Application of dihydromyricetin in the preparation of drugs for the prevention and / or treatment of poxvirus infection

Abstract

The application provides application of dihydromyricetin in preparation of a medicine for preventing and / or treating poxvirus infection. Dihydromyricetin effectively combines with a bispecific phosphatase coded by a poxvirus and inhibits in-vitro enzyme activity of the bispecific phosphatase, has obvious inhibiting effect on the poxvirus, and can be used for preparing the medicine for preventing and / or treating poxvirus infection. Further, a medicine composition with dihydromyricetin as an active ingredient can also be used for preparing the medicine for preventing and / or treating poxvirus infection.

Description

Technical Field

[0001] This invention relates to the fields of veterinary medicine and pharmaceutical technology, and in particular to the use of dihydromyricetin in the preparation of medicaments for the prevention and / or treatment of infections with multiple poxvirus family members. Background Technology

[0002] Poxviruses are an ancient and large family of viruses, including smallpox virus, vaccinia virus, cowpox virus, monkeypox virus, contagious pustular ovine virus, bovine papular stomatitis virus, sheep pox virus, bovine nodular dermatosis virus, swine pox virus, fowlpox virus, and many other poxviruses that are related to humans and animals. Many of these members are zoonotic, and infection in humans and animals often results in localized or systemic purulent skin lesions. They are important pathogens that seriously affect public health and safety and have attracted considerable attention.

[0003] Ovine contagious pustular virus (ORFV) is a representative species of the genus Parapoxvirus in the family Poxviridae. It primarily infects small and medium-sized ruminants such as sheep and goats, and occasionally wild cloven-toed mammals such as musk oxen, moose, reindeer, and camels. Infected animals are characterized by proliferative lesions on the skin / mucous membranes of the lips, gums, eyelids, perinasal area, ears, coronary band, tail base, and udder, including pustules, ulcers, and verrucous scabs. Clinically, infected animals experience feeding difficulties, leading to decreased growth / reproductive performance and even death, causing economic losses to the sheep farming industry. Humans can also become infected through direct or indirect contact with infected sheep, posing a potential occupational risk. Herders, veterinarians, butchers, feeders, and fur processors are particularly susceptible to infection. ORFV is widely distributed in sheep flocks in sheep-farming countries and regions worldwide, and outbreaks are frequent, severely hindering the development of the sheep farming industry and related sectors.

[0004] Protein phosphorylation mediated by protein kinases and phosphatases is the most prevalent, fundamental, and important mechanism for regulating and controlling the activity and function of proteins and enzymes. Protein phosphorylation and dephosphorylation modifications play a crucial role in the viral replication cycle by regulating the function of viral proteins; the poxvirus life cycle is also regulated by its own protein phosphorylation and dephosphorylation network. Bispecific phosphatases (vDUSPs) are widely distributed among members of the poxviridae family. They regulate viral transcription, influence viral particle morphogenesis, and interfere with the host's immune response by phosphorylating specific viral and cellular substrate tyrosine and serine residues, and dephosphorylating threonine residues. Given the critical role of bispecific phosphatases in the poxvirus life cycle, they are considered ideal targets for novel anti-poxvirus agents.

[0005] Previous studies have shown that dihydromyricetin has antioxidant, anti-inflammatory, anti-tumor, and liver-protective effects, but other pharmacological effects of dihydromyricetin are still unclear. Summary of the Invention

[0006] The purpose of this invention is to provide a novel application of dihydromyricetin in the preparation of drugs for the prevention and / or treatment of poxvirus infections. The research of this invention has revealed that dihydromyricetin can effectively inhibit the activity of poxvirus bispecific phosphatases, thereby enabling its use in the prevention and / or treatment of poxvirus infections, and further in the preparation of drugs for the prevention and / or treatment of poxvirus infections.

[0007] This invention provides, in one aspect, the use of dihydromyricetin in the preparation of medicaments for the prevention and / or treatment of poxvirus infections. Preferably, the poxvirus is a common poxvirus found in humans, livestock, and poultry, including at least one of ovine infectious pustular virus (ORFV), monkeypox virus (MPXV), sheep poxvirus (SPPV), bovine nodular dermatosis virus (LSDV), fowlpox virus (FWPV), goat poxvirus (GTPV), vaccinia virus (VACV), or swine poxvirus.

[0008] This application also provides a pharmaceutical composition for the prevention and / or treatment of poxvirus infection, comprising dihydromyricetin as the active ingredient. Preferably, the poxvirus is a common poxvirus found in humans, livestock, and poultry, including at least one of ovine infectious pustular virus (ORFV), monkeypox virus (MPXV), sheep poxvirus (SPPV), bovine nodular dermatosis virus (LSDV), fowlpox virus (FWPV), goat poxvirus (GTPV), vaccinia virus (VACV), or swine poxvirus.

[0009] Dihydromyricetin can effectively inhibit the activity of poxvirus bispecific phosphatase, thus enabling its use in the prevention and / or treatment of poxvirus infection, and consequently in the preparation of drugs for the prevention and / or treatment of poxvirus infection. Furthermore, pharmaceutical compositions containing dihydromyricetin can also be used to prepare drugs for the prevention and / or treatment of poxvirus infection.

[0010] To achieve the above objectives, the present invention provides the use of dihydromyricetin in the preparation of drugs for the prevention and / or treatment of poxvirus infection.

[0011] Preferably, the poxvirus includes at least one of sheep infectious pustular virus (ORFV), monkeypox virus (MPXV), sheep pox virus (SPPV), bovine nodular dermatosis virus (LSDV), fowlpox virus (FWPV), goatpox virus (GTPV), cowpox virus (VACV), or swine pox virus.

[0012] Preferably, dihydromyricetin inhibits the activity of the poxvirus bispecific phosphatase. Dihydromyricetin prevents and / or treats poxvirus infection by inhibiting the activity of the poxvirus bispecific phosphatase.

[0013] Preferably, the effective concentration of dihydromyricetin is greater than 0.1 μM, more preferably 0.1 μM to 100 μM. More preferably, it is 0.1, 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 μM and the range thereof.

[0014] Furthermore, the preferred concentration of dihydromyricetin for inhibiting the bispecific phosphatase of ovine infectious pustular virus is 0.1 μM to 100 μM, more preferably 0.1, 1, 10, 100 μM and the range thereof. Furthermore, the half-maximal effective concentration (IC50) of dihydromyricetin against the bispecific phosphatase of ovine infectious pustular virus is... 50 The concentration was 8.29 ± 1.06 μM. Furthermore, the half-maximal effective concentration (IC50) of dihydromyricetin against ovine infectious pustular virus was... 50 The value was 11.59 ± 1.79 μM.

[0015] Furthermore, the inhibitory concentration of dihydromyricetin against monkeypox virus bispecific phosphatase is 0.1 μM to 100 μM, more preferably 0.1, 1, 10, 100 μM and the range thereof. Furthermore, the half-maximal effective concentration (IC50) of dihydromyricetin against monkeypox virus bispecific phosphatase is... 50 The value was 11.09 ± 0.19 μM.

[0016] Furthermore, the preferred concentration of dihydromyricetin for inhibiting vaccinia virus bispecific phosphatase is 0.1 μM to 100 μM, more preferably 0.1, 1, 10, 100 μM and the range thereof. Furthermore, the half-maximal effective concentration (IC50) of dihydromyricetin against vaccinia virus bispecific phosphatase is... 50 The value was 7.31 ± 0.30 μM.

[0017] Furthermore, the preferred concentration of dihydromyricetin for inhibiting the bispecific phosphatase of sheep pox virus is 0.1 μM to 100 μM, more preferably 0.1, 1, 10, 100 μM and the range thereof. Furthermore, the half-maximal effective concentration (IC50) of dihydromyricetin against the bispecific phosphatase of sheep pox virus is... 50 The value was 28.37 ± 2.42 μM.

[0018] Furthermore, the preferred concentration of dihydromyricetin against bovine papular stomatitis virus bispecific phosphatase is 0.1 μM to 100 μM, more preferably 0.1, 1, 10, 100 μM and the range thereof. Furthermore, the half-maximal effective concentration (IC50) of dihydromyricetin against bovine papular stomatitis virus bispecific phosphatase is... 50 The value was 14.67 ± 2.40 μM.

[0019] The present invention also provides a pharmaceutical composition for the prevention and / or treatment of poxvirus infection, the pharmaceutical composition comprising dihydromyricetin.

[0020] Preferably, the pharmaceutical composition contains the active pharmaceutical ingredient dihydromyricetin, which is provided in monomeric form or in the form of a plant extract containing dihydromyricetin.

[0021] Preferably, the plant extract is derived from at least one of vine tea extract and Japanese raisin tree extract.

[0022] Preferably, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier and / or excipient.

[0023] Preferably, the pharmaceutically acceptable carrier and / or excipient is selected from at least one of solvents, diluents, disintegrants, flow aids, binders, lubricants, dispersants, suspending agents, isotonic agents, stabilizers, hydrating agents, emulsification accelerators, buffers, absorbents, release agents, coating agents, or antioxidants.

[0024] Preferably, the solvent includes distilled water, glycerol, dimethyl sulfoxide, ethanol, propylene glycol, polyethylene glycol, fatty oil, etc.

[0025] Preferably, the diluent includes starch, sucrose, dextrin, pregelatinized starch, mannitol, etc.

[0026] Preferably, the disintegrant includes microcrystalline cellulose, sodium carboxymethyl starch, crospovidone, etc.

[0027] Preferably, the flow aid includes micronized silica gel, talc, etc.

[0028] Preferably, the adhesive comprises carboxymethyl cellulose, gelatin, polyvinylpyrrolidone, povidone, starch paste, etc.

[0029] Preferably, the lubricant comprises sodium fumarate stearate, magnesium stearate, talc, hexagonal boron nitride, sodium benzoate, etc.

[0030] Preferably, the dispersant includes sodium pyrophosphate, sodium tripolyphosphate, polyoxyethylene alkylphenol ether, etc.

[0031] Preferably, the suspending agent includes glycerin, syrup, sorbitol, gum arabic, tragacanth gum, sodium alginate, methylcellulose, etc.

[0032] Preferably, the isotonic agent described above includes sodium chloride, glucose, glycerin, boric acid, borax, etc.

[0033] Preferably, the wetting agent includes polysorbate, polyoxyethylene castor oil, poloxamer, etc.

[0034] Preferably, the emulsifier includes fatty acids, sorbitan fatty acids, monoglycerides, lanolin, sodium lauryl sulfate, etc.

[0035] Preferably, the buffer includes acetic acid, sodium acetate, citric acid, sodium citrate, tartaric acid, sodium tartrate, lactic acid, disodium hydrogen phosphate, sodium dihydrogen phosphate, etc.

[0036] Preferably, the antioxidant includes sodium sulfite, sodium bisulfite, tert-butyl-p-hydroxyanisole, etc.

[0037] Preferably, the pharmaceutical composition is formulated as any one of the following dosage forms: powder, tablet, pill, emulsion, drop pill, capsule, suspension, or tincture. Attached Figure Description

[0038] Figure 1 The curves showing the inhibition rates of different concentrations of dihydromyricetin against the bispecific phosphatase of ovine infectious pustular virus in preferred embodiment 2 of the present invention.

[0039] Figure 2 The inhibition rate curves of different concentrations of dihydromyricetin against monkeypox virus bispecific phosphatase in preferred embodiment 2 of the present invention are shown.

[0040] Figure 3 The inhibition rate curves of different concentrations of dihydromyricetin against vaccinia virus bispecific phosphatase in preferred embodiment 2 of the present invention are shown.

[0041] Figure 4 The inhibition rate curves of different concentrations of dihydromyricetin against sheep pox virus bispecific phosphatase in preferred embodiment 2 of the present invention are shown.

[0042] Figure 5 The inhibition rate curves of different concentrations of dihydromyricetin against bovine papular stomatitis virus bispecific phosphatase in preferred embodiment 2 of the present invention are shown.

[0043] Figure 6 This invention relates to the preferred embodiment 3, which involves the determination of the toxicity of different concentrations of dihydromyricetin to OFTU cells.

[0044] Figure 7 The preferred embodiment of the present invention, 3, illustrates the inhibitory effect of different concentrations of dihydromyricetin on ovine infectious pustular virus. Detailed Implementation

[0045] The present invention will be described more clearly and completely through the following embodiments, but the described embodiments are only some embodiments of this application, and not all embodiments. The embodiments are provided to help understand the present invention and should not be construed as limiting the scope of protection of the present invention.

[0046] This invention does not impose any particular limitations on the extraction methods of *Curcuma longa* extract and *Hovenia dulcis* extract. Technicians can use existing techniques for extraction, all of which are applicable to this invention. Exemplary extraction methods include, but are not limited to: reflux extraction of *Curcuma longa* and / or *Hovenia dulcis* using n-butanol or ethanol; or, hot water extraction of *Curcuma longa* and / or *Hovenia dulcis* to obtain *Curcuma longa* extract and / or *Hovenia dulcis* extract containing dihydromyricetin.

[0047] The pharmaceutical composition of this invention, at a pharmaceutically acceptable dose of dihydromyricetin, i.e., the administration dose, can be varied based on the age / months of the subject, sex and weight, the specific disease or pathological state to be treated, the severity of the disease or pathological state, the route of administration, and the diagnostic assessment. Taking these factors into consideration, the administration dose is generally determined to be 0.01-1000 mg / kg / day, specifically 1-100 mg / kg / day. However, the scope of this disclosure is not limited in any way to the stated administration dose.

[0048] The present application will be described in detail below with reference to specific embodiments.

[0049] Dihydromyricetin (CAS No.: 27200-12-0) was purchased from Chengdu Ruifenside Biotechnology Co., Ltd. Its structural formula is as follows:

[0050]

[0051] Sources of materials used in the embodiments:

[0052] Virus and Cells: ORFV-SY17 (GenBank: MG712417.1) strain, which is a publicly disclosed strain in the prior art and can be obtained by the public through literature resource sharing; OFTu immortalized cells (sheep nasal turbinate bone immortalized cell line OFTu, CCTCC NO: C2022191) were prepared, constructed, and identified by our laboratory and are deposited at the China Center for Type Culture Collection (Wuhan, China). The culture was received by the collection on June 23, 2022 and registered; the collection completed the viability test of the culture on June 27, 2022, and the result was positive; deposit address: Wuhan University, Wuhan, China; telephone: 027-68752319.

[0053] Reagents: The CCK-8 reagent kit (Cell Counting Kit-8) was purchased from Meilun Biotechnology Co., Ltd., and fetal bovine serum was purchased from Biological Industries, Israel. All other reagents not mentioned in this invention are commercially available products.

[0054] Example 1

[0055] Example 1 demonstrates the inhibitory effect of dihydromyricetin on poxvirus bispecific phosphatase.

[0056] Dihydromyricetin was dissolved in dimethyl sulfoxide (DMSO) to prepare different working concentrations. 80 μL of each concentration of dihydromyricetin, purified bispecific phosphatase, and reaction buffer were added to 96-well microplates. A control group (DMSO only) and a blank group (no substrate) were included, and the plates were incubated at 37°C for 30 min. Then, 20 μL of the substrate pNPP (final concentration 1 mM) was added, and the plates were incubated at 37°C for another 30 min. Finally, 100 μL of 1 M NaOH stop solution was added to terminate the reaction, and the absorbance at 405 nm was measured.

[0057] Based on the absorbance value, the formula is: Relative enzyme activity (%) = 100% × [(OD200%) / (OD200%)] 实验 -OD 空白 ) / (OD 对照 -OD 空白 Inhibition rate (%) = 100% - relative enzyme activity (%). The inhibition rates of dihydromyricetin against bispecific phosphatases of ovine infectious pustular virus, monkeypox virus, vaccinia virus, sheep pox virus, and bovine papular stomatitis virus were calculated. An inhibition rate curve was plotted with dihydromyricetin concentration (μM) on the x-axis and inhibition rate on the y-axis, as shown below. Figures 1-5 As shown. Further calculation of the half-maximal inhibitory concentration (IC50) was performed. 50 Dihydromyricetin has an IC50 value against bispecific phosphatases of ovine infectious pustular virus, monkeypox virus, cowpox virus, sheeppox virus, and bovine papular stomatitis virus. 50 The values ​​were 8.29±1.06 μM, 11.09±0.19 μM, 7.31±0.30 μM, 28.37±2.42 μM, and 14.67±2.40 μM, respectively. These results indicate that dihydromyricetin can effectively inhibit various poxvirus bispecific phosphatases.

[0058] Example 2

[0059] Example 2 provides a molecular docking method for predicting the interaction between dihydromyricetin and different poxvirus bispecific phosphatases.

[0060] Preparation of the small molecule ligand dihydromyricetin: Download the structure of dihydromyricetin from https: / / www.rcsb.org / ; open it with ChemBioDraw Ultra 12.0 software, then convert it into a three-dimensional structure with ChemBio3D Ultra 12.0 software, and perform energy optimization using the MMFF94 force field. Next, use AutodockTools 1.5.6 to combine nonpolar hydrogens and define rotational bonds, and finally convert it to PDBQT format and save it.

[0061] Macromolecular receptor preparation: Download the resolved structures of poxvirus bispecific phosphatases from https: / / www.rcsb.org / or predict the structural models of unresolved poxvirus bispecific phosphatases from https: / / swissmodel.expasy.org / . Preferably, the structures of sheep infectious pustular virus bispecific phosphatases (PDB ID: 5NCR), monkeypox virus bispecific phosphatases (PDB ID: 8GZ4), and vaccinia virus bispecific phosphatases (PDB ID: 3CM3) are used. The structures of sheep poxvirus and bovine epidemic stomatitis virus bispecific phosphatases are obtained using SWISS-MODEL modeling. Polar hydrogens and charges are added using AutodockTools 1.5.6, and finally, the structures are converted to PDBQT format and saved.

[0062] A suitable active pocket coordinate system was selected: size_x = 15, size_y = 15, size_z = 15. The exhaustiveness parameter was set to 16 to increase the accuracy of the calculation. Unless otherwise specified, all other parameters used their default values. Finally, the conformation with the highest score was selected for result analysis using PyMoL 1.7.6.

[0063] The results are shown in Table 1:

[0064]

[0065] Example 3

[0066] Example 3 provides the inhibitory effect of dihydromyricetin on ovine infectious pustular virus.

[0067] Dihydromyricetin was dissolved in dimethyl sulfoxide (DMSO) to prepare different concentrations for use. Different concentrations of dihydromyricetin were added to dense monolayers of OFTU cells, incubated for 72 h, and then CCK-8 solution (10 μL / well) was added. The cells were incubated at 37°C for 3 h, and the absorbance at 450 nm was measured to evaluate the toxicity of dihydromyricetin to OFTU cells. The results are as follows: Figure 6As shown. The toxicity of different concentrations of dihydromyricetin to OFTU cells was determined using the CCK-8 assay, and the half-maximal toxicity concentration (CMC) of dihydromyricetin to OFTU cells was calculated. 50 The concentration was 423.9 ± 22.4 μM. To further clarify the effect of different concentrations of dihydromyricetin on ORFV infection, OFTU cells were inoculated with ORFV at MOI = 1. After 1 h of adsorption, the medium was replaced with maintenance medium containing different concentrations of dihydromyricetin for continued culture. Samples were collected after 72 h and analyzed using TCID50. 50 The viral titer was determined using a method described above. The experimental results are as follows: Figure 7 As shown, the viral titer decreased significantly with increasing dihydromyricetin concentration. The IC50 of dihydromyricetin against ORFV was calculated using software fitting. 50 The value was 11.59 ± 1.79 μM.

[0068] In summary, dihydromyricetin can inhibit the infection of ovine infectious pustular virus by inhibiting the activity of various poxvirus bispecific phosphatases. This indicates that dihydromyricetin can be used to prevent and / or treat poxvirus infection, and thus can be used to prepare drugs for the prevention and / or treatment of poxvirus infection.

[0069] Example 4

[0070] Example 4 provides a pharmaceutical composition comprising dihydromyricetin. The dihydromyricetin is provided in monomeric form.

[0071] Example 5

[0072] Example 5 provides a pharmaceutical composition comprising dihydromyricetin. The dihydromyricetin component is provided in the form of a plant extract.

[0073] Preferably, the plant extract is derived from at least one of vine tea extract and Japanese raisin tree extract.

[0074] Example 6

[0075] Example 6 provides a pharmaceutical composition comprising dihydromyricetin and a pharmaceutically acceptable carrier and / or excipient.

[0076] The pharmaceutically acceptable carrier and / or excipient is selected from at least one of solvents, diluents, disintegrants, glidants, binders, lubricants, dispersants, suspending agents, isotonic agents, stabilizers, hydrating agents, emulsification accelerators, buffers, absorbents, release agents, coating agents, or antioxidants.

[0077] The pharmaceutical composition is formulated as any one of the following dosage forms: powder, tablet, pill, emulsion, drop pill, capsule, suspension, or tincture.

[0078] The pharmaceutically acceptable carrier and / or excipient is selected from at least one of solvents, diluents, disintegrants, glidants, binders, lubricants, dispersants, suspending agents, isotonic agents, stabilizers, hydrating agents, emulsification accelerators, buffers, absorbents, release agents, coating agents, or antioxidants.

[0079] The solvent includes at least one of distilled water, glycerol, dimethyl sulfoxide, ethanol, propylene glycol, polyethylene glycol, and fatty oil.

[0080] The diluent includes at least one of starch, sucrose, dextrin, pregelatinized starch, mannitol, etc.

[0081] The disintegrant includes at least one of microcrystalline cellulose, sodium carboxymethyl starch, crospovidone, etc.

[0082] The flow aid includes at least one of micronized silica gel, talc, etc.

[0083] The adhesive includes at least one of carboxymethyl cellulose, gelatin, polyvinylpyrrolidone, polyvinylpyrrolidone, starch paste, etc.

[0084] The lubricant includes at least one of sodium fumarate stearate, magnesium stearate, talc, hexagonal boron nitride, sodium benzoate, etc.

[0085] The dispersant includes at least one of sodium pyrophosphate, sodium tripolyphosphate, polyoxyethylene alkylphenol ether, etc.

[0086] The suspending agent includes at least one of glycerin, syrup, sorbitol, gum arabic, tragacanth gum, sodium alginate, methylcellulose, etc.

[0087] The isotonic agent shown includes at least one of sodium chloride, glucose, glycerin, boric acid, borax, etc.

[0088] The wetting agent includes at least one of polysorbate, polyoxyethylene castor oil, poloxamer, etc.

[0089] The emulsifier includes at least one of fatty acids, sorbitan fatty acids, monoglycerides, lanolin, sodium lauryl sulfate, etc.

[0090] The buffer includes at least one of acetic acid, sodium acetate, citric acid, sodium citrate, tartaric acid, sodium tartrate, lactic acid, disodium hydrogen phosphate, and sodium dihydrogen phosphate.

[0091] The antioxidant includes at least one of sodium sulfite, sodium bisulfite, tert-butylhydroanisole, etc.

[0092] The above embodiments are merely illustrative examples and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. Use of dihydromyricetin for the preparation of a medicament for the prevention and / or treatment of a poxvirus infection, characterized in that, The poxvirus is at least one of Orf virus (ORFV), Monkeypox virus (MPXV), Sheep pox virus (SPPV), Bovine papular dermatosis virus, Vaccinia virus (VACV).

2. Use of a pharmaceutical composition for the manufacture of a medicament for the prevention and / or treatment of a poxvirus infection, characterized in that, The pharmaceutical composition comprises dihydromyricetin, and the poxvirus is at least one of Orf virus (ORFV), Monkeypox virus (MPXV), Sheep pox virus (SPPV), Bovine papular dermatosis virus, Vaccinia virus (VACV).

3. Use according to claim 2, wherein the compound is ###0002### The pharmaceutical composition comprises a pharmaceutically active ingredient dihydromyricetin, which is provided in a monomer form or in a plant extract form comprising dihydromyricetin ingredient.

4. The use according to claim 3, wherein the compound is ###0002### The plant extract is at least one of Ampelopsis grossedentata extract and Rhamnus utilis extract.

5. Use according to any one of claims 2 to 4, wherein the compound is ###0002### The pharmaceutical composition further comprises a pharmaceutically acceptable carrier and / or excipient.

6. Use according to claim 5, wherein The pharmaceutically acceptable carrier and / or excipient is at least one selected from a solvent, a diluent, a disintegrant, a glidant, a binder, a lubricant, a dispersant, a suspending agent, an isotonic agent, a stabilizer, a hydrating agent, an emulsification accelerator, a buffer, an absorbent, a release agent, a coating agent, or an antioxidant.

7. Use according to any one of claims 2 to 4, wherein the compound is ###0002### The pharmaceutical composition is formulated as any one of a powder, a tablet, a pill, an emulsion, a capsule, a suspension, or a tincture.

Images