WO2017217877A1 - Methods to reduce harmful effects of smoking cigarettes, cigars and tobacco, and of exposure to smoke from cigarettes, cigars and tobacco by using kynurenic acid in nanoparticle carrier systems - Google Patents

Methods to reduce harmful effects of smoking cigarettes, cigars and tobacco, and of exposure to smoke from cigarettes, cigars and tobacco by using kynurenic acid in nanoparticle carrier systems Download PDF

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WO2017217877A1
WO2017217877A1 PCT/PL2017/000064 PL2017000064W WO2017217877A1 WO 2017217877 A1 WO2017217877 A1 WO 2017217877A1 PL 2017000064 W PL2017000064 W PL 2017000064W WO 2017217877 A1 WO2017217877 A1 WO 2017217877A1
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Prior art keywords
tobacco
cigars
kynurenic acid
acid
smoke
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PCT/PL2017/000064
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French (fr)
Inventor
Michał TURSKI
Monika TURSKA
Gabrielle TURSKI
Christopher Turski
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Turski Michał
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Priority to EP17813671.9A priority Critical patent/EP3893676A4/en
Priority to RU2018146525A priority patent/RU2699595C1/en
Publication of WO2017217877A1 publication Critical patent/WO2017217877A1/en
Priority to ZA2019/05960A priority patent/ZA201905960B/en

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    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
    • A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
    • A24B15/18—Treatment of tobacco products or tobacco substitutes
    • A24B15/28—Treatment of tobacco products or tobacco substitutes by chemical substances
    • A24B15/30—Treatment of tobacco products or tobacco substitutes by chemical substances by organic substances
    • A24B15/36—Treatment of tobacco products or tobacco substitutes by chemical substances by organic substances containing a heterocyclic ring
    • A24B15/38—Treatment of tobacco products or tobacco substitutes by chemical substances by organic substances containing a heterocyclic ring having only nitrogen as hetero atom
    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24D—CIGARS; CIGARETTES; TOBACCO SMOKE FILTERS; MOUTHPIECES FOR CIGARS OR CIGARETTES; MANUFACTURE OF TOBACCO SMOKE FILTERS OR MOUTHPIECES
    • A24D3/00—Tobacco smoke filters, e.g. filter-tips, filtering inserts; Filters specially adapted for simulated smoking devices; Mouthpieces for cigars or cigarettes
    • A24D3/02—Manufacture of tobacco smoke filters
    • A24D3/0204—Preliminary operations before the filter rod forming process, e.g. crimping, blooming
    • A24D3/0212—Applying additives to filter materials
    • A24D3/0216—Applying additives to filter materials the additive being in the form of capsules, beads or the like
    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24D—CIGARS; CIGARETTES; TOBACCO SMOKE FILTERS; MOUTHPIECES FOR CIGARS OR CIGARETTES; MANUFACTURE OF TOBACCO SMOKE FILTERS OR MOUTHPIECES
    • A24D3/00—Tobacco smoke filters, e.g. filter-tips, filtering inserts; Filters specially adapted for simulated smoking devices; Mouthpieces for cigars or cigarettes
    • A24D3/04—Tobacco smoke filters characterised by their shape or structure
    • A24D3/048—Tobacco smoke filters characterised by their shape or structure containing additives
    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24D—CIGARS; CIGARETTES; TOBACCO SMOKE FILTERS; MOUTHPIECES FOR CIGARS OR CIGARETTES; MANUFACTURE OF TOBACCO SMOKE FILTERS OR MOUTHPIECES
    • A24D3/00—Tobacco smoke filters, e.g. filter-tips, filtering inserts; Filters specially adapted for simulated smoking devices; Mouthpieces for cigars or cigarettes
    • A24D3/06—Use of materials for tobacco smoke filters
    • A24D3/14—Use of materials for tobacco smoke filters of organic materials as additive
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds

Definitions

  • TITLE Methods to reduce harmful effects of smoking cigarettes, cigars and tobacco, and of exposure to smoke from cigarettes, cigars and tobacco by using kynurenic acid in nanoparticle carrier systems.
  • the invention relates to methods for reducing harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that kynurenic acid or a salt thereof in a nanoparticle carrier system is added to the cigarettes, cigars or tobacco.
  • the method to reduce the harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that kynurenic acid or a salt thereof in a nanoparticle carrier system is added into a cigarette filter, or a cigarette paper.
  • the method to reduce the harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that a component of the cigarette or cigar, or a combination of components of the cigarette or cigar, contain kynurenic acid or a salt thereof in a nanoparticle carrier system.
  • Another subject of the invention is a method to reduce the harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that the device for smoking tobacco (such as but not limited to a mouthpiece, cigarette holder, pipe, water pipe, shisha pipe, bong, shabong, filter, inhaler) is equipped with a component containing kynurenic acid or salts thereof in a nanoparticle carrier system.
  • the device for smoking tobacco such as but not limited to a mouthpiece, cigarette holder, pipe, water pipe, shisha pipe, bong, shabong, filter, inhaler
  • Another subject of the invention is a method to reduce the harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that kynurenic acid or a salt thereof in a nanoparticle carrier system is added to an inhaler.
  • Another subject of the invention is a method to reduce the harmful effects of smoking cigarettes, cigars, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that kynurenic acid or a salt thereof in a nanoparticle carrier system is added to electric fumi gators.
  • Another subject of the invention is a method to reduce the harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that kynurenic acid or a salt thereof in a nanoparticle carrier system is added to filters used in air conditioning systems.
  • Another subject of the invention is a method to reduce the harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that kynurenic acid or a salt thereof in a nanoparticle carrier system is added to filters used in the air supply system in a motor vehicle.
  • Another subject of the invention is a method to reduce the harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that kynurenic acid or a salt thereof in a nanoparticle carrier system is added to chewing gums, beverages, drinks, candies, tablets, softgels, capsules, or syrups.
  • Nanoparticle carrier systems facilitate the penetration of cell membranes in the human body (Zdrojewicz Z et al., Hig Med Dosw 69, 1196-1204, 2015).
  • Nano- particle carrier systems used in contemporary medicine include: polymeric nanoparticles such as sodium alginate, gelatine, polylactic acid, polyglycolic acid, and dextran; solid lipid nanoparticles such as tricaprin, tristearin, glyceryl monostearate, cetyl palmitate, and palmitic acid; nanoemulsions such as soybean lecithin, egg lecithin, polaxamer 188, polysorbate 80, polyoxyethylated castor oil, Cremophor EL, and tyloxapol; vesicle based systems such as phosphatidylcholine, distearoylphosphatidic acid, dipalmitoylphosphatidic acid, and cholesterol; and stabilizers such as poly vinyl alcohol, poly vinyl pyrrolidone
  • kynurenic acid or salts thereof added to the cigarette or tobacco in nanoparticle carrier systems can enter the lungs while smoking despite the fact that the combustion temperature of kynurenic acid is significantly lower than the temperature reached during smoking of tobacco (Baker RR, Nature 247, 405-406, 1974).
  • kynurenic acid or salt thereof in a nanoparticle carrier system increases the amount of kynurenic acid in the smoke formed during cigarette smoking more than that caused by the addition of kynurenic acid or salt thereof without nanoparticle carriers.
  • Example 1 Concentration of kynurenic acid in the cigarette smoke after adding kynurenic acid in a nanoparticle carrier system into a cigarette .
  • Kynurenic acid was dissolved in 0.1% aqueous Cremophor EL and NaOH solution. 0.1 ml of solution was inserted into the cigarette tobacco by means of Hamilton syringe. The amount of delivered kynurenic acid was 1 000 000 pmol/cigarette. Cigarettes were subsequently dried in the room temperature for the following 48 h. Cigarette was smoked in a device shown in Figure 1 , Smoke passed through the water filter (Fig. 2) and concentration of kynurenic acid was measured in water. The concentration of kynurenic acid in cigarette smoke before adding kynurenic acid to the cigarette tobacco varied from 18.4 to 30.6 pmol/cigarette and 33.7 to 51.0 pmol/g tobacco.
  • the concentration of kynurenic acid in cigarette smoke after adding kynurenic acid to the cigarette tobacco without nanoparticle carrier system varied from 52.4 to 233.4 pmol/cigarette and 87.5 to 429.0 pmol/g tobacco.
  • the concentration of kynurenic acid in cigarette smoke after adding kynurenic acid to the cigarette tobacco in a nanoparticle carrier system varied from 157.3 to 657.0 pmol/cigarette (Table 1).
  • Casablanca is a brand of commercial tobacco used for preparation of cigarettes.
  • Example 2 Concentration of kynurenic acid in the cigarette smoke after adding kynurenic acid in a nanoparticle carrier system into the cigarette filter.
  • Kynurenic acid was dissolved in 0.1% aqueous Cremophor EL and NaOH 110 solution. 0.1 ml of solution was inserted into the cigarette filter by means of Hamilton syringe. The amount of delivered kynurenic acid was 1 000 000 pmol/cigarette. Cigarettes were subsequently dried in the room temperature for the following 48 h. Cigarette was smoked in a device shown in Figure 1. Smoke passed through the water filter and kynerenic acid concentration was measured in water.
  • Adding kynurenic acid in the nanoparticle carrier into the cigarette filter increased its concentration in the cigarette smoke 12.5 times.
  • the increase in the concentration of kynurenic acid in the cigarette smoke achieved with the nanoparticle carrier after adding it into the cigarette filter was greater than that achieved without the use of a carrier that amounted to 7.7 times.
  • Example 3 Concentration of kynurenic acid in the cigarette smoke after spraying tobacco with kynurenic acid in a nanoparticle carrier system.
  • kynurenic acid dissolved in 0.1% aqueous Cremophor EL and NaOH solution
  • commercially available tobacco (Casablanca) was sprayed (with a spray dispenser) with a solution of kynurenic acid (10 mg kynurenic acid g tobacco) and dried at the room temperature for 48 h after adding kynurenic acid. Subsequently, the cigarette with a filter was made using a commercially available kit. Such a self-made cigarette was smoked in a device shown in Figure 1.
  • the concentration of kynurenic acid in the smoke of cigarette after spraying tobacco with kynurenic acid without a nanoparticle carrier ranged from 5318 to 7309 pmol/cigarette and 6044 to 14619 pmol/g tobacco.
  • the concentration of kynurenic acid in the cigarette smoke after spraying tobacco with kynurenic acid in the nanoparticle carrier was 12422 pmol/cigarette (Table 1).
  • Spraying tobacco with kynurenic acid in the nanoparticle carrier raised the concentration of kynurenic acid in the cigarette smoke by 1.70 and 1.97 times.
  • Example 4 Concentration of kynurenic acid in the rat lung after ora! administration of kynurenic acid in a nanoparticie carrier system.
  • Kynurenic acid was dissolved in the 0.1% aqueous Cremophor EL and NaOH solution. pH of solution was adjusted to 7.0.
  • Adult male Wistar rats were administered kynurenic acid into the stomach in the dose of 25 mg/kg.
  • the concentration of kynurenic acid was determined in rat lungs 30 min, 1, 2 and 4 h after administration.
  • the concentration of kynurenic acid in lungs was 158 pmol/g of wet tissue after administration of vehicle.
  • the concentration of kynurenic acid after administration of kynurenic acid without use of the nanoparticie carrier was 2325, 1487, 1385 and 1266 pmol/g of wet tissue at 30 min, 1, 2 and 4 hours after its administration, respectively (Table 2).
  • the concentration of kynurenic acid after administration of kynurenic acid using nanoparticie carrier was 2871, 2331, 1807 and 1422 pmol/g of wet tissue at 30 min, 1 ⁇ 2 and 4 hours after its administration, respectively (Table 2).

Abstract

Kynurenic acid is an endogenous constituent of the human body. The methods for increasing the concentration of kynurenic acid in the lungs by adding kynurenic acid or its salts in nanoparticle carrier systems to cigarettes or tobacco prior to their smoking are described.

Description

TITLE: Methods to reduce harmful effects of smoking cigarettes, cigars and tobacco, and of exposure to smoke from cigarettes, cigars and tobacco by using kynurenic acid in nanoparticle carrier systems.
DESCRIPTION
The invention relates to methods for reducing harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that kynurenic acid or a salt thereof in a nanoparticle carrier system is added to the cigarettes, cigars or tobacco.
Preferably, the method to reduce the harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that kynurenic acid or a salt thereof in a nanoparticle carrier system is added into a cigarette filter, or a cigarette paper.
Preferably, the method to reduce the harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that a component of the cigarette or cigar, or a combination of components of the cigarette or cigar, contain kynurenic acid or a salt thereof in a nanoparticle carrier system.
Another subject of the invention is a method to reduce the harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that the device for smoking tobacco (such as but not limited to a mouthpiece, cigarette holder, pipe, water pipe, shisha pipe, bong, shabong, filter, inhaler) is equipped with a component containing kynurenic acid or salts thereof in a nanoparticle carrier system.
Another subject of the invention is a method to reduce the harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that kynurenic acid or a salt thereof in a nanoparticle carrier system is added to an inhaler. Another subject of the invention is a method to reduce the harmful effects of smoking cigarettes, cigars, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that kynurenic acid or a salt thereof in a nanoparticle carrier system is added to electric fumi gators.
Another subject of the invention is a method to reduce the harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that kynurenic acid or a salt thereof in a nanoparticle carrier system is added to filters used in air conditioning systems.
Another subject of the invention is a method to reduce the harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that kynurenic acid or a salt thereof in a nanoparticle carrier system is added to filters used in the air supply system in a motor vehicle.
Another subject of the invention is a method to reduce the harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that kynurenic acid or a salt thereof in a nanoparticle carrier system is added to chewing gums, beverages, drinks, candies, tablets, softgels, capsules, or syrups.
BACKGROUND ART
Nanoparticle carrier systems facilitate the penetration of cell membranes in the human body (Zdrojewicz Z et al., Hig Med Dosw 69, 1196-1204, 2015). Nano- particle carrier systems used in contemporary medicine include: polymeric nanoparticles such as sodium alginate, gelatine, polylactic acid, polyglycolic acid, and dextran; solid lipid nanoparticles such as tricaprin, tristearin, glyceryl monostearate, cetyl palmitate, and palmitic acid; nanoemulsions such as soybean lecithin, egg lecithin, polaxamer 188, polysorbate 80, polyoxyethylated castor oil, Cremophor EL, and tyloxapol; vesicle based systems such as phosphatidylcholine, distearoylphosphatidic acid, dipalmitoylphosphatidic acid, and cholesterol; and stabilizers such as poly vinyl alcohol, poly vinyl pyrrolidone, polyacrylic acid, and hydroxypropyl methyl cellulose. The purpose of the study was to determine whether kynurenic acid or salts thereof added to the cigarette or tobacco in nanoparticle carrier systems can enter the lungs while smoking despite the fact that the combustion temperature of kynurenic acid is significantly lower than the temperature reached during smoking of tobacco (Baker RR, Nature 247, 405-406, 1974).
Surprisingly, the addition of kynurenic acid or salt thereof in a nanoparticle carrier system to tobacco or its placement in/on the specific components of the cigarette increases the amount of kynurenic acid in the smoke formed during cigarette smoking more than that caused by the addition of kynurenic acid or salt thereof without nanoparticle carriers.
DISCLOSURE OF THE INVENTION
Examples
Example 1: Concentration of kynurenic acid in the cigarette smoke after adding kynurenic acid in a nanoparticle carrier system into a cigarette .
Kynurenic acid was dissolved in 0.1% aqueous Cremophor EL and NaOH solution. 0.1 ml of solution was inserted into the cigarette tobacco by means of Hamilton syringe. The amount of delivered kynurenic acid was 1 000 000 pmol/cigarette. Cigarettes were subsequently dried in the room temperature for the following 48 h. Cigarette was smoked in a device shown in Figure 1 , Smoke passed through the water filter (Fig. 2) and concentration of kynurenic acid was measured in water. The concentration of kynurenic acid in cigarette smoke before adding kynurenic acid to the cigarette tobacco varied from 18.4 to 30.6 pmol/cigarette and 33.7 to 51.0 pmol/g tobacco. The concentration of kynurenic acid in cigarette smoke after adding kynurenic acid to the cigarette tobacco without nanoparticle carrier system varied from 52.4 to 233.4 pmol/cigarette and 87.5 to 429.0 pmol/g tobacco. The concentration of kynurenic acid in cigarette smoke after adding kynurenic acid to the cigarette tobacco in a nanoparticle carrier system varied from 157.3 to 657.0 pmol/cigarette (Table 1).
Conclusions: Adding kynurenic acid in a nanoparticle carrier system to the cigarette increased its concentration in the smoke by 2.8 and 3.0 times. The increase in the concentration of kynurenic acid in the cigarette smoke achieved with the nanoparticle carrier was greater than that achieved without a carrier (Table 1).
Table 1. Concentration of kynurenic acid in the smoke from cigarettes after adding kynurenic acid in a nanoparticle carrier system into a cigarette.
Figure imgf000005_0001
Casablanca is a brand of commercial tobacco used for preparation of cigarettes.
KYNA, kynurenic acid.
105
Example 2: Concentration of kynurenic acid in the cigarette smoke after adding kynurenic acid in a nanoparticle carrier system into the cigarette filter.
Kynurenic acid was dissolved in 0.1% aqueous Cremophor EL and NaOH 110 solution. 0.1 ml of solution was inserted into the cigarette filter by means of Hamilton syringe. The amount of delivered kynurenic acid was 1 000 000 pmol/cigarette. Cigarettes were subsequently dried in the room temperature for the following 48 h. Cigarette was smoked in a device shown in Figure 1. Smoke passed through the water filter and kynerenic acid concentration was measured in water.
Conclusions: Adding kynurenic acid in the nanoparticle carrier into the cigarette filter increased its concentration in the cigarette smoke 12.5 times. The increase in the concentration of kynurenic acid in the cigarette smoke achieved with the nanoparticle carrier after adding it into the cigarette filter was greater than that achieved without the use of a carrier that amounted to 7.7 times.
Example 3: Concentration of kynurenic acid in the cigarette smoke after spraying tobacco with kynurenic acid in a nanoparticle carrier system.
To achieve a homogenous distribution of the added kynurenic acid (kynurenic acid dissolved in 0.1% aqueous Cremophor EL and NaOH solution), commercially available tobacco (Casablanca) was sprayed (with a spray dispenser) with a solution of kynurenic acid (10 mg kynurenic acid g tobacco) and dried at the room temperature for 48 h after adding kynurenic acid. Subsequently, the cigarette with a filter was made using a commercially available kit. Such a self-made cigarette was smoked in a device shown in Figure 1. The concentration of kynurenic acid in the smoke of cigarette after spraying tobacco with kynurenic acid without a nanoparticle carrier ranged from 5318 to 7309 pmol/cigarette and 6044 to 14619 pmol/g tobacco. The concentration of kynurenic acid in the cigarette smoke after spraying tobacco with kynurenic acid in the nanoparticle carrier was 12422 pmol/cigarette (Table 1).
Conclusions:
• Spraying tobacco with kynurenic acid in the nanoparticle carrier raised the concentration of kynurenic acid in the cigarette smoke by 1.70 and 1.97 times.
• The increase in the concentration of kynurenic acid in the cigarette smoke achieved using the nanoparticie carrier was greater than that achieved without using a carrier (Table 1).
Example 4: Concentration of kynurenic acid in the rat lung after ora! administration of kynurenic acid in a nanoparticie carrier system.
Kynurenic acid was dissolved in the 0.1% aqueous Cremophor EL and NaOH solution. pH of solution was adjusted to 7.0. Adult male Wistar rats were administered kynurenic acid into the stomach in the dose of 25 mg/kg. The concentration of kynurenic acid was determined in rat lungs 30 min, 1, 2 and 4 h after administration. The concentration of kynurenic acid in lungs was 158 pmol/g of wet tissue after administration of vehicle. The concentration of kynurenic acid after administration of kynurenic acid without use of the nanoparticie carrier was 2325, 1487, 1385 and 1266 pmol/g of wet tissue at 30 min, 1, 2 and 4 hours after its administration, respectively (Table 2). The concentration of kynurenic acid after administration of kynurenic acid using nanoparticie carrier was 2871, 2331, 1807 and 1422 pmol/g of wet tissue at 30 min, 1} 2 and 4 hours after its administration, respectively (Table 2).
Conclusions:
• Intragastric administration of kynurenic acid in a nanoparticie carrier system increased its concentration in lungs. The increase was detected at 30 min after its administration and lasted for 4 h.
• Increase of kynurenic acid concentration in lungs achieved with a nanoparticie carrier was greater than that achieved without vehicle support (Table 2). Table 2. Concentration of kynurenic acid in the rat lung after oral administration of kynurenic acid in a nanoparticle carrier system.
Figure imgf000008_0001

Claims

A method to reduce the harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from the smoking cigarettes, cigars and tobacco characterized in that kynurenic acid or a salt thereof in a nanoparticle carrier system is added to the cigarettes, cigars or tobacco. A method according to claim 1 , characterized in that kynurenic acid or a salt thereof in a nanoparticle carrier system is added into a cigarette filter, or to a cigarette paper.
A method according to claim 1 , characterized in that the component of the cigarette or cigar, or a combination of components of the cigarette or cigar, contain kynurenic acid or a salt thereof in a nanoparticle carrier system.
A method according to claim 1, characterized in that the nanoparticle carrier used to add kynurenic acid or salt thereof is an aqueous Cremophor EL solution at a concentration of 0.0001-10%.
A method according to claim 1, characterized in that the nanoparticle carrier used to add kynurenic acid or salts thereof is a solution of sodium alginate, gelatin, lactic acid, glycolic acid, dextran, tricaprine, tristearine, glycerol monostearate, cetyl palmitate, palmitic acid, lecithin, Polysorbate 80, tyloxapol, phosphatidylcholine, distearoylphosphatidic acid, dipalmitoylphosphatidic acid, cholesterol, polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acid, and hydroxypropylmethyl- cellulose at concentrations of 0.0001-10%.
6. A method to reduce the harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that the device for smoking tobacco (such as but not limited to a mouthpiece, cigarette holder, pipe, water pipe, shisha pipe, bong, shabong, filter, inhaler) is equipped with a component containing kynurenic acid or salts thereof in a nanoparticle carrier system.
7. A method to reduce the harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that kynurenic acid or a salt thereof in a nanoparticle carrier system is added to an inhaler.
8. A method to reduce the harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that kynurenic acid or a salt thereof in a nanoparticle carrier systems is added to electric fumigator.
9. A method to reduce the harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that kynurenic acid or a salt thereof in a nanoparticle carrier system is added to filters used in air conditioning systems.
10. A method to reduce the harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that kynurenic acid or a salt thereof in a nanoparticle carrier system is added to filters used in air supply systems in motor vehicles.
11. A method to reduce the harmful effects of smoking cigarettes, cigars, and tobacco, and exposure to smoke from smoking cigarettes, cigars and tobacco characterized in that kynurenic acid or a salt thereof in a nanoparticle carrier system is added to chewing gums, beverages, drinks, candies, tablets, softgels, capsules, or syrups.
PCT/PL2017/000064 2016-06-15 2017-06-14 Methods to reduce harmful effects of smoking cigarettes, cigars and tobacco, and of exposure to smoke from cigarettes, cigars and tobacco by using kynurenic acid in nanoparticle carrier systems WO2017217877A1 (en)

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EP17813671.9A EP3893676A4 (en) 2016-06-15 2017-06-14 Methods to reduce harmful effects of smoking cigarettes, cigars and tobacco, and of exposure to smoke from cigarettes, cigars and tobacco by using kynurenic acid in nanoparticle carrier systems
RU2018146525A RU2699595C1 (en) 2016-06-15 2017-06-14 Methods for reducing the harmful effect of smoking cigarettes, cigars and tobacco, as well as tobacco smoke exposure in passive smoking, involving use of a nanoparticle kinurenic acid delivery system
ZA2019/05960A ZA201905960B (en) 2016-06-15 2019-09-10 Methods to reduce harmful effects of smoking cigarettes, cigars and tobacco, and of exposure to smoke from cigarettes, cigars and tobacco by using kynurenic acid in nanoparticle carrier systems

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PLP.417590 2016-06-15
PL417590A PL235970B1 (en) 2016-06-15 2016-06-15 Methods for reducing harmful effects of smoking cigarettes, cigars, tobacco and exposure to smoke, with burning cigarettes, cigars and tobacco by kynurenic acid in nanoparticle carrier systems

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PL235970B1 (en) 2020-11-16
EP3893676A4 (en) 2022-10-12
RU2699595C1 (en) 2019-09-06
ZA201905960B (en) 2021-07-28
EP3893676A1 (en) 2021-10-20
PL417590A1 (en) 2017-12-18

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