WO2022015138A1 - Antiseptic agent that can be deposited by spraying or inhaling into the lower respiratory tract system - Google Patents

Abstract

The invention relates to the combination of a device capable of orally or nasally dispersing a low-toxicity antiseptic agent that is slightly or moderately irritating, with a particle size less than 5 μm, such that it can be deposited in the lower respiratory tract, such as in the trachea, bronchi, lungs and alveoli, reaching the reservoir of infection, wherein the device is selected from an inhaler device with a pressurised cartridge, a fine-mist inhaler device, a dry-powder inhaler device, a nebulising device, a vaporisation device, an ultrasound nebulising device or a pneumatic or jet-type nebulising device.

Description

AN ANTISEPTIC AGENT DEPOSITABLE BY NASAL OR ORAL SPRAY OR INHALATION INTO THE LOWER RESPIRATORY TRACT SYSTEM

BACKGROUND Currently antiseptics are well known and used to disinfect various surfaces, including skin surfaces, however, antiseptics have not been used to reach the lower tract of the respiratory system reaching the alveoli and disinfecting the outer surface of the lungs , on the other hand, multiple devices have been used to introduce medications into the body that can reach the respiratory tract system, such as inhalation devices, ultrasound inhalation, vaporization or aerosols, so that the medication is pulverized to a very small size for that can reach the respiratory tract.

There are documents such as CN205569364 that refer to a medical fixation device for disinfection, made up of a bottle that in its upper part provides an entry of antiseptic and inhalable solution through the head of the phlegm tube that is inserted into the mouth, the bottom of the bottle is provided with the antiseptic from which the solution is drawn, and the outlet of the antiseptic solution is provided with the shut-off valve, depending on whether it is opened or closed. ES2325951 discloses a dosage device for topically administering a pharmaceutical formulation to the skin of a mammal, the device comprises a casing capable of containing at least one unit dose of a pharmaceutical formulation comprising a drug and a vehicle; an applicator adapted for topical administration; applying a unit dose of the pharmaceutical formulation directly to the skin; and an actuator, in which after activation, the device is capable of measuring a unit dose of the pharmaceutical formulation external to the device, from the housing to the applicator. JP2009526064 discloses a medicament including a solution containing pleconaril or a pharmaceutically acceptable salt thereof, wherein at least one solvent comprising said solution is a glyceride oil dissolving pleconaril, and the solution is suitable for administration by inhalation as an aerosol mist.

US6196218 this document relates to an inhaler that provides a controlled delivery of an inhalant and includes an inhaler housing and a mouthpiece attached to the inhaler housing, a piezoelectric dispensing head is attached to the inhaler housing and configured to engage the chamber dispensing, the piezoelectric dispensing head includes a number of delivery channels and a number of delivery nozzles, the set of delivery channels are formed with actuatable walls made at least partially of a piezoelectric material, the application of an electric field to the walls Selected laterals reduce a volume in an associated channel and create a pressure pulse of fluid substance in the associated channel through a dispensing nozzle.

Document GB179142 refers to a device to allow the inhalation of gas that has a powder in suspension, preferably a calcareous salt, comprises a cylindrical body, formed with one or more air inlet openings, and provided with a cover provided with a electric lamp or other means of heating, in front of the body and separated from it by a partition is a chamber in which is mounted a rotating brush adapted to be operated by hand or otherwise, above the chamber the cover is equipped with an inhalation mouthpiece and a joint piece is also installed, which allows the device to be connected to an antiseptic gas reservoir, in operation, the air passing through the openings is heated by the lamp and passes into the mouthpiece, joining in its passage through the reservoir gas, the release of the brush bristles throws the powder previously placed on the brush or fed onto the brush and the emission gas carries it to cape. CN101528290 discloses an actuator for an inhaler for administering drug by inhalation, comprising a casing for receiving a canister comprising a body including a base and a head and defining a chamber for containing the drug and a valve stem extending from the body and from which the administered drug is used by actuating the canister, an outlet through which an in-use user inhales, and a mouthpiece assembly providing drug delivery through the outlet, wherein the mouthpiece assembly nozzle comprises a nozzle block for receiving the valve stem of the container as a separately formed component, a nozzle outlet that is fluidly connected to the nozzle block and includes an outlet port through which the medicament is delivered in use Suspension formulations include aqueous suspensions, pharmaceutical particles, and optionally suspending agents, antiseptics, wetting agents, and antiseptic agents. ionicity adjustment.

However, none of the documents cited above uses an antiseptic agent that can be deposited by spraying or inhalation orally or nasally for deposition in the lower respiratory tract system, reaching the alveoli, for which the antiseptic composition needs to be supplied in particles smaller than 5 pm so that they can reach the alveoli and/or reservoir of infection in the lower tract system, and to achieve this it is required that the supply be through one of the devices that manage to propel and/or spray the antiseptic agent to this particle size, such as jet or ultrasonic nebulizer devices, metered-dose pressurized cartridge inhalers, spacer devices, and dry powder inhalers such as aerosolizers.

DETAILED DESCRIPTION

The present invention relates to an antiseptic agent that can be deposited by spraying or inhalation orally or nasally for deposition in the lower respiratory tract system, comprising an apparatus chosen from an inhaler device with a pressurized cartridge, a fine mist inhaler device, an inhaler device of dry powder, a nebulization device, a vaporization device, an ultrasonic nebulizer device, a pneumatic or jet-type nebulizer device, capable of storing an antiseptic composition with at least one dose of multi-particles of an antiseptic formulation, it being understood that when This antiseptic is used on skin, disinfectants are for another type of surface, the antiseptic used is to disinfect at least part of the lower respiratory tract system, reaching the reservoir of infection in the lower respiratory tract system, distributing said device after the actuation of at least one predetermined dose rminated of said multi-particles, the predetermined dose being distributed from the device substantially by spray, in which said antiseptic particles have an average diameter of less than 5 pm so that an effective dose of said antiseptic can be distributed to the lower respiratory tract system of a human patient. Said antiseptic agent is broad-spectrum, acting against viruses or bacteria, helping in the infection phase, this antiseptic agent is preferably of low toxicity that can be absorbed by the human body without toxic damage to treat lung infections and where the antiseptic composition is of low moderate irritability being below 8.9 as the test methodology Hen ^'s egg.

On the other hand, the antiseptic composition used contains antiseptics of low toxicity and moderate, slight to no irritation reaction, cataloged based on the methodology of the mucosal irritation test with chorioallantoic membrane. hen egg or test Hen ^'s egg chorioallantoic membrane test on (HETCAM) applied within 5 minutes. Where the semi quantitative irritability values according to Spielmann thrown by the test are considered below 8.9, so that they do not cause severe irritation in the lungs. The particle size of a composition determines whether the composition can reach the lungs or not, since if the particle size is greater than 5 pm, the particles have strong inertia, so they are deposited in the nasopharynx and epiglottis by turbulent flow, are responsible for systemic effects.

On the other hand, if the particle size is less than 5 pm, they have little inertia, and the particles are deposited in the lower respiratory tract by means of a laminar flow.

Among the antiseptic agents used, an antiseptic composition of low toxicity is required, the low toxicity being determined by the concentration of the antiseptic, since when the antiseptic agent is deposited in the lower pulmonary tract, the antiseptics can be toxic to the human body, therefore a low toxicity antiseptic agent is required, which can even be absorbed naturally by the body, so in the present invention the antiseptic agent used is chosen from oxidants such as hydrogen peroxide below 2 percent, chloramine, acid hypochlorous or potassium permanganate; acids and alkalis such as lactic acid, citric acid, ascorbic acid, acetic acid, sodium hydroxide, chlorine dioxide; heavy metals such as silver nitrate, silver sulfadiazine, silver sulfate, merbromine[(2'7'-Dibromo-3',6'-dihydroxy-3-oxospiro[isobenzofuran- (3H),9'-[9H]xanthen] -4'-yl)hydroxymercury disodium salt]; Anionic or cationic surfactants such as benzethonium chloride, cetylpyridinium chloride, cetrimide (mixture of different quaternary ammonium salts including cetrimonium bromide), benzalkonium chloride, quaternary ammonium salts; Halogenated such as povidone-iodine, cadexomer iodine, iodine solutions; Alcohols and ethers such as ethanol, isopropyl alcohol, pine oil or propolis; Biguanidines such as chlorhexidine or polyhexanide; or phenols such as triclosan; Repitel (Composition of carbomer, choline (3-sn-phosphatidyl) hydrogenated (Soy), sodium hydroxide, citric acid, disodium hydrogen phosphate, potassium iodate, povidone-iodine and purified water).

These antiseptic agents were chosen because they are of low toxicity, which also depends on the concentration of the antiseptic agent, and low to moderate irritability, and many of them can be naturally absorbed by the body into the blood or naturally disposed of. , without causing severe damage to the user, the invention therefore focuses on the combination of a device capable of dispersing orally or nasally an antiseptic agent of those mentioned above with a particle size of less than 5 pm so that it is deposited in the tract lower respiratory tract, and more specifically reaching the reservoir of infection in the lower respiratory tract, such as the lungs and alveoli.

In cases where the antiseptic agent is ethyl alcohol or citric acid or ascorbic acid or lactic acid or contains iodine (iodinated), it is absorbed and/or discarded naturally by the patient's body, since these components are included in the body of the patient, such as in the blood, naturally or they may be contained in the body of the patient and be disposed of naturally.

Another object of the present invention is an antiseptic agent depositable by spraying or inhalation in the lower respiratory tract system for use in the treatment of the lungs.

Another embodiment of the present invention lies in the use of an antiseptic agent such as the one mentioned above for the manufacture of a composition that is useful for the treatment of the lungs. Another embodiment of my invention relates to a kit for applying an antiseptic agent in the lower respiratory tract system, consisting of a device chosen from a pressurized cartridge inhaler device, a fine mist inhaler device, a dry powder inhaler device , a nebulizing device, a vaporizing device, an ultrasonic nebulizing device, or a pneumatic or jet-type nebulizing device, containing at least one dose of an antiseptic agent, for delivering the antiseptic when actuated by means of an actuator.

Claims

CLAIMS Having described my invention as above, I consider the contents of the following clauses a novelty and claim my property: 1.-An antiseptic agent depositable by nasal or oral spray or inhalation in the lower respiratory tract system, comprising at least one antiseptic element that is chosen from oxidants such as hydrogen peroxide below 2 percent, chloramine, hypochlorous acid or permanganate potassium; acids and alkalis such as lactic acid, citric acid, ascorbic acid, acetic acid, sodium hydroxide, chlorine dioxide; heavy metals such as silver nitrate, silver sulfadiazine, silver sulfate, [(2'7'-Dibromo-3',6'-dihydroxy-3-oxospiro[isobenzofuran-(3H),9'-[9H]xanthene]- 4'-yl)hydroxymercury disodium salt]; Anionic or cationic surfactants such as benzethonium chloride, cetylpyridinium chloride, cetrimide (mixture of different quaternary ammonium salts including cetrimonium bromide), benzalkonium chloride, quaternary ammonium salts; Halogenated such as povidone-iodine, cadexomer iodine, iodine solutions; Alcohols and ethers such as ethanol, isopropyl alcohol, pine oil or propolis; Biguanidines such as chlorhexidine or polyhexanide; or phenols such as triclosan; Composition of carbomer, choline (3-sn-phosphatidyl) hydrogenated (Soy), sodium hydroxide, citric acid, disodium hydrogen phosphate, potassium iodate, povidone iodine). 2. -An antiseptic agent depositable by spraying or inhalation in the lower respiratory tract system to be used in the treatment of the lungs, which comprises at least one antiseptic element that is chosen from oxidants such as hydrogen peroxide below 2 percent, chloramine, hypochlorous acid, or potassium permanganate; acids and alkalis such as lactic acid, citric acid, ascorbic acid, acetic acid, sodium hydroxide, chlorine dioxide; heavy metals such as silver nitrate, silver sulfadiazine, silver sulfate, [(2'7'-Dibromo-3',6'-dihydroxy-3-oxospiro[isobenzofuran-(3H),9'-[9H]xanthene]- 4'-yl)hydroxymercury disodium salt]; Anionic or cationic surfactants such as benzethonium chloride, chloride cetylpyridinium, cetrimide (mixture of different quaternary ammonium salts including cetrimonium bromide), benzalkonium chloride, quaternary ammonium salts; Halogenated such as povidone-iodine, cadexomer iodine, iodine solutions; Alcohols and ethers such as ethanol, isopropyl alcohol, pine oil or propolis; Biguanidines such as chlorhexidine or polyhexanide; or phenols such as triclosan; Carbomer composition, hydrogenated (3-sn-phosphatidyl) choline(Soy), sodium hydroxide, citric acid, disodium hydrogen phosphate, potassium iodate, povidone iodine); and wherein said solution is suitable for administration by nasal or oral inhalation as an aerosol mist by means of an apparatus selected from a pressurized cartridge inhaler device, a fine mist inhaler device, a dry powder inhaler device, a nebulizing device, a vaporizing device, an ultrasonic nebulizing device, or a pneumatic or jet-type nebulizing device. 3. -The use of an antiseptic agent according to claim 1 for the preparation of a composition that is useful for the treatment of the lungs. 4. -An antiseptic agent depositable by nasal or oral spray or inhalation in the lower respiratory tract system, according to claim 1, which presents a moderate, slight to no irritation reaction, cataloged based on the test methodology of mucosal irritation with chorioallantoic membrane of chicken egg, where the semi-quantitative irritability scores obtained by the test are considered below 8.9, so that they do not cause severe irritation in the lungs. 5. -An antiseptic agent depositable by nasal or oral spray or inhalation in the lower respiratory tract system according to claim 1, wherein the toxicity depends on the concentration of the antiseptic agent. 6. -An antiseptic agent depositable by nasal or oral spray or inhalation in the lower respiratory tract system according to claim 1, wherein in cases where the antiseptic agent is ethyl alcohol or citric acid or ascorbic acid or lactic acid or contains iodine (iodinated), it is absorbed and/or discarded naturally by the patient's body. 7. -A dosing device to administer an antiseptic agent by spray or inhalation, consisting of a device chosen from a pressurized cartridge inhaler device, a fine mist inhaler device, a dry powder inhaler device, a nebulization device, a vaporization device, an ultrasonic nebulizer device or a pneumatic or jet-type nebulizer device, the device being capable of storing at least one dose of an antiseptic agent according to claim 1, so that when the device is activated a predetermined dose of micro particles with an average diameter of less than 5 microns of antiseptic are dispersed under pressure reaching the lower respiratory tract system, made up of the trachea, bronchi, lungs and alveoli. 8. -A kit for application of an antiseptic agent in the lower respiratory tract system, consisting of a device chosen from among a pressurized cartridge inhaler device, a fine mist inhaler device, a dry powder inhaler device, a nebulization device , a vaporization device, an ultrasonic nebulizer device or a pneumatic or jet-type nebulizer device, containing at least one dose of an antiseptic agent according to claim 1.