RU2804658C2 - Suspension compositions of highly concentrated dispersions - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: carrier and delivery systems for active molecular compounds. In particular, the present invention provides suspension compositions of aqueous dispersions for administration to subjects (e.g. by injection) and methods of administration. Moreover, the said dispersion contains: a) hydrophilic clay in said dispersed phase and b) a quaternary ammonium compound in said dispersed phase.

EFFECT: new method.

24 cl, 2 ex, 5 tbl, 6 dwg

Description

Cross reference to related application

This application claims benefit from U.S. Provisional Patent Application No. 62/746,608, filed October 17, 2018, which is incorporated herein by reference in its entirety.

Field of the present invention

The present invention relates to the field of carrier and delivery systems for active molecular compounds. In particular, the present invention provides suspension compositions of aqueous dispersions for administration to subjects (eg, by injection).

Background of the present invention

In the United States, sepsis affects more than 750,000 patients annually and has a mortality rate of 30 to 65%, making it the tenth most common cause of death in the United States. The risk of sepsis appears to be inversely proportional to age. Sepsis is responsible for 60 to 80% of child deaths in developing countries. As a result of its prevalence, the number of hospitalizations due to sepsis or septicemia increased from 621,000 in 2000 to 1,141,000 in 2008. In economic terms, the total cost of treating sepsis in the United States increased at an average annual rate of 11.9% from 1997 to 2008, adjusted for inflation, reaching $14.6 billion in 2008 and currently exceeding $17 billion. . In addition to treatment of other illnesses in hospital settings, more than 2.5 million patients are admitted to intensive care units each year for treatment of sepsis, with the daily cost of treating a single ICU patient exceeding the total hospital costs of regular units by $5,000 or more, and In this case, the course of intensive therapy continues for at least two days and often for more than 20 days. In addition, approximately 50 percent of diagnosed sepsis cases in the United States are caused by hospital-acquired infections, which represent a major source of hospital costs due to little or no reimbursement from health insurance companies.

Sepsis is the body's response to infection. This response is characterized by the hallmarks of inflammation (eg, dilation of blood vessels, accumulation of leukocytes, and increased microvascular permeability) that are observed in tissues distant from the site of infection. Even a minor infection, such as strep throat or the flu, can trigger sepsis. Sepsis is not usually life-threatening, but complications of sepsis can cause serious illness and death.

Sepsis is a general term that describes immune reactions in a background that ranges from infection to multiple organ failure syndrome. Systemic inflammatory response syndrome is the presence of two or more signs including abnormal body temperature, heart rate, respiratory rate, or abnormal blood gases and white blood cells, with sepsis being defined as a systemic inflammatory response syndrome in response to an infectious process. Severe sepsis is defined as sepsis that causes sepsis-affected organ failure or insufficient tissue perfusion (manifestations such as low blood pressure, increased lactate, or decreased urine output). Severe sepsis occurs when the natural immune response to infection initiates widespread inflammation and blood clotting in microvessels throughout the body, which also involves damage to the body's vital organs and can thus lead to death. Finally, septic shock is severe sepsis associated with persistently low blood pressure.

Although existing technologies for the treatment of sepsis have improved therapeutic efficacy rates, additional treatments are required.

Summary of the present invention

The present invention relates to the field of carrier and delivery systems for active molecular compounds. In particular, the present invention provides suspension compositions of aqueous dispersions for administration to subjects (eg, by injection).

The compositions of the present invention are non-toxic, stable and suitable for administration into the body (eg, by oral administration or injection).

The compositions find use in the treatment of diseases and in the delivery of active substances (eg, drugs) in a variety of ways.

For example, according to some embodiments of the present invention, there is provided a composition comprising a suspension of a dispersion in a suspending agent (eg, glycerin), the dispersion comprising a dispersed phase in an aqueous phase, and wherein the dispersion contains: a) a hydrophilic clay in a dispersed phase; and b) a quaternary ammonium compound in the dispersed phase. In some embodiments, the suspension comprises 0.05% (e.g., 0.01 to 0.1%) of said dispersion in an aqueous solution containing 1% (e.g., 0.5 to 5.0%) of a suspending agent (e.g., glycerol). In some embodiments, the suspension is filtered (eg, through a filter having apertures of 0.45 microns or less). In some embodiments, the suspension contains or consists of particles that have a diameter of less than 0.45 microns. In some embodiments, the composition is non-toxic. In some embodiments, the composition is suitable for injection or oral administration. In some embodiments, the hydrophilic clay comprises one or more of smectite, laponite, and bentonite clays. In some embodiments, the quaternary ammonium compound is benzethonium chloride or derivatives thereof. In some embodiments, the dispersion further comprises an active ingredient (eg, containing, but not limited to, one or more of an antimicrobial agent, an analgesic agent, an antifungal agent, or an anti-inflammatory agent). In some embodiments, the dispersion and/or suspension contains one or more of a complexing agent, an emulsifier, a wetting agent, a humectant, a detackifier, an emollient, or a thickener. In some embodiments, the dispersion exhibits activity (eg, biological activity) in the absence of additional active ingredients.

The present invention is not limited to specific methods for making the dispersions and suspensions described. In some embodiments, the dispersion is made by a process comprising: i) dry mixing a hydrophilic clay and a quaternary ammonium compound to form a mixture; ii) adding water to the mixture; and iii) maintaining the mixture to obtain a dispersion. In some embodiments, the suspension is made by a method comprising: a) mixing the dispersion with glycerin; b) adding water to obtain a solution; and c) filtering the solution.

The compositions described herein can be formulated for any number of routes of use or administration. In some embodiments, the composition is an oral aerosol, mouthwash, eye drop, or disinfectant, although other specific compositions may be provided.

According to certain embodiments of the present invention, there is provided a method of making a suspension, comprising the following steps: a) mixing a dispersion made by a method comprising i) dry mixing a hydrophilic clay and a quaternary ammonium compound to obtain a mixture; ii) adding water to the mixture; and iii) maintaining the mixture to obtain a dispersion with glycerol; b) adding water to obtain a suspension; and c) filtering the suspension. In some embodiments, the suspension comprises 0.05% (eg, 0.01 to 0.1%) of said dispersion in an aqueous solution containing 1% (eg, 0.5 to 5.0%) glycerol.

According to the following embodiments, a pharmaceutical composition is provided comprising: a) a composition as described herein; and b) a pharmaceutically acceptable carrier.

According to additional embodiments, a kit is provided comprising: a) a composition as described herein; and b) an injection device. In some embodiments, a kit is provided in a dosage form.

According to some embodiments of the present invention, there is provided a dressing or wipe containing a composition as described herein.

According to the following embodiments, a method of administering an active ingredient to a subject is provided, comprising: administering a composition as described herein to a subject in need thereof. In some embodiments, the composition is for oral administration. In some embodiments, the composition is for intravenous, subcutaneous, intramuscular, or other administration.

In other embodiments, there is provided a method of disinfecting a part or surface of a body, comprising: contacting a composition as described herein with said part or surface, which is, for example, but not limited to, a joint, an eye, a throat, a wound, a burn, or the surface of a medical device, such as a surgical instrument, implantable medical device, syringe, or drug container.

In addition, a method of treating an infection in a subject is provided, comprising administering to the subject a composition as described herein. In some embodiments, the infection is a blood infection (eg, sepsis), and the composition is then administered intravenously. In some embodiments, the infection is an infection caused by bacteria, viruses, or fungi. In some embodiments, the composition adsorbs endotoxins.

According to further embodiments of the present invention, the use of a composition as described herein is provided for delivering an active ingredient to a subject or for disinfecting a part or surface of the body or treating an infection.

The present invention is not limited to specific subjects. In some embodiments, the subject is a human or non-human animal.

Embodiments are described hereinafter.

Brief description of the figures

In fig. 1 illustrates the bacterial adsorption capacity of compositions according to embodiments of the present invention for Escherichia coli 8739.

In fig. 2 illustrates the bacterial adsorption capacity of compositions according to embodiments of the present invention for Escherichia coli.

In fig. 3 depicts the Log10 reduction at 96,000 EU of compositions according to embodiments of the present invention.

In fig. 4 shows the bacterial adsorption capacity at 96,000 UE of compositions according to embodiments of the present invention.

In fig. 5 shows the bactericidal activity of compositions according to embodiments of the present invention against Escherichia coli.

In fig. 6 presents the bactericidal activity of compositions according to embodiments of the present invention against serration marcescens.

Definitions

As used herein, the term “dispersion” means a stable suspension. Such dispersions may be stable due to the particle size/or the presence of components that simultaneously contain hydrophilic and hydrophobic groups and are, for example, surfactants or emulsifiers. In some embodiments, the dispersion remains stable for more than one day, one week, one month, etc.

As used herein, the terms “continuous phase” and “dispersed phase” refer to a dispersion system in which a first material is dispersed in a second material in the form of fine solid or liquid particles. In such a dispersion system, the term "continuous phase" means the first phase, which is surrounded by a second "dispersed phase". The term "dispersed phase" means suspended particles or liquid droplets dispersed in a continuous phase.

As used herein, the term "emulsion" means a heterogeneous system containing a continuous phase and a discontinuous phase capable of forming droplets in the continuous phase.

As used herein, the term "emulsifier" means a substance that can reduce and/or eliminate surface and interfacial tension in a two-phase system. The emulsifying agent may simultaneously contain hydrophilic and lipophilic groups. The emulsifier may be present in the continuous phase, the dispersed phase, or both.

When used herein, the expression “in combination with” is intended to describe any or all of the following: chemical bonding, electrostatic attraction, entrapment, complete or partial dissolution, and suspension.

As used herein, the term “topical administration” means application of the compositions of the present invention to the surfaces of the skin, wound, and/or cells or tissues of the mucous membranes, such as, for example, the mucous membranes of the alveolar processes of the jaws, cheeks, tongue, chewing surfaces, nasal cavities, etc.

As used herein, the term "wetting agent" means a hygroscopic compound containing many hydrophilic groups, for example, glycerol, propylene glycol, etc.

As used herein, the term “humectant” means a composition that, when applied to a surface (eg, skin, mucosal tissue, wound, etc.), causes water to retain on the surface.

As used herein, the term "subject" means any animal (e.g., mammal), such as, but not limited to, humans, other primates, pets (e.g., dogs, cats, etc.), farm animals (e.g., horses, cows, goats, sheep, pigs, etc.), rodents, birds and other animals that must receive specific treatment.

As used herein, the term "pharmaceutical composition" means the combination of an active substance with a carrier, inert or active, which makes the composition particularly suitable for diagnostic or therapeutic use in vivo or in vitro.

As used herein, the term “toxic substance” means a substance that produces any adverse or harmful effects on cells or tissues compared to the same cells or tissues before the toxic substance was applied.

Detailed Description of the Present Invention

The present invention relates to the field of carrier and delivery systems for active molecular compounds. In particular, the present invention provides suspension compositions of aqueous dispersions for administration to subjects (eg, by injection).

For example, according to some embodiments of the present invention, suspension dispersion compositions are provided. Exemplary dispersion compositions are described below and in US Patent No. 8,858,970, which is incorporated herein by reference in its entirety.

Suspensions are prepared, for example, by mixing a dispersion as described herein with a suspending agent (eg, glycerol) in an aqueous solution and optionally filtering the solution. In some embodiments, the ratio of dispersion, suspending agent (eg, glycerol), and water is optimized to produce a uniform suspension. During the experiments described herein, it was determined that a dispersion of 0.05% (e.g., 0.01 to 0.10%) in a suspension containing 1% (e.g., 0.05 to 5%) glycerol provided optimal operational characteristics. However, other concentrations or ratios may be used.

In addition, it has been determined that filtering the suspension through a filter (eg, a 0.45 micron or other sized filter) produces a uniform suspension that is non-toxic.

Accordingly, in some embodiments, the suspensions described are non-toxic, uniform suspensions that are suitable for injection and oral administration. These suspensions find use in a variety of medical and industrial applications described herein.

According to some embodiments of the present invention, a suspension containing a dispersion containing a dispersed phase in a continuous or aqueous phase is provided. In some embodiments, the continuous phase contains a liquid or gel and may optionally contain one or more of a wetting agent, emollient, detackifier, humectant, thickener, complexing agent, or other additive. In some embodiments, the dispersed phase comprises a hydrophilic particle support containing electrically charged linking moieties, an intermediate component containing a hydrophobic moiety and an ionic moiety (e.g., an electrically charged moiety, a hydrophilic moiety), and optionally an active ingredient, e.g., a bioactive moiety (e.g. , antimicrobial substance, etc.) containing a hydrophobic fragment. In some embodiments, the ionic moiety of the intermediate is attracted to the electrically charged linking moieties of the hydrophilic particle support. In some embodiments, the hydrophobic moiety of the intermediate is attracted to the hydrophobic moiety of the active ingredient. In some embodiments, attractive forces between the intermediate component, the hydrophilic particle support, and the active ingredient cause the components to assemble to form a complex or supramolecular particle.

Example variances are described below.

Variances

In some embodiments, the compositions (eg, dispersions) have viscosity values of at least 100 centipoise (eg, greater than 100 centipoise, 100 to 150 centipoise, 150 to 200 centipoise, greater than 200 centipoise, 200 to 300 centipoise, greater than 300 centipoise, more than 500 centipoise). In some embodiments, the compositions have viscosity values ranging from 150 to 200 centipoise. In some embodiments, the compositions have viscosity values of greater than about 1000 centipoise (e.g., 1000 centipoise, 2000 centipoise, 5000 centipoise, 10,000 centipoise, 20,000 centipoise, 50,000 centipoise, 100,000 centipoise, 200,000 centipoise, etc. ). In some embodiments, the compositions are gels. In some embodiments, desired viscosities are achieved by adding gelling agents, high viscosity additives, and increasing solids concentration (e.g., above 10%, above 15%, above 20%, above 25%, above 30%, above 40%, above 50 % etc.).

In some embodiments, the dispersion comprises a continuous aqueous phase containing finely divided material held in suspension by a small particle size, such as submicron, or by an emulsifier. In some embodiments, the dispersion contains a suspended phase containing suspended microparticles or smaller particles, and may contain hydrophobic droplets. Droplets and sometimes solids can be held in suspension by an emulsifier. In some embodiments, the terms “aqueous continuous phase” or “aqueous phase” mean the continuous phase that surrounds the solid particles and/or hydrophobic droplets. Thus, the aqueous phase contains suspended or dissolved components, for example, thickeners, gelling agents, wetting agents, humectants, emulsifiers, complexing agents, stabilizers, skin enhancers, emollients, colorants and fragrances. Emollients and emulsifiers can be thought of as being in intermediate phases that separate the aqueous (polar) and non-polar (oil) phases. Particles and hydrophobic droplets can be considered as representing a suspended phase. The water used to form the aqueous phase is deionized water, obtained by any known methods, for example, using ion exchange resins or distillation in an inert system, for example, in non-reactive glass, or by the process of reverse osmosis.

In some embodiments, the compounds used as intermediates contain ligands that are associated with the core particle and are designed to accept additional components on the exposed portions. In some embodiments, the compound for use in the intermediate layer is a quaternary ammonium compound containing a hydrophobic radical; however, any other compound having an ionic structure can be used and used as described above.

Ligands having antimicrobial properties are compounds containing reactive inorganic cations, in particular those having one or more electrons available for chemical reactions (eg, transition metals), as well as compounds containing organic cations and known for their bactericidal activity. For example, the antimicrobial effects produced by quaternary ammonium compounds, iodophor compounds, phenolic compounds, alcohol, chlorine, peroxides, aldehydes and metals are well documented. Additional details can be found in US Pat. No. 6,288,076, which is incorporated herein by reference in its entirety. Ligands having antimicrobial properties that are particularly desirable for use as ligands according to the present invention are quaternary ammonium compounds, transition metals, organometallic compounds, perchlorates, charged halogen-containing compounds, charged organic peroxides, ionic polymers, ionic surfactants and mixtures of them.

Particularly desirable quaternary ammonium compounds are hexadecyltrimethylammonium bromide, trimethylphenylammonium chloride, and mixtures thereof. Particularly desirable transition metals are copper, iron, manganese, zinc, silver, mercury, and mixtures thereof. The antimicrobial agent of the present invention contains ligands attached to the colloidal particles and present in excess of more than 200% (for example, more than 250% or more than 300%) of the cation exchange capacity of the colloidal particles, resulting in a more effective antimicrobial agent.

A preferred quaternary compound having cationic activity is benzethonium chloride. Benzethonium chloride, which contains an ionic hydrophilic moiety and a hydrophobic radical and is antimicrobial and thus active, can be used in both the secondary and tertiary layers. Benzethonium chloride may be present in an amount of, for example, 0.5% by weight based on solids.

The quaternary ammonium compound may be used as the secondary layer and/or the antimicrobial tertiary layer, for example in an amount of, for example, 0.50% by weight on a solids basis.

When the compounds have such properties, they can be directly and indirectly deposited onto the particle support in two layers. Complete coverage of one layer can be considered 100% coverage, and when complete coverage occupies both intermediate (secondary and tertiary) layers, this coverage can be considered 200% coverage. The present invention can allow high coverage rates of 200% or even more due to additional complex interactions.

According to some embodiments of the present invention, particle supports are provided. In some embodiments, the particle supports are hydrophilic particle supports. In some embodiments, the particle supports are hydrophilic submicron particle supports. In some embodiments, the particle supports contain electrically charged bonding moieties. In some embodiments, the particulate supports contain hydrophilic moieties (eg, hydrophilic linking moieties). In some embodiments, hydrophilic moieties are formed due to ionic groups, including, for example, quaternary, carboxyl, sulfur, phosphorus, or polar groups, such as groups that may have a chemically bonded oxygen, nitrogen, sulfur, or phosphorus atom having an available electron pair. Such components may be compounds or assemblies. Specific examples are anionic, cationic and nonionic groups that may be present in surfactants. In some embodiments, the particle substrates have submicron diameters of, for example, less than 1 μm, less than 0.5 μm, less than 0.2 μm, less than 0.1 μm, less than 0.05 μm, less than 0.02 μm, less 0.01 microns, etc. In some embodiments, the submicron size provides stability. In some embodiments, the submicron particles are nanoparticles that do not require stabilization.

As used herein, the term “particle support” means particles that act as a support with which a substance, compound, ligand, reactive group, functional group, etc., reacts. Exemplary particulate supports that find use in the present invention are hydrophilic hydrated clays. Such clays are predominantly aluminosilicates in which some of the aluminum and silicon ions have been replaced by elements having different valence or charge values. For example, aluminum (Al ³⁺ ) can replace iron (Fe ²⁺ ) or magnesium (Mg ²⁺ ), creating a net negative charge. This charge attracts positive cations, which in turn can attract corresponding anions.

The particles may be organic or inorganic particles, including nanoparticles. Preferred inorganic materials have a specific surface area of 50 to 1000 m ² /g, with a specific surface area of 500 to 800 m ² /g being particularly desirable. Suitable synthetic clay-type minerals include synthetic hectorite, which is a layered hydrated magnesium silicate, such as laponite from Southern Clay Products (Gonzales, Texas, USA), synthetic mica montmorillonite, such as barasim from the Baroid division of NL Industries ( Houston, Texas, USA), and mixtures thereof. Suitable naturally occurring clay minerals are swelling clays such as aliettite, beidellite, bentonite, nontronite, saponite, soconite, stevensite, swinefordite, wolkonskoite, yahontovite, hectorite, montmorillonite (such as colloid BP) and mixtures thereof. Other suitable materials (including synthetic and naturally occurring) include, but are not limited to, polymers, zeolites, layered double hydroxides, illite, chlorite, kaolinite, hydrotalcite, talc, halloysite, sepiolite and palygorskite, among others minerals such as oxides, hydroxides, and silicates, to mention a few. Generally, the colloidal particles of the present invention have an average diameter of from 1 nm to 100 microns, with particles having an average diameter of less than 2 microns or less than 1 micron being preferred.

Preferred clays are hydrophilic clays such as smectite, laponite and bentonite having high cation exchange capacity. Other suitable particles are ion exchange resin particles and organic plastic particles containing charged moieties.

In some embodiments, the particles simultaneously exhibit high specific surface area and significant ion exchange capacity. Such ion exchange capacity values usually, but not always, represent cation exchange capacity (CEC) values. It should be understood that anion exchange resins, such as polyfunctional resins containing quaternary amino groups, may also be used. In general, when the term "CEC" is used herein, it should be understood that anion exchange resins may also be used in the appropriate context. The number of linking moieties of a particle can be defined as the number of linking moieties per mole when it is known that the structural formula of the resin is modified by surface characteristics, such as specific surface area, due to particle size effects. CEC values are known for specific materials, such as the laponites used in the examples described herein, which are known to have a CEC value of approximately 55.0 meq/100 g. The compositions described herein are unique in that for these, coatings with excess CEC values of, for example, more than 125% and up to 250% or more can be obtained.

The biologically active compositions prepared by implementing the methods of the present invention using a variety of supports, examples of which are presented below, complement a variety of biologically active compounds that are attached to the support. By varying the organic compounds that are used to ion-exchange the organic supports, the organic support can be modified to acquire hydrophilic or hydrophobic surface tension properties. In addition, by selecting an appropriate support, such as clay, as a carrier, which is used to further attach the organic compound to the organic support, the resulting antimicrobial agents can exhibit hydrophilic or hydrophobic properties. This allows the compositions to be used in aqueous or non-aqueous formulations.

In certain embodiments of the present invention, the active ingredients comprise a tertiary layer of fine particles. In some embodiments, the active ingredients (eg, tertiary layer formation molecules) contain a hydrophobic moiety (eg, a hydrophobic moiety). In other embodiments, the active ingredients (eg, tertiary layer formation molecules) contain a biologically active moiety. In certain embodiments, the active ingredients are quaternary compounds. In some embodiments, the active ingredients are antimicrobial agents, wetting agents, humectants, anti-inflammatory agents, and nutrients.

In some embodiments, the quaternary compound is one or more antimicrobial agents, including, but not limited to, lauryldimethylbenzylammonium chloride, benzalkonium chloride, alkyltrimethylammonium chloride, dialkyldimethylammonium chloride, alkyldimethylbenzylammonium chloride, alkyldimethyl(ethylbenzyl)ammonium chloride, combinations thereof, and etc. In other embodiments, the quaternary compound is one or more non-antimicrobial conditioning agents, including, but not limited to, the following: cetrimide, cetrimonium bromide, cetylamidopropyldimethylammonium chloride, stearyltrimethylammonium chloride, stearalkonium chloride, dihydrogenated tall oil dimethylammonium chloride, thereof combinations, etc.

Specific non-limiting examples of suitable hydrophobic active ingredients are: acetretin, albendazole, albuterol, aminoglutethimide, amiodarone, amlodipine, amphetamine, amphotericin B, atorvastatin, atovaquone, azithromycin, baclofen, beclomethasone, benezepril, benzonate, butamethasone, butafthione, busafe tanide, butefetantione, butafetanide , camphetanide, candesartan, capsaicin, carbamezepine, carotenes, celecoxib, cerivastatin, cetirizine, chlorpheniramine, cholecalciferol, cilostazol, cimetidine, cinnarizine, ciprofloxacin, cisapride, clarithromycin, clemastine, clomiphene, clomipramine, clopidogrel, codeine, coenzyme Q10, cyclobenzaprine, cyclosporine, danazol, dantrolene, dexchlorpheniramine, diclofenac, dicoumarin, digoxin, dehydroepiandrosterone, dihydroergotamine, dihydrotachysterol, dirithromycin, donezepil, efavirenz, eposartan, ergocalciferol, ergotamine, sources of essential fatty acids, etodolac, etoposide, famotidine, fenofibrate, fentanyl, fexofenadine, finasteride, fluconazole , flurbiprofen, fluvastatin, fosphenytoin, frovatriptan, furazolidone, gabapentin, gemfibrozil, glibenclamide, glipizide, glyburide, glimepiride, griseofulvin, halofantrine, ibuprofen, irbesartan, irinotecan, isosorbide dinitrate, isotretinoin, itraconazole, ivermectin, ketoconazole, ketorolac, lamotrigine, lanzoprazole, leflunomide, lisinopril, loperamide, loratadine, lovastatin, L-triroxine, lutein, lycopene, medroxyprogesterone, mifepristone, mefloquine, megestrol acetate, methadone, methoxalen, metronidazole, miconazole, midazolam, miglitol, minoxidil, mitoxantrone, montelukast, nabumet he, nalbuphine, naratriptan , nelfinavir, nifedipine, nilsolidipine, nilutanide, nitrofurantoin, nizatidine, omeprazole, oprevelkin, estradiol, oxaprozin, paclitaxel, paracalcitol, paroxetine, pentazocine, pioglitazone, pizofetin, pravastatin, prednisolone, probucol, progesterone, pseudoephedrine, pyridostigmine, rabeprazole, ral oxyphene, rofecoxib , repaglinide, rifabutin, rifapentine, rimexolone, ritanovir, rizatriptan, rosiglitazone, saquinavir, sertraline, sibutramine, sildenafil citrate, simvastatin, sirolimus, spironolactone, sumatriptan, tacrine, tacrolimus, tamoxifen, tamsulosin, targretin, tazarotene, telmisartan, teniposide, terbinafine, terazosin, tetrahydrocannabinol, tiagabine, ticlopidine, tirofibran, tizanidine, topiramate, topotecan, toremifene, tramadol, tretinoin, troglitazone, trovafloxacin, ubidecarenone, valsartan, venlafaxine, verteporfin, vigabatrin, vitamin A, vitamin D, vitamin E, vitamin K, zafirlukast, zileuton, zolmitriptan, zolpidem and zopiclone. In addition, salts, isomers and derivatives of the above hydrophobic active ingredients, as well as mixtures thereof, can also be used.

In some embodiments, the dispersion further comprises an active ingredient that is a drug (eg, an anti-inflammatory, analgesic, antibiotic, or other drug).

Dispersions may contain additional compounds including, but not limited to, emulsifiers, complexing agents, gelling agents, stabilizers, skin-enhancing agents, emollients, colorants, detackifiers, thickeners, non-aqueous humectants, anti-inflammatory agents, application-enhancing agents. substances and fragrances on the skin.

Dispersions may also contain detackifiers such as a phenyl silicone fluid, for example phenyl trimethicone. In some embodiments, the detackifier also acts as a wetting agent. In some embodiments, the dispersions contain an emollient, such as pentaerythrityl tetracaprylate.

In certain embodiments, the dispersion contains one or more dyes and/or pigments, including, but not limited to, the following: titanium dioxide, mined natural and synthetic iron oxides, mixtures of inorganic oxides and fillers (kaolin, talc, silica, mica), pharmaceutical and cosmetic dyes, food, pharmaceutical and cosmetic dyes, combinations thereof, etc. In some embodiments, the dispersion contains one or more colorants, including, but not limited to, the following: dispersed red 13, dispersed green 9, solvent black 3, dispersed blue 148, dispersed violet 63, dispersed blue, dispersed blue 14, orange solvent 15, orange solvent 7, blue solvent 14, dispersed yellow 82, 9-diethylamino-5H-benzo[alpha]phenoxazin-5-one, 1-dimethylamino-5-sulfamoylnaphthalene, pyrene, 1-pyrenecarbaldehyde, Reichardt dye, 4 -aminophthalimide, 4-(N,N-dimethylamino)phthalimide, bromonaphthalene, 2-(dimethylamino)naphthalene, solfatochromatic dye, combinations thereof, etc.

In certain embodiments, the dispersion contains one or more flavoring agents, including, but not limited to, the following: tea tree oil, citrus oils (eg, lemon oil, orange oil, etc.), herbal oils ( e.g. rosemary oil, thyme oil, oregano oil, etc.), tree oils (e.g. rosewood oil, cedarwood oil), cinnamaldehydes or cinnamon bark oil, eugenol or clove flower oil, cineole or eucalyptus oil, camphor or camphor tree oil, geraniol or geranium oil, citronella oil, geranium oil, cedrol, etc. In some embodiments of the present invention, any suitable essential oil is provided. In some embodiments, flavoring agents further provide antimicrobial, fungicidal, and/or insect repellent functionality.

In some embodiments, the dispersion contains one or more emulsifiers, including, but not limited to, the following: PEG dimethicones, polyglycerol dimethicones, sorbitol oleate, glycerol esters, C12-15 alkyl benzoate, castor oil, cetearyl alcohol, cetyl alcohol , cetyl alcohol esters, cetyl palmitate, diisopropyl adipate, emu oil, isopropyl myristate, isopropyl palmitate, lanolin, Indian mango seed oil, mineral oil, myristyl myristate, sorbitol oleate, safflower oil, oleaginous seed oil, stearic acid, stearyl alcohol, calcium stearoyl lactylate, ceteareth -20, cocamide MEA, glyceryl laurate, glyceryl stearate, glyceryl stearate and PEG-100 stearate, glyceryl stearate SE, glycol distearate, glycol stearate, isoceteth-20, isosteareth-20, lauramide DEA, laureth-23, laureth-4, linoleamide DEA, sesquistea rat methylglucose , Olet-10, Olet-10/Polyoxyl-10 Oleyl Ether NF, Olet-2, Olet-20, PEG-100 Stearate, PEG-20 Mandelic Glycerides, Methyl Glucose Sesquistearate, PEG-25 Hydrogenated Castor Oil, PEG-30 Dipolyhydroxystearate , PEG-4 dilaurate, PEG-40 sorbitol peroleate, PEG-60 mande glycerides, PEG laurate, PEG-80 sorbitol laurate, polysorbate 20, polysorbate 60, polysorbate 80, polysorbate 85, sodium stearoyl lactylate, sorbitol isostearate, sorbitol laurate, sesquioleate sorbitol, sorbitol stearate, sorbitol stearate and sucrose cocoate, sorbitol trioleate, MEA stearamide, steareth-2, steareth-21, combinations thereof, etc.

The dispersion may contain one or more wetting agents, including, but not limited to, the following: polyglycerol dimethicones, gelatin, glycerin, honey, hyaluronic acid, panthenol, propylene glycol, sodium ammonium lactate, sodium pyrrolidine carboxylate, sorbitol, urea, 1 ,2,6-hexanetriol, hexylene-and butylene glycol, dipropylene glycol, hexylene glycol, panthegnol, phytanitriol, sodium pyrrolidone carboxylate, triethylene glycol, oleylglyceryl sorbitol, glucose, fructose, polydextrose, potassium pyrrolidone carboxylate, hydrogenated honey, inositol, hexanediol-beeswax , hexanetriol-beeswax , hydrolyzed elastin, hydrolyzed collagen, hydrolyzed silk, hydrolyzed keratin, erythritol, capryl glycol, isoceteth-(3-10, 20, 30), isolaureth-(3-10, 20, 30), lanet-(5-50), laureth -(1-30), steareth-(4-20), trideceth-(5-50), sucrose, glucose, aloe, alpha hydroxy acids (AHA), combinations thereof, etc.

In some embodiments, the dispersion contains one or more thickeners and/or stabilizers, including, but not limited to, dimethicone gums, dimethicone cross-polymers, stearic acid, cetyl alcohol stearic acid, cellulose, carbopol, polyacrylic acid , clays, carrageenan, pectin and locust bean gum, xanthan gum, carbomer (a homopolymer of acrylic acid having a high molecular weight and cross-linked using any of several allyl ether polyalcohols), combinations thereof, etc.

In certain embodiments, the dispersion contains one or more tackifiers and/or emollients, including, but not limited to, the following: dimethicone cross-polymers, cyclomethicone, vegetable oils, polyisobutene, squaline, ceramides such as lactoceramide, essential fatty acids (linoleic acid), fatty acids and esters of fatty alcohols and fatty acids, lanolin, lauric acids, stearic and palmitic acids with a chain containing, respectively, 16 and 18 carbon atoms (coconut oil, grape seed oil and palm kernel oil ), ceramides, their combinations, etc. In some embodiments, proteins are present that, as emollients, contract when applied to the skin (or wound), leaving a film that smoothes the skin and thereby prevents water loss (e.g., collagen, keratin, elastin, mixtures of proteins such like wheat protein).

In various embodiments, the dispersion contains one or more alcohols, including, but not limited to, acyclic alcohols (eg, ethanol), isopropyl alcohol, etc.

In other embodiments, the dispersion contains one or more skin application enhancers and/or film formers, including, but not limited to, trimethylsiloxysilicates, acrylates/dimethicones, etc.

In some embodiments, the dispersion contains one or more conditioning agents, including, but not limited to, dimethicone gums, amine-modified silicones, cetrimide, cetrimonium bromide, cetylamidopropyldimethylammonium chloride, combinations thereof, etc.

In specific embodiments, the dispersion contains one or more preservatives, including, but not limited to, the following: phenonip, parabens and parabenzoic acid esters (phenoxyethanol), antioxidants (tocopherol, butylated hydroxytoluene (BHT), combinations thereof, etc. .

In various embodiments, the dispersion contains one or more fats and/or waxes, including, but not limited to, the following: tunga moluccan seed oil, NF almond oil, USP anhydrous lanolin, apricot kernel oil, avocado oil, babassu oil , beeswax, borage seed oil, Brazil nut oil, hemp oil, canola oil, caprylic/capric acid triglyceride, carrot seed oil, ceresin, coconut oil, carrot root extract, dimethicone, rose hip oil, evening primrose oil, grapeseed oil Kernel Oil, Hybrid Safflower Oil, Jojoba Oil, Macadamia Nut Oil, Indian Mango Seed Oil, Olive Oil, Rice Seed Oil, NF Peanut Oil, Petrolatum, PPG-15 Steroid Ester, Retinyl Palmitate, Sesame Oil, Soybean Oil, Sunflower Oil , sweet almond oil, cocoa butter, tocopherol, combinations thereof, etc.

In some embodiments, the compositions may also contain a humectant (humectant). Moisturizers prevent and treat dry skin, protect sensitive skin, improve skin color and texture, and camouflage imperfections. Moisturizers are often complex mixtures of chemicals specifically designed to make the outer layers of the skin (epidermis) softer and more flexible by increasing their water content by reducing evaporation. The components of the moisturizing composition may be, for example, naturally occurring skin lipids and sterols, as well as artificial or natural oils, wetting agents, emollients and lubricants. One example of a humectant that finds use in the present invention is glycerin. Other skin moisturizers contemplated for use in the present invention include, but are not limited to, the following: urea, ammonium lactate, sodium pyrrolidone carboxylate, saccharides, simple sugars, hygroscopic salts and glycerin, often present in combination with an emollient such as such as oleaginous fruit oil, soybean glycine sterol, annual sunflower oil and olive oil. As mentioned above, another suitable humectant is glucolactone, which is combined with sodium benzoate.

Complexing agents, eg, gluconate, can be used to complex with substances that may interfere with desired reactions and combinations, for example, a complexing agent may be present to complex with compounds that may interfere with the binding of the quaternary compound to the colloidal support. Complexing agents are usually optional. A complexing agent may be present, being, for example, a solution containing from 20% to 60% gluconic acid and sodium gluconate when determined after neutralization.

In some embodiments, dispersions are provided in the form of a topical antimicrobial carrier system, wherein the fine particulate material comprises a hydrophilic clay, a secondary layer contains a quaternary ammonium compound, and a tertiary layer contains an antimicrobial compound. In some embodiments, the dispersions contain a quaternary compound, such as benzethonium chloride. In some embodiments, the dispersions are present in the form of a topical anti-inflammatory composition, for example where the tertiary layer contains an anti-inflammatory compound such as an omega-3 fatty acid. In some embodiments, the dispersions are present in the form of a local anesthetic composition, for example where the tertiary layer contains capsaicin or lidocaine.

In some embodiments, dispersions or suspensions for use by injection contain pharmaceutically acceptable carriers. For example, compositions and preparations for parenteral, intrathecal or intraventricular administration may contain sterile aqueous solutions, which may also contain buffers, diluents and other suitable additives such as, but not limited to, penetration enhancers, carrier compounds and other pharmaceuticals. acceptable carriers or excipients.

In some embodiments, dispersions or suspensions for use in oral care products contain one or more components that are typically found in oral care products (such as, for example, mouthwash, toothpaste, etc.). Examples include, but are not limited to, cetylpyridinium chloride, chlorhexidine, essential oils, fluoride, peroxide, alcohol and flavoring agents.

In some embodiments, dispersions or suspensions for use in eye products contain one or more components that are typically present in eye products. Examples include, but are not limited to, saline, steroids, antihistamines, sympathomimetic agents, beta blockers, parasympathomimetic agents, parasympatholytic agents, prostaglandins, nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, antifungals, or local anesthetics.

The dispersions of the present invention provide significant advantages over the administration of active ingredients using other carriers and/or systems, including, but not limited to, the following advantages: increased adsorption capacity for bacterial cells and toxins, reduced toxicity of active ingredients, increased duration of activity for active ingredients, sustained release characteristics, controlled release of active ingredients, ease of use, increase in active ingredient content up to 200% ion exchange capacity or more, reduced irritation and increased effectiveness.

The methods of the present invention may include the following steps: combining a hydrophilic clay in the form of particles containing charged moieties with a compound containing an ionic moiety and a hydrophobic radical to form a precombination and introducing the precombinant into an aqueous phase to form an intermediate dispersion and combining the hydrophobic active compound with an intermediate dispersion to obtain a further particle dispersion comprising support particles with which are combined an intermediate secondary layer containing a hydrophobic radical and a tertiary layer containing the active compound.

Additional examples of detailed methods for making and using dispersions according to the present invention include, but are not limited to, the following methods. According to certain embodiments of the present invention, methods for making a dispersion are provided, comprising one or more of the following steps: adding a wetting agent to deionized water to form an aqueous suspension; uniform mixing of hydrophilic clay and quaternary compound; adding water to the resulting mixture of clay and quaternary compound to form a combination of hydrophilic clay and quaternary ammonium compound; combining the aqueous suspension and the combination of a hydrophilic clay and a quaternary ammonium compound to form a suspension; heating the suspension to a temperature of from 70 to 90°C; optionally dispersing together with at least one active ingredient to form a dispersion; heating the dispersion to a temperature of from 70 to 90°C; mixing the dispersion with the suspension; application of vacuum and homogenization of the resulting composition. According to some embodiments of the present invention, methods are provided for making a carrier system for a bioactive compound containing a cationic moiety and a hydrophobic moiety, comprising one or more of the following steps: mixing the bioactive compound and a hydrophilic clay to form a mixture of the active compound and the hydrophilic clay; suspending the mixture of the active compound and the hydrophilic clay in an aqueous liquid to form a suspension; and introducing the suspension into the carrier. Any of the methods listed above or below may include adjusting the pH if necessary, for example, by adding KOH to the mixture contents to adjust the pH to about 5.2 to 6.2.

Methods

The present invention finds use in a variety of administration methods and compositions. Exemplary routes of administration and compositions are presented below. These examples should not be considered limiting; on the contrary, modifications and combinations of these embodiments are within the scope of the present invention.

The suspensions described herein find use in a variety of applications. Examples include, but are not limited to, the following applications: injection applications, oral applications, oral care applications, ophthalmic applications, wound care applications, surgical applications, burn care applications, and industrial applications.

For example, in some embodiments, suspensions find use in delivering an active ingredient (eg, a drug) by injection or topical administration to an eye, throat, wound, or burn.

In some embodiments, the suspension serves as an antimicrobial agent without the addition of additional active ingredients. Such suspensions are used, for example, to kill bacteria in the throat, eyes, wounds or inside the body (for example, in the case of sepsis). In some embodiments, the suspension adsorbs endotoxins (eg, in the blood).

In some embodiments, the suspensions find use in the disinfection of medical devices (such as, for example, but not limited to, a surgical instrument, an implantable medical device, a syringe, or a drug container (eg, an IV bag)).

Additional applications of the suspension compositions described herein are presented below.

In addition, the present invention provides a method for topical disinfection of an epidermal surface, comprising the step of contacting the epidermal surface with a composition according to the present invention, wherein the tertiary layer contains an antimicrobial compound.

According to another embodiment of the present invention, there is provided a method for topical application of drugs to an epidermal surface, comprising the use of a composition according to the present invention, in which the tertiary layer contains the drug.

In some embodiments, compositions are provided that are antimicrobial compositions. These compositions find use in subjects including, but not limited to, the following: healthcare workers, nurses, doctors, veterinarians, surgeons, patients, pre- and post-surgical patients, schoolchildren, teachers, students, travelers, flight attendants, sanitation workers hygiene service, etc. Antimicrobial compositions (e.g., containing suspensions described herein) may find use in protecting against the spread of and/or killing a wide variety of pathogens, including, but not limited to, the following microorganisms: gram-positive bacteria (e.g., methicillin-resistant Staphylococcus aureus Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus faecalis, Clostridium spp., Listeria spp., Bacillus spp., etc.), gram-negative bacteria (e.g. Escherichia coli, Serracia marcescens, Pseudomonas aeruginosa, Salmonella spp., Helicobacter, Akinetobacter Baumann and etc.), yeast (e.g. candida alba, cryptococcal fungus, candida glabrata, etc.), mold (e.g. Aspergillus nigra, cladosporium, acremonium, etc.), viruses (e.g. adenovirus, spp. influenza, rotavirus, rhinovirus, etc.) etc. In some preferred embodiments, the active ingredient in the antimicrobial compositions is benzethonium chloride.

The compositions described herein are suitable for any number of delivery systems. In some embodiments, the compositions are for injection (such as, for example, intravenous, intramuscular, epidural, intra-arterial, intraperitoneal, intrathecal, or subcutaneous injection). In some embodiments, the injectable compositions are pharmaceutical compositions as described above.

In some embodiments, compositions are provided in the form of a kit containing a suspension containing one or more active ingredients, as well as an administration component or device. In some embodiments, the injectable composition comprises a syringe, a self-injection syringe, an intravenous administration device, an infusion device, etc. In some embodiments, the topical composition comprises a nebulizer or is a drinkable composition. In some embodiments, the kits contain the composition in unit dose form.

In some embodiments, antimicrobial compositions find use in the treatment of infectious diseases (caused, for example, by viruses, fungi, or bacteria) in the body (including, for example, blood-borne or other infections of the body).

In some embodiments, the compositions described herein are used in veterinary medicine to treat infections.

Veterinary compositions are administered, for example, as dietary supplements, liquids, injections, oral agents, impregnations, collars, disinfectant solutions, powder pouches, etc.

The compositions described herein find use in the treatment of any number of infections affecting primates, farm animals, pets, etc. Examples of common livestock diseases and infectious agents include, but are not limited to, bovine respiratory syndrome (BRDC), clostridial disease, bovine respiratory syncytial virus (BRSV), bovine viral diarrhea (BVD), Haemophilus somnus , infectious bovine rhinotracheitis (IBR), parainfluenza infection type 3 (PI3), Pasteurella haemolytica and Pasteurella multocida, brucellosis and tuberculosis, foot and oral diseases, tetanus, equine viral encephalomyelitis, equine viral herpes: EHV-1 and EVH- 4, West Nile virus, respiratory infections that cause Streptococcus suis, Pasteurella, as well as actinobacillus pleuropneumonia, Brachyspira hyodysenteriae, mastitis and parvovirus.

Examples of common diseases and infectious agents in companion animals include, but are not limited to, parvovirus, rabies, ringworm, canine brucellosis, canine distemper virus (CDV), leptospirosis, ehrlichiosis, feline immunodeficiency virus (FIV) and feline leukemia virus (FelV). .

It should be understood that the present invention is not limited to the specific methods, materials and modifications described, which may therefore vary. In addition, it should be understood that the terminology used herein is intended solely for the purpose of describing specific aspects and is not intended to limit the scope of the present invention, which is limited only by the appended claims. Although any methods, devices or materials similar or equivalent to those described herein may be used for the practice or investigation of the present invention, they should not be construed as limiting.

experimental part

The following examples use a BC200 dispersion containing laponite and benzethonium chloride. The BC200 dispersion was obtained in the following way:

Example 1

This example describes the preparation of an injectable dispersion composition. Method of preparation: Weighed 900 g of a dispersion containing laponite and benzethonium chloride (see, for example, US Pat. No. 8,858,970, which is incorporated herein by reference in its entirety). Sample 1 contained 0.05% dispersion (BC200), 1.0% glycerol and 98.9% sterile water (BZT content was 0.011%). Sample 2 contained 0.5% BC200, 10% glycerol and 89.0% sterile water (BZT content was 0.1100%). The sample weight was adjusted to 10 g by adding glycerol. Place 1 ml of sample into a 100 ml volumetric flask and add water to 100 ml. The solution was filtered through a 0.45 micron filter using vacuum filtration.

High Performance Liquid Chromatography (HPLC) Extraction Method: Place 1 mL of sample in a 20 mL volumetric flask, add methanol to make 20 mL, and filter twice through a 0.45 micron filter using a syringe. For HPLC analysis, 1 ml of the final solution was used.

Theoretical detection calculations for variance (Busumite variance)

1.9 g Busumite in glycerin (1 ml in 100 ml water) → 0.19 g total or 0.0019 g/ml

11% Busumite is benzethonium chloride

0.0019 g/ml × 0.11=0.000209 g/ml × 1000=0.0209 g/ml benzethonium chloride

1 ml of this final solution was placed in 20 ml for extraction

0.0209 g/ml / 20 ml × 1000=10.45 μg/ml

HPLC data

Sample 1

Detection before filtration - 10.3257 µg/ml

Detection after filtration - 5.2723 µg/ml

Sample 2

Detection before filtration 11.1991 µg/ml

Detection after filtration - 5.0742 µg/ml

The data shows complete detection of both layers in the samples before filtration. Detection in samples after filtration shows losses of approximately 50% during filtration. A homogeneous suspension of BC200 in an aqueous solution containing glycerol was obtained by reducing the particle size due to the optimal ratio of BC200, glycerol and water and reducing the particle size by filtration (which removes any agglomerates).

Cytotoxicity studies of suspensions were carried out using the rules of the US Pharmacopoeia. Before testing, the samples were mixed using a vortex method. After 48-72 hours of plating, the culture medium from duplicate wells with an area of 10 cm ² in each case contained a monolayer of mouse fibers of L-929 regional cells (American Type Culture Collection (ATCC) cell line CCL 1, National Type Culture Collection (NCTC) clone 929 )) was pumped out and replaced with 2 ml Dulbecco's phosphate buffered saline (PBS) to wash away any contaminants. The PBS was pumped out and replaced with 0.8 ml of 5% serum-containing cell culture medium (minimal maintenance medium (MEM)). Neutral red dye was also mixed with MEM before placement into cell culture wells. For every 2 ml of MEM, 20 μl of neutral red dye was added.

Sterile filter paper with a flat surface measured to have a total surface area of 1.0 cm ² was saturated with approximately 0.1 ml of test sample and placed directly on the cell culture monolayer in the center of a 10 cm ² well. Duplicate preparations were made.

Description and preparation of negative control sample: Standard high density polyethylene (HDPE) according to the United States Pharmacopoeia (USP) was used as a negative control sample. The negative control sample was kept in a Pacific BioLabs autoclave before use. A negative control sample (measured area 1.0 cm ² ) was placed in the center of a 10 cm ² well containing mouse fibroblast cells. The negative control sample was made in duplicate.

Description and preparation of positive control sample: A latex surgical glove was used as a positive control sample. A positive control sample (measured area 1.0 cm ² ) was placed in the center of a 10 cm ² well containing mouse fibroblast cells. The positive control sample was prepared in duplicate.

Incubation: All wells were incubated in a humidified incubator at 5±1% CO ₂ and 37±1°C for at least 24 hours.

Counting: After incubation, test samples and control samples were removed from the wells. Cell cultures were examined by inverted light microscopy at 100x magnification to determine the cytotoxic reaction.

After filtration, the dispersion of sample 1 did not exhibit cytotoxicity. Before filtration, the dispersion exhibited moderate cytotoxicity.

Example 2

This example describes the antibacterial activity of BC200. Table 1 shows the bacterial binding of BC200 and the combination of benzethonium and laponite. In fig. Figures 1-4 show bacterial adsorption of BC200 and a combination of benzethonium and laponite. Tables 2 and 3 present the adsorption capacity and efficiency of a variety of materials. Table 2 presents the experimental conditions, and Table 3 presents the results. In tables 4-5 and fig. 5-6 shows the bactericidal activity of various materials. Table 4 and Fig. 5 shows activity against Escherichia coli. In Table 5 and Fig. Figure 6 shows the activity against serration marcescens.

Claims (41)

1. A composition for delivering the active substance to a subject, containing: a suspension of a dispersion in glycerol, wherein said dispersion contains a dispersed phase in an aqueous phase, and wherein the dispersion contains: a) hydrophilic clay in said dispersed phase; And b) a quaternary ammonium compound in said dispersed phase, wherein said hydrophilic clay contains one or more of smectite, laponite and bentonite clays; wherein said quaternary ammonium compound contains benzethonium chloride; wherein said suspension contains from 0.01% to 0.1% of said dispersion in an aqueous solution containing from 0.5% to 5% glycerol. 2. The composition according to claim 1, in which the specified suspension contains 0.05% of the specified dispersion in an aqueous solution containing 1% glycerol. 3. Composition according to claims. 1, 2, in which said suspension is filtered. 4. The composition of claim 3, wherein said filter has openings of 0.45 microns or less. 5. Composition according to any one of paragraphs. 1-4, said composition being suitable for injection or oral administration. 6. Composition according to any one of paragraphs. 1-5, wherein said hydrophilic clay comprises laponite clay. 7. Composition according to any one of paragraphs. 1-6, in which said dispersion additionally contains an active substance. 8. The composition according to claim 7, in which the specified active substance contains one or more of: an antimicrobial agent, an analgesic agent, an antifungal agent and an anti-inflammatory agent. 9. Composition according to any one of paragraphs. 1-8, wherein said dispersion contains one or more of a complexing agent, an emulsifier, a wetting agent, a humectant, a detackifier, an emollient and a thickener. 10. Composition according to any one of paragraphs. 1-9, in which said suspension contains particles whose diameter is less than 0.45 microns. 11. Method for producing a suspension according to any one of paragraphs. 1-10, including the following stages: a) mixing the dispersion made by the method of i) dry mixing the specified hydrophilic clay and the specified Quaternary ammonium compound to obtain a mixture; ii) adding water to said mixture; and iii) maintaining said mixture to obtain said dispersion with glycerin; b) adding water to obtain a suspension; And c) filtering said suspension, wherein said hydrophilic clay contains one or more of smectite, laponite and bentonite clays; wherein said quaternary ammonium compound contains benzethonium chloride; wherein said suspension contains from 0.01% to 0.1% of said dispersion in an aqueous solution containing from 0.5% to 5% glycerol. 12. The method according to claim 11, in which the specified suspension contains 0.05% of the specified dispersion in an aqueous solution containing 1% glycerol. 13. Pharmaceutical composition containing: a) a composition according to any one of paragraphs. 1-10; And b) a pharmaceutically acceptable carrier. 14. A kit for delivering the active substance to a subject, containing: a) a composition according to any one of paragraphs. 1-10 or 13; And b) a device for administering composition a). 15. The kit according to claim 14, in which the specified composition is present in dosage form. 16. Composition according to any one of paragraphs. 1-10, wherein said composition is formulated as an oral aerosol, mouthwash, eye drop or disinfectant. 17. A bandage for delivering the active substance to a subject, containing the composition according to any one of paragraphs. 1-10 or 13. 18. A napkin for delivering the active substance to a subject, containing the composition according to any one of paragraphs. 1-10 or 13. 19. A method of administering an active substance to a subject, including administering a composition according to any one of claims. 1-10 or 13 to the subject in need, wherein said administration is selected from the group consisting of oral administration, intravenous administration, intramuscular administration, subcutaneous administration and local administration. 20. The method of claim 19, wherein said subject is selected from the group consisting of a human, a domestic animal, and a farm animal. 21. Method according to paragraphs. 19-20, wherein said composition treats an infection or condition treatable by the antibacterial activity of the composition in said subject. 22. The method of claim 21, wherein said condition is sepsis. 23. The method according to claim 21, in which the specified composition adsorbs endotoxins. 24. Use of the composition according to any one of paragraphs. 1-10 or 13 to deliver the active substance to the subject.