A pharmaceutical composition for improving sleep quality and its preparation method and application

Abstract

The present invention belongs to the field of Chinese medicine, and in particular to a pharmaceutical composition for improving sleep quality, and its preparation method and application. The pharmaceutical composition of the present invention includes, by mass, 90-120 parts of Codonopsis pilosula, 225-300 parts of Radix Polygoni Multiflori, 225-300 parts of Cortex Albizziae, 110-150 parts of Rhizoma Chuanxiong, 150-200 parts of Semen Ziziphi Spinosae, 75-100 parts of Radix Ophiopogonis, 75-100 parts of Rhizoma Anemarrhenae, 75-100 parts of Longan pulp, and 225-300 parts of Floating Wheat. Retrospective case analysis of the pharmaceutical composition of the present invention shows that the pharmaceutical composition of the present invention can comprehensively improve the sleep condition of insomnia patients of deficiency-cold type, including improving the overall sleep quality total score, improving the daytime dysfunction of patients, reducing the use of hypnotic drugs in patients, improving sleep disorders, improving sleep efficiency, reducing the time to fall asleep and improving sleep quality, and having good safety.

Description

Technical Field

[0001] The invention belongs to the field of traditional Chinese medicine, and particularly relates to a pharmaceutical composition for improving sleep quality, a preparation method and an application thereof. Background Art

[0002] Sleep disorders are common diseases in modern society. In 2020, there are about 700 million insomniacs in the world. The course of this disease is prolonged and the recurrence rate is high after cure. Long-term insomnia increases the risk of patients suffering from or suffering from comorbid physical and mental diseases.

[0003] At present, chemical drugs for the treatment of insomnia mainly include sedative hypnotic drugs such as benzodiazepine receptor agonists (BZRAs), melatonin receptor agonists, orexin receptor antagonists and antidepressants with hypnotic effects. However, adverse reactions during medication have always been a difficulty faced by chemical drugs in the treatment of insomnia. For example, long-term use can cause adverse reactions such as weight gain, metabolic disorders and cardiovascular events. In addition, memory loss, decreased attention, fatigue, decreased quality of life, withdrawal reactions, and tolerance and dependence problems after long-term medication are all reasons why insomnia patients resist these drugs.

[0004] Traditional Chinese medicine focuses on the overall, comprehensive conditioning, and treating the root of the disease, and has certain advantages in treating insomnia. At present, the commonly used prescriptions for treating insomnia include Suanzaoren Decoction, Tianwang Buxin Dan, Ganmai Dazao Decoction, Guizhi Jia Longgu Muli Decoction, Wendan Decoction, Jiaotai Pills, etc. These prescriptions are mainly for nourishing yin, clearing heat, and calming the mind. They are mainly used for insomnia caused by yin deficiency and excessive fire, restlessness, and heat. However, in clinical practice, a large number of insomnia types that are biased towards cold can also be seen due to insufficient qi and blood, qi deficiency, spleen deficiency, spleen and kidney deficiency, spleen and kidney deficiency and cold, spleen and kidney deficiency, etc. At present, there are few prescription combinations for this type of insomnia, which is difficult to meet clinical needs. Summary of the invention

[0005] The first object of the present invention is to provide a pharmaceutical composition for improving sleep quality. The second object of the present invention is to provide a method for preparing the pharmaceutical composition. The third object of the present invention is to provide an application of the pharmaceutical composition.

[0006] According to a first aspect of the present invention, a pharmaceutical composition for improving sleep quality is provided, wherein the main active ingredients thereof include, by weight: 90-120 parts of Codonopsis pilosula, 225-300 parts of Polygonum multiflorum vine, 225-300 parts of Albizzia julibrissin bark, 110-150 parts of Ligusticum chuanxiong, 150-200 parts of Semen Ziziphi Spinosae, 75-100 parts of Ophiopogon japonicus, 75-100 parts of Anemarrhena asphodeloides, 75-100 parts of Longan pulp, and 225-300 parts of Floating wheat.

[0007] The present invention believes that the etiology and pathogenesis of insomnia of deficiency-cold type are: excessive fatigue or long-term illness and aging can all lead to spleen deficiency or spleen and kidney deficiency-cold. Spleen deficiency leads to poor transportation and transformation of the middle jiao, lack of source of qi and blood production, resulting in insufficient qi and blood, which cannot be served to the heart. Spleen and kidney deficiency-cold leads to disharmony between the heart and kidney, loss of nourishment of the mind, and inability to fall asleep.

[0008] The present invention uses Codonopsis pilosula, Rhizoma Chuanxiong and Semen Ziziphi Spinosae as the main medicine, has the effects of invigorating qi and nourishing blood, and calming the nerves, can reconcile the balance of qi and blood in the body, and nourish the heart and calm the nerves. Use Radix Polygoni Multiflori, Radix Ophiopogonis and Rhizoma Longan as the ministerial medicine, nourish the liver and kidney, strengthen the effects of nourishing the heart and calming the nerves, can relieve fatigue, and enhance the quality of sleep. Use Cortex Albizziae Julibrissin, Rhizoma Anemarrhenae and Rhizoma Tritici as the adjuvant, can clear away heat and reduce false fire, and promote sleep. All medicines are combined, can achieve the effects of invigorating qi and nourishing blood, nourishing the heart and calming the nerves, soothing the liver and regulating qi, and is suitable for insomnia patients with cold deficiency-cold types due to deficiency of qi and blood, qi deficiency, spleen deficiency, deficiency of spleen and kidney, spleen and kidney deficiency-cold, spleen and kidney deficiency, etc.

[0009] The sources of raw materials for this recipe are as follows:

[0010] Codonopsis: The dried root of Codonopsis pilosula (Franch.) Nannf., Codonopsis pilosula Nannf. var. modesta (Nannf.) LTShen or Codonopsis tangshen Oliv. of the Campanulaceae family. It tastes sweet and is neutral in nature.

[0011] Polygonum multiflorum Thunb.: The dried vine stem of Polygonum multiflorum Thunb., a plant of the Polygonaceae family. It tastes bitter and astringent, and is warm in nature.

[0012] Albizia Julibrissin Bark: The bark of the leguminous plant Albizia julibrissin Durazz. It tastes bitter and astringent, and is cold in nature.

[0013] Chuanxiong: The rhizome of the Umbelliferae herb LigusticumchuanxiongHost. It tastes spicy and bitter, and is warm in nature.

[0014] Ziziphus jujaba seeds: dried mature seeds of Ziziphus jujaba Mill.var.spinosa (Bunge) Hu exH.F.Chou, a plant of the Rhamnaceae family. They are sweet, sour and warm in nature.

[0015] Ophiopogon japonicus: The dried root of Ophiopogon japonicus (Thunb.) Ker-Gawl., a plant of the Liliaceae family. It tastes sweet and light, and is cool in nature.

[0016] Anemarrhena asphodeloides Bunge: The dried rhizome of Anemarrhena asphodeloides Bunge. It tastes bitter and sweet and is cool in nature.

[0017] Longan pulp: the aril of Dimocarpus longan Lour., a plant of the Sapindaceae family. It tastes sweet and has a neutral nature.

[0018] Floating wheat: The dried, light, shrunken fruit of Triticum aestivum L., a plant of the Gramineae family. It tastes sweet and is cool in nature.

[0019] In some embodiments, the main active ingredients include, by mass: 100 parts of Codonopsis pilosula, 250 parts of Polygonum multiflorum vine, 250 parts of Albizzia julibrissin bark, 125 parts of Ligusticum chuanxiong, 167 parts of Semen Ziziphi Spinosae, 83 parts of Ophiopogon japonicus, 83 parts of Anemarrhena asphodeloides, 83 parts of Longan pulp, and 250 parts of Floating wheat.

[0020] In some embodiments, the codonopsis pilosula is cooked codonopsis pilosula, which is a cooked product of codonopsis pilosula, and after being fried, has a better effect on warming and tonifying the spleen and stomach than codonopsis pilosula.

[0021] In some embodiments, the Chinese jujube kernel is stir-fried Chinese jujube kernel. Stir-fried Chinese jujube kernel is a stir-fried product of Chinese jujube kernel, which has a warmer medicinal property and further enhances the effect of warming and nourishing qi and blood.

[0022] In some embodiments, a medically acceptable excipient is also included.

[0023] In some embodiments, the pharmaceutical composition is in the form of a decoction, an oral solution, a pill, a tablet, a capsule or a granule.

[0024] According to a second aspect of the present invention, a method for preparing the above-mentioned pharmaceutical composition for improving sleep quality is provided. When the dosage form of the pharmaceutical composition is an oral liquid, the preparation method comprises the following steps:

[0025] Mix the raw medicinal materials according to the proportion, add 8 times the total weight of the raw materials and boil for 2 to 3 times, each time for 40 to 60 minutes, filter the decoction, combine the filtrate, concentrate the combined filtrate to a relative density of 1.08 to 1.16 at 80°C, then cool to room temperature, add ethanol to make the alcohol content reach 70%, let it stand for 24 to 48 hours, then filter, recover the ethanol, then add water, sucrose, ethylparaben, sodium benzoate, and continue boiling for 5 to 10 minutes minutes, stir until completely dissolved, then add water to form a clear paste with a relative density of not less than 1.121, then add medicinal charcoal to the clear paste while it is hot, stir evenly, then refrigerate at 2-10°C for 24-48 hours, filter, add sodium citrate and sodium bisulfite to the filtrate, stir evenly, then let stand for 24-48 hours, filter again, add water to the filtrate to 1000ml, adjust the pH to 3.5-6.5 with sodium hydroxide, fill and sterilize.

[0026] In some embodiments, 30-60 parts of sucrose, 0.25-0.5 parts of ethylparaben, 1.5-3 parts of sodium benzoate, 0.5-1 parts of medicinal charcoal, 1-2 parts of sodium citrate, and 0.5-1 parts of sodium bisulfite are added by weight.

[0027] According to a third aspect of the present invention, there is provided a use of the above-mentioned pharmaceutical composition for improving sleep quality in the preparation of a drug for treating insomnia. Specifically, the insomnia is of the deficiency-cold type.

[0028] The beneficial effects of the present invention include:

[0029] (1) The pharmaceutical composition of the present invention can nourish qi and blood, nourish the heart and calm the mind, soothe the liver and regulate qi, and is used for insomnia of the deficiency-cold type due to qi and blood deficiency, qi deficiency, spleen deficiency, spleen and kidney deficiency, spleen and kidney deficiency, spleen and kidney deficiency, etc., with symptoms such as difficulty falling asleep, frequent dreams, easy awakening, palpitations, fatigue, weakness, irritability, and dry mouth.

[0030] (2) Retrospective case analysis of the pharmaceutical composition of the present invention shows that the pharmaceutical composition of the present invention can comprehensively improve the sleep condition of patients with insomnia of the deficiency-cold type, including improving the overall sleep quality score, improving the daytime dysfunction of patients, reducing the use of hypnotic drugs by patients, improving sleep disorders, improving sleep efficiency, reducing the time to fall asleep and improving sleep quality, and has good safety. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 It is the change of the total PSQI score of the patients before and after treatment in the retrospective case analysis of the present invention.

[0032] Figure 2 It is the changes of other PSQI indicators of patients before and after treatment in the retrospective case analysis of the present invention. DETAILED DESCRIPTION

[0033] The present invention is further described in detail below in conjunction with specific examples. Unless otherwise specified, the raw materials and reagents used in the present invention are all purchased from the market.

[0034] Example 1

[0035] The oral liquid for improving sleep quality of this embodiment is prepared from the following components: 100g of Codonopsis pilosula, 250g of Polygonum multiflorum vine, 250g of Albizzia julibrissin, 125g of Ligusticum chuanxiong, 167g of Semen Ziziphi Spinosae, 83g of Ophiopogon japonicus, 83g of Anemarrhena asphodeloides, 83g of Longan pulp, and 250g of Floating Wheat.

[0036] Its preparation method is:

[0037] The raw medicinal materials were mixed according to the proportion, decocted 3 times with water 8 times the total weight of the raw materials, the first decoction was 1 hour, the second and third decoctions were 45 minutes each, the decoction was filtered, the filtrate was combined, the combined filtrate was concentrated to a relative density of about 1.12 (80°C), then cooled to room temperature, ethanol was added to make the alcohol content reach 70%, and it was allowed to stand for 36 hours, then filtered, the ethanol was recovered, and then water, 60g of sucrose, 0.5g of ethylparaben, 3g of sodium benzoate were added. g, continue boiling for 10 minutes, stir until completely dissolved, then add water to form a clear paste with a relative density of not less than 1.121, then add 1 g of medicinal charcoal to the clear paste while it is hot, stir evenly, then refrigerate at 5°C for 36 hours, filter, add 2 g of sodium citrate and 1 g of sodium bisulfite to the filtrate, stir evenly, then let it stand for 24 hours, filter again, add water to the filtrate to 1000 ml, adjust the pH to 5.0 with sodium hydroxide, seal, and sterilize.

[0038] The prepared oral liquid is packaged according to the specification of 6 bottles per box, each bottle is 10 ml. The daily dosage for adults is 3-6 bottles.

[0039] Example 2

[0040] The oral liquid for improving sleep quality of this embodiment is prepared from the following components: 90g of Codonopsis pilosula, 225g of Polygonum multiflorum vine, 225g of Albizzia julibrissin, 110g of Ligusticum chuanxiong, 150g of Semen Ziziphi Spinosae, 75g of Ophiopogon japonicus, 75g of Rhizoma Anemarrhenae, 75g of Longan pulp, and 225g of Floating Wheat.

[0041] The preparation method is similar to that of Example 1.

[0042] Example 3

[0043] The oral liquid for improving sleep quality of this embodiment is prepared from the following components: 120g of Codonopsis pilosula, 300g of Polygonum multiflorum vine, 300g of Albizzia julibrissin, 150g of Ligusticum chuanxiong, 200g of Semen Ziziphi Spinosae, 100g of Ophiopogon japonicus, 100g of Anemarrhena asphodeloides, 100g of Longan pulp, and 300g of Floating Wheat.

[0044] The preparation method is similar to that of Example 1.

[0045] Next, to illustrate the therapeutic effect of the pharmaceutical composition for improving sleep quality of the present invention on insomnia, the oral liquid for improving sleep quality prepared in Example 1 (hereinafter referred to as the oral liquid for invigorating qi, nourishing the heart and calming the mind) was used to conduct a retrospective analysis of clinical data.

[0046] 1. Source of cases

[0047] Clinical patient medical records of an outpatient hospital in Guangdong Province from January 1, 2018 to December 31, 2022.

[0048] 2. Research Design

[0049] A retrospective analysis method was used to compare before and after treatment.

[0050] III. Inclusion and Exclusion Criteria

[0051] 1. Inclusion criteria:

[0052] (1) Outpatients diagnosed with insomnia (insomnia, sleep disorders);

[0053] (2) Patients diagnosed with deficiency of qi and blood, qi deficiency, spleen deficiency, spleen and kidney deficiency, spleen and kidney deficiency and cold, spleen and kidney deficiency, etc.;

[0054] (3) Outpatients who were treated with the Qi-Yin Yang Xin An Shen oral liquid prepared in Example 1 of the present invention as the only drug.

[0055] 2. Exclusion criteria:

[0056] (1) Patients with syndromes that tend to be heat-related, such as yin deficiency, yang hyperactivity, and hyperactivity of heart fire;

[0057] (2) Outpatients who are treated with other oral medications.

[0058] IV. Evaluation Indicators

[0059] The Pittsburgh Sleep Quality Inventory (PSQI) was used for evaluation.

[0060] The main indicator was the total score of PSQI.

[0061] Secondary indicators included "daytime dysfunction", "use of hypnotic drugs", "sleep disorders", "sleep efficiency score", "sleep onset time" and "sleep quality".

[0062] The above indicators were compared before and after the subjects used the drug. At the same time, the subjects' discomfort with the drug was collected during the follow-up.

[0063] V. Statistical Methods

[0064] SPSS19 software was used for statistics, and the results were analyzed by paired t-test.

[0065] 6. Research Results

[0066] 1. Overall situation

[0067] A total of 113 medical records were included in the statistics, including 41 males and 72 females, with an average age of 40.77±14.98 years old, and an average oral liquid consumption of 4.32±2.76 boxes (6 vials per box, 10 ml per vial).

[0068] 2. Main evaluation indicators

[0069] The changes in the total score of the Pittsburgh Sleep Scale before and after treatment are shown in Table 1 and Figure 1 .

[0070] Table 1 Changes in PSQI total score

[0071] project Before treatment (mean ± standard deviation) After treatment (mean ± SD) P-value PSQI Total Score 10.52±2.11 5.87±2.73 0.00*

[0072] Note: * indicates statistically significant differences.

[0073] From Table 1 and Figure 1 It can be seen that the total PSQI score of the patient was significantly reduced after taking the Yiqi Yangxin Anshen oral liquid of the present invention.

[0074] 3. Secondary evaluation indicators

[0075] Before and after treatment, the daytime dysfunction, hypnotic drug use, sleep disturbance, sleep efficiency, sleep onset time and sleep quality in PSQI are shown in Table 2 and Figure 2 .

[0076] Table 2: Scores of other PSQI indicators

[0077] project Before treatment (mean ± standard deviation) After treatment (mean ± SD) P-value Daytime dysfunction 1.96±0.74 0.95±0.84 0.00* Hypnotic drug use 0.16±0.53 0.06±0.41 0.00* Sleep disorders 1.19±0.45 0.98±0.44 0.00* Sleep efficiency 1.59±1.12 0.76±0.95 0.00* Bedtime 2.04±0.76 1.25±0.76 0.00* Sleep quality 1.92±0.42 0.95±0.73 0.00*

[0078] Note: * indicates statistically significant differences.

[0079] From Table 2 and Figure 2 It can be seen that the scores of each secondary evaluation index of the patient were significantly reduced after taking the Yiqi Yangxin Anshen oral liquid of the present invention.

[0080] 4. Medication discomfort

[0081] No obvious discomfort symptoms were found in all patients included in the statistics.

[0082] VII. Research Conclusion

[0083] (1) After taking the Yiqi Yangxin Anshen oral liquid of the present invention, the patient's total PSQI score was 10.52±2.11 points before treatment, and dropped to 5.87±2.73 points after treatment, with a statistically significant difference.

[0084] (2) After taking the Yiqi Yangxin Anshen oral liquid of the present invention, the patients' daytime dysfunction, use of hypnotic drugs, sleep disorders, sleep efficiency, sleep onset time and sleep quality were significantly improved, and the differences were statistically significant.

[0085] (3) The oral liquid for replenishing qi, nourishing the heart and calming the mind of the present invention has good safety.

[0086] It can be seen that the pharmaceutical composition of the present invention can effectively improve the overall sleep quality score, improve the patient's daytime functional disorders, reduce the patient's use of hypnotic drugs, improve sleep disorders, improve sleep efficiency, reduce the time to fall asleep and improve sleep quality, and the drug is safe.

[0087] The above are only some specific embodiments of the present invention. For those skilled in the art, several modifications and improvements can be made without departing from the creative concept of the present invention, which all belong to the protection scope of the present invention.

Claims

1. A pharmaceutical composition for improving the sleep quality of insomnia due to deficiency and cold, characterized in that: The raw material medicine composition is as follows by weight: 90-120 parts of Codonopsis pilosula, 225-300 parts of Polygonum multiflorum vine, 225-300 parts of Albizzia julibrissin bark, 110-150 parts of Ligusticum chuanxiong, 150-200 parts of Ziziphus jujuba seeds, 75-100 parts of Ophiopogon japonicus, 75-100 parts of Anemarrhena asphodeloides, 75-100 parts of Longan pulp and 225-300 parts of Floating wheat.

2. The pharmaceutical composition for improving the sleep quality of insomnia due to deficiency-cold type according to claim 1, characterized in that: The raw material composition is as follows by mass: 100 parts of Codonopsis pilosula, 250 parts of Polygonum multiflorum vine, 250 parts of Albizzia julibrissin bark, 125 parts of Ligusticum chuanxiong, 167 parts of Ziziphus jujuba seeds, 83 parts of Ophiopogon japonicus, 83 parts of Anemarrhena asphodeloides, 83 parts of Longan pulp, and 250 parts of Floating wheat.

3. The pharmaceutical composition for improving the sleep quality of insomnia caused by deficiency-cold type according to claim 1 or 2, characterized in that: The Codonopsis pilosula is cooked Codonopsis pilosula, and the Ziziphus jujuba seeds are stir-fried Ziziphus jujuba seeds.

4. The pharmaceutical composition for improving the sleep quality of insomnia caused by deficiency-cold type according to claim 1 or 2, characterized in that: Pharmaceutically acceptable excipients may also be added.

5. The pharmaceutical composition for improving the sleep quality of insomnia due to deficiency-cold type according to claim 1 or 2, characterized in that: The dosage form of the pharmaceutical composition is decoction, oral liquid, dripping pill, tablet, capsule or granule.

6. The method for preparing the pharmaceutical composition for improving the sleep quality of insomnia due to deficiency-cold type according to claim 5, characterized in that: When the dosage form of the pharmaceutical composition is an oral solution, the preparation method thereof comprises the following steps: The raw medicinal materials are mixed according to the proportion, 1 part of the raw material mass is 1g, 8 times the total weight of the raw material is added with water and boiled for 2 to 3 times, each time for 40 to 60 minutes, the decoction is filtered, the filtrate is combined, and the combined filtrate is concentrated to a relative density of 1.08 to 1.16 at 80°C, then cooled to room temperature, ethanol is added to make the alcohol content reach 70%, and it is allowed to stand for 24 to 48 hours, then filtered, the ethanol is recovered, and then water, sucrose, ethylparaben, sodium benzoate are added, and continued Boil for 5 to 10 minutes, stir until completely dissolved, add water to form a clear paste with a relative density of not less than 1.121, then add medicinal charcoal to the clear paste while it is hot, stir evenly, then refrigerate at 2 to 10°C for 24 to 48 hours, filter, add sodium citrate and sodium bisulfite to the filtrate, stir evenly, then let stand for 24 to 48 hours, filter again, add water to the filtrate to 1000 ml, adjust the pH to 3.5-6.5 with sodium hydroxide, seal, and sterilize.

7. The method for preparing the pharmaceutical composition for improving the sleep quality of insomnia due to deficiency-cold type according to claim 6, characterized in that: In parts by mass, add 30-60 parts of sucrose, 0.25-0.5 parts of ethylparaben, 1.5-3 parts of sodium benzoate, 0.5-1 parts of medicinal charcoal, 1-2 parts of sodium citrate, and 0.5-1 parts of sodium bisulfite.

8. Use of the pharmaceutical composition for improving sleep quality of insomnia due to deficiency and cold according to any one of claims 1 to 5 in the preparation of a drug for treating insomnia due to deficiency and cold.

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