Oral solid composition for post-alcohol-consumption nutritional support and preparation method thereof

Abstract

The present invention discloses an oral solid composition for post-alcohol-consumption nutritional support and a preparation method thereof, and relates to the technical field of functional foods. The oral solid composition consists, in parts by weight, of 18-22 parts of Hovenia dulcis extract, 10-14 parts of Pueraria lobata extract, 20-26 parts of embedded L-cysteine granules, 38-46 parts of curcumin-corn oligopeptide composite granules, and 4-10 parts of oral solid excipients. The embedded L-cysteine granules comprise L-cysteine hydrochloride monohydrate, β -cyclodextrin, hydroxypropyl methylcellulose, ethyl cellulose, shellac and silicon dioxide. The curcumin-corn oligopeptide composite granules comprise a curcuminoid component, corn oligopeptide, hydroxypropyl-β -cyclodextrin, hydroxypropyl methylcellulose and silicon dioxide. The composition of the present invention is a hard capsule or a coated tablet, and may be used for post-alcohol-consumption nutritional support for non-therapeutic purposes.

Description

[0001] DESCRIPTION

[0002] Oral Solid Composition for Post-Alcohol-Consumption Nutritional Support and Preparation Method Thereof

[0003] Technical Field

[0004] The present invention relates to the technical field of functional foods, and in particular to an oral solid composition for post-alcohol-consumption nutritional support and a preparation method thereof.

[0005] Background Art

[0006] After alcohol consumption, people often experience daily discomforts such as dry mouth, fatigue, stomach discomfort and a heavy-headed feeling. Existing post-alcohol-consumption support products are mostly compounded with ingredients such as Hovenia dulcis, Pueraria lobata, curcumin, corn oligopeptide, L-cysteine and B vitamins. Hovenia dulcis and Pueraria lobata are both traditional anti-alcohol ingredients and are widely used in related products; combinations of curcumin and corn oligopeptide have also been reported, for example, an existing patent discloses a protein bar for alcohol relief and liver protection containing corn oligopeptide and curcumin.

[0007] Invention patent publication No. CN101731630B discloses a health food having alcohol-relieving and liver-protecting effects, the components of which include corn oligopeptide powder, cysteine, glutathione, Hovenia dulcis extract, Pueraria lobata extract and the like. This patent directly mixes cysteine with various amino acids and plant extracts, and does not address the odor treatment of cysteine. In addition, invention patent publication No. CN106620640A discloses an alcohol-relieving and liver-protecting composition comprising corn oligopeptide powder, curcumin microcapsules, Hovenia dulcis extract, Pueraria lobata extract and the like. Although this patent adopts curcumin microcapsule embedding technology, corn oligopeptide is still directly mixed with other components in powder form.

[0008] In the above prior art, raw materials such as Hovenia dulcis, PuerariaDESCRIPTION

[0009] lobata, curcumin and corn oligopeptide are mostly used by simple mixing. L-cysteine has a certain sulfur-containing odor; when directly used in capsules or tablets, problems such as odor of the contents, sulfur odor upon bottle opening, and enhanced odor during storage are likely to occur. Curcuminoid components have poor water dispersibility and tend to exhibit uneven dispersion and fluctuations in content uniformity in ordinary blended powder; corn oligopeptide has certain hygroscopicity and, after direct mixing with plant extracts, may affect powder flowability and capsule fill-weight stability.

[0010] Summary of the Invention

[0011] The purpose of the present invention is to make up for deficiencies in the prior art and provide an oral solid composition for post-alcohol-consumption nutritional support and a preparation method thereof. By preparing L-cysteine into embedded granules and preparing curcumin and corn oligopeptide into composite granules, product odor, stability and formulation compatibility are improved without adding N-acetyl-L-cysteine, glutathione, exogenous vitamins and other ingredients.

[0012] In order to solve the above technical problems, the present invention provides the following technical solution: in one aspect, an oral solid composition for post-alcohol-consumption nutritional support, wherein the oral solid composition consists of the following components in parts by weight:

[0013] 18-22 parts of Hovenia dulcis extract;

[0014] 10-14 parts of Pueraria lobata extract;

[0015] 20-26 parts of embedded L-cysteine granules;

[0016] 38-46 parts of curcumin-corn oligopeptide composite granules;DESCRIPTION

[0017] 4-10 parts of oral solid excipients;

[0018] through the cooperation of the embedded granules and the composite granules, free sulfur-containing amino acids and directly mixed curcumin are replaced, thereby avoiding the sulfur-containing odor generated by free L-cysteine and improving the dispersion uniformity of curcuminoid components in the formulation;

[0019] wherein the oral solid composition is free of N-acetyl-L-cysteine, glutathione, prickly pear cactus, exogenously added vitamins, acetaldehyde dehydrogenase and broccoli seed water extract;

[0020] wherein the embedded L-cysteine granules comprise L-cysteine hydrochloride monohydrate, -cyclodextrin, hydroxypropyl methylcellulose, ethyl cellulose, shellac and silicon dioxide;

[0021] wherein the curcumin-corn oligopeptide composite granules comprise a curcuminoid component, corn oligopeptide, hydroxypropyl- -cyclodextrin, hydroxypropyl methylcellulose and silicon dioxide;

[0022] wherein the oral solid composition is a hard capsule or a coated tablet. Further, the Hovenia dulcis extract is a water extract of Hovenia dulcis fruit, a water extract of a Hovenia dulcis fruit peduncle, an ethanol-water extract of Hovenia dulcis fruit, an ethanol-water extract of a Hovenia dulcis fruit peduncle, a concentrated powder of Hovenia dulcis fruit, a concentrated powder of a Hovenia dulcis fruit peduncle, a spray-dried powder of Hovenia dulcis fruit or a spray-dried powder of a Hovenia dulcis fruit peduncle;

[0023] wherein the Hovenia dulcis extract has a total flavonoid content of 15-35% and a dihydromyricetin content of 2-10%.DESCRIPTION

[0024] Further, the Pueraria lobata extract is an extract of the root of Pueraria lobata, and the puerarin content in the Pueraria lobata extract is 20-60%.

[0025] Further, the embedded L-cysteine granules consist of the following components by weight percentage:

[0026] 60-72% of L-cysteine hydrochloride monohydrate;

[0027] 10-18% of 3 -cyclodextrin;

[0028] 3-8% of hydroxypropyl methylcellulose;

[0029] 2-6% of ethyl cellulose;

[0030] 2-6% of shellac;

[0031] 0.5-3% of silicon dioxide;

[0032] wherein the embedded L-cysteine granules have a particle size D50 of 150-450 p m and a moisture content of not higher than 6%;

[0033] L-cysteine hydrochloride monohydrate forms a pre-embedded matrix with 3 -cyclodextrin and hydroxypropyl methylcellulose, and then forms a double-layer physical isolation structure through fluidized-bed coating with ethyl cellulose and shellac, so as to reduce the release amount of sulfur-containing odor from the free thiol groups of L-cysteine during storage and administration.

[0034] Further, the curcumin-corn oligopeptide composite granules consist of the following components by weight percentage:

[0035] 6-15% of a curcuminoid component;

[0036] 65-82% of corn oligopeptide;

[0037] 5-15% of hydroxypropyl- 3 -cyclodextrin;DESCRIPTION

[0038] 0.5-3% of silicon dioxide;

[0039] wherein the curcumin-corn oligopeptide composite granules have a particle size D50 of 80-350 p m and a moisture content of not higher than 8%;

[0040] wherein the curcumin-corn oligopeptide composite granules are free of piperine, nano-curcumin, liposomal curcumin and phospholipid-complexed curcumin;

[0041] the curcuminoid component and the corn oligopeptide are co-granulated with hydroxypropyl- 3 -cyclodextrin and hydroxypropyl methylcellulose, so that hydrophobic curcumin is uniformly dispersed in a hydrophilic peptide matrix, thereby improving the content uniformity and flowability of curcumin in the total blended powder.

[0042] Further, the corn oligopeptide is prepared from corn protein by enzymolysis, separation, concentration and drying, and peptide segments having a molecular weight lower than 1000 Da account for not less than 70% of the corn oligopeptide;

[0043] the proportion of small-molecule peptide segments having a molecular weight lower than 1000 Da being not less than 70% is used to ensure rapid dissolution and an absorbable state of the corn oligopeptide in the gastrointestinal tract.

[0044] Further, the oral solid excipients are selected from one or more of microcrystalline cellulose, hydroxypropyl methylcellulose, croscarmellose sodium, silicon dioxide, magnesium stearate, a vegetable capsule shell, a gelatin capsule shell and a film-coating premix.DESCRIPTION

[0045] Further, the oral solid composition is a hard capsule, and the content weight of each capsule is 650-750 mg.

[0046] Further, the oral solid composition is a coated tablet, the tablet core weight is 800-900 mg, and the film-coating weight gain is 2-4%.

[0047] In another aspect, a preparation method of an oral solid composition for post-alcohol-consumption nutritional support, applicable to an oral solid composition for post-alcohol-consumption nutritional support, wherein the preparation method comprises the following steps:

[0048] 51, mixing L-cysteine hydrochloride monohydrate, -cyclodextrin, hydroxypropyl methylcellulose and silicon dioxide, adding an ethanol-water mixed solution for granulation, and drying and sizing the granules to obtain pre-embedded granules;

[0049] 52, coating the pre-embedded granules with ethyl cellulose and shellac in a fluidized bed to obtain embedded L-cysteine granules;

[0050] 53, mixing a curcuminoid component, corn oligopeptide, hydroxypropyl- -cyclodextrin, hydroxypropyl methylcellulose and silicon dioxide, adding an ethanol-water mixed solution for granulation, and drying and sizing the granules to obtain curcumin-corn oligopeptide composite granules;

[0051] 54, mixing the Hovenia dulcis extract, the Pueraria lobata extract, the embedded L-cysteine granules, the curcumin-corn oligopeptide composite granules and the oral solid excipients to obtain a total blended powder;

[0052] 55, filling the total blended powder into hard capsule shells to obtain the oral solid composition in the form of hard capsules, or compressing the total blended powder into tablet cores and performing film coating to obtain theDESCRIPTION

[0053] oral solid composition in the form of coated tablets;

[0054] a stepwise granulation process in which the embedded granules and the composite granules are respectively prepared first and then subjected to total blending is adopted, so that sulfur-containing odorous substances are embedded inside the granules, the hydrophobic curcuminoid component is dispersed in the composite-granule matrix, and a decrease in the flowability of the total blended powder caused by hygroscopicity resulting from direct contact between corn oligopeptide and plant extract powders is avoided.

[0055] Compared with the prior art, the oral solid composition for post-alcohol-consumption nutritional support and preparation method thereof have the following beneficial effects:

[0056] First, in the present invention, L-cysteine hydrochloride monohydrate, -cyclodextrin and hydroxypropyl methylcellulose are prepared into pre-embedded granules, and then fluidized-bed coating is performed with ethyl cellulose and shellac to form a double-layer physical isolation structure, so that the free thiol groups of L-cysteine are effectively shielded during storage and administration and the release of sulfur-containing odor is reduced. Meanwhile, by co-granulating the curcuminoid component with corn oligopeptide, hydroxypropyl- -cyclodextrin and hydroxypropyl methylcellulose, the hydrophobic curcuminoid component is uniformly dispersed in the hydrophilic corn oligopeptide matrix, the dispersion uniformity of curcumin in the total blended powder is improved, and the problem of reduced flowability of the total blended powder caused by hygroscopicity when corn oligopeptide directly contacts plant extract powdersDESCRIPTION

[0057] is alleviated, thereby improving formulation compatibility of the product in hard capsule filling and tablet compression production.

[0058] Second, by using two types of granule structures, namely embedded L-cysteine granules and curcumin-corn oligopeptide composite granules, in cooperation with plant extract powders, the present invention achieves overall improvements in sulfur-containing odor, content uniformity, powder flowability and storage stability without adding N-acetyl-L-cysteine, glutathione, exogenously added vitamins and other ingredients. Meanwhile, the composition can be prepared into either hard capsules or coated tablets, is suitable for different product development requirements and production conditions, and has good industrial applicability.

[0059] Other advantages, objectives and features of the present invention will be set forth to some extent in the following description and, to some extent, will be apparent to those skilled in the art based on examination of the following, or may be learned from practice of the present invention.

[0060] Brief Description of Drawings

[0061] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for describing the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are merely some embodiments of the present invention, and those of ordinary skill in the art may obtain other drawings based on these drawings without creative effort.

[0062] FIG. 1 is a process flow chart of the preparation method of the present invention;

[0063] FIG. 2 is a schematic diagram of the preparation process of theDESCRIPTION

[0064] embedded L-cysteine granules of the present invention.

[0065] Detailed Description of Embodiments

[0066] In order to further describe the technical means and effects adopted by the present invention for achieving the intended purpose of the invention, the specific embodiments, structures, features and effects according to the present invention are described in detail below with reference to the drawings and preferred embodiments.

[0067] As shown in FIG. 1, the preparation method of the oral solid composition for post-alcohol-consumption nutritional support provided by the present invention mainly comprises five steps: preparation of pre-embedded granules, preparation of embedded L-cysteine granules by fluidized-bed coating, preparation of curcumin-corn oligopeptide composite granules, total blending, and hard capsule filling or tablet compression and coating forming.

[0068] Before implementing the present invention, the respective raw materials need to be inspected and confirmed to meet the requirements:

[0069] The Hovenia dulcis extract is prepared by using dried mature fruits of Hovenia dulcis Thunb., a plant of the family Rhamnaceae, as the raw material, and by extraction with water or an ethanol-water solution, followed by concentration and drying. The extraction method may be reflux extraction, percolation extraction or dynamic extraction, the extraction solvent is water or an ethanol-water solution having an ethanol volume fraction of 30-70%, the extraction temperature is controlled at 60-80° C, the extraction time is 1-3 h, and the number of extractions is 1-3. After the extracts are combined, they are concentrated under reduced pressure to an extract having a relative density of 1.10-1.30 (measured at 60° C), and then subjected to spray drying or vacuum drying to obtain extract powder. Upon testing, the Hovenia dulcis extract used has a total flavonoid content of 15-35% and a dihydromyricetin content of 2-10%. The total flavonoid content is determined by ultravioletDESCRIPTION

[0070] spectrophotometry using rutin as a reference substance, and the dihydromyricetin content is determined by high-performance liquid chromatography.

[0071] The Pueraria lobata extract is prepared by using the dried root of Pueraria lobata, a plant of the family Fabaceae, as the raw material, followed by extraction with water or an ethanol-water solution, purification and drying. The extraction method may refer to the method for the Hovenia dulcis extract, and macroporous adsorption resin purification may be further adopted after extraction to increase the puerarin content. Upon testing, the puerarin content in the Pueraria lobata extract used is 20-60%. The puerarin content is determined by high-performance liquid chromatography under the following chromatographic conditions: Cl 8 chromatographic column (4.6 mm X 250 mm, 5 p m), methanol-water gradient elution as the mobile phase, and detection wavelength of 250 nm.

[0072] The embedded L-cysteine granules and the curcumin-corn oligopeptide composite granules are respectively prepared according to the following methods.

[0073] As shown in FIG. 2, the preparation process of the embedded L-cysteine granules is divided into two stages: pre-embedding granulation and fluidized-bed coating.

[0074] By weight percentage, the formula of the embedded L-cysteine granules is: 60-72% of L-cysteine hydrochloride monohydrate, 10-18% of 3 -cyclodextrin, 3-8% of hydroxypropyl methylcellulose, 2-6% of ethyl cellulose, 2-6% of shellac and 0.5-3% of silicon dioxide. In a specific embodiment, the respective components are weighed in the following proportions: 68 kg of L-cysteine hydrochloride monohydrate, 15 kg of 3 -cyclodextrin, 5 kg of hydroxypropyl methylcellulose, 5 kg of ethyl cellulose, 5 kg of shellac and 2 kg of silicon dioxide. The L-cysteine hydrochlorideDESCRIPTION

[0075] monohydrate is a white crystal or crystalline powder, and the content calculated on a dry basis is not less than 98.5%.

[0076] L-cysteine hydrochloride monohydrate, -cyclodextrin, hydroxypropyl methylcellulose and silicon dioxide are sequentially charged into a wet granulator. The charging order is as follows: first, the larger-amount L-cysteine hydrochloride monohydrate and -cyclodextrin are added, stirring and mixing are started for 3-5 min, hydroxypropyl methylcellulose and silicon dioxide are then added, and stirring and mixing are continued for 5-10 min until all components are uniformly distributed.

[0077] An ethanol-water mixed solution is prepared as a wetting agent. Ethanol having a volume fraction of 95% and purified water are mixed at a volume ratio of 1:1 and stirred uniformly to obtain the solution. The mixed solution is slowly added into the wet granulator with stirring, and the liquid addition amount is about 25-35% of the total dry powder mass. When the material reaches a soft-mass state in which it forms a mass when held by hand and disperses upon light pressing, liquid addition is stopped. The prepared soft mass is transferred to an oscillating granulator and granulated through an 18-mesh screen (pore size about 1.0 mm).

[0078] The wet granules are uniformly spread in a material tray of a fluidized-bed dryer, the inlet air temperature is set to 45 ° C ± 2 ° C, and the granules are dried until the moisture content is not higher than 6%. The drying time is usually 30-60 min, specifically subject to the moisture test result. The moisture content is determined at 105 ° C using a rapid moisture analyzer. The dried granules are sized through a 20-mesh screen (pore size about 0.85 mm) using a sizing machine to obtain pre-embedded granules.

[0079] The pre-embedded granules are placed in a fluidized-bed coating machine. In a bottom-spray manner, ethyl cellulose and shellac are dissolved in ethanol having a volume fraction of 95% to prepare a coating liquid, inDESCRIPTION

[0080] which the solid content of ethyl cellulose and shellac is 8-12%. The process parameters of the fluidized bed are set as follows: inlet air temperature of 40-50° C, material temperature controlled at 35-45° C, atomization pressure of 0.15 MPa-0.25 MPa, and spray rate of 5-10 mL / min. During coating, the material temperature is continuously monitored to avoid degradation of L-cysteine hydrochloride monohydrate caused by an excessively high temperature. The coating weight gain is controlled at 8-15% of the mass of the pre-embedded granules. After coating is completed, hot air at 40 C is continuously introduced into the fluidized bed for drying for 15-30 min to remove residual ethanol. The coated granules are sized through a 30-mesh screen (pore size about 0.6 mm) and a 100-mesh screen (pore size about 0.15 mm) using a sizing machine, and the intermediate fraction is collected to obtain embedded L-cysteine granules.

[0081] Upon testing, the obtained embedded L-cysteine granules have a particle size D50 of 150-450 p m and a moisture content of not higher than 6%. D50 is determined by a laser particle size analyzer using a dry method.

[0082] By weight percentage, the formula of the curcumin-corn oligopeptide composite granules is: 6-15% of a curcuminoid component, 65-82% of corn oligopeptide, 5-15% of hydroxypropyl- 3 -cyclodextrin, 2-8% of hydroxypropyl methylcellulose and 0.5-3% of silicon dioxide. In a specific embodiment, the respective components are weighed in the following proportions: 10 kg of the curcuminoid component, 75 kg of corn oligopeptide, 8 kg of hydroxypropyl- 3 -cyclodextrin, 5 kg of hydroxypropyl methylcellulose and 2 kg of silicon dioxide.

[0083] The curcuminoid component is an extract of the rhizome of Curcuma longa L., a plant of the family Zingiberaceae, and mainly contains a mixture of curcumin, demethoxycurcumin and bisdemethoxycurcumin, with a total curcuminoid content of not less than 90%. The corn oligopeptide is preparedDESCRIPTION

[0084] from corn protein by enzymolysis, separation, concentration and drying, wherein peptide segments having a molecular weight lower than 1000 Da account for not less than 70%. The molecular weight distribution is determined by high-performance gel filtration chromatography. Hydroxypropyl- 3 -cyclodextrin with a degree of substitution of about 4-6 is selected, and this excipient has good water solubility and inclusion ability.

[0085] The curcuminoid component, corn oligopeptide, hydroxypropyl- 3 -cyclodextrin, hydroxypropyl methylcellulose and silicon dioxide are sequentially charged into a wet granulator. Since the powder characteristics of the curcuminoid component and corn oligopeptide differ greatly (the curcuminoid component has strong hydrophobicity, and corn oligopeptide has certain hygroscopicity), sufficient mixing is required after charging. Low-speed stirring and mixing are first performed for 5 min, and then medium-speed stirring and mixing are performed for 10 min to ensure uniform distribution of all components.

[0086] An ethanol-water mixed solution is prepared as a wetting agent, wherein ethanol having a volume fraction of 95% and purified water are mixed at a volume ratio of 1:1.5. The mixed solution is slowly added into the wet granulator, and the liquid addition amount is about 30-40% of the total dry powder mass. Since corn oligopeptide has relatively strong hygroscopicity, the material state needs to be observed during liquid addition to avoid excessive liquid addition causing the soft mass to become overly sticky. When the material reaches a soft-mass state in which it forms a mass when held by hand and disperses upon light pressing, liquid addition is stopped. The soft mass is transferred to an oscillating granulator and granulated through a 20-mesh screen (pore size about 0.85 mm).

[0087] The wet granules are uniformly spread in a material tray of a fluidized-bed dryer, the inlet air temperature is set to 50 ° C ± 2 ° C, andDESCRIPTION

[0088] the granules are dried until the moisture content is not higher than 8%. The drying time is usually 40-70 min. The dried granules are sized through a 40-mesh screen (pore size about 0.45 mm) and a 120-mesh screen (pore size about 0.125 mm) using a sizing machine, and the intermediate fraction is collected to obtain curcumin-corn oligopeptide composite granules.

[0089] Upon testing, the obtained curcumin-corn oligopeptide composite granules have a particle size D50 of 80-350 p m and a moisture content of not higher than 8%. The composite granules are free of piperine, nano-curcumin, liposomal curcumin and phospholipid-complexed curcumin.

[0090] Based on 700 mg of contents per capsule, the following components are weighed:

[0091] 140 g of Hovenia dulcis extract, 84 g of Pueraria lobata extract, 168 g of embedded L-cysteine granules, 280 g of curcumin-corn oligopeptide composite granules, 18 g of microcrystalline cellulose, 5 g of silicon dioxide and 5 g of magnesium stearate. The above amounts are the charging amounts for preparing 1000 hard capsules.

[0092] The Hovenia dulcis extract, Pueraria lobata extract and microcrystalline cellulose are respectively passed through an 80-mesh screen (pore size about 0.18 mm). The three screened materials are charged into a three-dimensional motion mixer and mixed for 15 min. Then, the embedded L-cysteine granules and the curcumin-corn oligopeptide composite granules are added, the mixer rotation speed is set to 8-12 r / min, and mixing is performed for 10 min. Finally, silicon dioxide and magnesium stearate are added, and mixing is continued for 5 min to obtain a total blended powder.

[0093] The total blended powder is taken, and powder properties such as angle of repose and bulk density are tested. The angle of repose is measured by a fixed funnel method, and bulk density and tapped density are measured by a measuring cylinder method.DESCRIPTION

[0094] The total blended powder is filled into gelatin hollow hard capsule shells or hydroxypropyl methylcellulose hollow hard capsule shells. During filling, samples are taken every 15 min to test the fill weight once, so as to ensure that the fill-weight variation is controlled within ± 7.5%. The content weight of each capsule is 650-750 mg, preferably 700 mg. After filling, polishing and sorting are performed to obtain the oral solid composition in the form of hard capsules.

[0095] Based on 850 mg per tablet, the following components are weighed:

[0096] 170 g of Hovenia dulcis extract, 102 g of Pueraria lobata extract, 204 g of embedded L-cysteine granules, 340 g of curcumin-corn oligopeptide composite granules, 18 g of croscarmellose sodium, 6 g of silicon dioxide and 10 g of magnesium stearate. The above amounts are the charging amounts for preparing 1000 coated tablets.

[0097] The Hovenia dulcis extract, Pueraria lobata extract and croscarmellose sodium are respectively passed through an 80-mesh screen. The three screened materials are charged into a three-dimensional motion mixer and mixed for 15 min. Then, the embedded L-cysteine granules and the curcumin-corn oligopeptide composite granules are added, the mixer rotation speed is set to 8-12 r / min, and mixing is performed for 10 min. Finally, silicon dioxide and magnesium stearate are added, and mixing is continued for 5 min to obtain a total blended powder.

[0098] The total blended powder is compressed into tablet cores using a rotary tablet press. The tablet compression parameters are set as follows: main pressure of 15-25 kN, pre-pressure of 5-10 kN, and compression speed of 30-40 r / min. The tablet core hardness is controlled at 80-120 N, and friability does not exceed 1%. The tablet core weight is 800-900 mg, preferably 850 mg.

[0099] A film-coating liquid is prepared. A hydroxypropyl methylcelluloseDESCRIPTION

[0100] film-coating premix (containing hydroxypropyl methylcellulose, polyethylene glycol, titanium dioxide, talc and the like) is taken and prepared with purified water into a coating suspension having a solid content of 12-16%. The suspension is stirred uniformly and then passed through a 100-mesh screen for later use.

[0101] The tablet cores are placed in a high-efficiency coating machine, with the inlet air temperature set to 55-65 ° C, the tablet bed temperature set to 40-45 ° C, the atomization pressure set to 0.2-0.3 MPa, and the spray rate set to 2-4 mL / min. During coating, the coating liquid is continuously stirred to prevent sedimentation. The coating weight gain is controlled at 2-4% of the tablet core mass. After coating is completed, hot air at 40-45 ° C is continuously blown in the coating machine for drying for 10-15 min to obtain the oral solid composition in the form of coated tablets.

[0102] In order to verify the effect of the composition of the present invention in actual application scenarios, the following three groups of application verification tests were respectively carried out.

[0103] Verification of recovery support after social drinking: Thirty healthy adult volunteers aged 25-45 years were selected; all had a history of alcohol consumption and commonly experienced discomfort symptoms of different degrees after drinking. The volunteers were randomly divided into two groups, with 15 persons in each group. The experimental group took the prepared hard capsules within 30 min after drinking, 2 capsules each time (total content amount of 1400 mg). The control group took an equivalent amount of placebo capsules (containing only microcrystalline cellulose) at the same time. On the next morning (about 10-12 h after drinking), all volunteers were surveyed by questionnaire to evaluate the severity of four symptoms: dry mouth, fatigue, heavy-headed feeling and stomach discomfort. The scoring standard was 0-4 points (0 points representing no symptom and 4 points representing severeDESCRIPTION

[0104] symptoms). The results showed that the average scores of the four symptoms in the experimental group were respectively 1.2 points for dry mouth, 1.5 points for fatigue, 1.1 points for heavy-headed feeling and 0.9 points for stomach discomfort; the average scores of the four symptoms in the control group were respectively 2.8 points for dry mouth, 3.1 points for fatigue, 2.6 points for heavy-headed feeling and 2.3 points for stomach discomfort. The symptom scores of the experimental group were lower than those of the control group for all items, indicating that the composition of the present invention has an improvement effect on common discomfort after alcohol consumption.

[0105] Verification of plant antioxidant nutritional support: The contents of the prepared hard capsules were taken and evaluated using an in vitro antioxidant model. Using the DPPH free-radical scavenging rate as the index, a sample solution having a mass concentration of 2 mg / mL was prepared; 0.1 mL of the sample solution was mixed with 3.9 mL of DPPH solution (0.1 mmol / L), reacted at room temperature in the dark for 30 min, and then the absorbance was measured at a wavelength of 517 nm to calculate the free-radical scavenging rate. At the same time, separate solutions of Hovenia dulcis extract, Pueraria lobata extract, embedded L-cysteine granules and curcumin-corn oligopeptide composite granules at the same concentration were used as controls. The results showed that the DPPH free-radical scavenging rate of the composition of the present invention (total blended powder) was 72.6%, significantly higher than the scavenging rates of the respective single components (32.4% for Hovenia dulcis extract, 28.7% for Pueraria lobata extract, 18.3% for embedded L-cysteine granules and 45.2% for curcumin-corn oligopeptide composite granules). The scavenging rate of the composition was higher than the sum of the scavenging rates of the respective single components (124.6%), indicating that a synergistic antioxidant effect exists among the components, rather than a simpleDESCRIPTION

[0106] superposition of effects.

[0107] Verification of formulation stability and administration compliance: The prepared hard capsules and prepared coated tablets were respectively placed under normal-temperature conditions (25 C ± 2 ° C, relative humidity 60% ± 5%) for 6 months, and samples were taken once every month for testing. At the same time, 50 consumers with drinking habits were randomly selected to conduct a trial-use experience survey, comparing the bottle-opening odor and administration experience of the hard capsules of the present invention with a commercially available similar product containing unembedded L-cysteine. Bottle-opening odor was scored on a 10-point scale (0 points representing no odor and 10 points representing an extremely strong odor). The results showed that the bottle-opening odor score of the hard capsules of the present invention was maintained between 4.5 and 5.2 points throughout the 6-month storage period, whereas the initial score of the commercially available control product was 7.8 points and increased to 8.3 points after storage for 3 months. In terms of administration experience, 92% of the trial users considered that the hard capsules of the present invention had no obvious sulfur odor or discomfort, whereas only 28% of the trial users were satisfied with the commercially available control product. In terms of stability, after 6 months of storage at normal temperature, the L-cysteine retention rates of the hard capsules and coated tablets of the present invention were 93.6% and 94.2%, respectively, and the curcumin retention rates were 94.1% and 94.8%, respectively, all remaining above 90%.

[0108] In order to better illustrate the advantages of the technical solution of the present invention, the following comparative embodiments were set up.

[0109] Comparative Embodiment 1: Unembedded L-cysteine hydrochloride monohydrate was used to directly replace the embedded L-cysteine granules, while the remaining components and proportions were unchanged, and hardDESCRIPTION

[0110] capsules were prepared according to the same method. It was found that this comparative sample emitted an obvious pungent sulfur-containing odor during the preparation process, and the operators needed to wear protective masks. After the finished product was opened, the sulfur odor was obvious, and the sensory-evaluation score for bottle-opening sulfur odor was 7.6 points, much higher than the 4.8 points of the hard capsules of the present invention.

[0111] Comparative Embodiment 2: The curcuminoid component and corn oligopeptide were directly mixed in powder form (without being prepared into composite granules), while the remaining components and proportions were unchanged, and hard capsules were prepared according to the same method. It was found that this comparative sample had poor curcumin content uniformity, and the relative standard deviation of 10 parallel samples was 9.2%, higher than the 4.1% of the hard capsules of the present invention. Meanwhile, the angle of repose of the total blended powder was 42.8 ° , indicating poor flowability, and the relative standard deviation of capsule fill weight during capsule filling was 4.8%, higher than the 2.1% of the hard capsules of the present invention.

[0112] Comparative Embodiment 3: Both the embedded L-cysteine granules and the curcumin-corn oligopeptide composite granules were replaced with the corresponding untreated raw material powders, that is, all components were directly mixed and then filled into hard capsules. It was found that, in an accelerated test (40° C, 75% relative humidity, 90 d), the L-cysteine retention rate of this comparative sample was only 68.7%, and the curcumin retention rate was only 80.8%, both significantly lower than the corresponding values of the hard capsules of the present invention (87.4% for L-cysteine and 90.7% for curcumin).

[0113] The results of the above comparative embodiments show that the technical solution using embedded granules and composite granules accordingDESCRIPTION

[0114] to the present invention has obvious advantages in odor control, content uniformity, flowability, storage stability and fill-weight variation.DESCRIPTION

[0115] For intuitive comparison, the key indicators of the above embodiments and comparative embodiments are summarized in Table 1.

[0116] Table 1. Comparison of key indicators of the embodiments:

[0117] Bottle-opening

[0118] sulfur odor score

[0119] Embodiment L-cysteine 90 d Curcumin Angle of Fill-weight (10-point scale) retention rate content RSD repose RSD

[0120] Hard capsule 4.8 87.4% 4.1% 36.5° 2.1% Coated tablet 4.6 88.2% 3.8% — — Comparative 7.6

[0121] Embodiment 1 — — — — Comparative

[0122] Embodiment 2 — — 9.2% 42.8° 4.8% Comparative — 68.7% 80.8%

[0123] Embodiment 3 — —

[0124]

[0125] As can be seen from the data in Table 1, the hard capsules and coated tablets of the embodiments of the present invention are superior to the corresponding comparative embodiments in all evaluation indicators. The bottle-opening sulfur odor score is reduced by about 36-41%, the 90 d retention rate of L-cysteine under accelerated conditions is increased by about 18 percentage points, curcumin content uniformity is improved by about 5 percentage points, the powder angle of repose is reduced by about 6 ° , and the capsule fill-weight RSD is reduced by about 2.7 percentage points.

[0126] Based on the verification results of the above embodiments and comparative embodiments, the oral solid composition for post-alcohol-consumption nutritional support provided by the present invention effectively solves formulation problems such as obvious sulfur-containing odor, uneven curcumin dispersion and reduced flowability caused by hygroscopicity of corn oligopeptide by preparing L-cysteine as embedded granules and preparing the curcuminoid component and corn oligopeptide as composite granules, without adding N-acetyl-L-cysteine, glutathione, exogenously added vitamins and other ingredients. The composition can be prepared into either hard capsules or coated tablets, has good industrial applicability and product stability, and is suitable for dailyDESCRIPTION

[0127] nutritional support scenarios after alcohol consumption.

[0128] The above description is merely preferred embodiments of the present invention and does not limit the present invention in any form. Although the present invention has been disclosed above by way of preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art may, without departing from the scope of the technical solution of the present invention, make slight changes or modifications to the technical contents disclosed above as equivalent embodiments with equivalent changes. Any simple modifications, equivalent changes and modifications made to the above embodiments according to the technical essence of the present invention, without departing from the contents of the technical solution of the present invention, shall still fall within the scope of the technical solution of the present invention.

Claims

CLAIMS1. An oral solid composition for post-alcohol-consumption nutritional support, characterized in that the oral solid composition consists of the following components in parts by weight:18-22 parts of Hovenia dulcis extract;10-14 parts of Pueraria lobata extract;20-26 parts of embedded L-cysteine granules;38-46 parts of curcumin-corn oligopeptide composite granules;4-10 parts of oral solid excipients;wherein the oral solid composition is free of N-acetyl-L-cysteine, glutathione, prickly pear cactus, exogenously added vitamins, acetaldehyde dehydrogenase and broccoli seed water extract;wherein the embedded L-cysteine granules comprise L-cysteine hydrochloride monohydrate, 3 -cyclodextrin, hydroxypropyl methylcellulose, ethyl cellulose, shellac and silicon dioxide;wherein the curcumin-corn oligopeptide composite granules comprise a curcuminoid component, corn oligopeptide, hydroxypropyl- -cyclodextrin, hydroxypropyl methylcellulose and silicon dioxide;wherein the oral solid composition is a hard capsule or a coated tablet.

2. The oral solid composition for post-alcohol-consumption nutritional support according to claim 1, characterized in that the Hovenia dulcis extract is a water extract of Hovenia dulcis fruit, a water extract of a Hovenia dulcis fruit peduncle, an ethanol-water extract of Hovenia dulcis fruit, an ethanol-water extract of a Hovenia dulcis fruit peduncle, a concentrated powder of Hovenia dulcis fruit, a concentrated powder of a Hovenia dulcis fruit peduncle, a spray-dried powder of Hovenia dulcis fruit or a spray-dried powder of a Hovenia dulcis fruit peduncle;wherein the Hovenia dulcis extract has a total flavonoid content of 15-35% and a dihydromyricetin content of 2-10%.CLAIMS3. The oral solid composition for post-alcohol-consumption nutritional support according to claim 1, characterized in that the Pueraria lobata extract is an extract of the root of Pueraria lobata, and the puerarin content in the Pueraria lobata extract is 20-60%.

4. The oral solid composition for post-alcohol-consumption nutritional support according to claim 1, characterized in that the embedded L-cysteine granules consist of the following components by weight percentage:60-72% of L-cysteine hydrochloride monohydrate;10-18% of 3 -cyclodextrin;3-8% of hydroxypropyl methylcellulose;2-6% of ethyl cellulose;2-6% of shellac;0.5-3% of silicon dioxide;wherein the embedded L-cysteine granules have a particle size D50 of 150-450 p m and a moisture content of not higher than 6%.

5. The oral solid composition for post-alcohol-consumption nutritional support according to claim 1, characterized in that the curcumin-corn oligopeptide composite granules consist of the following components by weight percentage:6-15% of a curcuminoid component;65-82% of corn oligopeptide;5-15% of hydroxypropyl- -cyclodextrin;2-8% of hydroxypropyl methylcellulose;0.5-3% of silicon dioxide;wherein the curcumin-corn oligopeptide composite granules have a particle size D50 of 80-350 p m and a moisture content of not higher than 8%;wherein the curcumin-corn oligopeptide composite granules are free of piperine, nano-curcumin, liposomal curcumin and phospholipid-complexedCLAIMScurcumin.

6. The oral solid composition for post-alcohol-consumption nutritional support according to claim 1, characterized in that the corn oligopeptide is prepared from corn protein by enzymolysis, separation, concentration and drying, and peptide segments having a molecular weight lower than 1000 Da account for not less than 70% of the corn oligopeptide.

7. The oral solid composition for post-alcohol-consumption nutritional support according to claim 1, characterized in that the oral solid excipients are selected from one or more of microcrystalline cellulose, hydroxypropyl methylcellulose, croscarmellose sodium, silicon dioxide, magnesium stearate, a vegetable capsule shell, a gelatin capsule shell and a film-coating premix.

8. The oral solid composition for post-alcohol-consumption nutritional support according to claim 1, characterized in that the oral solid composition is a hard capsule, and the content weight of each capsule is 650-750 mg.

9. The oral solid composition for post-alcohol-consumption nutritional support and preparation method thereof according to claim 1, characterized in that the oral solid composition is a coated tablet, the tablet core weight is 800-900 mg, and the film-coating weight gain is 2-4%.

10. A preparation method of an oral solid composition for post-alcohol-consumption nutritional support, applicable to the oral solid composition for post-alcohol-consumption nutritional support according to any one of claims 1-9, characterized in that the preparation method comprises the following steps:51, mixing L-cysteine hydrochloride monohydrate, -cyclodextrin, hydroxypropyl methylcellulose and silicon dioxide, adding an ethanol-water mixed solution for granulation, and drying and sizing the granules to obtain pre-embedded granules;52, coating the pre-embedded granules with ethyl cellulose and shellac in a fluidized bed to obtain embedded L-cysteine granules;CLAIMS53, mixing a curcuminoid component, corn oligopeptide, hydroxypropyl- -cyclodextrin, hydroxypropyl methylcellulose and silicon dioxide, adding an ethanol-water mixed solution for granulation, and drying and sizing the granules to obtain curcumin-corn oligopeptide composite granules;54, mixing the Hovenia dulcis extract, the Pueraria lobata extract, the embedded L-cysteine granules, the curcumin-corn oligopeptide composite granules and the oral solid excipients to obtain a total blended powder;55, filling the total blended powder into hard capsule shells to obtain the oral solid composition in the form of hard capsules, or compressing the total blended powder into tablet cores and performing film coating to obtain the oral solid composition in the form of coated tablets.

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