Traditional Chinese medicine composition for treating yin and blood deficiency type depression

Abstract

The invention provides a traditional Chinese medicine composition for treating yin and blood deficiency type depression. The composition is mainly prepared from the following traditional Chinese medicines in parts by weight: 25 to 400 parts of colla corii asini, 25 to 400 parts of semen ziziphi spinosae, 30 to 500 parts of fructus mori, 30 to 500 parts of fructus citri sarcodactylis, 30 to 600 parts of semen persicae and 30 to 600 parts of poria cocos. The composition has the advantages of nourishing yin and blood, soothing liver-qi stagnation, promoting blood circulation to restore menstrual flow, and clearing away heart fire and soothing nerves. Animal experiments show that the traditional Chinese medicine composition can effectively improve depression-like symptoms of mice with depression, the anti-depression effect of the traditional Chinese medicine composition is equivalent to that of a positive drug fluoxetine, and no obvious adverse drug reaction exists. In addition, the composition also has a remarkable curative effect of nourishing yin and enriching blood, and a positive drug fluoxetine does not have a response effect. The composition is simple, raw materials are easy to obtain, the adaptation specificity is high, the preparation process is simple, and the composition is suitable for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a traditional Chinese medicine composition for treating depression caused by yin and blood deficiency. Background Technology

[0002] Depressive disorder is a mental illness characterized by significant and persistent low mood and loss of interest as its core symptoms. It is characterized by high prevalence, high suicide rate, and high relapse rate, and has become a significant global public health challenge. World Health Organization (WHO) data shows that as of 2021, there were approximately 375 million people with depressive disorders worldwide, including over 27.3 million in China, and the incidence rate is increasing year by year. Epidemiological surveys indicate that the prevalence of depressive disorders in women is significantly higher than in men, approximately 1.5 to 2 times higher. This gender difference may be closely related to women's unique physiological characteristics (such as hormonal fluctuations, pregnancy, perinatal and menopausal changes), psychological traits (such as higher emotional sensitivity), and social role pressures (such as family responsibilities and workplace discrimination). However, current mainstream antidepressants (such as SSRIs and SNRIs) have significant limitations in efficacy and safety in women: on the one hand, women metabolize drugs more slowly, making them more prone to side effects such as gastrointestinal reactions, sexual dysfunction, and weight gain; on the other hand, some drugs may interfere with estrogen levels, exacerbating premenstrual syndrome or menopausal symptoms. Therefore, developing treatment options tailored to the specific physical characteristics of women is urgently needed. However, while the current Chinese medicine market has no shortage of antidepressant compound formulas (such as Xiaoyao San and Guipi Tang), it lacks standardized and refined products specifically for women with yin and blood deficiency syndrome. Most prepared medicines are still mainly general "liver-soothing and depression-relieving" formulas, which cannot meet the personalized needs of female patients. Summary of the Invention

[0003] To overcome the above-mentioned technical deficiencies, this invention provides a traditional Chinese medicine composition for treating depression caused by yin and blood deficiency. The composition, by weight, mainly consists of the following traditional Chinese medicines:

[0004] 25-400 parts of donkey-hide gelatin, 25-400 parts of jujube seed, 30-500 parts of mulberry, 30-500 parts of Buddha's hand, 30-600 parts of peach kernel, and 30-600 parts of Poria cocos.

[0005] The composition also includes 30-150 parts of stir-fried yam.

[0006] One of the preferred formulations is:

[0007] 25 parts donkey-hide gelatin, 25 parts jujube seed, 500 parts mulberry, 500 parts Buddha's hand, 600 parts peach kernel, 600 parts poria cocos, and 150 parts stir-fried yam.

[0008] The second preferred formulation is:

[0009] 150 parts donkey-hide gelatin, 150 parts jujube seed, 80 parts mulberry, 80 parts Buddha's hand, 200 parts peach kernel, 200 parts poria cocos, and 100 parts stir-fried yam.

[0010] The third preferred formula is: 100 parts donkey-hide gelatin, 300 parts jujube seed, 300 parts mulberry, 150 parts Buddha's hand, 150 parts peach kernel, and 150 parts Poria cocos.

[0011] In the formula, donkey-hide gelatin can be replaced by one or two of the following ingredients: yellow gelatin and polygonatum; jujube seed can be replaced by cypress seed; mulberry can be replaced by one or two of the following ingredients: wolfberry and privet fruit; Buddha's hand can be replaced by one or two of the following ingredients: cyperus and bupleurum; peach kernel can be replaced by one or two of the following ingredients: safflower and salvia miltiorrhiza; poria can be replaced by one or two of the following ingredients: coix seed and atractylodes macrocephala; and stir-fried yam can be replaced by one or two of the following ingredients: white hyacinth bean and lotus seed.

[0012] According to conventional pharmaceutical manufacturing processes, the above raw materials can be prepared into commonly used clinical drug dosage forms, such as pills, tablets, granules, oral liquids, capsules, ointments, emulsions, chewable tablets, and injections.

[0013] Wash all the medicinal materials except for donkey-hide gelatin, mix them in the specified proportions, and soak them in 8-10 times their total weight of water for 30-60 minutes. Then, decoct each batch to 400 ml and combine the two decoctions. For the donkey-hide gelatin, pour the hot decoction into a bowl, add the crushed or powdered donkey-hide gelatin while it's still hot, and stir until completely dissolved. Finally, combine all the decoctions, filter, and concentrate to obtain a concentrated extract. Then, freeze-dry the extract to obtain a freeze-dried powder.

[0014] The composition of this invention has the advantages of nourishing yin and blood, soothing the liver and relieving depression, promoting blood circulation and regulating menstruation, and calming the mind and soothing the nerves. Animal experiments show that this invention can effectively improve depressive-like symptoms in mice with depression, and its antidepressant effect is comparable to that of the positive control drug fluoxetine, with no obvious adverse drug reactions. In addition, this composition also has significant effects in nourishing yin and blood, while the positive control drug fluoxetine has no responsive effect. The formulation of this composition is simple, the raw materials are readily available, the indications are highly specific, the preparation process is simple, and it is suitable for industrial production. Attached Figure Description

[0015] Figure 1 The illustration shows the effects of different doses of the novel compound of the present invention on depressive-like behavior in a CUMS depressed mouse model.

[0016] Figure 2 This is a diagram illustrating the effect of the example on the phenotype of Yin and Blood Deficiency in CUMS model animals.

[0017] Figure 3 This is a diagram illustrating the effect of the example on the phenotype of menstrual disorders in CUMS model animals.

[0018] Figure 4 It is a diagram showing the effect of the compositions of Formulas 1 to 9 on reducing the sucrose preference rate in model animals.

[0019] Figure 5 It is a diagram showing the effect of the compositions of Formulas 10 to 18 on reducing the sucrose preference rate in model animals.

[0020] Figure 6 It is a diagram showing the effect of the compositions of Formulas 19 to 27 on reducing the sucrose preference rate in model animals.

[0021] Figure 7 It is a diagram showing the effect of the compositions of Formulas 28 to 31 on reducing the sucrose preference rate in model animals. Detailed implementation manners

[0022] The present invention will be further described below with reference to specific embodiments.

[0023] I. Pharmacodynamic verification of the composition of the present invention and determination of the optimal dosage

[0024] 1. Experimental method

[0025] 1.1 Establishment and grouping of experimental animal models

[0026] 120 SPF-grade C57BL / 6J mice, female, 7 weeks old, from Beijing Vital River Laboratory Animal Technology Co., Ltd., animal license number: SCXK (Beijing) 2021-0006. The feeding environment temperature was 25 ± 2 °C, the humidity was 55 ± 5%, with 12h light-dark cycle illumination, and the animals had free access to food and drinking water during the experiment.

[0027] After one week of adaptive feeding of the animals, all animals were subjected to an open field test to exclude animals with abnormal mental states or impaired motor abilities, so as to ensure the progress of subsequent experiments.

[0028] 1.2 Chronic unpredictable mild stress (CUMS) model

[0029] Select C57BL / 6J mice and use CUMS to establish a stress depression model animal. The model group mice were exposed to the following stressors, as shown in Table 1.

[0030] Table 1 CUMS modeling stimulation schedule

[0031]

[0032] 1.3 Drug preparation

[0033] The test drug, the original drug of this invention, is a yellowish-brown freeze-dried powder of traditional Chinese medicine. The specific proportions are: 100 parts donkey-hide gelatin, 300 parts jujube seed, 300 parts mulberry, 150 parts Buddha's hand, 150 parts peach kernel, and 150 parts Poria cocos. According to the dosage requirements, the freeze-dried powder of this invention is dissolved in pure water to prepare three dosages: high, medium, and low. Fluoxetine is dissolved in pure water to prepare a 20 mg / ml solution as a positive control. The drug is administered by gavage at a rate of 10 ml / kg, i.e., dosages of 22.8 g crude drug / kg (high dose), 11.4 g crude drug / kg (medium dose), and 5.7 g crude drug / kg (low dose). Fluoxetine at 20 mg / kg serves as the positive control group, and the blank control group is given the same volume of pure water.

[0034] 1.4 Drug treatment

[0035] After modeling, the model mice were randomly divided into 5 groups of 12 mice each: CUMS model group, CUMS + low-dose new formulation group, CUMS + medium-dose new formulation group, CUMS + high-dose new formulation group, and CUMS + fluoxetine group. The blank control group and CUMS model group were administered pure water by gavage once daily; the CUMS + low-dose, medium-dose, and high-dose new formulation groups were administered a lyophilized aqueous solution of the new formulation by gavage once daily; and the CUMS + fluoxetine group was administered fluoxetine aqueous solution by gavage once daily. Behavioral experiments were conducted 14 days after drug administration.

[0036] 1.5 Evaluation of Depression-like Phenotype (see Table 2 for details)

[0037] Table 2 Evaluation indicators of depressive behavior in mice

[0038]

[0039] 1.6 Statistical Methods

[0040] Statistical analysis was performed using SPSS 19.0 software. Experimental results are expressed as mean ± standard error (Mean ± SEM). One-way ANOVA was used to test the significance of the data. * indicates p < 0.05, and ** indicates p < 0.01. The final results were imported into Prism 9.3 for plotting.

[0041] 2. Experimental Results

[0042] Depressive-like behaviors in CUMS mice were assessed using body weight, sucrose test, and forced swimming test.

[0043] 2.1 Changes in mouse body weight

[0044] Fourteen days after administration, the CUMS group mice showed a significant decrease in body weight compared to the blank control group. However, after drug treatment, mice in the low, medium, and high doses of the new compound and the positive control group (fluoxetine) showed an increase in body weight, demonstrating that the new compound can improve the weight loss in CUMS mice, and its efficacy is comparable to that of the positive control group (see...). Figure 1 A).

[0045] 2.2 Sugar Water Preference Experiment

[0046] The results of saccharide preference analysis showed that, compared with the blank control group, the saccharide preference rate of mice in the CUMS model group was significantly reduced; while the saccharide preference rate of mice in the low, medium and high dose groups of the new compound was significantly increased. This indicates that the anhedonia phenotype in CUMS model mice was improved after administration of the new compound, and that this therapeutic effect was comparable to that of fluoxetine (see [link to study].) Figure 1 B).

[0047] 2.3 Forced Swimming Experiment

[0048] Forced swimming test results showed that, compared with the blank control group, the immobility time of CUMS model mice was significantly reduced; the immobility time of mice in the high-dose group of the new compound was significantly reduced, while the low-dose group had no effect on improving the immobility time of model mice. This indicates that the medium and high doses of the new compound can have the same effect as fluoxetine in improving the despair behavior of CUMS model mice, and the therapeutic effect is comparable to that of fluoxetine (see...). Figure 1 C).

[0049] Based on the above, low, medium, and high doses of the new compound significantly improved the weight loss and sucrose preference in CUMS mice; however, the low dose did not improve the despair state in CUMS mice. Secondly, considering the difficulty of gavage administration of high-dose new compound, this study subsequently selected the medium dose of the new compound as the experimental study dose.

[0050] II. Detection of Yin-deficiency-like behavior in mice using the composition of the present invention.

[0051] 1. Materials and Methods

[0052] The experimental animals, experimental instruments, experimental reagents, establishment and grouping of experimental animal models, chronic unpredictable mild stress (CUMS) models, drug preparation, drug treatment, and statistical methods are the same as above.

[0053] 2. Determination of Indicators for Yin Deficiency Detection in Mice

[0054] By searching CNKI, Wanfang, Sinomed, PubMed, and Web of Science for 3766 clinical articles related to depression and 3014 clinical articles related to Yin deficiency up to 2024, inclusion and exclusion criteria were established for these articles. Articles that did not meet the inclusion criteria were removed. Data extraction and standardization were then performed on the collected articles. Standardized data resulted in a database of depressive symptoms / signs and a database of Yin deficiency symptoms / signs. Based on similar symptom_ids in both databases, common symptoms were summarized, resulting in 184 common symptoms of depression and Yin deficiency. After screening, the following indicators were finally established as the detection indicators for "Yin deficiency" in mice (see Table 3).

[0055] Table 3 Indicators for Yin Deficiency Detection in Mice

[0056]

[0057]

[0058] 3. Experimental Results

[0059] The open field test and grip test were used to assess the "fatigue" state of mice, and the rectal temperature and body surface temperature were used to assess whether mice had a fever. The results of whole blood analysis of mice were used to assess the "anemia" manifestations of mice.

[0060] 3.1 Evaluation of "fatigue" symptoms in CUMS mice

[0061] Compared with the control group, CUMS mice exhibited significantly reduced total distance and mean velocity, while treatment with the new compound significantly increased both total open field distance and mean velocity in CUMS mice (see [link to treatment]). Figure 2 (AB). Compared with the blank control group, the grip strength of mice in the CUMS group was significantly reduced; after treatment with the new compound, the grip strength of mice was significantly increased (see AB). Figure 2 C). Both the open field test and the grip test demonstrated that CUMS mice exhibited a "weak" phenotype, and this phenomenon could be improved after treatment with the new compound, but fluoxetine administration had no effect on improving the above indicators.

[0062] 3.2 Evaluation of "fever" symptoms in CUMS mice

[0063] Compared with the control group, the body surface temperature and rectal temperature of the model group mice were elevated, indicating that CUMS mice exhibited certain "fever" symptoms (see...). Figure 2 DE); however, after administration of the new compound, the body surface temperature and rectal temperature of CUMS mice decreased significantly, but the administration of fluoxetine did not have an improving effect.

[0064] 3.3 Evaluation of "blood deficiency" symptoms in CUMS mice

[0065] In the CUMS group, the red blood cell count (RBC), white blood cell count (WBC), hemoglobin content (HGB), and platelet parameters (PLT) were significantly lower than those in the normal control group. Compared with the CUMS group, the new compound group showed significantly higher red blood cell count, white blood cell count, hemoglobin content, and platelet parameters, while fluoxetine did not improve these indicators in CUMS mice (see...). Figure 2 FI).

[0066] III. Detection of the menstrual disorder phenotype in mice using the composition of the present invention.

[0067] 1. Materials and Methods

[0068] The experimental animals, experimental instruments, experimental reagents, establishment and grouping of experimental animal models, chronic unpredictable mild stress (CUMS) models, drug preparation, drug treatment, and statistical methods are the same as above.

[0069] 2. The detection of menstrual irregularity behavior in mice is shown in Table 4.

[0070] Table 4. Indicators for detecting menstrual irregularities in mice

[0071]

[0072] 3. Experimental Results

[0073] Menstrual irregularity behavior in CUMS mice was assessed by detecting changes in hormone levels, estrous cycles, and ovarian tissue.

[0074] 3.1 Changes in hormone levels in CUMS mice

[0075] Compared with the control group, the CUMS group mice showed significantly lower serum estradiol (E2) levels and significantly higher follicle-stimulating hormone (FSH) levels; compared with the model group mice, the new compound group mice showed significantly higher serum E2 levels and significantly lower FSH levels (see...). Figure 3 (AB). Hormone testing results showed that the CUMS group mice exhibited typical endocrine disorder characteristics of "decreased E2-decreased FSH". The new compound treatment could effectively regulate this endocrine imbalance and restore normal levels of E2 and FSH, but fluoxetine treatment did not show a similar therapeutic effect.

[0076] 3.2 Evaluation of the estrous cycle in CUMS mice

[0077] Compared with the control group, CUMS mice exhibited significant estrous cycle disorder, with a significantly shortened estrus duration and a significantly prolonged proestrus-interestrus period (see...).Figure 3 C) This suggests that stress significantly disrupts the reproductive cycle in mice. After intervention, the estrus duration in the new compound group was significantly longer than that in the CUMS group, while the interestrus-proestrus period was significantly shorter, indicating that the new compound can effectively improve stress-induced reproductive cycle disorders. Notably, the duration of each stage of the estrus cycle in the fluoxetine group was not significantly different from that in the CUMS group, suggesting that the traditional antidepressant fluoxetine has limited effect on improving reproductive cycle disorders.

[0078] 3.3 Evaluation of ovarian tissue in CUMS mice

[0079] Compared with the control group, the CUMS group mice showed a significant decrease in the number of primary and secondary oocytes, while the number of corpus luteum cells was significantly increased. After administration of the new compound, the number of primary and secondary oocytes in the model mice increased, while the number of corpus luteum cells decreased significantly. These findings demonstrate that the new compound helps improve reproductive dysfunction caused by CUMS, but fluoxetine did not have the aforementioned improving effect (see...). Figure 3 DF).

[0080] III. Antidepressant efficacy experiments of different proportions of this traditional Chinese medicine composition

[0081] The experimental drugs were prepared according to the proportions in Table 5, and the antidepressant efficacy of different proportions of this traditional Chinese medicine composition was compared. The drug preparation and detection methods were the same as above.

[0082] The sucrose preference test has become the most commonly used behavioral detection method for depression in the CUMS model due to its direct association with core depressive symptoms, ease of operation, high sensitivity, and well-defined neural mechanisms. Therefore, the efficacy of this traditional Chinese medicine composition was assessed using the sucrose preference test, with the specific method described above. The results are shown in Table 5. Figures 4 to 7 As shown.

[0083] Table 5

[0084] Group No. Donkey-hide gelatin Semen zizyphi spinaosae Semen zizyphi spinaosae Semen zizyphi spinaosae Semen zizyphi spinaosae Semen zizyphi spinaosae Semen zizyphi spinaosae Antidepressant effect 1 25 25 500 500 500 500 150 Similar to fluoxetine, 2 300 20 30 30 400 100 150 Similar to fluoxetine, 3 250 400 500 500 30 90 150 Similar to fluoxetine, 4 150 400 500 100 100 400 30 Similar to fluoxetine, 5 40 300 100 500 60 60 150 Similar to fluoxetine, 6 40 300 100 50 60 60 100 Similar to fluoxetine, 7 25 25 500 500 500 500 150 Similar to fluoxetine, 8 300 100 30 30 300 300 150 Similar to fluoxetine, 9 200 400 30 30 500 30 150 Similar to fluoxetine, 10 350 400 500 500 30 30 150 Similar to fluoxetine, 11 400 400 500 500 100 100 30 Similar to fluoxetine, 12 400 400 500 500 250 300 150 Similar to fluoxetine, 13 400 400 500 500 330 150 150 Similar to fluoxetine, 14 100 400 500 500 400 400 150 Similar to fluoxetine, 15 400 300 500 500 350 350 150 Similar to fluoxetine, 16 60 60 180 180 200 200 100 Similar to fluoxetine, 17 150 150 80 80 200 200 100 Similar to fluoxetine, 18 150 60 180 180 100 100 100 Similar to fluoxetine, 19 150 120 180 180 200 200 100 Similar to fluoxetine, 20 160 160 180 180 200 200 100 Similar to fluoxetine, 21 60 150 180 180 180 200 100 Similar to fluoxetine, 22 60 150 180 180 200 200 100 Similar to fluoxetine, 23 150 60 150 180 200 200 100 Similar to fluoxetine, 24 80 80 180 180 160 160 80 Similar to fluoxetine, 25 120 120 100 100 160 160 80 Similar to fluoxetine, 26 270 270 150 150 160 160 80 Similar to fluoxetine, 27 120 120 150 180 160 200 80 Similar to fluoxetine, 28 120 120 150 180 160 200 80 Similar to fluoxetine, 29 360 150 120 120 130 130 65 Similar to fluoxetine, 30 100 100 120 120 130 130 65 Similar to fluoxetine, 31 120 120 150 150 160 160 80 Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to fluoxetine, Similar to

[0085] Animal experiments have shown that the different formulations of this invention can effectively improve depressive-like symptoms in mice with depression, with an antidepressant effect comparable to that of the positive control drug fluoxetine, and no obvious adverse drug reactions. Furthermore, this traditional Chinese medicine composition also has significant effects in nourishing yin and replenishing blood, while the positive control drug fluoxetine has no corresponding effect.

Claims

1. A traditional Chinese medicine composition for treating depression due to yin and blood deficiency, characterized in that, This traditional Chinese medicine composition, by weight, mainly consists of the following traditional Chinese medicines: 25-400 parts of donkey-hide gelatin, 25-400 parts of jujube seed, 30-500 parts of mulberry, 30-500 parts of Buddha's hand, 30-600 parts of peach kernel, and 30-600 parts of Poria cocos.

2. The traditional Chinese medicine composition as described in claim 1, characterized in that, The composition also includes 30-150 parts of stir-fried yam.

3. The traditional Chinese medicine composition as described in claim 2, characterized in that, The composition consists of the following traditional Chinese medicines: 25 parts donkey-hide gelatin, 25 parts jujube seed, 500 parts mulberry, 500 parts Buddha's hand, 600 parts peach kernel, 600 parts poria cocos, and 150 parts stir-fried yam.

4. The traditional Chinese medicine composition as described in claim 2, characterized in that, The composition consists of the following traditional Chinese medicines: 150 parts donkey-hide gelatin, 150 parts jujube seed, 80 parts mulberry, 80 parts Buddha's hand, 200 parts peach kernel, 200 parts poria cocos, and 100 parts stir-fried yam.

5. The traditional Chinese medicine composition according to claim 1, characterized in that, The composition consists of the following traditional Chinese medicines: 100 parts donkey-hide gelatin, 300 parts jujube seed, 300 parts mulberry, 150 parts Buddha's hand, 150 parts peach kernel, and 150 parts Poria cocos.

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