A traditional chinese medicine composition for treating schizophrenia

Abstract

The application provides a traditional Chinese medicine composition for treating schizophrenia, which is prepared from the following raw materials: gypsum 380-650 parts by weight, rehmannia 180-500 parts by weight, scrophularia 70-280 parts by weight, dogwood 70-280 parts by weight, nacre 380-650 parts by weight, turtle shell 70-280 parts by weight, poria 50-250 parts by weight, radix curculiginis 50-250 parts by weight, curcuma 150-400 parts by weight, salvia 150-400 parts by weight, and siler 45-210 parts by weight.

Description

Technical Field

[0001] This invention relates to a traditional Chinese medicine composition, specifically a traditional Chinese medicine composition for treating schizophrenia and its preparation method, belonging to the field of medicine. Background Technology

[0002] Schizophrenia is a highly disabling and harmful severe mental illness. According to the neurodevelopmental theory of schizophrenia, it is divided into the pre-illness stage, prodromal stage, illness stage, and remission stage. The prodromal stage refers to the period from the onset of subtle psychomotor abnormalities to the point before these abnormalities meet the diagnostic criteria for schizophrenia. Schizophrenia is a chronic, progressive disease; therefore, intervention during the prodromal stage can improve the effectiveness of treatment. Currently, identifying and intervening in the prodromal stage of schizophrenia has become a hot research topic internationally.

[0003] In the realm of Traditional Chinese Medicine (TCM), schizophrenia falls under the category of "epilepsy," and its etiology and manifestations have been recorded in ancient texts for a long time. Modern physicians also often use a combination of syndrome differentiation and disease differentiation to classify the prodromal stage of schizophrenia. The "TCM Intervention Guidelines for the Prodromal Stage of Schizophrenia" published by the China Association of Traditional Chinese Medicine classifies the disease into five syndrome types: liver qi stagnation affecting the brain, liver qi stagnation transforming into fire disturbing the brain, spleen and kidney deficiency failing to nourish the brain, phlegm accumulation obscuring the sensory orifices, and deficiency of both heart and spleen leading to malnourishment of the brain.

[0004] In treating the prodromal stage of schizophrenia, Western medicine uses low-dose antipsychotics and natural active substances. However, long-term use of antipsychotics has significant side effects and ethical risks, and the efficacy of natural active substances is uncertain. Traditional Chinese medicine (TCM) adopts a differentiated treatment strategy, achieving more targeted and significant results. TCM treatment for the prodromal stage of schizophrenia is increasingly valued and favored by clinicians due to its proven efficacy and minimal adverse effects. Summary of the Invention

[0005] To address the problems existing in the prior art, the present invention provides a traditional Chinese medicine composition that has significant therapeutic effects on schizophrenia and low toxicity and side effects.

[0006] As one aspect of the present invention, the present invention provides a traditional Chinese medicine composition for treating schizophrenia, the traditional Chinese medicine composition being made from the following raw materials: gypsum, rehmannia root, scrophularia root, cornus fruit, mother-of-pearl, tortoise shell, poria cocos, bamboo shavings, turmeric, salvia miltiorrhiza, and saposhnikovia root.

[0007] In a specific embodiment, the traditional Chinese medicine composition is made from the following raw materials: gypsum 380-650 parts by weight, rehmannia glutinosa 180-500 parts by weight, scrophularia ningpoensis 70-280 parts by weight, cornus officinalis 70-280 parts by weight, mother-of-pearl 380-650 parts by weight, tortoise shell 70-280 parts by weight, poria cocos 50-250 parts by weight, bamboo shavings 50-250 parts by weight, turmeric 150-400 parts by weight, salvia miltiorrhiza 150-400 parts by weight, and saposhnikovia divaricata 45-210 parts by weight.

[0008] Preferably, the traditional Chinese medicine composition is made from the following raw materials: gypsum 410-590 parts by weight, rehmannia glutinosa 195-450 parts by weight, scrophularia ningpoensis 85-240 parts by weight, cornus officinalis 85-240 parts by weight, mother-of-pearl 410-590 parts by weight, tortoise shell 85-240 parts by weight, poria cocos 70-220 parts by weight, bamboo shavings 70-220 parts by weight, turmeric 180-360 parts by weight, salvia miltiorrhiza 180-360 parts by weight, and saposhnikovia divaricata 60-175 parts by weight.

[0009] More preferably, the traditional Chinese medicine composition is made from the following raw materials: gypsum 450-550 parts by weight, rehmannia glutinosa 285-400 parts by weight, scrophularia ningpoensis 110-210 parts by weight, cornus officinalis 110-210 parts by weight, mother-of-pearl 450-550 parts by weight, tortoise shell 110-210 parts by weight, poria cocos 90-180 parts by weight, bamboo shavings 90-180 parts by weight, turmeric 210-320 parts by weight, salvia miltiorrhiza 210-320 parts by weight, and saposhnikovia divaricata 75-135 parts by weight.

[0010] Most preferably, the traditional Chinese medicine composition is made from the following raw materials: 500 parts by weight of gypsum, 333 parts by weight of rehmannia root, 167 parts by weight of scrophularia root, 167 parts by weight of cornus fruit, 500 parts by weight of mother-of-pearl, 167 parts by weight of tortoise shell, 133 parts by weight of poria cocos, 133 parts by weight of bamboo shavings, 266 parts by weight of turmeric, 266 parts by weight of salvia miltiorrhiza, and 100 parts by weight of saposhnikovia root.

[0011] Alternatively, 485 parts by weight of gypsum, 350 parts by weight of rehmannia root, 140 parts by weight of scrophularia root, 180 parts by weight of cornus fruit, 485 parts by weight of mother-of-pearl, 180 parts by weight of tortoise shell, 115 parts by weight of poria cocos, 150 parts by weight of bamboo shavings, 250 parts by weight of turmeric, 280 parts by weight of salvia miltiorrhiza, and 90 parts by weight of saposhnikovia root.

[0012] Alternatively, 515 parts by weight of gypsum, 315 parts by weight of rehmannia root, 180 parts by weight of scrophularia root, 140 parts by weight of cornus fruit, 515 parts by weight of mother-of-pearl, 140 parts by weight of tortoise shell, 150 parts by weight of poria cocos, 115 parts by weight of bamboo shavings, 280 parts by weight of turmeric, 250 parts by weight of salvia miltiorrhiza, and 110 parts by weight of saposhnikovia root.

[0013] The traditional Chinese medicine composition described in this invention can be a composition formed by mixing various raw materials after pulverizing them, or an extract obtained by mixing or extracting them individually, or an effective part obtained by further refining and purifying the extract, or a conventional dosage form made by adding pharmaceutically acceptable excipients.

[0014] The extraction methods include decoction extraction, reflux extraction, maceration extraction, ultrasonic extraction, percolation extraction, and microwave extraction; the purification methods include water extraction and alcohol precipitation, alkali dissolution and acid precipitation, and various column chromatography purification methods, such as macroporous resin columns, silica gel columns, gel columns, and reversed-phase columns; the conventional dosage forms include, but are not limited to, injections, capsules, tablets, granules, gels, sustained-release preparations, oral liquids, pellets, or nano-preparations; the pharmaceutically acceptable excipients include: fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, and matrices. Fillers include: starch, pregelatinized starch, lactose, mannitol, chitosan, microcrystalline cellulose, sucrose, etc.; disintegrants include: starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, croscarmellose, low-substituted hydroxypropyl cellulose, croscarmellose sodium, etc.; lubricants include: magnesium stearate, sodium lauryl sulfate, talc, silica, etc.; suspending agents include: polyvinylpyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropyl methylcellulose, etc.; binders include: starch paste, polyvinylpyrrolidone, hydroxypropyl methylcellulose, etc.

[0015] As a second aspect of the present invention, the present invention also provides a traditional Chinese medicine composition for treating schizophrenia, the traditional Chinese medicine composition being made from the following raw materials: 410-590 parts by weight of gypsum extract, 195-450 parts by weight of Rehmannia glutinosa extract, 85-240 parts by weight of Scrophularia ningpoensis extract, 85-240 parts by weight of Cornus officinalis extract, 410-590 parts by weight of mother-of-pearl extract, 85-240 parts by weight of tortoise shell extract, 70-220 parts by weight of Poria cocos extract, 70-220 parts by weight of Bambusa textilis extract, 180-360 parts by weight of Curcuma longa extract, 180-360 parts by weight of Salvia miltiorrhiza extract, and 60-175 parts by weight of Saposhnikovia divaricata extract.

[0016] Preferably, the traditional Chinese medicine composition is made from the following raw materials: 450-550 parts by weight of gypsum extract, 285-400 parts by weight of Rehmannia glutinosa extract, 110-210 parts by weight of Scrophularia ningpoensis extract, 110-210 parts by weight of Cornus officinalis extract, 450-550 parts by weight of mother-of-pearl extract, 110-210 parts by weight of tortoise shell extract, 90-180 parts by weight of Poria cocos extract, 90-180 parts by weight of Bambusa textilis extract, 210-320 parts by weight of Curcuma longa extract, 210-320 parts by weight of Salvia miltiorrhiza extract, and 75-135 parts by weight of Saposhnikovia divaricata extract.

[0017] Most preferably, the traditional Chinese medicine composition is made from the following raw materials: 500 parts by weight of gypsum extract, 333 parts by weight of rehmannia extract, 167 parts by weight of scrophularia extract, 167 parts by weight of cornus extract, 500 parts by weight of mother-of-pearl extract, 167 parts by weight of tortoise shell extract, 133 parts by weight of poria extract, 133 parts by weight of bamboo shavings extract, 266 parts by weight of turmeric extract, 266 parts by weight of salvia miltiorrhiza extract, and 100 parts by weight of saposhnikovia extract.

[0018] The extracts are either extracts obtained from the raw materials through water or organic solvent extraction, or effective fractions obtained after further purification.

[0019] As a third aspect of the present invention, the present invention provides the use of the traditional Chinese medicine composition in the preparation of a medicament for treating schizophrenia.

[0020] Preferably, the traditional Chinese medicine composition is used in the preparation of a medicament for treating the prodromal stage of schizophrenia.

[0021] The raw materials of this invention, namely gypsum, rehmannia, scrophularia, cornus officinalis, mother-of-pearl, tortoise shell, poria cocos, bamboo shavings, turmeric, salvia miltiorrhiza, and saposhnikovia divaricata, are all included in the 2015 edition of the Chinese Pharmacopoeia.

[0022] This application presents a traditional Chinese medicine composition. Gypsum clears heat and drains fire, nourishes yin and calms the mind; Rehmannia clears heat and relieves irritability. The brain is the seat of the spirit, and it prefers clarity and tranquility. The combination of these two herbs clears the pathogenic heat disturbing the mind and restores mental clarity, thus serving as the principal herbs. Mother-of-pearl calms the liver and suppresses yang, sedates and calms the mind; tortoise shell nourishes yin and suppresses yang, tonifies the kidneys and replenishes essence; Cornus officinalis tonifies the kidneys and replenishes essence; Scrophularia ningpoensis nourishes yin and clears heat, thus serving as the assistant herbs; Curcuma longa, Saposhnikovia divaricata, Poria cocos, and Bambusa textilis regulate qi and resolve phlegm; Salvia miltiorrhiza invigorates blood and calms the mind, thus serving as the adjuvant herbs. The entire formula clears heat and nourishes yin, and has a strong calming effect on the mind.

[0023] This formula heavily utilizes gypsum, which is pungent, sweet, and slightly cold in nature. It not only primarily enters the lung meridian to clear excessive heat in the qi level, but can also be combined with various guiding herbs such as saposhnikovia root and turmeric to clear the fire evil disturbing the brain spirit from the five internal organs, thus calming the mind. Saposhnikovia root is sweet and warm in nature. In this formula, it can not only unblock the five internal organs, tonify the middle jiao, and benefit the spirit, but also serve as a guiding herb, combined with gypsum and other herbs to clear the fire evil disturbing the brain spirit. Detailed Implementation

[0024] Example 1

[0025] Formula: 50g gypsum, 15g rehmannia root, 15g scrophularia root, 15g cornus fruit, 30g mother-of-pearl, 10g tortoise shell, 20g poria cocos, 10g bamboo shavings, 10g turmeric, 15g salvia miltiorrhiza, 5g saposhnikovia root;

[0026] Preparation method: Add water and decoct (decocted by the hospital's Chinese medicine pharmacy). Take 400mL of the decoction for each dose and have the patient take it warm twice a day, morning and evening.

[0027] Example 2

[0028] Formula: Gypsum 500g, Rehmannia glutinosa 333g, Scrophularia ningpoensis 167g, Cornus officinalis 167g, Mother-of-pearl 500g, Tortoise shell 167g, Poria cocos 133g, Bambusa textilis 133g, Curcuma longa 266g, Salvia miltiorrhiza 266g, Saposhnikovia divaricata 100g;

[0029] Preparation method:

[0030] Take the tortoise shell, crush it, add water and decoct twice, each time adding 10 times the amount of water, decoct for 3 hours each time, filter, and reserve the filtrate; add 10 times the amount of water to the remaining ten ingredients, add gypsum and mother-of-pearl, decoct for 1 hour first, then add the remaining eight ingredients, decoct 3 times, each time adding 10 times the amount of water, decoct for 1 hour each time, combine the decoctions, filter, combine the filtrate with the tortoise shell extract, concentrate under reduced pressure to a thick paste with a relative density of 1.25-1.30 (50℃), dry, pulverize, add an appropriate amount of dextrin, mix well, and make 1000g of granules.

[0031] Example 3

[0032] Formula: Gypsum 485g, Rehmannia glutinosa 350g, Scrophularia ningpoensis 140g, Cornus officinalis 180g, Mother-of-pearl 485g, Tortoise shell 180g, Poria cocos 115g, Bambusa textilis 150g, Curcuma longa 250g, Salvia miltiorrhiza 280g, Saposhnikovia divaricata 90g;

[0033] The preparation method is the same as in Example 2.

[0034] Example 4

[0035] Formula: Gypsum 515g, Rehmannia glutinosa 315g, Scrophularia ningpoensis 180g, Cornus officinalis 140g, Mother-of-pearl 515g, Tortoise shell 140g, Poria cocos 150g, Bambusa textilis 115g, Curcuma longa 280g, Salvia miltiorrhiza 250g, Saposhnikovia divaricata 110g;

[0036] The preparation method is the same as in Example 2.

[0037] Example 5

[0038] Formula: Gypsum 460g, Rehmannia glutinosa 380g, Scrophularia ningpoensis 120g, Cornus officinalis 200g, Mother-of-pearl 460g, Tortoise shell 200g, Poria cocos 100g, Bambusa textilis 170g, Curcuma longa 230g, Salvia miltiorrhiza 300g, Saposhnikovia divaricata 80g;

[0039] Preparation method:

[0040] The above eleven ingredients are extracted twice by reflux with 75% ethanol solution, each extraction lasting 1 hour. The extracts are combined, filtered, and the filtrate is concentrated under reduced pressure to a thick paste with a relative density of 1.25-1.30 (50℃). The paste is dried, pulverized, and mixed with an appropriate amount of dextrin. The mixture is then granulated, encapsulated, and the final product is obtained.

[0041] Example 6

[0042] Formula: Gypsum 530g, Rehmannia glutinosa 300g, Scrophularia ningpoensis 200g, Cornus officinalis 120g, Mother-of-pearl 530g, Tortoise shell 120g, Poria cocos 170g, Bambusa textilis 100g, Curcuma longa 300g, Salvia miltiorrhiza 230g, Saposhnikovia divaricata 120g;

[0043] The preparation method is the same as in Example 5.

[0044] Example 7

[0045] Formula: Gypsum 430g, Rehmannia glutinosa 420g, Scrophularia ningpoensis 100g, Cornus officinalis 220g, Mother-of-pearl 430g, Tortoise shell 220g, Poria cocos 80g, Bambusa textilis 200g, Curcuma longa 200g, Salvia miltiorrhiza 340g, Saposhnikovia divaricata 65g;

[0046] The preparation method is the same as in Example 5.

[0047] Example 8

[0048] Formula: Gypsum 570g, Rehmannia glutinosa 270g, Scrophularia ningpoensis 220g, Cornus officinalis 100g, Mother-of-pearl 570g, Tortoise shell 100g, Poria cocos 200g, Bambusa textilis 80g, Curcuma longa 340g, Salvia miltiorrhiza 200g, Saposhnikovia divaricata 150g;

[0049] Preparation method:

[0050] The above eleven ingredients were extracted twice with 75% ethanol solution using ultrasound, each extraction lasting 40 minutes. The extracts were combined, filtered, and the filtrate was concentrated under reduced pressure to a thick paste with a relative density of 1.25–1.30 (50°C). The paste was dried, pulverized, and mixed with an appropriate amount of dextrin. The paste was then compressed into tablets to obtain the final product.

[0051] Example 9

[0052] Formula: 600g gypsum, 235g rehmannia, 260g scrophularia, 80g cornus, 600g mother-of-pearl, 80g tortoise shell, 230g poria, 65g bamboo shavings, 375g turmeric, 165g salvia miltiorrhiza, 185g saposhnikovia divaricata;

[0053] The preparation method is the same as in Example 8.

[0054] Example 10

[0055] Formula: 400g gypsum, 480g rehmannia root, 80g scrophularia root, 260g cornus fruit, 400g mother-of-pearl, 260g tortoise shell, 650g poria cocos, 230g bamboo shavings, 165g turmeric, 375g salvia miltiorrhiza, 55g saposhnikovia root;

[0056] The preparation method is the same as in Example 8.

[0057] Example 11

[0058] Formula: 500g gypsum extract, 333g rehmannia extract, 167g scrophularia extract, 167g cornus extract, 500g mother-of-pearl extract, 167g tortoise shell extract, 133g poria cocos extract, 133g bamboo shavings extract, 266g turmeric extract, 266g salvia miltiorrhiza extract, 100g saposhnikovia divaricata extract.

[0059] Example 12

[0060] Formula: 485g gypsum extract, 350g rehmannia extract, 140g scrophularia extract, 180g cornus extract, 485g mother-of-pearl extract, 180g tortoise shell extract, 115g poria cocos extract, 150g bamboo shavings extract, 250g turmeric extract, 280g salvia miltiorrhiza extract, and 90g saposhnikovia divaricata extract.

[0061] Example 13

[0062] Formula: 515g gypsum extract, 315g rehmannia extract, 180g scrophularia extract, 140g cornus extract, 515g mother-of-pearl extract, 140g tortoise shell extract, 150g poria cocos extract, 115g bamboo shavings extract, 280g turmeric extract, 250g salvia miltiorrhiza extract, 110g saposhnikovia divaricata extract.

[0063] Example 14

[0064] Formula: 460g gypsum extract, 380g rehmannia extract, 120g scrophularia extract, 200g cornus extract, 460g mother-of-pearl extract, 200g tortoise shell extract, 100g poria cocos extract, 170g bamboo shavings extract, 230g turmeric extract, 300g salvia miltiorrhiza extract, and 80g saposhnikovia divaricata extract.

[0065] Example 15

[0066] Formula: 530g gypsum extract, 300g rehmannia extract, 200g scrophularia extract, 120g cornus extract, 530g mother-of-pearl extract, 120g tortoise shell extract, 170g poria cocos extract, 100g bamboo shavings extract, 300g turmeric extract, 230g salvia miltiorrhiza extract, and 120g saposhnikovia divaricata extract.

[0067] Example 16

[0068] Formula: 430g gypsum extract, 420g rehmannia extract, 100g scrophularia extract, 220g cornus extract, 430g mother-of-pearl extract, 220g tortoise shell extract, 80g poria cocos extract, 200g bamboo shavings extract, 200g turmeric extract, 340g salvia miltiorrhiza extract, and 65g saposhnikovia divaricata extract.

[0069] Example 17

[0070] Formula: 570g gypsum extract, 270g rehmannia extract, 220g scrophularia extract, 100g cornus extract, 570g mother-of-pearl extract, 100g tortoise shell extract, 200g poria cocos extract, 80g bamboo shavings extract, 340g turmeric extract, 200g salvia miltiorrhiza extract, and 150g saposhnikovia divaricata extract.

[0071] The extracts described in Examples 11-17 above are water extracts of the respective active pharmaceutical ingredients.

[0072] Example 18 Comparative Example

[0073] Lycium and Chrysanthemum Decoction

[0074] Formula: 10g wolfberry, 10g chrysanthemum, 20g prepared rehmannia root, 15g poria cocos, 10g peony bark, 10g alisma plantago-aquatica, 15g yam, 15g cornus officinalis.

[0075] Preparation method: Add water and decoct (decocted by the hospital's Chinese medicine pharmacy). Take 400mL of the decoction for each dose and have the patient take it warm twice a day, morning and evening.

[0076] Example 19: Clinical Trial Results (I)

[0077] 1. Clinical Data

[0078] Forty patients in the prodromal stage of schizophrenia from the outpatient department of Beijing Anding Hospital affiliated to Capital Medical University were randomly assigned to the experimental group and the control group in a 1:1 ratio using a random number table.

[0079] 2. Drug composition and usage

[0080] Control group: Lycium barbarum and Rehmannia glutinosa decoction prepared according to Example 18;

[0081] Experimental group: Traditional Chinese medicine decoction prepared according to Example 1.

[0082] 3 Treatment Plans

[0083] 3.1 Inclusion criteria

[0084] A. Meets the criteria for Brief Intermittent Psychosis Syndrome (BIPS) and Mild Positive Symptom Syndrome (APS) in the COPS (High Risk of Psychosis Syndrome) criteria; B. Age 12-35 years (inclusive); C. Voluntarily signs informed consent and is able to follow the research protocol; D. No significant intellectual disability (IQ ≥ 80 points) and can understand the follow-up questionnaire; E. Meets the criteria for the TCM syndrome of kidney deficiency and liver hyperactivity in psychiatry.

[0085] 3.2 Exclusion Criteria

[0086] A. Individuals with severe suicidal tendencies; B. Individuals experiencing depressive episodes secondary to other mental or physical illnesses; C. Individuals with severe or unstable internal medical conditions such as heart, liver, kidney, endocrine, or hematological diseases; D. Individuals who have been taking antipsychotic medication within the four weeks prior to enrollment; E. Individuals who are unsupervised or unable to take medication as prescribed; F. Individuals whose baseline score on the schizophrenia risk profile scale for the very high-risk population has decreased by ≥25% compared to the screening score; G. Individuals who meet the criteria for genetic risk plus functional decline syndrome (GRDS) in the COPS (very high-risk) criteria for psychotic risk syndrome.

[0087] 3.3 Research Methods

[0088] Patients who had not taken antipsychotic medication for nearly one week were enrolled and began taking the study drug. Those who had been taking antipsychotic medication had to stop taking it for one week for washout before starting the study drug. Patients in the control group took one packet of Lycium barbarum and Rehmannia glutinosa orally (twice a day, after breakfast and dinner); patients in the experimental group took one packet of the herbal composition of this invention orally (twice a day, after breakfast and dinner).

[0089] Treatment duration: Both the treatment and control groups underwent 8 weeks of treatment.

[0090] During the observation period, the original medications for treating physical illnesses may be used, and the types and dosages of medications should be kept as unchanged as possible; other types of antidepressants, antipsychotics, anti-anxiety drugs, mood stabilizers and other Western medicines are prohibited; other Chinese medicines or proprietary Chinese medicine preparations besides the Chinese medicines used in this plan are prohibited; physical therapy such as electroconvulsive therapy is prohibited.

[0091] 4. Observation of therapeutic effects

[0092] 4.1 Observation Indicators

[0093] Changes in the Schizophrenia Very High Risk Population Scale (SIPS), Global Assessment of Functioning (GAF), and Positive and Negative Symptom Rating Scales (PANSS) were assessed in both groups at baseline and at the end of weeks 4 and 8 of treatment. Cognitive functioning, including the Connecting Test (TMT) and the Consistent Performance Test (CPT), was also assessed in both groups at baseline and at the end of weeks 4 and 8 of treatment.

[0094] 4.2 Statistical Processing Methods

[0095] The full analysis dataset was used, and SAS 9.4 software was applied for statistical analysis. Normally distributed continuous data are expressed as mean ± standard deviation. A mixed-effects model with repeated measures (MMRM) was used to analyze the main symptom response scores (PANSS and SOPS scores) and cognitive function scores (TMT-A connect-the-dots test and CPT). The treatment group was a fixed variable, and the follow-up time was a repeated measures test; missing values ​​were not estimated. Two-tailed hypothesis testing was performed, with a significance level of α = 0.05.

[0096] 5 Results

[0097] 5.1 General Information: Results are shown in Table 1. There were no significant differences in age or years of education between the two groups (P > 0.05). There were no significant differences in PANSS and SOPS scores at baseline between the two groups (t = 0.14 and t = 0.86, P > 0.05), nor in the scores of the TMT-A cognitive assessment and CPT (t = 0.7 and t = 1.32, P > 0.05).

[0098] Table 1. Demographic data for the two groups

[0099] entry experimental group control group t-value p-value Age (years) 19.95±4.12 21.4±5.03 1.00 0.33 Years of education 12.65±2.41 13.00±2.62 0.44 0.66 PANSS 61.90±12.71 61.35±13.03 0.14 0.89 SOPS 31.00±14.43 27.65±9.62 0.86 0.39 Connection test 34.23±10.97 37.06±14.54 0.70 0.49 Continuous operation test 37.06±2.72 3.03±0.87 1.32 0.19

[0100] 5.2 Comparison of clinical efficacy between the experimental group and the control group:

[0101] The results are shown in Table 2. PANSS analysis showed no significant main effect of differences between groups (F = 1.18, P > 0.05), but a significant time effect (F = 18.89, P < 0.001), and no interaction between time and group (F = 1.66, P > 0.05). Further analysis revealed that only the experimental group showed improvement over time (F = 9.87, P < 0.01).

[0102] SOPS analysis showed no significant main effect of differences between groups (F = 0.13, P > 0.05), but a significant time effect (F = 13.61, P < 0.001), and no interaction between time and group (F = 1.88, P > 0.05). Further analysis revealed that only the experimental group showed improvement over time (F = 7.44, P < 0.01).

[0103] 5.3 Comparison of cognitive function between the experimental group and the control group:

[0104] The results are shown in Table 2. Analysis of the connection test results showed no significant difference between the two groups (F = 2.92, P > 0.05), a significant time effect (F = 6.39, P < 0.01), and no significant group-time interaction (F = 0.49, P > 0.05). Further simple effects analysis showed that only the experimental group showed improvement over time (F = 4.48, P < 0.05), while the control group showed no improvement (F = 0.77, P > 0.05).

[0105] Analysis of the results of the continuous performance test showed no significant difference between the two groups (F = 0.32, P > 0.05), and the time effect was not significant (F = 2.39, P > 0.05). However, there was an interaction effect between groups × time (F = 5.32, P < 0.01), indicating a difference in performance between the two groups over time. Further simple effects analysis showed that only the experimental group showed improvement over time (F = 5.03, P < 0.01), while the control group showed no improvement (F = 0.45, P > 0.05).

[0106] Table 2. Symptom scores and cognitive function scores.

[0107]

[0108] Example 20: Clinical Trial Results (II)

[0109] 1. Clinical Data

[0110] Fifty-four patients in the prodromal phase of schizophrenia from the outpatient department of Beijing Anding Hospital, affiliated with Capital Medical University, all met the diagnostic criteria for kidney deficiency and liver hyperactivity in Traditional Chinese Medicine, aged between 13 and 35 years, and with a disease duration between 0.5 and 8 years. They were randomly divided into two groups: a treatment group and a control group, with 27 patients in each group. There were no significant differences between the two groups in terms of gender, age, disease duration, and the Structured Predromal Syndrome Study (SIPS) score.

[0111] 2. Drug composition and usage

[0112] Positive control group: aripiprazole, trade name: Aopai, 5mg per tablet, manufactured by Shanghai Zhongxi Pharmaceutical Co., Ltd.

[0113] Experimental group: Granules of the traditional Chinese medicine composition of the present invention were prepared according to Example 2;

[0114] 3 Treatment Plans

[0115] 3.1 Inclusion criteria

[0116] A. Meets the criteria for Brief Intermittent Psychosis Syndrome (BIPS) and Mild Positive Symptom Syndrome (APS) in the COPS (High Risk of Psychosis Syndrome) criteria; B. Age 12-35 years (inclusive); C. Voluntarily signs informed consent and is able to follow the research protocol; D. No significant intellectual disability (IQ ≥ 80 points) and can understand the follow-up questionnaire; E. Meets the criteria for the TCM syndrome of kidney deficiency and liver hyperactivity in psychiatry.

[0117] 3.2 Exclusion Criteria

[0118] A. Individuals with severe suicidal tendencies; B. Individuals experiencing depressive episodes secondary to other mental or physical illnesses; C. Individuals with severe or unstable internal medical conditions such as heart, liver, kidney, endocrine, or hematological diseases; D. Individuals who have been taking antipsychotic medication within the four weeks prior to enrollment; E. Individuals who are unsupervised or unable to take medication as prescribed; F. Individuals whose baseline score on the schizophrenia risk profile scale for the very high-risk population has decreased by ≥25% compared to the screening score; G. Individuals who meet the criteria for genetic risk plus functional decline syndrome (GRDS) in the COPS (very high-risk) criteria for psychotic risk syndrome.

[0119] 3.3 Research Methods

[0120] Patients who have not taken antipsychotic medication for nearly one week will start taking the study drug after enrollment. Those who have been taking antipsychotic medication must stop taking the medication for one week for washout before they can start taking the study drug.

[0121] The positive control group received oral aripiprazole (1-2 tablets once daily, after breakfast);

[0122] The experimental group took the herbal composition of this invention orally (1 sachet each time, twice a day, after breakfast and dinner);

[0123] Treatment duration: Both the treatment and control groups underwent a 12-week treatment course.

[0124] During the observation period, the original medications for treating physical illnesses may be used, and the types and dosages of medications should be kept as unchanged as possible; other types of antidepressants, antipsychotics, anti-anxiety drugs, mood stabilizers and other Western medicines are prohibited; other Chinese medicines or proprietary Chinese medicine preparations besides the Chinese medicines used in this plan are prohibited; physical therapy such as electroconvulsive therapy is prohibited.

[0125] 4. Observation of therapeutic effects

[0126] 4.1 Observation Indicators

[0127] Both groups of patients underwent assessments at baseline and at the end of weeks 4, 8, and 12 of treatment, based on changes in the Schizophrenia Very High Risk Scale (SIPS), Global Assessment of Functioning (GAF), and Positive and Negative Symptom Rating Scales (PANSS). Cognitive tests, including symbol coding, linking tests, word learning, graphic memory, STROOPS, and CPT (Continuous Performance Test), were performed at baseline and at the end of week 8 and 12 of treatment. Physical examinations and routine blood, urine, and stool tests, liver and kidney function tests, and electrocardiograms, as well as other relevant safety-related examinations, were conducted at baseline and 12 weeks after treatment.

[0128] 4.2 Statistical Processing Methods

[0129] SPSS 15.0 statistical analysis software was used. The χ² test was used for count data, and the test was used for continuous data. The differences at each time point were calculated using repeated measures ANOVA, and the differences between groups were analyzed using independent samples t-tests. P < 0.05 was considered statistically significant.

[0130] 5 Results

[0131] 5.1 General Information: There were no statistically significant differences in age and disease duration between the two groups. There were also no statistically significant differences in baseline scores on any of the scales between the two groups. See Table 3.

[0132] Table 3 General Information for the Two Groups

[0133] entry Positive control group experimental group t-value p-value Age (years) 20.04±4.98 19.12±4.27 0.726 0.471 Years of education 13.29±2.61 12.15±2.40 1.657 0.104 GAF Total Score 47.04±5.51 45.85±4.52 0.863 0.389 PANSS total score 60.79±12.34 61.50±12.21 0.931 0.358 SIPS total score 26.75±10.35 26.42±8.25 0.214 0.832 Dosage (mg) 6.79±2.44 - - -

[0134] At baseline, there were no significant differences between the two groups in GAF, PANSS, and SIPS scores (t = 0.87, p = 0.39; t = 0.21, p = 0.83; t = 0.13, p = 0.90).

[0135] 5.2 Comparison of clinical efficacy between the experimental group and the control group: see Table 4.

[0136] Table 4 Clinical efficacy of experimental group and control group

[0137]

[0138]

[0139] The results of the Repeated Measure MANOVA analysis showed that:

[0140] Regarding GAF: the main effect of subject grouping was not significant (F = 0.04, P > 0.05), the main effect of time was significant (F = 27.16, P < 0.001), and the interaction between subject grouping and time was significant (F = 4.17, P < 0.05). This means that both groups improved patients' GAF scores.

[0141] On the PANSS: the main effect of subject grouping was not significant (F = 0.05, P > 0.05), the main effect of time was significant (F = 59.91, P < 0.001), and the interaction between subject grouping and time was significant (F = 7.44, P < 0.05). In other words, both groups improved patients' PANSS scores.

[0142] On SIPS: the main effect of subject grouping was not significant (F = 0.15, P > 0.05), the main effect of time was significant (F = 55.92, P < 0.001), and the interaction between subject grouping and time was significant (F = 8.02, P < 0.05). This means that both groups improved patients' PANSS scores.

[0143] 5.3 Comparison of cognitive function between the experimental group and the control group: see Table 5.

[0144] There was no significant difference in cognitive function between the two groups at baseline (P > 0.05). Except for the continuous performance evaluation test, both groups showed improvement in cognitive function after 3 months of treatment compared to before treatment (P < 0.05). However, in the continuous performance evaluation test, the group treated with the composition of this invention showed improvement (P < 0.05), while the aripiprazole treatment group showed no significant improvement (P > 0.05).

[0145] Table 5 Changes in cognitive function before and after treatment in the two groups

[0146]

[0147]

[0148] 5.4 Comparison of adverse reactions between the experimental group and the control group

[0149] Regarding adverse reactions, there was no significant difference in the frequency of adverse reactions between the treatment group using the composition of this invention and the treatment group using aripiprazole (P>0.05), but the manifestations of the adverse reactions differed. Common adverse reactions in the composition group included gastrointestinal discomfort, mainly manifested as abdominal pain, nausea, and increased bowel movements, which were more pronounced in the first week and then less so. Common adverse reactions in the aripiprazole treatment group included extrapyramidal reactions and drowsiness, mainly manifested as tremor, increased muscle tone, increased sleep, and weight gain.

[0150] Example 21 Acute Toxicity Test

[0151] Mice were administered 2.69 g crude drug / ml of the granules prepared in Example 2 twice daily via gavage, with a single administration volume of 0.4 ml / 10 g body weight, and a cumulative dose of 215.20 g crude drug / kg. After 14 days of observation following administration, no toxic reactions were observed. The maximum dose of the herbal composition of this invention to mice was 215.20 g crude drug / kg (equivalent to 158.24 times the clinical dose of 1.36 g crude drug / kg).

Claims

1. A traditional Chinese medicine composition for treating schizophrenia, characterized in that, The traditional Chinese medicine composition is made from the following raw materials: 380-650 parts by weight of gypsum, 180-500 parts by weight of rehmannia root, 70-280 parts by weight of scrophularia root, 70-280 parts by weight of cornus fruit, 380-650 parts by weight of mother-of-pearl, 70-280 parts by weight of tortoise shell, 50-250 parts by weight of poria cocos, 50-250 parts by weight of bamboo shavings, 150-400 parts by weight of turmeric, 150-400 parts by weight of salvia miltiorrhiza, and 45-210 parts by weight of saposhnikovia root.

2. The traditional Chinese medicine composition as described in claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials: gypsum 410-590 parts by weight, rehmannia glutinosa 195-450 parts by weight, scrophularia ningpoensis 85-240 parts by weight, cornus officinalis 85-240 parts by weight, mother-of-pearl 410-590 parts by weight, tortoise shell 85-240 parts by weight, poria cocos 70-220 parts by weight, bamboo shavings 70-220 parts by weight, turmeric 180-360 parts by weight, salvia miltiorrhiza 180-360 parts by weight, and saposhnikovia divaricata 60-175 parts by weight.

3. The traditional Chinese medicine composition as described in claim 2, characterized in that, The traditional Chinese medicine composition is made from the following raw materials: gypsum 450-550 parts by weight, rehmannia glutinosa 285-400 parts by weight, scrophularia ningpoensis 110-210 parts by weight, cornus officinalis 110-210 parts by weight, mother-of-pearl 450-550 parts by weight, tortoise shell 110-210 parts by weight, poria cocos 90-180 parts by weight, bamboo shavings 90-180 parts by weight, turmeric 210-320 parts by weight, salvia miltiorrhiza 210-320 parts by weight, and saposhnikovia divaricata 75-135 parts by weight.

4. The traditional Chinese medicine composition as described in claim 3, characterized in that, The traditional Chinese medicine composition is made from the following raw materials: 500 parts by weight of gypsum, 333 parts by weight of rehmannia root, 167 parts by weight of scrophularia root, 167 parts by weight of cornus fruit, 500 parts by weight of mother-of-pearl, 167 parts by weight of tortoise shell, 133 parts by weight of poria cocos, 133 parts by weight of bamboo shavings, 266 parts by weight of turmeric, 266 parts by weight of salvia miltiorrhiza, and 100 parts by weight of saposhnikovia root. Alternatively, 485 parts by weight of gypsum, 350 parts by weight of rehmannia root, 140 parts by weight of scrophularia root, 180 parts by weight of cornus fruit, 485 parts by weight of mother-of-pearl, 180 parts by weight of tortoise shell, 115 parts by weight of poria cocos, 150 parts by weight of bamboo shavings, 250 parts by weight of turmeric, 280 parts by weight of salvia miltiorrhiza, and 90 parts by weight of saposhnikovia root. Alternatively, 515 parts by weight of gypsum, 315 parts by weight of rehmannia root, 180 parts by weight of scrophularia root, 140 parts by weight of cornus fruit, 515 parts by weight of mother-of-pearl, 140 parts by weight of tortoise shell, 150 parts by weight of poria cocos, 115 parts by weight of bamboo shavings, 280 parts by weight of turmeric, 250 parts by weight of salvia miltiorrhiza, and 110 parts by weight of saposhnikovia root.

5. The traditional Chinese medicine composition according to any one of claims 1-4, characterized in that, The traditional Chinese medicine composition is a composition formed by mixing various raw materials after pulverizing them, or an extract obtained by mixing or extracting various raw materials individually, or a conventional dosage form made by adding pharmaceutically acceptable excipients.

6. The traditional Chinese medicine composition as described in claim 5, characterized in that, The extraction methods include decoction extraction, reflux extraction, maceration extraction, ultrasonic extraction, percolation extraction, and microwave extraction; the conventional dosage forms include injections, capsules, tablets, granules, gels, sustained-release preparations, oral liquids, pellets, or nano-preparations.

7. A traditional Chinese medicine composition for treating schizophrenia, characterized in that, The traditional Chinese medicine composition is made from the following raw materials: 410-590 parts by weight of gypsum extract, 195-450 parts by weight of Rehmannia glutinosa extract, 85-240 parts by weight of Scrophularia ningpoensis extract, 85-240 parts by weight of Cornus officinalis extract, 410-590 parts by weight of mother-of-pearl extract, 85-240 parts by weight of tortoise shell extract, 70-220 parts by weight of Poria cocos extract, 70-220 parts by weight of Bambusa textilis extract, 180-360 parts by weight of Curcuma longa extract, 180-360 parts by weight of Salvia miltiorrhiza extract, and 60-175 parts by weight of Saposhnikovia divaricata extract.

8. The traditional Chinese medicine composition according to claim 7, characterized in that, The traditional Chinese medicine composition is made from the following raw materials: 450-550 parts by weight of gypsum extract, 285-400 parts by weight of Rehmannia glutinosa extract, 110-210 parts by weight of Scrophularia ningpoensis extract, 110-210 parts by weight of Cornus officinalis extract, 450-550 parts by weight of mother-of-pearl extract, 110-210 parts by weight of tortoise shell extract, 90-180 parts by weight of Poria cocos extract, 90-180 parts by weight of Bambusa textilis extract, 210-320 parts by weight of Curcuma longa extract, 210-320 parts by weight of Salvia miltiorrhiza extract, and 75-135 parts by weight of Saposhnikovia divaricata extract.

9. The traditional Chinese medicine composition as described in claim 8, characterized in that, The traditional Chinese medicine composition is made from the following raw materials: 500 parts by weight of gypsum extract, 333 parts by weight of rehmannia extract, 167 parts by weight of scrophularia extract, 167 parts by weight of cornus extract, 500 parts by weight of mother-of-pearl extract, 167 parts by weight of tortoise shell extract, 133 parts by weight of poria extract, 133 parts by weight of bamboo shavings extract, 266 parts by weight of turmeric extract, 266 parts by weight of salvia miltiorrhiza extract, and 100 parts by weight of saposhnikovia extract.

10. The use of the traditional Chinese medicine composition according to any one of claims 1-4 and 7-9 in the preparation of a medicament for treating schizophrenia.

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