A method for preparing a chitosan-sodium alginate complex containing plant extracts

Abstract

The present invention discloses a method for preparing a chitosan-sodium alginate complex containing plant extracts. The present invention uses glacial acetic acid, chitosan and sodium alginate as raw materials to encapsulate a water-in-oil-in-water emulsion containing a datura flower extract, an iris fringe extract and a spiny jujube seed extract, and respectively embeds flavonoids, saponins and alkaloid compounds as active ingredients in the datura flower extract, the iris fringe extract and the spiny jujube seed extract.

Description

Technical Field

[0001] The present disclosure relates to the technical field of drug preparation, and in particular to a method for preparing a chitosan-sodium alginate complex containing a plant extract. Background Art

[0002] Fritillaria truncatum Fritillaria snowflakes Re-gel or Fritillaria cirrhosa Fritillaria pallidiflora The dried bulb of Schrenk is one of the medicinal Fritillaria. It is mainly distributed in the Yili River Basin of Xinjiang Uygur Autonomous Region. It has the functions of clearing heat and moistening the lungs, resolving phlegm and relieving cough, and dispersing nodules. It is used for cough with phlegm and heat, sputum with blood, and scrofula, sores, and swelling. The chemical components of Ilex Fritillaria are isosteroidal alkaloids, saponins, and flavonoids. Ilex Fritillaria has high yield, strong disease resistance, and low price of medicinal materials. In particular, its physiological activities such as expectoration and antitussive are slightly stronger than those of Fritillaria cirrhosa. It has attracted much attention in recent years.

[0003] Ziziphus jujuba Ziziphus jujuba Mill. var. spinosa The dried mature seeds of (Bunge)Hu exH. F. Chou have the effects of nourishing the heart and liver, calming the mind and tranquilizing the nerves, astringing sweat, and promoting the production of body fluids. They are used to treat symptoms such as insomnia, palpitations and dreams, excessive sweating due to physical weakness, and thirst due to loss of body fluids. Modern research shows that the seeds of the Chinese date contain a variety of substances such as fatty oils, saponins, flavonoids, and alkaloids.

[0004] Datura Metal thickness L. is a plant of the genus Datura in the Solanaceae family. The 2020 edition of the Chinese Pharmacopoeia records that its medicinal part is the flower, which has the effects of relieving asthma and cough, analgesia, antispasmodic, and anesthetic. The main chemical components of Datura are withanolides, flavonoids, and alkaloids, which have a wide range of biological activities such as anti-inflammatory, anti-itching, and cell protection, especially in the clinical treatment of psoriasis. However, in recent years, through the study of the chemical composition of Datura leaves, it was found that Datura leaves also contain flavonoids and alkaloids with multiple biological activities such as anti-inflammatory, antibacterial, antioxidant, and immunosuppressive. The effective active ingredients of Fritillaria cirrhosa, Semen Ziziphi Spinosae and Flos Daturae all include flavonoids, saponins and alkaloids. Among them, most alkaloids and flavonoids have poor water solubility, but glycosylated flavonoids and some alkaloids are easily soluble in water, and saponins generally have good water solubility. In addition, alkaloids are easily oxidized. Therefore, there is an urgent need for a pharmaceutical composition that can effectively encapsulate flavonoids, saponins and alkaloids in plant extracts such as Fritillaria cirrhosa, so as to facilitate preservation and absorption by the human body. Summary of the invention

[0005] The present disclosure provides a method for preparing a chitosan-sodium alginate complex containing a plant extract to solve the deficiencies in the related art.

[0006] According to a first aspect of an embodiment of the present disclosure, there is provided a method for preparing a chitosan-sodium alginate complex containing a plant extract, comprising:

[0007] Step 1-a: Add glacial acetic acid, chitosan and sodium alginate to water at 75°C-85°C, and stir for 1-3 hours to obtain the product of step 1-a;

[0008] Step 2-a: lower the temperature to 55°C-65°C, add citric acid dropwise to the product of step 1-a under stirring, keep the temperature unchanged, and continue stirring for 1-3 hours to obtain the product of step 2-a;

[0009] Step 3-a: lower the temperature to 40°C-50°C, add the first plant extract, keep the temperature unchanged, and continue stirring for 1-3 hours to obtain the product of step 3-a;

[0010] Step 4-a: lowering the temperature to room temperature, adding the second plant extract and the cross-linking agent, maintaining the temperature unchanged, and continuing stirring for 0.5-1.5 hours to obtain the product of step 4-a;

[0011] Step 5-a: subjecting the product of step 4-a to freeze-thaw treatment to obtain the product of step 5-a;

[0012] Step 6-a: freeze-dry the product of step 5-a, and then grind and sieve it to obtain the chitosan-sodium alginate complex containing the plant extract.

[0013] In one aspect of the disclosed embodiments, in step 1-a, the mass ratio of acetic acid, chitosan and sodium alginate is (0.03-0.08):(1-3):(0.5-1). Preferably, in step 1-a, the mass ratio of acetic acid, chitosan and sodium alginate is (0.04-0.06):(1.8-2.2):(0.6-0.8).

[0014] In one aspect of the embodiments of the present disclosure, specifically, in step 1-a, the mass ratio of glacial acetic acid, chitosan and sodium alginate is selected from 0.05:2:0.75.

[0015] In one aspect of the disclosed embodiments, in step 2-a, the mass of the citric acid added is 0.8%-1.5% of the mass of the chitosan added in step 1-a. Preferably, in step 2-a, the mass of the citric acid added is 1.0%-1.4% of the mass of the chitosan added in step 1-a.

[0016] In one aspect of the embodiments of the present disclosure, specifically, in step 2-a, the mass of the added citric acid is 1.2% of the mass of the chitosan added in step 1-a.

[0017] In one aspect of the embodiments of the present disclosure, in step 3-a, the first plant extract is a water-in-oil-in-water emulsion containing a datura flower extract. In one aspect of the embodiments of the present disclosure, in step 3-a, the mass of the first plant extract added is 15%-150% of the mass of the chitosan added in step 1-a; but not limited thereto.

[0018] In one aspect of the embodiments of the present disclosure, in step 3-a, a third plant extract is further added, and the third plant extract is a water-in-oil-in-water type emulsion containing a Ziziphus jujuba seed extract. In one aspect of the embodiments of the present disclosure, in step 3-a, the mass of the third plant extract added is 10%-120% of the mass of the chitosan added in step 1-a; but it is not limited thereto.

[0019] In one aspect of the embodiments of the present disclosure, in step 4-a, the second plant extract is a water-in-oil-in-water emulsion containing an extract of Ilex iberis. In one aspect of the embodiments of the present disclosure, in step 4-a, the mass of the second plant extract added is 10%-120% of the mass of the chitosan added in step 1-a; but not limited thereto.

[0020] In one aspect of the disclosed embodiments, in step 4-a, the cross-linking agent is selected from MgCl2, CaCl2 or glutaraldehyde. In one aspect of the disclosed embodiments, in step 4-a, the mass of the added cross-linking agent is 0.3%-0.8% of the mass of the chitosan added in step 1-a. Specifically, the mass of the added cross-linking agent is 0.5% of the mass of the chitosan added in step 1-a.

[0021] In one aspect of the embodiments of the present disclosure, preferably, in step 4-a, the cross-linking agent is selected from glutaraldehyde.

[0022] In one aspect of the embodiments of the present disclosure, in step 5-a, the freeze-thaw treatment includes: freezing at -80°C to -60°C for 3-6 hours, and then thawing at 4°C-10°C; repeating the above process 2-5 times to obtain the product of step 5-a.

[0023] In one aspect of the embodiments of the present disclosure, specifically, in step 5-a, the freeze-thaw treatment includes: freezing at -75°C for 4 hours, and then thawing at 5°C; repeating the above process 3 times to obtain the product of step 5-a.

[0024] In one aspect of the embodiments of the present disclosure, the process of crushing and screening includes: crushing with a crusher and then passing through a 20-50 mesh sieve.

[0025] In one aspect of the disclosed embodiments, the first plant extract comprises a datura flower extract; the first plant extract is obtained by following steps 1-b1 to 3-b1:

[0026] Step 1-b1: preparing an extract of datura flower extract;

[0027] Step 2-b1: mixing the extract of the datura flower extract with the first oil phase to prepare the water-in-oil emulsion of step 2-b1;

[0028] Step 3-b1: adding the water-in-oil type emulsion of step 2-b1 to the first aqueous phase to prepare a first water-in-oil-in-water type plant extract emulsion.

[0029] In one aspect of the embodiments of the present disclosure, the volume ratio of the extract of the datura truncatula extract to the first oil phase is selected from (0.1-0.3):1, but is not limited thereto.

[0030] In one aspect of the embodiments of the present disclosure, the extract of the datura flower extract and the first oil phase are stirred at a rate of 800-1500 rpm to form a water-in-oil emulsion of step 2-b1.

[0031] In one aspect of the embodiments of the present disclosure, the water-in-oil type emulsion of step 2-b1 and the first aqueous phase are stirred at a rate of 1800-2200 rpm to form a water-in-oil-in-water type first plant extract emulsion.

[0032] In one aspect of the embodiments of the present disclosure, the first oil phase comprises phospholipids, neutral lipids, a first stabilizer and vegetable oil; wherein the first stabilizer is selected from sucrose polyesters or sucrose fatty acid esters.

[0033] In one aspect of the disclosed embodiments, in the first oil phase, the mass percentage of vegetable oil is 35%-60%, the mass percentage of phospholipids is 25%-45%, the mass percentage of neutral lipids is 10%-20%, and the mass percentage of the first stabilizer is 2%-7%.

[0034] In one aspect of the embodiments of the present disclosure, in the present disclosure, the vegetable oil used is sweet almond oil or soybean oil, but is not limited thereto.

[0035] In one aspect of the embodiments of the present disclosure, the first aqueous phase comprises a first osmotic pressure regulator and water; wherein the osmotic pressure regulator is selected from arginine, glycine, lysine, sorbitol or mannitol.

[0036] In one aspect of the embodiments of the present disclosure, in the first aqueous phase, the mass percentage of the first osmotic pressure regulator is 1%-5%, but is not limited thereto.

[0037] In one aspect of the presently disclosed embodiments, the phospholipid is selected from soybean lecithin, hydrogenated soybean lecithin, cephalin, dimyristoylphosphatidylcholine, dimyristoylphosphatidylglycerol, dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylglycerol, dipalmitoylphosphatidylglycerol, dioleoylphosphatidylglycerol, distearoylphosphatidylcholine or distearoylphosphatidylglycerol.

[0038] In one aspect of the disclosed embodiments, the neutral lipid is selected from triglycerides or diglycerides.

[0039] In one aspect of the embodiments of the present disclosure, the extract of the datura flower extract is obtained by following steps 1-b2 to 3-b2:

[0040] Step 1-b2: Weigh the dried Datura leaves, extract with 5-8 times the mass of 60% ethanol at 75°C-85°C for 1.5-2.5h, reflux extraction 3-5 times, combine the ethanol solutions and filter; obtain the filter residue and the total ethanol extract of step 1-b2;

[0041] Step 2-b2: reflux the filter residue with 5-8 times the mass of water at 75°C-85°C for 1.5-2.5h, reflux extraction 3-5 times to obtain the water extract of step 2-b2;

[0042] Step 3-b2: The water extract of step 2-b2 and the total ethanol extract of step 1-b2 are combined and concentrated, and then 95% ethanol solution is added thereto to a final concentration of 90%, and the solution is allowed to stand overnight to obtain a precipitate and a supernatant. The precipitate is dried, and the supernatant is directly freeze-dried. The two are combined, and water is added to make up the volume to obtain an extract of datura flower extract.

[0043] In one aspect of the disclosed embodiments, the second plant extract comprises an extract of Ilex iberis; the second plant extract is obtained by following steps 1-c1 to 3-c1:

[0044] Step 1-c1: preparing an extract of the Bulbus Fritillariae Cibotii extract and adding the extract to an aqueous solution containing a second stabilizer;

[0045] Step 2-c1: mixing the extract of the Bulbus Fritillariae Ilex extract with the second oil phase to prepare the water-in-oil emulsion of step 2-c1;

[0046] Step 3-c1: adding the water-in-oil type emulsion of step 2-c1 into water to prepare a water-in-oil-in-water type second plant extract emulsion.

[0047] In one aspect of the embodiments of the present disclosure, the second stabilizer is selected from zein or soy whey protein.

[0048] In one aspect of the embodiments of the present disclosure, in the aqueous solution containing the second stabilizer, the mass percentage of the second stabilizer is selected from 2%-8%.

[0049] In one aspect of the embodiments of the present disclosure, the second oil phase comprises polyglycerol castor oil, a second surfactant and vegetable oil; wherein the second surfactant is selected from sodium stearoyl lactylate or calcium stearoyl lactylate.

[0050] In one aspect of the embodiments of the present disclosure, the extract of the Bulbus Fritillariae Ilex extract and the second oil phase are stirred at a rate of 800-1500 rpm to form the water-in-oil emulsion of step 2-c1.

[0051] In one aspect of the embodiments of the present disclosure, the water-in-oil type emulsion of step 2-c1 is stirred with water at a stirring rate of 1800-2200 rpm to form a water-in-oil-in-water type second plant extract emulsion.

[0052] In one aspect of the disclosed embodiments, the extract of the Bulbus Fritillariae Cibotii extract is obtained by following steps 1-c2 to 3-c2:

[0053] Step 1-c2: weigh the powder of Ilex iberis, add 5-8 times the weight of 95% ethanol, reflux extract at 75°C-85°C for 1.5-2.5h, reflux extract 3-5 times, combine the ethanol solution and filter; obtain the filter residue and the total ethanol extract of step 1-c2;

[0054] Step 2-c2: reflux the filter residue with 5-8 times the mass of water at 75°C-85°C for 1.5-2.5h, reflux extraction 3-5 times to obtain the water extract of step 2-c2;

[0055] Step 3-c2: Combine and concentrate the water extract of step 2-c2 and the total ethanol extract of step 1-c2, then extract with ethyl acetate for multiple times, combine the extracts, and concentrate under vacuum to obtain an extract of Fritillaria cirrhosa.

[0056] In one aspect of the embodiments of the present disclosure, preferably, the second stabilizer is selected from soy whey protein. Specifically, the soy whey protein can be obtained by following steps 1-c3 to 3-c3:

[0057] Step 1-c3: adding a neutral salt to the soybean whey water from which insoluble impurities have been removed, and adjusting the pH to 4.0-5.8 to obtain the product of step 1-c3;

[0058] Step 2-c3: Concentrate the product of step 1-c3 until the solid matter accounts for 8%-40% of the mass of the mixed liquid, and then separate to obtain solid phase curd;

[0059] Step 3-c3: Add an appropriate amount of water to dissolve the solid phase curd to obtain the soy whey protein.

[0060] In one aspect of the embodiment of the present disclosure, the mass percentage of the second stabilizer in the aqueous solution is selected from 3%-8%, but is not limited thereto.

[0061] In one aspect of the disclosed embodiments, in step 2-a, a third plant extract is further added, wherein the third plant extract comprises a Ziziphus jujuba seed extract; the third plant extract is obtained by following steps 1-d1 to 3-d1:

[0062] Step 1-d1: preparing an extract of the Chinese date seed extract;

[0063] Step 2-d1: mixing the extract of the Chinese date seed extract with the third oil phase to prepare the water-in-oil emulsion of step 2-d1;

[0064] Step 3-d1: adding the water-in-oil type emulsion of step 2-d1 into the third aqueous phase to prepare a third water-in-oil-in-water type plant extract emulsion.

[0065] In one aspect of the embodiments of the present disclosure, the third oil phase comprises phospholipids, neutral lipids, a first stabilizer and vegetable oil; wherein the first stabilizer is selected from sucrose polyester or sucrose fatty acid ester.

[0066] In one aspect of the disclosed embodiments, in the third oil phase, the mass percentage of vegetable oil is 45%-65%, the mass percentage of phospholipids is 20%-30%, the mass percentage of neutral lipids is 5%-10%, and the mass percentage of the first stabilizer is 2%-7%.

[0067] In one aspect of the embodiments of the present disclosure, the third aqueous phase comprises a first osmotic pressure regulator and water; wherein the osmotic pressure regulator is selected from arginine, glycine, lysine, sorbitol or mannitol.

[0068] In one aspect of the embodiment of the present disclosure, in the third aqueous phase, the mass percentage of the first osmotic pressure regulator is 1%-5%, but is not limited thereto.

[0069] In one aspect of the presently disclosed embodiments, the phospholipid is selected from soybean lecithin, hydrogenated soybean lecithin, cephalin, dimyristoylphosphatidylcholine, dimyristoylphosphatidylglycerol, dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylglycerol, dipalmitoylphosphatidylglycerol, dioleoylphosphatidylglycerol, distearoylphosphatidylcholine or distearoylphosphatidylglycerol.

[0070] In one aspect of the disclosed embodiments, the neutral lipid is selected from triglycerides or diglycerides.

[0071] In one aspect of the embodiments of the present disclosure, the extract of the Ziziphus jujuba seed extract and the third oil phase are stirred at a rate of 800-1500 rpm to form the water-in-oil emulsion of step 2-d1.

[0072] In one aspect of the embodiments of the present disclosure, the water-in-oil type emulsion of step 2-d1 is stirred with water at a stirring rate of 1800-2200 rpm to form a water-in-oil-in-water type third plant extract emulsion.

[0073] In one aspect of the disclosed embodiments, the extract of the Chinese date seed extract is obtained by following steps 1-d2 to 3-d2:

[0074] Step 1-d2: After the stir-fried Chinese jujube kernels are dried, they are crushed and passed through a 40-mesh sieve, and then defatted for 3-6 hours with 5-8 times the mass of petroleum ether, and then dried and passed through a 40-mesh sieve to obtain defatted Chinese jujube kernel powder;

[0075] Step 2-d2: adding the defatted powder of Chinese jujube kernel to 75% ethanol, ultrasonicating at 200-300 kHz for 1.5-3 hours, and then filtering to obtain an ethanol extract of the defatted powder of Chinese jujube kernel;

[0076] Step 3-d2: freeze-dry the alcohol extract of the defatted powder of the Chinese jujube seeds to obtain a powder, add water to make up the volume, and obtain an extract of the Chinese jujube seeds extract.

[0077] According to a second aspect of an embodiment of the present disclosure, a pharmaceutical composition is provided, comprising a chitosan-sodium alginate complex containing a plant extract prepared by a preparation method.

[0078] The technical solution provided by the embodiments of the present disclosure may have the following beneficial effects:

[0079] It can be seen from the above embodiments that the present disclosure provides a method for preparing a chitosan-sodium alginate complex containing plant extracts. The complex prepared by this method not only has the effect of relieving cough and inflammation, but also greatly prolongs the shelf life of its active ingredients.

[0080] It is to be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the present disclosure. DETAILED DESCRIPTION

[0081] In order to make the purpose, technical scheme and advantages of the present application clearer, the technical scheme of the present application will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are part of the embodiments of the present application, rather than all the embodiments. The relevant embodiments described herein are illustrative and are used to provide a basic understanding of the present application. The embodiments of the present application should not be interpreted as limiting the present application.

[0082] For simplicity, only some numerical ranges are specifically disclosed herein. However, any lower limit can be combined with any upper limit to form an unspecified range; and any lower limit can be combined with other lower limits to form an unspecified range, and any upper limit can be combined with any other upper limit to form an unspecified range. In addition, each separately disclosed point or single value can itself be combined as a lower limit or upper limit with any other point or single value or with other lower limits or upper limits to form an unspecified range.

[0083] In this article, the terms "comprises", "comprising" or any other variations thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device that includes a series of elements includes not only those elements, but also includes other elements not explicitly listed, or also includes elements inherent to such process, method, article or device. In the absence of more restrictions, an element defined by the sentence "comprising a ..." does not exclude the presence of other identical elements in the process, method, article or device that includes the element.

[0084] In the description herein, unless otherwise specified, “above” and “below” include the number.

[0085] Unless otherwise specified, the terms used in this disclosure have the commonly known meanings generally understood by those skilled in the art. Unless otherwise specified, the numerical values ​​of the various parameters mentioned in this disclosure can be measured using various measurement methods commonly used in the art (for example, they can be tested according to the methods given in the embodiments of this disclosure).

[0086] The term "about" is used to describe and illustrate small changes. When used in conjunction with an event or situation, the term may refer to an example in which the event or situation occurs precisely and an example in which the event or situation occurs very approximately. For example, when used in conjunction with a numerical value, the term may refer to a range of variation less than or equal to ±10% of the numerical value, such as less than or equal to ±5%, less than or equal to ±4%, less than or equal to ±3%, less than or equal to ±2%, less than or equal to ±1%, less than or equal to ±0.5%, less than or equal to ±0.1%, or less than or equal to ±0.05%. In addition, amounts, ratios, and other numerical values ​​are sometimes presented in this article in a range format. It should be understood that such a range format is for convenience and simplicity, and should be flexibly understood to include not only numerical values ​​explicitly designated as range limits, but also all individual 10 numerical values ​​or subranges encompassed within the range, as if each numerical value and subrange were explicitly designated.

[0087] A list of items connected by the terms "at least one of," "at least one of," "at least one of," or other similar terms may mean any combination of the listed items. For example, if items A and B are listed, the phrase "at least one of A and B" means only A; only B; or A and B. In another example, if items A, B, and C are listed, the phrase "at least one of A, B, and C" means only A; or only B; only C; A and B (excluding C); A and C (excluding B); B and C (excluding A); or all of A, B, and C. Item A may contain a single component or multiple components. Item B may contain a single component or multiple components. Item C may contain a single component or multiple components.

[0088] The main chemical components of Datura extract are withanolides, flavonoids and alkaloids, which have a wide range of biological activities such as anti-inflammatory, anti-itching and cell protection. Among them, the alkaloid compounds in Datura include the following compounds with anti-inflammatory effects: N-trans-p-coumaroyltyramine ( N-trans-p -coumaroyltyramine), N-trans-p-coumaryl octopamine ( N-trans-p-coumaroyloctopamine), eleutherazine B, naphthisoxazol A, 1-carbomethoxy-β-carboline, 2-amino adenosine, 3-indolecarboxaldehyde, aurantiamide acetate, etc., among which, for example, eleutherazine B as a diketopiperazine compound, naphthisoxazol A as a naphthoxazolyl compound, its solubility in water at room temperature is poor, and indole alkaloids such as 3-indolecarboxaldehyde are insoluble in water. The flavonoids in Datura stramonium include the following compounds with anti-inflammatory effects: kaempferol-3- O -α- L -rhamnopyranoside, astragaloside, isoquercetin, , isorhamnetin-3- O -β- D -Glucopyranose-7- O -α- L -Rhamnoside (isorhamnetin-3- O -β- D -glucopyranosyl-7- O -α- L -rhamnopyranoside), apigenin-7- O -β- D -pyranoglucoside (apigenin-7- O -β- D -glucopyranoside), etc., and the above glycosylated flavonoids are easily soluble in water; therefore, they can be respectively embedded and encapsulated using the water-in-oil-in-water type emulsion provided by the present disclosure, which is beneficial to storage and absorption by the human body.

[0089] The main chemical components of the extract of Fritillaria cirrhosae are isosteroidal alkaloids, saponins, flavonoids, polysaccharides, nucleosides, starch, flavonoids, coumarins, fatty acid glycerides, sphingolipids, amino acids, polypeptides, fatty acids, phenolic glycosides and other chemical components. Among them, the fat-soluble single components that exert the drug effect include fritillary glycosides, fritillary alkaloids and fritillary glycoside B; the water-soluble single components that exert the drug effect include β-thymidine and adenosine. Similarly, the water-in-oil-in-water type emulsion provided by the present disclosure can be used to embed and encapsulate them respectively, so as to facilitate storage and absorption by the human body.

[0090] The main chemical components of the Chinese jujube seed extract are saponins, flavonoids, alkaloids, fatty acids and the like; the saponins in the Chinese jujube seed extract include Chinese jujube saponin; specifically including Chinese jujube saponin A, Chinese jujube saponin B, Chinese jujube saponin B1, Chinese jujube saponin A1, Chinese jujube saponin C, acetylated Chinese jujube saponin B, original Chinese jujube saponin A, original Chinese jujube saponin B, original Chinese jujube saponin B1 and Chinese jujube saponin G; Chinese jujube saponin has good solubility in water but poor solubility in oils and fats.

[0091] The flavonoid components in the extract of Chinese jujube seeds include apigenin-type flavonoid carbon glycosides, isoflavones and flavonol glycosides, including spinosin, swertisin, puerarin, 6'''-feruloylisospinosin, isospinosin, 6'''-ferloylisospinosin, isovitexin, isovitexin-2''- O -β- D -glucopyranoside, zivulgarin, 6'''-sinapoylspinosin, 6'''-p-coumaroylspinsin, 6'''-p-hydroxybenzoylspinosin, 6'''-p-hydroxybenzoylspinosin, 6,8-dicarbonyl glucosylapigenin, 6'''-(4'''- O -β- D -glucopyranosyl)-vanilloylspinosin, 6'''-dihydrophaseoyl spinosin, 6'',6'''-diferuloyl spinosin, 4,2',4',6'-tetrahydroxychalcone, naringenin, eriodictyol, pratensein, luteolin-7-glucuronide O -glucuronide), delphinidin 3- O -Glucoside (delphinidin-3- O -glucoside), neohesperidin, apigenin 5- O-glucoside (apigenin-5- O -glucoside), rutin, pelargonidin, pinocembrin, pinobanksin, dihydrokaempferol, phloretin, L-epicatechin, catechin, prunetin, diosmetin, hispidulin, pinostrobin chalcone, di-O-methylquercetin, quercetin-3- O -glucoside (isoquercitrin), quercetin-7- O -glucoside (quercetin-7- O -Glucoside), cyanidin 3- O -glucoside(cyanidin-3- O -glucoside), saponarin, naringin, etc.; among them, glycoside flavonoids have good solubility in water but poor solubility in oil, while isoflavones have the opposite. Similarly, they can be respectively embedded and encapsulated using the water-in-oil-in-water type emulsion provided by the present disclosure, which is beneficial to storage and absorption by the human body.

[0092] The present invention is further described below by way of specific examples. The various chemical reagents used in the embodiments of the present disclosure are obtained through conventional commercial channels unless otherwise specified. Unless otherwise specified, the contents described below are all weight contents. Unless otherwise specified, it is understood that the process is carried out at room temperature.

[0093] Embodiment 1: Embodiment 1 comprises the following steps:

[0094] A. Preparation of Datura stramonium extract:

[0095] Weigh 7 g of dried Datura leaves, add 8 times the mass of 60% ethanol, reflux extract at 80°C for 2 h, repeat 3 times, then combine the ethanol solutions and filter; obtain the filter residue and the total ethanol extract of Datura;

[0096] The filter residue was refluxed and extracted with ultrapure water 6 times the mass at 80°C for 2 hours, and the reflux extraction was repeated 3 times to obtain the water extract of Datura datura.

[0097] The water extract of Datura datura and the total ethanol extract of Datura datura are combined and concentrated, and then 95% ethanol solution is added thereto to make the final concentration of the solution 90%, and the solution is allowed to stand overnight to obtain a precipitate and a supernatant. The precipitate is dried, and the supernatant is directly freeze-dried. The two are combined, 50 mL of water is added, and an extract of Datura datura extract is obtained for later use.

[0098] B. Preparation of extract of Fritillaria cirrhosa extract:

[0099] Weigh 5.5 g of Ilex pilosa powder, extract with 8 times the mass of 95% ethanol at 80°C for 2 h, perform reflux extraction 4 times, combine the ethanol solutions and filter, and obtain the filter residue and the total ethanol extract of Ilex pilosa;

[0100] The filter residue was refluxed and extracted with ultrapure water 6 times the mass at 85°C for 2 hours, and the reflux extraction was repeated 4 times to obtain the water extract of Fritillaria cirrhosa.

[0101] The water extract of Ilex pilosa and the total ethanol extract of Ilex pilosa are combined and concentrated, and then extracted with ethyl acetate for 4 times. The extracts are combined and concentrated in vacuo to obtain an extract of Ilex pilosa extract for use.

[0102] C. Preparation of water-in-oil-in-water emulsion of datura flower extract:

[0103] The extract of the datura flower extract prepared above was weighed and mixed with the first oil phase, wherein the volume ratio of the extract of the datura flower extract to the first oil phase was 0.2:1; in the first oil phase, the mass percentage of soybean oil was 50%, the mass percentage of cephalin was 35%, the mass percentage of diglyceride was 12%, and the mass percentage of sucrose polyester was 3%. The extract of the datura flower extract and the first oil phase formed an oil-in-water type emulsion at a stirring rate of 1000 rpm;

[0104] Ultrapure water 3 times the volume of the first oil phase was weighed, and 2% glycine was added thereto; the mixture was stirred at a rate of 2000 rpm, and then the water-in-oil emulsion was slowly added to the water to form a water-in-oil-in-water emulsion.

[0105] D. Preparation of water-in-oil-in-water emulsion of Fritillaria cirrhosa extract:

[0106] Weigh the extract of the Bulbus Fritillariae Ilex extract prepared above, and add it to an aqueous solution containing soy whey protein with a mass percentage of 4 times the mass of the aqueous solution, wherein the mass percentage of soy whey protein in the aqueous solution is 5%;

[0107] The aqueous solution is mixed with a second oil phase, wherein the volume ratio of the extract of the aqueous solution to the second oil phase is 0.18:1; the second oil phase contains polyglycerol castor oil alcohol fat, sodium stearoyl lactylate and vegetable oil, the mass percentage of polyglycerol castor oil alcohol fat is 8%, the mass percentage of sodium stearoyl lactylate is 5%, and the rest is soybean oil; the aqueous solution and the second oil phase form a water-in-oil type emulsion at a stirring rate of 1000 rpm;

[0108] Ultrapure water 3 times the volume of the second oil phase was weighed and stirred at a rate of 2000 rpm, and then the water-in-oil emulsion was slowly added into the water to form a water-in-oil-in-water emulsion.

[0109] Embodiment 2: Embodiment 2 comprises the following steps:

[0110] A. Preparation of extract of Fritillaria cirrhosae:

[0111] Weigh 5.5 g of Ilex pilosa powder, extract with 8 times the mass of 95% ethanol at 80°C for 2 h, perform reflux extraction 4 times, combine the ethanol solutions and filter, and obtain the filter residue and the total ethanol extract of Ilex pilosa;

[0112] The filter residue was refluxed and extracted with ultrapure water 6 times the mass at 85°C for 2 hours, and the reflux extraction was repeated 4 times to obtain the water extract of Fritillaria cirrhosa.

[0113] The water extract of Ilex pilosa and the total ethanol extract of Ilex pilosa are combined and concentrated, and then extracted with ethyl acetate for 4 times. The extracts are combined and concentrated in vacuo to obtain an extract of Ilex pilosa extract for use.

[0114] B. Preparation of water-in-oil-in-water emulsion of Fritillaria cirrhosa extract:

[0115] The extract of the Ilex bulgur extract prepared above was weighed, added to a 4-fold aqueous solution to form an extract of the Ilex bulgur extract, and mixed with the first oil phase, wherein the volume ratio of the extract of the Ilex bulgur extract to the first oil phase was 0.2:1; in the first oil phase, the mass percentage of soybean oil was 50%, the mass percentage of cephalin was 35%, the mass percentage of diglyceride was 12%, and the mass percentage of sucrose polyester was 3%. The extract of the Ilex bulgur extract and the first oil phase formed an oil-in-water type emulsion at a stirring rate of 1000 rpm;

[0116] Ultrapure water 3 times the volume of the first oil phase was weighed, and 2% glycine was added thereto; the mixture was stirred at a rate of 2000 rpm, and then the water-in-oil emulsion was slowly added to the water; as a result, separation of the water-oil phase occurred, and Example 2 could not form a water-in-oil-in-water emulsion.

[0117] Example 3: The steps of Example 3 are basically the same as those of Example 2, except that the mass ratio of glycine in ultrapure water is 5%; as a result, separation of the water-oil two phases occurs, and Example 3 still cannot form a water-in-oil-in-water type emulsion.

[0118] Example 4: The steps of Example 4 are basically the same as those of Example 2, except that sucrose fatty acid ester is used instead of sucrose polyester; as a result, separation of the water-oil two phases occurs, and Example 4 still cannot form a water-in-oil-in-water type emulsion.

[0119] Example 5: The steps of Example 5 are basically the same as those of Example 2, except that, in the first oil phase, the mass percentage of soybean oil is 40%, the mass percentage of cephalin is 40%, the mass percentage of diglyceride is 15%, and the mass percentage of sucrose polyester is 5%; as a result, stratification of the water-oil two phases occurs, and Example 5 still cannot form a water-in-oil-in-water type emulsion.

[0120] Embodiment 6: Embodiment 6 comprises the following steps:

[0121] A. Preparation of Datura extract:

[0122] Weigh 7 g of dried Datura leaves, add 8 times the mass of 60% ethanol, reflux extract at 80°C for 2 h, repeat 3 times, then combine the ethanol solutions and filter; obtain the filter residue and the total ethanol extract of Datura;

[0123] The filter residue was refluxed and extracted with ultrapure water 6 times the mass at 80°C for 2 hours, and the reflux extraction was repeated 3 times to obtain the water extract of Datura datura.

[0124] The water extract of Datura datura and the total ethanol extract of Datura datura are combined and concentrated, and then 95% ethanol solution is added thereto to make the final concentration of the solution 90%, and the solution is allowed to stand overnight to obtain a precipitate and a supernatant. The precipitate is dried, and the supernatant is directly freeze-dried. The two are combined, 50 mL of water is added, and an extract of Datura datura extract is obtained for later use.

[0125] B. Preparation of extract of Fritillaria cirrhosa extract:

[0126] Weigh 5.5 g of Ilex pilosa powder, extract with 8 times the mass of 95% ethanol at 80°C for 2 h, perform reflux extraction 4 times, combine the ethanol solutions and filter, and obtain the filter residue and the total ethanol extract of Ilex pilosa;

[0127] The filter residue was refluxed and extracted with ultrapure water 6 times the mass at 85°C for 2 hours, and the reflux extraction was repeated 4 times to obtain the water extract of Fritillaria cirrhosa.

[0128] The water extract of Ilex pilosa and the total ethanol extract of Ilex pilosa are combined and concentrated, and then extracted with ethyl acetate for 4 times. The extracts are combined and concentrated in vacuo to obtain an extract of Ilex pilosa extract for use.

[0129] C. Preparation of water-in-oil-in-water emulsion of datura flower extract:

[0130] The extract of the datura flower extract prepared above was weighed and mixed with the first oil phase, wherein the volume ratio of the extract of the datura flower extract to the first oil phase was 0.2:1; in the first oil phase, the mass percentage of soybean oil was 50%, the mass percentage of cephalin was 35%, the mass percentage of diglyceride was 12%, and the mass percentage of sucrose polyester was 3%. The extract of the datura flower extract and the first oil phase formed an oil-in-water type emulsion at a stirring rate of 1000 rpm;

[0131] Ultrapure water 3 times the volume of the first oil phase was weighed, and 2% glycine was added thereto; the mixture was stirred at a rate of 2000 rpm, and then the water-in-oil emulsion was slowly added to the water to form a water-in-oil-in-water emulsion.

[0132] D. Preparation of water-in-oil-in-water emulsion of Fritillaria cirrhosa extract:

[0133] Weigh the extract of the Bulbus Fritillariae Ilex extract prepared above, and add it to an aqueous solution containing soy whey protein with a mass percentage of 4 times the mass of the aqueous solution, wherein the mass percentage of soy whey protein in the aqueous solution is 5%;

[0134] The aqueous solution is mixed with a second oil phase, wherein the volume ratio of the extract of the aqueous solution to the second oil phase is 0.18:1; the second oil phase contains polyglycerol castor oil alcohol fat, sodium stearoyl lactylate and vegetable oil, the mass percentage of polyglycerol castor oil alcohol fat is 8%, the mass percentage of sodium stearoyl lactylate is 5%, and the rest is soybean oil; the aqueous solution and the second oil phase form a water-in-oil type emulsion at a stirring rate of 1000 rpm;

[0135] Ultrapure water 3 times the volume of the second oil phase was weighed and stirred at a rate of 2000 rpm, and then the water-in-oil emulsion was slowly added into the water to form a water-in-oil-in-water emulsion.

[0136] E. Preparation of chitosan-sodium alginate complex:

[0137] 0.5 g of glacial acetic acid (475 μL), 20 g of chitosan and 7.5 g of sodium alginate were added to 80°C water (500 mL) and stirred for 2 h. The temperature was then lowered to 60°C, and 0.24 g of citric acid (155 μL) was added dropwise while stirring. The temperature was kept constant and stirring was continued for 2 h.

[0138] Then, the temperature was lowered to 45°C, and the water-in-oil-in-water emulsion of the datura flower extract prepared above was added, and the temperature was kept constant and stirring was continued for 2 hours;

[0139] Then lower the temperature to room temperature, add the water-in-oil-in-water emulsion of the Ilex bulgurii extract prepared above and 0.1 g of cross-linking agent glutaraldehyde, keep the temperature unchanged, and continue stirring for 1 hour; then freeze the solution at -75°C for 4 hours, and then thaw at 5°C; repeat the above process 3 times to obtain a gel-like product; the gel-like product is freeze-dried, then crushed and passed through a 40-mesh sieve to obtain the chitosan-sodium alginate complex of Example 6.

[0140] Example 7: The steps of Example 7 are basically the same as those of Example 6, except that the masses of glacial acetic acid, chitosan and sodium alginate are 1.5 g, 20 g and 7.5 g, respectively.

[0141] Example 8: The steps of Example 8 are basically the same as those of Example 6, except that the masses of glacial acetic acid, chitosan and sodium alginate are 0.15 g, 20 g and 7.5 g, respectively.

[0142] Example 9: The steps of Example 9 are basically the same as those of Example 6, except that the mass of citric acid added is 0.5 g.

[0143] Comparative Example 1: The steps of Comparative Example 1 are substantially the same as those of Example 6, except that glacial acetic acid is not added in the preparation of the chitosan-sodium alginate composite.

[0144] Comparative Example 2: The steps of Comparative Example 2 are substantially the same as those of Example 6, except that the preparation process of the chitosan-sodium alginate complex includes:

[0145] 0.5 g of glacial acetic acid (475 μL), 20 g of chitosan and 7.5 g of sodium alginate were added to 80°C water (500 mL) and stirred for 2 h; then the temperature was lowered to 45°C, the water-in-oil-in-water emulsion of the datura flower extract prepared above was added, the temperature was kept constant, and stirring was continued for 2 h;

[0146] Then the temperature was lowered to room temperature, and the water-in-oil-in-water emulsion of the Bulbus Fritillariae Bulbs extract prepared above and 0.1 g of cross-linking agent glutaraldehyde were added, the temperature was kept constant, and stirring was continued for 1 hour; the solution was then frozen at -75°C for 4 hours, and then thawed at 5°C; the above process was repeated 3 times to obtain a gel-like product; the gel-like product was freeze-dried, then crushed, and passed through a 40-mesh sieve to obtain the chitosan-sodium alginate complex of Comparative Example 2 (i.e., without adding citric acid).

[0147] Comparative Example 3: Comparative Example 3 comprises the following steps:

[0148] A. Preparation of Datura stramonium extract:

[0149] Weigh 7 g of dried Datura leaves, add 8 times the mass of 60% ethanol, reflux extract at 80°C for 2 h, repeat 3 times, then combine the ethanol solutions and filter; obtain the filter residue and the total ethanol extract of Datura;

[0150] The filter residue was refluxed and extracted with ultrapure water 6 times the mass at 80°C for 2 hours, and the reflux extraction was repeated 3 times to obtain the water extract of Datura datura.

[0151] The water extract of Datura datura and the total ethanol extract of Datura datura are combined and concentrated, and then 95% ethanol solution is added thereto to make the final concentration of the solution 90%, and the solution is allowed to stand overnight to obtain a precipitate and a supernatant. The precipitate is dried, and the supernatant is directly freeze-dried. The two are combined, 50 mL of water is added, and an extract of Datura datura extract is obtained for later use.

[0152] B. Preparation of water-in-oil-in-water emulsion of datura flower extract:

[0153] The extract of the datura flower extract prepared above was weighed and mixed with the first oil phase, wherein the volume ratio of the extract of the datura flower extract to the first oil phase was 0.2:1; in the first oil phase, the mass percentage of soybean oil was 50%, the mass percentage of cephalin was 35%, the mass percentage of diglyceride was 12%, and the mass percentage of sucrose polyester was 3%. The extract of the datura flower extract and the first oil phase formed an oil-in-water type emulsion at a stirring rate of 1000 rpm;

[0154] Ultrapure water 3 times the volume of the first oil phase was weighed, and 2% glycine was added thereto; the mixture was stirred at a rate of 2000 rpm, and then the water-in-oil emulsion was slowly added to the water to form a water-in-oil-in-water emulsion.

[0155] E. Preparation of chitosan-sodium alginate complex:

[0156] 0.5 g of glacial acetic acid (475 μL), 20 g of chitosan and 7.5 g of sodium alginate were added to 80°C water (500 mL) and stirred for 2 h. The temperature was then lowered to 60°C, and 0.24 g of citric acid (155 μL) was added dropwise while stirring. The temperature was kept constant and stirring was continued for 2 h.

[0157] Then, the temperature was lowered to 45°C, and the water-in-oil-in-water emulsion of the datura flower extract prepared above was added, and the temperature was kept constant and stirring was continued for 2 hours;

[0158] Then the temperature was lowered to room temperature, 0.1 g of cross-linking agent glutaraldehyde was added, the temperature was kept constant, and stirring was continued for 1 hour; the solution was then frozen at -75°C for 4 hours, and then thawed at 5°C; the above process was repeated 3 times to obtain a gel-like product; the gel-like product was freeze-dried, then crushed, and passed through a 40-mesh sieve to obtain the chitosan-sodium alginate complex of Comparative Example 3.

[0159] Comparative Example 4: Comparative Example 4 comprises the following steps:

[0160] A. Preparation of extract of Fritillaria cirrhosae:

[0161] Weigh 5.5 g of Ilex pilosa powder, extract with 8 times the mass of 95% ethanol at 80°C for 2 h, perform reflux extraction 4 times, combine the ethanol solutions and filter, and obtain the filter residue and the total ethanol extract of Ilex pilosa;

[0162] The filter residue was refluxed and extracted with ultrapure water 6 times the mass at 85°C for 2 hours, and the reflux extraction was repeated 4 times to obtain the water extract of Fritillaria cirrhosa.

[0163] The water extract of Ilex pilosa and the total ethanol extract of Ilex pilosa are combined and concentrated, and then extracted with ethyl acetate for 4 times. The extracts are combined and concentrated in vacuo to obtain an extract of Ilex pilosa extract for use.

[0164] B. Preparation of water-in-oil-in-water emulsion of Fritillaria cirrhosa extract:

[0165] Weigh the extract of the Bulbus Fritillariae Ilex extract prepared above, and add it to an aqueous solution containing soy whey protein with a mass percentage of 4 times the mass of the aqueous solution, wherein the mass percentage of soy whey protein in the aqueous solution is 5%;

[0166] The aqueous solution is mixed with a second oil phase, wherein the volume ratio of the extract of the aqueous solution to the second oil phase is 0.18:1; the second oil phase contains polyglycerol castor oil alcohol fat, sodium stearoyl lactylate and vegetable oil, the mass percentage of polyglycerol castor oil alcohol fat is 8%, the mass percentage of sodium stearoyl lactylate is 5%, and the rest is soybean oil; the aqueous solution and the second oil phase form a water-in-oil type emulsion at a stirring rate of 1000 rpm;

[0167] Ultrapure water 3 times the volume of the second oil phase was weighed and stirred at a rate of 2000 rpm, and then the water-in-oil emulsion was slowly added into the water to form a water-in-oil-in-water emulsion.

[0168] C. Preparation of chitosan-sodium alginate complex:

[0169] 0.5 g of glacial acetic acid (475 μL), 20 g of chitosan and 7.5 g of sodium alginate were added to 80°C water (500 mL) and stirred for 2 h. The temperature was then lowered to 60°C, and 0.24 g of citric acid (155 μL) was added dropwise while stirring. The temperature was kept constant and stirring was continued for 2 h.

[0170] Then lower the temperature to room temperature, add the water-in-oil-in-water emulsion of the Ilex bulgurii extract prepared above and 0.1 g of cross-linking agent glutaraldehyde, keep the temperature unchanged, and continue stirring for 1 hour; then freeze the solution at -75°C for 4 hours, and then thaw at 5°C; repeat the above process 3 times to obtain a gel-like product; the gel-like product is freeze-dried, then crushed and sieved through a 40-mesh sieve to obtain the chitosan-sodium alginate complex of Comparative Example 4.

[0171] Comparative Example 5: Comparative Example 5 comprises the following steps:

[0172] A. Preparation of Datura extract:

[0173] Weigh 7 g of dried Datura leaves, add 8 times the mass of 60% ethanol, reflux extract at 80°C for 2 h, repeat 3 times, then combine the ethanol solutions and filter; obtain the filter residue and the total ethanol extract of Datura;

[0174] The filter residue was refluxed and extracted with ultrapure water 6 times the mass at 80°C for 2 hours, and the reflux extraction was repeated 3 times to obtain the water extract of Datura datura.

[0175] The water extract of Datura datura and the total ethanol extract of Datura datura are combined and concentrated, and then 95% ethanol solution is added thereto to make the final concentration of the solution 90%, and the solution is allowed to stand overnight to obtain a precipitate and a supernatant. The precipitate is dried, and the supernatant is directly freeze-dried. The two are combined, 50 mL of water is added, and an extract of Datura datura extract is obtained for later use.

[0176] B. Preparation of extract of Fritillaria cirrhosa extract:

[0177] Weigh 5.5 g of Ilex pilosa powder, extract with 8 times the mass of 95% ethanol at 80°C for 2 h, perform reflux extraction 4 times, combine the ethanol solutions and filter, and obtain the filter residue and the total ethanol extract of Ilex pilosa;

[0178] The filter residue was refluxed and extracted with ultrapure water 6 times the mass at 85°C for 2 hours, and the reflux extraction was repeated 4 times to obtain the water extract of Fritillaria cirrhosa.

[0179] The water extract of Ilex pilosa and the total ethanol extract of Ilex pilosa are combined and concentrated, and then extracted with ethyl acetate for 4 times. The extracts are combined and concentrated in vacuo to obtain an extract of Ilex pilosa extract for use.

[0180] C. Preparation of chitosan-sodium alginate complex:

[0181] 0.5 g of glacial acetic acid (475 μL), 20 g of chitosan and 7.5 g of sodium alginate were added to 80°C water (500 mL) and stirred for 2 h. The temperature was then lowered to 60°C, and 0.24 g of citric acid (155 μL) was added dropwise while stirring. The temperature was kept constant and stirring was continued for 2 h.

[0182] Then lower the temperature to 45°C, add the extract of the Datura stramonium extract prepared above, keep the temperature unchanged, and continue stirring for 2 hours;

[0183] Then lower the temperature to 45°C, dissolve the extract of the Ilex iberis extract prepared above in an appropriate amount of water, add 0.1 g of cross-linking agent glutaraldehyde, keep the temperature unchanged, and continue stirring for 1 hour; then freeze the solution at -75°C for 4 hours, and then thaw at 5°C; repeat the above process 3 times to obtain a gel-like product; after freeze-drying the gel-like product, crush it and pass it through a 40-mesh sieve to obtain the chitosan-sodium alginate complex of Comparative Example 3.

[0184] Cough suppressant efficacy experiment:

[0185] 1. Reagents and instruments, etc.:

[0186] Reagents: 25% concentrated ammonia water, etc.

[0187] Instruments: 1 / 10,000 balance, multifunctional cough and wheeze inducing instrument (model: YLS-8A), surgical instruments, etc.

[0188] Experimental animals: SD rats, male, 6-8 weeks

[0189] 2. Experimental methods:

[0190] Healthy SD rats were taken and randomly divided into a model group and an embodiment group; the rats in the model group were atomized with 15% ammonia water for 25 seconds, the modeling period was 1 day, and the preventive medication was given for 3 days. The samples of Examples 6-9 and Comparative Examples 1-3 were placed at room temperature for 1 day, 7 days and 20 days, and then diluted with 5‰ CMC-Na and administered by gavage, and preventive medication was given 3 days in advance. Fasting but not water for 24 hours before the last administration, 1 hour after the last administration, the SD rats were placed in a multifunctional cough-inducing and wheezing instrument, sprayed with 15% concentrated ammonia water, and atomized for 25 seconds, and the number of coughs of the SD rats within 4 minutes was recorded. The symptoms of cough are a large contraction or swelling of the abdomen and a wide mouth. The experimental results are shown in Table 1 (the values ​​in Table 1 are the number of coughs within 4 minutes), among which the number of coughs of the rats in the model group was 84 times:

[0191] Table 1:

[0192] .

[0193] From the values ​​in Table 1, it can be seen that for the chitosan-sodium alginate composite provided by the present disclosure, glacial acetic acid and citric acid can have a pore expansion effect, and a larger porosity can be used to coat more plant extract components, but the larger specific surface area caused by the larger porosity will accelerate the oxidation of the plant extract components; by comparing Example 6 with Example 7 and Example 9, it can be seen that the antitussive effects of the three samples after standing for 1 day are similar, but after standing for 7 days and 20 days, Example 6 is significantly better than Example 7 and Example 9; by comparing Example 6 with Example 8, Comparative Example 1 and Comparative Example 2, it can be seen that the antitussive effects of Example 8, Comparative Example 1 and Comparative Example 2 after standing do not decrease significantly, but there is a significant difference between the sample standing for 1 day and Example 6.

[0194] Those skilled in the art will readily appreciate other embodiments of the present disclosure after considering the specification and practicing the disclosure disclosed herein. The present disclosure is intended to cover any variations, uses or adaptations of the present disclosure that follow the general principles of the present disclosure and include common knowledge or customary technical means in the art that are not disclosed in the present disclosure.

Claims

1. A method for preparing a chitosan-sodium alginate complex containing a plant extract, characterized in that: The preparation method comprises the following steps 1-a to 6-a: Step 1-a: adding glacial acetic acid, chitosan and sodium alginate to water at 75°C-85°C, stirring for 1-3h, to obtain the product of step 1-a; in step 1-a, the mass ratio of glacial acetic acid, chitosan and sodium alginate is (0.03-0.08):(1-3):(0.5-1); Step 2-a: lowering the temperature to 55°C-65°C, adding citric acid dropwise to the product of step 1-a under stirring, keeping the temperature constant, and continuing stirring for 1-3 hours to obtain the product of step 2-a; in step 2-a, the mass of the citric acid added is 0.8%-1.5% of the mass of the chitosan added in step 1-a; Step 3-a: lower the temperature to 40°C-50°C, add the first plant extract, keep the temperature unchanged, and continue stirring for 1-3 hours to obtain the product of step 3-a; Step 4-a: lowering the temperature to room temperature, adding the second plant extract and the cross-linking agent, maintaining the temperature unchanged, and continuing stirring for 0.5-1.5 hours to obtain the product of step 4-a; Step 5-a: subjecting the product of step 4-a to freeze-thaw treatment to obtain the product of step 5-a; Step 6-a: freeze-drying the product of step 5-a, and then crushing and sieving to obtain the chitosan-sodium alginate complex containing the plant extract; Wherein, the first plant extract comprises a datura flower extract, and the second plant extract comprises a fritillaria cirrhosa extract; The first plant extract is obtained by the following steps: Weigh 7 g of dried Datura leaves, add 8 times the mass of 60% ethanol, reflux extract at 80°C for 2 h, repeat 3 times, then combine the ethanol solutions and filter; obtain the filter residue and the total ethanol extract of Datura; The filter residue was refluxed and extracted with ultrapure water 6 times the mass at 80°C for 2 hours, and the reflux extraction was repeated 3 times to obtain the water extract of Datura datura. The water extract of the datura flower and the ethanol total extract of the datura flower are combined and concentrated, and then a 95% ethanol solution is added to a final concentration of 90% of the solution, and the solution is allowed to stand overnight to obtain a precipitate and a supernatant, the precipitate is dried, and the supernatant is directly freeze-dried, and the two are combined, and 50 mL of water is added to obtain an extract of the datura flower extract; The extract of the datura flower extract is weighed and mixed with the first oil phase, wherein the volume ratio of the extract of the datura flower extract to the first oil phase is 0.2:1; in the first oil phase, the mass percentage of soybean oil is 50%, the mass percentage of cephalin is 35%, the mass percentage of diglyceride is 12%, and the mass percentage of sucrose polyester is 3%, and the extract of the datura flower extract and the first oil phase form an oil-in-water type emulsion at a stirring rate of 1000 rpm; Weigh ultrapure water 3 times the volume of the first oil phase, add 2% glycine thereto; stir at a speed of 2000 rpm, and then slowly add the water-in-oil type emulsion into the water to form a first water-in-oil-in-water type plant extract; The second plant extract is obtained by the following steps: Weigh 5.5 g of Ilex pilosa powder, extract with 8 times the mass of 95% ethanol at 80°C for 2 h, perform reflux extraction 4 times, combine the ethanol solutions and filter, and obtain the filter residue and the total ethanol extract of Ilex pilosa; The filter residue was subjected to reflux extraction at 85° C. for 2 h with ultrapure water 6 times the mass thereof, and the reflux extraction was repeated 4 times to obtain a water extract of Fritillaria cirrhosa; The water extract of Ilex pilosa and the total ethanol extract of Ilex pilosa are combined and concentrated, and then extracted with ethyl acetate for 4 times, the extracts are combined, and vacuum concentrated to obtain an extract of Ilex pilosa; Weigh the extract of the Bulbus Fritillariae Ilex extract, and add it to an aqueous solution containing soy whey protein with a mass percentage of 4 times the mass of the aqueous solution containing soy whey protein, wherein the mass percentage of soy whey protein in the aqueous solution containing soy whey protein is 5%; The aqueous solution is mixed with a second oil phase, wherein the volume ratio of the aqueous solution to the second oil phase is 0.18:1; the second oil phase comprises polyglycerol castor oil alcohol fat, sodium stearoyl lactylate and vegetable oil, the mass percentage of polyglycerol castor oil alcohol fat is 8%, the mass percentage of sodium stearoyl lactylate is 5%, and the rest is soybean oil; the aqueous solution and the second oil phase form a water-in-oil type emulsion at a stirring rate of 1000 rpm; Ultrapure water 3 times the volume of the second oil phase was weighed and stirred at a speed of 2000 rpm, and then the water-in-oil type emulsion was slowly added into the water to form a water-in-oil-in-water type second plant extract.

2. The preparation method according to claim 1, characterized in that: The cross-linking agent is selected from MgCl2, CaCl2 or glutaraldehyde.

3. A pharmaceutical composition, characterized in that The pharmaceutical composition comprises a chitosan-sodium alginate complex containing a plant extract prepared by the preparation method according to claim 1 or 2.