Masking preparations and compounds from Dracaena draco (Dragon's Blood)

Abstract

The present invention mainly relates to the use of a compound according to formula (I) or a mixture comprising a compound according to formula (I) for reducing, modulating and / or masking the bitter impression of one or more bitter substances. Furthermore, the present invention also relates to an extract comprising a compound as defined above, and a food or feed composition comprising one or more bitter substances and a compound as defined above.

Description

Technical Field

[0001] This invention primarily relates to the use of a compound according to formula (I) or a mixture comprising a compound according to formula (I) for reducing, adjusting, and / or masking the bitterness impression of one or more bitter substances. Furthermore, this invention also relates to an extract comprising a compound according to formula (I), and a food or feed composition comprising one or more bitter substances and a compound according to formula (I) or an extract according to the invention.

[0002] Further aspects of the invention will be derived from the following description, particularly from the embodiments and from the appended patent claims. Background Technology

[0003] Bitterness is generally considered an unpleasant taste. However, bitter substances are known to have pleasant effects on the human organism, particularly on physiological processes. Bitter substances stimulate bitter taste receptors (TAS2Rs), which are then antagonized by bitter masking substances. TAS2Rs are known to be used in the oral cavity to detect bitter substances in food and other stimuli from the environment.

[0004] Identifying novel agonists and antagonists is a highly sought-after goal in the food and pharmaceutical industries, with the pharmaceutical sector focusing on novel substances that can serve as alternatives for treating respiratory and digestive system disorders. A significant advantage of bitter-masking substances acting as GPCR or TAS2R antagonists / agonists is their ability to reduce the bitterness of the drug, thereby reducing undesirable side effects. Therefore, it is important to provide substances that can reduce the bitterness of substances in mixtures or formulations. Preferably, such substances are available from natural resources, such as plants.

[0005] Generally, bitter taste perception is mediated by the bitter taste receptor TAS2R, a G protein-coupled receptor (GPCR) located in the taste buds on the tongue in the oral cavity. TAS2R activates via a neural pathway to the brain, thereby enabling the recognition of bitter taste. To date, 26 different TAS2Rs are known, divided into three distinct groups: broadly tuned, narrowly tuned, and intermediate. TAS2R14 is a broadly tuned receptor, particularly agonistic to quinine, caffeine, and quercetin. Bitter taste masking agents such as 6-methoxyflavanones or 3',6-dimethoxyflavanones, both phenolic compounds, antagonize TAS2R14. Summary of the Invention

[0006] The primary objective of this invention is to provide a compound suitable for masking bitter tastes in mixtures, extracts, or food / feed compositions, preferably suitable for masking bitter tastes in quinine and / or proteins or protein-containing products. Furthermore, an objective of this invention is to provide a cost-effective and readily available biologically derived compound. Another objective of this invention is to improve the quality of protein formulations, preferably for use in alternative protein products.

[0007] Further fundamental objectives of the present invention are derived from the following description and the claims of this patent.

[0008] According to a first aspect of the invention, the stated object is achieved by the use of a compound according to formula (I) or a mixture comprising a compound according to formula (I) for reducing, adjusting and / or masking the bitter impression of one or more bitter substances:

[0009]

[0010] (I).

[0011] Surprisingly, it has been found that compounds according to formula (I) are suitable for reducing, adjusting, and / or masking the bitterness of one or more bitter substances. Furthermore, in the context of its own research, which forms the basis of this invention, it has been found that compounds according to formula (I) and extracts containing compounds according to formula (I) are particularly advantageous for the purposes defined above, among various isolated fractions and substances of extracts from the resin of the plant *Daemonorops draco*.

[0012] To investigate the potential bitterness-masking properties of specific compounds in plants, extracts are typically fractionated by chromatography and then applied to subsequent sensory analyses and cell-based assays. In the context of this invention, extracts of the plant *Dracaena cochinchinensis* are studied in this manner. Various fractions have been obtained from extracts of the resin of *Dracaena cochinchinensis* (also known as dragon's blood), and several substances have been isolated.

[0013] The phytochemistry of Daemonorops draco is described in various publications (Novel Flavonoids in Dragon's Blood of Daemonorops draco, K.-I. Nakashima, N. Abe, F. Kamiya, T. Ito, M. Oyama and M. Iinuma, Helv. Chim. Acta, 2009, Vol. 92, No. 10, pp. 1999-2008; DRAGON'S BLOOD FROM DRACACENAE DRACO, STRUCTURE OF NOVEL HOMOlSOFLAVANOIDS, L. Camarda, L. Merlini and G. Nasini, Heterocycles, 1983, Vol. 20, No. 1, pp. 39-43; Retro-dihydrochalcones from the resin of Daemonorops draco and their inhibitory activities against renal fibrosis, B.-L. Zhang, C.-T. Tao, L.-S. Zhang and Y.-X. Cheng, Fitoterapia, 2023, Vol. 168, p. 105515, DOI: https: / / doi.org / 10.1016 / j.fitote.2023.105515.

[0014] The well-established HGT-1 cell system was used to identify the cellular bitterness response of extracts, fractions, and substances. Therefore, low IPX values ​​were associated with bitter substances, while high IPX values ​​were associated with less intense bitterness. (Liszt, KI; Ley, JP; Lieder, B.; Behrens, M.; Stoger, V.; Reiner, A.; Hochkogler, CM; Kock, E.; Marchiori, A.; Hans, J. et al. Caffeine induces gastric acid secretion via bitter taste signaling in gastric parietal cells. Proc Natl Acad Sci US A2017, 114 (30), E6260-E6269. DOI: 10.1073 / pnas.1703728114.) Furthermore, this cell line was modified via CRISPR-Cas9 knockout.

[0015] According to a preferred embodiment of the invention, the mixture is an extract, preferably wherein the extract is an extract as defined below or in the corresponding patent claims.

[0016] A preferred embodiment of the present invention is the use as defined above, wherein the bitter substance is selected from the group consisting of: TAS2R receptor modulators, preferably TAS2R1, TAS2R4, TAS2R3, TAS2R5, TAS2R7, TAS2R8, TAS2R9, TAS2R10, TAS2R13, TAS2R14, TAS2R16, TAS2R38, TAS2R39, TAS2R40, and TAS2R41. TAS2R42, TAS2R43, TAS2R44, TAS2R45, TAS2R46, TAS2R47, TAS2R48, TAS2R49, TAS2R50 and / or TAS2R60 receptor modulators, more preferably TAS2R4, TAS2R7, TAS2R10, TAS2R14, TAS2R39, TAS2R40, TAS2R43, TAS2R44 and / or TAS2R46 receptor modulators.

[0017] Surprisingly, the experiment particularly demonstrated the involvement of the TAS2R14 receptor in cellular bitterness responses.

[0018] The use of compounds as defined above is particularly advantageous because preferably more than one receptor can be modulated by TAS2R receptor modulators.

[0019] TAS2R modulatory substances are preferably capable of modulating one or more TAS2R receptors. In the context of this invention, modulation is preferably understood as activation. Furthermore, the receptors preferably relate to human TAS2R receptors and / or to homologs that are actually present in the species.

[0020] A preferred embodiment of the present invention is the use as defined above, wherein the bitter substance is selected from the group consisting of: flavonoids, preferably naringin, neohesperidin, quercetin, quercetin glycoside, kaempferol glycoside, kaempferol glycoside ester, preferably kaempferol 3-O-(2'''-O-sinosyl-β-sophoroside); hydroxy fatty acids; saponins, preferably soybean saponins; glycoalkaloids, preferably solanine; bitter amino acids, preferably L-leucine, L- Isoleucine, L-valine, L-phenylalanine, L-arginine, L-tryptophan; bitter peptides, quinine, caffeine, humulone isomer, cucurbitacin E, artemisia annua, acesulfame K, acetaminophen, thiourea, aloe-emodin, allyl isothiocyanate, gentioside, D-amygynin, andrographolide, arbutin, agrarin, aristolochic acid, artemisia capillaris lactone, azathioprine, benzamide, benzoin, strychnine, camphor, caprolactam Caliprolol, rhamnocortine, chloramphenicol, chlorhexidine, chlorpheniramine, chloroquine, cypermethrin, colchicine, coumarin, crispolide, cromoglycine, cucurbitacin B, cyclohexylimide, dapsone, benzylammonium benzoate, dextromethorphan, dimethylformamide, diphenhydramine, difenidol, diphenylthiourea, divinyl sulfoxide, erythromycin, ethylpyrazine, N-ethylthiourea, N,N'-ethylidene thiourea, pholcaenekynediol, famotidine, flufenamic acid, Daphne odorin, fluoperidol, meadowsweet, hydrocortisone, 4-hydroxyanisole, limonene, methimazole, 4(6)-methyl-2-thiouracil, methylthiourea, noscapine, ophiopogonin, papaverine, ternolactone, Stephania tetrandra, 1,10-phenanthroline, phenethyl isothiocyanate, PTC, PROP, quassin, saccharin, D-salicylic acid, sinigrin, sodium benzoate, sodium cyclohexane, sodium thiocyanate, strychnine, tatridin B, thiamine, thujone (-)-α and yohimbine.

[0021] The use of compounds as defined above is particularly advantageous because the bitterness of a wide range of bitter substances can preferably be reduced, adjusted, and / or masked.

[0022] A preferred embodiment of the invention is the use as defined above, wherein the bitterness of proteins and / or products containing proteins is reduced, adjusted and / or masked.

[0023] The use of compounds as defined above is particularly beneficial for reducing, adjusting, and / or masking the bitter taste of proteins.

[0024] Proteins are preferably understood as: natural proteins or mixtures of proteins prepared or isolated from natural sources; or processed products of such natural proteins or mixtures of proteins comprising partial or complete hydrolysis. Therefore, in the context of this disclosure, proteins are also preferably understood to further comprise bitter byproducts or non-covalently bound secondary metabolites from said sources, peptides and / or amino acids from non-enzymatic or enzymatically partially or completely hydrolyzed proteins.

[0025] A preferred embodiment of the invention is the use as defined above, wherein the bitterness of quinine and / or products containing quinine is reduced, adjusted and / or masked.

[0026] The use of compounds as defined above is particularly beneficial for reducing, adjusting, and / or masking the bitter taste of quinine.

[0027] According to a second aspect of the invention, the stated objective is achieved by an extract comprising a compound according to formula (I):

[0028]

[0029] (I),

[0030] Wherein, the amount of the compound according to formula (I) in the extract is sufficient to reduce, adjust and / or mask the bitterness of a bitter substance or correspondingly one or more bitter substances, and / or wherein, in each case, the amount is in the range of 0.5 wt.% to 80 wt.%, preferably in the range of 1 wt.% to 65 wt.%, based on the total amount of the extract.

[0031] According to a preferred embodiment of the invention, an extract as defined above is particularly preferred, wherein the total amount of the compound according to formula (I) is sufficient to reduce bitterness by at least 10%, preferably 15%, and preferably at a significance level of 0.05% compared to the corresponding extract which does not contain the compound according to formula (I).

[0032] Bitterness is typically determined using various test concentrations of bitter compounds, such as quinine (2, 4, 6, 8, 10, and 12 mg / kg water) or caffeine (300, 400, 500, 600, 700, and 800 mg / kg water). Panel members rate bitterness on an unstructured scale ranging from 1% to 100%. Typically, panel members rate 10 mg / kg quinine as approximately 50% + / - 10%. Similar results were obtained for 500 mg / kg caffeine.

[0033] A preferred embodiment of the present invention is an extract as defined above, wherein the bitter substance is selected from the group consisting of: TAS2R receptor modulators, preferably TAS2R1, TAS2R4, TAS2R3, TAS2R5, TAS2R7, TAS2R8, TAS2R9, TAS2R10, TAS2R13, TAS2R14, TAS2R16, TAS2R38, TAS2R39, TAS2R40, and TAS2R41. TAS2R42, TAS2R43, TAS2R44, TAS2R45, TAS2R46, TAS2R47, TAS2R48, TAS2R49, TAS2R50 and / or TAS2R60 receptor modulators, more preferably TAS2R4, TAS2R7, TAS2R10, TAS2R14, TAS2R39, TAS2R40, TAS2R43, TAS2R44 and / or TAS2R46 receptor modulators.

[0034] Extracts as defined above are particularly advantageous because preferably more than one receptor can be modulated by TAS2R receptor modulators.

[0035] A preferred embodiment of the present invention is an extract as defined above, wherein the bitter substances are selected from the group consisting of: flavonoids, preferably naringin, neohesperidin, quercetin, quercetin glycoside, kaempferol glycoside, kaempferol glycoside ester, preferably kaempferol 3-O-(2'''-O-sinosyl-β-sophoroside); hydroxy fatty acids; saponins, preferably soybean saponins; glycoalkaloids, preferably solanine; bitter amino acids, preferably L-leucine, L... -Isoleucine, L-valine, L-phenylalanine, L-arginine, L-tryptophan; bitter peptides, quinine, caffeine, humulone isomer, cucurbitacin E, artemisia annua, acesulfame K, acetaminophen, thiourea, aloe-emodin, allyl isothiocyanate, gentioside, D-amygynol, andrographolide, arbutin, agrarin, aristolochic acid, artemisia capillaris lactone, azathioprine, benzamide, benzoin, strychnine, camphor, caprolactam Caliprolol, rhamnocortine, chloramphenicol, chlorhexidine, chlorpheniramine, chloroquine, cypermethrin, colchicine, coumarin, crispolide, cromoglycine, cucurbitacin B, cyclohexylimide, dapsone, benzylammonium benzoate, dextromethorphan, dimethylformamide, diphenhydramine, difenidol, diphenylthiourea, divinyl sulfoxide, erythromycin, ethylpyrazine, N-ethylthiourea, N,N'-ethylidene thiourea, pholcaenekynediol, famotidine, flufenamic acid, Daphne odorin, fluoperidol, meadowsweet, hydrocortisone, 4-hydroxyanisole, limonene, methimazole, 4(6)-methyl-2-thiouracil, methylthiourea, noscapine, ophiopogonin, papaverine, ternolactone, Stephania tetrandra, 1,10-phenanthroline, phenethyl isothiocyanate, PTC, PROP, quassin, saccharin, D-salicylic acid, sinigrin, sodium benzoate, sodium cyclohexane, sodium thiocyanate, strychnine, tatridin B, thiamine, thujone (-)-α and yohimbine.

[0036] Extracts as defined above are particularly advantageous because the bitterness of a wide range of bitter substances can preferably be reduced, adjusted, and / or masked.

[0037] A preferred embodiment of the invention is an extract as defined above, wherein the amount of the compound according to formula (I) in the extract is sufficient to reduce, adjust and / or mask the bitterness of proteins and / or products containing proteins.

[0038] Extracts as defined above are advantageous because, in particular, the bitter taste of proteins can be reduced, adjusted, and / or masked.

[0039] A preferred embodiment of the invention is an extract as defined above, wherein the amount of the compound according to formula (I) in the extract is sufficient to reduce, adjust and / or mask the bitterness of quinine and / or products containing quinine.

[0040] Extracts as defined above are advantageous because, in particular, the bitter taste of quinine is reduced, adjusted, and / or masked.

[0041] A preferred embodiment of the present invention is an extract as defined above, wherein the extract is an extract of the plant *Dracaena cochinchinensis*, preferably an extract of the resin of the plant *Dracaena cochinchinensis*.

[0042] Preferably, the extract is as defined above, wherein the extract is a crude extract prepared with ethanol (100% anhydrous ethanol or 96% azeotropic ethanol or 70% to 95% diluted ethanol) or ethyl acetate; and preferably wherein, prior to extraction, the resin is treated with hexane or another unipolar solvent (e.g., pentane, and liquid or supercritical propane, butane, or CO2) to remove lipophilic compounds such as fats; and preferably wherein the crude extract is dried, and preferably further separated or enriched by liquid-solid or liquid-liquid chromatography, more preferably by liquid-solid reversed-phase chromatography using a commonly used solvent system, preferably water, ethanol, methanol, acetonitrile, ethyl acetate, acetone, methyl tert-butyl ether, formic acid, acetic acid, or buffer salts; and preferably wherein the secondary enriched or purified extract may be dried again; and optionally wherein the extract may be recrystallized at each stage.

[0043] Extracts as defined above, preferably extracts obtained as described above, are advantageous because extracts of the plant *Dracaena cochinchinensis* have properties particularly suitable for reducing, adjusting, and / or masking bitterness impressions in the sense of this invention.

[0044] According to another aspect of the invention, the stated objective is achieved by a food or feed composition comprising: one or more bitter substances and a compound according to formula (I);

[0045] Or mixtures, preferably extracts as defined above, comprising compounds according to formula (I).

[0046]

[0047] (I),

[0048] Wherein, the amount of the compound according to formula (I) in the food or feed composition is sufficient to reduce, adjust and / or mask the bitterness of a bitter substance or correspondingly one or more bitter substances, and / or wherein, based on the total amount of the composition, the amount is in the range of 5 mg / kg to 250 mg / kg, more preferably in the range of 25 mg / kg to 150 mg / kg.

[0049] According to a preferred embodiment of the invention, a composition as defined above is particularly preferred, wherein the total amount of the compound according to formula (I) is sufficient to reduce bitterness by at least 10%, preferably 15%, and preferably at a significance level of 0.05% compared to a corresponding composition that does not contain the compound according to formula (I).

[0050] A preferred embodiment of the invention is a composition as defined above, wherein a bitter substance or correspondingly said bitter substance is selected from the group consisting of: TAS2R receptor modulators, preferably TAS2R1, TAS2R4, TAS2R3, TAS2R5, TAS2R7, TAS2R8, TAS2R9, TAS2R10, TAS2R13, TAS2R14, TAS2R16, TAS2R38, TAS2R39, TAS2R40, etc. S2R41, TAS2R42, TAS2R43, TAS2R44, TAS2R45, TAS2R46, TAS2R47, TAS2R48, TAS2R49, TAS2R50 and / or TAS2R60 receptor modulators, more preferably TAS2R4, TAS2R7, TAS2R10, TAS2R14, TAS2R39, TAS2R40, TAS2R43, TAS2R44 and / or TAS2R46 receptor modulators.

[0051] The composition as defined above is particularly advantageous because preferably more than one receptor can be modulated by the TAS2R receptor modulator.

[0052] A preferred embodiment of the present invention is a composition as defined above, wherein the bitter substance is selected from the group consisting of: flavonoids, preferably naringin, neohesperidin, quercetin, quercetin glycoside, kaempferol glycoside, kaempferol glycoside ester, preferably kaempferol 3-O-(2'''-O-sinosyl-β-sophoroside); hydroxy fatty acids, saponins, preferably soybean saponins; glycoalkaloids, preferably solanine; bitter amino acids, preferably L-leucine, L... -Isoleucine, L-valine, L-phenylalanine, L-arginine, L-tryptophan; bitter peptides, quinine, caffeine, humulone isomer, cucurbitacin E, artemisia annua, acesulfame K, acetaminophen, thiourea, aloe-emodin, allyl isothiocyanate, gentioside, D-amygynol, andrographolide, arbutin, agrarin, aristolochic acid, artemisia capillaris lactone, azathioprine, benzamide, benzoin, strychnine, camphor, caprolactam Caliprolol, rhamnocortine, chloramphenicol, chlorhexidine, chlorpheniramine, chloroquine, cypermethrin, colchicine, coumarin, crispolide, cromoglycine, cucurbitacin B, cyclohexylimide, dapsone, benzylammonium benzoate, dextromethorphan, dimethylformamide, diphenhydramine, difenidol, diphenylthiourea, divinyl sulfoxide, erythromycin, ethylpyrazine, N-ethylthiourea, N,N'-ethylidene thiourea, pholcaenekynediol, famotidine, flufenamic acid, Daphne odorin, fluoperidol, meadowsweet, hydrocortisone, 4-hydroxyanisole, limonene, methimazole, 4(6)-methyl-2-thiouracil, methylthiourea, noscapine, ophiopogonin, papaverine, ternolactone, Stephania tetrandra, 1,10-phenanthroline, phenethyl isothiocyanate, PTC, PROP, quassin, saccharin, D-salicylic acid, sinigrin, sodium benzoate, sodium cyclohexane, sodium thiocyanate, strychnine, tatridin B, thiamine, thujone (-)-α and yohimbine.

[0053] The compositions defined above are particularly advantageous because the bitterness of a wide range of bitter substances is preferably reduced, adjusted, and / or masked.

[0054] A preferred embodiment of the invention is a composition as defined above, wherein the composition is a product comprising protein and / or containing quinine, preferably wherein the protein is selected from the group consisting of: proteins derived from whey, soybean, pea, broad bean, lentil, rapeseed, lupin, potato, wheat, chickpea, quinoa, millet / sorghum, legumes, other legumes, algae, fungi, yeast, and bacteria.

[0055] Compositions as defined above are advantageous because, in particular, the bitter impressions of proteins and / or quinine are reduced, adjusted, and / or masked.

[0056] According to another aspect of the invention, the stated objective is achieved by a method for producing a bitterness-reducing product comprising: a compound according to formula (I), preferably a compound as defined above.

[0057]

[0058] (I);

[0059] Or an extract comprising a compound according to formula (I), preferably an extract as defined above.

[0060]

[0061] (I);

[0062] Or a composition comprising a compound according to formula (I), preferably a composition as defined above.

[0063]

[0064] (I),

[0065] The method includes the following steps:

[0066] (a) Provide a compound, mixture (e.g., extract) or corresponding composition according to formula (I) as defined above,

[0067] (b) Add the component provided in step (a) to the product for which bitterness is to be reduced, preferably in an amount sufficient to reduce, adjust and / or mask the bitterness of one or more bitter substances in the product.

[0068] Preferably, the method further includes the step of: prior to adding component (a) to the product, assessing the amount of component (a) suitable for the purposes of the invention, i.e., the amount used to reduce, adjust and / or mask the bitter impression of one or more bitter substances in the product.

[0069] In view of the above preferred embodiments and in conjunction with other aspects of the invention, other preferred embodiments of this method become apparent.

[0070] The invention will now be described in more detail with reference to embodiments. Further aspects of the invention are disclosed in the appended claims. Attached Figure Description

[0071] Figure 1The effects of quinine [10 ppm] and ethyl acetate extract of draco (DD) [100 ppm] on proton secretion in HGT-1 wild-type cells were shown. Significance was tested using Student's t-test, **** ... p≤0.001. Quinine [10 ppm] induced proton secretion compared to control-treated cells (KRHB) (p<0.05). Data are presented as mean ± SEM, n=4, tr=4–6. AUC was calculated based on intracellular proton index (IPX) and compared to quinine-treated cells (C(control) = 0.00).

[0072] Figure 2 The effects of quinine [10 ppm] and compound according to formula (I) (DMDHE) [100 ppm] on proton secretion in HGT-1 wild-type (wt) cells and TAS2R14 knockout cells were shown. Cells treated with both incubators were significantly different from the control by ANOVA assay; furthermore, significant differences between these incubators are indicated by (*) (p ≤ 0.05). Data are presented as mean ± SEM, n = 3, tr = 4–6. AUC was calculated based on intracellular proton index (IPX) and compared with the control (= quinine). Detailed Implementation

[0073] Example

[0074] 1) Extracting compounds according to formula (I) from dragon's blood (dragon's blood).

[0075] The resinous secretions from the fruit of *Dracaena cochinchinensis* were dissolved in pure ethanol and filtered to remove particles. The ethanol was removed, and the resin was dissolved in dichloromethane, loaded onto a solid-phase material, and eluted sequentially with n-hexane, ethyl acetate (ethyl acetate extract of *Dracaena cochinchinensis*), and finally with 95% ethanol (ethanol extract of *Dracaena cochinchinensis*).

[0076] Preparative column chromatography of ethyl acetate extract of *Dracaena cochinchinensis*:

[0077] Preparative column chromatography was performed on a C18 5 µm 100 A 250 × 21.2 mm (Luna, AXIA Pack First, Phenomenex) column using a P2.1L HPLC system (Knauer) equipped with a 20 °C column oven (Jetstream), a fraction collector (Foxy R1), and a UV detector (S2600, Knauer). The sample was loaded onto the column at a 250 µL volume, and separation was performed using a water / acetonitrile gradient of 60 / 40 for 2 min, followed by a changeover to 35 / 65 over 18 min, then 30 / 70 over 25 min, and finally 5 / 95 over 28 min. Acetonitrile was removed by rotary evaporation, and the remaining aqueous phase was lyophilized. Fine fractionation was performed using the same system equipped with a 5 µm 100 A 250 × 21.2 mm silica column (Luna, AXIA, Phenomenex) using a hexane / ethyl acetate gradient: the hexane concentration was reduced from 55% to 50% over 18 minutes, further to 40% over another 7 minutes, and further to 5% over another 3 minutes, and held at 5% hexane / 95% ethyl acetate for 6 minutes, yielding a total fraction of 172 mg. The major component, having an area percentage of 65% and a molecular weight of 286, was further characterized by NMR according to GC-MS and designated as a compound according to formula (I).

[0078] The spectra and spectroscopic data of the compounds according to formula (I):

[0079] 2,3-Dihydro-5,7-Dihydroxy-3-[(4-hydroxyphenyl)methyl]-4H-1-benzopyran-4-one (mass 286, C16H14O5, common name 4'-demethyl-3,9-dihydroeucomin): 1 H NMR (600 MHz, DMSO) δ 12.17 (s, 1H), 7.05 – 7.00 (m, 2H), 6.72 – 6.67 (m, 2H), 5.88 (d, J = 2.2 Hz, 1H), 5.86 (d, J = 2.1 Hz, 1H), 4.25 (dd, J = 11.4, 4.5Hz, 1H), 4.07 (dd, J = 11.4, 8.1 Hz, 1H), 3.00 (dd, J = 13.9, 5.0 Hz, 1H), 2.95 (ddt, J = 9.5, 8.1, 4.7 Hz, 1H), 2.58 (dd, J = 13.9, 9.5 Hz, 1H);13 C NMR(151 MHz, DMSO) δ 197.83, 166.56, 163.79, 162.82, 155.89, 129.93, 128.04,115.26, 101.26, 95.91, 94.73, 68.85, 45.59, 39.94, 39.80, 39.66, 39.52,39.38, 39.24, 39.10, 31.16.

[0080] 2) Human sensory testing

[0081] For each test, trained teams were given two samples: one containing the bitter substance quinine (10 mg / kg in water), and the other containing a potential bitter masking substance or mixture. During the test, team members wore nose clips to eliminate any olfactory impressions. Samples with 3-digit codes were provided in a sensory chamber with yellow-red light. Team members were asked to rate the bitterness intensity on a scale of 0%–100%. Data were recorded and statistically analyzed using Eyequestion 4 and Logic8 BV.

[0082] Paired-component sensory tests showed that the ethyl acetate extract of draco (500 ppm) exhibited significant bitterness masking properties, achieving a reduction of -33.0% (p≤0.000). Furthermore, for fractions of the draco vinyl acetate extract containing compounds according to formula (I), a bitterness masking activity of 27.1% was detected (p≤0.000) (Table 1).

[0083] Table 1: Sensory studies. Paired comparative sensory tests of the selected dragon's blood components against the bitterness of quinine (10 ppm).

[0084]

[0085] *Reference Material

[0086] Further experiments were conducted using caffeine as a bittering substance, which showed that bitterness was reduced by applying the compound of formula (I) (Table 2).

[0087] Table 2: Sensory studies. Paired sensory tests of caffeine with and without compounds according to formula (I).

[0088]

[0089] 3) In vitro cell assay

[0090] The effects of quinine [10 ppm] and ethyl acetate extract of draco [100 ppm] on proton secretion in HGT-1 wild-type cells were tested. Figure 1 Cell-based studies show that: compared with quinine [10 ppm] (AUC) 0-30分钟 Compared to -0.22±0.20 (p≤0.001), the reaction was altered after co-incubation of quinine [10 ppm] with the ethyl acetate extract of damselfish resin [100 ppm] (AUC). 0-30分钟 (2.26±0.62). The anti-secretion effect indicates that the extract of *Dracaena cochinchinensis* has the ability to mask the bitterness of quinine.

[0091] The effects of quinine [10 ppm] and the compound according to formula (I) (DMDHE) [100 ppm] on proton secretion in HGT-1 wild-type (wt) cells and TAS2R14 knockout cells were further investigated. Figure 2 The combination of compound (I) [100 ppm] and quinine [10 ppm] according to formula (AUC) 0-30分钟 (58.82±1.77) and quinine alone (AUC) 0-30分钟 Compared to HGT-1 wt cells (AUC: -0.36±0.60), it reduced cellular response. Furthermore, compared to HGT-1 wt cells (AUC: -0.36±0.60), it reduced cellular response. 0-30分钟 Compared to HGT-1 TAS2R14ko cells (AUC 58.82±1.77, p≤0.01), the AUC 58.82±1.77 was significantly lower. 0-30分钟 The response in (46.36±3.88) was altered, indicating that the bitter taste receptor TAS2R14 is involved in the DMDHE-mediated cellular response. These data are consistent with the sensory data presented above, suggesting that DMDHE is a bitter taste masking compound.

[0092] 4) Food or feed compositions

[0093] Taste Improvement of Vegan Patties: Vegan patties have been produced using the following ingredients: water, legume protein isolate, sunflower oil, legume protein concentrate, coconut oil, methylcellulose, fiber, salt, starch, lactic acid, and sodium diacetate. Water, thickener, and starch are mixed with water, the pH is adjusted, then protein is added, followed by fiber and oil components. Finally, flavor masking ingredients according to Table 3 are added. The ingredients are thoroughly mixed, and the dough is shaped into patties. The patties are baked in an oven at 200°C. After cooling, the patties are sliced, and samples are coded for blind tasting by a panel.

[0094] Table 3: Sensory characteristics of vegan meat patties with compounds according to formula (I) compared to a control without a bitterness masking agent.

[0095]

Claims

1. Use of a compound according to formula (I) or a mixture comprising a compound according to formula (I) for reducing, adjusting, and / or masking the bitterness impression of one or more bitter substances. （I）。 2. The use according to claim 1, wherein, The bitter substances are selected from the group consisting of: TAS2R receptor modulators, preferably TAS2R1, TAS2R4, TAS2R3, TAS2R5, TAS2R7, TAS2R8, TAS2R9, TAS2R10, TAS2R13, TAS2R14, TAS2R16, TAS2R38, TAS2R39, TAS2R40, TAS2R41, TAS2R42, and TAS2R... 43, TAS2R44, TAS2R45, TAS2R46, TAS2R47, TAS2R48, TAS2R49, TAS2R50 and / or TAS2R60 receptor modulators, more preferably TAS2R4, TAS2R7, TAS2R10, TAS2R14, TAS2R39, TAS2R40, TAS2R43, TAS2R44 and / or TAS2R46 receptor modulators.

3. The use according to claim 1 or 2, wherein, The bitter substances are selected from the group consisting of: flavonoids, preferably naringin, neohesperidin, quercetin, quercetin glycoside, kaempferol glycoside, kaempferol glycoside ester, preferably kaempferol 3-O-(2'''-O-sinosyl-β-sophoroside); hydroxy fatty acids; saponins, preferably soybean saponins; glycoalkaloids, preferably solanine; bitter amino acids, preferably L-leucine, L-isoleucine, L-valine, L-phenylalanine, L- Arginine, L-tryptophan; bitter peptides, quinine, caffeine, humulone isomer, cucurbitacin E, artemisia annua, acesulfame K, acetaminophen, thiourea, aloe-emodin, allyl isothiocyanate, gentioside, D-amygynin, andrographolide, arbutin, agrarin, aristolochic acid, artemisia capillaris lactone, azathioprine, benzamide, benzoin, strychnine, camphor, caprolactam, carboplatin, rhamnosine, chloramphenicol Chlorhexidine, chlorpheniramine, chloroquine, cypermethrin, colchicine, coumarin, crispolide, cromoglycine, cucurbitacin B, cyclohexylimide, dapsone, benzylammonium benzoate, dextromethorphan, dimethylformamide, diphenhydramine, difenidol, diphenylthiourea, divinyl sulfoxide, erythromycin, ethylpyrazine, N-ethylthiourea, N,N'-ethylidene thiourea, folicaene diol, famotidine, flufenamic acid, baicalein, fluorine Piperidinol, meadowsweet, hydrocortisone, 4-hydroxyanisole, limonene, methimazole, 4(6)-methyl-2-thiouracil, methylthiourea, noscapine, ophiopogonin, papaverine, ternolactone, tebufenozide, 1,10-phenanthroline, phenethyl isothiocyanate, PTC, PROP, quassin, saccharin, D-salicylic acid, sinigrin, sodium benzoate, sodium cyclohexane, sodium thiocyanate, strychnine, tatridin B, thiamine, thujone (-)-α and yohimbine.

4. The use according to any one of claims 1 to 3, wherein, The bitterness of proteins and / or products containing proteins can be reduced, adjusted, and / or masked.

5. The use according to any one of claims 1 to 4, wherein, The bitterness of quinine and / or products containing quinine can be reduced, adjusted, and / or masked.

6. An extract comprising a compound according to formula (I) （I）， in, The amount of the compound according to formula (I) in the extract is sufficient to reduce, adjust and / or mask the bitterness of a bitter substance or correspondingly one or more bitter substances, and / or wherein, in each case, the amount is in the range of 0.5 wt.% to 80 wt.%, preferably in the range of 1 wt.% to 65 wt.%, based on the total amount of the extract.

7. The extract according to claim 6, wherein, The bitter substances are selected from the group consisting of: TAS2R receptor modulators, preferably TAS2R1, TAS2R4, TAS2R3, TAS2R5, TAS2R7, TAS2R8, TAS2R9, TAS2R10, TAS2R13, TAS2R14, TAS2R16, TAS2R38, TAS2R39, TAS2R40, TAS2R41, TAS2R42, and TAS2R... 43, TAS2R44, TAS2R45, TAS2R46, TAS2R47, TAS2R48, TAS2R49, TAS2R50 and / or TAS2R60 receptor modulators, more preferably TAS2R4, TAS2R7, TAS2R10, TAS2R14, TAS2R39, TAS2R40, TAS2R43, TAS2R44 and / or TAS2R46 receptor modulators.

8. The extract according to claim 6 or 7, wherein, The bitter substances are selected from the group consisting of: flavonoids, preferably naringin, neohesperidin, quercetin, quercetin glycoside, kaempferol glycoside, kaempferol glycoside ester, preferably kaempferol 3-O-(2'''-O-sinosyl-β-sophoroside); hydroxy fatty acids; saponins, preferably soybean saponins; glycoalkaloids, preferably solanine; bitter amino acids, preferably L-leucine, L-isoleucine, L-valine, L-phenylalanine, L- Arginine, L-tryptophan; bitter peptides, quinine, caffeine, humulone isomer, cucurbitacin E, artemisia annua, acesulfame K, acetaminophen, thiourea, aloe-emodin, allyl isothiocyanate, gentioside, D-amygynin, andrographolide, arbutin, agrarin, aristolochic acid, artemisia capillaris lactone, azathioprine, benzamide, benzoin, strychnine, camphor, caprolactam, carboplatin, rhamnosine, chloramphenicol Chlorhexidine, chlorpheniramine, chloroquine, cypermethrin, colchicine, coumarin, crispolide, cromoglycine, cucurbitacin B, cyclohexylimide, dapsone, benzylammonium benzoate, dextromethorphan, dimethylformamide, diphenhydramine, difenidol, diphenylthiourea, divinyl sulfoxide, erythromycin, ethylpyrazine, N-ethylthiourea, N,N'-ethylidene thiourea, folicaene diol, famotidine, flufenamic acid, baicalein, fluorine Piperidinol, meadowsweet, hydrocortisone, 4-hydroxyanisole, limonene, methimazole, 4(6)-methyl-2-thiouracil, methylthiourea, noscapine, ophiopogonin, papaverine, ternolactone, tebufenozide, 1,10-phenanthroline, phenethyl isothiocyanate, PTC, PROP, quassin, saccharin, D-salicylic acid, sinigrin, sodium benzoate, sodium cyclohexane, sodium thiocyanate, strychnine, tatridin B, thiamine, thujone (-)-α and yohimbine.

9. The extract according to any one of claims 6 to 8, wherein, The amount of the compound of formula (I) in the extract is sufficient to reduce, adjust and / or mask the bitterness of proteins and / or products containing proteins.

10. The extract according to any one of claims 6 to 9, wherein, The amount of the compound of formula (I) in the extract is sufficient to reduce, adjust and / or mask the bitterness of quinine and / or products containing quinine.

11. The extract according to any one of claims 6 to 10, wherein, The extract is an extract of the plant *Dracaena cochinchinensis*, preferably an extract of the resin of the plant *Dracaena cochinchinensis*.

12. A food or feed composition comprising: one or more bitter substances and a compound according to formula (I); Or mixtures, preferably extracts according to any one of claims 6 to 11, comprising compounds according to formula (I). （I）， in, The amount of the compound according to formula (I) in the food or feed composition is sufficient to reduce, adjust and / or mask the bitterness of a bitter substance or correspondingly one or more bitter substances, and / or wherein, based on the total amount of the composition, the amount is in the range of 5 mg / kg to 250 mg / kg, more preferably in the range of 25 mg / kg to 150 mg / kg.

13. The composition according to claim 12, wherein, A bitter substance, or correspondingly, said bitter substance, is selected from the group consisting of: TAS2R receptor modulators, preferably TAS2R1, TAS2R4, TAS2R3, TAS2R5, TAS2R7, TAS2R8, TAS2R9, TAS2R10, TAS2R13, TAS2R14, TAS2R16, TAS2R38, TAS2R39, TAS2R40, TAS2R41, and TAS2R42. TAS2R43, TAS2R44, TAS2R45, TAS2R46, TAS2R47, TAS2R48, TAS2R49, TAS2R50 and / or TAS2R60 receptor modulators, more preferably TAS2R4, TAS2R7, TAS2R10, TAS2R14, TAS2R39, TAS2R40, TAS2R43, TAS2R44 and / or TAS2R46 receptor modulators.

14. The composition according to claim 12 or 13, wherein, The bitter substances are selected from the group consisting of: flavonoids, preferably naringin, neohesperidin, quercetin, quercetin glycoside, kaempferol glycoside, kaempferol glycoside ester, preferably kaempferol 3-O-(2'''-O-sinosyl-β-sophoroside); hydroxy fatty acids; saponins, preferably soybean saponins; glycoalkaloids, preferably solanine; bitter amino acids, preferably L-leucine, L-isoleucine, L-valine, L-phenylalanine, L- Arginine, L-tryptophan; bitter peptides, quinine, caffeine, humulone isomer, cucurbitacin E, artemisia annua, acesulfame K, acetaminophen, thiourea, aloe-emodin, allyl isothiocyanate, gentioside, D-amygynin, andrographolide, arbutin, agrarin, aristolochic acid, artemisia capillaris lactone, azathioprine, benzamide, benzoin, strychnine, camphor, caprolactam, carboplatin, rhamnosine, chloramphenicol Chlorhexidine, chlorpheniramine, chloroquine, cypermethrin, colchicine, coumarin, crispolide, cromoglycine, cucurbitacin B, cyclohexylimide, dapsone, benzylammonium benzoate, dextromethorphan, dimethylformamide, diphenhydramine, difenidol, diphenylthiourea, divinyl sulfoxide, erythromycin, ethylpyrazine, N-ethylthiourea, N,N'-ethylidene thiourea, folicaene diol, famotidine, flufenamic acid, baicalein, fluorine Piperidinol, meadowsweet, hydrocortisone, 4-hydroxyanisole, limonene, methimazole, 4(6)-methyl-2-thiouracil, methylthiourea, noscapine, ophiopogonin, papaverine, ternolactone, tebufenozide, 1,10-phenanthroline, phenethyl isothiocyanate, PTC, PROP, quassin, saccharin, D-salicylic acid, sinigrin, sodium benzoate, sodium cyclohexane, sodium thiocyanate, strychnine, tatridin B, thiamine, thujone (-)-α and yohimbine.

15. The composition according to any one of claims 12 to 14, wherein, The composition is a product containing protein and / or a product containing quinine, preferably wherein the protein is selected from the group consisting of: proteins derived from whey, soybean, pea, broad bean, lentil, rapeseed, lupin, potato, wheat, chickpea, quinoa, millet / sorghum, legumes, other legumes, algae, fungi, yeast, and bacteria.

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