Composition for improving fatigue type senescence accompanied with depressive symptom and preparation method thereof

Abstract

The invention discloses a composition for improving fatigue type senescence accompanied with depressive symptom and a preparation method thereof, and belongs to the technical field of health food, the composition is prepared from the following raw materials by weight: 500-1000 parts of dried lily, 500-1000 parts of dried day lily, 0.5-1 part of pyrroloquinoline quinone disodium salt, and 8-12 parts of gamma-aminobutyric acid. According to the composition for improving the fatigue type senescence accompanied with depression symptoms, PQQ contained in the composition can promote energy metabolism of mitochondria; flavone and polysaccharide components contained in the day lily can inhibit skin collagen degradation and systematically resist inflammation; the contained GABA and lily cooperate with each other to promote emotional soothing; the PQQ and quercetin contained in the day lily cooperate with each other to regulate and protect the neuroendocrine system for a long time.

Description

Technical Field

[0001] The invention relates to a composition for improving fatigue-type aging accompanied by depression and a preparation method thereof, belonging to the technical field of health food. Background Art

[0002] Exhaustion-induced aging refers to the aging caused by long-term stress and stress reactions experienced at work and school. High-intensity mental activity, long periods of desk work, insufficient sleep, and prolonged exposure to air-conditioned office environments overtax the health of middle-aged professionals, causing symptoms such as neck and shoulder muscle soreness, fatigue, and palpitations. Depression refers to a mood disorder characterized by a significant and persistent low mood due to various causes. Chronic work, life, and psychological pressures can lead to anxiety, restlessness, and depression in some middle-aged professionals.

[0003] Fatigue and depression have become important factors leading to the progression of exhaustion-type aging in some middle-aged white-collar workers, and fatigue is one of the common symptoms of depression. Therefore, exhaustion-type aging and depression often occur together. The subjective feelings are usually accompanied by drowsiness, weakness, irritability, etc. Physically, there are often muscle soreness in parts such as shoulders, neck, and waist. Psychologically, there are negative emotional reactions such as anxiety, irritability, and depression. Summary of the Invention

[0004] In order to solve the problems existing in the prior art, the present invention provides a composition for improving fatigue-type aging with depression symptoms and a preparation method thereof, which can effectively improve the sleep quality and HAMD-17, SF-36PF, and Pain VAS scores of patients with fatigue-type aging combined with depression of the heart and spleen deficiency type.

[0005] The present invention achieves the above-mentioned purpose by adopting the following technical solutions:

[0006] On the one hand, the present invention provides a composition for improving fatigue-type aging accompanied by depression symptoms, which is made from the following raw materials in parts by weight: 500-1000 parts of dried lily, 500-1000 parts of dried daylily, 0.5-1 part of pyrroloquinoline quinone disodium salt (PQQ), and 8-12 parts of gamma-aminobutyric acid (GABA).

[0007] Preferably, the composition for improving fatigue-type aging with depression symptoms provided by the present invention is made from the following raw materials in parts by weight: 750 parts of dried lily, 750 parts of dried daylily, 0.75 parts of pyrroloquinoline quinone disodium salt (PQQ), and 10 parts of gamma-aminobutyric acid (GABA).

[0008] In another aspect, the present invention provides a method for preparing the composition, comprising the steps of:

[0009] S1. Extracting dried lily and dried daylily into lily water-extracted paste and daylily water-extracted paste respectively;

[0010] S2. Mixing the lily water extract paste and the daylily water extract paste with pharmaceutically acceptable excipients to prepare an oral preparation.

[0011] In a preferred embodiment, the method for preparing the water-extracted clear paste comprises the following steps:

[0012] S101. Mix dried lily bulbs and dried daylily buds, add 8 to 12 times their weight of water, boil for 1 to 2 hours, and filter to obtain a primary residue and a primary filtrate;

[0013] S102, adding 8 to 10 times the weight of water to the primary filter residue, boiling for 0.5 to 1.5 hours, and filtering to obtain a secondary filter residue and a secondary filtrate;

[0014] S103. Combine the primary filtrate and the secondary filtrate, and concentrate under reduced pressure at 50-60° C. to prepare a water-extracted clear paste having a relative density of 1.03-1.10 at 50° C.

[0015] Preferably, the oral preparation is an oral liquid, granules, tablets, capsules or pills.

[0016] Furthermore, the auxiliary materials are sucralose, sorbitol, maltodextrin and microcrystalline cellulose.

[0017] Wherein, when preparing granules, step S2 is:

[0018] S201, adding sucralose, sorbitol, and maltodextrin to the lily water extract paste and the daylily water extract paste, mixing evenly, and spray drying;

[0019] S202. Add pyrroloquinoline quinone disodium salt, γ-aminobutyric acid, and microcrystalline cellulose, mix well, and perform dry granulation to prepare granules.

[0020] Furthermore, the percentages of sucralose, sorbitol, maltodextrin and microcrystalline cellulose in the total weight of the lily water extract and the daylily water extract are as follows: sucralose 0.02% to 0.03%, sorbitol 4% to 6%, maltodextrin 9% to 11%, microcrystalline cellulose 1.8% to 2.0%;

[0021] Among them, lily water extract dry paste and daylily water extract dry paste are the dried products of lily water extract clear paste and daylily water extract clear paste respectively.

[0022] The beneficial effects of the present invention include but are not limited to:

[0023] The present invention provides a composition for improving depressive symptoms associated with fatigue-induced aging. The PQQ contained in the composition can increase the number and activity of mitochondria and enhance cellular energy metabolism. The flavonoids and polysaccharides contained in daylily can inhibit skin collagen degradation and provide systemic anti-inflammatory effects. The GABA contained in the composition synergizes with lily to promote emotional soothing. The PQQ and quercetin contained in daylily synergize to provide long-term regulation and protection of the neuroendocrine system. These components work together to establish a multi-target synergistic network of mitochondrial activation, neurotransmitter regulation, and systemic anti-inflammatory and antioxidant effects, thereby improving depressive symptoms associated with fatigue-induced aging. DETAILED DESCRIPTION

[0024] The present invention will be described in further detail below. However, it should be noted that the following specific embodiments are merely illustrative examples of the specific operation of the present invention, and the scope of protection of the present invention is not limited thereto. The scope of protection of the present invention is limited solely by the claims. It will be apparent to those skilled in the art that various other improvements and substitutions can be made to the embodiments of the present invention within the scope of protection defined by the claims of the present invention, and that the same technical effects can still be achieved, thereby achieving the ultimate technical purpose of the present invention.

[0025] Description of the medicinal materials used in this invention application:

[0026] Lily is the dried fleshy scales of Lilium lancifolium Thunb., Lilium brownii F.E. Brown var. viridulum Baker, or Lilium pumilum DC., all members of the Liliaceae family. They are harvested in autumn, cleaned, peeled, briefly blanched in boiling water, and dried. Lily has a sweet and cold nature and enters the heart and lung meridians, nourishing yin and moistening the lungs, clearing the heart and calming the mind, and tonifying the middle and replenishing qi. Lily's main components are steroidal saponins and phenolic acids, as well as polysaccharides, amino acids, alkaloids, and other compounds (alkanes, alcohols, volatile oils, vitamins, etc.), primarily monophenolic acids and phenolic acid glycerides and their glycosides.

[0027] Daylily (Hemerocallis citrina Baroni) belongs to the genus Hemerocallis in the Liliaceae family. It enters the heart, liver, and spleen meridians and has benefits such as relieving depression, stopping bleeding, nourishing the blood, calming the liver, and acting as a diuretic. Its main components include flavonoids (such as rutin, quercetin, kaempferol, and isorhamnetin), anthraquinones (such as emodin-type anthraquinones), volatile oils (furfurals and their derivatives, esters and their derivatives), polyphenols (such as chlorogenic acid and vanillic acid), alkaloids (such as colchicine), and other compounds (such as amino acids, polysaccharides, steroidal saponins, and vitamins).

[0028] Pyrroloquinoline quinone, abbreviated as PQQ, is a coenzyme of oxidoreductase, which has an ortho-benzoquinone structure.

[0029] γ-aminobutyric acid (GABA), also known as aminobutyric acid, is a natural non-protein amino acid widely existing in prokaryotes and eukaryotes.

[0030] Example 1:

[0031] The composition for improving tired and depressed symptoms of senile depression provided in the embodiment is made of the following raw materials by weight: 15 kg of dried lily, 15 kg of dried day lily, 15 g of pyrroloquinoline quinone disodium salt (PQQ), and 200 g of γ-aminobutyric acid (GABA).

[0032] The preparation method of the composition comprises the following steps:

[0033] S1, the dried lily and the dried day lily are respectively subjected to water extraction process to prepare lily water extraction concentrate and day lily water extraction concentrate; the preparation method of the water extraction concentrate comprises the following steps:

[0034] S101, the dried lily and the dried day lily are mixed, 10 times the weight of water is added, and decoction is performed for 2 hours, then filtration is performed to obtain first filter residue and first filter liquor;

[0035] S102, 9 times the weight of water is added to the first filter residue, decoction is performed for 1.5 hours, and then filtration is performed to obtain second filter residue and second filter liquor;

[0036] S103, the first filter liquor and the second filter liquor are combined, and vacuum concentration is performed at 50-60℃ to prepare water extraction concentrate with a relative density of 1.03-1.10 at 50℃.

[0037] S2, the lily water extraction concentrate and the day lily water extraction concentrate are mixed with pharmaceutically acceptable excipients to prepare granules, and the specific method is as follows:

[0038] S201, sucralose, sorbitol, and malt dextrin are added to the water extraction concentrate and mixed uniformly, and then spray drying is performed;

[0039] S202, pyrroloquinoline quinone disodium salt, γ-aminobutyric acid, and microcrystalline cellulose are added and mixed uniformly, and then dry granulation is performed to prepare granules.

[0040] Among them, the percentages of sucralose, sorbitol, malt dextrin, and microcrystalline cellulose in the sum of the weights of the lily water extraction dry extract and the day lily water extraction dry extract are as follows: sucralose 0.02%, sorbitol 5%, malt dextrin 10%, and microcrystalline cellulose 2%.

[0041] The dried paste of lily water extract and the dried paste of daylily water extract are the dried products of lily water extract and daylily water extract respectively.

[0042] Example 2:

[0043] The composition for improving fatigue-type aging accompanied by depression provided in this embodiment is prepared from the following raw materials in parts by weight: 1 kg of dried lily, 1 kg of dried daylily, 1 g of pyrroloquinoline quinone disodium salt (PQQ), and 16 g of gamma-aminobutyric acid (GABA).

[0044] S101, mixing dried lily bulbs and dried daylily buds, adding 12 times the weight of water, boiling for 1.5 hours, and filtering to obtain a primary residue and a primary filtrate;

[0045] S102, adding 8 times the weight of water to the primary filter residue, boiling for 1 hour, filtering to obtain a secondary filter residue and a secondary filtrate;

[0046] S103, combining the primary filtrate and the secondary filtrate, concentrating under reduced pressure at 50-60° C. to prepare a water-extracted clear paste having a relative density of 1.03-1.10 at 50° C.;

[0047] S201, adding sucralose, sorbitol, and maltodextrin to the water-extracted paste, mixing evenly, and spray drying;

[0048] S202. Add pyrroloquinoline quinone disodium salt, γ-aminobutyric acid, and microcrystalline cellulose, mix well, and perform dry granulation to prepare granules.

[0049] The weight percentages of sucralose, sorbitol, maltodextrin and microcrystalline cellulose in the water-extracted dry paste are respectively: sucralose 0.02%, sorbitol 5%, maltodextrin 10% and microcrystalline cellulose 2%; the water-extracted dry paste is the dry substance of the water-extracted clear paste.

[0050] Example 3:

[0051] The composition for improving fatigue-type aging accompanied by depression provided in this embodiment is made from the following raw materials by weight: 2000 g of dried lily, 2000 g of dried daylily, 2 g of pyrroloquinoline quinone disodium salt (PQQ), and 24 g of gamma-aminobutyric acid (GABA).

[0052] The preparation method of the composition for improving fatigue-type aging accompanied by depression provided in this example is the same as that in Example 1.

[0053] In order to verify the therapeutic effect of the composition provided by the present invention for improving fatigue-type aging accompanied by depression symptoms, the inventors of the present application conducted the following clinical experiments.

[0054] 1. Materials and Methods

[0055] 1.1 General Information

[0056] 30 patients with fatigue type of aging combined with heart and spleen deficiency type of depression were selected as the research object, aged 30-59 years old, and the control group and the treatment group were 15 people.

[0057] 1.2 Diagnostic criteria

[0058] The diagnosis is mainly based on the working environment, accompanied by fatigue syndrome and depression. Therefore, the following diagnostic criteria for fatigue type of aging combined with heart and spleen deficiency type of depression are proposed.

[0059] (1) Long-term work in poor ventilation office environment, the working environment is mostly central air conditioning, easy to be affected by ozone, dust, radiation, noise and electromagnetic interference generated by equipment such as copiers, printers, scanners and fax machines;

[0060] (2) Chronic fatigue, which cannot be relieved after adequate rest; inattention or memory loss; muscle aches in the shoulder, neck and waist; sleep disorders such as difficulty falling asleep, dreaming and waking up at night;

[0061] (3) Meet the diagnostic criteria of ICD-10 depressive episode, Hamilton Depression Scale-17 (HAMD-17) score ≥ 17 points.

[0062] (4) Heart and spleen deficiency type of depression syndrome:

[0063] Psychiatric symptoms: ① depressed mood; ② prone to crying; ③ lethargy and lack of energy; ④ palpitations and easy fright; ⑤ decreased interest or lack of interest.

[0064] Physical symptoms: ① pale or yellowish complexion; ② poor appetite, abdominal distension and loose stools; ③ pale tongue or tooth marks; ④ weak pulse.

[0065] Patients must have at least 3 of the psychiatric symptoms and at least 2 of the physical symptoms, and the "*" "is a necessary symptom.

[0066] (5) The above symptoms last for more than half a year;

[0067] (6) Exclude chronic fatigue that can be explained by primary diseases.

[0068] 1.3 Inclusion criteria

[0069] (1) Meet the diagnostic criteria for fatigue type of aging combined with heart and spleen deficiency type of depression;

[0070] (2) Age 30-59 years old;

[0071] (3) Patients who sign the informed consent form.

[0072] 1.4 Exclusion criteria

[0073] (1) The following organic causes may lead to chronic fatigue: malignant tumors, acute or chronic liver disease (hepatitis, cirrhosis), anemia, tuberculosis, chronic lung disease, cardiovascular disease (heart failure, hypertension), endocrine / metabolic diseases (diabetes, hyperthyroidism, hypothyroidism, severe obesity (body mass index ≥ 35), autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis);

[0074] (2) The following psychosocial causes may lead to fatigue: major depression, anxiety neurosis, recent severe stress, schizophrenia, alcoholism or eating disorders (anorexia nervosa, bulimia nervosa);

[0075] (3) taking the following medications within the previous 2 weeks: antidepressants, antianxiety drugs, sleeping pills, or antihistamines;

[0076] (4) currently taking the currently recommended vitamin and mineral supplements;

[0077] (5) Patients with severe heart, lung, or cerebrovascular diseases, or liver and kidney dysfunction, who are unable to undergo aerobic exercise or medication;

[0078] (6) Those who are currently participating in other clinical trials.

[0079] 1.5 Elimination criteria

[0080] (1) Case selection did not meet the inclusion criteria or met the exclusion criteria;

[0081] (2) Have not used the products provided in this study;

[0082] (3) No data were available after randomization.

[0083] 2. Treatment Methods

[0084] All subjects underwent a standard aerobic exercise regimen based on the 2017 American College of Sports Medicine recommendations. In addition, the experimental group received the product prepared in Example 1 of the present invention, taking one 5g bag twice daily, two hours after breakfast and dinner, for 28 consecutive days. The control group only underwent aerobic exercise.

[0085] The aerobic exercise program consists of three phases: (1) Warm-up phase: Choose an outdoor space, relax your shoulders, and swing your arms for 5 minutes; (2) Exercise phase: Start with 5 minutes of aerobic exercise daily and increase by one to two minutes daily, up to a maximum of 20 minutes per day; (3) Cool-down phase: Do 10 minutes of slow walking or stretching.

[0086] 3. Observation indicators

[0087] 3.1 Baseline indicators

[0088] Age, gender, disease duration (months), body mass index, heart rate, blood pressure, smoking, diet, exercise frequency (per week) of the subjects.

[0089] 3.2 Primary efficacy indicators

[0090] (1) Personal fatigue intensity questionnaire (CIS) score: The score ranges from 8 (not tired) to 56 (severe fatigue), and a score higher than 35 indicates severe fatigue.

[0091] (2) Sleep quality: Including sleep duration and sleep stage (light sleep / deep sleep), measured by wearing a sports bracelet.

[0092] (3) HAMD-17 score: Used to assess the depressive state of patients in both groups;

[0093] (4) SF-36PF score: The total score is between 0 and 100, and the higher the score, the healthier.

[0094] (5) Pain VAS score: The score ranges from 0 to 10, and the higher the score, the more severe the pain.

[0095] 3.4 Safety indicators

[0096] (1) Vital signs: Pulse, respiration, blood pressure, body temperature;

[0097] (2) Other adverse events.

[0098] 3.5 Observation time

[0099] This study has 3 follow-up visits, and the participant's study schedule is shown in Table 1. Baseline information collection is completed at enrollment (V0). The first, second and third follow-up visits (V1, V2, V3) are scheduled on the 14th, 28th and 35th days after the intervention of exercise and the product provided by this study, and CIS, sleep quality, HAMD-17, SF-36PF, Pain VAS safety and compliance observation are completed.

[0100] Table 1 Study schedule

[0101]

[0102]

[0103] 3.6 Statistical methods

[0104] Statistical analysis was performed using SPSS 20.0 software. Quantitative indicators included the CIS, sleep quality (sleep time, light sleep, deep sleep), HAMD-17, SF-36PF, and Pain VAS. These indicators were expressed as mean ± standard deviation (SD) and compared between and within groups before and after the intervention. A P value < 0.05 was considered statistically significant.

[0105] 4. Comprehensive therapeutic effects

[0106] 4.1 General Data Comparison

[0107] The study included 30 patients with fatigue-induced aging and depression associated with heart and spleen deficiency. Twelve of them were male, and 18 were female, aged 30-59 years. Fifteen patients were included in the control group and 15 in the treatment group. The following is a detailed comparison of the general information of the two groups. No statistically significant differences were found between the treatment and control groups.

[0108] Table 2 Comparison of age, gender, disease course, body mass index, heart rate and blood pressure between the two groups

[0109]

[0110] 4.2 Comparison of CIS and sleep quality between the two groups

[0111] Compared with the treatment group before treatment, the CIS and sleep indicators of the treatment group were significantly improved after treatment (P < 0.05). Compared with the control group after treatment, the CIS reduction and sleep quality of the treatment group were better than those of the treatment group (P < 0.05). See Table 3.

[0112] Table 3 Comparison of CIS and sleep quality indicators between the two groups before and after treatment

[0113]

[0114] Compared with the group at the time of enrollment, *P<0.05; compared with the control group after treatment, #P<0.05.

[0115] 2.3 Comparison of HAMD-17, SF-36PF, and Pain VAS Scores

[0116] Compared with the treatment group before treatment, the HAMD-17 index of the patients in the treatment group using the product prepared by the present invention was significantly improved (P<0.05). Compared with the control group after treatment, the reduction range of HAMD-17 in the treatment group was better than that in the treatment group (P<0.05). The SF-36PF index of both the treatment group and the control group was improved compared with that before treatment (P>0.05), and the improvement effect of the treatment group was better than that of the control group (P>0.05). The Pain VAS index of both the treatment group and the control group was significantly improved compared with that before treatment (P<0.05), and the improvement effect of the treatment group was better than that of the control group (P>0.05), as shown in Table 4.

[0117] Table 4 Comparison of HAMD-17, SF-36PF and Pain VAS indicators before and after treatment between the two groups

[0118]

[0119] Compared with the group at the time of enrollment*P<0.05; compared with the control group after treatment#P<0.05

[0120] During the study period, there were no significant changes in vital signs (weight, blood pressure, heart rate) in either group, and no adverse events were reported in the treatment group during the trial.

[0121] The above specific implementation manner cannot be used as a limitation on the protection scope of the present invention. For those skilled in the art, any replacement, improvement or transformation made to the implementation manner of the present invention falls within the protection scope of the present invention.

[0122] Any matters not described in detail in the present invention are well-known technologies to those skilled in the art.

Claims

1. A composition for improving fatigue-type aging accompanied by depression symptoms, characterized in that: The invention is prepared from the following raw materials in parts by weight: 500-1000 parts of dried lily bulbs, 500-1000 parts of dried day lily, 0.5-1 part of pyrroloquinoline quinone disodium salt and 8-12 parts of gamma-aminobutyric acid.

2. The composition according to claim 1, characterized in that The invention is prepared from the following raw materials in parts by weight: 750 parts of dried lily bulbs, 750 parts of dried day lily buds, 0.75 parts of pyrroloquinoline quinone disodium salt and 10 parts of gamma-aminobutyric acid.

3. The method for preparing the composition according to claim 1 or 2, wherein: The steps include: S1. Extracting dried lily and dried daylily into lily water-extracted paste and daylily water-extracted paste respectively; S2. Mixing the lily water extract paste and the daylily water extract paste with pharmaceutically acceptable excipients to prepare an oral preparation.

4. The preparation method according to claim 3, characterized in that The preparation method of the water-extracted clear paste comprises the following steps: S101. Mix dried lily bulbs and dried daylily buds, add 8 to 12 times their weight of water, boil for 1 to 2 hours, and filter to obtain a primary residue and a primary filtrate; S102, adding 8 to 10 times the weight of water to the primary filter residue, boiling for 0.5 to 1.5 hours, and filtering to obtain a secondary filter residue and a secondary filtrate; S103. Combine the primary filtrate and the secondary filtrate, and concentrate under reduced pressure at 50-60° C. to prepare a water-extracted clear paste having a relative density of 1.03-1.10 at 50° C.

5. The preparation method according to claim 3, characterized in that The oral preparation is oral liquid, granules, tablets, capsules or pills.

6. The preparation method according to claim 3, characterized in that The oral preparation is a granule, and the excipients are sucralose, sorbitol, maltodextrin and microcrystalline cellulose.

7. The preparation method according to claim 6, characterized in that When preparing granules, step S2 is: S201, adding sucralose, sorbitol, and maltodextrin to the lily water extract paste and the daylily water extract paste, mixing evenly, and spray drying; S202. Add pyrroloquinoline quinone disodium salt, γ-aminobutyric acid, and microcrystalline cellulose, mix well, and perform dry granulation to prepare granules.

8. The preparation method according to claim 6, characterized in that The percentages of sucralose, sorbitol, maltodextrin and microcrystalline cellulose in the total weight of the lily water extract and the daylily water extract are as follows: sucralose 0.02% to 0.03%, sorbitol 4% to 6%, maltodextrin 9% to 11%, microcrystalline cellulose 1.8% to 2.0%; Among them, lily water extract dry paste and daylily water extract dry paste are the dried products of lily water extract clear paste and daylily water extract clear paste respectively.

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