is vaccine development. Unfortunately, this remains a distant dream due to unresolved scientific challenges, intellectual property issues, and regulatory compliance concerns (Rohan & Sassi, 2009).

[0020] Current HIV / AIDS treatment strategies, involving a wide variety of antiretroviral drugs, are effective in reducing mortality while simultaneously improving the quality of life for patients diagnosed with HIV / AIDS. Unfortunately, this successful treatment approach is not equally available worldwide. In particular, in sub-Saharan Africa, socioeconomic conditions and challenges such as insufficient drug stability at high temperatures hinder the effective implementation of HIV / AIDS drug management (Turpin JA, 2002; Krishnan et al., 2008). Since STIs generally increase the risk of HIV infection tenfold by impairing mucosal defense mechanisms (i.e., increased vaginal pH and epithelial damage), prevention strategies targeting STIs are considered an effective approach to limiting HIV infection (Ndesendo et al., 2008). Therefore, a broad focus of HIV prevention programs should include protection against STIs using reasonable and safe approaches that are affordable and socially acceptable for the global female population.

[0021] Maintaining an acidic vaginal environment is crucial for preventing HIV infection, as the virulence of HIV virions is dramatically reduced under acidic conditions (Jay et al., 2009). Previous studies have demonstrated that HIV virions are highly infectious at pH 7.4, but lose their pathogenicity when the environmental pH is maintained below pH 5.0. Currently, the most effective strategies for preventing STIs and HIV infection rely on various microbiotacitides. These chemical agents interfere with the biological functions of pathogens during interaction, thereby preventing or at least reducing the development of STIs and HIV / AIDS. Topical administration of vaginal microbiotacitides for local intervention is facilitated by various delivery systems, including gels, tablets, and vaginal rings (Jay et al., 2009). Microbiotic agents currently being investigated in clinical trials are classified as follows: first-generation microbiotic agents that inactivate the virus by disrupting the HIV protein envelope structure (e.g., nonoxynol-9); second-generation microbiotic agents, including fusion inhibitors that block HIV virion entry into cells by competing for endocytosis receptor binding (e.g., PRO2000, carrageenan); and third-generation microbiotic agents that inhibit reverse transcriptase activity, i.e., inhibit viral DNA polymerase, a critical enzyme required for viral replication (e.g., tenofovir, UC781) (Weber et al., 2005). Large-scale clinical trials in developing countries using bioadhesive vaginal microbiotic agent delivery systems containing polymers such as Carbopol® or hydroxyethylcellulose have demonstrated promising results against HIV infection (e.g., Buffer Gel, PRO2000) (Karim et al., 2011).

[0022] In mammals, the skin and a wide variety of mucous membranes form a complex protective barrier that shields the underlying anatomical structures from exposure to external factors. The epidermis is the outermost layer of skin, forming a protective barrier that covers the body surface. Mucous membranes (i.e., mucous membranes) line cavities exposed to the external environment and internal organs. These can be attached to the skin, such as the nostrils, mouth, lips, eyelids, and genitals, but are also found within body cavities, such as the stomach, anus, trachea, and ear. Most mucous membranes secrete a sticky, viscous fluid called mucus, which promotes several barrier functions and provides a moist environment. Mucous membranes are highly specialized in each organ to cope with different conditions. The greatest variation is seen in the epithelium lining the mucous membrane. Together, the skin and mucous membranes form a barrier immune system, which is considered a component of the innate immune system. These structures correspond to physical or mechanistic barriers that prevent chemical molecules, as well as unicellular and multicellular organisms, from entering the body in various ways. While the skin simply prevents penetration into underlying tissues, more specialized mechanisms, such as mucociliary clearance in the trachea, exist to actively protect internal organs from exposure to external factors. In addition, the barrier immune system also constitutes chemical barriers that contribute to protective mechanisms. Notable examples include the acidity of the stomach, which kills the majority of microorganisms, and the secretion of antimicrobial peptides in mucosal epithelial tissue.

[0023] The barrier immune system is the first line of defense, protecting the underlying tissues and organs from exposure to unwanted external molecules and single-celled and multicellular organisms. However, this natural barrier can be breached by cuts and scrapes. In addition, infections caused by pathogens can weaken the mechanistic and / or chemical properties of the barrier immune system, thus allowing unwanted external molecules and single-celled and multicellular organisms to reach undesirable internal areas of the body.

[0024] III. Therapy A. Pharmaceutical formulations and routes of administration In some aspects, with respect to administration to patients requiring such treatment, a pharmaceutical preparation (also referred to as a pharmaceutical preparation, pharmaceutical composition, pharmaceutical product, drug, medicine, agent, or pharmacopoeia) comprises a therapeutically effective amount of the composition of this disclosure, formulated with one or more excipients and / or drug carriers suitable for the indicated route of administration. In some embodiments, the compositions disclosed herein are formulated in a manner applicable to the treatment of human patients and / or veterinary animals. In some embodiments, formulation involves mixing or combining one or more of the compositions disclosed herein with one or more of the following excipients: lactose, sucrose, starch powder, cellulose esters of alkanates, cellulose alkyl esters, talc, stearic acid, magnesium stearate, magnesium oxide, sodium and calcium salts of phosphoric acid and sulfate, gelatin, acacia, sodium alginate, polyvinylpyrrolidone, and / or polyvinyl alcohol. In some embodiments, the pharmaceutical preparation may be tableted or encapsulated, for example, for oral administration. In some embodiments, the composition may be dissolved or slurryed in water, polyethylene glycol, propylene glycol, ethanol, corn oil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodium chloride, and / or various buffers. In some embodiments, the pharmaceutical formulation may be subjected to pharmaceutical operations such as sterilization and / or may contain drug carriers and / or excipients, such as preservatives, stabilizers, wetting agents, emulsifiers, encapsulating agents such as lipids, dendrimers, polymers, proteins such as albumin, nucleic acids, and buffers.

[0025] Pharmaceutical formulations can be administered by a variety of methods, for example, orally or by injection (e.g., subcutaneously, intravenously, and intraperitoneally). Depending on the route of administration, the compositions disclosed herein may be coated with materials to protect the compounds from the action of acids and other natural conditions that may inactivate them. To administer the active compound by means other than parenteral administration, it may be necessary to coat the compound with a material to prevent its inactivation or to administer it simultaneously with such material. In some embodiments, the active compound may be administered to the patient in a suitable carrier, such as liposomes or a diluent. Pharmaceutically acceptable diluents include physiological saline and buffered aqueous solutions. In addition to conventional liposomes, liposomes include water-in-oil-in-water corn gluten feed (CGF) emulsions.

[0026] The compositions disclosed herein may also be administered parenterally, intraperitoneally, intraspinally, or intracerebrally. Dispersions can be prepared in glycerol, liquid polyethylene glycol, and mixtures thereof, as well as in oil. Under normal storage and use conditions, these preparations may contain preservatives to prevent microbial growth.

[0027] Suitable pharmaceutical compositions for injection include sterile aqueous solutions (if water-soluble) or dispersions, as well as sterile powders for the immediate preparation of sterile injection solutions or dispersions. The carrier may be a solvent or dispersion medium containing, for example, water, ethanol, polyols (such as glycerol, propylene glycol, and liquid polyethylene glycol), suitable mixtures thereof, and vegetable oils. Appropriate fluidity can be maintained, for example, by the use of coatings such as lecithin, by maintaining the desired particle size in the case of dispersions, and by the use of surfactants. Prevention of microbial action can be achieved by various antibacterial and antifungal agents, such as parabens, chlorobutanol, phenol, ascorbic acid, and thimerosal. In many cases, it is preferable to include isotonic agents, such as sugars, sodium chloride, or polyhydric alcohols such as mannitol and sorbitol, in the composition. Extending the absorption of the injectable composition can be achieved by including absorption-delaying agents, such as aluminum monostearate or gelatin, in the composition.

[0028] In some embodiments, it may be advantageous to formulate parenteral compositions in unit dosage forms to facilitate administration and ensure uniformity of dosage. As used herein, a unit dosage form refers to a physically discontinuous unit adapted as a unit dose for a patient being treated; each unit contains a predetermined amount of the therapeutic compound, calculated to produce a desired therapeutic effect in conjunction with the required pharmaceutical carrier. In some embodiments, the specifications of the unit dosage forms of this disclosure are defined and directly depended upon by (a) the unique characteristics of the therapeutic compound and the specific therapeutic effect to be achieved, and (b) limitations inherent in the field in which such therapeutic compounds are formulated for the treatment of a selected condition in a patient. In some embodiments, the active compound is administered in a therapeutically effective dose sufficient to treat a condition relevant to the patient's condition. For example, the efficacy of a compound can be evaluated in an animal model system that may provide a predictor of its efficacy in treating a disease in humans or other animals.

[0029] In some embodiments, the effective dosage range of a therapeutic compound can be inferred from the effective dosages determined in animal experiments on a variety of different animals. In some embodiments, a human equivalent dose (HED) (mg / kg) can be calculated according to the following formula (see, for example, Reagan-Shaw et al., FASEB J., 22(3):659-661, 2008, which is incorporated herein by reference). HED (mg / kg) = animal dosage (mg / kg) × (animal K m / human K m ) The use of the conversion factor K m results in an HED value based not only on body mass but rather on body surface area (BSA). The K m values for humans and various animals are well known. For example, the K 2 for an average 60 kg human (BSA 1.6 m m ) is 37, while a 20 kg child (BSA 0.8 m 2 ) has a K m value of 25. The K m values for several relevant animal models are also well known. For example, mouse K m is 3 (assuming a weight of 0.02 kg and BSA of 0.007); hamster K m is 5 (assuming a weight of 0.08 kg and BSA of 0.02); rat K m is 6 (assuming a weight of 0.15 kg and BSA of 0.025), and monkey K m is 12 (assuming a weight of 3 kg and BSA of 0.24).

[0030] The exact amount of the therapeutic composition depends on the judgment of the practitioner and is specific to each individual. Nevertheless, the calculated HED dosage provides a general guideline. Other factors that can affect dosage include the patient's physical and clinical condition, the route of administration, the intended treatment goal, and the potency, stability, and toxicity of the particular therapeutic formulation.

[0031] The actual dose of the compounds or compositions containing the compounds disclosed administered to a patient may be determined by physical and physiological factors such as the species, age, sex, body weight, severity of condition, type of disease being treated, previous or concurrent therapeutic interventions, patient idiopathy, and route of administration. These factors may be determined by those skilled in the art. The practitioner responsible for administration will typically determine the concentration of the active ingredient in the composition and the appropriate dose for each individual patient. In the event of any complications, the dose may be adjusted by the individual healthcare professional.

[0032] In some embodiments, the therapeutically effective dose typically varies (depending on the mode of administration and the factors mentioned above) in one or more daily doses over one to several days, ranging from approximately 0.001 mg / kg to approximately 1000 mg / kg, approximately 0.01 mg / kg to approximately 750 mg / kg, approximately 100 mg / kg to approximately 500 mg / kg, approximately 1 mg / kg to approximately 250 mg / kg, and approximately 10 mg / kg to approximately 150 mg / kg. Other appropriate dose ranges include 1 mg to 10,000 mg per day, 100 mg to 10,000 mg per day, 500 mg to 10,000 mg per day, and 500 mg to 1,000 mg per day. In some embodiments, the dose is less than 10,000 mg per day and ranges from 750 mg to 9,000 mg per day.

[0033] In some embodiments, the amount of the active compound in the pharmaceutical formulation is about 2 to about 75 percent by weight. In some of these embodiments, the amount is about 25 to about 60 percent by weight.

[0034] A single-dose or multi-dose agent is intended. The desired time interval for the delivery of multi-dose agents can be determined even by those skilled in the art who have only performed routine experiments. For example, two doses may be administered to a patient daily at approximately 12-hour intervals. In some embodiments, the agent is administered once daily.

[0035] The agent may be administered on a regular schedule. As used herein, a regular schedule refers to a predetermined period. A regular schedule may include multiple periods of the same or different lengths, as long as the schedule is predetermined. For example, a regular schedule may include administration three times a day, twice a day, daily, every two days, every three days, every four days, every five days, every six days, weekly, monthly, or any set number of days or weeks in between. Alternatively, a predetermined regular schedule may include administration twice a day for the first week, followed by daily administration for the following months, etc. In other embodiments, the present invention specifies that the agent may be taken orally, and that the timing of its administration may or may not depend on food intake. Thus, for example, the agent may be taken every morning and / or every evening, regardless of when the patient has eaten or will eat.

[0036] B. Treatment method Specifically, compositions that may be used in the treatment of diseases or disorders in subjects (e.g., human subjects) are disclosed herein. These compositions are preferably administered to mammals (e.g., rodents, humans, non-human primates, dogs, cattle, sheep, horses, cattle, etc.) in an effective amount, i.e., an amount that can produce a desired result in the subject being treated (e.g., delay, stop, reduce, or eliminate one or more symptoms or underlying causes of the disease). The toxicity and therapeutic efficacy of the compositions used in the methods of this disclosure can be determined by standard pharmaceutical methods. As is well known in the fields of medicine and veterinary medicine, the dose for any single animal depends on many factors, including the size of the subject, body surface area, body weight, age, the specific composition administered, the time and route of administration, overall health status, clinical symptoms, and other drugs administered concurrently. In some embodiments, the amount of compound used is calculated to be between about 0.01 mg and about 10,000 mg / day. In some embodiments, the dose is approximately 1 mg to approximately 1,000 mg / day. In some embodiments, these dosages may be reduced or increased based on specific patient biological factors, such as increased or decreased metabolic breakdown of the drug or decreased uptake by the gastrointestinal tract when administered orally. Furthermore, the compound may have a higher potency, and therefore a smaller dose may be required to achieve a similar effect. Such doses are usually administered once daily over several weeks or until a sufficient clinical benefit is achieved.

[0037] The therapeutic methods (including prophylactic measures) disclosed herein generally involve administering a therapeutically effective amount of the compositions described herein to subjects in need, including mammals, particularly humans. Such measures are appropriately administered to subjects, particularly humans, who have, are susceptible to, or are at risk of having, a disease, disorder, or symptoms thereof. The determination of these “at-risk” subjects may be made by any objective or subjective determination, such as by diagnostic tests or by the opinion of the subject or healthcare provider (e.g., genetic testing, enzyme or protein markers, family history, etc.).

[0038] C. Combination therapy The compositions described herein are intended to be used in combination with one or more additional therapies or compounds that alleviate one or more side effects experienced by a patient. Combining multiple treatment approaches is common practice in the medical field. The following are general considerations regarding therapies that may be used in combination with the therapies described herein.

[0039] To treat a disease or disorder using the methods and compositions of this disclosure, cells or subjects are generally brought into contact with the composition and at least one other therapy. These therapies are provided in combination doses effective in achieving a reduction of one or more disease parameters. This process may include bringing cells / subjects into contact with both agents / therapies simultaneously, for example, using a single composition or pharmacological formulation containing both agents, or bringing cells / subjects into contact with two separate compositions or formulations simultaneously (where one composition contains a compound and the other contains another agent).

[0040] Alternatively, the compounds described herein may precede or follow other treatments with intervals ranging from several minutes to several weeks. In general, it is essential to ensure that the advantageous combined effect on cells / subjects does not expire significantly between each delivery point. In such cases, it is intended that cells be brought into contact with both formulas within approximately 12 to 24 hours of each other, or within approximately 6 to 12 hours of each other, or with a delay of only about 1 to 2 hours. However, in some situations, if several days (2, 3, 4, 5, 6, or 7) to several weeks (1, 2, 3, 4, 5, 6, 7, or 8) pass between each administration, it may be desirable to significantly extend the duration of treatment.

[0041] It is also conceivable that it may be desirable to administer either the compound or other therapies multiple times. If the compound of this disclosure is referred to as "A" and the other therapy as "B", various combinations may be used, as illustrated below. Other combinations are also being considered. Considerations of other potential therapies that may be used in combination with the compounds of this disclosure are presented elsewhere in this document.

[0042] IV. Definition When used in conjunction with the term “including” in the claims and / or specification, the use of the words “one (a)” or “one (an)” may mean “one,” but also coincide with the meanings of “one or more,” “at least one,” and “one or more than one.”

[0043] Throughout this application, the term “approximately” is used to indicate that a value includes inherent variations in the error relating to the device, the method used to determine the value, or variations present among the study subjects or patients. Unless otherwise specified, the term “approximately” is used to indicate a value within ±10%, preferably ±5%, of the reported value. It should be understood that whenever the term “approximately” is used, a specific reference to the exact numerical value indicated is also included.

[0044] An "active ingredient" (AI) or "pharmaceutical active ingredient" (API) (also called an active compound, active substance, activator, pharmaceutical agent, agent, biologically active molecule, or therapeutic compound) is a biologically active component in a pharmaceutical drug.

[0045] The terms “comprise,” “have,” and “include” are open-ended linking verbs. Any one or more forms and tenses of these verbs, such as “comprises,” “comprising,” “has,” “having,” “includes,” and “including,” are also open-ended. For example, any way of “comprise,” “having,” or “containing” one or more processes is not limited to having only those one or more processes, but also covers other processes that are not listed.

[0046] Where the term “effective” is used in the specification and / or claims, it means adequate to achieve the desired, expected, or intended result. Where used in the context of treating a patient or subject with the compound, “effective dose,” “therapeutic effective dose,” or “pharmaceutical effective dose” means that the amount of the compound administered to a patient or subject is sufficient to result in the treatment or prevention of a disease as those terms are defined below.

[0047] An “excipient” is a pharmaceutically acceptable substance that is formulated together with the active ingredient of a drug, pharmaceutical composition, formulation, or drug delivery system. Excipients may be used, for example, to stabilize a composition, to increase the volume of a composition (and therefore often called a “bulker,” “filler,” or “diluent” when used for this purpose), or to impart therapeutic enhancement effects to the active ingredient in the final dosage form, such as enhancing drug absorption, reducing viscosity, or increasing solubility. Excipients include pharmaceutically acceptable versions of anti-adhesion agents, binders, coatings, colorants, disintegrants, fragrances, fluidizers, lubricants, preservatives, adsorbents, sweeteners, and vehicles. The primary excipient that serves as a medium for transporting the active ingredient is usually called a vehicle. Excipients may also be used in the production process to assist in handling the active substance by promoting the flowability or non-stick properties of the powder, in addition to helping with in vitro stability, such as preventing denaturation or aggregation over the expected storage period. The appropriateness of excipients usually varies depending on the route of administration, dosage form, active ingredient, and other factors.

[0048] When used as a modifier for a compound, the term "hydrate" means that the compound contains less than one water molecule (e.g., hemihydrate), one water molecule (e.g., monohydrate), or more than one water molecule (e.g., dihydrate).

[0049] As used herein, the terms “patient” or “subject” refer to living mammals such as humans, monkeys, cattle, sheep, goats, dogs, cats, mice, rats, guinea pigs, or their transgenic species. In certain embodiments, the patient or subject is a primate. Non-limiting examples of human patients include adults, adolescents, infants, and fetuses.

[0050] As used herein, “pharmaceutically acceptable” means a compound, material, composition, and / or dosage form that, within the bounds of sound medical judgment, is suitable for use in contact with human and animal tissues, organs, and / or bodily fluids without excessive toxicity, irritation, allergic reactions, or other problems or complications, at a reasonable benefit-to-risk ratio.

[0051] "Pharmacologically acceptable salt" means a salt of a compound disclosed herein that is pharmaceutically acceptable as defined above and possesses desirable pharmacological activity. Such salts may be formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid, or with 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, 2-naphthalenesulfonic acid, 3-phenylpropionic acid, 4,4'-methylenebis(3-hydroxy-2-ene-1-carboxylic acid), 4-methylbicyclo[2.2.2]octa-2-ene-1-carboxylic acid, acetic acid, aliphatic monocarboxylic and dicarboxylic acids, aliphatic sulfuric acid, aromatic sulfuric acid, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, carbonic acid, cinnamic acid, citric acid, and cyclopentanepropion. Acid addition salts are formed with acids and organic acids such as ethanesulfonic acid, fumaric acid, glucoheptonic acid, gluconic acid, glutamic acid, glycolic acid, heptanoic acid, hexanoic acid, hydroxynaphthoic acid, lactic acid, lauryl sulfate, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, muconic acid, o-(4-hydroxybenzoyl)benzoic acid, oxalic acid, p-chlorobenzenesulfonic acid, phenyl-substituted alkanic acid, propionic acid, p-toluenesulfonic acid, pyruvic acid, salicylic acid, stearic acid, succinic acid, tartaric acid, tert-butylacetic acid, and trimethylacetic acid. Pharmaceutically acceptable salts also include base addition salts, which can be formed when the present acidic protons can react with an inorganic or organic base. Acceptable inorganic bases include sodium hydroxide, sodium carbonate, potassium hydroxide, aluminum hydroxide, and calcium hydroxide. Acceptable organic bases include ethanolamine, diethanolamine, triethanolamine, tromethamine, and N-methylglucamine. It should be recognized that individual anions or cations forming part of any salt of the present invention are not critical insofar as the salt as a whole is pharmacologically acceptable.Further examples of pharmaceutically acceptable salts and methods of their preparation and use are presented in *Handbook of Pharmaceutical Salts: Properties, and Use* (PH Stahl & CG Wermuth eds., Verlag Helvetica Chimica Acta, 2002).

[0052] A "pharmaceutically acceptable carrier," "drug carrier," or simply "carrier" is a pharmaceutically acceptable substance formulated with a drug, such as an active ingredient, that is involved in carrying, delivering, and / or transporting a chemical agent. Drug carriers may be used to improve the delivery and efficacy of drugs, including, for example, controlled-release techniques to modulate the bioavailability of a drug, reduce drug metabolism, and / or reduce drug toxicity. Some drug carriers may increase the effectiveness of drug delivery to specific target sites. Examples of carriers include liposomes, microspheres (e.g., made from poly(lactic acid-coglycolic acid)), albumin microspheres, synthetic polymers, nanofibers, protein-DNA complexes, protein conjugates, erythrocytes, virososomes, and dendrimers.

[0053] "Prevention" or "prevention" includes: (1) inhibiting the onset of the disease in subjects or patients who may be at risk of the disease and / or are susceptible to the disease but have not yet experienced or exhibited any or all of the pathologies or overall symptoms of the disease; and / or (2) delaying the onset of the pathologies or overall symptoms of the disease in subjects or patients who may be at risk of the disease and / or are susceptible to the disease but have not yet experienced or exhibited any or all of the pathologies or overall symptoms of the disease.

[0054] "Prodrug" means a compound that can be metabolically converted in vivo to the pharmaceutically active ingredient of the present invention. The prodrug itself may or may not be active in its prodrug form. For example, a compound containing a hydroxyl group may be administered as an ester that is converted in vivo by hydrolysis to a hydroxyl compound. Non-limiting examples of suitable esters that can be converted in vivo to a hydroxyl compound include acetate esters, citrate esters, lactate esters, phosphate esters, tartaric acid esters, malonic acid esters, oxalic acid esters, salicylic acid esters, propionic acid esters, succinic acid esters, fumarate esters, maleic acid esters, methylene-bis-β-hydroxynaphthoate esters, gentisinate esters, isethionate esters, di-p-toluyl tartaric acid esters, methanesulfonic acid esters, ethanesulfonic acid esters, benzenesulfonic acid esters, p-toluenesulfonic acid esters, cyclohexylsulfamic acid esters, quinic acid esters, and amino acid esters. Similarly, compounds containing an amine group can be administered as amides, which are converted to amine compounds by hydrolysis in vivo.

[0055] "Treatment" or "to treat" includes: (1) inhibiting the disease in a subject or patient experiencing or exhibiting the pathology or overall symptoms of the disease (e.g., preventing further development of the pathology and / or overall symptoms); (2) relieving the disease in a subject or patient experiencing or exhibiting the pathology or overall symptoms of the disease (e.g., reversing the pathology and / or overall symptoms); and / or (3) resulting in any measurable reduction in the disease or its symptoms in a subject or patient experiencing or exhibiting the pathology or overall symptoms of the disease.

[0056] The term "unit dose" refers to a formulation of a compound or composition that is prepared in a manner sufficient to provide a patient with a single therapeutically effective dose of the active ingredient in a single administration. Such unit dose formulations that may be used include, but are not limited to, a single tablet, capsule, or other oral formulation, or a single vial having a syringe-fillable liquid or other injectable formulation.

[0057] The definitions above supersede any conflicting definitions in any other document incorporated herein by reference. However, the fact that certain terms are defined should not be considered to indicate that any undefined terms are unclear. Rather, all terms used are intended to describe the present invention in a manner that a person skilled in the art can grasp and practice the scope of the present invention. [Examples]

[0058] V. Examples The following embodiments are included to demonstrate preferred embodiments of the Disclosure. Those skilled in the art should understand that the techniques disclosed in the following embodiments are representative of the techniques discovered by the inventors to function well in practice of the Disclosure and may therefore be considered to constitute a preferred form for such practice. However, those skilled in the art should understand that many modifications are possible to the specific embodiments disclosed in light of the Disclosure, and that similar or comparable results can still be obtained without departing from the spirit and scope of the Disclosure.

[0059] Example 1 - Analysis of semi-solid bioresponsive polymer seals A semi-solid bioresponsive polymer seal composed of a hydrated Carbopol® 974P / PVP (CP / PVP) polymer blend generates a meaningful physical barrier in response to alkaline semen simulated material (SFS) at pH 7.6, as demonstrated by the increased work of shear required to spread the semi-solid composition (see Figure 3). Standard batches of the bioresponsive hydrogel were prepared by gradually suspending the CP / PVP polymer mixture in 0.01 N NaOH with stirring. The final CP concentration was 4% (w / w), and the final PVP concentration ranged from 0 to 40% (w / w). To quantify the changes in structural and viscoelastic gel properties under various simulated vaginal conditions, the spreadability of fully hydrated gel formulations was measured using a TA-XT Plus texture analyzer (Stable Microsystems, UK). Fully hydrated gel formulations were evaluated using a conical cap assembly (Figure 3A). For a single measurement, 0.5 g of hydrogel was packed into a 45° acrylic cap and combined with SFS in various volume ratios (Owen & Katz, 2005). After 60 seconds of incubation at room temperature, a coaxially aligned 45° cone was lowered at a test speed of 1 mm / s (i.e., compression mode) until a maximum load of 5 N was reached. This value was chosen because it corresponds to the average physiological intravaginal pressure in the supine position exerted by the soft tissue surrounding the pelvic floor near the vagina (Morgan et al., 2008). The area under the force-distance curve is equal to the total work done to spread (i.e., shear) the gel formulation. Therefore, shear work is a suitable quantitative in vitro parameter for comparing the dynamics of gel spreading under various simulated intravaginal conditions.

[0060] The combination of the gel composition with SFS results in a volumetric dilution of the acidic CP polymer from 4% to 1%. During this dilution process, the shear work required to spread the hydrogel increases, demonstrating an increase in viscoelastic properties after exposure to alkaline SFS. In the absence of PVP, the maximum shear work recorded after diluting the gel to 1% CP was 6.49 ± 0.01 N × s (Figure 3B). Increasing the concentration of PVP in the composition significantly increased the shear work required to spread the gel composition at the same CP level. Compared to the 4% CP gel alone, the shear work of the hydrogel with 40% PVP added increased by almost 40% (8.88 ± 0.87 N × s vs. 6.49 ± 0.01 N × s). These results highlight the additive effect of PVP in increasing the pH-dependent increase in the viscoelastic properties of this hydrogel composition upon interaction with alkaline SFS. In parallel with the evaluation of spreadability, quantitative measurement of the gel phase pH value using a DeltaTrak® Pocket ISFET pH meter (DeltaTrak, Inc., Pleasanton, CA) equipped with an ion-sensitive field-effect transistor pH sensor and an integrated temperature sensor revealed that the hydrated CP / PVP polymer blend, in response to alkaline SFS, generates a significant chemical barrier as demonstrated by its strong buffering capacity (see Table 1). Dilution of the CP 4% / PVP 4% hydrogel with a larger volume fraction of SFS gradually increased the gel phase pH value from pH 3.4 ± 0.1 to pH 4.5 ± 0.1 at volumetric unity. Maintaining such an acidic vaginal environment despite the presence of alkaline SFS is predicted to significantly impair sperm motility and viability, as well as the infectivity of HIV / AIDS virions (Garg et al., 2001; Jay et al., 2009). This significant buffering capacity depends on the composition of the CP / PVP polymer blend and can therefore be individually adjusted to suit the intended preventive and / or therapeutic purposes.

[0061] (Table 1) Buffering capacity of bioresponsive polymer seals formed by hydrated acidic / nonionic polymer blends after exposure to pH 7.6 semen simulated material (SFS). TIFF2026511100000002.tif49138 a Carbopol (registered trademark) 974P, b Poly(N-vinylpyrrolidone)

[0062] To estimate the mucosal adhesion properties of the fully hydrated CP / PVP polymer blend, 0.5 g of hydrogel was placed on a microscope glass, vertically aligned, and brought into contact with a parallel microscope glass assembly mounted on a TA-XT Plus texture analyzer. After a 10-second contact time using a maximum load of 5 N, the top plate was removed at a test speed of 0.1 mm / s, and the work of adhesion was measured from the force-distance plot. The results summarized in Table 2 demonstrate that the mucosal adhesion properties of the CP / PVP hydrogel under simulated vaginal conditions are significantly improved by using a larger mass ratio of PVP in the polymer blend. Furthermore, the work of adhesion consistently increased with dilution using alkaline SFS in the hydrogel, suggesting effective intravaginal retention of the hydrated CP / PVP polymer blend after forming a bioresponsive contraceptive seal in the presence of semen.

[0063] (Table 2) Mucosal adhesion properties of bioresponsive polymer seals formed after exposure of hydrated acidic / nonionic polymer blends to a pH 7.6 semen-like substance (SFS). TIFF2026511100000003.tif49138 a Carbopol (registered trademark) 974P, b Poly(N-vinylpyrrolidone)

[0064] Example 2 - Analysis of xerogel bioresponsive polymer seals Semi-solid bioresponsive polymer seals are also established after hydration of xerogels composed of equiweight Carbopol® 974P and PVP (CP / PVP) polymer blends. Bioresponsive xerogel devices are generally manufactured by lyophilization. Briefly, volumetric aliquots of a fully hydrated CP / PVP gel formulation were filled into polypropylene syringe barrels and frozen at -80°C for 6 hours. Prior to lyophilization, the frozen gel cylinders were discharged from the syringe barrels onto a pre-cooled aluminum pan and subjected to a conventional lyophilization cycle (i.e., a primary drying phase of 6 hours at -20°C followed by a secondary drying phase of 3 hours at +25°C after a linear temperature gradient of 3.5°C / min) using a VirTis AdVantage 2.0 lyophilizer (SP Industries, Gardiner, NY, USA) at 40 mTorr. The spreadability of xerogel devices after incubation with different buffer solutions was quantified as outlined for hydrogels (see Example 1). Due to the rigid structure of the cylindrical xerogel devices, the experimental design was modified from a conical cap to a parallel glass plate assembly that allowed for perpendicular alignment of the cylindrical surface of the lyophilized device and the upper plate. Reproducible fluid administration was achieved by spraying specified amounts of acidic VFS and alkaline SFS onto the surface of the xerogel device at a constant distance of 16 mm onto a 1 cm surface using a plastic syringe equipped with a MAD Nasal® intranasal mucosal atomizing nozzle (Teleflex, Wayne, PA), which produces a fine mist of fluid particles ranging in size from 30 to 100 μm. After a 2-minute incubation period at room temperature, excess fluid present on the device surface was removed by blotting, and then the upper glass plate was lowered at a test speed of 0.2 mm / s until a maximum load of 5 N was reached. Each experiment was performed in triplicate using a new gel sample. Following intravaginal administration, the initial exposure of this xerogel device was expected to be limited to vaginal fluid only, resulting in a spreadability baseline value of 2.43 ± 0.20 N × s (Figure 4).The incremental addition of alkaline SFS transformed the xerogel device into a partially hydrated bioresponsive CP / PVP polymer composition exhibiting improved spreadability. After combining the xerogel device with four times the volume of SFS compared to the initial VFS exposure, the shear work recorded to spread the partially hydrated CP / PVP polymer blend under a simulated intravaginal pressure of 5 N was nearly 70% greater than the corresponding value measured after interaction with acidic VFS (4.13 ± 0.13 N × s⁻¹ vs. 2.43 ± 0.20 N × s⁻¹). These results demonstrate an increase in the viscoelastic properties of the partially hydrated CP / PVP xerogel device in response to alkaline SFS. The presence of this bioresponsive seal is predicted to effectively limit the migration of spermatogonial cells and HIV / AIDS virions deposited in the vagina during ejaculation, thereby preventing pregnancy and STIs. The semi-solid, bioresponsive polymer seal established by the CP / PVP xerogel device after exposure to alkaline SFS also generates a significant chemical barrier. Similar to the experimental outlines described for the CP / PVP hydrogel composition (see Example 1), the pH of the partially hydrated gel phase of the CP / PVP xerogel device was quantified using a DeltaTrak® Pocket ISFET pH meter. The data summarized in Table 3 highlight the robust buffering capacity of the CP / PVP xerogel device in response to SFS (see Table 3). Even in the presence of a four-fold larger volume fraction of alkaline SFS, the measured gel pH was 4.2 ± 0.1, which falls within the pH range of a healthy vaginal environment reported for humans, and most importantly, under acidic conditions, sperm motility and viability are impaired, and the infectivity of HIV / AIDS virions is significantly reduced (Garg et al., 2001; Jay et al., 2009).

[0065] (Table 3) Buffering capacity of bioresponsive polymer seals formed after partial hydrated xerogels composed of equal weights of acidic / nonionic polymer blends were exposed to semen-like substance (SFS) at pH 7.6. TIFF2026511100000004.tif30134CP=Carbopol(registered trademark)974P, PVP=Poly(N-vinylpyrrolidone)

[0066] Example 3 - Analysis of a nonwoven fiber mat bioresponsive polymer seal The bioresponsive polymer seal is also established after hydration of a nonwoven fiber mat composed of a 50:50 (w / w) Carbopol® 974P / PVP (CP / PVP) polymer blend, manufactured by single-nozzle electrospinning using a protocol described separately (Moyers-Montoya et al., 2016). The spreadability of the nonwoven CP / PVP fiber mat after incubation with different buffer solutions was quantified as outlined in Example 2, with the following modifications. The polymer fiber mat was cut into 3 cm × 3 cm squares and placed as a single layer on a circular glass surface in a custom platform, as shown in Figure 5A. Reproducible fluid administration was achieved by spraying a specified amount of pH 8.0 phosphate buffer onto the fiber mat surface from a constant distance of 37 mm using a plastic syringe fitted with a MAD Nasal® nasal mucosal microparticle nozzle. The specified distance between the fiber mat and the syringe nozzle was 380 mm. 2This resulted in uniform dispersion of a fine buffer mist across a consistent fiber mat surface. After a 5-minute incubation period at room temperature, the upper glass plate was lowered at a test speed of 0.1 mm / s until a maximum load of 5 N was reached. Each experiment was performed in triplicate using new polymer fiber mat samples. Figure 5B summarizes the results, demonstrating that the spreadability profiles of nonwoven fiber mats prepared using CP / PVP polymer blends ranging from 1:1 to 1:10 (w / w), after incubation with pH 8 phosphate buffer at various volume fractions, remained within a narrow baseline value of 4–5 N×s until the gel CP concentration reached approximately 10% (w / v). Further dilution with this alkaline buffer solution increased the gel phase's resistance to spreadability, which was most pronounced at CP concentrations below 3.5% (w / v). Note that the spreadability of hydrogel compositions with similar CP concentrations but different PVP concentrations correlated positively with the increasing presence of PVP. These results are consistent with the ductility data shown in Figure 3B, highlighting the additive effect of non-ionized PVP polymers in the formation of a meaningful physical barrier after exposure to alkaline solutions. These findings are unique when compared to pH-dependent rheological data (Lubrizol 2010) for CP gel compositions where ductility increases proportionally with CP concentration.

[0067] Similar to the performance of the CP / PVP xerogel and hydrogel compositions described in Examples 1 and 2, the bioresponsive polymer seals established on nonwoven CP / PVP fiber mats after exposure to alkaline buffering solutions such as pH 8.0 phosphate buffer also constitute a significant chemical barrier exhibiting substantial acid buffering capacity. Compared to fiber mats made solely of PVP, the pH of the partially hydrated gel phase, quantified using a DeltaTrak® Pocket ISFET pH meter after combining the fiber mats with various volume fractions of pH 8 phosphate buffer, remained below pH 6.4, even in the presence of a 1:20 volume dilution (Table 4). Incorporating a larger CP mass fraction into electrospinned fiber mats significantly amplified this essential buffering capacity, which correlates with impaired sperm motility and viability, as well as reduced infectivity of HIV / AIDS virions (Garg et al., 2001; Jay et al., 2009). With a uniform CP / PVP fiber mat mass ratio, the pH value of the reconstituted gel phase, measured at the same 1:20 volume dilution using pH 8 phosphate buffer, was equal to the critical pH threshold at which human sperm cease to meet WHO fertility criteria within 15 minutes of exposure (Zhou et al., 2015).

[0068] (Table 4) Buffering capacity of bioresponsive polymer seals formed after a nonwoven fiber mat layer composed of an acidic / nonionic polymer blend was exposed to alkaline phosphate buffer (PB8) at pH 8.0. TIFF2026511100000005.tif56140 a Carbopol (registered trademark) 974P, b Poly(N-vinylpyrrolidone), PB8=pH8 phosphate buffer.

[0069] To investigate dose-dependent bioresponsive changes in spreadability under simulated vaginal conditions, eight-layer nonwoven CP / PVP (50:50, w / w) from two different manufacturing batches were combined using the same experimental design as above, increasing the volume fraction of VFS or SFS. This resulted in gel compositions with CP concentrations ranging from approximately 95% to approximately 10% (w / v). In the presence of acidic VFS, the shear work recorded for the reconstituted gel phase consistently decreased after the combination of increasing volume fraction VFS with the dry CP / PVP fiber mat (Figure 6). This rheological behavior appears to be directly correlated with the decreasing CP concentration in the gel phase and is likely due to the progressive weakening of the dispersion of coiled polymer particles. In contrast, the interaction of increasing volume fraction alkaline SFS with the dry CP / PVP fiber mat consistently increased the shear work required to spread the gel phase, thus enhancing the physical barrier properties of this polymer seal. These results are consistent with the hypothesis of decoilation of polymer particles due to electrostatic repulsion of deprotonated carboxhelate groups, as described in Example 1. Interestingly, the viscoelastic properties of the bioresponsive gel phase when reconstructed from multiple CP / PVP fiber mat layers appear to be fairly constant within the CP concentration range of approximately 80% to 20% (w / w). It is hypothesized that the slow penetration rate of alkaline SFS across different fiber mat layers may be the cause of this stable plateau effect. Consistent with the results obtained with a single fiber mat layer (see Figure 5B), the most effective physical barrier established by alkaline SFS after hydration of multiple CP / PVP fiber mat layers is associated with the lowest CP concentration present in the gel phase, as demonstrated by the measured maximum shear work.

[0070] The effectiveness of the polymer seal compositions described herein for preventing unintended pregnancy and STIs depends on the long-term retention time of sperm and infectious particles within the bioresponsive gel phase. Therefore, the intravaginal retention of the reconstituted gel phase was estimated by quantifying the mucosal adhesion properties of the partially hydrated nonwoven CP / PVP fiber mat using the same experimental design described above for spreadability evaluation. After a 10-second contact time of the reconstituted gel phase with a load of 5 N (Morgan et al., 2008), equivalent to the mean physiological intravaginal pressure in the supine position exerted by the soft tissue surrounding the pelvic floor near the vagina, the upper plate was removed at a test speed of 0.1 mm / s, and the work of adhesion was measured from the force-distance plot. The results summarized in Table 5 demonstrate that the mucosal adhesion properties of the reconstituted CP / PVP hydrogel under simulated intravaginal conditions are significantly improved in the presence of an increased SFS volume. The inverse correlation between the measured adhesive work and the polymer concentration in the reconstituted gel phase suggests a more effective interaction between the decoiled polymer particles and the polar vaginal mucus layer, which is predicted to promote good intravaginal retention of the hydrated CP / PVP polymer blend after forming a mucosal adhesive contraceptive seal in the presence of semen.

[0071] (Table 5) Mucosal adhesion properties of bioresponsive polymer seals formed after nonwoven fiber mats composed of Carbopol® 974P / PVP (CP / PVP) polymer blend (50:50, w / w) were combined with different volume fractions of pH 7.6 semen-like substances (SFS). TIFF2026511100000006.tif46128 a Carbopol (registered trademark) 974P, b Poly(N-vinylpyrrolidone)

[0072] Example 4 - Bioresponsive polymer seal for pregnancy prevention To determine whether the favorable biophysical properties of the polymer composition, measured under simulated vaginal conditions, translate to contraceptive efficacy, the percentage of viable human sperm capable of crossing such bioresponsive polymer seals was quantified in vitro according to a protocol previously described by Chen and collaborators (Chen et al., 2011). Briefly, human liquid semen samples at pH 7.8–8.5 were added to the donor compartment of a Transwell® dual-chamber system (Figure 7A). The basolateral receiver compartment was filled with human tubular fluid buffer at pH 7.4. The two compartments were separated by a semipermeable polycarbonate membrane with an average pore size of 8 μm, which provided physical support for the deposition of the bioresponsive polymer composition. The proportion of human sperm migrating from the donor compartment to the receiver compartment was microscopically quantified after 60 minutes at 37°C using a conventional Makler® counting chamber, both in the presence and absence of a reconstituted gel phase composed of a bioresponsive polymer blend. Total sperm motility in the donor and receiver compartments was evaluated in pairs by blinded technicians, in accordance with the WHO manual (WHO, 2021). The results were normalized to a control experiment performed with only a semipermeable filter membrane and summarized in Figure 7B. Including a 1% (w / v) methylcellulose gel barrier, corresponding to the viscoelastic properties of cervical mucus during ovulation (Ivic et al., 2002), moderately reduced the percentage of viable sperm appearing in the receiver compartment from 99.0±7.6% to 66.7±18.8%, an average decrease of approximately 33%, although the total sperm motility before and after crossing the gel barrier remained similar (73.8±10.0% vs. 56.6±18.2%). In contrast, the percentage of sperm recovered from the receiver compartment after traversing the reconstituted bioresponsive CP / PVP polymer blend gel phase barrier decreased dramatically by over 90%. Simultaneously, the motility of spermatids that were able to overcome the bioresponsive gel barrier was less than 10%. According to WHO criteria, these results are a strong indicator of in vivo infertility (WHO, 2021).Direct comparison with the spermicidal VCF® gel revealed that including pharmacological agents such as nonoxynol-9, which negatively affect sperm viability, provides only a slight additive benefit to contraceptive efficacy.

[0073] Further evaluation of contraceptive efficacy was performed in vivo using untouched New Zealand rabbits, randomly assigned to four treatment groups of 10 rabbits each. In addition, as previously described (Zeitlin et al., 2001), four proven male breeder rabbits of the same origin and strain were used as semen donors. On the day of the experiment, the animal vaginal cavity was flushed with 5 mL of VFS to lower the pH to a physiologically acidic environment for humans. After vaginal douching, female rabbits were intravaginally administered either a 1 cm long rabbit-sized xerogel device or a 2 mL hydrogel composition prepared from a bioresponsive CP / PVP polymer blend as outlined in Examples 1 and 2, using a 1 mL tuberculin syringe without a needle tip and with a blunt tip as the applicator. Other treatment groups included a "positive control" administered 2 mL of contraceptive VCF® gel containing 4% (w / v) nonoxynol-9, and a "false control" in which animals were exposed only to empty syringe applicators. Collection and sperm cell count: 2.5–3.5 × 10⁶ 7Artificial insemination was performed in female rabbits of each treatment group within 15 minutes using 0.25 mL of pooled semen obtained from fertile male rabbits within 1 hour of preparation to embryos / mL. Immediately after artificial insemination, each female rabbit was administered 20 USP units / kg of human chorionic gonadotropin via the marginal aural vein. Twelve days later, the female rabbits were euthanized with an intravenous dose of pentobarbital sodium. The reproductive tract was dissected from the abdominal cavity, and embryos in the uterine horn were counted. The results summarized in Figure 8 demonstrate a 90% pregnancy rate in rabbits in the negative control group treated only with empty vaginal applicators (i.e., sham treatment). Intravaginal administration of a CP / PVP xerogel device manufactured by lyophilization from bioresponsive CP4% / PVP4% hydrogel provided significant contraceptive efficacy, as demonstrated by a 40% reduction in pregnancy rate compared to sham-treated control animals. When a bioresponsive CP / PVP polymer blend was administered vaginally as a fully hydrated gel composition consisting of 8% (w / v) polymer components, each being acidic and nonionic, further improvement in contraceptive efficacy was observed. Compared to results obtained with VCF® gel, which achieves contraceptive efficacy by killing spermatids using nonoxynol-9 as a pharmacological activator, the contraceptive failure rate associated with the drug-free bioresponsive polymer seal established by the 8% CP / 8% PVP hydrogel was only 10% higher than after administration of the spermicidal VCF® gel.

[0074] Example 5 - Bioresponsive polymer seal for the prevention of STIs The ability of bioresponsive polymer seals to serve as an on-demand multi-purpose preventive technology providing contraceptive efficacy in parallel with protection from transvaginally transmitted STIs depends on the individually tuned drug release characteristics after intravaginal administration of the antimicrobial agent incorporated into the bioresponsive polymer composition. To experimentally evaluate this requirement, metronidazole (MTZ) (Brandt et al., 2008; Augostini et al., 2023), an antibacterial agent with an established clinical safety and efficacy profile in the treatment and management of highly prevalent vaginal infections in women, including bacterial vaginosis and trichomoniasis, was incorporated at 0.5% (w / w) into a CP4% / PVP4% hydrogel prepared as described above in Example 1. The time-dependent release of MTZ from the bioresponsive phase was measured at 37°C in a VFS using a dual-chamber Transwell® design (see Figure 5A). Briefly, aliquots of MTZ-containing CP4% / PVP4% hydrogel were added to a filter insert, and 1 mL of VFS was added to the receiver compartment. Drug release kinetics were determined by periodically removing 50 μL aliquots from the receiver compartment and processing them for quantitative drug analysis using a validated HPLC method for MTZ with UV detection. Figure 9 shows the cumulative drug volume released over 24 hours at 37°C, normalized to the total drug dose administered at t=0 min. This profile demonstrates that MTZ can successfully dissociate from the bioresponsive gel phase at a sustained release rate under physiologically relevant acidic conditions. After this 24-hour incubation period, only 5% of the total drug dose added to the system at t=0 min still remained in the gel phase, suggesting a nearly quantitative release of this antibacterial agent. More importantly, the initial release rates measured under these simulated vaginal conditions suggest that the drug concentration in vaginal fluid exceeds the pharmacodynamically effective antimicrobial concentration of ≥50 μg / mL (Augostini et al., 2023) within 60 seconds after intravaginal administration.

[0075] Following experimental demonstration of clinically relevant drug release rates of MTZ from drug-added CP / PVP hydrogel compositions exhibiting bioresponsive properties under simulated vaginal conditions, the pharmacodynamic effects of the released antimicrobial agents against STI-related microorganisms were evaluated using a human-derived ex vivo co-culture model of bacterial vaginosis. Briefly, a suspension of Prevotella vivia isolate, originally collected from human subjects and widely prevalent in the microflora of patients diagnosed with bacterial vaginosis, was used to colonize immortalized human vaginal epithelial Vk2 / E6E7B cells at a bacterial / epithelial cell ratio of 10:1 (Fichorova et al., 2011). After incubation of the co-culture under anaerobic conditions for 24 hours, loosely attached bacteria were removed by washing. Viable bacteria bound to epithelial cells were quantified by conventional colony-forming unit (CFU) counting. Figure 10 summarizes the number of viable Prevotella vivia bacteria recovered from this co-culture model after 6 hours of treatment with different compositions. Compared to the results obtained after medium treatment (=negative control), only MTZ-containing compositions, including drug-supplemented CP4% / PVP4% hydrogel containing 0.5% (w / v) MTZ and a commercially available NUVESSA® gel product containing 1.3% (w / v) MTZ, significantly reduced the number of Prevotella vivia bacteria. These data highlight the validity of this human-derived ex vivo co-culture model in evaluating the potential for prevention against STI-related vaginal pathogens. Note that the MTZ-containing CP / PVP hydrogel was more effective than the vaginal NUVESSA® gel in suppressing the growth of this Prevotella vivia strain after 6 hours of incubation. These results suggest different drug release kinetics of MTZ from these two gel compositions, which is advantageous for the pharmacodynamic benefits of a rapidly releasing MTZ-containing CP / PVP hydrogel.

[0076] All compositions and / or methods disclosed and claimed herein can be prepared and performed without undue experimentation in light of this disclosure. While the compositions and methods of this disclosure have been described in terms of preferred embodiments, it will be apparent to those skilled in the art that modifications can be made to the compositions and / or methods described herein, as well as to the steps or order of steps of the methods described herein, without departing from the concepts, spirit, and scope of this disclosure. More specifically, it will be apparent that certain chemically and physiologically relevant agents can be used in place of the agents described herein, and the same or similar results can be achieved. All such similar substitutions and modifications that are apparent to those skilled in the art are deemed to be within the spirit, scope, and concepts of this disclosure as defined by the appended claims.

[0077] VI. References The following references are incorporated herein by reference to the extent that they provide exemplary methods or other details that supplement what is described herein. TIFF2026511100000007.tif171147TIFF2026511100000008.tif224147TIFF2026511100 000009.tif224146TIFF2026511100000010.tif210147TIFF2026511100000011.tif30146

Claims

1. A medical device comprising a polymer composition containing a polycarboxylic acid-containing polymer and a polylactone-containing polymer, wherein the polymer coating essentially contains no cellulosic polymers.

2. The medical device according to claim 1, wherein the polycarboxylic acid-containing polymer comprises two or more carboxylic acids or carboxylic acid esters per repeating unit.

3. The medical device according to claim 1 or claim 2, wherein the polycarboxylic acid-containing polymer comprises acrylate repeating units or methacrylate repeating units containing carboxylic acid or carboxylic acid ester from 1.

4. The medical device according to any one of claims 1 to 3, wherein the polycarboxylic acid-containing polymer comprises about 50% w / w to about 75% w / w of carboxylic acid groups or carboxylic acid ester groups.

5. The medical device according to any one of claims 1 to 3, wherein the polycarboxylic acid-containing polymer further comprises one or more types of crosslinking agents.

6. The medical device according to claim 5, wherein the crosslinking agent is a sugar or a sugar alcohol.

7. The medical device according to claim 6, wherein the sugar is a polysaccharide.

8. The device according to claim 6, wherein the polysaccharide is sucrose.

9. The medical device according to claim 6, wherein the sugar alcohol is erythritol.

10. The medical device according to any one of claims 1 to 9, wherein the polylactone-containing polymer is a polypyrrolidone-containing polymer.

11. The medical device according to any one of claims 1 to 10, wherein the polypyrrolidone-containing polymer is polyvinylpyrrolidone.

12. The medical device according to any one of claims 1 to 11, wherein the polycarboxylic acid-containing polymer and the polypyrrolidone-containing polymer are present in a ratio of 15:1 to 1:

15.

13. The medical device according to claim 12, wherein the ratio is 10:1 to 1:

10.

14. The medical device according to claim 13, wherein the ratio is 5:1 to 1:

5.

15. A medical device according to either claim 12 or claim 13, wherein the ratio is 1:

1.

16. The medical device according to claim 12, wherein the ratio is 15:1 to 1:

1.

17. The medical device according to claim 16, wherein the ratio is 15:1 to approximately 5:

1.

18. The medical device according to any one of claims 1 to 17, wherein the polymer composition is anhydrous.

19. The medical device according to any one of claims 1 to 17, wherein the polymer composition is a hydrate.

20. A medical device according to any one of claims 1 to 19, used for preventing pregnancy.

21. A medical device according to any one of claims 1 to 20, used to prevent the transmission of sexually transmitted infections.

22. The device according to any one of claims 1 to 21, wherein the medical device is used to treat an infectious disease.

23. A medical device according to any one of claims 1 to 22, designed to be inserted into the vagina.

24. A medical device according to any one of claims 1 to 23, which forms a barrier between the inside of the vagina and the outside of the body.

25. The medical device according to claim 24, wherein the barrier is formed when the polymer composition of the medical device is exposed to a physiological fluid.

26. The medical device according to claim 24 or claim 25, wherein the barrier is formed when the polymer coating of the medical device is exposed to a liquid having a pH of at least 7.

27. The medical device according to claim 26, wherein the pH is approximately 7 to approximately 8.

9.

28. The medical device according to claim 26 or claim 27, wherein the pH is approximately 7.

6.

29. The medical device according to any one of claims 1 to 28, wherein the polymer composition of the medical device forms a barrier that is formed upon exposure to semen.

30. The medical device according to any one of claims 1 to 29, wherein the polymer composition further comprises one or more excipients.

31. The medical device according to claim 30, wherein the excipient is a pore-forming excipient.

32. The medical device according to claim 31, wherein the pore-forming excipient is a sugar or a sugar alcohol.

33. The medical device according to claim 31, wherein the sugar or sugar alcohol is mannitol.

34. The medical device according to any one of claims 30 to 33, wherein the polymer composition comprises the polymer composition in an amount of about 0.1% w / w to 25% w / w.

35. The medical device according to claim 34, wherein the amount of the polymer composition is approximately 1% w / w to approximately 10% w / w.

36. A medical device according to any one of claims 1 to 35, further comprising a pharmaceutical active ingredient.

37. The medical device according to claim 36, wherein the pharmaceutically active ingredient is a hormone, a contraceptive, an anti-inflammatory agent, an antimicrobial agent, or a spermicide.

38. The medical device according to claim 37, wherein the pharmaceutically active ingredient is a hormone.

39. The medical device according to claim 37, wherein the pharmaceutical active ingredient is a contraceptive.

40. The medical device according to claim 37, wherein the pharmaceutically active ingredient is an anti-inflammatory agent.

41. The medical device according to claim 40, wherein the anti-inflammatory agent is a non-steroidal anti-inflammatory drug (NSAID).

42. The medical device according to claim 37, wherein the pharmaceutically active ingredient is an antimicrobial agent.

43. The medical device according to claim 42, wherein the antimicrobial agent is an antibiotic.

44. The medical device according to claim 42, wherein the antimicrobial agent is an antiviral agent.

45. The medical device according to claim 42, wherein the antimicrobial agent is an antifungal agent.

46. The medical device according to claim 37, wherein the pharmaceutically active ingredient is a spermicide.

47. The medical device according to any one of claims 1 to 30, wherein the cellulose-based polymer is nonionic cellulose.

48. The medical device according to claim 47, wherein the nonionic cellulose is hydropropylmethylcellulose.

49. A medical device according to any one of claims 1 to 48, which is coated with the polymer composition to form a polymer coating.

50. The medical device according to claim 49, wherein the polymer coating is present to a thickness of at least 1 nm.

51. The medical device according to claim 50, wherein the thickness is at least 10 nm.

52. A method for preventing infection, comprising the step of inserting a medical device according to any one of claims 1 to 51 into a patient's vagina.

53. The method according to claim 52, wherein the infectious disease is a sexually transmitted infection or a sexually transmitted disorder.

54. The method according to claim 53, wherein the sexually transmitted infection or sexually transmitted disorder is HIV or AIDS.

55. The method according to claim 52, wherein the infection is a vaginal infection.

56. The method according to either claim 52 or claim 55, wherein the infectious disease is a yeast infection.

57. The method according to any one of claims 52 to 56, wherein the medical device is inserted into the vagina without the use of an applicator.

58. The method according to claim 57, wherein the medical device is inserted into the vagina by a finger.

59. A kit comprising a medical device according to any one of claims 1 to 51.

60. (A) Polycarboxylic acid-containing polymers comprising approximately 55% w / w to approximately 70% w / w carboxylic acid groups and an acrylate skeleton; and (B) Polyvinylpyrrolidone polymer A polymer composition comprising, It contains polycarboxylic acid and polyvinylpyrrolidone polymers in a ratio of 5:1 to approximately 1:5, and is essentially free of any cellulosic substances. The aforementioned polymer composition.

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