Pharmaceutical preparation for suppressing body odor

Abstract

There is provided a pharmaceutical preparation comprising an anticholinergic agent and a ternary solvent, the ternary solvent comprising 5% to 15% v / v of a diol, 60% to 70% v / v of an alcohol, and 5% to 20% v / v of water. There is also provided a method of preparing a pharmaceutical preparation as disclosed herein, comprising the step of mixing an anticholinergic agent with a mixture containing an alcohol, a diol, water, a humectant, and a pH buffer at room temperature. There is also provided a method of suppressing non-pathological body odor in a mammal. There is also provided a method of treating apocrine secretion causing odor and reducing microbial overgrowth in a mammalian subject, and the use of the pharmaceutical preparation.

Description

Technical Field

[0001] The present invention relates to pharmaceutical preparations, methods for their preparation and their uses. Background Art

[0002] Axillary bromhidrosis, or commonly known as "axillary / underarm odor", is a very common problem among adults and causes severe social embarrassment and functional impairment. The link between body odor, apocrine glands in the armpits and underarm bacteria was first discovered in the 1950s. The secretions of apocrine glands become malodorous when decomposed by bacteria, which is the main cause of axillary bromhidrosis.

[0003] In humans, apocrine sweat glands only occur in certain parts of the body: the armpits, areola and nipples, ear canals, eyelids, alae nasi, perianal area and certain parts of the external genitalia. Apocrine glands are located in the lower part of the reticular dermis and subcutaneous tissue. There are more apocrine glands in men than in women. Racial differences in body odor are related to differences in the number of apocrine glands in different races. The exact mechanism that stimulates human apocrine glands is not yet clear, but existing evidence suggests that it is caused by catecholamines, and the cholinergic sympathetic nervous system indirectly affects this process. In humans, apocrine glands are mainly located in the armpits, and axillary bromhidrosis is the main source of body odor.

[0004] The pathogenesis of apocrine axillary bromhidrosis is dual; the secretions of apocrine glands are subsequently decomposed by resident bacteria, producing unsaturated fatty acids, especially trans-3-methyl-2-hexenoic acid, isovaleric acid and propionic acid, releasing an unpleasant odor. Current treatment options, especially topical applications, are limited and scarce. The most common topical applications include deodorants, topical antibiotics and antibacterial agents, and antiperspirants containing aluminum salts. Deodorants mask body odor, but they do not prevent odor. The fragrances found in deodorants often cause contact dermatitis. Topical antibiotics and antibacterial agents, including antibacterial soaps, help limit the growth of bacteria that contribute to the decomposition of apocrine secretions. However, these are often ineffective or have a short-lived effect. Antiperspirants containing aluminum salts inhibit sweating by forming a temporary blockage in the sweat pores. Although this is currently the best topical option, it often causes inflammation around the blocked sweat pores, resulting in itchy rashes. Antiperspirants also stain clothes and do not work for many people. There are non-topical treatment options available, but they are inconvenient (iontophoresis), or invasive and expensive (botulinum toxin, laser, microwave ablation and surgery).

[0005] Due to the deficiencies of existing therapies, many people do not receive treatment for axillary bromhidrosis. Therefore, there is a need to provide a new treatment in the form of a pharmaceutical preparation and a method for its preparation that overcomes or improves one or more of the above disadvantages.

[0006] In small mammals such as cats and dogs, apocrine glands are widely distributed throughout the body because they are associated with each hair follicle. When the sympathetic and / or parasympathetic nervous systems that innervate these glands are stimulated, these apocrine glands have the ability to produce sweat, but are not greatly affected by emotional or thermal stimuli. This secretion is also easily decomposed by bacteria and releases a foul odor. This often occurs in the skin folds of animals, and the skin folds near the limbs or neck are prone to trapping heat, moisture, and bacteria.

[0007] This pharmaceutical preparation helps reduce the overall unpleasant odor in the skin folds of animals. It is not applicable for treating infections of the ceruminous glands or the circumanal glands of the anal sacs. Summary of the Invention

[0008] The present invention relates to a pharmaceutical preparation comprising an anticholinergic agent and a ternary solvent, the ternary solvent comprising 5% to 15% v / v of a diol, 60% to 70% v / v of an alcohol, and 5% to 20% v / v of water.

[0009] In one aspect, the present disclosure relates to a pharmaceutical preparation comprising glycopyrronium bromide and a ternary solvent, the ternary solvent comprising 5% to 15% v / v of propylene glycol, 60% to 70% v / v of isopropyl alcohol, and 5% to 20% v / v of water.

[0010] In another aspect, the present disclosure relates to a pharmaceutical preparation consisting essentially of glycopyrronium bromide and a ternary solvent, the ternary solvent comprising 5% to 15% v / v of propylene glycol, 60% to 70% v / v of isopropyl alcohol, and 5% to 20% v / v of water.

[0011] Advantageously, the pharmaceutical preparation can effectively target two steps involved in bromhidrosis, where the anticholinergic agent inhibits apocrine secretion, and the high-concentration alcohol in the ternary solvent acts as a broad-spectrum antimicrobial agent, restricting the growth of bacteria that contribute to the decomposition of apocrine secretions.

[0012] When sweat penetrates the stratum corneum of the skin fold area such as the armpit, the swelling and accumulation of water in the intercellular area can lead to the narrowing of the infundibular region of the hair follicle. This results in the obstruction of the skin penetration of the anticholinergic agent through the hair follicle pathway. More advantageously, the pharmaceutical preparation can enhance the skin permeability of the anticholinergic agent through the transcellular and intercellular pathways, avoiding the problem of reduced bioavailability of hydrophilic anticholinergic agents.

[0013] Even more advantageously, the pharmaceutical preparation may not cause sweat pore blockage, which can lead to inflammation around the sweat ducts.

[0014] Even more advantageously, the pharmaceutical preparation can be easily applied to the skin and dries quickly after application.

[0015] The present disclosure relates to a method for preparing a pharmaceutical preparation disclosed herein, comprising the step of mixing an anticholinergic agent with a mixture containing an alcohol, a diol, water, a humectant, and a pH buffer at room temperature.

[0016] In another aspect, the present disclosure relates to a method for preparing a pharmaceutical preparation disclosed herein, which comprises the step of mixing glycopyrronium bromide with a mixture containing isopropyl alcohol, propylene glycol, water, a humectant, and a pH buffer at room temperature.

[0017] The present disclosure relates to a method for suppressing non-pathological body odor in a mammal, comprising the step of administering a pharmaceutical preparation to a region of the mammal to suppress apocrine secretion and inhibit the activity of microorganisms residing on the region or prevent their overgrowth, wherein the pharmaceutical preparation comprises an anticholinergic agent and a ternary solvent, and the ternary solvent comprises 5% to 15% v / v of a diol, 60% to 70% v / v of an alcohol, and 5% to 20% v / v of water.

[0018] In another aspect, the present disclosure relates to a method for suppressing non-pathological body odor in a mammal, which comprises the step of administering a pharmaceutical preparation to a region of the mammal to suppress apocrine secretion and inhibit the activity of microorganisms residing on the region or prevent their overgrowth, wherein the pharmaceutical preparation comprises glycopyrronium bromide and a ternary solvent, and the ternary solvent comprises 5% to 15% v / v of propylene glycol, 60% to 70% v / v of isopropyl alcohol, and 5% to 20% v / v of water.

[0019] In another aspect, the present disclosure relates to a method for suppressing non-pathological body odor in a mammal, which comprises the step of administering a pharmaceutical preparation to a region of the mammal to suppress apocrine secretion and inhibit the activity of microorganisms residing on the region or prevent their overgrowth, wherein the pharmaceutical preparation consists essentially of glycopyrronium bromide and a ternary solvent, and the ternary solvent comprises 5% to 15% v / v of propylene glycol, 60% to 70% v / v of isopropyl alcohol, and 5% to 20% v / v of water.

[0020] Advantageously, the method for suppressing non-pathological body odor can result in an average reduction of about 63.0%, about 64.0%, about 65.0%, about 66.0%, about 67.0%, about 68.0%, about 69.0%, about 70.0%, about 71.0%, about 72.0%, or about 73.0% in axillary body odor in human subjects.

[0021] More advantageously, the method for suppressing non-pathological body odor can result in an average reduction of about 53.0%, about 54.0%, about 55.0%, about 56.0%, about 57.0%, about 58.0%, about 59.0%, about 60.0%, about 61.0%, about 62.0%, or about 63.0% in axillary body odor in canine subjects.

[0022] The present disclosure relates to a method for treating apocrine secretion causing odor and reducing microbial overgrowth in a mammalian subject, comprising administering a pharmaceutical preparation to an area of the mammalian subject exhibiting said microbial overgrowth, wherein the pharmaceutical preparation comprises an anticholinergic agent and a ternary solvent, and the ternary solvent comprises 5% to 15% v / v of a diol, 60% to 70% v / v of an alcohol, and 5% to 20% v / v of water.

[0023] In another aspect, the present disclosure relates to a method for treating apocrine secretion causing odor and reducing microbial overgrowth in a mammalian subject, which comprises administering a pharmaceutical preparation to an area of the mammalian subject exhibiting said microbial overgrowth, wherein the pharmaceutical preparation comprises glycopyrronium bromide and a ternary solvent, and the ternary solvent comprises 5% to 15% v / v of propylene glycol, 60% to 70% v / v of isopropyl alcohol, and 5% to 20% v / v of water.

[0024] The present disclosure relates to a pharmaceutical preparation for treating apocrine secretion causing odor and reducing microbial overgrowth in a mammalian subject, wherein the pharmaceutical preparation comprises an anticholinergic agent and a ternary solvent, and the ternary solvent comprises 5% to 15% v / v of a diol, 60% to 70% v / v of an alcohol, and 5% to 20% v / v of water.

[0025] In another aspect, the present disclosure relates to a pharmaceutical preparation for treating apocrine secretion causing odor and reducing microbial overgrowth in a mammalian subject, wherein the pharmaceutical preparation comprises glycopyrronium bromide and a ternary solvent, and the ternary solvent comprises 5% to 15% v / v of propylene glycol, 60% to 70% v / v of isopropyl alcohol, and 5% to 20% v / v of water.

[0026] The present disclosure relates to the use of a pharmaceutical preparation in the manufacture of a medicament for treating apocrine secretion causing odor and reducing microbial overgrowth in a mammalian subject, wherein the pharmaceutical preparation comprises an anticholinergic agent and a ternary solvent, and the ternary solvent comprises 5% to 15% v / v of a diol, 60% to 70% v / v of an alcohol, and 5% to 20% v / v of water.

[0027] In another aspect, the present disclosure relates to the use of a pharmaceutical preparation in the manufacture of a medicament for treating apocrine secretion causing odor and reducing microbial overgrowth in a mammalian subject, wherein the preparation comprises glycopyrronium bromide and a ternary solvent, and the ternary solvent comprises 5% to 15% v / v of propylene glycol, 60% to 70% v / v of isopropyl alcohol, and 5% to 20% v / v of water.

[0028] Definitions

[0029] The following words and terms used herein shall have the indicated meanings:

[0030] As used herein, the term "anticholinergic" refers to the ability of a substance to prevent the neurotransmitter acetylcholine from binding to acetylcholine receptors on multiple parts of the body, including sweat glands.

[0031] As used herein, the term "bromhidrosis" refers to a condition of abnormal or offensive body odor, mainly due to the microbial decomposition of apocrine gland secretions.

[0032] As used herein, the term "antimicrobial agent" refers to the ability to cause cell inhibition, cell damage, cell death, or control the growth of target bacterial and fungal microorganisms.

[0033] As used herein, the term "ternary solvent" refers to a mixture system composed of three different component liquids that can dissolve anticholinergic agents.

[0034] As used herein, the term "mammal" refers to a vertebrate characterized by the presence of mammary glands that produce milk to nourish its young, neocortex, fur or hair, three middle ear bones, and a four-chambered heart.

[0035] As used herein, the term "topical" refers to application on the body surface.

[0036] As used herein, the term "non-pathological" refers to being unrelated to pathology or disease and not indicating being caused by pathology or disease.

[0037] As used herein, the term "malodor" refers to an offensive odor.

[0038] Unless otherwise specified, the terms "comprising" and "comprise" and their grammatical variants are intended to represent "open-ended" or "inclusive" language, such that they include the recited elements, but also allow the inclusion of other unrecited elements.

[0039] As used herein, in the context of the concentration of formulation components, the term "about" generally refers to + / - 5% of the stated value, more typically + / - 4% of the stated value, more typically + / - 3% of the stated value, more typically + / - 2% of the stated value, even more typically + / - 1% of the stated value, and even more typically + / - 0.5% of the stated value.

[0040] Throughout this disclosure, certain embodiments may be disclosed in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as a rigid limitation on the scope of the disclosed range. Accordingly, the description of a range should be considered to have specifically disclosed all possible sub-ranges as well as individual numerical values within that range. For example, a description of a range such as 1 to 6 should be considered to have specifically disclosed sub-ranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., as well as individual numbers within that range, such as 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

[0041] Certain embodiments may also be described herein in broad and general terms. Every narrower species and sub-generic grouping falling within the general scope of disclosure also forms part of this disclosure. This includes a general description of the embodiments, with conditional or negative limitations removing any subject matter from the genus, whether or not the excised material is specifically recited herein.

[0042] Detailed disclosure of embodiments

[0043] Exemplary, non-limiting embodiments of pharmaceutical formulations will now be disclosed.

[0044] A pharmaceutical formulation comprising an anticholinergic agent and a ternary solvent comprising 5% to 15% v / v of a diol, 60% to 70% v / v of an alcohol, and 5% to 20% v / v of water.

[0045] A pharmaceutical formulation consisting of an anticholinergic agent and a ternary solvent consisting of 5% to 15% v / v of a diol, 60% to 70% v / v of an alcohol, and 5% to 20% v / v of water.

[0046] A pharmaceutical formulation consisting essentially of an anticholinergic agent and a ternary solvent consisting essentially of 5% to 15% v / v of a diol, 60% to 70% v / v of an alcohol, and 5% to 20% v / v of water.

[0047] When sweat penetrates the stratum corneum of skin fold areas such as the axilla, the development of swelling and water accumulation in the intercellular region can cause narrowing of the infundibular region of the hair follicle. This results in obstruction of the skin penetration of the anticholinergic agent through the hair follicle pathway. The pharmaceutical formulation can enhance the skin permeability of the anticholinergic agent through transcellular and intercellular pathways, avoiding this problem of reduced bioavailability of hydrophilic anticholinergic agents.

[0048] The anticholinergic agent may be selected from: glycopyrronium bromide, hyoscyamine, atropine, scopolamine, benzatropine, clidinium bromide, cyclopentolate, darifenacin, dicyclomine, solifenacin, homatropine hydrobromide, ipratropium bromide, orphenadrine, oxybutynin, propantheline, methscopolamine, solifenacin, tiotropium bromide, tolterodine, trihexyphenidyl, trospium chloride, and mixtures thereof.

[0049] The alcohol may be selected from ethanol and isopropanol.

[0050] The diol may be selected from propylene glycol, butylene glycol and pentylene glycol.

[0051] The amount of the anticholinergic agent may be about 1.0% w / v, about 2.0% w / v, about 3.0% w / v, about 4.0% w / v, about 5.0% w / v or about 6.0% w / v of the pharmaceutical preparation.

[0052] The concentration of the components in the ternary solvent may be as follows:

[0053] The diol is about 5.0% v / v, about 6.0% v / v, about 7.0% v / v, about 8.0% v / v, about 9.0% v / v, about 10.0% v / v, about 11.0% v / v, about 12.0% v / v, about 13.0% v / v, about 14.0% v / v, or about 15.0% v / v of the pharmaceutical preparation;

[0054] The alcohol is about 60.0% v / v, about 61.0% v / v, about 62.0% v / v, about 63.0% v / v, about 64.0% v / v, about 65.0% v / v, about 66.0% v / v, about 67.0% v / v, about 68.0% v / v, about 69.0% v / v, or about 70.0% v / v of the pharmaceutical preparation; and

[0055] Water is about 5.0% v / v, about 6.0% v / v, about 7.0% v / v, about 8.0% v / v, about 9.0% v / v, about 10.0% v / v, about 11.0% v / v, about 12.0% v / v, about 13.0% v / v, about 14.0% v / v, about 15% v / v, about 16% v / v, about 17% v / v, about 18% v / v, about 19% v / v, or about 20.0% v / v of the pharmaceutical preparation.

[0056] When the anticholinergic agent is glycopyrronium bromide and the alcohol is isopropanol, the proportions of the components in the ternary solvent may be such that the ratio of propylene glycol:isopropanol:water is 2:13:2.5 v / v.

[0057] The pharmaceutical preparation may further comprise an excipient material suitable for topical administration.

[0058] The excipient material may be selected from antibacterial agents, antifungal agents, humectants, emulsifiers, preservatives, dispersants, emollients, surfactants, structuring agents, absorption promoters, antibacterial agents, anesthetics, keratolytic agents, wound healing agents, lubricants, antiperspirants, depilatory agents, ultraviolet protectants, anti-inflammatory agents, steroids, antioxidants, antihistamines, skin and hair conditioners, fragrances, essential oils and natural plant extracts.

[0059] The humectant can be selected from glycerol, propanetriol, lecithin, gelatin, lactic acid, hyaluronic acid, glyceryl triacetate, hexylene glycol, butylene glycol, sorbitol, allantoin, sodium hyaluronate, sodium lactate, ammonium lactate, sodium pyrrolidone, and urea.

[0060] The pharmaceutical preparation can be used for topical application.

[0061] The pharmaceutical preparation can be anticholinergic and antimicrobial.

[0062] The pharmaceutical preparation can be anticholinergic and antibacterial.

[0063] The pharmaceutical preparation can be in a form selected from solutions, lotions, creams, ointments, gels, pastes, aerosols, foams, and sprays.

[0064] When the pharmaceutical preparation is in the form of a spray for human use, the pharmaceutical preparation can be applied 1 or 2 times per day at least once on the axilla, with one application in the morning and optionally one application in the afternoon, depending on individual needs.

[0065] When the pharmaceutical preparation is in the form of a spray for canine use, the pharmaceutical preparation can be sprayed on the diseased skin at a frequency of 1 to 3 times per day, with a spray interval of 4 to 8 hours.

[0066] The amount of the anticholinergic agent in each spray application can be about 2.00 mg, about 2.10 mg, about 2.20 mg, about 2.30 mg, about 2.40 mg, about 2.50 mg, about 2.60 mg, about 2.70 mg, or about 2.80 mg.

[0067] Exemplary non-limiting embodiments of a method for preparing a pharmaceutical preparation will now be disclosed.

[0068] A method for preparing a pharmaceutical preparation as disclosed herein, comprising the step of mixing an anticholinergic agent with a mixture containing an alcohol, a diol, water, a humectant, and a pH buffer at room temperature.

[0069] The alcohol can be selected from ethanol and isopropanol.

[0070] The pH buffer can be selected from organic acids, amino acids, polyamino carboxylic acids, citrates, polyphosphates, and combinations thereof.

[0071] The pH buffer can be selected from citric acid, acetic acid, tartaric acid, ethylenediaminetetraacetic acid, 2,3-dimercaptopropanesulfonic acid, thiamine tetrahydrofurfuryl disulfide, α-lipoic acid, glycine, sodium citrate, potassium citrate, sodium phosphate, and combinations thereof.

[0072] The amount of the humectant can be about 5.0% w / v, about 6.0% w / v, about 7.0% w / v, about 8.0% w / v, about 9.0% w / v, about 10.0% w / v, about 11.0% w / v, about 12.0% w / v, about 13.0% w / v, about 14.0% w / v, about 15.0% w / v, about 16.0% w / v, about 17.0% w / v, about 18.0% w / v, about 19.0% w / v or about 20.0% w / v of the pharmaceutical preparation.

[0073] The amount of the pH buffer can range from about 0.05% w / v to about 1.00% w / v, about 0.10% w / v to about 1.00% w / v, about 0.20% w / v to about 1.00% w / v, about 0.40% w / v to about 1.00% w / v, about 0.60% w / v to about 1.00% w / v, about 0.80% w / v to about 1.00% w / v, about 0.05% w / v to about 0.10% w / v, about 0.05% w / v to about 0.20% w / v, about 0.05% w / v to about 0.40% w / v, about 0.05% w / v to about 0.60% w / v, about 0.05% w / v to about 0.80% w / v, about 0.10% w / v to about 0.20% w / v, about 0.10% w / v to about 0.40% w / v, about 0.10% w / v to about 0.60% w / v, about 0.10% w / v to about 0.80% w / v, about 0.20% w / v to about 0.40% w / v, about 0.20% w / v to about 0.60% w / v, about 0.20% w / v to about 0.80% w / v, about 0.40% w / v to about 0.60% w / v, about 0.40% w / v to about 0.80% w / v or about 0.60% w / v to about 0.80% w / v of the pharmaceutical preparation.

[0074] Exemplary, non - limiting embodiments of methods for suppressing non - pathological body odor and methods for treating apocrine secretion causing odor and reducing microbial overgrowth in mammalian subjects will now be disclosed.

[0075] A method for suppressing non - pathological body odor in a mammal is provided, comprising the step of administering a pharmaceutical preparation to an area of the mammal to inhibit apocrine secretion and inhibit the activity of or prevent the overgrowth of microorganisms resident on the area, wherein the pharmaceutical preparation comprises an anticholinergic agent and a ternary solvent, and the ternary solvent comprises 5% to 15% v / v of a diol, 60% to 70% v / v of an alcohol, and 5% to 20% v / v of water.

[0076] There is also provided a method for suppressing non-pathological body odor in a mammal, comprising the step of applying a pharmaceutical preparation to an area of the mammal to suppress apocrine secretion and to suppress the activity of microorganisms resident on the area or to prevent their overgrowth, wherein the pharmaceutical preparation consists of an anticholinergic agent and a ternary solvent, and the ternary solvent consists of 5% to 15% v / v of a diol, 60% to 70% v / v of an alcohol, and 5% to 20% v / v of water.

[0077] There is also provided a method for suppressing non-pathological body odor in a mammal, comprising the step of applying a pharmaceutical preparation to an area of the mammal to suppress apocrine secretion and to suppress the activity of microorganisms resident on the area or to prevent their overgrowth, wherein the pharmaceutical preparation mainly consists of an anticholinergic agent and a ternary solvent, and the ternary solvent mainly consists of 5% to 15% v / v of a diol, 60% to 70% v / v of an alcohol, and 5% to 20% v / v of water.

[0078] When the body odor of a mammal is non-pathological, overgrowth of microorganisms can be defined as less than 10 5 organisms per gram of tissue or per milliliter of biological fluid.

[0079] The method for suppressing non-pathological body odor can result in an average reduction in axillary body odor of about 63.0%, about 64.0%, about 65.0%, about 66.0%, about 67.0%, about 68.0%, about 69.0%, about 70.0%, about 71.0%, about 72.0%, or about 73.0% in human subjects.

[0080] The method for suppressing non-pathological body odor can result in an average reduction in axillary body odor of about 53.0%, about 54.0%, about 55.0%, about 56.0%, about 57.0%, about 58.0%, about 59.0%, about 60.0%, about 61.0%, about 62.0%, or about 63.0% in canine subjects.

[0081] The mammal can be selected from primates, Caniformia, and Artiodactyla.

[0082] The microorganism can be selected from species of the genus Corynebacterium (Corynebacterium spp.), Corynebacterium minutissimum, Corynebacterium striatum, Corynebacterium jeikeium, species of the genus Staphylococcus (Staphylococcus spp.), Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus pseudintermedius, species of the genus Streptococcus (Streptococcus spp.), species of the genus Micrococcus (Micrococcus spp.), species of the genus Propionibacterium (Propionbacterium spp.), Propionibacterium acnes, species of the genus Anaerococcus (Anaerococcus spp.), species of the genus Candida (Candida spp.), Escherichia coli, Malassezia pachydermatis, and Sphingomonas paucimobilis.

[0083] There is also provided a method for treating apocrine secretion causing odor and reducing microbial overgrowth in a mammalian subject, comprising administering a pharmaceutical preparation to an area of the mammalian subject showing the microbial overgrowth, wherein the pharmaceutical preparation comprises an anticholinergic agent and a ternary solvent, and the ternary solvent comprises 5% to 15% v / v of a diol, 60% to 70% v / v of an alcohol, and 5% to 20% v / v of water.

[0084] There is also provided a method for treating apocrine secretion causing odor and reducing microbial overgrowth in a mammalian subject, comprising administering a pharmaceutical preparation to an area of the mammalian subject showing the microbial overgrowth, wherein the pharmaceutical preparation consists of an anticholinergic agent and a ternary solvent, and the ternary solvent consists of 5% to 15% v / v of a diol, 60% to 70% v / v of an alcohol, and 5% to 20% v / v of water.

[0085] There is also provided a method for treating apocrine gland odor and reducing microbial overgrowth in a mammalian subject, comprising administering a pharmaceutical preparation to an area of the mammalian subject that exhibits said microbial overgrowth, wherein the pharmaceutical preparation consists essentially of an anticholinergic agent and a ternary solvent, and the ternary solvent consists essentially of 5% to 15% v / v of a diol, 60% to 70% v / v of an alcohol, and 5% to 20% v / v of water.

[0086] Microbial overgrowth can be defined as greater than 10 5 organisms per gram of tissue or per milliliter of biological fluid.

[0087] The mammalian subject can be selected from primates, Caniformia, and Artiodactyla.

[0088] Microbial overgrowth can be caused by microorganisms selected from: species of Corynebacterium (Corynebacterium spp.), Corynebacterium minutissimum, Corynebacterium striatum, Corynebacterium jeikeium, species of Staphylococcus (Staphylococcus spp.), Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus pseudintermedius, species of Streptococcus (Streptococcus spp.), species of Micrococcus (Micrococcus spp), species of Propionibacterium (Propionbacterium spp.), Propionibacterium acnes, species of Anaerococcus (Anaerococcus spp.), species of Candida (Candida spp.), Escherichia coli, Malassezia pachydermatis, and Sphingomonas paucimobilis.

[0089] Exemplary, non-limiting embodiments of the use of the pharmaceutical preparation will now be disclosed.

[0090] There is provided a pharmaceutical preparation for treating apocrine secretion causing odor and reducing microbial overgrowth in a mammalian subject, wherein the pharmaceutical preparation comprises an anticholinergic agent and a ternary solvent, and the ternary solvent comprises 5% to 15% v / v of a diol, 60% to 70% v / v of an alcohol, and 5% to 20% v / v of water.

[0091] There is provided a pharmaceutical preparation for treating apocrine secretion causing odor and reducing microbial overgrowth in a mammalian subject, wherein the pharmaceutical preparation consists of an anticholinergic agent and a ternary solvent, and the ternary solvent consists of 5% to 15% v / v of a diol, 60% to 70% v / v of an alcohol, and 5% to 20% v / v of water.

[0092] There is provided a pharmaceutical preparation for treating apocrine secretion causing odor and reducing microbial overgrowth in a mammalian subject, wherein the pharmaceutical preparation mainly consists of an anticholinergic agent and a ternary solvent, and the ternary solvent mainly consists of 5% to 15% v / v of a diol, 60% to 70% v / v of an alcohol, and 5% to 20% v / v of water.

[0093] There is also provided the use of the pharmaceutical preparation in the manufacture of a medicament for treating apocrine secretion causing odor and reducing microbial overgrowth in a mammalian subject, wherein the pharmaceutical preparation comprises an anticholinergic agent and a ternary solvent, and the ternary solvent comprises 5% to 15% v / v of a diol, 60% to 70% v / v of an alcohol, and 5% to 20% v / v of water.

[0094] There is also provided the use of the pharmaceutical preparation in the manufacture of a medicament for treating apocrine secretion causing odor and reducing microbial overgrowth in a mammalian subject, wherein the pharmaceutical preparation consists of an anticholinergic agent and a ternary solvent, and the ternary solvent consists of 5% to 15% v / v of a diol, 60% to 70% v / v of an alcohol, and 5% to 20% v / v of water.

[0095] There is also provided the use of the pharmaceutical preparation in the manufacture of a medicament for treating apocrine secretion causing odor and reducing microbial overgrowth in a mammalian subject, wherein the pharmaceutical preparation mainly consists of an anticholinergic agent and a ternary solvent, and the ternary solvent mainly consists of 5% to 15% v / v of a diol, 60% to 70% v / v of an alcohol, and 5% to 20% v / v of water.

[0096] The mammalian subject can be selected from primates, Caniformia, and Artiodactyla.

[0097] Overgrowth of microorganisms can be caused by microorganisms selected from the group consisting of: species of Corynebacterium (Corynebacterium spp.), Corynebacterium minutissimum, Corynebacterium striatum, Corynebacterium jeikeium, species of Staphylococcus (Staphylococcus spp.), Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus pseudintermedius, species of Streptococcus (Streptococcus spp.), species of Micrococcus (Micrococcus spp), species of Propionibacterium (Propionbacterium spp.), Propionibacterium acnes, species of Anaerococcus (Anaerococcus spp.), species of Candida (Candida spp.), Escherichia coli, Malassezia pachydermatis, and Sphingomonas paucimobilis.

[0098] Brief Description of the Drawings

[0099] The drawings illustrate the disclosed embodiments and are used to explain the principles of the disclosed embodiments. However, it should be understood that the drawings are designed for illustrative purposes only and not as a definition limiting the present invention.

[0100] Figure 1

[0101] Figure 1 ​is an illustration of the preparation of a pharmaceutical formulation in a spray bottle, delivered at 0.10 to 0.14 mL per spray, where weighted citric acid (100) and sodium citrate (200) are added to beaker 1 (400) containing purified water (300) to prepare a buffer solution. Thereafter, glycerol (500) and propylene glycol (600) are added to beaker 1 (400) containing the buffer solution and thoroughly mixed. The resulting mixture in beaker 1 (400) is added to beaker 2 (800) containing isopropyl alcohol (700), and then the anticholinergic agent glycopyrronium bromide (900) is dissolved using the combined mixture. The final volume of the pharmaceutical formulation in beaker 2 (800) is adjusted to 100% (v / v) using purified water (1000), and then it is packaged into individual spray bottles (1100) as samples for human and animal studies. Example

[0102] Non-limiting examples of the present invention will be described in further detail by reference to specific examples, which should not be construed as limiting the scope of the present invention in any way.

[0103] Materials and Methods

[0104] All reagents were obtained from commercial suppliers and, as shown in Table 1, were used without further purification.

[0105] Example 1: Preparation of a Pharmaceutical Formulation

[0106] A pharmaceutical formulation was prepared using the following chemical components in the amounts shown in Table 1.

[0107] Table 1: Composition of the pharmaceutical preparation

[0108]

[0109] A schematic diagram of the procedure for preparing the pharmaceutical formulation is as Figure 1 shown. Briefly, glycopyrronium bromide powder (12 g), citric acid (1.92 g), and sodium citrate (0.504 g) were weighed separately on weighing paper. The citric acid and sodium citrate were dissolved in some purified water (70 ml) to make a buffer solution. Glycerol (60 ml) and propylene glycol (60 ml) were added to the buffer solution and thoroughly mixed by stirring. Isopropyl alcohol (390 ml) was added to the mixture to form a ternary solvent, and then it was used to dissolve the anticholinergic agent glycopyrronium bromide powder. The final volume of the formulation was adjusted to 100% (v / v) using purified water. The pharmaceutical formulation was packaged into individual bottles and labeled separately as samples for human and animal studies in Examples 2 and 3.

[0110] Example 2: Human Studies Using the Pharmaceutical Formulation

[0111] The pharmaceutical preparation prepared in Example 1 was used by a confidential test group consisting of five people reporting axillary osmidrosis, as a preliminary assessment of the efficacy of the preparation on the human body. The profiles and comparison results before and after the test group used the pharmaceutical preparation are shown in Table 2. The severity of sweating (hyperhidrosis) self-reported by the test group was graded on a scale of 1 to 4 (HDSS, Hyperhidrosis Disease Severity Scale), with 1 being the mildest and 4 being the most severe. The percentage reduction in axillary osmidrosis after using the pharmaceutical preparation was self-reported by the test group, and the average percentage reduction in axillary osmidrosis was calculated.

[0112] Table 2: General situation and comparison results of human subjects before and after using the pharmaceutical preparation

[0113]

[0114]

[0115] According to the results in Table 2, it shows that the pharmaceutical preparation of the test group can effectively reduce axillary osmidrosis, and the total reduction rate of axillary osmidrosis is 73%. There are also no reports of irritation and adverse reactions to the human body. The pharmaceutical preparation does not cause skin dryness or darkening.

[0116] Example 3: Animal study using the pharmaceutical preparation

[0117] The pharmaceutical preparation prepared in Example 1 was applied to a Shetland sheepdog with axillary osmidrosis as a preliminary assessment of the efficacy of the preparation on dogs. The profiles and comparison results before and after the test dog used the pharmaceutical preparation are shown in Table 3.

[0118] Table 3: General situation and comparison results of test dogs before and after using the pharmaceutical preparation

[0119]

[0120]

[0121] According to the results in Table 3, it shows that the pharmaceutical preparation of the test dog can effectively reduce axillary osmidrosis, and the reduction rate of axillary osmidrosis is 62.5%. There are also no reports of irritation and adverse reactions to the test dog.

[0122] Industrial applicability

[0123] The pharmaceutical preparation can be used to treat pathological or non-pathological body odors in humans and dogs. The pharmaceutical preparation is suitable for various applications, but is not limited to the consumer care, healthcare, and cosmetics industries.

[0124] Obviously, various other modifications and adjustments to the present invention will be apparent to those skilled in the art after reading the foregoing disclosure, without departing from the spirit and scope of the present invention, and all such modifications and adjustments are intended to fall within the scope of the appended claims.

Claims

1. A pharmaceutical preparation comprising glycopyrronium bromide and a ternary solvent, wherein the ternary solvent is 5% to 15% v / v propylene glycol, 60% to 70% v / v isopropanol and 5% to 20% v / v water of the pharmaceutical preparation, and wherein the amount of glycopyrronium bromide is about 1.0% w / v, about 2.0% w / v, about 3.0% w / v, about 4.0% w / v, about 5.0% w / v or about 6.0% w / v of the pharmaceutical preparation, where "about" means + / - 5% of the value.

2. The pharmaceutical preparation according to claim 1, wherein the concentrations of the components in the ternary solvent are: propylene glycol is 5.0% v / v, 6.0% v / v, 7.0% v / v, 8.0% v / v, 9.0% v / v, 10.0% v / v, 11.0% v / v, 12.0% v / v, 13.0% v / v, 14.0% v / v or 15.0% v / v of the pharmaceutical preparation; isopropanol is 60.0% v / v, 61.0% v / v, 62.0% v / v, 63.0% v / v, 64.0% v / v, 65.0% v / v, 66.0% v / v, 67.0% v / v, 68.0% v / v, 69.0% v / v or 70.0% v / v of the pharmaceutical preparation; and water is 5.0% v / v, 6.0% v / v, 7.0% v / v, 8.0% v / v, 9.0% v / v, 10.0% v / v, 11.0% v / v, 12.0% v / v, 13.0% v / v, 14.0% v / v, 15% v / v, 16% v / v, 17% v / v, 18% v / v, 19% v / v or 20.0% v / v of the pharmaceutical preparation.

3. The pharmaceutical preparation according to claim 1, wherein the ratio of the components in the ternary solvent is such that the ratio of propylene glycol:isopropanol:water is 2:13:2.5 v / v.

4. The pharmaceutical preparation according to claim 1, which further comprises an excipient material suitable for topical application.

5. The pharmaceutical preparation according to claim 4, wherein the excipient material is selected from humectants, emulsifiers, preservatives, dispersants, absorption promoters or lubricants.

6. The pharmaceutical preparation according to claim 5, wherein the humectant is selected from glycerol, lecithin, gelatin, lactic acid, hyaluronic acid, glyceryl triacetate, hexylene glycol, butylene glycol, sorbitol, allantoin, sodium hyaluronate, sodium lactate, ammonium lactate, sodium pyrrolidone and urea.

7. The pharmaceutical preparation according to claim 1 or 2, further comprising emollients, surfactants, antibacterial agents, keratolytic agents, antiperspirants, antioxidants or pH buffers.

8. The pharmaceutical preparation according to claim 7, wherein the antibacterial agent is an antibacterial or antifungal agent.

9. The pharmaceutical preparation according to claim 1 or 2, wherein the pharmaceutical preparation is for topical use.

10. The pharmaceutical preparation according to claim 1 or 2, wherein the pharmaceutical preparation is in a form selected from solutions, creams, ointments, gels, pastes, aerosols, foams and sprays.

11. The pharmaceutical preparation according to claim 1 or 2, wherein the pharmaceutical preparation is in the form of an emulsion.

12. The pharmaceutical preparation according to claim 1 or 2, wherein when the pharmaceutical preparation is in the form of a spray, the amount of glycopyrronium bromide in each spray administered is 2.00 mg, 2.10 mg, 2.20 mg, 2.30 mg, 2.40 mg, 2.50 mg, 2.60 mg, 2.70 mg or 2.80 mg.

13. The pharmaceutical preparation according to claim 4, wherein the ratio of the components in the ternary solvent is such that the ratio of propylene glycol: isopropanol: water is 2:13:2.5 v / v and the pharmaceutical preparation is for topical use.

14. A method for preparing the pharmaceutical preparation according to claim 1 or 2, comprising the step of mixing the glycopyrronium bromide with a mixture containing isopropanol, propylene glycol, water, a humectant and a pH buffer at room temperature.

15. The method according to claim 14, wherein the pH buffer is an organic acid.

16. The method according to claim 14, wherein the pH buffer is selected from amino acids, polyamino carboxylic acids, citrates, polyphosphates and combinations thereof.

17. The method according to claim 14, wherein the pH buffer is selected from citric acid, acetic acid, tartaric acid, ethylenediaminetetraacetic acid, 2,3-dimercaptopropanesulfonic acid, thiamine tetrahydrofurfuryl disulfide, alpha-lipoic acid, glycine, sodium citrate, potassium citrate, sodium phosphate and combinations thereof.

18. The method according to claim 14, wherein the amount of the humectant is 5.0% w / v, 6.0% w / v, 7.0% w / v, 8.0% w / v, 9.0% w / v, 10.0% w / v, 11.0% w / v, 12.0% w / v, 13.0% w / v, 14.0% w / v, 15.0% w / v, 16.0% w / v, 17.0% w / v, 18.0% w / v, 19.0% w / v or 20.0% w / v of the pharmaceutical preparation.

19. The method according to claim 14, wherein the amount of the pH buffer is in the range of 0.05% w / v to 1.00% w / v of the pharmaceutical preparation.

20. The method according to claim 17, wherein the amount of the humectant is 5.0 % w / v, 6.0 % w / v, 7.0 % w / v, 8.0 % w / v, 9.0 % w / v, 10.0 % w / v, 11.0 % w / v, 12.0 % w / v, 13.0 % w / v, 14.0 % w / v, 15.0 % w / v, 16.0 % w / v, 17.0 % w / v, 18.0 % w / v, 19.0 % w / v or 20.0 % w / v of the pharmaceutical preparation, and wherein the amount of the pH buffer is in the range of 0.05 % w / v to 1.00 % w / v of the pharmaceutical preparation.

21. Use of a pharmaceutical preparation in the manufacture of a medicament for treating apocrine secretion causing body odor and reducing microbial overgrowth in a mammalian subject, wherein, The pharmaceutical preparation comprises glycopyrronium bromide and a ternary solvent, the ternary solvent being 5% to 15% v / v of propylene glycol, 60% to 70% v / v of isopropyl alcohol and 5% to 20% v / v of water of the pharmaceutical preparation, wherein the amount of the glycopyrronium bromide is about 1.0% w / v, about 2.0% w / v, about 3.0% w / v, about 4.0% w / v, about 5.0% w / v or about 6.0% w / v of the pharmaceutical preparation, wherein about means + / - 5% of the value.

22. The use according to claim 21, wherein the mammalian subject is selected from primates, Caniformia and Artiodactyla.

23. The use according to claim 21, wherein the mammalian is a human and the pharmaceutical preparation is in the form of a spray and is administered 1 or 2 sprays at least once a day on the axilla, once in the morning and optionally once in the afternoon, depending on individual needs.

24. The use according to claim 21, wherein the mammalian is a dog and the pharmaceutical preparation is in the form of a spray and is sprayed on the diseased skin at a frequency of 1 to 3 times a day, with a spray interval of 4 to 8 hours.

25. Use according to any one of claims 21 to 24, wherein the microbial overgrowth is caused by a microorganism selected from the species of Corynebacterium spp., Corynebacterium minutissimum, Corynebacterium striatum, Corynebacterium jeikeium, the species of Staphylococcus spp., Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus pseudintermedius, the species of Streptococcus spp., the species of Micrococcus spp., the species of Propionbacterium spp., Propionbacterium acnes, the species of Anaerococcus spp., the species of Candida spp., Escherichia coli, and Malassezia pachydermatis.

Images