CONDENSATION PRODUCT FOR USE IN A METHOD FOR THE TREATMENT OF COVID-19

Abstract

The present invention relates to a condensation product obtainable by reaction of a1) at least one aromatic system or heteroaromatic system, a2) at least one carbonyl compound, a3) if appropriate at least one sulfonating agent, and a4) if appropriate at least one urea derivative, where the condensation product has a molecular weight Mw of at least 300 g/mol, for use in a method for the treatment of COVID-19. The invention further relates to a use of the condensation product in a therapeutic method for the treatment of COVID-19; to a use of the condensation product as disinfectant against the virus SARS-CoV-2; and to a use of the condensation product for the production of a medicament which is an antiviral agent against SARS-CoV-2.

Claims

1. A condensation product obtained by reacting b1) at least one compound selected from phenol and dihydroxydiphenylsulfone, b2) at least one aldehyde selected from formaldehyde, acetaldehyde, and propionaldehyde, b3) if appropriate concentrated sulfuric acid, and b4) if appropriate at least one urea derivative selected from urea, melamine, ##STR00004## wherein the condensation product has a molecular weight Mw in a range of from 4,000 to 7,000 g/mol, for use in a method for the treatment of COVID-19.

2. The condensation product according to claim 1, wherein the condensation product is obtained by reacting a1) phenol, a2) formaldehyde, a3) concentrated sulfuric acid, and a4) urea.

3. The method according to claim 5, where the condensation product is administered in form of a spray or an aqueous solution.

4. The method according to claim 5, where COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

5. A therapeutic method for the treatment of COVID-19 comprising administration of a condensation product according to claim 1.

6. A method of disinfecting against the virus SARS-CoV-2 comprising applying the condensation product of claim 1.

7. The method according to claim 6 where the condensation product is present in dissolved form in water.

8. A method of producing a medicament, which is an antiviral agent against SARS-CoV-2, comprising adding a condensation product as defined in claim 1 to a physiologically tolerable vehicle.

9. (canceled)

10. (canceled)

11. (canceled)

Description

EXAMPLES

[0090] Solutions are understood as meaning aqueous solutions if not expressly specified otherwise. ppm relates to parts by weight.

[0091] The molecular weight determinations are carried out using gel permeation chromatography (GPC): Stationary phase: poly(2-hydroxymethacrylate) gel crosslinked with ethylene glycol dimethacrylate, obtainable commercially as HEMA BIO from PSS, Mainz, Germany. Eluent: mixture of 30% by weight of tetrahydrofuran (THF), 10% by weight of acrylonitrile, 60% by weight of 1 molar NaNO.sub.3 solution

[0092] Internal standard: 0.001% by weight of benzophenone, based on eluent Flow: 1.5 ml/min Concentration: 1% by weight in the eluent containing internal standard Detection: UV/V is spectrometrically at 254 nm Calibration using polystyrene calibration part from PSS. M.sub.n: number-average molecular weight in [g/mol] M.sub.w: weight-average molecular weight in [g/mol]

[0093] For the determination of free formaldehyde, a flow injection apparatus according to Huber is employed, see Fresenius Z. Anal. Chem. 1981, 309, 389. The column chosen is a thermostatted reaction column 170×10 mm, filled with glass beads, which is operated at 75° C. The detector (continuous flow detector) is set at a wavelength of 412 nm. The procedure is as follows: For the preparation of a reagent solution, 62.5 g of ammonium acetate are dissolved in 500 ml of distilled water, 7.5 ml of concentrated acetic acid and 5.0 ml of acetylacetone are added and filled up to 1000 ml with distilled water. 0.1 g of the condensation product to be investigated is weighed into a 10 ml volumetric flask, filled up to 10 ml with distilled water and the respective sample solution is obtained. 100 μl of sample solution in each case are added, mixed with reagent solution and a mean residence time of 1.5 minutes is set, which corresponds to a flow of 35 ml/min.

[0094] For the determination of the absolute values, the flow injection apparatus is calibrated with formaldehyde solutions of known content.

Example 1

[0095] Reactants were: a) phenol, b) concentrated sulfuric acid, c) formaldehyde, d) urea

[0096] 2.04 kg of phenol are introduced into a stirring apparatus and treated with 2.48 kg of concentrated sulfuric acid (96% by weight) for 20 minutes. Care is to be taken here that the temperature does not exceed 105° C. Subsequently, the reaction mixture is stirred at 100 to 105° C. for 2 hours and then diluted with 0.34 kg of water of 20° C. and cooled to 70° C.

[0097] 2.06 kg of aqueous urea solution (68% by weight) are metered in, the temperature rising to 95° C.; subsequently the mixture is cooled to 75° C.

[0098] 4.10 kg of aqueous formaldehyde solution (30% by weight) are added over a period of 90 minutes, care being taken that the temperature does not rise above 75° C.

[0099] Subsequently, it is partially neutralized using 0.78 kg of aqueous sodium hydroxide solution (50% by weight), 0.30 kg of water are added, and the mixture is subsequently stirred for 30 minutes and cooled further.

[0100] 1.36 kg of phenol are added at a temperature of 50° C. 1.14 kg of aqueous formaldehyde solution (30% by weight) are subsequently metered in at 50° C. over 20 minutes and the mixture is subsequently stirred for a further 30 minutes at 55° C.

[0101] The final adjustment of concentration and pH is carried out by addition of 1.40 kg of sodium hydroxide solution (50% by weight) and 2.5 kg of water. 18.5 kg of reaction solution 1.1 are obtained containing 43% by weight of nonvolatile fractions.

[0102] The analysis of the reaction solution affords the following values:

[0103] sodium sulfate by IC (based on nonvolatile fractions): 6.8% by weight; phenol by HPLC (based on nonvolatile fractions): 0.36% by weight; 4-phenolsulfonic acid by HPLC (based on nonvolatile fractions): 2.89% by weight; free formaldehyde: 75 ppm, based on nonvolatile fractions. M.sub.n 890 g/mol, M.sub.w 7820 g/mol, determined by GPC.

Example 2

[0104] Reactants were: a) phenol, b) concentrated sulfuric acid, c) formaldehyde,

[0105] 2.75 kg of phenol are introduced into a stirring apparatus and treated with 1.48 kg of concentrated sulfuric acid (96% by weight) for 20 minutes. Care is to be taken here that the temperature does not exceed 105° C. Subsequently, the reaction mixture is stirred at 100 to 105° C. for 3 hours and then cooled to 50° C.

[0106] 2.00 kg of aqueous formaldehyde solution (30% by weight) are added over a period of approximately one hour, care being taken that the temperature does not exceed 55° C. Subsequently, the mixture is stirred at 50 to 55° C. for 10 hours, then 1.80 kg of water are added and it is finally stirred at 95 to 100° C. for 4 hours.

[0107] After cooling to room temperature, the final adjustment of concentration and pH is carried out by addition of aqueous sodium hydroxide solution (50% by weight) and water. 10.2 kg of reaction solution 1.2 are obtained containing 40% by weight of nonvolatile fractions.

[0108] The analysis of reaction solution affords the following values: sodium sulfate by IC (based on nonvolatile fractions): 15.4% by weight; phenol by HPLC (based on nonvolatile fractions): 0.11% by weight; 4-phenolsulfonic acid by HPLC (based on nonvolatile fractions): 5.34% by weight; free formaldehyde: 8 ppm, based on nonvolatile fractions. M.sub.n 1810 g/mol, M.sub.w 9040 g/mol, determined by GPC.

Example 3

[0109] Reactants were a) phenol, b) concentrated sulfuric acid, c) formaldehyde, d) urea

[0110] 2.04 kg of phenol are introduced into a stirring apparatus and treated with 2.48 kg of concentrated sulfuric acid (96% by weight) for 20 minutes. Care is to be taken here that the temperature does not exceed 105° C. Subsequently, the reaction mixture is stirred at 100 to 105° C. for 2 hours and then diluted with 340 g of water.

[0111] 2.05 kg of urea solution (68% by weight) are metered in, care being taken that the temperature does not exceed 95° C.

[0112] 3.60 kg of aqueous formaldehyde solution (30% by weight) are then added at 83 to 93° C. over a period of 1.5 hours.

[0113] After a stirring time of 15 minutes, 800 g of aqueous sodium hydroxide solution (50% by weight) are added, care being taken that the temperature does not exceed 85° C., so that the pH is subsequently between 7.3 and 7.5. 11.3 kg of reaction solution 1.3 containing 47% by weight of nonvolatile fractions are obtained.

[0114] The analysis of reaction solution affords the following values:

[0115] sodium sulfate by IC (based on nonvolatile fractions): 10.3% by weight; phenol by HPLC (based on nonvolatile fractions): 0.74% by weight; 4-phenolsulfonic acid by HPLC (based on nonvolatile fractions): 1.36% by weight; free formaldehyde: 99 ppm, based on nonvolatile fractions. M.sub.n 1990 g/mol, M.sub.w 17.020 g/mol, determined by GPC.