CN117180243B

CN117180243B - Use of carnosone in preparing medicine for preventing and/or treating Alzheimer disease

Info

Publication number: CN117180243B
Application number: CN202311195979.8A
Authority: CN
Inventors: 贾建平; 梁玉梅
Original assignee: Xuanwu Hospital
Current assignee: Xuanwu Hospital
Priority date: 2023-09-15
Filing date: 2023-09-15
Publication date: 2024-05-07
Anticipated expiration: 2043-09-15
Also published as: CN117180243A

Abstract

The invention relates to the use of salvinphenol ketone or a pharmaceutically acceptable derivative thereof for the preparation of a medicament for the prevention and/or treatment of Alzheimer's disease. The invention discovers and proves through experiments for the first time that the carnosone can protect nerve cells and obviously lighten the toxicity of the Abeta 42 oligomer to the nerve cells, thereby being capable of preventing, relieving, improving or treating the Alzheimer disease or delaying the progress of the Alzheimer disease, thereby being hopeful to become a candidate therapeutic drug for the Alzheimer disease and having great clinical application prospect and value.

Description

Use of carnosone in preparing medicine for preventing and/or treating Alzheimer disease

Technical Field

The invention relates to the technical field of medicines, in particular to application of carnosone or a pharmaceutically acceptable derivative thereof in preparing medicines for preventing and/or treating Alzheimer disease.

Background

Alzheimer's Disease (AD) is a disease which is mainly manifested by dysmnesia and functional impairment, seriously affects the autonomous life ability of patients, and brings great economic burden to families and society. Although the pathogenesis of AD is complex and diverse, the intracellular deposition of aβ still plays a crucial role in the development and progression of AD; aβ can exacerbate the severity of brain pathological changes and symptoms in AD patients by inducing mechanisms such as neuroinflammation, oxidative stress, neuronal death, energy metabolism abnormalities, and the like.

Traditional medicines for treating AD comprise donepezil, rivastigmine, galantamine, memantine and donepezil and memantine compound preparations, and although the medicines can relieve the symptoms of AD, the medicines can not improve the brain pathology of beta-amyloid (beta-amyoid, abeta) deposition and can not reverse the disease progress; since 2003, only the drug approved by the FDA for treating AD comprises the Ab Du Nashan antibody (aducanaumab) and the Lemcanemab (lecanemab), and the Ab Du Nashan antibody and the Lemcanemab can remove the Ab in the brain of a patient to a certain extent, but have side effects such as cerebral hemorrhage, cerebral edema and the like, and are high in price, so that the development of the drug which can inhibit the Ab toxicity, is relatively safe and reasonable in price has important social significance and medical significance.

The structural formula of the carnosone (Salviolone, C ₁₈H₂₀O₂, CAS: 119400-86-1) is as follows:

Salvia phenol ketone is a small molecular weight natural bisnorditerpenoid compound extracted from Saviae Miltiorrhizae radix, and has therapeutic potential for resisting inflammation, oxidative stress, and tumor.

Disclosure of Invention

Object of the Invention

The invention aims to provide the use of carnosone or a pharmaceutically acceptable derivative thereof in the preparation of a medicament for preventing and/or treating Alzheimer's disease.

The salvinphenol ketone is a traditional Chinese medicine monomer component in traditional Chinese medicine plants, is a natural compound, has the advantages of wide sources, small side effects and the like, can prevent, relieve, improve or treat AD diseases or delay the progress of AD diseases by influencing an Abeta mechanism, and provides a new and effective treatment choice for AD diseases.

Solution scheme

In order to achieve the above purpose, the invention adopts the following technical scheme:

in a first aspect, the present invention provides the use of salvinphenol ketone or a pharmaceutically acceptable derivative thereof in the manufacture of a medicament for the prevention and/or treatment of alzheimer's disease.

In particular embodiments, the carnosone or a pharmaceutically acceptable derivative thereof may be a pharmaceutically acceptable salt, prodrug, hydrate or solvate of carnosone.

The prodrug of salvinphenol ketone is a drug which can be converted into salvinphenol ketone in an organism.

The salt of carnosone is usefully a salt form of carnosone selected from the following: hydrochloride, nitrate, sulfate, phosphate, bromate, hydrobromate, citrate, formate, acetate, mesylate, ethanesulfonate, p-toluenesulfonate, benzoate, phthalate, malonate, maleate, perchlorate, fumarate, succinate, tartrate, lactate, gluconate, pamoate, aspartate or glutamate.

In the above uses, the treating alzheimer's disease comprises one or more of the following:

(1) Delay the progress rate of Alzheimer's disease;

(2) Improving symptoms caused by Alzheimer's disease; preferably, the symptoms such as cognitive dysfunction, neuropsychological symptoms, mental symptoms, behavioral abnormalities, sleep disorders, and the like are ameliorated;

in specific embodiments, the improvement in neuropsychological symptoms is an improvement in anxiety and/or depression.

In the above use, the prevention and/or treatment of Alzheimer's disease is achieved by a mechanism selected from the group consisting of:

i) Reducing the production or aggregation of, or scavenging, beta-amyloid;

ii) reduce the production or aggregation of phosphorylated tau protein, or eliminate phosphorylated tau protein;

iii) Improving neuronal apoptosis;

iv) ameliorating neuronal synaptic injury;

v) ameliorating mitochondrial energy metabolism disorder;

vi) inhibiting oxidative stress injury, neuroinflammatory response or immune response, reducing nerve injury and death;

vii) promote autophagy processes, clearing abnormal proteins and metabolites;

viii) improving cerebrovascular function, promoting cerebral blood circulation;

ix) improving blood brain barrier function;

x) promote synthesis or release of neurotrophic factors, increase nerve cell activity or promote nerve regeneration;

xi) regulate the balance of neurotransmitters such as acetylcholine, glutamate and dopamine, improving neurotransmission.

In the above use, preferably, the medicament comprises a prophylactically and/or therapeutically effective amount of carnosone or a pharmaceutically acceptable derivative thereof, and a pharmaceutically acceptable carrier and/or excipient.

The drug is administered by one or more of the following modes: oral, injectable, implantable, spray and/or inhalable.

The dosage form of the medicament is one or more selected from the following: injection, oral liquid, powder, tablet, granule, capsule, syrup, decoction, sustained and controlled release preparation, enteric-coated preparation, aerosol or suspension.

In a second aspect, the present invention provides a method for preventing and/or treating alzheimer's disease, the method comprising: administering to a subject in need thereof a prophylactically and/or therapeutically effective amount of carnosone or a pharmaceutically acceptable derivative thereof.

The term "effective amount" refers to an amount or dose of an active ingredient that provides the desired effect to a patient being diagnosed or treated via single or multiple administrations of the active ingredient to the patient. The effective amount can be determined by the attending diagnostician as a person skilled in the art by known techniques and by observations made in similar circumstances. In determining an effective amount or dosage of an active ingredient to be administered, the attending diagnostician should consider a variety of factors, including, but not limited to: species of mammal; volume, age, and general health; specific diseases involved; the extent or severity of the disease involved; response of the individual patient; the particular compound being administered; mode of administration; the bioavailability properties of the administered formulation; the selected dosing regimen; concomitant use of drug therapy; as well as other related situations.

Advantageous effects

The invention provides the use of salvinphenol ketone or a pharmaceutically acceptable salt, prodrug or hydrate thereof in the preparation of a medicament for preventing and/or treating Alzheimer's disease. Experiments prove that the carnosone can protect nerve cells and obviously lighten the toxicity of the Abeta 42 oligomer to the nerve cells, thereby being capable of preventing, relieving, improving or treating AD diseases or delaying the progress of the AD diseases and being a very promising candidate therapeutic drug for Alzheimer's disease.

Drawings

One or more embodiments are illustrated by way of example and not limitation in the figures of the accompanying drawings. The word "exemplary" is used herein to mean "serving as an example, embodiment, or illustration. Any embodiment described herein as "exemplary" is not necessarily to be construed as preferred or advantageous over other embodiments.

FIG. 1 shows a comparison of cell viability of HT22 cells treated for 24 hours at different Abeta 42 oligomer concentrations according to example 1 of the present invention; wherein the abscissa shows each treatment group, and the ordinate shows cell viability (%); in the abscissa, 0 μm represents the negative control group, and the rest represent the aβ42 oligomer-treated group at the indicated concentrations; * *: p <0.01 compared to the negative control group; * ***: p <0.0001 compared to the negative control group.

FIG. 2 shows the safety dose test results of various concentrations of salvinphenol ketone on HT22 cells according to example 2 of the present invention; wherein the abscissa shows each treatment group, and the ordinate shows cell viability (%); in the abscissa, 0 μm represents the negative control group, and the rest represent the salvinphenol ketone-treated group at the indicated concentration.

FIG. 3 shows the prophylactic and therapeutic effects of various concentrations of salviol according to example 3 on HT22 cells modeled with 10. Mu M A. Beta.42 oligomer; wherein the abscissa shows each treatment group, and the ordinate shows cell viability (%); * ***: p <0.0001 compared to negative control group; # # # #: p <0.001 compared to the aβ42 oligomer group; # #. P <0.01 compared to the Aβ42 oligomer group.

FIG. 4 shows a comparison of cell viability of BV2 cells treated for 24 hours at different Abeta 42 oligomer concentrations of example 4 of the present invention; wherein the abscissa shows each treatment group, and the ordinate shows cell viability (%); in the abscissa, 0 μm represents the negative control group, and the rest represent the aβ42 oligomer-treated group at the indicated concentrations; * ***: p <0.0001 compared to the negative control group.

FIG. 5 shows the safety dose test results of various concentrations of salvinphenol ketone on BV2 cells according to example 5 of the present invention; wherein the abscissa shows each treatment group, and the ordinate shows cell viability (%); in the abscissa, 0 μm represents the negative control group, and the rest represent the carnosone-treated group at the indicated concentration; * : p <0.05 compared to negative control group; * ***: p <0.0001 compared to the negative control group.

FIG. 6 shows the prophylactic and therapeutic effects of various concentrations of salviol according to example 6 on BV2 cells modeled with 10. Mu. M A β42 oligomer; wherein the abscissa shows each treatment group, and the ordinate shows cell viability (%); * ***: p <0.0001 compared to negative control group; #: p <0.05 compared to the aβ42 oligomer group.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the technical solutions of the present invention will be clearly and completely described in the following examples. It will be apparent that the described embodiments are some, but not all, embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.

In addition, numerous specific details are set forth in the following description in order to provide a better illustration of the invention. It will be understood by those skilled in the art that the present invention may be practiced without some of these specific details. In some embodiments, materials, elements, methods, means, etc. well known to those skilled in the art are not described in detail in order to highlight the gist of the present invention.

Throughout the specification and claims, unless explicitly stated otherwise, the term "comprise" or variations thereof such as "comprises" or "comprising", etc. will be understood to include the stated element or component without excluding other elements or components.

The invention is illustrated in further detail by the following examples.

In the following examples, raw materials were all commercially available, with salosone from the pharmaceutical Ming Bo (Wuhan) chemical technology Co., ltd, and Abeta 42 oligomer from Shanghai Yao biotechnology Co., ltd.

In the following examples, AD cell models were constructed using a neuronal-like HT22 cell line induced by a human beta-amyloid 1-42 (beta-amyloid 1-42, abeta 1-42) oligomer (hereinafter referred to as "Abeta 42 oligomer") and a BV2 microglial cell line; and, setting a concentration gradient of the carnosone, and obtaining a safe dosage range of the carnosone in an HT22 cell line and a BV2 cell line through a cytotoxicity experiment; further, the effectiveness of carnosone against AD disease was determined by pre-protecting the drug prior to establishing an AD cell model and then continuing the treatment with the drug after establishing an AD cell model, wherein three independent experiments were performed, such that the experimental results were reliable and reproducible.

Example 1: construction of AD cell model by acting A beta 42 oligomer on HT22 cell line

1) Synthesis of Abeta 42 oligomer

Aβ42 oligomer was completed by Shanghai blaze Biotechnology Co., ltd; specifically, the A beta oligomer form is synthesized in vitro based on human beta-amyloid 1-42 (beta-amylase 1-42, A beta 1-42) monomer (hereinafter referred to as "A beta 1-42 monomer"); the specific synthetic method for synthesizing the oligomer in vitro is as follows: the aβ1-42 monomers were dissolved in Hexafluoroisopropanol (HFIP) solvent at a concentration of 1mg/ml, after 1 hour, HFIP was removed in a vacuum concentrator, immersed in a tube bottom in transparent gel flakes, incubated with dimethyl sulfoxide (dimethyl sulfoxide, DMSO), oligomerized, stored at 4 ℃ for 24 hours, and whether aβ oligomers were formed was determined by electron microscopy (methods can be referenced in Li et al, J Alzheimers Dis,2021 and Li et al, mol Neurobiol, 2022). Aβ42 oligomer was prepared as 1mM powder with a purity of 95%.

2) Preparation of Abeta 42 oligomer working solution

Dissolving Abeta 42 oligomer in DMSO to prepare a storage solution with the concentration of 5mM, and storing the storage solution at-80 ℃; the stock solution was diluted to 100. Mu.M with DMEM to prepare an A.beta.42 oligomer intermediate solution, which was then centrifuged at 14,000Xg for 10 minutes to remove any insoluble aggregates. Before use, working fluid diluted to a desired concentration with DMEM medium was set to have a concentration gradient of 1.25 μm, 2.5 μm, 5 μm, 10 μm, 20 μm, 40 μm for use.

3) Construction of AD cell model

Construction of Abeta 42 oligomer-based AD cell models is disclosed in various published papers (e.g., ,Yu et al.,Psychopharmacology,2022;Toledo et al.,Front Neurosci,2021;Kam et al.,Cell Biol Toxicol,2019;Kim et al.,Free Radical Bio Med,2016),, which is a widely accepted method for constructing AD cell models), the specific procedure is to add 5mL of fetal bovine serum with 500. Mu.l of diabody (50U/mL penicillin and 50g/mL streptomycin solution) to 44.5mL of DMEM medium to prepare 50mL of DMEM complete medium, at which the fetal bovine serum concentration is 10%, the diabody concentration is 1%, sealing the sealing membrane, and storing at 4℃for 30 days in the above-configured complete medium, and to inoculate HT22 cells in a humid environment of 37℃5% CO ₂ and 95% air overnight until the cells grow to log phase.

Counting and seeding the cultured HT22 cells in 96 well plates, wherein 5000 cells are seeded per well, and HT22 cells are diluted to the desired cell mass with complete medium as described above, and 100 μl of cell culture broth is allowed per well; one for each column (6 wells per group), where one column was empty with no cells and only medium. The HT22 cells inoculated 96-well plate was placed in 37 degrees C, 5% CO ₂ and 95% air in a humid environment for overnight culture, then, the complete medium in the wells was aspirated off, one for each column, each: blank (without cells), negative control (control) (with cells, without aβ42 oligomer), concentration gradient of aβ42 oligomer groups (see table 1 for the group), wherein concentration gradient of aβ42 oligomer groups were supplemented with corresponding concentration of aβ42 oligomer solutions (prepared in serum-free DMEM medium, 100 μl per well), and 100 μl serum-free DMEM medium was added to each of the blank and negative control (control), and incubated in an incubator at 37 ℃ for 24 hours.

Table 1, grouping in 96 well plates

In table 1 above, the aβ42 oligomer groups are divided into groups according to the concentration gradient of aβ42 oligomer, one concentration corresponding to each group; and, the medium refers to a serum-free DMEM medium.

4) Cytotoxicity experiments to determine the toxic concentration required for aβ42 oligomer to construct AD cell models

And 3) adding 10 μl of CCK-8 solution (purchased from New Saimei Biotechnology Co., ltd., the CCK-8 solution is 10% of the volume of the culture solution) into the culture solution after the step 3) to continue the culture for 2 hours, stopping the culture, placing the culture on an enzyme-linked immunosorbent assay (Thermo) to incubate for 2 minutes in a dark place, measuring the absorbance at 450nm, and recording the results to obtain absorbance values of a blank group, a negative control group (control) and an Abeta 42 oligomer group with various concentration gradients. And (3) zeroing by taking a blank group as a reference, and calculating the toxic effects of the Abeta 42 oligomer with different concentrations on HT22 cells so as to determine the conditions required by AD cell model construction.

Cell viability (%) of specific concentration aβ42 oligomer group= (average value of absorbance of aβ42 oligomer group-absorbance of blank group)/(average value of absorbance of negative control group-average value of absorbance of blank group) ×100% of the specific concentration aβ42 oligomer group

Cell viability (%) of negative control (control) = (negative control absorbance-average of blank absorbance)/(negative control absorbance average-average of blank absorbance) ×100%

All data are presented as mean+ -SEM, using one-WAY ANALYSIS of variance (ANOVA) to detect differences between three or more groups, and Tukey's post hoc test for comparison between two groups; wherein the difference is significant when P < 0.05. Data and plots were analyzed using GRAPHPAD PRISM.0.1 software.

The results are shown in FIG. 1, and the results of FIG. 1 indicate that: treatment of HT22 cells with 10. Mu. M A β42 oligomer for 24 hours resulted in significant cytotoxicity and significant decrease in HT22 cell viability, suggesting that AD cell model construction was successful, and therefore subsequent experiments employed 10. Mu. M A β42 oligomer as the A.beta.42 oligomer modeling concentration.

Example 2: determination of safe dose range of carnosone in HT22 cell line

In this example, the safe dose range of carnosone in HT22 cell lines was determined by the following procedure:

Dissolving carnosone original drug with DMSO to prepare a storage solution with a concentration of 33.3mM, and storing at-80 ℃; diluting the storage solution into an intermediate solution with a concentration of 100 mu M by using a serum-free DMEM medium, and storing at-20 ℃; when in use, the intermediate liquid is diluted into working liquid by serum-free DMEM culture medium, and the working liquid with the following concentration gradient is prepared: 10. Mu.M, 20. Mu.M, 30. Mu.M, 40. Mu.M, 50. Mu.M, 60. Mu.M, 70. Mu.M, 80. Mu.M.

Counting and seeding the HT22 cells cultured in step 2) of example 1 in 96 well plates, wherein 5000 cells are seeded per well, diluted to the desired cell volume with complete medium, and such that 100 μl of cell culture broth is contained per well; each column corresponds to a group (each group has 6 compound holes), wherein only the culture medium is added into one column without adding cells as a blank group; the 96-well plate inoculated with HT22 cells was incubated overnight in a humidified atmosphere of 37℃5% CO ₂ and 95% air, then the medium in the wells was aspirated, fresh medium or salvinol solution was added according to the groupings of Table 2, and after incubation in an incubator at 37℃for 24 hours, cytotoxicity experiments were performed (cytotoxicity experiment procedure was the same as step 4 of example 1).

Table 2 grouping conditions in 96 well plates

In table 2 above, the salviol groups are divided into groups according to the concentration gradient of salviol, one salviol concentration corresponding to each group; the culture medium refers to serum-free DMEM medium, and the carnosone solution refers to a solution prepared by using serum-free DMEM medium according to different gradient concentrations.

The cell viability was calculated as in example 1.

The results are shown in fig. 2, and the results of fig. 2 indicate that: no cytotoxicity was produced by treatment of cells with carnosone for 24 hours at a dose range of 10-80 μm, so subsequent experiments set up a gradient of carnosone concentration in this dose range.

Example 3: therapeutic effects of salviol on AD cell models constructed by treatment of HT22 cells with aβ42 oligomers

In this example, the therapeutic effect of carnosone on the AD cell model constructed in example 1 was examined by the following procedure:

1) The salvinol was diluted with serum-free DMEM medium to obtain the following concentration gradient solutions: 10. Mu.M, 20. Mu.M;

2) Preparing a 10 mu M A beta 42 oligomer solution by adopting a serum-free DMEM culture medium;

3) Preparing a mixed solution of carnosone and Abeta 42 oligomer by adopting a serum-free DMEM culture medium, and obtaining a mixed solution with the following concentration: 10. Mu.M salviol+10. Mu M A β42, 20. Mu.M salviol+10. Mu M A β42;

4) Counting and inoculating the cultured HT22 cells into a 96-well plate, diluting the complete culture medium to the required cell amount by 5000 cells per well, and enabling each well to contain 100 mu l of cell culture solution; each column corresponds to a group (each group has 6 compound holes), wherein only the culture medium is added into one column without adding cells as a blank group; the 96-well plate inoculated with HT22 cells was incubated overnight in a humid environment at 37 ℃, 5% CO ₂ and 95% air; then, the medium in the wells was aspirated, and fresh medium or a monomer solution of the traditional Chinese medicine was added in accordance with the group of Table 3, and cultured in an incubator at 37℃for 4 hours.

Table 3 grouping conditions in 96 well plates

In table 3 above, the aβ42 oligomer modeling pre-protection groups were divided into groups according to the concentration gradient of salviol, one corresponding to each group; the culture medium refers to serum-free DMEM medium, and the carnosone solution refers to a solution prepared by using serum-free DMEM medium according to different gradient concentrations.

4) After the culture, the medium in the wells was aspirated, and a new medium, an aβ42 oligomer or a mixed solution of carnosol and aβ42 oligomer was added in accordance with the group of table 4, and the mixture was cultured in an incubator at 37 ℃ for 24 hours to perform a cytotoxicity test (cytotoxicity test procedure is the same as that in step 4 of example 1).

TABLE 4 case of each component in 96 well plate

In table 4 above, the aβ42 oligomer modeling treatment groups were divided into groups according to the concentration gradient of the mixed solution of carnosol and aβ42 oligomer, one concentration corresponding to each group; the medium refers to serum-free DMEM medium, the 10 μma β42 oligomer solution refers to the solution prepared by using serum-free DMEM medium, and the mixed solution of carnosone and aβ42 oligomer refers to the solution prepared by using serum-free DMEM medium according to different gradient concentrations.

The cell viability was calculated as in example 1.

The results are shown in fig. 3, and the results of fig. 3 indicate that: pre-protection with 10 μm and 20 μm salvinphenol ketone for 4 hours and treatment for 24 hours significantly reduced the toxicity of aβ42 oligomer to HT22 cells, indicating: salvianolic ketone has obvious effect of preventing and treating AD diseases.

Example 4: construction of AD cell model by acting A beta 42 oligomer on BV2 cell line

The model building method has been disclosed in a number of published articles (e.g., wang et al, biomed Pharmacother,2023; li et al, J Alzheimers Dis, 2021), and is a widely accepted method of AD cell model building. For specific operation reference is made to example 1. The cell viability was calculated as in example 1.

The results are shown in fig. 4, and the results of fig. 4 indicate that: treatment of BV2 cells with 10 μ M A β42 oligomer for 24 hours resulted in significant cytotoxicity, and significant decrease in BV2 cell viability, suggesting successful construction of AD cell models, therefore, subsequent experiments employed 10 μ M A β42 oligomer as the modeling concentration of Aβ42 oligomer.

Example 5: determination of safe dose range of carnosone in BV2 cell line

In this example, the safe dose range of carnosone in BV2 cell line was determined by referring to the procedure described in example 2. The cell viability was calculated as in example 1.

The results are shown in fig. 5, and the results of fig. 5 indicate that: the cell cytotoxicity can be obviously generated by treating the cell for 24 hours with the carnosone with the concentration of 40 mu M and above, and the activity of BV2 cells is obviously reduced, so that the concentration gradient of the carnosone is set in the dosage range of 10-20 mu M in the subsequent experiments.

Example 6: therapeutic effects of salvinphenol ketone on AD cell model constructed by treating BV2 cells with Abeta 42 oligomer

In this example, the therapeutic effect of carnosol on AD cell models constructed by treating BV2 cells with aβ42 oligomers was determined by referring to the procedure described in example 3. The cell viability was calculated as in example 1.

The results are shown in fig. 6, and the results of fig. 6 indicate that: pre-protection with 10 μm and 20 μm salvinphenol ketone for 4 hours and treatment for 24 hours significantly reduced the toxicity of aβ42 oligomer to BV2 cells, indicating: salvianolic ketone has obvious effect of preventing and treating AD diseases.

Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and are not limiting; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. Use of salvinphenol ketone or a pharmaceutically acceptable salt thereof as sole active ingredient in the manufacture of a medicament for the prevention and/or treatment of alzheimer's disease.

2. The use according to claim 1, characterized in that the salt of salvinphenol ketone is a salt form of salvinphenol ketone selected from the group consisting of: hydrochloride, nitrate, sulfate, phosphate, bromate, hydrobromate, citrate, formate, acetate, benzoate, phthalate, malonate, maleate, perchlorate, fumarate, succinate, tartrate, lactate, gluconate, aspartate or glutamate.

3. The use according to claim 1, wherein the medicament comprises a prophylactically and/or therapeutically effective amount of carnosone or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier and/or excipient.

4. The use according to claim 1, wherein the medicament is administered in a manner selected from one or more of the following: oral, injectable, implantable, spray and/or inhalable.

5. The use according to any one of claims 1 to 4, wherein the pharmaceutical dosage form is one or more selected from the group consisting of: injection, oral liquid, powder, tablet, granule, capsule, syrup, decoction, sustained and controlled release preparation, enteric-coated preparation, aerosol or suspension.