A composition, preparation for the treatment of skin pruritus, and methods of making and using the same

Abstract

The present application provides a kind of composition, preparation and its preparation method and purposes for treating skin pruritus.The composition for treating skin pruritus is composed of hydrocarbon halide and / or hydrocarbon.The hydrocarbon halide is one, two or more than three combinations of difluoromonochloromethane, difluoromethane, trifluoromonochloromethane, tetrafluoromethane, dichlorotrifluoroethane, difluoroethane, monochlorodifluoroethane, tetrafluoroethane, hexafluoroethane, chloroethane, pentafluoropropane and / or octafluoropropane.The hydrocarbon is one, two or more than three combinations of methane, ethane, propane, butane, cycloethane, cyclopropane and / or cyclobutane.The composition or preparation of the present application has excellent effects when used as a drug for treating skin pruritus, such as relieving pruritus symptoms quickly, reducing the risk of infection, shortening the course of the disease and reducing the economic burden of patients.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to a composition, preparation, preparation method, and use for treating pruritus. Background Technology

[0002] Pruritus is a common symptom that can occur in a variety of clinical situations. In addition to causing skin damage, secondary infections, scarring, and reduced sleep, pruritus can also lead to mood disorders such as anxiety and depression.

[0003] Currently, the main treatments for pruritus include topical corticosteroids (including topical corticosteroids and occlusive therapy), calcineurin inhibitors, systemic therapy (including antihistamines and sedatives), physical therapy (for refractory lesions, narrowband UVB, CO2 fractional laser technology, ultrasound induction, and focused ultrasound can be used), topical moisturizing creams and wet dressings, as well as traditional Chinese medicine and psychological support. For example, CN110573152B discloses a pharmaceutical composition containing pyrazole derivatives as active ingredients for the prevention or treatment of pruritus. This composition relieves pruritus symptoms by inhibiting the activity of intracellular MrgprX1 and by inhibiting the activity of intracellular hH1R, thus it can also be used as a drug for the prevention or treatment of histamine-mediated pruritus. CN114642825A discloses an adjunctive treatment method for neurodermatitis based on microneedle patches, which can relieve pruritus, prevent unconscious scratching, and promote rapid recovery from neurodermatitis.

[0004] About one-third of patients with pruritus have histamine-mediated pruritus (histamine-induced pruritus), which can be relieved by taking antihistamines. However, most patients with pruritus have a G protein-coupled receptor (Mrgprs), which is a non-histamine pruritus receptor that is only expressed in peripheral tissue neurons. Among them, MrgpreX1 is distributed in the dorsal root ganglion. Patients with non-histamine pruritus do not respond well to antihistamines.

[0005] There is still a lack of universal treatments for pruritus. Summary of the Invention

[0006] This invention provides a safe and effective universal treatment for pruritus, which can relieve patients' symptoms of itchy skin and reduce the risk of skin lesions and infections caused by itching-scratching-itching.

[0007] Specifically, the present invention provides a composition for treating pruritus, the composition comprising hydrocarbon halides and / or hydrocarbons.

[0008] In one embodiment, the hydrocarbon halide is preferably a fluorine- and / or chlorine-substituted hydrocarbon compound.

[0009] In one embodiment, the hydrocarbon halide is preferably a fluorine- and / or chlorine-substituted saturated hydrocarbon halide.

[0010] In one embodiment, the hydrocarbon halide is preferably a fluorinated and / or chlorinated derivative of methane, ethane, propane, butane, cyclohexane, cyclopropane, and / or cyclobutane, wherein the fluorinated and / or chlorinated derivative is a derivative in which fluorine and / or chlorine are partially or completely substituted.

[0011] In one embodiment, the hydrocarbon halide is one, two, or a combination of three or more of the following: difluorochloromethane, difluoromethane, trifluorochloromethane, tetrafluoromethane, dichlorotrifluoroethane, difluoroethane, dichlorodifluoroethane, tetrafluoroethane, hexafluoroethane, chloroethane, pentafluoropropane, and / or octafluoropropane.

[0012] In one embodiment, the hydrocarbon halide is preferably one, two, or a combination of three or more of tetrafluoroethane, pentafluoropropane, octafluoropropane, and / or chloroethane.

[0013] In one embodiment, the hydrocarbon halide preferably includes tetrafluoroethane.

[0014] In one embodiment, the hydrocarbon halide preferably includes pentafluoropropane.

[0015] In one embodiment, the hydrocarbon halide preferably includes pentafluoropropane and octafluoropropane, with a mass ratio of pentafluoropropane to octafluoropropane of (1-5):(95-99), preferably 3:97.

[0016] In one embodiment, the hydrocarbon halide preferably includes tetrafluoroethane and pentafluoropropane, with a mass ratio of tetrafluoroethane to pentafluoropropane of (2-6):(94-98), preferably 5:95.

[0017] In one embodiment, the hydrocarbon halide preferably includes chloroethane.

[0018] In one embodiment, the hydrocarbon halide preferably includes chloroethane and octafluoropropane, with the mass ratio of chloroethane to octafluoropropane being (1-4):(96-99), preferably 2:98.

[0019] In one embodiment, the hydrocarbon halide preferably includes chloroethane and tetrafluoroethane, wherein the mass ratio of chloroethane to tetrafluoroethane is (1-6):(94-99), preferably 4:96.

[0020] In one embodiment, the hydrocarbon is one, two, or a combination of three or more of methane, ethane, propane, butane, cyclohexane, cyclopropane, and / or cyclobutane.

[0021] In one embodiment, the hydrocarbon preferably includes propane, n-butane, and isobutane, with a mass ratio of propane:n-butane:isobutane of (1-4):(75-85):(15-25), preferably 2:80:18.

[0022] In one embodiment, the hydrocarbon preferably includes n-butane.

[0023] In one embodiment, the hydrocarbon preferably includes propane and isobutane, with a propane:isobutane mass ratio of (0.5-3):(97-99.5), preferably 1:99.

[0024] In one embodiment, the composition for treating pruritus of the present invention consists of a hydrocarbon halide and a hydrocarbon compound, wherein the mass ratio of the hydrocarbon halide to the hydrocarbon compound is (50-100):(0-50).

[0025] In one embodiment, the composition for treating pruritus of the present invention comprises a hydrocarbon halide and a hydrocarbon compound, wherein the mass ratio of the hydrocarbon halide to the hydrocarbon compound is (50-100):(0-50). The hydrocarbon halide is one, two, or a combination of three or more of the following: difluorochloromethane, difluoromethane, trifluorochloromethane, tetrafluoromethane, dichlorotrifluoroethane, difluoroethane, dichlorodifluoroethane, tetrafluoroethane, hexafluoroethane, chloroethane, pentafluoropropane, and / or octafluoropropane. The hydrocarbon compound is one, two, or a combination of three or more of the following: methane, ethane, propane, butane, cyclohexane, cyclopropane, and / or cyclobutane.

[0026] In one embodiment, the composition for treating pruritus of the present invention comprises a hydrocarbon halide and a hydrocarbon compound, wherein the mass ratio of the hydrocarbon halide to the hydrocarbon compound is (80-95):(5-20).

[0027] In one embodiment, the composition for treating pruritus of the present invention comprises a hydrocarbon halide and a hydrocarbon compound, wherein the mass ratio of the hydrocarbon halide to the hydrocarbon compound is (80-95):(5-20). The hydrocarbon halide is preferably one, two, or a combination of three or more of tetrafluoroethane, pentafluoropropane, octafluoropropane, and / or chloroethane, and the hydrocarbon compound is preferably propane, n-butane, and / or isobutane.

[0028] In one embodiment, the composition for treating pruritus of the present invention comprises a hydrocarbon halide and a hydrocarbon compound, wherein the mass ratio of the hydrocarbon halide to the hydrocarbon compound is (80-95):(5-20), wherein the hydrocarbon halide is preferably octafluoropropane and / or chloroethane, and the hydrocarbon compound is preferably propane and / or isobutane.

[0029] In one embodiment, the composition for treating pruritus of the present invention preferably comprises tetrafluoroethane, pentafluoropropane, and n-butane. The mass ratio of tetrafluoroethane:pentafluoropropane:n-butane is preferably (1-5):(80-90):(1-10); further, the above mass ratio is preferably (1-3):(85-90):(2-5).

[0030] In one embodiment, the composition for treating pruritus of the present invention is preferably composed of tetrafluoroethane and pentafluoropropane. The mass ratio of tetrafluoroethane to pentafluoropropane is preferably (0-50):(50-100); further, the above mass ratio is preferably (3-5):(95-97).

[0031] In one embodiment, the composition for treating pruritus of the present invention preferably comprises propane, isobutane, octafluoropropane, and pentafluoropropane. The preferred mass ratio of propane:isobutane:octafluoropropane:pentafluoropropane is (1-4):(2-5):(1-3):(90-95).

[0032] In one embodiment, the composition for treating pruritus of the present invention preferably comprises tetrafluoroethane, n-butane, and chloroethane. The preferred mass ratio of tetrafluoroethane: n-butane: chloroethane is (1-5):(1-5):(90-97).

[0033] In one embodiment, the composition for treating pruritus of the present invention preferably comprises propane, isobutane, octafluoropropane, and chloroethane. The preferred mass ratio of propane:isobutane:octafluoropropane:chloroethane is (1-4):(2-5):(1-3):(90-95).

[0034] In this invention, the composition for treating pruritus is a non-azeotropic composition.

[0035] Non-azeotropic compositions exhibit varying evaporation temperatures, with lower-boiling-point components evaporating preferentially, causing the boiling point of the composition to continuously increase as evaporation proceeds. This invention, by matching the physicochemical properties of each component in the composition, prepares a non-azeotropic composition with a suitable evaporation temperature variation, demonstrating excellent efficacy in treating pruritus.

[0036] In one embodiment, the skin pruritus treatment composition of the present invention comprises the above-mentioned hydrocarbon halides and / or hydrocarbons, and the skin pruritus treatment composition is linearly sprayed onto the surface of itchy skin or broken itchy skin using a spraying device. The skin pruritus treatment composition sprayed by the spraying device is in liquid form.

[0037] In one embodiment, the composition for treating pruritus of the present invention is composed of the above-mentioned hydrocarbon halides and / or the above-mentioned hydrocarbons, and the sprayed liquid of the composition for treating pruritus is linear.

[0038] In one embodiment, the contact area between the linear spray liquid and the skin surface is greater than the nozzle area of ​​the spraying device.

[0039] Preferably, after the spraying device sprays the composition for treating pruritus, the diameter of the sprayed liquid changes very little.

[0040] Preferably, after the spraying device sprays the composition for treating pruritus, the diameter of the sprayed liquid increases by a factor of less than 3, and more preferably less than 2, for every 4 cm increase in distance from the nozzle.

[0041] In this invention, the multiple by which the diameter of the sprayed liquid increases with every 4cm increase in distance from the nozzle is closely related to the composition of the composition for treating pruritus and the therapeutic effect of pruritus.

[0042] In one embodiment, the contact temperature between the composition for treating pruritus and itchy skin or broken itchy skin is above 0°C.

[0043] In one embodiment, the contact temperature between the composition for treating pruritus and itchy skin or broken itchy skin is 0°C-7°C.

[0044] In one embodiment, the boiling vaporization temperature of the composition for treating pruritus is preferably 7°C.

[0045] The present invention also provides a formulation for treating pruritus, comprising the above-described composition for treating pruritus. Optionally, the formulation for treating pruritus of the present invention may or may not include pharmaceutically acceptable excipients.

[0046] In one embodiment, the pharmaceutically acceptable excipient of the present invention may be a trace amount of flavoring agent such as fragrance.

[0047] In one embodiment, the preparation for treating pruritus of the present invention is an aerosol.

[0048] In one embodiment, the aerosol is preferably sterile.

[0049] This invention also provides a method for preparing a formulation for treating pruritus, comprising a solution preparation step, a sterilization step, and a filling step. The formulation for treating pruritus prepared by this invention is sterile.

[0050] In one embodiment, during the solution preparation step, the temperature of the mixture of the prepared composition for treating pruritus is preferably 0°C-10°C. Controlling the temperature of the prepared mixture according to the present invention facilitates the aseptic production of the preparation for treating pruritus.

[0051] In one embodiment, it is preferred that the present invention preserves each component of the composition at a specific temperature for a specific time before the solution preparation step.

[0052] Preferably, at the specific temperature described above in this invention, at least one component does not boil at normal pressure.

[0053] Preferably, at least one component is stored at a specific temperature below its boiling point.

[0054] The composition for treating pruritus of the present invention comprises only hydrocarbon halides and / or hydrocarbons, excluding other components. This composition for treating pruritus without other components is less expensive, more effective, and has better manufacturing compliance.

[0055] The present invention also provides the use of the above-described composition for treating pruritus or the above-described preparation for treating pruritus in medicaments for treating pruritus.

[0056] This invention relates to a topical medication for pruritus, which is applied directly to itchy or broken itchy skin. The medication is applied using a spray device in a linear pattern to the surface of the itchy or broken itchy skin.

[0057] The composition and drug for treating pruritus of the present invention are suitable for use in conjunction with a linear spray device. The combined use of the composition and drug for treating pruritus with a linear spray device plays an important role in achieving the therapeutic effect, as the spray area is controllable, thus better leveraging the therapeutic effect of the non-azeotropic composition of the present invention.

[0058] This invention comprises a composition for treating pruritus that includes both hydrocarbon halides and hydrocarbons. When used in conjunction with a linear spraying device, the sprayed liquid exhibits higher linear concentration and better therapeutic effect compared to compositions for treating pruritus that only include hydrocarbon halides or hydrocarbons.

[0059] In one embodiment, the pruritus medication of the present invention is applied by spraying for 3-15 seconds each time. The nozzle of the spraying device is 3-15 cm away from the skin. There is an interval of at least 2 minutes between each spray. It is applied 3-8 times per day.

[0060] In one embodiment, the present invention provides a composition for treating pruritus, comprising a hydrocarbon halide and a hydrocarbon compound in a mass ratio of (80-95):(5-20). The hydrocarbon halide is one, two, or a combination of three or more of tetrafluoroethane, pentafluoropropane, octafluoropropane, and / or chloroethane, and the hydrocarbon compound is propane, n-butane, and / or isobutane. The composition is a non-azeotropic composition. The composition is linearly sprayed onto the surface of itchy or broken itchy skin using a spraying device, with the contact area between the linear spray and the skin surface being larger than the nozzle area of ​​the spraying device. After the composition is sprayed, the diameter of the spray increases by less than 3 times for every 4 cm increase in distance from the nozzle. The vaporization temperature of the composition is -4°C to 10°C. Furthermore, the use of this composition for treating pruritus in pruritus medications, wherein the contact temperature between the composition and itchy or broken itchy skin is above 0°C, preferably 0-7°C. When using the pruritus medication, each spray lasts 3-15 seconds, the nozzle of the spray device is 3-15 cm away from the skin, the interval between each spray is at least 2 minutes, and the spray is performed 3-8 times per day.

[0061] In one embodiment, the present invention provides a composition for treating pruritus, comprising propane, isobutane, octafluoropropane, and pentafluoropropane, wherein the mass ratio of propane:isobutane:octafluoropropane and pentafluoropropane is (1-4):(2-5):(1-3):(90-95), and the composition is a non-azeotropic composition. The composition is applied linearly to the surface of itchy or broken itchy skin using a spraying device. The contact area between the linearly sprayed liquid and the skin surface is larger than the nozzle area of ​​the spraying device. After the composition is sprayed, the diameter of the sprayed liquid increases by less than 3 times for every 4 cm increase in distance from the nozzle. The composition is also used in pruritus medications, and the contact temperature between the composition and itchy or broken itchy skin is 0°C-7°C. When using medication for pruritus, spray for 3-15 seconds each time, keep the nozzle 3-15cm away from the skin, and allow at least 2 minutes between each spray. Spray 3-8 times a day.

[0062] In one embodiment, the present invention provides a composition for treating pruritus, comprising tetrafluoroethane, n-butane, and chloroethane, wherein the mass ratio of tetrafluoroethane:n-butane:chloroethane is (1-5):(1-5):(90-97), and the composition is a non-azeotropic composition. The composition is applied linearly to the surface of itchy or broken itchy skin using a spraying device. The contact area between the linear spray and the skin surface is larger than the nozzle area of ​​the spraying device. After the composition is sprayed, the diameter of the spray increases by less than 3 times for every 4 cm increase in distance from the nozzle. Furthermore, the composition is used in pruritus medications, wherein the contact temperature between the composition and the itchy or broken itchy skin is above 0°C. When using pruritus medications, each spray lasts 3-15 seconds, the nozzle is 3-15 cm from the skin, the interval between sprays is at least 2 minutes, and the spray is performed 3-8 times per day.

[0063] In one embodiment, the present invention provides a composition for treating pruritus, comprising propane, isobutane, octafluoropropane, and chloroethane, wherein the mass ratio of propane:isobutane:octafluoropropane:chloroethane is (1-4):(2-5):(1-3):(90-95), and the composition is a non-azeotropic composition. The composition is applied linearly to the surface of itchy or broken itchy skin using a spraying device. The contact area between the linearly sprayed liquid and the skin surface is larger than the nozzle area of ​​the spraying device. After the composition is sprayed, the diameter of the sprayed liquid increases by less than 3 times for every 4 cm increase in distance from the nozzle. Furthermore, the composition is used in pruritus medications, and the contact temperature between the composition and itchy or broken itchy skin is above 0°C. When using medication for pruritus, spray for 3-15 seconds each time, keep the nozzle 3-15cm away from the skin, and allow at least 2 minutes between each spray. Spray 3-8 times a day.

[0064] In one embodiment, the present invention provides a composition for treating pruritus, comprising tetrafluoroethane, pentafluoropropane, and n-butane, wherein the mass ratio of tetrafluoroethane:pentafluoropropane:n-butane is (1-5):(80-90):(1-10), and the composition is a non-azeotropic composition. The composition is applied linearly to the surface of itchy or broken itchy skin using a spraying device. The contact area between the linearly sprayed liquid and the skin surface is larger than the nozzle area of ​​the spraying device. After the composition is sprayed, the diameter of the sprayed liquid increases by less than 2 times for every 4 cm increase in distance from the nozzle. Furthermore, the use of this composition in pruritus medications is also provided, wherein the contact temperature between the composition and itchy or broken itchy skin is 0°C-7°C. When using medication for pruritus, spray for 3-15 seconds each time, keep the nozzle 3-15cm away from the skin, and allow at least 2 minutes between each spray. Spray 3-8 times a day.

[0065] The skin pruritus composition and drug of this invention will not cause necrosis of the skin or lesions or rupture of cell membranes when in contact with itchy or broken itchy skin, thus exhibiting high safety. The skin pruritus composition and drug of this invention boil and vaporize at approximately 7°C. When used correctly, ensuring therapeutic efficacy, the skin temperature at the treatment site remains above 0°C, minimizing risk and providing a gentle effect.

[0066] In one embodiment, the pruritus medication is a medication for pruritus in mammals. The mammals include animals and humans, preferably humans.

[0067] In one implementation, the pruritus includes pruritus caused by diseases such as skin dysfunction, autoimmune diseases, viral and bacterial infections, insect bites, and infectious skin diseases such as folliculitis.

[0068] In one implementation, the pruritus is associated with a medical procedure or treatment.

[0069] In one embodiment, the pruritus is preferably associated with inflammatory skin diseases selected from allergic dermatitis, nodular prurigo, atopic dermatitis, mastocytosis, and urticaria.

[0070] In one embodiment, the skin itching is preferably allergic dermatitis pruritus.

[0071] Allergic dermatitis is a common chronic inflammatory skin disease characterized by paroxysmal itching and swollen skin, associated with cutaneous nerve dysfunction. Its most prominent feature is severe, recurrent itching.

[0072] In one embodiment, the composition or drug of the present invention is preferably used to treat pruritus caused by allergic dermatitis.

[0073] In one embodiment, the composition or drug of the present invention is preferably used to treat one or more pruritic skin diseases caused by localized dermatitis or disseminated dermatitis caused by allergic dermatitis.

[0074] In one embodiment, the skin pruritus composition and drug of the present invention also have a significant effect in reducing skin crusting and hyperplasia caused by scratching of itchy skin or broken itchy skin.

[0075] The compositions and drugs of this invention have achieved surprising and unexpected results in treating pruritus. They can rapidly relieve itching symptoms, reduce edema and inflammation in surrounding tissues, effectively shorten the course of the disease, control and reduce skin crusting and hyperplasia after scratching, and reduce the risk of infection. This is a safe and effective new method for treating pruritus. In particular, it provides a drug that can rapidly and effectively eliminate itching symptoms for patients with pruritus who do not respond to antihistamines.

[0076] The main mechanisms of the composition and drug of this invention in treating pruritus include: (1) Inhibition of nerve conduction: Hydrocarbon halides and / or hydrocarbons act on the skin, which can directly inhibit the excitation and conduction of superficial tissue nerve cells, immediately reducing the signal transmission of discomfort such as pain and itching, thereby relieving skin symptoms. (2) Change in neurotransmitter release: Hydrocarbon halides and / or hydrocarbons can lower the temperature of local superficial tissues, which can affect the ion concentration inside nerve cells, thereby changing the release of neurotransmitters such as serotonin and adrenaline. This can reduce nerve excitation and relieve the symptoms of neurodermatitis. (3) Improvement of microcirculation: After the use of hydrocarbon halides and / or hydrocarbons, the skin blood vessels will temporarily constrict and then dilate, which is conducive to the clearance of blood flow in the inflamed area, reducing tissue edema and inflammatory exudation, and relieving symptoms. (4) Inhibition of inflammatory mediators: Hydrocarbon halides and / or hydrocarbons can inhibit the generation and release of inflammatory mediators such as cytokines, histamine, and proteases in local tissues, reducing their stimulating effect on the skin and nerves, thereby relieving symptoms. (5) Promote the release of endogenous analgesic substances: Hydrocarbon halides and / or hydrocarbons can activate TRPM8 receptors, causing a cooling sensation in the skin. They can also activate the opioid receptor system in the body, promoting the release of endogenous opioid substances such as endorphins, producing analgesic and antipruritic effects, and relieving skin discomfort. (6) Regulate immune function: The moderate cooling sensation caused by hydrocarbon halides and / or hydrocarbons can produce a short-term stress response, promoting changes in skin immune function, thereby inhibiting the excessive immune response of autoimmune skin diseases and achieving the purpose of treatment.

[0077] The composition and drug of this invention act on the stratum corneum and nerve endings of the epidermis, affecting neuronal excitability and neurotransmitters. They can block the recognition and transmission of external stimuli for a certain period of time, effectively blocking signal transmission in superficial tissues and producing a relatively long-lasting skin anesthetic effect. At the same time, they can also act directly on nerve membranes and neural networks, blocking the connections between neurons, preventing itching signals from being effectively transmitted within the network, thus achieving an anesthetic and antipruritic effect. They have low neurotoxicity and a wide and relatively long-lasting effect.

[0078] The compositions and drugs of this invention avoid the toxic side effects of commonly used hormone drugs, and can provide patients with safe and effective treatment.

[0079] The composition and drug of this invention treat pruritus through multiple mechanisms. They can directly inhibit nerve conduction, alter neuroendocrine function, improve microcirculation, suppress inflammatory responses, activate the endogenous analgesic system, and regulate immune function, thereby alleviating skin symptoms and achieving the goal of treating pruritus. The synergistic effect of these mechanisms makes the composition and drug of this invention highly effective in clinical practice. This invention provides a new, safer, more effective, convenient, and faster option for treating pruritus.

[0080] The compositions and drugs of the present invention are "sterile" compositions and drugs, which avoid the risk of infection when patients experience skin damage due to the vicious cycle of "itching-scratching-itching".

[0081] The composition and drug of this invention are physical therapy methods for treating pruritus, which fill the gaps in the physical therapy content of existing treatment guidelines and provide patients with pruritus with a novel, convenient, and immediately effective sterile preparation formula and method.

[0082] The compositions and drugs of this invention are effective not only for treating histamine-induced pruritus but also for nonhistamine-induced pruritus. The compositions and drugs of this invention can also prevent the aforementioned pruritus.

[0083] The compositions and drugs of this invention also have a good antipruritic effect on hypertrophic skin lesions.

[0084] The composition and drug of this invention were developed based on extensive experimental research, theoretical exploration, and clinical practice, and are used for the first time to treat pruritus caused by diseases such as allergic dermatitis. This product is of great significance for rapidly relieving itching symptoms, improving the physical barrier, reducing the risk of infection, increasing therapeutic efficacy, reducing costs, alleviating the economic burden on patients, and being portable. Detailed Implementation

[0085] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0086] Unless otherwise stated, the raw materials and reagents used in the following examples are commercially available products or can be prepared by known methods.

[0087] Example 1: Composition Formulation

[0088] The formulation of the composition for treating pruritus of the present invention is shown in Table 1.

[0089] Table 1

[0090]

[0091] Example 2 Preparation of the formulation

[0092] Formulation 1 (prepared using composition 1):

[0093] Preparation: Clean and disinfect the outer packaging of raw materials, aerosol cans, aerosol valves, valve actuators, caps, etc., with 75% ethanol. Then, proceed through the inner packaging airlock to the clean area for later use. The pressure difference between the inner packaging airlock and the inner packaging removal area should be greater than 10 Pa. The aerosol cans should be linear spray aerosol devices (nozzle diameter 0.1-3 mm, internal pressure 1-3 atmospheres, sprayed as a linear liquid).

[0094] Raw material processing: Tetrafluoroethane and n-butane are stored at -5℃ for 4 hours before filling, and pentafluoropropane is stored at 7℃ for 8 hours before filling.

[0095] Solution preparation: Pentafluoropropane is controlled at 7°C and then uniformly mixed with a measured amount of tetrafluoroethane and n-butane to obtain a mixed solution. The temperature of the mixed solution is 0°C-10°C. The temperature of the solution preparation room is 10-28°C, the relative humidity is 35-75%, and the relative negative pressure is ≥5Pa.

[0096] Sterilization: The aerosol can is cleaned and dried, and then dry heat sterilized at 170-180℃ using an extended and widened tunnel oven; the aerosol valve, valve actuator, and cap that are matched with the aerosol can are sterilized by cobalt-60 irradiation before assembly;

[0097] Filling: Sterilized aerosol cans are conveyed to the filling production line through a tunnel drying oven. The aerosol valve, valve actuator, and cap enter the filling and sealing room through a cleaning process. The sterilization breathing bag is removed, the aerosol valve is placed into the hopper with automatic valve loading, and the valve actuator is placed into the stopper hopper. The mixture is then filtered through two stages of 0.22μm filter elements before being filled into the aerosol cans. The Class 100 laminar flow hood is opened for self-cleaning for more than 15 minutes. The aerosol valve is automatically loaded and locked, and the valve actuator and can cap are automatically loaded before the cans are transferred out of the filling and sealing room.

[0098] Leak testing: After filling, the aerosol cans are tested for leaks. The leak testing involves placing the aerosol cans in an environment of 48-50℃ for more than 8 hours, and discarding aerosol cans with large weight errors.

[0099] Warehousing: After leak detection, label, package, and store for later use.

[0100] Formulation 2 (prepared using composition 2):

[0101] The preparation, sterilization, filling, leak detection, and warehousing steps for formulation 2 are the same as those for formulation 1. The difference lies in the raw material processing and liquid preparation steps.

[0102] Raw material processing: Before filling, propane, isobutane, and octafluoropropane should be stored at -5℃ for 4 hours, and pentafluoropropane should be stored at 7℃ for 8 hours.

[0103] Solution preparation: The pentafluoropropane is controlled at 7°C and then uniformly mixed with a certain amount of propane, isobutane and octafluoropropane to obtain a mixed solution. The temperature of the mixed solution is 0°C-10°C. The temperature of the solution preparation room is 10-28°C, the relative humidity is 35-75%, and the relative negative pressure is ≥5Pa.

[0104] Formulation 3 (prepared using composition 3):

[0105] The preparation, sterilization, filling, leak detection, and warehousing steps of formulation 3 are the same as those of formulation 1. The difference lies in the raw material processing and liquid preparation steps.

[0106] Raw material processing: Tetrafluoroethane and n-butane are stored at -5℃ for 4 hours before filling, and chloroethane is stored at 5℃ for 8 hours before filling;

[0107] Solution preparation: Chloroethane is controlled at 5°C and then uniformly mixed with a certain amount of tetrafluoroethane and n-butane to obtain a mixed solution. The temperature of the mixed solution is 0°C-10°C. The temperature of the solution preparation room is 10-28°C, the relative humidity is 35-75%, and the relative negative pressure is ≥5Pa.

[0108] Formulation 4 (prepared using composition 4):

[0109] The preparation, sterilization, filling, leak detection, and warehousing steps for formulation 4 are the same as those for formulation 1. The difference lies in the raw material processing and liquid preparation steps.

[0110] Raw material processing: Propane, isobutane, and octafluoropropane are stored at -5℃ for 4 hours before filling, and chloroethane is stored at 5℃ for 8 hours before filling.

[0111] Solution preparation: Ethyl chloride is controlled at 5°C and then uniformly mixed with a measured amount of propane, isobutane, and octafluoropropane to obtain a mixed solution. The temperature of the mixed solution is 0°C-10°C. The temperature of the solution preparation room is 10-28°C, the relative humidity is 35-75%, and the relative negative pressure is ≥5Pa.

[0112] Formulation 5 (prepared using composition 5):

[0113] The preparation, sterilization, filling, leak detection, and warehousing steps of formulation 5 are the same as those of formulation 1. The difference lies in the raw material processing and liquid preparation steps.

[0114] Raw material processing: Store n-butane at -5°C for 4 hours before filling;

[0115] Solution preparation: The n-butane is controlled at -5℃ and does not need to be mixed with other components; the temperature of the solution preparation room is 10-15℃, the relative humidity is 35-75%, and the relative negative pressure is ≥5Pa.

[0116] Formulation 6 (prepared using composition 6):

[0117] The preparation, sterilization, filling, leak detection, and warehousing steps of Formulation 6 are the same as those of Formulation 1. The difference lies in the raw material processing and liquid preparation steps.

[0118] Raw material processing: Tetrafluoroethane was stored at -5°C for 4 hours before filling, and pentafluoropropane was stored at 7°C for 8 hours before filling.

[0119] Solution preparation: Pentafluoropropane is controlled at 7°C and then uniformly mixed with a measured amount of tetrafluoroethane to obtain a mixed solution. The temperature of the mixed solution is 0°C-10°C. The temperature of the solution preparation room is 10-28°C, the relative humidity is 35-75%, and the relative negative pressure is ≥5Pa.

[0120] Formulation 7 (prepared using composition 7):

[0121] The preparation, sterilization, filling, leak detection, and warehousing steps for formulation 7 are the same as those for formulation 1. The difference lies in the raw material processing and liquid preparation steps.

[0122] Raw material processing: Store pentafluoropropane at 7°C for 8 hours before filling;

[0123] Solution preparation: The pentafluoropropane is controlled at 7°C and does not need to be mixed with other components; the temperature of the solution preparation room is 10-28°C, the relative humidity is 35-75%, and the relative negative pressure is ≥5Pa.

[0124] Example 3: Treatment of Pruritus

[0125] Treatment of pruritus using formulation 1 of the present invention:

[0126] Mr. Li, male, 56 years old. In 2019, he developed dermatitis due to oral rosufastatin, resulting in patchy erythema on both armpits and groins, accompanied by unbearable itching. He needed to scratch vigorously to find relief, repeatedly experiencing a cycle of itching-scratching-itching. The local skin lesions were severe, and the skin was thickened. Despite treatment with oral fexofenadine and diazepam, topical loratadine ointment, and thymosin injections, his condition continued to recur. Each flare-up required 2-3 months of treatment before the itching could be relieved. In January 2023, severe pruritus recurred at the aforementioned skin lesions. Treatment was initiated with Preparation 1 of the present invention. For the first application, Preparation 1 of the present invention was sprayed onto the itchy skin for 10 seconds each time, and the itching was immediately relieved. After a 5-minute interval, the product was sprayed again for 10 seconds each time. Subsequently, the product was sprayed three times a day for 10 seconds each time for three consecutive days, and the itching symptoms disappeared. Seven days later, the dark reddish-brown lesions at the original skin lesions faded.

[0127] Treatment of pruritus using formulation 2 of the present invention:

[0128] Mr. Wu, male, 38 years old. Due to long-term work stress, he experienced intense itching on the left side of his forehead, scratching the lesions at night, and was diagnosed with psoriasis. The hospital prescribed oral desloratadine and 10mg zolpidem tartrate tablets before bedtime. He also applied loratadine ointment and TEA TREE MEDICATED GEL FOR ACNE ointment (made in Australia) alternately to the itchy areas using cotton swabs. After 3 years of treatment, the local itching continued to recur, and the skin at the itchy areas thickened, forming a cycle of "itching-scratching-itching." On the first day, the patient was sprayed with the preparation of this invention for 10 seconds each time. The itching symptoms immediately subsided. After a 5-minute interval, the patient was sprayed again for 10 seconds each time, and the itching symptoms disappeared. Subsequently, the patient was sprayed three times a day for 10 seconds each time for 7 consecutive days, and the patient's itching symptoms were completely eliminated. This treatment effect was astonishing; the severe pruritus that had plagued the patient for 3 years was resolved in just 7 days. This treatment method is convenient and rapid, and has significant clinical importance.

[0129] Treatment of pruritus using formulation 3 of the present invention:

[0130] Ms. Chen, female, 48 years old, works in finance. She has suffered from nodular prurigo for over 5 years, experiencing itching and localized redness and swelling in both temples and auricles, often resulting in skin damage due to scratching. She has used topical corticosteroid ointments, oral antihistamines, and long-term thymosin injections, but the itching persists and is unbearable. In June 2023, she applied the preparation 3 of this invention to the itchy areas of her temples and auricles for the first time. The itching stopped immediately within 8-10 seconds, and the itch-free period lasted for 5 hours. After 5 hours, she continued to use the same method, applying the preparation 3 of this invention once more. The local itching symptoms disappeared immediately, and the accompanying localized redness and swelling subsided.

[0131] Treatment of pruritus using formulation 4 of this invention:

[0132] Mr. Zhang, male, 36 years old, works in architectural design. Two days ago, the patient developed right upper quadrant pain without any obvious cause. The pain was intermittent, of unclear nature, and did not radiate to other areas. It was more severe at night and could be relieved by pressure. He also experienced fatigue and poor appetite. He received intravenous treatment at a community hospital (details unknown), but the above symptoms did not improve significantly. Currently, the symptoms have worsened, with increased intensity and frequency of pain. A linear red rash and small blisters are visible in the right hypochondrium. He consulted a dermatologist and was diagnosed with herpes zoster. He was prescribed acyclovir 0.4mg, red light therapy for 30 minutes once daily, and topical application of Lancofuran five times daily. After two days of treatment, the patient's pain symptoms did not lessen, and he developed severe itching in the right hypochondrium. While maintaining the original treatment plan, the agent of the present invention 4 was applied topically to the rash and to relieve pain and itching. It was applied 5 times a day for 10 seconds each time. The pain and itching were relieved immediately after application. The treatment continued with the addition of the agent of the present invention 4 until the 7th day. The rash on the right intercostal region completely disappeared, and the pain and itching were relieved.

[0133] The formulation of this invention can be used alone to treat pruritus, or it can be used in combination with conventional treatment regimens to further shorten the course of the disease.

[0134] This invention recruited 54 patients diagnosed with localized nodular prurigo from March 2022 to April 2023. The affected areas were: axilla (20 cases), dorsum of hand (12 cases), dorsum of foot (12 cases), and lower leg (10 cases). The smallest lesion area was 0.5cm × 1.2cm, and the largest was 7.8cm × 15cm. All patients were randomly divided into 5 groups. There were no statistically significant differences in gender, age, and disease duration among the 5 groups (P>0.05), indicating comparability.

[0135] The experimental group was treated with: (1) Preparations 1, 5, 6 or 7 of this invention; (2) Halometasone cream (trade name: Aoneng), manufactured by Aomei Pharmaceutical Factory (Hong Kong).

[0136] The control group received halometasone cream (trade name: Aoneng), manufactured by Aomei Pharmaceutical Factory (Hong Kong).

[0137] Treatment methods:

[0138] Experimental group: On the first day, patients were sprayed with "Preparation 1, Preparation 5, Preparation 6 or Preparation 7 of this invention" for 4-10 seconds per application, with a 5-minute interval before another 4-10 second application. Subsequently, the product was applied topically 3 times a day, each application lasting 4-10 seconds, for 3 consecutive days. Simultaneously, halometasone cream (trade name: Aoneng) was applied evenly to the affected area twice daily for 3 consecutive days, following the instructions for use of halometasone cream (trade name: Aoneng).

[0139] Control group: treated with halometasone cream (trade name: Aoneng), applied evenly to the affected area twice a day for 3 consecutive days.

[0140] result:

[0141] Comparison of pruritus scores before and after treatment (x±s)

[0142]

[0143] Note: * indicates that compared with the control group, P<0.05; ** indicates that compared with the control group, P<0.01; ## indicates that compared with other preparation groups, P<0.01.

[0144] Comparison of treatment effects (n%, %)

[0145]

[0146] Note: Compared with the control group, **, P<0.01.

[0147] Analysis of the experimental results showed that, compared with the control group, the experimental groups (formulation 1), (formulation 5), (formulation 6), and (formulation 7) all exhibited superior therapeutic effects, which were statistically significant. The experimental groups of this invention demonstrated excellent therapeutic effects and exhibited safety and efficacy within the specified timeframe.

[0148] Employing a linear spraying device, the linear spraying concentration of formulations 1-4 in this invention is high, with the spraying area concentrated within a diameter range of 1-2 cm. Specifically, for every 4 cm increase in distance from the nozzle, the diameter of the sprayed liquid increases by less than 2 times for formulation 1, and for formulations 2-4, the diameter increases by less than 3 times for every 4 cm increase in distance from the nozzle. The linear spraying area of ​​formulations 5-7 is concentrated within a diameter range of 3-4 cm, which is related to the physicochemical properties of the formulation components.

[0149] The research results of this invention show that the skin pruritus product of this invention has the advantages of definite curative effect, convenient use, and high safety, and maximizes its effect. It is easy to promote and apply. As the number of skin pruritus patients increases year by year, the demand for treatment drugs will also increase. Therefore, this invention can generate greater economic and social benefits.

[0150] In summary, this invention actively adapts to the needs of modern medical and scientific research, as well as the demand for humanized services, making it an ideal product for the clinical prevention and treatment of pruritus. Currently, there are no reports of similar products in other countries worldwide.

[0151] The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiments. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A composition for treating pruritus, characterized in that: The composition comprises a hydrocarbon halide and a hydrocarbon compound, wherein the hydrocarbon halide is tetrafluoroethane and pentafluoropropane, and the hydrocarbon compound is n-butane, and the mass ratio of tetrafluoroethane:pentafluoropropane:n-butane is 3:95:

2. The composition for treating pruritus is a non-azeotropic composition, and the contact temperature between the composition for treating pruritus and itchy skin is 0-7°C.

2. A preparation for treating pruritus, characterized in that: It includes the composition of claim 1 and optional pharmaceutically acceptable excipients.

3. The method for preparing the formulation according to claim 2, characterized in that: The preparation of formulations for the treatment of pruritus includes the steps of solution preparation, sterilization and bottling.

4. Use of the composition of claim 1 or the formulation of claim 2 in the preparation of a medicament for treating pruritus.

5. The use according to claim 4, characterized in that: The medication for pruritus is for external use and comes into contact with itchy skin during application.

6. The use according to claim 5, characterized in that: The medication for pruritus is applied to the itchy skin surface using a spraying device in a linear pattern.

7. The use according to claim 6, characterized in that: When using the medication for pruritus, spray for 3-15 seconds each time, keep the nozzle of the spray device 3-15cm away from the skin, and allow at least 2 minutes between each spray. Spray 3-8 times a day.

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