Production process and application of fritillary bulb extract

Abstract

The invention discloses a production process and application of a fritillary bulb extract, and belongs to the technical field of traditional Chinese medicine extraction. The technical problem to be solved is to provide the production process of the fritillary bulb extract with higher extract yield, higher total alkaloid content and higher monomer alkaloid content. According to the technical scheme, the preparation method comprises the following steps: S1, crushing bulbus fritillariae ussuriensis until the particle size is less than 0.5 mm, adding 16-20 times by mass of water, soaking, and extracting at 62-88 DEG C for 18-50 minutes to obtain an extracting solution; s2, performing vacuum concentration on the extracting solution in the step S1 at 50-75 DEG C to obtain extract; and drying to obtain the product.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine extraction technology, and in particular to a production process and application of Fritillaria cirrhosa extract. Background Technology

[0002] For understanding the technical content of this invention: Fritillariae Ussuriensis Bulbus, the dried bulb of the lily family plant Fritillariae Ussuriensis Bulbus, is harvested in spring. The outer skin, fibrous roots, and dirt are removed, and it is then sun-dried or dried at low temperature. Fritillariae Ussuriensis is bitter, sweet, and slightly cold in nature, and enters the lung and heart meridians. It has the functions of clearing heat and moistening the lungs, resolving phlegm and relieving cough; it is used for dry cough due to lung heat, dry cough with little phlegm, yin deficiency cough, and coughing up blood. It is mainly produced in the three northeastern provinces of China, and the commercial product is mostly cultivated. The *Shennong Bencao Jing* (Shennong's Classic of Materia Medica) lists Fritillariae Ussuriensis as a medium-grade herb, stating that it is "pungent and neutral in nature, non-toxic, and treats typhoid fever, fever, urinary tract infections, hernia, sore throat, and difficulty in lactation." Traditional Chinese medicine believes that Fritillariae Ussuriensis enters the heart and lung meridians, and has the effects of clearing heat, moistening the lungs, relieving cough, resolving phlegm, and dispersing accumulations. In the Korean medical classic *Dongui Susebowon*, Fritillariae Ussuriensis is classified as a medicine for the Taiyin meridian. Modern medical research shows that Fritillaria cirrhosa mainly contains alkaloids, which have significant pharmacological effects such as antitussive, expectorant, antiasthmatic, anti-ulcer, anti-platelet aggregation, and anti-inflammatory properties.

[0003] Ancient texts describe sun-drying as the processing method for fritillaria-like medicinal materials, consistent with the current "sun-drying or low-temperature drying" method in the Chinese Pharmacopoeia. Most existing technologies for processing fritillaria materials involve "removing impurities and crushing before use." However, different particle sizes of medicinal materials result in varying degrees of dissolution of active ingredients during decoction. Crushing the materials increases the specific surface area, thus facilitating the extraction of active ingredients. The "crushing before use" method makes it difficult to control particle size; excessively coarse or fine particles are detrimental to the extraction of active ingredients and also results in low crushing efficiency. Existing technologies for extracting active ingredients from Fritillaria cirrhosa are not highly efficient. Therefore, developing an extraction process with stable yield, total alkaloid content, monomeric alkaloid content, and transfer rate is a research hotspot and direction for researchers in this field.

[0004] Relevant patent documents retrieved: The document, published in China (CN104207282A) on December 17, 2014, discloses a method for preparing an aqueous extract of Fritillaria cirrhosa. Specifically, the Fritillaria cirrhosa is washed, soaked in water for 30 hours to remove bitterness, dried, pulverized, and extracted by reflux for 1 hour with 5 times its weight of water. The extract is then passed through a 100-200 mesh sieve, centrifuged at 3500 rpm, and concentrated to 1 / 4-1 / 3 of its original volume for later use.

[0005] This document, published in China (CN104407064A) on March 11, 2015, discloses a method for the identification and content determination of Fritillaria thunbergii. It involves ethanol extraction followed by high-performance liquid chromatography (HPLC) using a neutral alumina column. Combined with the characteristic chromatograms of the medicinal material, this method can effectively identify Fritillaria thunbergii, Fritillaria cirrhosa, and Fritillaria thunbergii var. chinensis, and determine the content of fritillary acetylcholine A and B. The extraction procedure is as follows: Fritillaria thunbergii is ground into powder and placed in a flask. 50-100% ethanol is added, and extraction is carried out for 1-6 hours. The mixture is filtered, the solvent is recovered from the filtrate to obtain the residue, which is then dissolved and loaded onto a neutral alumina column for elution. The eluent is collected.

[0006] Relevant non-patent literature retrieved: The journal or book title is "Agriculture and Technology," and the article title is "Research Progress on Extraction and Purification Methods and Bioactivity of Fritillaria thunbergii Alkaloids," Volume 45, No. 06, 2025, Publication Date: January 20, 2025. This article reviews the extraction techniques, separation, purification, and bioactivity characteristics of Fritillaria thunbergii alkaloids. The alkaloid extraction methods include decoction, lipophilic organic solvent extraction, cold soaking, reflux extraction, ultrasound-assisted extraction, supercritical CO2 extraction, and enzyme-assisted extraction.

[0007] The prior art represented by the aforementioned documents has at least the following unresolved technical problems or defects: The effects of the preparation process on the total alkaloid content, yield, and monomeric alkaloid content are not considered simultaneously; generally, only the total alkaloid content or the content of a single monomeric alkaloid is recorded.

[0008] In solving the above problems or overcoming the above defects, the present invention encountered the following difficulties and obstacles: 1. When extracting Fritillaria cirrhosa using conventional extraction methods, if the herb is crushed before extraction, it will cause blockage of the extraction tank, making it difficult to separate the extract. If it is not crushed, the extraction effect is poor, with less extract and lower content. 2. Conventional water extraction of alkaloids has a very low transfer rate. Summary of the Invention

[0009] The purpose of this invention is to provide: A production process for Fritillaria cirrhosa extract and related technologies, providing a production process or combination thereof for Fritillaria cirrhosa extract with higher yield, higher total alkaloid content, and higher monomeric alkaloid content.

[0010] Terminology Explanation: Unless otherwise defined, all technical terms in this document have the same meanings as commonly understood by one of ordinary skill in the art to which the subject matter of the claims pertains. Unless otherwise stated, all patents, patent inventions, and publications cited in this document are incorporated herein by reference in their entirety. If multiple definitions exist for terms in this document, the definitions in this chapter shall prevail.

[0011] It should be understood that the above brief description and the following detailed description are exemplary and for illustrative purposes only, and do not limit the subject matter of the invention in any way. In this invention, the singular is used in conjunction with the plural unless otherwise specifically stated. It should also be noted that, unless otherwise stated, the use of “or” or “or” means “and / or”. Furthermore, the use of the term “comprising” and other forms such as “including,” “containing,” and “contains” are not limiting.

[0012] Definitions of standard chemical terms can be found in the reference "Pharmacopoeia of the People's Republic of China (2020 Edition)".

[0013] Unless otherwise stated, conventional methods within the scope of the art, such as heating, stirring, boiling, mixing, granulation, etc., shall be used.

[0014] Unless specifically defined herein, the use of all commercially available products herein employs standard techniques. For example, it may be carried out using the manufacturer's instructions for use with the kit, or in accordance with methods known in the art or the description of this invention. The techniques and methods described herein can generally be implemented according to conventional methods well known in the art, based on the descriptions in the various summary and more specific documents cited and discussed in this specification.

[0015] The term "production process" as used in this article refers to the work, methods, and techniques by which production workers use production tools and equipment to process or handle various raw materials, materials, and semi-finished products, ultimately turning them into finished products.

[0016] The term "crush" as used in this article refers to the breaking of an object into powder.

[0017] The term "immersion" as used in this article refers to the complete immersion of an object in a liquid.

[0018] The term "extraction" as used in this article refers to the process of dissolving, separating, and purifying the effective components in Chinese medicinal materials through specific methods, ultimately obtaining effective monomeric components.

[0019] The term "extract" as used in this article refers to a preparation made by extracting and concentrating the active ingredients from animal and plant raw materials through a specific process.

[0020] The term "reduced pressure concentration" as used in this article refers to the technique of reducing the pressure in a sealed container by drawing a vacuum, thereby causing the liquid to evaporate at a temperature below the boiling point of atmospheric pressure.

[0021] As used herein, the term "pharmaceutically acceptable carrier" refers to a pharmaceutically acceptable material, such as liquid or solid fillers, stabilizers, dispersants, suspending agents, diluents, excipients, thickeners, solvents, or encapsulating materials, relating to the carrying or transport of any pharmaceutical composition from one organ or part of the body to another organ or part of the body. Each carrier must be "acceptable" in the sense of compatibility with other components of the pharmaceutical composition and harmlessness to the patient.

[0022] The term "extract" as used in this article refers to volatile oils, fats, extracts, fluid extracts, dry extracts, active ingredients, and active components obtained from a single Chinese herbal medicine or a compound Chinese herbal medicine through a specific extraction method and used for pharmaceutical preparation.

[0023] In a first aspect, the present invention provides: a production process for Fritillaria cirrhosa extract, comprising the following steps: S1: Crush Fritillaria cirrhosa to a particle size <5000μm, add 16-20 times the weight of water, soak, and extract at 62-88℃ for 18-50 min to obtain the extract; S2: The extract from step S1 is concentrated under reduced pressure at 50-75℃ to obtain an extract; it is then dried to obtain the final product.

[0024] These include technical features such as particle size, water usage, soaking, extraction, vacuum concentration, extract, and drying.

[0025] In this invention, the technical effect can be achieved by any point value or any range between two points within the particle size range of <5000μm. The particle size includes, but is not limited to, 100μm, 200μm, 300μm, 340μm, 400μm, 500μm, 600μm, 700μm, 800μm, 880μm, 900μm, 1000μm, 1100μm, 1200μm, 1300μm, 1400μm, 1500μm, 1600μm, 1700μm, 1800μm, 1900μm, 2000μm, 2100μm, 2200μm, 2300μm, and 2400μm. The values ​​are within the range of m, 2500μm, 2600μm, 2700μm, 2800μm, 2900μm, 3000μm, 3100μm, 3200μm, 3300μm, 3400μm, 3500μm, 3600μm, 3700μm, 3800μm, 3900μm, 4000μm, 4100μm, 4200μm, 4300μm, 4400μm, 4500μm, 4600μm, 4700μm, 4800μm, 4900μm, or the range between any two points within the range of <5000μm, such as 100-4900μm, 340-880μm, 342-879μm, etc.

[0026] Preferably, the particle size is selected from 340-880 μm.

[0027] More preferably, the particle size is 342-879 μm.

[0028] The amount of water used in this invention can be selected from any point value or any two points within the range of 16-20 times the mass of the water to achieve the technical effect of this invention. This includes, but is not limited to, 16 times, 16.5 times, 17 times, 17.5 times, 18 times, 18.5 times, 19 times, 19.5 times, or 20 times the mass of the water.

[0029] Preferably, the amount of water used is 18-20 times its mass.

[0030] More preferably, the amount of water used is 18 or 20 times its mass.

[0031] Among them, the technical feature of soaking is selected from: soaking time of 25-35 minutes.

[0032] The technical effects of the present invention can be achieved by any point value or any range between two points within the above range. The soaking time includes, but is not limited to, 25 min, 26 min, 27 min, 28 min, 29 min, 30 min, 31 min, 32 min, 33 min, 34 min, and 35 min.

[0033] The soaking is further preferably carried out for 30 minutes.

[0034] In this invention, the technical effects of the invention can be achieved at temperatures ranging from 62 to 88°C. The extraction temperatures include, but are not limited to, 62°C, 65°C, 66°C, 67°C, 68°C, 69°C, 70°C, 71°C, 72°C, 73°C, 74°C, 75°C, 76°C, 77°C, 78°C, 79°C, 80°C, 81°C, 82°C, 83°C, 84°C, 85°C, and 88°C.

[0035] Preferably, the extraction temperature is 65-85℃.

[0036] More preferably, the extraction temperature is 65°C, 75°C, or 85°C.

[0037] In this invention, the technical effects of the invention can be achieved within a time range of 18-50 minutes for the extraction of technical features. The extraction time includes, but is not limited to, 18 min, 20 min, 21 min, 22 min, 23 min, 24 min, 25 min, 26 min, 27 min, 28 min, 29 min, 30 min, 31 min, 32 min, 33 min, 34 min, 35 min, 36 min, 37 min, 38 min, 39 min, 40 min, 41 min, 42 min, 43 min, 44 min, 45 min, 46 min, 47 min, 48 min, 49 min, and 50 min.

[0038] Preferably, the extraction time is 20-40 minutes.

[0039] More preferably, the extraction time is 20 min, 30 min, or 40 min.

[0040] In this invention, the technical effects of the invention can be achieved at a vacuum concentration temperature range of 50-75°C. The vacuum concentration temperature includes, but is not limited to, 50°C, 55°C, 60°C, 65°C, 66°C, 67°C, 68°C, 69°C, 70°C, 71°C, 72°C, 73°C, 74°C, and 75°C.

[0041] Preferably, the temperature for vacuum concentration is 65-75°C.

[0042] More preferably, the temperature for vacuum concentration is 65°C, 75°C, or 85°C.

[0043] The technical characteristic extract is selected from those with a relative density of 1.01-1.08 at 70±5℃.

[0044] Any point value or range between two points within the above range can achieve the technical effect of the present invention. For example, the relative density at 70±5℃ includes, but is not limited to, 1.01, 1.02, 1.03, 1.04, 1.05, 1.06, 1.07, and 1.08.

[0045] The technical feature drying is selected from: spray drying or vacuum belt drying.

[0046] The preferred method for drying the technical feature is spray drying.

[0047] Among them, the technical feature of spray drying is further preferably: The parameters are as follows: the inlet air temperature is selected from 160℃, 161℃, 162℃, 163℃, 164℃, 165℃, 166℃, 167℃, 168℃, 169℃, 170℃, 171℃, 172℃, 173℃, 174℃, 175℃, 176℃, 177℃, 178℃, 179℃, 180℃, 181℃, 182℃, 183℃, 184℃, 185℃, 186℃, 187℃, 188℃, 189℃, and 189℃. The outlet air temperature can be selected from 75℃, 78℃, 79℃, 80℃, 81℃, 82℃, 83℃, 84℃, 85℃, 86℃, 87℃, 88℃, 89℃, 90℃, 91℃, 92℃, 93℃, 94℃, and 95℃. The atomizer frequency can be selected from 30Hz, 31Hz, 32Hz, 33Hz, 34Hz, 35Hz, 36Hz, 37Hz, 38Hz, 39Hz, 40Hz, 41Hz, 42Hz, 43Hz, 44Hz, 45Hz, 46Hz, 47Hz, 48Hz, 49Hz, and 50Hz.

[0048] The preferred technical feature of vacuum belt drying is a temperature of 75-85℃ and a time of 4-8 hours.

[0049] The preferred technical feature of vacuum belt drying is: a temperature of 75℃, 76℃, 77℃, 78℃, 79℃, 80℃, 81℃, 82℃, 83℃, 84℃, or 85℃, and a time of 4h, 5h, 6h, 7h, or 8h.

[0050] The preferred technical feature of pressure-reducing belt drying is a temperature of 80°C and a time of 8 hours.

[0051] Secondly, the present invention provides: The application of Fritillaria cirrhosa extract prepared by the above-described production process in the preparation of Fritillaria cirrhosa preparations.

[0052] This includes technical features such as formulations.

[0053] Among them, the technical characteristics of the formulation are selected from: the dosage form is selected from solid dosage form, liquid dosage form, semi-solid dosage form or gas dosage form.

[0054] Among them, the preferred solid dosage forms are: tablets, capsules, powders, granules, and pills.

[0055] Among them, the preferred liquid formulations are emulsions, suspensions, solutions, syrups, and sols.

[0056] Among them, the preferred semi-solid preparations are ointments, suppositories, and gels.

[0057] Among them, the preferred technical feature gaseous formulations are: aerosols, sprays, and powders.

[0058] Preferably, the technically characteristic formulation further includes pharmaceutically acceptable excipients.

[0059] Among them, the pharmaceutically acceptable excipients with technical characteristics are further preferred to be: Including but not limited to excipients, buffers, emulsifiers, stabilizers, diluents, binders, preservatives, lubricants, pH adjusters, cryoprotectants, flavoring agents, fillers, and antioxidants.

[0060] The technical excipient is selected from at least one of microcrystalline cellulose, lactose, pregelatinized starch, cyclodextrin, carboxymethyl cellulose, mannitol, magnesium stearate, starch, calcium phosphate, ethyl cellulose, methyl cellulose, alginate, gelatin, gum arabic, glyceryl monostearate, sodium glycolate, guar gum, glycerol, and propylene glycol.

[0061] The technical feature buffer is selected from at least one of sodium dihydrogen phosphate, sodium bicarbonate, ammonium bicarbonate, sodium acetate, citrate, histidine, and succinate.

[0062] The emulsifier, as a technical feature, is selected from at least one of magnesium stearate, zinc stearate, calcium stearate, glyceryl stearate, sorbitan isostearate, sorbitan oleate, and polyglycerol-3 polyricinoleate.

[0063] The technical characteristic stabilizer is selected from at least one of acacia gum, agar, alginic acid, cellulose ether, and carboxymethyl chitosan.

[0064] The technical feature diluent is selected from at least one of erythritol, mannitol, sorbitol, xylitol, lactose, sucrose, corn starch, potato starch, calcium phosphate, calcium citrate, and crystalline cellulose.

[0065] The technical feature adhesive is selected from at least one of ethanol, starch paste, pregelatinized starch, dextrin, syrup, hydroxypropyl methylcellulose, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyvinyl alcohol, polyethylene glycol, sodium alginate, polyvinylpyrrolidone, gum arabic, gelatin, and alginic acid.

[0066] The preservative in the technical feature is selected from at least one of methylparaben, propylparaben, methylparaben, ethylparaben, propylparaben, chlorobutanol, thimerosal, mercuric oxycyanide, phenoxyethanol, chlorhexidine, benzoic acid, sodium benzoate, chlorocresol, benzalkonium bromide, benzalkonium chloride, and ethylparaben.

[0067] The technical feature lubricant is selected from at least one of magnesium stearate, zinc stearate, glyceryl monostearate, polyethylene glycol, stearic acid, talc, sodium chloride, sodium oleate, sodium lauryl sulfate, magnesium lauryl sulfate, sodium stearate fumarate, and poloxamer.

[0068] The technical feature of pH adjuster is selected from at least one of citric acid, fumaric acid, succinic acid, tartaric acid, malic acid, and ascorbic acid.

[0069] The flavoring agent is selected from at least one of sweet orange flavoring, vanilla flavoring, strawberry flavoring, milk flavoring, banana flavoring, and cherry flavoring.

[0070] The technical feature filler is selected from at least one of mannitol, xylitol, sorbitol, maltose, microcrystalline cellulose, glucose, lactose, sucrose, dextrin, starch, sodium alginate, and sodium bicarbonate.

[0071] The antioxidant in the technical feature can be selected from at least one of L-cysteine ​​hydrochloride, L-cysteine ​​base, 4,4-(2,3-dimethyltetramethylenediamine), extracts rich in tocopherol (natural vitamin E), α-tocopherol (synthetic vitamin E), β-tocopherol, 6-tocopherol, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate, octyl gallate, dodecyl gallate, tert-butylhydroquinone (TBHQ), fumaric acid, malic acid, ascorbic acid (vitamin C), sodium ascorbate, calcium ascorbate, potassium ascorbate, ascorbate palmitate, and ascorbate stearate.

[0072] The present invention has at least the following beneficial effects: Compared with existing technologies, this invention has better technical effects in terms of the content of Fritillaria cirrhosa, total alkaloid content and transfer rate, content and transfer rate of monomeric alkaloids (Fritillaria cirrhosa, Fritillaria A, Fritillaria B), and transfer rate of Fritillaria cirrhosa content in the production process (including extraction, concentration, extracting, and processing into medicinal slices). It provides a production process for Fritillaria cirrhosa extract with higher yield, higher total alkaloid content, and higher monomeric alkaloid content. Detailed Implementation

[0073] The following non-limiting embodiments are intended to enable those skilled in the art to gain a more comprehensive understanding of the present invention, but do not limit the invention in any way. The following content is merely an exemplary description of the scope of protection claimed by the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, and such changes should also fall within the scope of protection claimed by the present invention.

[0074] The present invention will be further described below by way of specific embodiments. Unless otherwise specified, all instruments, devices, equipment, reagents, products, etc., used in the embodiments of the present invention are obtained through conventional commercial means.

[0075] instrument: ME104 electronic balance (Mettler-Toledo); BSA125D electronic balance (Sartorius Instruments (Beijing) Co., Ltd.); DK98-Ⅱ Single-row Six-hole Water Bath (Tianjin Tester Instrument Co., Ltd.); GZX-9240MBE Electric Heating Blower Drying Oven (Shanghai Boxun Industrial Co., Ltd. Medical Equipment Factory).

[0076] Example 1 Clean and pulverize Fritillaria cirrhosa to a particle size of 342-350 μm. Place the pulverized powder in a dynamic extraction tank, add 18 times the volume of drinking water, soak for 0.5 hours, then heat to 75°C. Once the solution reaches 75°C, turn on the stirrer, start timing, and adjust the speed to 25-45 rpm. Decoct for 0.5 hours, collect the filtrate in a storage tank, and label it. Maintain the steam pressure at 0.15-0.25 MPa during heating. After boiling, maintain the steam pressure at 0.01-0.03 MPa, and keep the decoction temperature at 75°C. Concentrate under reduced pressure (75°C) to a relative density of 1.01-1.08 (70±5°C), then spray dry. Maintain the inlet air temperature at 170°C, the outlet air temperature at 85°C, and the nebulizer frequency at 40Hz to obtain the Fritillaria cirrhosa extract.

[0077] Add appropriate amounts of excipients, mix well, granulate, and make 1000g of product. Packaging specifications are 1g / bag with all-aluminum film and 5g / bag with all-aluminum film. Store in a sealed container to obtain Fritillaria cirrhosa slices.

[0078] Example 2 Clean and pulverize Fritillaria cirrhosa to a particle size of 850μm-879μm. Place the pulverized powder in a dynamic extraction tank, add 20 times the amount of drinking water, soak for 0.5 hours, then heat to 85℃. Once the solution reaches 85℃, turn on the stirrer, start timing, and adjust the speed to 25-45 rpm. Decoction for 40 minutes. Collect the filtrate in a storage tank and label it. Maintain the steam pressure at 0.15-0.25MPa during heating. After boiling, maintain the steam pressure at 0.01-0.03MPa and the decoction temperature at 85℃. Concentrate under reduced pressure (65℃) to a relative density of 1.01-1.08 (70±5℃), then spray dry. Maintain the inlet air temperature at 160℃, the outlet air temperature at 75℃, and the nebulizer frequency at 30Hz to obtain the Fritillaria cirrhosa extract.

[0079] Add appropriate amounts of excipients, mix well, granulate, and make 1000g of product. Packaging specifications are 1g / bag with all-aluminum film and 5g / bag with all-aluminum film. Store in a sealed container to obtain Fritillaria cirrhosa slices.

[0080] Example 3 Clean and pulverize Fritillaria cirrhosa to 500μm-600μm and place it in a dynamic extraction tank. Add 16 times the amount of drinking water and soak for 0.5 hours. Heat the solution until it reaches 65℃, then turn on the stirrer, start timing, and adjust the speed to 25-45 rpm. Decoction for 20 minutes. Collect the filtrate in a storage tank and label it. Control the steam pressure at 0.15-0.25MPa during heating. After the solution boils, control the steam pressure at 0.01-0.03MPa and maintain the decoction temperature at 65℃. Concentrate under reduced pressure (70℃) to a relative density of 1.01-1.08 (70±5℃), then spray dry. Control the inlet air temperature at 190℃, the outlet air temperature at 75℃, and the nebulizer frequency at 50Hz to obtain Fritillaria cirrhosa extract.

[0081] Add appropriate amounts of excipients, mix well, granulate, and make 1000g of product. Packaging specifications are 1g / bag with all-aluminum film and 5g / bag with all-aluminum film. Store in a sealed container to obtain Fritillaria cirrhosa slices.

[0082] Example 4 Clean and pulverize Fritillaria cirrhosa to a particle size of 342-350 μm. Place the pulverized powder in a dynamic extraction tank, add 18 times the volume of drinking water, soak for 0.5 hours, then heat to 75°C. Once the solution reaches 75°C, turn on the stirrer, start timing, and adjust the stirring speed to 25-45 rpm. Decoct for 0.5 hours, collect the filtrate in a storage tank, and label it. Maintain the steam pressure at 0.15-0.25 MPa during heating. After boiling, maintain the steam pressure at 0.01-0.03 MPa, and keep the decoction temperature at 75°C. Concentrate under reduced pressure (75°C) to a relative density of 1.01-1.08 (70±5°C), and then belt dry under reduced pressure at 80°C for 8 hours to obtain the Fritillaria cirrhosa extract.

[0083] Add appropriate amounts of excipients, mix well, granulate, and make 1000g of product. Packaging specifications are 1g / bag with all-aluminum film and 5g / bag with all-aluminum film. Store in a sealed container to obtain Fritillaria cirrhosa slices.

[0084] Comparative Example 1 Compared to Example 1, only the particle size was changed: The Fritillaria cirrhosa was cleaned and then directly added to the dynamic extraction tank without being crushed. The rest of the process was the same as in Example 1.

[0085] Comparative Example 2 Compared to Example 1, only the particle size was changed: The Fritillaria cirrhosa was cleaned, pulverized to 5500 μm, and then placed into a dynamic extraction tank. The rest of the process was the same as in Example 1.

[0086] Comparative Example 3 Compared to Example 1, the extraction temperature, material-to-liquid ratio, and time were changed: Clean and pulverize Fritillaria cirrhosa to a particle size of 342-350 μm. Place the pulverized powder in a dynamic extraction tank, add 22 times the volume of drinking water, soak for 1 hour, then heat to 55°C. Turn on the stirrer, start timing, and adjust the speed to 25-45 rpm. Decoction for 1 hour. Collect the filtrate in a storage tank and label it. Maintain the steam pressure at 0.15-0.25 MPa during heating. After boiling, maintain the steam pressure at 0.01-0.03 MPa and the decoction temperature at 60°C. Concentrate under reduced pressure (75°C) to a relative density of 1.01-1.08 (70±5°C), then spray dry. Maintain the inlet air temperature at 170°C, the outlet air temperature at 85°C, and the nebulizer frequency at 40Hz to obtain Fritillaria cirrhosa extract.

[0087] Add appropriate amounts of excipients, mix well, granulate, and make 1000g of product. Packaging specifications are 1g / bag with all-aluminum film and 5g / bag with all-aluminum film. Store in a sealed container to obtain Fritillaria cirrhosa slices.

[0088] Comparative Example 4 Compared to Example 1, the extraction temperature, material-to-liquid ratio, and time were changed: Clean and pulverize Fritillaria cirrhosa to a particle size of 342-350 μm. Place the pulverized powder in a dynamic extraction tank, add 15 times the volume of drinking water, soak for 15 minutes, then heat to 90°C. Turn on the stirrer, start timing, and adjust the speed to 25-45 rpm. Decoction for 1 hour. Collect the filtrate in a storage tank and label it. Maintain the steam pressure at 0.15-0.25 MPa during heating. After boiling, maintain the steam pressure at 0.01-0.03 MPa and the decoction temperature at 90°C. Concentrate under reduced pressure (75°C) to a relative density of 1.01-1.08 (70±5°C), then spray dry. Maintain the inlet air temperature at 170°C, the outlet air temperature at 85°C, and the nebulizer frequency at 40Hz to obtain Fritillaria cirrhosa extract.

[0089] Add appropriate amounts of excipients, mix well, granulate, and make 1000g of product. Packaging specifications are 1g / bag with all-aluminum film and 5g / bag with all-aluminum film. Store in a sealed container to obtain Fritillaria cirrhosa slices.

[0090] Comparative Example 5 Compared to Example 1, the temperature of vacuum concentration and the parameters of spray drying were changed: Clean and pulverize Fritillaria cirrhosa to a particle size of 342-350 μm. Place the pulverized powder in a dynamic extraction tank, add 18 times the volume of drinking water, soak for 0.5 hours, then heat to 75°C. Once the solution reaches 75°C, turn on the stirrer, start timing, and adjust the speed to 25-45 rpm. Decoct for 0.5 hours, collect the filtrate in a storage tank, and label it. Maintain the steam pressure at 0.15-0.25 MPa during heating. After boiling, maintain the steam pressure at 0.01-0.03 MPa, and keep the decoction temperature at 75°C. Concentrate under reduced pressure (80°C) to a relative density of 1.01-1.08 (70±5°C), then spray dry. Maintain the inlet air temperature at 150°C, the outlet air temperature at 100°C, and the nebulizer frequency at 60Hz to obtain the Fritillaria cirrhosa extract.

[0091] Add appropriate amounts of excipients, mix well, granulate, and make 1000g of product. Packaging specifications are 1g / bag with all-aluminum film and 5g / bag with all-aluminum film. Store in a sealed container to obtain Fritillaria cirrhosa slices.

[0092] Test Example 1 1) Determination of extract yield: Extract yield (%) = [Dry extract weight (g) × Extract volume (mL)] / [Measured extract volume (mL) × Herb weight (g)] × 100%.

[0093] Weigh the extract, shake well, and weigh out about 2g. Weigh the 2g and place it in a pre-weighed evaporating dish. Evaporate to dryness in a water bath, place in a 105℃ electric hot air drying oven, and dry for 5 hours. Remove the extract, place it in a desiccator for 0.5 hours, weigh it, and then place it in a 105℃ electric hot air drying oven for 1 hour. Remove the extract, place it in a desiccator for 0.5 hours, weigh it, and calculate the extract yield.

[0094] Concentrated extract yield (%) = [Dry extract weight (g) × Concentrated extract volume (mL)] / [Measured concentrated extract volume (mL) × Herbal weight (g)] × 100%.

[0095] Weigh the concentrate, shake well, weigh out about 2g, weigh it and place it in a pre-weighed evaporating dish, evaporate to dryness in a water bath, place it in a 105℃ electric hot air drying oven, dry for 5 hours, take it out, place it in a desiccator for 0.5 hours, weigh it, place it in a 105℃ electric hot air drying oven again, dry for 1 hour, take it out, place it in a desiccator for 0.5 hours, weigh it, and calculate the paste yield.

[0096] Extract yield (%) = [Powder weight (g)] / [Medicinal material weight (g)] × 100%; Granule yield (%) = [granule weight (g)] / [medicinal material weight (g)] × 100%.

[0097] 2) The content of active substances in the Fritillaria cirrhosa extracts prepared in the examples and comparative examples was determined by high performance liquid chromatography (General Chapter 0512 of Chinese Pharmacopoeia 2020).

[0098] Chromatographic conditions and system suitability tests were performed using an Agilent Extend C18 column (4.6 × 250 mm, 5 μm); mobile phase A was 0.01% diethylamine, mobile phase B was acetonitrile, and the flow rate was 0.4 mL / min. Gradient elution was performed according to Table 1, and detection was performed using an evaporative light scattering detector. The column temperature was 35℃. The theoretical plate number, calculated based on the fritillary peak, should be no less than 5000. The elution gradient is shown in Table 1 below. Table 1. Gradient elution table for the determination of alkaloid content in Fritillaria cirrhosa.

[0099] The detection results of Examples 1-4 and Comparative Examples 1-5 are shown in Tables 2-4 below: Table 2. Test results of the production process in Examples 1-4 and Comparative Examples 1-5

[0100] Table 3. Results of total alkaloid detection

[0101] Table 4. Results of detection of monomeric alkaloids

[0102] Test Example 2 Preparation of intermediates: Take 5000g of Fritillaria cirrhosa slices prepared in Examples 1-4 and Comparative Examples 1-5, decoct with water, filter, concentrate the filtrate into a clear extract (dry extract yield range: 11%-21%), dry to make fine powder, and obtain Fritillaria cirrhosa intermediate. Add appropriate amount of excipients, mix well, granulate to make 1000g, and obtain the finished Fritillaria cirrhosa product.

[0103] The fritillary flavonoid content of the intermediate and the fritillary bulb slices were tested separately, and the results are shown in Table 5 below.

[0104] Table 5. Fritillaria cirrhosa value transfer table

[0105] The above data shows that the specific extraction process of this invention (including extraction, concentration, extract preparation, and processed medicinal slices) exhibits better technical effects in terms of the content of Fritillaria cirrhosa, total alkaloid content and transfer rate, content and transfer rate of monomeric alkaloids (Fritillaria cirrhosa, Fritillaria A, Fritillaria B), and transfer rate of Fritillaria cirrhosa content. A production process for Fritillaria cirrhosa extract with higher yield, higher total alkaloid content, and higher monomeric alkaloid content is provided. Finally, it should be noted that the above content is only used to illustrate the technical solution of this invention and is not intended to limit the scope of protection of this invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of this invention do not depart from the essence and scope of the technical solution of this invention.

Claims

1. A production process for Fritillaria cirrhosa extract, characterized in that, Includes the following steps: S1: Crush Fritillaria cirrhosa to a particle size <5000μm, add 16-20 times the weight of water, soak, and extract at 62-88℃ for 18-50 min to obtain the extract; S2: The extract from step S1 is concentrated under reduced pressure at 50-75℃ to obtain an extract; after drying, the Fritillaria cirrhosa extract is obtained.

2. The production process according to claim 1, characterized in that, In step S1, the particle size is 340μm-880μm.

3. The production process according to claim 2, characterized in that, In step S1, the particle size is 342μm-879μm.

4. The production process according to claim 1, characterized in that, In step S1, the amount of water used is 18-20 times its mass.

5. The production process according to claim 1, characterized in that, In step S1, the soaking time is 25-35 minutes.

6. The production process according to claim 1, characterized in that, In step S1, the extraction temperature is 65-85℃ and the extraction time is 20-40 min.

7. The production process according to claim 1, characterized in that, In step S2, the temperature for vacuum concentration is 65-75°C.

8. The production process according to claim 1, characterized in that, In step S2, the drying is either spray drying or depressurized belt drying.

9. The production process according to claim 8, characterized in that, The parameters for spray drying are: inlet air temperature of 160-190℃, outlet air temperature of 75-95℃, and atomizer frequency of 30-50Hz.

10. The use of the Fritillaria cirrhosa extract prepared by the production process according to any one of claims 1-9 in the preparation of Fritillaria cirrhosa preparations.

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