Use of a Tibetan medicine composition in the preparation of a medicament for preventing or treating autism spectrum disorder

Abstract

The present application relates to the technical field of medicine, in particular to a Tibetan medicine composition for preparing a medicine for preventing or treating autism spectrum disorder, wherein the Tibetan medicine composition comprises nacre, mace, nutmeg, cardamom, galangal, lime, safflower, clove, Zhidasazeng, licorice and pomegranate seed, and research finds that the Tibetan medicine composition has a positive therapeutic effect on autism spectrum disorder (especially autism).

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to the use of a Tibetan medicine composition in the preparation of a medicine for the prevention or treatment of autism spectrum disorder. Background Technology

[0002] Autistic Spectrum Disorder (ASD) is a pervasive developmental disorder caused by differences in brain development. Its symptoms include abnormal language and social skills, restricted interests, and repetitive behavioral patterns. ASD encompasses classic autism, Asperger's syndrome, and childhood disintegrative disorder; the term "autism" commonly refers to ASD in a broader sense. The global prevalence of ASD is currently estimated at 0.6%-1%. For over 80 years since its discovery, scientists have tirelessly searched for a cure. The number of new cases of autism is steadily increasing each year. The large number of cases and the lack of a cure have made autism one of the most studied childhood developmental disorders. Current ASD treatment primarily focuses on symptomatic relief, targeting symptoms that interfere with daily functioning and quality of life. Because the impact of ASD varies from person to person, each patient has different treatment needs, and treatment plans often involve multiple specialties.

[0003] To date, there is no specific drug that can cure ASD or treat its core symptoms, but medications can be used to treat comorbid problems. Therefore, a significant number of children and adolescents with ASD use medication. A survey from the Autism Treatment Network (ATN) found that among 2,853 registered children and adolescents aged 2-17 with ASD, 763 (27%) were taking at least one psychiatric medication, with 15% taking one, 7.4% taking two, and 4.5% taking at least three. The pathogenesis of ASD is currently unclear, but it is mainly attributed to genetic factors, organic brain factors, neurobiochemical factors, and cognitive deficits. However, according to an article titled "Advances in Research on Gut Microbiota and Autism" published in *Science Bulletin*, Vol. 63, No. 18, 2018, by Wu Xiaoli et al. from the Institute of Psychology, Chinese Academy of Sciences, they argue that the rapid increase in autism prevalence in recent years does not conform to the Hardy-Weinberg equilibrium, indicating that environmental factors have a far greater impact than genetic factors. Autism is closely related to gut microbiota imbalance and gut-brain axis abnormalities. Traditional Chinese medicine and Tibetan medicine offer numerous treatments for intestinal diseases and have achieved significant results. For example, modern medicine's treatments for inflammatory bowel diseases such as ulcerative colitis and Crohn's disease, which involve environmental, genetic, infectious, and immune factors, lack effective cures and can only address the symptoms.

[0004] Therefore, giving full play to the advantages of traditional Chinese medicine or Tibetan medicine and developing effective Chinese or Tibetan medicines for the prevention or treatment of autism has become an urgent issue that needs to be addressed. Summary of the Invention

[0005] Therefore, the object of the present invention is to provide a use of a Tibetan medicine composition in the preparation of a medicine for the prevention or treatment of autism spectrum disorder.

[0006] This invention provides the use of a Tibetan medicine composition in the preparation of a medicine for the prevention or treatment of autism spectrum disorder, the Tibetan medicine composition comprising mother-of-pearl, nutmeg, cardamom, amomum tsao-ko, travertine, safflower, clove, zhida sazeng, licorice, and pomegranate seeds.

[0007] Further, according to the weight parts, the Tibetan medicine composition includes 45-55 parts of mother-of-pearl, 25-50 parts of nutmeg, 25-45 parts of cardamom, 25-45 parts of amomum tsao-ko, 25-45 parts of travertine, 25-45 parts of safflower, 25-45 parts of clove, 25-30 parts of zhida sazeng, 25-30 parts of licorice, and 25-30 parts of pomegranate seeds.

[0008] Further, according to the weight parts, the Tibetan medicine composition comprises: 50 parts mother-of-pearl, 45 parts nutmeg, 45 parts cardamom, 45 parts amomum tsao-ko, 45 parts travertine, 45 parts safflower, 45 parts clove, 30 parts Zhida Sazeng, 30 parts licorice, and 30 parts pomegranate seeds; or, the Tibetan medicine composition comprises: 50 parts mother-of-pearl, 25 parts nutmeg, 25 parts cardamom, 25 parts amomum tsao-ko, 25 parts travertine, 25 parts safflower, 25 parts clove, 25 parts Zhida Sazeng, 25 parts licorice, and 25 parts pomegranate seeds; or, the Tibetan medicine composition comprises: 50 parts mother-of-pearl, 50 parts nutmeg, 45 parts cardamom, 45 parts amomum tsao-ko, 45 parts travertine, 45 parts safflower, 45 parts clove, 30 parts Zhida Sazeng, 30 parts licorice, and 30 parts pomegranate seeds.

[0009] Furthermore, the medicine comprises the Tibetan medicine composition described above, or optionally one or more pharmaceutically acceptable excipients.

[0010] Furthermore, the dosage form of the drug is a gel, cream, tablet, capsule, powder, mixture, pill, granule, oral liquid, syrup, decoction, suppository, aerosol, plaster, ointment, injection, spray, liniment, tincture, wet compress, paste, or lotion.

[0011] Further, the pharmaceutically acceptable excipients are selected from at least one of the following pharmaceutically acceptable solvents, solubilizers, co-solvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, flow aids, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesives, binding agents, penetration enhancers, pH adjusters, buffers, plasticizers, surfactants, thickeners, inclusion agents, humectants, absorbents, diluents, flocculants and anti-flocculation agents, filter aids, release inhibitors, polymeric framework materials, and film-forming materials.

[0012] Furthermore, the preparation method of the drug includes weighing mother-of-pearl, nutmeg, cardamom, amomum tsao-ko, travertine, safflower, clove, citronella, and pomegranate seeds according to selected weight proportions, mixing them, and adding or not adding pharmaceutically acceptable excipients, and preparing the drug according to conventional pharmaceutical processes.

[0013] Furthermore, the preparation method of the drug includes weighing mother-of-pearl, nutmeg, cardamom, amomum tsao-ko, travertine, safflower, clove, gentasamogen, licorice, and pomegranate seeds according to the selected weight proportions, mixing them, and then using water as a binder to make pills.

[0014] Furthermore, the autism spectrum disorder is selected from autism, Rett syndrome, Asperger's syndrome, or childhood disintegrative disorder.

[0015] The technical solution of this invention has the following advantages:

[0016] The Tibetan medicine composition provided by this invention is used in the preparation of drugs for the prevention or treatment of autism spectrum disorder. The Tibetan medicine composition includes mother-of-pearl, nutmeg, cardamom, amomum tsao-ko, travertine, safflower, clove, dasazan, licorice, and pomegranate seed. In the formula, mother-of-pearl, dasazan, and licorice are the principal drugs, which awaken the mind and open the orifices, and clear the meridians; nutmeg, cardamom, clove, and amomum tsao-ko are the assistant drugs, which have the effect of regulating and tonifying; travertine and safflower are the guiding drugs, which have the effect of clearing heat; and pomegranate seed is an auxiliary drug for harmonizing febrile diseases.

[0017] Animal experiments have shown that the Tibetan medicine composition of this invention (especially the modified Bami Ruyi Pill) has a positive therapeutic effect on autism spectrum disorders (especially autism). Detailed Implementation

[0018] The following embodiments are provided to better understand the present invention and are not limited to the preferred embodiments described. They do not constitute a limitation on the content and scope of protection of the present invention. Any product that is the same as or similar to the present invention, derived by any person under the guidance of the present invention or by combining the features of the present invention with other prior art, falls within the protection scope of the present invention.

[0019] For experiments not specifically described in the examples, the procedures or conditions should be followed according to the conventional experimental procedures described in the literature in this field. Reagents or instruments whose manufacturers are not specified are all commercially available conventional reagent products.

[0020] Example 1

[0021] The Tibetan medicine composition of this embodiment includes the following raw materials:

[0022] 50g mother-of-pearl, 25g nutmeg, 25g cardamom, 25g black cardamom, 25g travertine, 25g safflower, 25g cloves, 25g citronella, 25g licorice, 25g pomegranate seeds.

[0023] This embodiment also provides an Eight-Flavor Ruyi Pill, comprising the above-mentioned Tibetan medicine composition. Preparation method: The above-mentioned raw materials are pulverized into a fine powder, sieved, mixed evenly, formed into pills with water, dried, and prepared into pills.

[0024] Example 2

[0025] The Tibetan medicine composition of this embodiment includes the following raw materials:

[0026] Mother-of-pearl 50g, nutmeg 45g, cardamom 45g, amomum tsao-ko 45g, travertine 45g, safflower 45g, clove 45g, citronella 30g, licorice 30g, pomegranate seed 30g.

[0027] The pharmaceutical composition of this embodiment is prepared into granules according to conventional processes.

[0028] Example 3

[0029] The Tibetan medicine composition of this embodiment includes the following raw materials:

[0030] 50g mother-of-pearl, 25g nutmeg, 25g cardamom, 25g black cardamom, 25g travertine, 25g safflower, 25g cloves, 25g citronella, 25g licorice, 25g pomegranate seeds.

[0031] The pharmaceutical composition of this embodiment is formulated into a powder by adding pharmaceutically acceptable excipients and following conventional processes.

[0032] Example 4

[0033] The Tibetan medicine composition of this embodiment includes the following raw materials:

[0034] Mother-of-pearl 50g, nutmeg 45g, cardamom 45g, amomum tsao-ko 45g, travertine 45g, safflower 45g, clove 45g, citronella 30g, licorice 30g, pomegranate seed 30g.

[0035] The pharmaceutical composition of this embodiment is formulated into tablets by adding pharmaceutically acceptable excipients and following conventional processes.

[0036] Example 5

[0037] The Tibetan medicine composition of this example comprises the following raw medicinal materials:

[0038] Concha Margaritifera Usta 50g, Semen Myristicae 50g, Fructus Amomi Rotundus 45g, Fructus Tsaoko 45g, Concretio Silicea Bambusae 45g, Flos Carthami 45g, Flos Caryophylli 45g, Zhidasa Zeng 30g, Radix Glycyrrhizae 30g, Fructus Granati 30g.

[0039] The pharmaceutical composition of this example is added with pharmaceutically acceptable excipients and made into capsules according to conventional processes.

[0040] Experimental Example 1

[0041] 1. Preparation of animal model

[0042] C57BL / 6J mice, female, pregnant mice at 2 - 3 months old with visible vaginal plugs. These experimental animals were raised in the SPF - level animal house of Beijing Zhuokai Biotechnology Co., Ltd. The feeding temperature was maintained at 18 - 26°C, the humidity was maintained at 40 - 70%, and a 12h:12h light cycle was adopted. The welfare and usage regulations of experimental animals stipulated by the Beijing Laboratory Animal Management Committee were strictly followed. Facility license number: SCXK(Beijing)2022 - 0010. The technical operations of this experiment were carried out in accordance with the company's internal SOP (draft) for the management of animal experiment use licenses, and the animal experiment plan was approved by the Animal Management Committee of Zhongyan Zichuang (Beijing) Biotechnology Co., Ltd.

[0043] 40 pregnant mice (C57B / L6) at 0.5 days of pregnancy were purchased. At 12.5 days of pregnancy, 30 of them were intraperitoneally injected with a VPA solution of 600 mg / kg (the sodium valproate powder was prepared into a 25 mg / ml solution with 0.9% normal saline), and 10 were intraperitoneally injected with the same volume of 0.9% normal saline. After the newborn mice were born, the female mice and female newborn mice were culled and separated into cages 24 days later, and the males were retained. The male mice were used for experiments after growing to 1 month old.

[0044] 12 male mice obtained from the pregnant mice intraperitoneally injected with the VPA solution were randomly divided into 2 groups, a model group and a drug - administration group. The drug - administration group was intragastrically administered with an aqueous solution of the Bawei Ruyi Pills prepared in Example 1 (concentration: 10 mg / ml), administered twice a day, morning and evening, for 3 consecutive days. Calculated according to the mass of the Bawei Ruyi Pills, the dosage per administration was 1 g / kg. 6 male mice obtained from the pregnant mice intraperitoneally injected with 0.9% normal saline were designated as the blank group. The male mice were used for experiments after growing to 2 months old. [[ID=!]]

[0045] 2. Test method

[0046] Referring to the literature (Wang Jianfei et al., Behavioral Testing Methods for a Mouse Model of Autism Spectrum Disorder), a three-box social interaction test was used. An open field 1 meter long and 40 centimeters wide was evenly divided into three areas: Area A and Area B on either side, with the central area (or blank area) between Area A and Area B. The test consisted of three phases: an adaptation period (30 minutes), the first testing phase where an unfamiliar mouse was placed in Area A (30 minutes), and the second testing phase where an unfamiliar mouse was placed in Area B and a familiar mouse was placed in Area A (30 minutes). The test chamber was cleaned each time, but the restraint cages were not changed. Six male mice were used, with unfamiliar animals in the restraint cages.

[0047] Adaptation Period (DAY 1): Place restraint cages in the center of areas A and B. Allow each group of 6 animals to acclimatize to the environment for 30 minutes. The purpose of this stage is to allow the test animals to become accustomed to the experimental environment and eliminate potential environmental stress. Record the animals' movements, focusing on the time the animals spend within 5 cm of the restraint cage (areas A-1 and B-1).

[0048] First testing phase: (DAY2-1, 1st hour of the second day): Restraint cages were placed in the center of areas A and B. Six experimental animals from each group were tested sequentially for 30 minutes. An unfamiliar animal was placed in one of the restraint cages (area A), and the animal's trajectory was recorded. The focus was on observing the time the animal stayed within 5 cm of the restraint cage (areas A-1 and B-1) (considered as prosocial behavior).

[0049] The second testing phase (DAY 2-4H-LATER, after the 4th hour of the second day): Restraint cages were placed in the center of areas A and B. Six experimental animals from each group were tested sequentially for 30 minutes. One animal that had already interacted with the animals was placed in one restraint cage (area A), and an unfamiliar animal was placed in the other restraint cage (area B). The animals' movements were recorded, with a focus on observing the time the animals remained within 5 cm of the restraint cages (areas A-1 and B-1) (considered novelty behavior).

[0050] Areas A-1 and B-1 refer to the areas within 5 centimeters of the restraint cages in areas A and B, respectively.

[0051] 3. Data statistics and analysis

[0052] The experimental results are presented as mean ± standard error (SEM). Unpaired t-tests were used for comparisons between groups, assuming a normal distribution. A p-value < 0.05 was considered statistically significant.

[0053] 4. Experimental Results

[0054] The experimental results are shown in Table 1. During the 30-minute adaptation period, there was no significant difference in the total time spent in A-1 and B-1 among the blank control group, model group, and drug-treated group mice. In the first test phase (social behavior), the time spent in A-1 by the drug-treated group mice was significantly longer than that of the model group mice; in the second test phase (novelty behavior), the time spent in B-1 by the drug-treated group mice was significantly longer than that of the model control group and the drug-treated group mice (P < 0.05), indicating that Bawei Ruyi Wan significantly improved the social and novelty behaviors of mice.

[0055] Table 1. Outcomes of prosocial behavior (mean ± SEM)

[0056]

[0057] in, # This indicates that the p-value between the model group and the blank control group is <0.05; * This indicates that the p-value between the treatment group and the model group is <0.05.

[0058] In summary, this invention is the first to apply Bawei Ruyi Pill to the prevention and treatment of autism, providing a new therapeutic drug and method for the clinical treatment of autism, thereby providing technical support for precision medicine in clinical practice.

[0059] Obviously, the above embodiments are merely illustrative examples for clear explanation 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 here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. The use of a Tibetan medicine composition in the preparation of a medicament for the prevention or treatment of autism, characterized in that, The Tibetan medicine composition consists of 45-55 parts of mother-of-pearl, 25-50 parts of nutmeg, 25-45 parts of cardamom, 25-45 parts of amomum tsao-ko, 25-45 parts of travertine, 25-45 parts of safflower, 25-45 parts of clove, 25-30 parts of zhida sazeng, 25-30 parts of licorice, and 25-30 parts of pomegranate seeds.

2. The use according to claim 1, characterized in that, According to the weight parts, the Tibetan medicine composition consists of 50 parts mother-of-pearl, 45 parts nutmeg, 45 parts cardamom, 45 parts amomum tsao-ko, 45 parts travertine, 45 parts safflower, 45 parts clove, 30 parts Zhida Sazeng, 30 parts licorice, and 30 parts pomegranate seeds; or, the Tibetan medicine composition consists of 50 parts mother-of-pearl, 25 parts nutmeg, 25 parts cardamom, 25 parts amomum tsao-ko, 25 parts travertine, 25 parts safflower, 25 parts clove, 25 parts Zhida Sazeng, 25 parts licorice, and 25 parts pomegranate seeds; or, the Tibetan medicine composition consists of 50 parts mother-of-pearl, 50 parts nutmeg, 45 parts cardamom, 45 parts amomum tsao-ko, 45 parts travertine, 45 parts safflower, 45 parts clove, 30 parts Zhida Sazeng, 30 parts licorice, and 30 parts pomegranate seeds.

3. The use according to claim 1 or 2, characterized in that, The medicine comprises the Tibetan medicine composition of claim 1 or 2, and optionally one or more pharmaceutically acceptable excipients.

4. The use according to claim 3, characterized in that, The dosage forms of the drug are gels, creams, tablets, capsules, powders, mixtures, pills, granules, oral liquids, syrups, decoctions, injections, and tinctures.

5. The use according to claim 3, characterized in that, The pharmaceutically acceptable excipients are selected from at least one of the following pharmaceutically acceptable solvents, solubilizers, co-solvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, flow aids, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesives, binding agents, penetration enhancers, pH adjusters, buffers, plasticizers, surfactants, thickeners, inclusion agents, humectants, absorbents, diluents, flocculants and anti-flocculation agents, filter aids, release inhibitors, polymeric framework materials, and film-forming materials.

6. The use according to claim 1 or 2, characterized in that, The preparation method of the drug includes weighing mother-of-pearl, nutmeg, cardamom, amomum tsao-ko, travertine, safflower, clove, gentasamogen, licorice, and pomegranate seeds according to selected weight proportions, mixing them, and adding or not adding pharmaceutically acceptable excipients, and preparing the drug according to conventional pharmaceutical processes.

7. The use according to claim 1 or 2, characterized in that, The preparation method of the drug includes weighing mother-of-pearl, nutmeg, cardamom, amomum tsao-ko, travertine, safflower, clove, gentasamogen, licorice and pomegranate seeds according to the selected weight proportions, mixing them and then making them into pills with water as a binder.

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