Composition, preparation method therefor, and use thereof

Abstract

A composition, a preparation method therefor, and the use thereof. The composition comprises the following raw materials: 26-225 parts of a plant extract, 20-100 parts of a probiotic powder, and 10-50 parts of L-glutamine. The composition can be used in the preparation of foods, health foods, formula foods for special medical purposes, dietary supplements, or pharmaceutical products for regulating stress, improving mood, improving intestinal function, relieving fatigue, improving sleep, and enhancing concentration and memory.

Description

A composition, a method for preparation, and its use Technical Field

[0001] This invention relates to a composition, preparation method, and use, specifically to a probiotic compound capsule, belonging to the technical fields of food, health food, dietary supplements, special medical purpose formula food, and pharmaceuticals. Background Technology

[0002] In recent years, with rapid industrialization and increasingly fierce social competition, the pressure of life, study, and work has increased significantly, leading to a rise in emotional problems such as depression, tension, irritability, anxiety, and even mood swings. Research has found that if the clearance of ion metabolites (such as K+), energy metabolites (such as adenosine and lactic acid), and protein metabolites (such as amyloid Aβ) produced by neuronal activity is slowed, these metabolic wastes can cause neuronal dysfunction, resulting in poor mental state, low mood, and severely impacting students' learning outcomes, work efficiency, and ultimately, quality of life.

[0003] Improving the overall mood of healthy adults, reducing feelings of depression, tension, irritability, stress, anxiety, and fatigue, and increasing vitality has become a pursuit for more and more people. If anxiety is not effectively managed, it can lead to depression. Depression, also known as depressive disorder, is a mental disorder with a high incidence, high clinical cure rate but low treatment acceptance rate and high relapse rate. Its main characteristic is significant and persistent low mood. Some patients may exhibit self-harm or suicidal behavior, and may even experience psychotic symptoms such as delusions and hallucinations. Severe depression can lead to somatization reactions. Somatization refers to the physical manifestation of inner pain and discomfort when facing psychological stress or emotional distress. These symptoms may include headaches, stomach aches, palpitations, difficulty breathing, gastrointestinal discomfort, sleep disturbances, and persistent fatigue, seriously affecting people's lives.

[0004] Currently, there are numerous mood-enhancing products on the market. Saffron, a plant with both medicinal and edible properties, is frequently used in these products. Saffron (also known as crocus or crassirhizoma saffron) belongs to the genus Crocus in the Iridaceae family. It is a perennial bulbous herb native to Mediterranean countries such as Iran and Greece, and is now cultivated in countries including my country and Japan. Saffron is the only species in the Crocus genus that can be used medicinally. The medicinal part is the dried stigma of the style, which is usually made into an extract. Saffron extract contains crocin, which has strong free radical scavenging, antioxidant, and anti-cancer activities. Saffron is also often used as an ingredient in mood-regulating products, compounded with other ingredients to prepare mood-enhancing products. In our research on similar products containing saffron extract, we found that saffron extract is easily degraded. This may be due to the influence of the types and amounts of other materials used on its stability. Often, the content of the active ingredients in saffron extract products degrades quickly, resulting in low levels that do not achieve the desired product efficacy and do not meet market expectations.

[0005] In addition, the traditional probiotic capsule preparation process has problems such as complex preparation process, low utilization rate of live bacteria, insufficient number of live bacteria in the finished product, limited effect and insufficient conditioning ability.

[0006] Ensuring the stability of the number of probiotics and the saffron content in saffron probiotic products to guarantee their effectiveness, while maintaining the stability of all product properties, places extremely high demands on the formulation and processing.

[0007] Therefore, providing a product that regulates stress, improves mood, has stable efficacy and properties, and also improves gut health, relieves fatigue, and enhances concentration and memory is a pressing issue in this field. Summary of the Invention

[0008] This invention provides a composition that regulates stress, improves mood, improves gut health, relieves fatigue, improves sleep, and enhances concentration and memory. This invention also provides a method for preparing the composition and its applications.

[0009] This invention provides a composition comprising the following ingredients: 26-225 parts of plant extract, 20-100 parts of probiotic powder, and 10-50 parts of L-glutamine;

[0010] The plant extract is selected from at least one of turmeric extract, saffron extract, black pepper extract, black cohosh extract, hops extract, chamomile extract, and valerian extract;

[0011] The probiotic powder contains ≥5*10 live bacteria. 10 cfu / g; The probiotic powder contains at least one strain of Bifidobacterium longum, Lactobacillus helveticus, and Lactobacillus plantarum.

[0012] The content of L-glutamine is ≥99%.

[0013] Preferably, the weight ratio of the plant extract is as follows:

[0014] Turmeric extract 25-200 parts, saffron extract 1-20 parts, black pepper extract 0.1-3.0 parts.

[0015] More preferably, it comprises the following ingredients in the indicated weight ratios: 55-98 parts turmeric extract, 40-80 parts probiotic powder, 20-40 parts L-glutamine, 5-15 parts saffron extract, and 0.5-3.0 parts black pepper extract.

[0016] The composition of this invention also includes prebiotics; specifically, it includes the following raw materials in the following weight ratios: 70-90 parts of turmeric extract, 40-60 parts of probiotic powder, 28-32 parts of L-glutamine, 7.0-8.5 parts of saffron extract, 1.0-2.2 parts of black pepper extract, and 20-50 parts of prebiotics;

[0017] The prebiotic is selected from at least one of xylooligosaccharide, inulin, polydextrose, isomaltooligosaccharide, galactooligosaccharide, fructooligosaccharide, and resistant dextrin.

[0018] The total curcumin content in the turmeric extract is ≥95%;

[0019] The black pepper extract contains ≥95% piperine;

[0020] The saffron extract includes saffron aldehyde and total saffron glycosides; the content of saffron aldehyde and total saffron glycosides is ≥3.5%;

[0021] The probiotic powder contains three strains: Lactobacillus helveticus R-0052, Lactobacillus plantarum R-1012, and Bifidobacterium longum R-0175.

[0022] The composition of the present invention is an oral preparation made by adding acceptable excipients or auxiliary ingredients to the raw materials as functional components; the excipients or auxiliary ingredients are selected from at least one of diluents, alkalis, lubricants, and flow aids; the oral preparation is a capsule, tablet, granule, pill, or chewable tablet.

[0023] The diluent is selected from at least one of maltodextrin, cyclodextrin, microcrystalline cellulose, and corn starch;

[0024] And / or the alkaline agent is selected from at least one of sodium bicarbonate, disodium hydrogen phosphate, calcium phosphate, sodium acetate, sodium citrate, sodium vitamin C, sodium tartrate, and sodium malate;

[0025] And / or the lubricant is selected from at least one of stearic acid and magnesium stearate;

[0026] And / or the flow aid is selected from at least one of silica, colloidal silica, and talc.

[0027] The capsule shell used in the capsule preparation is an acid-resistant capsule shell or an enteric-coated capsule shell.

[0028] The acid-resistant capsule shell contains at least one of hydroxypropyl methylcellulose, gellan gum, and guar gum; and / or the enteric-coated capsule shell contains at least one of gelatin, hydroxypropyl methylcellulose acetate succinate, shellac, guar gum, silk protein, povidone, polysorbate 80, and castor oil.

[0029] The composition of this invention comprises the following raw materials in the indicated weight ratios: 70-90 parts turmeric extract, 40-60 parts probiotic powder, 28-32 parts L-glutamine, 7.0-8.5 parts saffron extract, 1.0-2.2 parts black pepper extract, 20-50 parts prebiotics, 4.0-80 parts diluent, 2.0-5.0 parts lubricant, and 2.0-5.0 parts flow aid.

[0030] The prebiotic is selected from at least one of xylooligosaccharide, inulin, polydextrose, isomaltooligosaccharide, galactooligosaccharide, fructooligosaccharide, and resistant dextrin.

[0031] The diluent is selected from at least one of maltodextrin, cyclodextrin, microcrystalline cellulose, and corn starch;

[0032] The lubricant is selected from at least one of stearic acid and magnesium stearate;

[0033] The flow aid is selected from at least one of silica, colloidal silica, and talc.

[0034] More preferably, the composition of the present invention comprises raw materials in the following weight ratios:

[0035] 75 parts turmeric extract, 50 parts probiotic powder, 30 parts L-glutamine, 7.0 parts saffron extract, 1.25 parts black pepper extract, 20 parts xylooligosaccharide, 4.32 parts maltodextrin, 4.24 parts stearic acid, 2.12 parts silicon dioxide;

[0036] Alternatively, 75 parts turmeric extract, 50 parts probiotic powder, 30 parts L-glutamine, 8.0 parts saffron extract, 2 parts black pepper extract, 20 parts xylooligosaccharides, 80 parts microcrystalline cellulose, 3 parts stearic acid, and 3 parts colloidal silica.

[0037] Alternatively, 90 parts turmeric extract, 50 parts probiotic powder, 31.98 parts L-glutamine, 8.08 parts saffron extract, 1.26 parts black pepper extract, 20 parts xylooligosaccharide, 4.32 parts maltodextrin, 4.24 parts stearic acid, and 2.12 parts silicon dioxide;

[0038] Alternatively, 90 parts turmeric extract, 50 parts probiotic powder, 30 parts L-glutamine, 8 parts saffron extract, 1.25 parts black pepper extract, 20 parts xylooligosaccharide, 4.32 parts maltodextrin, 4.24 parts stearic acid, and 2.12 parts silicon dioxide.

[0039] The present invention also provides a method for preparing the composition, wherein the materials are premixed, and after total mixing, the total mixed powder is vacuum-pressurized under a negative pressure of 0.07~0.08Mpa; then capsule filling is performed, and the filled capsules are placed at a temperature of -85℃~-45℃ and a pre-chamber drying temperature of 15℃~25℃ for 10-20 hours.

[0040] The present invention also provides the use of the composition in the preparation of foods, health foods, foods for special medical purposes, dietary supplements or pharmaceuticals that regulate stress, improve mood, improve gut health, relieve fatigue, improve sleep, and enhance concentration and memory.

[0041] The raw materials of this invention include turmeric extract containing total curcumin, which comes from plants of the genus Curcuma in the ginger family (Zingiberaceae). Curcumin is a diketone compound extracted from the rhizomes of some plants in the ginger and araceae families. It can increase the body's resistance and treat various inflammatory and infectious diseases. Total curcumin mainly includes three components: curcumin (CUR), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC).

[0042] L-Glutamine is an amino acid that plays an important role in immune function. Glutamine supplements may help improve immune function and preserve protein stores in the body; glutamine is an energy source for the gut and immune cells, it also helps maintain the barrier between the gut and the rest of the body, and contributes to the normal growth of intestinal cells.

[0043] Saffron extract: Extracted from the upper part of the style and stigma of saffron (Crocus sativus L.), a plant of the Iridaceae family, it is a food and medicine homology material, mainly used to promote blood circulation, remove blood stasis, and relieve stagnation. Studies have shown that it can improve sleep quality in people with poor sleep quality; for adolescents with depressive symptoms, taking saffron extract can improve mild to moderate anxiety and depressive symptoms in adolescents.

[0044] Black pepper: A perennial woody vine belonging to the genus *Piper nigrum* in the family Piperaceae. In traditional Chinese medicine, it is used to treat symptoms such as indigestion, neurasthenia, and flatulence.

[0045] Probiotic powder, according to research, can cause subtle changes in brain activity and functional connectivity in healthy subjects. It acts on the microbiome-gut-brain axis, supporting a healthy response to daily stress without side effects; it can help improve mood and provide relief during occasional stress.

[0046] Prebiotics: Prebiotics are non-digestible food components that, as dietary supplements, selectively stimulate the growth and activity of one or a few bacterial colonies to have a beneficial effect on the host, thereby improving the host's health.

[0047] The capsule composition of this invention has good acid resistance and good solubility in the intestine, which can improve the intestinal tract; its functional effects make it have a good effect on regulating stress and improving mood, which can help sleep, relieve fatigue, improve concentration and memory, and has no toxic side effects; it has a functional effect on improving the mood of healthy individuals, which can reduce low mood, tension, irritability, fatigue, anxiety and even depression in healthy individuals or patients with depression, and increase vitality.

[0048] Meanwhile, this composition effectively delays the degradation of saffron extract, ensuring stable saffron extract content, stable composition properties, and consequently, stable efficacy. The capsule preparation process for this composition is simple and practical, guaranteeing the survival rate of various probiotics in the composition, resulting in high survival and utilization rates. Detailed Implementation

[0049] In the embodiment described:

[0050] The materials described in this invention can all be purchased from the market or prepared by methods well known to those skilled in the art.

[0051] The probiotic powder contains: Bifidobacterium longum R-0175, Lactobacillus helveticus R-0052, Lactobacillus plantarum R-1012, fructooligosaccharides, ascorbic acid, and maltodextrin. The probiotic powder was purchased from Lallemand Health Solutions Inc. Live bacteria count: 58.8 x 10⁻⁶. 9 cfu / g.

[0052] The L-glutamine content was 99.8%; it was purchased from Aktin Chemicals, Inc.

[0053] The total curcumin content in the turmeric extract was 95.19%; purchased from Aktin Chemicals, Inc.

[0054] The piperine content in the black pepper extract is 96.5%; purchased from SAMI-SABINSA GROUP LIMITED;

[0055] The saffron extract includes crocetin and total crocin; the content of crocetin and total crocin is 4.29%; purchased from: Pharmactive Biotech Products, S.L.

[0056] "Parts" in the embodiments of the present invention represent the unit of "mg".

[0057] Composition of Example 1

[0058] 75 parts of turmeric extract, 50 parts of probiotic powder, 30 parts of L-glutamine, 7.0 parts of saffron extract, 1.25 parts of black pepper extract, 20 parts of xylo-oligosaccharide, 4.32 parts of maltodextrin, 4.24 parts of stearic acid, 2.12 parts of silicon dioxide.

[0059] Composition of Example 2

[0060] 75 parts of turmeric extract, 50 parts of probiotic powder, 30 parts of L-glutamine, 8.0 parts of saffron extract, 2 parts of black pepper extract, 20 parts of xylo-oligosaccharide, 80 parts of microcrystalline cellulose, 3 parts of stearic acid, 3 parts of colloidal silicon dioxide.

[0061] Composition of Example 3

[0062] 90 parts of turmeric extract, 50 parts of probiotic powder, 31.98 parts of L-glutamine, 8.08 parts of saffron extract, 1.26 parts of black pepper extract, 20 parts of xylo-oligosaccharide, 4.32 parts of maltodextrin, 4.24 parts of stearic acid, 2.12 parts of silicon dioxide.

[0063] Composition of Example 4

[0064] 90 parts of turmeric extract, 50 parts of probiotic powder, 30 parts of L-glutamine, 8 parts of saffron extract, 1.25 parts of black pepper extract, 20 parts of xylo-oligosaccharide, 4.32 parts of maltodextrin, 4.24 parts of stearic acid, 2.12 parts of silicon dioxide.

[0065] Composition of Example 5

[0066] 70 parts of turmeric extract, 50 parts of probiotic powder, 28 parts of L-glutamine, 8.5 parts of saffron extract, 1.5 parts of black pepper extract, 50 parts of isomaltooligosaccharide, 55.5 parts of maltodextrin, 2.5 parts of magnesium stearate, 5.0 parts of talc.

[0067] The compositions obtained in Examples 1-5 of this invention have a bulk density of 0.412-0.591 g / ml, a tap density of 0.637-0.847 g / ml, and an angle of repose of 42.4°-45.8°.

[0068] Example 6: Composition Capsules

[0069] 75 parts turmeric extract, 50 parts probiotic powder, 30 parts L-glutamine, 7.0 parts saffron extract, 1.25 parts black pepper extract, 20 parts xylooligosaccharide, 4.32 parts maltodextrin, 4.24 parts stearic acid, and 2.12 parts silicon dioxide.

[0070] Example 7: Composition Capsules

[0071] 75 parts turmeric extract, 50 parts probiotic powder, 30 parts L-glutamine, 8.0 parts saffron extract, 2 parts black pepper extract, 20 parts xylooligosaccharide, 80 parts microcrystalline cellulose, 3 parts stearic acid, and 3 parts colloidal silica.

[0072] Example 8: Composition Capsules

[0073] 90 parts turmeric extract, 50 parts probiotic powder, 31.98 parts L-glutamine, 8.08 parts saffron extract, 1.26 parts black pepper extract, 20 parts xylooligosaccharide, 4.32 parts maltodextrin, 4.24 parts stearic acid, and 2.12 parts silicon dioxide.

[0074] Example 9: Composition Capsules

[0075] 90 parts turmeric extract, 50 parts probiotic powder, 30 parts L-glutamine, 8 parts saffron extract, 1.25 parts black pepper extract, 20 parts xylooligosaccharide, 4.32 parts maltodextrin, 4.24 parts stearic acid, and 2.12 parts silicon dioxide.

[0076] Example 10: Composition Capsules

[0077] 70 parts turmeric extract, 50 parts probiotic powder, 28 parts L-glutamine, 8.5 parts saffron extract, 1.5 parts black pepper extract, 50 parts isomaltooligosaccharide, 55.5 parts maltodextrin, 2.5 parts magnesium stearate, and 5.0 parts talc.

[0078] The preparation process of the capsules of the compositions in Examples 6-10 is as follows:

[0079] The production process selected is direct filling, which includes the steps of "mixing and dispersing, sieving and dispersing, premixing, total mixing, and capsule filling". Environmental control: relative humidity ≤ RH50%.

[0080] (1) Pretreatment: Weigh an appropriate amount of lubricant and transfer it to the crushing and sieving room, and use a vibrating screen (60 mesh screen) for sieving.

[0081] (2) Ingredients: Turmeric extract and saffron extract were weighed according to 100% of the formula amount after drying and set aside. The dry amount calculation was: Actual amount of material = Theoretical amount of material / [(Material weight - moisture weight measured after drying) / Material weight];

[0082] Weigh out the black pepper extract, gliding agent, lubricant, L-glutamine, prebiotic, diluent, and probiotic powder in the correct order according to the formula, and label them for later use.

[0083] (3) Dispersion

[0084] 1. Mixing and Dispersion: Add the weighed diluent, turmeric extract, probiotic powder, L-glutamine, prebiotics, saffron extract, black pepper extract, and glidant to the mixer in sequence. Set the mixer speed to 16 rpm and the mixing time to 15 minutes.

[0085] 2. Sieving and dispersing: The mixture is sieved through a 30-mesh sieve. All sieved materials are collected in pharmaceutical low-density polyethylene bags to obtain dispersed materials.

[0086] (4) Premixing: Add the dispersed material to the mixer, set the mixing speed to 16 rpm and the mixing time to 15 min to obtain premixed powder.

[0087] (5) Final mixing: Add the lubricant to the mixer after the premixing process. Set the mixing speed to 16 rpm and mix for 5 minutes to obtain the final powder.

[0088] The total powder mixture was stored in a vacuum pressure chamber at a negative pressure of 0.08 MPa.

[0089] (6) Filling: Capsules: GRAS grade acid-resistant capsules or GRAS grade enteric-coated capsules are selected. Acid-resistant capsules: The main components are hydroxypropyl methylcellulose and gellan gum; Enteric-coated capsules: The main components are hydroxypropyl methylcellulose acetate succinate and gelatin.

[0090] Capsule selection: Use a capsule screening and polishing machine to polish and remove waste capsules, and then remove defective capsules by visual inspection.

[0091] (7) Drying: The qualified capsules are dried using a freeze dryer with the cold well temperature set at -65℃ and the pre-drying temperature at 25℃ for 12 hours.

[0092] Theoretical fill weight: Fill at 0.212g. After confirming the parameters, start the filling machine, take samples to check the fill weight range and average fill weight, and adjust the filling rod according to the check results so that the average fill weight is between 95-105% of the theoretical fill weight and the particle weight difference is between 90-110% of the theoretical fill weight. Example 11

[0093] The difference from Example 8 is as follows:

[0094] (5) Final mixing: Add the lubricant to the mixer after the premixing process. Set the mixing speed to 16 rpm and mix for 5 minutes to obtain the final powder.

[0095] The total powder mixture was stored in a vacuum pressure chamber at a negative pressure of 0.07 MPa.

[0096] (7) Drying: The qualified capsules are dried using a freeze dryer. The cold well temperature is set to -45℃ and the pre-chamber drying temperature is 15℃. The drying is continued for 20 hours. Example 12

[0097] The difference from Example 8 is as follows:

[0098] (5) Final mixing: Add the lubricant to the mixer after the premixing process. Set the mixing speed to 16 rpm and mix for 5 minutes to obtain the final powder.

[0099] The total powder mixture was stored in a vacuum pressure chamber at a negative pressure of 0.075 MPa.

[0100] (7) Drying: The qualified capsules are dried using a freeze dryer with the cold well temperature set at -85℃ and the pre-chamber drying temperature at 20℃ for 15 hours.

[0101] The compositions of Examples 6-12 of this invention have no risk of sticking or impaction after capsule filling, and the weight difference of each capsule is within -10% to 10%, which meets the requirements for capsule filling.

[0102] Comparative composition capsule formulation screening

[0103] Table 1 Screening of Composition Capsule Formulations

[0104]

[0105] Table 1 shows that, using potato starch as a diluent, except for Comparative Example 2 which had poor flowability, the angle of repose of the other formulations was below 50°, meeting the filling requirements. However, based on the filling results, all formulations exhibited sticking and impaction, and the particle weight difference did not meet the requirements, indicating that using potato starch as a diluent increases the risk of sticking and impaction in the total mixed powder. The proportions in Comparative Example 5 were unreasonable and outside the scope of this invention, resulting in unmet particle weight difference requirements. The composition in Comparative Example 6 had an angle of repose of 53.32°, indicating poor flowability and failing to meet the capsule filling requirements (extremely poor material flowability or particularly large particle weight difference both fail to meet capsule filling requirements).

[0106] Experimental Example 1: Stability Study of the Composition for Acid-Resistant Capsules

[0107] Stability tests were conducted using capsules containing the composition of Example 7, with the capsule shell being a GRAS-grade acid-resistant capsule shell.

[0108] The capsules were tested at temperatures of 2–8℃, 25±2℃, RH 60±5%, 40±2℃, and RH 75±5% for 0 days, 1 month, and 3 months, respectively. The quality stability of the capsules was assessed using key indicators such as disintegration time, the specific components of easily degradable saffron extract, and the content of total curcumin and L-glutamine. The results are shown in Tables 2-4 below.

[0109] 1. Measurement method:

[0110] 1.1 Moisture content: Refer to General Chapter 0832, Method 1 of ChP2020;

[0111] 1.2 Disintegration time limit: Refer to USP2040;

[0112] 1.3 Key components: Referring to HPLC method; specifically:

[0113] 1.4 Determination of saffron extract (calculated as Lepticrosalides):

[0114] Test solution: Weigh the contents of the capsule and prepare a solution of 13.3 mg / ml (solvent is 50% ethanol), shake well, filter, and collect the filtrate.

[0115] Reference solution: Take appropriate amounts of crocin I and crocin aldehyde reference standards, accurately weigh them, dissolve them in solvent, and prepare solutions containing approximately 12.5 μg of crocin I and approximately 0.25 μg of crocin aldehyde per 1 ml.

[0116] Chromatographic conditions: The column was packed with octadecylsilane-bonded silica gel; mobile phase A was 0.02 mol / L potassium dihydrogen phosphate solution (adjusted to pH 7.0 with 20% sodium hydroxide solution), and mobile phase B was acetonitrile, with gradient elution performed according to the table below; a diode array detector was used to scan in the range of 200 nm to 500 nm, with the detection wavelength of crocin at 440 nm and the detection wavelength of crocinaldehyde at 315 nm; the flow rate was 1.0 mL per minute, the column temperature was 25 °C, and the injection volume was 20 μL.

[0117]

[0118] System suitability requirements: The theoretical plate number, calculated based on the crocin I peak, shall not be less than 5000.

[0119] Determination: Accurately measure the test solution and reference solution, and inject them separately into the liquid chromatograph, recording the chromatograms. If the chromatogram of the test solution contains a peak with the same spectrum as that of crocin I in the chromatogram of the reference solution, calculate the content of total crocin by summing the peak areas using the external standard method. If the chromatogram of the test solution contains a peak with the same retention time as that of crocin aldehyde in the chromatogram of the reference solution, calculate the content of crocin aldehyde by peak area using the external standard method. Lepticrosalides is the sum of total crocin and crocin aldehyde. The major peaks include crocin I, which is located by the retention time of the chromatographic peak of crocin I in the reference solution; crocin II, whose peak area is calculated by being located at a relative retention time of approximately 1.07 with crocin I; the unknown crocin at a relative retention time RRT-1.22 with crocin I, and its peak area represents the content of this unknown glycoside; the minor peaks are other unknown crocins, and their content is the sum of the peak areas of other unknown glycosides whose spectra are consistent with crocin-I in the chromatogram of the reference solution (not shown in the relevant tables).

[0120] 1.5L-Glutamine Determination:

[0121] Test solution: Weigh the contents of the capsule, prepare an aqueous solution of about 3.53 mg / ml, shake well, filter, and collect the filtrate.

[0122] Reference solution: Take an appropriate amount of L-glutamine reference standard, accurately weigh it, dissolve it in water and dilute it quantitatively to prepare a solution containing about 0.5 mg per 1 ml.

[0123] Chromatographic conditions: The column was packed with octadecylamide-bonded silica gel; the mobile phase was 0.05 mol / L sodium dihydrogen phosphate aqueous solution (adjusted to pH 4.0 with phosphoric acid) - acetonitrile (30:70); the detection wavelength was 210 nm; the flow rate was 1.0 mL per minute; the column temperature was 25 °C; and the injection volume was 20 μL.

[0124] Assay: Accurately measure the test solution and the reference solution, inject them separately into the liquid chromatograph, and record the chromatograms for 10 minutes.

[0125] 1.6 Determination of turmeric extract (calculated as total curcumin):

[0126] Test solution: Accurately weigh approximately 140 mg of capsule contents, place in a 100 ml volumetric flask, add approximately 80 ml of methanol, sonicate for 5 min, cool, dilute to the mark with methanol, shake well, and filter. Accurately measure 1 ml of the filtrate, place in a 50 ml volumetric flask, dilute to the mark with methanol, and shake well.

[0127] Reference solution: Take an appropriate amount of curcumin reference standard, accurately weigh it, and add methanol to prepare a solution containing 7.5 μg per ml.

[0128] Chromatographic conditions: The column was packed with octadecylsilane-bonded silica gel; the mobile phase was acetonitrile-4% glacial acetic acid solution (48:52); the detection wavelength was 420 nm; the flow rate was 1.0 ml per minute; the column temperature was 25 ℃; and the injection volume was 20 μl.

[0129] System applicability requirements: The theoretical plate number, calculated based on the curcumin peak, should be no less than 5000.

[0130] Assay: Accurately measure 20 μl each of the test solution and the reference solution, and inject them separately into the liquid chromatograph. Record the chromatograms for 20 minutes. In the chromatogram of the test solution, peaks will elute sequentially in the order of bis(demethoxy)curcumin, demethoxycurcumin, and curcumin. The peak areas of bis(demethoxy)curcumin and demethoxycurcumin will be calculated using the external standard method based on the corrected peak areas (multiplied by correction factors of 0.96 and 0.94, respectively). Curcumin will be calculated using the external standard method based on the peak area. Total curcumin is the sum of the contents of bis(demethoxy)curcumin, demethoxycurcumin, and curcumin.

[0131] 1.7 The acceptable standard is:

[0132] Appearance: The contents are yellow powder with visible fine pink powder; there are no other abnormal colored powders or visible impurities.

[0133] Moisture: ≤5.0%;

[0134] Disintegration time limit: Complete disintegration should occur within 30 minutes (pH 4.5 acetate buffer);

[0135] Lepticrosalide (the core component of saffron extract, a collective term for saffron aldehyde and total saffron glycosides): ≥0.9g / kg.

[0136] 2. Test Results:

[0137] Stability and appearance data: Day 0: Contents are yellow powder with visible fine pinkish-red powder; no other abnormal colored powders or visible impurities; meets standard requirements. Month 1: Capsule shell shows no significant change; contents are yellow powder with visible fine pinkish-red powder; no other abnormal colored powders or visible impurities; meets standard requirements. Month 3: Capsule shell shows no significant change; contents are yellow powder with visible fine pinkish-red powder; no other abnormal colored powders or visible impurities; meets standard requirements.

[0138] Table 2. Capsule test results under refrigeration test (2~8℃)

[0139]

[0140] Table 3. Capsule test results under long-term test (25±2℃, RH60±5%)

[0141]

[0142] Table 4. Capsule test results under accelerated testing (40±2℃, RH75±5%)

[0143]

[0144] As can be seen from the experimental test results in Tables 2-4, the components of the saffron extract in the composition and capsules of the present invention are stable, and the degradation of saffron is very slow under the formulation of the present invention; the content of L-glutamine and total curcumin changes only slightly. It can be seen that the main components of the composition and capsules of the present invention are stable under long-term and accelerated conditions, suitable for long-term storage, and fully meet the efficacy requirements during product use.

[0145] Comparative Experiment Example 1: Degradation Study of Saffron Extract:

[0146] The degradation of saffron extract under high humidity (RH 75%±5%) was investigated, as shown in Table 5-7 below.

[0147] Table 5. Degradation results of saffron extract under high humidity (RH 75%)

[0148]

[0149] Table 6. Degradation results of saffron extract with the addition of other components at high humidity (RH 75%±5%).

[0150]

[0151] Table 7. Degradation results of saffron extract with the addition of other components at high humidity (RH 75%±5%).

[0152]

[0153] Table 5 shows that under high humidity (RH 75%) and 25℃, the degradation rate of lepsticrosalide in saffron extract was 20.6%. Tables 6 and 7 show that the addition of probiotic powder, turmeric extract, L-glutamine, black pepper extract, xylooligosaccharides, and / or excipients (microcrystalline cellulose, colloidal silica, stearic acid) resulted in a lower degradation rate of lepsticrosalide, the main active ingredient in saffron extract, compared to its own degradation rate. This indicates that the addition of probiotic powder, turmeric extract, L-glutamine, black pepper extract, xylooligosaccharides, and / or excipients (microcrystalline cellulose, colloidal silica, stearic acid) can delay the degradation of saffron extract under high humidity conditions. Table 4 shows that the capsules described in this invention degraded by 2.80% of lepsticrosalide in one month at 40±2℃ and RH 75±5%. Compared to Table 5, the degradation of lepsticrosalide in the contents of the capsules described in this invention is far less than its own degradation rate, demonstrating that the composition of this invention has excellent formulation stability and superior product quality.

[0154] The degradation of saffron extract under high temperature conditions (60℃±2℃) is shown in Table 8-10 below.

[0155] Table 8. Degradation results of saffron extract at high temperature (60℃±2℃)

[0156]

[0157] Table 9. Degradation results of saffron extract at high temperature (60℃±2℃) with the addition of other components.

[0158]

[0159] Table 10. Degradation results of saffron extract at high temperature (60℃±2℃) with the addition of other components

[0160]

[0161] As shown in Table 8-10, under extreme high temperature conditions (60℃±2℃), the addition of probiotic powder, turmeric extract, L-glutamine, black pepper extract, xylooligosaccharides, and / or excipients (microcrystalline cellulose, colloidal silica, stearic acid) resulted in less degradation of saffron's main active ingredient, Lepsticrosalide, than Lepsticrosalide itself. This indicates that the addition of probiotic powder, turmeric extract, L-glutamine, black pepper extract, xylooligosaccharides, and / or excipients (microcrystalline cellulose, colloidal silica, stearic acid) can delay the degradation of saffron under high temperature conditions.

[0162] Experimental Example 2

[0163] The viable counts of various probiotics in the capsules of the composition obtained in Example 8 (capsule shells are GRAS grade acid-resistant capsule shells) were tested, and the test method was determined according to GB4789.35-2023.

[0164] The test results showed that the number of viable bacteria in the capsules containing the composition obtained in Example 8 was 3.9*10^6. 9 CFU / capsule. At a dosage of 4 capsules per day, the total probiotic count can reach 1.56 x 10^6. 10 The CFU / d ratio ensures the efficacy of the probiotics, further guaranteeing the efficacy of the capsule composition.

[0165] Comparative Test Example 2

[0166] The composition in Example 2 was used to fill capsules according to the capsule preparation process described below, and the capsule shell was a GRAS grade acid-resistant capsule shell.

[0167] The capsule preparation process is as follows:

[0168] The production process selected is direct filling, which includes the steps of "mixing and dispersing, sieving and dispersing, premixing, total mixing, and capsule filling". Environmental control: relative humidity ≤ RH50%.

[0169] (1) Pretreatment: Weigh an appropriate amount of lubricant and transfer it to the crushing and sieving room, and use a vibrating screen (60 mesh screen) for sieving.

[0170] (2) Ingredients: Turmeric extract and saffron extract were weighed according to 100% of the formula amount after drying and set aside. The dry amount calculation was: Actual amount of material = Theoretical amount of material / [(Material weight - moisture weight measured after drying) / Material weight];

[0171] Weigh out the black pepper extract, gliding agent, lubricant, L-glutamine, prebiotic, diluent, and lactic acid bacteria powder in the correct order according to the formula, and label them for later use.

[0172] (3) Dispersion

[0173] 1. Mixing and Dispersion: Add the weighed diluent, turmeric extract, lactic acid bacteria powder, L-glutamine, prebiotics, saffron extract, black pepper extract, and glidant to the mixer in sequence. Set the mixer speed to 16 rpm and the mixing time to 15 minutes.

[0174] 2. Sieving and dispersing: The mixture is sieved through a 30-mesh sieve. All the sieved material is collected in a pharmaceutical low-density polyethylene bag to obtain the dispersed material.

[0175] (4) Premixing: Add the dispersed material to the mixer, set the mixing speed to 16 rpm and the mixing time to 15 min to obtain premixed powder.

[0176] (5) Final mixing: Add the lubricant to the mixer after the premixing process. Set the mixing speed to 16 rpm and mix for 5 minutes to obtain the final powder.

[0177] (6) Filling: Capsules: GRAS grade acid-resistant capsules: main components are hydroxypropyl methylcellulose and gellan gum.

[0178] Theoretical fill weight: Fill at 0.212g. After confirming the parameters, start the filling machine, take samples to check the fill weight range and average fill weight, and adjust the filling rod according to the check results so that the average fill weight is between 95-105% of the theoretical fill weight and the particle weight difference is between 90-110% of the theoretical fill weight.

[0179] The number of live probiotics in the capsules obtained from Comparative Experiment Example 2 was tested, and the test method was determined according to GB4789.35-2023.

[0180] The test results showed that the number of viable bacteria in the capsule of Comparative Experiment Example 2 was 3.09*10^6. 9 CFU / capsule. At a dosage of 4 capsules per day, the total probiotic count reaches 1.236*10^4. 10 CFU / d; however, compared to Example 2, the number of live bacteria decreased by 20.8%, indicating that the preparation process of the present invention can well ensure the survival of live bacteria, and the utilization rate of probiotics is high, which further effectively ensures the efficacy of the composition capsules and makes its efficacy more advantageous.

[0181] The capsule composition of this invention exhibits good acid resistance and intestinal solubility, thus improving gut health. Its functional components effectively regulate stress and improve mood, thereby relieving fatigue and enhancing focus and memory. Furthermore, the composition effectively slows down the degradation of saffron extract, resulting in stable properties and efficacy. The capsule preparation process is simple and practical, ensuring high survival rates and utilization of various probiotics, with the product containing up to 3.9 x 10^9 probiotics. 9 CFU / capsule, taken at a dose of 4 capsules per day, provides a total probiotic count of 1.56 x 10^6 bacteria. 10 CFU / d ensures the effectiveness of probiotics.

[0182] The composition of this invention can regulate stress and improve mood; it has a functional effect on improving the mood of healthy individuals, reducing low mood, tension, irritability, fatigue, anxiety, and even depression in healthy individuals and patients with depression, and increasing their vitality. It is also stable in nature and therefore has stable efficacy, and has the effects of improving gut health, relieving fatigue, and improving concentration and memory; the preparation method is simple and it is highly usable.

Claims

1. A composition characterized in that, It includes the following ingredients: 26-225 parts plant extracts, 20-100 parts probiotic powder, and 10-50 parts L-glutamine; The plant extract is selected from at least one of turmeric extract, saffron extract, black pepper extract, black cohosh extract, hops extract, chamomile extract, and valerian extract; The probiotic powder contains ≥5*10 live bacteria. 10 cfu / g; The probiotic powder contains at least one strain of Bifidobacterium longum, Lactobacillus helveticus, and Lactobacillus plantarum. The content of L-glutamine is ≥99%.

2. The composition of claim 1, wherein, The weight ratio of the plant extracts is as follows: Turmeric extract 25-200 parts, saffron extract 1-20 parts, black pepper extract 0.1-3.0 parts.

3. The composition of claim 2, wherein, It comprises the following ingredients in the indicated weight ratios: 55-98 parts turmeric extract, 40-80 parts probiotic powder, 20-40 parts L-glutamine, 5-15 parts saffron extract, and 0.5-3.0 parts black pepper extract.

4. The composition according to any one of claims 1 to 3, characterized in that, It also includes prebiotics; specifically, it includes the following ingredients in the following weight ratios: 70-90 parts turmeric extract, 40-60 parts probiotic powder, 28-32 parts L-glutamine, 7.0-8.5 parts saffron extract, 1.0-2.2 parts black pepper extract, and 20-50 parts prebiotics; The prebiotic is selected from at least one of xylooligosaccharide, inulin, polydextrose, isomaltooligosaccharide, galactooligosaccharide, fructooligosaccharide, and resistant dextrin.

5. The composition according to any one of claims 1 to 4, characterized in that, The total curcumin content in the turmeric extract is ≥95%; The black pepper extract contains ≥95% piperine; The saffron extract includes saffron aldehyde and total saffron glycosides; the content of saffron aldehyde and total saffron glycosides is ≥3.5%; The probiotic powder contains three strains: Lactobacillus helveticus R-0052, Lactobacillus plantarum R-1012, and Bifidobacterium longum R-0175.

6. The composition according to any one of claims 1 to 5, characterized in that, It is an oral preparation made from the raw materials as functional components and with the addition of acceptable excipients or auxiliary components; the excipients or auxiliary components are selected from at least one of diluents, alkalis, lubricants, and flow aids; the oral preparation is a capsule, tablet, granule, pill, or chewable tablet. The diluent is selected from at least one of maltodextrin, cyclodextrin, microcrystalline cellulose, and corn starch; And / or the alkaline agent is selected from at least one of sodium bicarbonate, disodium hydrogen phosphate, calcium phosphate, sodium acetate, sodium citrate, sodium vitamin C, sodium tartrate, and sodium malate; And / or the lubricant is selected from at least one of stearic acid and magnesium stearate; And / or the flow aid is selected from at least one of silica, colloidal silica, and talc.

7. The composition according to claim 6, characterized in that, The capsule shell used in the capsule formulation is an acid-resistant capsule shell or an enteric-coated capsule shell.

8. The composition according to claim 7, characterized in that, The acid-resistant capsule shell contains at least one of hydroxypropyl methylcellulose, gellan gum, and guar gum; and / or the enteric-coated capsule shell contains at least one of gelatin, hydroxypropyl methylcellulose acetate succinate, shellac, guar gum, silk protein, povidone, polysorbate 80, and castor oil.

9. The composition according to any one of claims 1 to 8, characterized in that, It comprises the following ingredients in the indicated weight ratios: 70-90 parts turmeric extract, 40-60 parts probiotic powder, 28-32 parts L-glutamine, 7.0-8.5 parts saffron extract, 1.0-2.2 parts black pepper extract, 20-50 parts prebiotics, 4.0-80 parts diluent, 2.0-5.0 parts lubricant, and 2.0-5.0 parts flow aid; The prebiotic is selected from at least one of xylooligosaccharide, inulin, polydextrose, isomaltooligosaccharide, galactooligosaccharide, fructooligosaccharide, and resistant dextrin. The diluent is selected from at least one of maltodextrin, cyclodextrin, microcrystalline cellulose, and corn starch; The lubricant is selected from at least one of stearic acid and magnesium stearate; The flow aid is selected from at least one of silica, colloidal silica, and talc.

10. The composition of claim 9, wherein, It comprises the following raw materials in the following weight ratio: 75 parts turmeric extract, 50 parts probiotic powder, 30 parts L-glutamine, 7.0 parts saffron extract, 1.25 parts black pepper extract, 20 parts xylooligosaccharide, 4.32 parts maltodextrin, 4.24 parts stearic acid, 2.12 parts silicon dioxide; Alternatively, 75 parts turmeric extract, 50 parts probiotic powder, 30 parts L-glutamine, 8.0 parts saffron extract, 2 parts black pepper extract, 20 parts xylooligosaccharides, 80 parts microcrystalline cellulose, 3 parts stearic acid, and 3 parts colloidal silica. Alternatively, 90 parts turmeric extract, 50 parts probiotic powder, 31.98 parts L-glutamine, 8.08 parts saffron extract, 1.26 parts black pepper extract, 20 parts xylooligosaccharide, 4.32 parts maltodextrin, 4.24 parts stearic acid, and 2.12 parts silicon dioxide; Alternatively, 90 parts turmeric extract, 50 parts probiotic powder, 30 parts L-glutamine, 8 parts saffron extract, 1.25 parts black pepper extract, 20 parts xylooligosaccharide, 4.32 parts maltodextrin, 4.24 parts stearic acid, and 2.12 parts silicon dioxide.

11. Process for the preparation of a composition according to any one of claims 1-10, characterized in that: The materials are premixed and then mixed together. The mixed powder is then vacuum-pressurized under a negative pressure of 0.07~0.08Mpa. Subsequently, capsules are filled and placed at a temperature of -85℃~-45℃ and a pre-chamber drying temperature of 15℃~25℃ for 10-20 hours.

12. Use of the composition according to any one of claims 1-10 in the preparation of foods, health foods, foods for special medical purposes, dietary supplements or pharmaceuticals that regulate stress, improve mood, improve intestinal function, relieve fatigue, improve sleep, and enhance concentration and memory.

Images