TW201817426A - Uses of a triterpenoid mixture for treating multiple sclerosis - Google Patents

Abstract

Disclosed herein is a novel use of a triterpenoid mixture for the treatment of multiple sclerosis (MS). The triterpenoid mixture consists of, ganoderic acid A (GAA), ganoderic acid B (GAB), ganoderic acid C (GAC), ganoderic acid C5(GAC5), ganoderic acid C6(GAC6), ganoderic acid D (GAD), ganoderic acid E (GAE), ganoderic acid G (GAG), and ganoderenic acid D. The triterpenoid mixture may be administered to a subject suffering from MS in a dose of about 1 to 10 mg/Kg to ameliorate or alleviate symptoms associated with MS.

Description

Use of triterpenoid mixture for the treatment of multiple sclerosis

The present invention is generally directed to the novel use of a triterpene mixture for the treatment of multiple sclerosis (MS).

Multiple sclerosis (MS) is a disease caused by the individual's immune system attacking the central nervous system (such as the brain, spinal cord, and optic nerve). When part of the immune system attacks the central nervous system, diffuse lumps of myelin are often observed in the brain and spinal cord, leading to a variety of neurological conditions and symptoms, and often recurrent and remission. At present, there is no cure for multiple sclerosis. However, there are therapies for soothing multiple sclerosis symptoms, such as oral corticosteroids or vitamin B ₁₂ , and subcutaneous injection of interferon beta. However, the use of adrenal corticosteroids is limited to acute episodes, and long-term use of steroids may cause undesirable side effects. As for interferon beta, it is expensive, and therefore, long-term use of such treatment will incur a large amount of cost. Moreover, subcutaneous injection of interferon beta needs to be performed in a hospital, and the patient's willingness to receive treatment is further reduced.

Accordingly, there is a need in the related art for an improved drug that can ameliorate and/or soothe the symptoms of multiple sclerosis, wherein the drug is suitable for oral administration, which is effective for treating multiple sclerosis without causing any side effects.

In order to provide a reader-based understanding, a brief summary of the case will be presented below. This Summary is not an extensive overview of the present invention, and is not intended to identify the essential elements of the invention or the scope of the invention. Its purpose is to present the concepts disclosed herein in a simplified form as a

Overall, the disclosure of this case relates to an unanticipated new discovery for the novel use of a mixture of triterpenoids for the treatment of individuals suffering from multiple sclerosis (MS). Therefore, the triterpene mixture is quite useful for developing a pharmaceutical for treating multiple sclerosis-related diseases and/or symptoms.

Accordingly, the first object of the present disclosure is a new use of a triterpene mixture that can be used to manufacture a pharmaceutical product suitable for treating MS.

According to an embodiment of the present disclosure, the pharmaceutical product comprises from 10 to 1,000 mg of a triterpene mixture; preferably from 50 to 500 mg of a triterpene mixture; more preferably from 100 to 300 mg of a triterpene mixture.

According to a preferred embodiment of the present disclosure, the triterpene mixture is composed of ganoderic acid A (GAA), ganoderic acid B (GAB), ganoderic acid C (GAC), and ganoderma lucidum. acid _{C 5 (ganoderic acid C 5,} GAC 5), Ganoderma acid _{C 6 (ganoderic acid C 6,} GAC 6), Ganoderma acid D (ganoderic acid D, GAD) , Ganoderma acid E (ganoderic acid E, GAE) , Ganoderma Acid G (GAOD), and ganoderenic acid D, wherein GAA accounts for about 30-40% by weight of the mixture, and GAB, GAC, GAD, and GAG account for the mixture. The weight is about 10-15%, and the weight of GAC ₅ , GAC ₆ , GAE and Ganoderma acid D in the mixture is about 3-6%, wherein the total weight of the triterpene mixture is regarded as 100%.

According to a preferred embodiment of the present disclosure, the pharmaceutical product is suitable for oral administration.

A second aspect of the present disclosure is directed to a method of treating an individual suffering from MS. The method comprises administering to the individual a mixture of the foregoing triterpenes at a dose of from about 1 to 10 mg/kg to improve or alleviate the symptoms associated with multiple sclerosis.

According to a preferred embodiment of the present disclosure, the weight of the GAA in the mixture is about 30-40%, and the weights of GAB, GAC, GAD, and GAG in the mixture are about 10-15%, respectively, GAC ₅ , GAC. _{6. The} weight of the GAE and the ganoderma acid D in the mixture is about 3-6%, wherein the total weight of the triterpene mixture is regarded as 100%.

In accordance with a preferred embodiment of the present disclosure, the triterpene mixture is administered orally to the subject.

According to a preferred embodiment of the present disclosure, the system is a mammal, preferably a human.

Details regarding one or more implementation aspects of the present disclosure will be set forth in the following description. Other features and advantages of the present invention are apparent from the detailed description and claims.

It is to be understood that the above summary, as well as the following detailed description, are intended to provide a further description of the invention claimed.

Detailed description of preferred embodiments

The detailed description and the accompanying drawings are intended to be illustrative,

1. definition

For convenience, the specific terms used in this disclosure are summarized herein. All technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains, unless otherwise defined.

The term "treatment" as used herein is used to mean obtaining a desired pharmaceutical and/or physiological effect, for example, inhibiting or suppressing the course of MS. The effect may be prophylactic, meaning to completely or partially prevent the disease or condition, and/or therapeutic, meaning to partially or completely cure a disease and/or an adverse reaction caused by the disease. The term "treatment" as used herein includes prophylactic (eg, prophylactic), curative or palliative treatment of a mammal, particularly a human disease; and includes: (1) prophylactic (eg, prophylactic), curative Or alleviating the treatment of a disease or condition (such as MS), preventing the disease or symptom from occurring in an individual who may have a predisposition to the disease but has not yet been diagnosed; (2) inhibiting a disease (eg, by stopping it) Development); or (3) alleviating a disease (eg, slowing the symptoms associated with the disease).

The terms "administered", "administering" or "administration" are used interchangeably herein to mean a mode of delivery, including but not limited to intravenous, intramuscular, intraperitoneal. An agent of the invention (for example, a triterpene mixture of the present invention) is administered intra-arterially, intracranically or subcutaneously. In some embodiments, the triterpene mixture disclosed herein is in the form of a powder for mixing with a suitable vehicle (e.g., a buffer solution) prior to use, such as prior to intravenous injection. In other embodiments, the triterpene mixture disclosed herein is in the form of a powder and is administered orally with a suitable excipient.

The term "an effective dose" as used herein is used to mean an effective amount of the desired result in the treatment of a disease caused by MS, both in dose and in time. For example, the presented triterpene mixture can be effective in reducing, preventing, delaying, inhibiting, or stopping any clinical signs of MS in treating MS. An effective dose of a reagent does not necessarily cure a disease or condition, but provides a treatment for a disease or condition, delays, prevents or prevents the occurrence of the disease or condition, or improves the disease or condition. The specific effect or sufficient dose will vary depending on factors such as the particular condition being treated, the physiological condition of the patient (eg, the patient's weight, age or sex), the mammal or animal species being treated, during treatment, and concurrently. The nature of the therapy, if any, and the specific formula used. The effective dose can be expressed in the form of a total amount of active agent (e.g., grams, milligrams, or micrograms), or a ratio of active agent to body weight, such as milligrams per kilogram of body weight (mg/kg). The effective dose can be divided into one, two or several doses, administered in one suitable form, one, two or several times over a specified period of time.

The terms "individual" or "patient" are used interchangeably herein to mean that a mammal that can be treated by a compound of the invention comprises a human. The term "mammal" refers to all members of the Mammalia classification, including humans, primates, livestock and farm animals, such as rabbits, pigs, sheep and cattle, as well as zoos, race animals and pets; and rodents such as mice and Rat. In addition, the term "individual" or "patient" means both male and female genders unless one of the genders is specifically indicated. Therefore, the term "individual" or "patient" encompasses any mammal that can benefit from the treatments disclosed in this case. Examples of "individual" or "patient" include, but are not limited to, a human, a rat, a mouse, a guinea pig, a monkey, a pig, a goat, a cow, a horse, a dog, a cat, a bird, and a bird. In a preferred embodiment, the individual is a human.

The term "pharmaceutically acceptable" means that when a molecule or composition is administered to a body, such as a human, there is no adverse reaction or undesired reaction.

The term "excipient" as used herein means any inert substance (e.g., a powder or liquid) which can form a carrier/carrier for the active substance. Excipients are generally safe, non-toxic, and broadly include any material known in the pharmaceutical industry to be useful in the preparation of pharmaceutical compositions, such as fillers, diluents, aggregators, binders, lubricants, glidants , stabilizers, colorants, wetting agents, disintegrating agents, and the like.

Notwithstanding that the numerical ranges and parameters of the invention are intended to be <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; However, any numerical value inherently inevitably contains standard deviations due to individual test methods. Also, as used herein, the term "about" generally means within 10%, 5%, 1%, or 0.5% of the value or range provided. Alternatively, the term "about" is used in the recognition of those of ordinary skill in the art to which the invention pertains, within the standard tolerance of the average. Except in the operating examples, or unless otherwise explicitly indicated, all ranges, quantities, values, and percentages disclosed herein, such as describing the amount of material used, the length of time, temperature, operating conditions, quantity ratios, and the like, are It should be understood as a modification of "about". Therefore, the numerical parameters disclosed in the present disclosure and the scope of the accompanying claims are all approximate values, and may be changed as needed, unless otherwise stated. At a minimum, these numerical parameters should be understood as the number of significant digits indicated and the values obtained by applying the general carry method.

The singular forms "a", "the", "the", and "the"

2. Detailed description of preferred embodiments

The disclosure of the present invention is based, at least in part, on an unexpected finding that it has been found that a mixture of triterpenes prepared in accordance with the present disclosure may suppress or inhibit the course of multiple sclerosis. Therefore, the triterpene mixture of the present invention can be used for the development of a medicament for treating a disease, abnormality or symptom associated with multiple sclerosis.

A detailed description of the practice of the triterpene mixture of the present invention is provided below. The triterpene mixture is composed of Ganoderma lucidum A (GAA), Ganoderma lucidum B (GAB), Ganoderma lucidum C (GAC), Ganoderma lucidum C ₅ (GAC ₅ ), Ganoderma lucidum. C ₆ (GAC ₆ ), Ganoderma D (GAD), Ganoderma E (GAE), Ganoderma G (GAG), and Ganoderma acid D; it can be used to prepare a pharmaceutical, prevent or treat a body or The MS of the patient or the disease caused by it. The results of this study, as described below, show that the triterpene mixture of this case has the lowest amount of cytotoxicity or no cytotoxicity to normal cells, and can reduce the inflammatory cytokine IL-17 in the blood, thereby inhibiting the course of MS in vivo. development of.

The application of this case relates in a first aspect to a method of treating an individual having MS. The method comprises the steps of: administering to a desired individual an effective dose of a triterpene mixture comprising Ganoderma lucidum A (GAA), Ganoderma lucidum B (GAB), Ganoderma lucidum C (GAC), Ganoderma lucidum C ₅ (GAC ₅₎ ), Ganoderma C ₆ (GAC ₆₎ , Ganoderma D (GAD), Ganoderma E (GAE), Ganoderma G (GAG), and Ganoderma acid D; to alleviate or alleviate the symptoms associated with multiple sclerosis .

According to an embodiment of the present disclosure, the weight of the GAA in the mixture is about 30-40%, and the weight of the GAB, GAC, GAD, and GAG in the mixture is about 10-15%, respectively, GAC ₅ , GAC ₆ , GAE And the weight of the ganoderma acid D in the mixture is about 3-6%, wherein the total weight of the triterpene mixture is regarded as 100%. According to one particular embodiment of the present disclosure, the weight of GAA in the mixture is about 35%, and the weights of GAB, GAC, GAD, and GAG in the mixture are about 12%, respectively, GAC ₅ , GAC ₆ , GAE, and Ganoderma acid D is about 3, 6, 3.5, and 4.5% by weight of the mixture, respectively, wherein the total weight of the triterpene mixture is considered to be 100%.

According to a preferred embodiment of the present disclosure, the triterpene mixture is administered orally, intravenously or subcutaneously at a dose of 0.1 to 100 mg/kg of the individual body weight, preferably 0.5-50 mg / Kg individual body weight; more preferably, the dose is 1-10 mg/Kg body weight.

According to an embodiment of the present disclosure, the triterpene mixture can be used together with other anti-MS agents, and the anti-MS agents suitable for use with the triterpene mixture of the present invention include, for example, adrenal corticosteroids, vitamin B ₁₂ and interferon beta. .

The application of this case relates to a pharmaceutical product for treating MS in the second aspect. The pharmaceutical product comprises an effective amount of a triterpene mixture and a pharmaceutically acceptable excipient.

In general, the weight percentage of the triterpenoid mixture in the present invention is from about 0.01% to 99.9% by weight based on the total weight of the pharmaceutical product. In certain embodiments, the weight percent of the triterpene mixture of the present invention in the pharmaceutical product is at least about 0.1% by weight of the total weight of the pharmaceutical product. In certain specific embodiments, the weight percent of the triterpene mixture of the present invention in the pharmaceutical product is at least 5% of the total weight of the pharmaceutical product. In some other embodiments, the weight percentage of the triterpene mixture of the present invention in the pharmaceutical product is about 10% of the total weight of the pharmaceutical product. In some other embodiments, the weight percent of the triterpene mixture of the present invention in the pharmaceutical product is at least about 25% of the total weight of the pharmaceutical product.

According to an embodiment of the present disclosure, each pharmaceutical product comprises 10 to 1,000 mg of a triterpene mixture; preferably 50 to 500 mg of a triterpene mixture; more preferably 100 to 300 mg of a triterpene mixture.

In some embodiments, the pharmaceutical of the present invention further comprises an agent (e.g., an anti-MS agent) known to alleviate or alleviate the symptoms of multiple sclerosis. Examples of prior agents include, but are not limited to, adrenal corticosteroids, vitamin B ₁₂ and interferon beta. In one example, the interferon beta is administered in conjunction with the triterpene mixture of the present invention.

A pharmaceutically acceptable excipient that is compatible with the other ingredients of the formulation and which is biologically acceptable.

The pharmaceutical product may contain different forms of excipients depending on the route to be administered. The pharmaceutical composition of the case can be intravenous, intradermal, intraarterial, intraperitoneal, damaged, intracranial, intranasal, intrathoracic, intratracheal, intrarectal, local, intramuscular, subcutaneous, intracystic, pericardial. Intraocular, oral, specific, topical, injection, inhalation, infusion, and topical perfusion are administered in any suitable form, such as powders, emulsions, liquids, and sprays.

The actual dosage of the pharmaceutical product can be determined by the physician participating in the treatment based on the physical and physiological factors of the individual. Such factors include, but are not limited to, age, sex, weight, disease being treated, severity of symptoms, prior medical history, other pharmaceuticals used, routes of administration, and the like. According to a non-limiting example of the disclosure of the present invention, the dose per administration is 0.1-100 mg of a mixture of triterpenoids per kilogram of body weight, for example, 0.1, 0.2, 0.3, 0.4 per kilogram of body weight per application dose. , 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 , 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45 , 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70 , 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95 , 96, 97, 98, 99 and 100 mg of a mixture of triterpenoids; preferably, the dose per application is 0.5-50 mg of a mixture of triterpenoids per kilogram of body weight, for example, the dose per administration is per kilogram. Weight given 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 1 7, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 and 50 mg of the triterpene mixture; more preferably, the dose per administration is 1-10 mg of the triterpene mixture per kg of body weight, for example, each application The dose is administered in a ratio of 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 mg of triterpene per kg of body weight.

The pharmaceutical product comprising the triterpenoid mixture of the present invention may be in a form suitable for oral administration, such as tablets, troches, aqueous or oily suspensions, dispersible powders or granules, emulsifiers, hard or soft capsules, syrups or elixirs. The pharmaceutical intended for oral administration can be prepared according to any method known in the art for preparing pharmaceutical compositions, and such compositions may comprise one or more agents selected from the group consisting of sweeteners, flavoring agents, coloring agents, and preservatives. A group of agents for the preparation of exquisite and tasty pharmaceuticals. Tablets comprise a triterpene mixture of the present invention and a non-toxic pharmaceutically acceptable excipient which is suitable for use in the manufacture of tablets. The excipient can be, for example, an inert diluent such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; or a granulating and disintegrating agent such as corn starch or alginic acid; or a binding agent such as starch. , gelatin or gum arabic; and a lubricant such as magnesium stearate, stearic acid or talc.

The tablet may be uncoated or may be coated with conventional techniques to delay disintegration and absorption in the gastrointestinal tract to provide a longer duration of action. For example, monoglyceride stearate or diglyceride stearate can be used. The tablets may also utilize an envelope to form an osmotic therapeutic tablet to control its release.

The oral formulation can also be presented in the form of a hard capsule, wherein the active ingredient is mixed with an inert solid diluent such as calcium carbonate, calcium phosphate or kaolinite, or a soft capsule, wherein the active ingredient is a water-soluble solvent Such as propylene glycol, PEG mixed with ethanol, or mixed with oily medium, such as peanut oil, liquid paraffin or olive oil.

For example, a solid oral pharmaceutical such as a tablet or capsule may contain from 1 to 99% (w/w) of the triterpene mixture; from 0 to 99% (w/w) diluent or filler; from 0 to 20 % (w/w) disintegrant; 0 to 5% (w/w) lubricant; 0 to 5% (w/w) flow aid; 0 to 50% (w/w) granulation Agent or binder; 0 to 5% (w/w) antioxidant; and 0 to 5% (w/w) pigment. A controlled release tablet may further comprise from 0 to 90% (w/w) controlled release of the multimolecule.

A non-oral formulation (eg, a solution or suspension for injection, or a solution for perfusion) may comprise from 1 to 50% (w/w) of the triterpene mixture; and 50% (w/w) ) to 99% (w/w) of a liquid or semi-liquid carrier (eg, a solvent such as water); and 0-20% (w/w) of one or more excipients such as buffer solvents, antioxidants, suspension stabilizers , tension modifiers and preservatives.

One of the drugs of the present invention may be an oil-in-water emulsion. The oil phase may be a vegetable oil such as olive oil or peanut oil, or a mineral oil such as liquid paraffin, or a mixture thereof. Suitable emulsifiers may be naturally occurring phospholipids such as soy, lecithin, and esters or partial esters derived from fatty acids and hexitol anhydrides, such as sorbitan monooleate, and the partial esters and ethylene oxide. Condensation products such as polyoxyethylene sorbitol monooleate. The emulsion may also contain a sweetener and a flavoring agent.

Syrups and elixirs may be formulated with sweetening agents such as, for example, glycerol, propylene glycol, sorbitol or sucrose. Such formulations may contain a preservative, flavoring, and coloring agent. The pharmaceutical product may be in the form of a sterile aqueous or oily suspension for injection. The suspension may be formulated according to conventional techniques using suitable dispersing or wetting agents or suspending agents. Sterile Injectable Formulations Sterile injectable solutions or suspensions may be dissolved in a non-toxic, injectionally acceptable diluent or solvent, for example, in 1,3-butanediol. Among the acceptable carriers and solvents, for example, water, Ringers solution, and isotonic sodium chloride solution can be used. Cosolvents such as ethanol, propylene glycol, or polyethylene glycol are also suitable. In addition, sterile, fixed oils may also be employed as a solvent or suspension medium. For the foregoing purposes, any odorless, non-volatile oil may be employed, including synthetic mono- or di-glycerides. In addition, fatty acids such as oleic acid can also be used in the preparation of injectables.

The triterpene mixture of the present invention can also be administered as a suppository, and the drug is administered rectally. These compositions can be prepared by mixing a triterpene mixture with a suitable non-irritating excipient which is solid at room temperature but which will melt into the rectum and release the drug at rectal temperatures. Such materials include cocoa butter and polyethylene glycol.

When used topically, a cream, ointment, gel, solution or suspension containing the triterpene mixture of the present invention may be employed (for topical use, the topical use should include a mouthwash). Formulations for topical use may generally comprise a pharmaceutically acceptable carrier, cosolvent, emulsifier, penetration enhancer, preservative system, and emollient.

The following examples are provided to illustrate the specific aspects of the invention and to assist those of ordinary skill in the art to practice the invention. These examples are not intended to limit the scope of the invention in any way. It is believed that one skilled in the art can fully utilize and implement the present invention in light of the teachings of the present invention without further elaboration.

Example

Materials and Methods

Animals: The C57BL/6J mouse system is housed in an animal facility that provides food and water for its own food.

Multiple sclerosis (MS) Experimental mode : Experimental autoimmune encephalomyelitis (Experimental Autoimmune Encephalomyelitis, EAE)

In order to induce EAE, 200 μL of myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 was injected subcutaneously (sc) in the flank of 10 weeks old female C57BL/6J mice. MOG35-55) is mixed with an immunization mixture of Complete Freund's Adjuvant (CFA). The immunization mixture was prepared by mixing MOG35-55 (2 mg/mL) with CFA in a ratio of 1:1 until an emulsified mixture was formed. On the second day after immunization, pertussis toxin (Pertussis toxin, PT, 400 ng) was administered intraperitoneally. The clinical signs of the mice were evaluated daily until the 14th day after inoculation. The severity of the clinical signs is shown in Table 1, and is assessed from 0-5 points.

Table 1

Treatment: The triterpene mixture of the present invention is administered orally to MOG/CFA-immunized mice at a dose of 600 mg/kg for seven consecutive days, wherein the mice have a clinical score of at least 1. The mice were sacrificed at the final stage of the experiment.

Hematoxylin and eosin (Hematoxylin and Eosin, H & E ) staining: H & E stained using EAE mice show acute, CFA control mice and acute EAE mice by treatment of the mixture is the case of spinal cord white matter of the difference in the case of infiltration. All staining was performed on the tissues collected in the final stage of the experiment according to standard procedures.

IL-17 ELISA :

The IL-17 line was analyzed using a commercial ELISA kit (Invitrogen cat # KMC3021) according to the manufacturer's instructions. The standard curve was obtained and the content of IL-17 was determined from the standard curve according to the standard statistical method.

Example 1 In this case, the mixture of triterpenoids EAE Mouse efficacy

EAE is a disease in which the central nervous system (CNS) is demyelinated by CD4+ T cells, which serves as a model for human MS. The pathological mechanism of EAE development includes activation of antigen-specific T cells and Th1 differentiation of T cells and macrophages after penetration into the CNS. IL-17 causes pathology of multiple sclerosis (MS). Previous studies have indicated that human patients with MS lesions will show an increased IL-17. Therefore, the efficacy of the triterpenoid mixture in this case for EAE mice as MS mode was evaluated by H&E staining and IL-17 content in blood.

EAE mice were induced and treated according to the procedures described in the "Materials and Methods" section. The results of the experiments are summarized in Table 2 and Figures 1 to 3.

According to the data in Table 2 and Figure 1, the clinical symptoms of MS in EAE mice appeared on the second day. If the treatment was not received, EAE knew that the condition gradually increased over time to 3.5, and on the contrary, the three cases were accepted. The EAE mice treated with the mixture had a low score, which clearly showed that the triterpene mixture of the present invention can effectively inhibit the development of MS in EAE mice.

Table 2

The foregoing results were further confirmed by histological analysis in which the spinal cord of all mice was used to prepare 6-10 um tissue sections at the final stage of the experiment. These tissues were subjected to H&E staining to show the condition of inflamed infiltration, and the results of a representative example are shown in Fig. 2. In Figure 2, significant numbers of inflammatory cells, demyelinated cells, and apoptotic cells were observed in the control animals (Fig. 2A); while tissues removed from animals treated with the triterpenoid mixture maintained their health (Fig. 2B). .

IL-17 is a well-known chemokine that activates T cells and other types of immune cells and manifests in a variety of immune diseases such as rheumatoid arthritis, lupus, asthma and multiple hardening. Previous studies have confirmed that there is a significant amount of IL-17 protein in the spinal cord of EAE mice, so the IL-17 content is a good indicator that can be used as an evaluation candidate for MS treatment. The IL-17 content in EAE mice receiving and not receiving the triterpenoids in this case is shown in Figure 3.

As shown in Figure 3, the triterpene mixture of the present invention can reduce the IL-17 content of EAE mice, which is consistent with the findings of Figures 1 and 2, which may suppress or inhibit the development of MS.

It is to be understood that the above-described embodiments are only provided to provide examples, and various modifications may be made by those skilled in the art. The above description, examples, and data sets provide a description of the embodiments of the invention and its structural details. Although the various embodiments of the present invention have been described above with a certain degree of detail, or with respect to one or more independent embodiments, those of ordinary skill in the art may, without departing from the spirit and scope of the disclosure. , to make various changes to the implementation of the disclosure.

The following figures are included to form and constitute a part of this specification, which illustrates various illustrative systems, methods, and other embodiments of various aspects of the invention. The details of the present invention can be more clearly understood by the following detailed description in the following detailed description, wherein FIG. 1 depicts the clinical score of EAE mice in one embodiment according to the disclosure of the present disclosure; DISCLOSURE OF THE INVENTION In one embodiment, photographs of spinal cord tissue taken from EAE mice were stained with H&E, wherein A: control group vector, and B: treated with the mixture of triterpenoids in this case, 100x magnification, inflammatory cells, myelin sheath The depleted and/or apoptotic cell lines are indicated by boxes; and Figure 3 is a bar graph depicting the effect of the triterpenoid mixture on the IL-17 content in the blood in one embodiment of the present disclosure.

Claims (3)

A use of a mixture for the preparation of a medicament for treating multiple sclerosis (MS), wherein the mixture is composed of ganoderic acid A (GAA), ganoderic acid B (GAB), ganoderic acid C (ganoderic acid C, GAC) , Ganoderma acid _{C 5 (ganoderic acid C 5,} GAC 5), Ganoderma acid _{C 6 (ganoderic acid C 6,} GAC 6), Ganoderma acid D (ganoderic acid D, GAD) , Ganoderma acid E (ganoderic acid E, GAE), ganoderic acid G (GAG), and ganoderenic acid D. The use of the first aspect of the patent application, wherein the weight of the GAA in the mixture is about 30-40%, and the weight of the GAB, GAC, GAD, and GAG in the mixture is about 10-15%, respectively, GAC ₅ , The weight of GAC ₆ , GAE and Ganoderma acid D in the mixture is approximately 3-6%. The use of the second aspect of the patent application, wherein the weight of the GAA in the mixture is about 35%, and the weight of the GAB, GAC, GAD, and GAG in the mixture is about 12%, respectively, GAC ₅ , GAC ₆ , GAE And the weight of the ganoderma acid D in the mixture is about 3, 6, 3.5, and 4.5%, respectively.