Multilayer encapsulated gastroprotective soft capsule of root extract of litsea cubeba and preparation method thereof

Abstract

The application discloses a multi-layer encapsulated gastrointestinal protective soft capsule of root extract of Litsea cubeba, which comprises a soft capsule content and a capsule shell, the soft capsule content is the root extract of Litsea cubeba, the capsule shell comprises an inner layer, a middle layer and an outer layer, the components of the inner layer are sodium alginate, high acyl gellan gum and shellac, the component of the middle layer is chitosan hydrochloride, and the component of the outer layer is tremella polysaccharide; wherein the soft capsule content is arranged in the inner layer of the capsule shell, and the density of the root extract of Litsea cubeba is 8.333 g / mL. The sodium alginate, the high acyl gellan gum and the shellac are used as the composite inner layer of the soft capsule shell, the chitosan hydrochloride is used as the middle layer material of the soft capsule shell, the soft capsule shell is digested in intestinal juice to achieve the purpose of protecting the intestine, the tremella polysaccharide is used as the outer layer material of the soft capsule shell, the soft capsule shell is digested in gastric juice to achieve the purpose of protecting the stomach, and finally the active components in the root extract of Litsea cubeba in the soft capsule content are released in the intestinal tract.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of medicine, and particularly relates to a multi-layer encapsulated gastroprotection soft capsule of root extract of Litsea cubeba and a preparation method thereof. BACKGROUND

[0002] The root of Litsea cubeba, also known as Douchi ginger, is a traditional Chinese medicine with a pungent, slightly bitter taste and warm nature. It has the functions of dispelling wind and cold, removing dampness, warming the middle and regulating qi to relieve pain, and is often used for colds, headache, stomachache, abdominal pain and diarrhea. However, the root extract of Litsea cubeba is unstable and easily affected by external conditions, which causes the inactivation of some active substances in it and restricts its application. At present, one of the main methods to achieve drug sustained release is to prepare a multi-layer encapsulated gastroprotection soft capsule. Soft capsules have the advantages of high bioavailability, masking of bad odor, prevention of drug contact with air, etc., and are often used as an effective delivery system for irritating drugs, easily oxidized drugs, volatile drugs, hydrophobic drugs and various health oils, and are widely used in the medical, cosmetic and health product industries. The selection of soft capsule wall materials has a great influence on the overall performance of the soft capsule. Traditional methods often use gelatin and agar as soft capsule wall materials, but they are easily disintegrated in an acidic environment and are not suitable for use as wall materials for enteric capsules.

[0003] The preparation method of the gastroprotection soft capsule is also a major factor affecting the performance of the gastroprotection soft capsule. The methods for preparing soft capsules mainly include formaldehyde immersion, enteric material coating, raw material mixing, etc. Different preparation methods, different wall materials and reaction conditions in the preparation process of the gastroprotection soft capsule will directly affect the embedding rate and sustained release effect of the product. For example, the gastroprotection soft capsule prepared by the formaldehyde immersion method is easily affected by the environment, resulting in unstable preparations; the soft capsule prepared by the enteric material coating method has good stability, but may pollute the environment.

[0004] A Chinese patent with the application number CN201511023661.7 discloses a plant type enteric soft capsule and a preparation method thereof, which relates to a preparation method of a soft capsule by using sodium alginate and gelatin to prepare a gel, and then adding a filler, pressing the soft capsule and drying to prepare the soft capsule. However, the soft capsule of the invention focuses on providing a plant type enteric soft capsule with good transparency and simple preparation process, and the preparation method cannot prepare a soft capsule which is digested layer by layer in different digestive fluids. A Chinese patent with the application number CN201580023702.4 discloses an enteric soft capsule and a preparation method thereof, which uses gelatin and low methoxyl pectin with an amidation degree of 5-25% as the outer shell of the enteric soft capsule, and encapsulates the content by a punching method. However, the soft capsule focuses on providing a soft capsule with enteric solubility and excellent preparation, and does not use a multi-layer encapsulation technology. A Chinese patent application with the application number CN202310357775.3 discloses a probiotic enteric soft capsule and a preparation method and application thereof, which uses sodium alginate as a film-forming material and an acid-resistant component, uses carrageenan and gellan gum as a gelling agent, uses water as a solvent, and uses glycerol, maltitol and the like as a plasticizer to prepare a plant capsule skin. The soft capsule provided by the invention focuses on isolating external air and water to prolong the shelf life of probiotics, but cannot make the capsule have the effect of resisting the harsh environment in the stomach. Therefore, there is an urgent need to research a soft capsule which can prevent the degradation of bioactive ingredients during the digestion process and efficiently transport them to the intestine for absorption. SUMMARY

[0005] In order to solve the above problems, the present application provides a multi-layer encapsulated beibush root extract gastroprotection soft capsule and a preparation method thereof.

[0006] The technical scheme of the present application is as follows:

[0007] One of the purposes of the present application is to provide a multi-layer encapsulated beibush root extract gastroprotection soft capsule, which comprises a soft capsule content and a capsule skin, the soft capsule content is beibush root extract, the capsule skin comprises an inner layer, a middle layer and an outer layer, the components of the inner layer are sodium alginate, high-acyl gellan gum and shellac, the component of the middle layer is chitosan hydrochloride, and the component of the outer layer is tremella polysaccharide; wherein the soft capsule content is arranged in the inner layer of the capsule skin, and the density of the beibush root extract is 8.333 g / mL.

[0008] The second purpose of the present application is to provide a preparation method of a multi-layer encapsulated beibush root extract gastroprotection soft capsule, which comprises the following steps:

[0009] S1: drying the washed beibush root blocks, cutting them into thin slices, placing the beibush root slices in water for water bath heating, filtering out the residue, taking the filtrate for vacuum concentration, preparing beibush root extract, and placing it at 20℃ for standby;

[0010] S2: Dissolve sodium alginate and high acyl gellan gum in water, stir to dissolve, to obtain a sodium alginate-high acyl gellan gum solution, ready for use;

[0011] S3: Add shellac to anhydrous ethanol, stir to dissolve, to obtain a shellac solution, ready for use;

[0012] S4: Mix the sodium alginate-high acyl gellan gum solution of step S2 with the shellac solution of step S3, stir evenly, and adjust the pH to 7.5 with NaOH solution, to obtain a sodium alginate-high acyl gellan gum-shellac solution;

[0013] S5: Disperse the Litsea cubeba root extract of step S1 in the sodium alginate-high acyl gellan gum-shellac solution of step S4, stir evenly at 60-80℃, to make a mixed solution;

[0014] S6: Drop the mixed solution of step S5 into a calcium chloride solution, stand for 30-60 min, filter, and wash with deionized water, to obtain a one-layer encapsulated soft capsule;

[0015] S7: Add the one-layer encapsulated soft capsule of step S6 to chitosan hydrochloride, stir, then filter, and wash with deionized water, to obtain a two-layer encapsulated soft capsule;

[0016] S8: Add the two-layer encapsulated soft capsule of step S7 to tremella polysaccharide, stir, then filter, and wash with deionized water, to finally obtain the multi-layer encapsulated Litsea cubeba root extract gastroprotection soft capsule.

[0017] Further, in step S1, the drying temperature is 55-65℃, the thickness of the Litsea cubeba root slice is 0.1 cm, the mass ratio of the Litsea cubeba root slice to water is 1:12, the water bath heating temperature is 100℃, and the time is 2 h, and the temperature for vacuum concentration is 60-70℃.

[0018] Further, in step S2, the concentration of sodium alginate in the sodium alginate-high acyl gellan gum solution is 1.5-15% w / v, the concentration of high acyl gellan gum is 0.5-5% w / v, the mass ratio of sodium alginate to high acyl gellan gum is 3:1, the stirring speed is 700-900 rpm, and the time is 1-2 h.

[0019] Further, in step S3, the concentration of the shellac solution is 20% w / v, the stirring speed is 700-900 rpm, and the time is 1-2 h.

[0020] Further, in step S4, the volume ratio of sodium alginate-high acyl gellan gum solution to shellac solution in the sodium alginate-high acyl gellan gum-shellac solution is 3:1, the stirring speed is 500-600 rpm, and the stirring time is 30-60 min.

[0021] Further, in step S5, the volume ratio of Chinese litse root extract to sodium alginate-high acyl gellan gum-shellac solution in the mixed solution is 1:4, the stirring speed is 500-600 rpm, and the stirring time is 1-2 h.

[0022] Further, in step S6, the concentration of the calcium chloride solution is 1-3% w / v.

[0023] Further, in step S7, the concentration of the chitosan hydrochloride is 0.2-2% w / v, the stirring speed is 100 rpm, and the stirring time is 20-60 min.

[0024] Further, in step S8, the concentration of the tremella polysaccharide is 0.2-2% w / v, the stirring speed is 100 rpm, and the stirring time is 20-60 min.

[0025] Compared with the prior art, the present application has the following beneficial effects:

[0026] 1. The multi-layer encapsulated gastrointestinal protective soft capsule of the invention is prepared by using sodium alginate, high acyl gellan gum and shellac as the inner layer of the soft capsule shell, using chitosan hydrochloride as the middle layer material of the soft capsule shell, so that it is digested in the intestinal juice to achieve the purpose of protecting the intestine, using tremella polysaccharide as the outer layer material of the soft capsule shell, so that it is digested in the gastric juice to achieve the purpose of protecting the stomach, and finally the active ingredients in the soft capsule content of the root extract of the plant are released in the intestinal tract. The combination of sodium alginate and high acyl gellan gum significantly improves the swelling index, which helps the root extract of the plant to be uniformly and continuously released in the intestinal tract, and improves the solubility and absorption rate of the root extract of the plant in the intestinal tract, thereby enhancing the gastrointestinal protection effect. At the same time, the sodium alginate-shellac soft capsule has low porosity, which can effectively protect the root extract of the plant from the influence of the gastrointestinal environment, thereby significantly improving the storage stability of the active ingredients. The cationic polysaccharide chitosan hydrochloride is used as the middle layer material of the soft capsule shell, which has excellent water solubility and can quickly swell in a humid environment, solving the problem of high brittleness of traditional soft capsule membranes. Due to the good stability of the amino group protonation, chitosan hydrochloride cannot be easily degraded or hydrolyzed in an acidic environment, so the soft capsule can effectively resist gastric acid erosion and ensure the continuous and targeted release of active substances in the intestinal environment. The anionic polysaccharide tremella polysaccharide is used as the outer layer material of the soft capsule shell, which has the functions of anti-inflammatory, anti-tumor and regulating gastrointestinal flora. It can be decomposed in gastric juice, exposing the chitosan hydrochloride layer, and the intestinal juice can preliminarily digest the chitosan hydrochloride layer and further digest the sodium alginate-high acyl gellan gum-shellac layer, thereby maximizing the protection of the active ingredients in the root extract of the plant and targeting the release of the active ingredients to the intestinal tract. As a delivery system for bioactive substances, the soft capsule can effectively prevent the degradation of bioactive ingredients during digestion and efficiently transport them to the intestinal tract for absorption, ensuring the continuous and directional release of the root extract of the plant.

[0027] 2. The preparation method of the multi-layer encapsulated gastrointestinal protective soft capsule of the invention is prepared by using the electrostatic self-assembly method to prepare the composite inner layer material of the soft capsule shell with anionic polysaccharides sodium alginate, high acyl gellan gum and shellac, and through electrostatic interaction, the cationic polysaccharide is adsorbed as the middle layer of the soft capsule shell, and the anionic polysaccharide tremella polysaccharide is wrapped in the outer layer of the soft capsule. The preparation conditions of the electrostatic self-assembly method are simple and can be carried out under mild conditions. The selective adsorption between different materials can be promoted by charge interaction, the number of layers, the thickness of the soft capsule and the arrangement and combination between the materials can be accurately controlled, thereby giving the soft capsule the characteristics of uniformity, stability and controlled release. BRIEF DESCRIPTION OF DRAWINGS

[0028] Figure 1Fig. 1 is a schematic diagram of soft capsules prepared in Example 1 and Comparative Examples 2-4 immersed in simulated gastrointestinal fluid for 4 h in the present application;

[0029] Figure 2 Fig. 2 is a line graph of the in vitro drug release rate of soft capsules prepared in Example 1 and Comparative Examples 1-4 in the present application;

[0030] Figure 3 Fig. 3 is a column graph of the encapsulation efficiency of soft capsules prepared in Example 1 and Comparative Examples 1-4 in the present application. DETAILED DESCRIPTION

[0031] The following further describes the present application in conjunction with preferred embodiments, and the endpoints of the ranges and any values disclosed in the present application are not to be construed as limiting the exact range or value; these ranges and values are to be understood to encompass values close thereto; for numerical ranges, the endpoints of each range, the endpoints of each range and individual point values, and individual point values can be combined to form one or more new numerical ranges, which are to be considered as specifically disclosed herein; the materials, reagents, etc. used in the following examples are commercially available unless otherwise specified; the experimental methods used in the following examples are conventional unless otherwise specified.

[0032] Example 1

[0033] The present embodiment provides a multi-layer encapsulated Litsea cubeba root extract gastroprotection soft capsule, which comprises a soft capsule content and a capsule shell, the soft capsule content is Litsea cubeba root extract, the capsule shell comprises an inner layer, a middle layer and an outer layer, the components of the inner layer are sodium alginate, high acyl gellan gum and shellac, the component of the middle layer is chitosan hydrochloride, and the component of the outer layer is tremella polysaccharide; wherein the soft capsule content is arranged in the inner layer of the capsule shell, and the density of the Litsea cubeba root extract is 8.333 g / mL.

[0034] The present embodiment also provides a preparation method of a multi-layer encapsulated Litsea cubeba root extract gastroprotection soft capsule, which comprises the following steps:

[0035] S1: The washed Litsea cubeba root block is dried at 60°C, cut into 0.1 cm thin slices, 1 kg of the Litsea cubeba root thin slices are weighed and placed in 12 L of water, heated in a water bath at 100°C for 2 h, filtered to remove the residue, and the filtrate is concentrated to 0.12 L under reduced pressure at 65°C to prepare Litsea cubeba root extract, which is prepared at 20°C for standby;

[0036] S2: 0.9 g of sodium alginate and 0.3 g of high acyl gellan gum are dissolved in 60 mL of water, stirred at a speed of 700 rpm for 2 h to make them dissolve, to obtain a sodium alginate-high acyl gellan gum solution, which is prepared for standby;

[0037] S3: 6 g of shellac was added to 30 mL of anhydrous ethanol, and dissolved by stirring at a speed of 700 rpm for 1 h to obtain a shellac solution, which was prepared for use;

[0038] S4: 60 mL of the sodium alginate-high acyl gellan gum solution of step S2 was mixed with 20 mL of the shellac solution of step S3, stirred at a speed of 500 rpm for 30 min, and adjusted to pH 7.5 with a NaOH solution to obtain a sodium alginate-high acyl gellan gum-shellac solution;

[0039] S5: 20 mL of the Litsea cubeba root extract of step S1 was dispersed in 80 mL of the sodium alginate-high acyl gellan gum-shellac solution of step S4, and stirred at a speed of 500 rpm at 60°C for 2 h to prepare a mixed solution;

[0040] S6: The mixed solution of step S5 was added dropwise to a calcium chloride solution with a concentration of 1% w / v, and allowed to stand for 30 min, then filtered and washed with deionized water to obtain a one-layer encapsulated soft capsule;

[0041] S7: The one-layer encapsulated soft capsule of step S6 was added to a chitosan hydrochloride solution with a concentration of 0.2% w / v, stirred at a speed of 100 rpm for 20 min, then filtered and washed with deionized water to obtain a two-layer encapsulated soft capsule;

[0042] S8: The two-layer encapsulated soft capsule of step S7 was added to a tremella polysaccharide solution with a concentration of 0.2% w / v, stirred at a speed of 100 rpm for 20 min, then filtered and washed with deionized water to finally obtain the multi-layer encapsulated Litsea cubeba root extract gastroprotection soft capsule.

[0043] Example 2

[0044] The present embodiment provides a multi-layer encapsulated Litsea cubeba root extract gastroprotection soft capsule, which comprises a soft capsule content and a capsule skin, the soft capsule content is a Litsea cubeba root extract, the capsule skin comprises an inner layer, a middle layer and an outer layer, the components of the inner layer are sodium alginate, high acyl gellan gum and shellac, the component of the middle layer is chitosan hydrochloride, and the component of the outer layer is tremella polysaccharide; wherein the soft capsule content is arranged in the inner layer of the capsule skin, and the density of the Litsea cubeba root extract is 8.333 g / mL.

[0045] The present embodiment also provides a preparation method of a multi-layer encapsulated Litsea cubeba root extract gastroprotection soft capsule, which comprises the following steps:

[0046] S1: The washed Litsea cubeba root pieces were dried at 55°C, cut into 0.1 cm thin slices, and 1 kg of the Litsea cubeba root slices were placed in 12 L of water and heated in a water bath at 100°C for 2 h. The residue was removed by filtration, and the filtrate was concentrated to 0.12 L at 70°C under reduced pressure to obtain a Litsea cubeba root extract, which was stored at 20°C for later use;

[0047] S2: 9 g of sodium alginate and 3 g of high acyl gellan gum were dissolved in 100 mL of water by stirring at a speed of 750 rpm for 2 h to obtain a sodium alginate-high acyl gellan gum solution, which was stored for later use;

[0048] S3: 6 g of shellac was dissolved in 30 mL of anhydrous ethanol by stirring at a speed of 750 rpm for 1.5 h to obtain a shellac solution, which was stored for later use;

[0049] S4: 90 mL of the sodium alginate-high acyl gellan gum solution of step S2 was mixed with 30 mL of the shellac solution of step S3, and stirred at a speed of 550 rpm for 45 min. The pH was adjusted to 7.5 with a NaOH solution to obtain a sodium alginate-high acyl gellan gum-shellac solution;

[0050] S5: 30 mL of the Litsea cubeba root extract of step S1 was dispersed in 120 mL of the sodium alginate-high acyl gellan gum-shellac solution of step S4, and stirred at a speed of 550 rpm at 65°C for 1.5 h to obtain a mixed solution;

[0051] S6: The mixed solution of step S5 was added dropwise to a calcium chloride solution with a concentration of 1.5% w / v, and allowed to stand for 60 min. The solution was filtered and washed with deionized water to obtain a one-layer encapsulated soft capsule;

[0052] S7: The one-layer encapsulated soft capsule of step S6 was added to a chitosan hydrochloride solution with a concentration of 0.6% w / v, and stirred at a speed of 100 rpm for 30 min. The solution was filtered and washed with deionized water to obtain a two-layer encapsulated soft capsule;

[0053] S8: The two-layer encapsulated soft capsule of step S7 was added to a tremella polysaccharide solution with a concentration of 0.6% w / v, and stirred at a speed of 100 rpm for 30 min. The solution was filtered and washed with deionized water to obtain the multi-layer encapsulated Litsea cubeba root extract gastroprotection soft capsule.

[0054] Example 3

[0055] The embodiment provides a multi-layer encapsulated gastroprotective soft capsule of torxeri root extract, which comprises soft capsule contents and a capsule shell, the soft capsule contents are torxeri root extract, the capsule shell comprises an inner layer, a middle layer and an outer layer, components of the inner layer are sodium alginate, high-acyl gellan gum and shellac, components of the middle layer are chitosan hydrochloride, and components of the outer layer are tremella polysaccharide; wherein the soft capsule contents are arranged in the inner layer of the capsule shell, and the density of the torxeri root extract is 8.333 g / mL.

[0056] The embodiment also provides a preparation method of the multi-layer encapsulated gastroprotective soft capsule of torxeri root extract, which comprises the following steps:

[0057] S1: dried washed torxeri root blocks at 65 DEG C, cut into 0.1 cm slices, weighed 1 kg of torxeri root slices, placed in 12 L of water, heated in a water bath at 100 DEG C for 2 h, filtered to remove residues, and concentrated the filtrate to 0.12 L at 60 DEG C under reduced pressure to prepare torxeri root extract, which is placed at 20 DEG C for standby;

[0058] S2: 18 g of sodium alginate and 6 g of high-acyl gellan gum are dissolved in 120 mL of water, stirred at a speed of 800 rpm for 1.5 h to make them dissolve, to obtain a sodium alginate-high-acyl gellan gum solution, which is standby;

[0059] S3: 8 g of shellac is added to 40 mL of anhydrous ethanol, stirred at a speed of 800 rpm for 2 h to make it dissolve, to obtain a shellac solution, which is standby;

[0060] S4: 120 mL of the sodium alginate-high-acyl gellan gum solution of step S2 is mixed with 40 mL of the shellac solution of step S3, stirred at a speed of 500 rpm for 30 min, and the pH is adjusted to 7.5 with a NaOH solution, to obtain a sodium alginate-high-acyl gellan gum-shellac solution;

[0061] S5: 40 mL of the torxeri root extract of step S1 is dispersed in 160 mL of the sodium alginate-high-acyl gellan gum-shellac solution of step S4, stirred at a speed of 600 rpm at 70 DEG C for 2 h to prepare a mixed solution;

[0062] S6: the mixed solution of step S5 is added dropwise to a calcium chloride solution with a concentration of 2% w / v, stands for 45 min, filtered, and washed with deionized water to prepare a one-layer encapsulated soft capsule;

[0063] S7: the one-layer encapsulated soft capsule of step S6 is added to a chitosan hydrochloride solution with a concentration of 1.0% w / v, stirred at a speed of 100 rpm for 40 min, and then filtered and washed with deionized water to obtain a two-layer encapsulated soft capsule;

[0064] S8: The two-layer encapsulated soft capsules of step S7 are added to the tremella polysaccharide with a concentration of 1.0% w / v, stirred at a speed of 100 rpm for 40 min, then filtered, washed with deionized water, and finally the multi-layer encapsulated ileogastraceae root extract gastroprotection soft capsules are obtained.

[0065] Example 4

[0066] The present embodiment provides a multi-layer encapsulated ileogastraceae root extract gastroprotection soft capsule, which comprises a soft capsule content and a capsule shell, the soft capsule content is ileogastraceae root extract, the capsule shell comprises an inner layer, a middle layer and an outer layer, the components of the inner layer are sodium alginate, high-acyl-konjac gum and shellac, the component of the middle layer is chitosan hydrochloride, and the component of the outer layer is tremella polysaccharide; wherein the soft capsule content is arranged in the inner layer of the capsule shell, and the density of the ileogastraceae root extract is 8.333 g / mL.

[0067] The present embodiment also provides a preparation method of a multi-layer encapsulated ileogastraceae root extract gastroprotection soft capsule, which comprises the following steps:

[0068] S1: The washed ileogastraceae root block is dried at 60°C, cut into 0.1 cm thin slices, 1 kg of ileogastraceae root slices are weighed and placed in 12 L of water, heated in a water bath at 100°C for 2 h, filtered to remove the residue, and the filtrate is concentrated to 0.12 L under reduced pressure at 65°C to prepare ileogastraceae root extract, which is placed at 20°C for standby;

[0069] S2: 2.1 g of sodium alginate and 0.7 g of high-acyl-konjac gum are dissolved in 140 mL of water, stirred at a speed of 850 rpm for 1 h to dissolve, to obtain a sodium alginate-high-acyl-konjac gum solution, which is standby;

[0070] S3: 10 g of shellac is added to 50 mL of anhydrous ethanol, stirred at a speed of 850 rpm for 1 h to dissolve, to obtain a shellac solution, which is standby;

[0071] S4: 150 mL of the sodium alginate-high-acyl-konjac gum solution of step S2 is mixed with 50 mL of the shellac solution of step S3, stirred at a speed of 500 rpm for 30 min, and the pH is adjusted to 7.5 with NaOH solution to obtain a sodium alginate-high-acyl-konjac gum-shellac solution;

[0072] S5: 50 mL of the ileogastraceae root extract of step S1 is dispersed in 200 mL of the sodium alginate-high-acyl-konjac gum-shellac solution of step S4, stirred at a speed of 500 rpm at 75°C for 1 h to prepare a mixed solution;

[0073] S6: The mixed solution of step S5 is added dropwise into a calcium chloride solution with a concentration of 2.5% w / v, and is allowed to stand for 30 min, filtered, and washed with deionized water to obtain a one-layer encapsulated soft capsule;

[0074] S7: The one-layer encapsulated soft capsule of step S6 is added into a chitosan hydrochloride solution with a concentration of 1.5% w / v, stirred at a speed of 100 rpm for 50 min, and then filtered and washed with deionized water to obtain a two-layer encapsulated soft capsule;

[0075] S8: The two-layer encapsulated soft capsule of step S7 is added into a tremella polysaccharide solution with a concentration of 1.5% w / v, stirred at a speed of 100 rpm for 50 min, and then filtered and washed with deionized water to finally obtain the multi-layer encapsulated Litsea cubeba root extract gastroprotection soft capsule.

[0076] Example 5

[0077] The present embodiment provides a multi-layer encapsulated Litsea cubeba root extract gastroprotection soft capsule, which comprises a soft capsule content and a capsule skin, the soft capsule content is a Litsea cubeba root extract, the capsule skin comprises an inner layer, a middle layer and an outer layer, the components of the inner layer are sodium alginate, high-acyl-konjac gum and shellac, the component of the middle layer is chitosan hydrochloride, and the component of the outer layer is tremella polysaccharide; wherein the soft capsule content is arranged in the inner layer of the capsule skin, and the density of the Litsea cubeba root extract is 8.333 g / mL.

[0078] The present embodiment also provides a preparation method of a multi-layer encapsulated Litsea cubeba root extract gastroprotection soft capsule, which comprises the following steps:

[0079] S1: The washed Litsea cubeba root block is dried at 60°C, cut into 0.1 cm thin slices, 1 kg of the Litsea cubeba root thin slices are weighed and placed in 12 L of water, heated in a water bath at 100°C for 2 h, filtered to remove the residue, and the filtrate is concentrated to 0.12 L under reduced pressure at 65°C to obtain a Litsea cubeba root extract, which is prepared and stored at 20°C;

[0080] S2: 2.4 g of sodium alginate and 0.8 g of high-acyl-konjac gum are dissolved in 160 mL of water, stirred at a speed of 900 rpm for 2 h to make them dissolve, to obtain a sodium alginate-high-acyl-konjac gum solution, which is prepared and stored;

[0081] S3: 12 g of shellac is added to 60 mL of anhydrous ethanol, stirred at a speed of 900 rpm for 2 h to make it dissolve, to obtain a shellac solution, which is prepared and stored;

[0082] S4: 180 mL of the sodium alginate-high acyl gellan gum solution of step S2 was mixed with 60 mL of the shellac solution of step S3, stirred at a rotation speed of 600 rpm for 60 min, and adjusted to pH 7.5 with a NaOH solution to obtain a sodium alginate-high acyl gellan gum-shellac solution;

[0083] S5: 60 mL of the Litsea cubeba root extract of step S1 was dispersed in 240 mL of the sodium alginate-high acyl gellan gum-shellac solution of step S4, stirred at a rotation speed of 600 rpm at 80°C for 2 h to prepare a mixed solution;

[0084] S6: The mixed solution of step S5 was added dropwise to a calcium chloride solution with a concentration of 3% w / v, allowed to stand for 30 min, filtered, and washed with deionized water to prepare a one-layer encapsulated soft capsule;

[0085] S7: The one-layer encapsulated soft capsule of step S6 was added to a chitosan hydrochloride solution with a concentration of 2% w / v, stirred at a rotation speed of 100 rpm for 60 min, then filtered and washed with deionized water to obtain a two-layer encapsulated soft capsule;

[0086] S8: The two-layer encapsulated soft capsule of step S7 was added to a tremella polysaccharide solution with a concentration of 2.0% w / v, stirred at a rotation speed of 100 rpm for 60 min, then filtered and washed with deionized water to finally obtain the multi-layer encapsulated Litsea cubeba root extract gastroprotection soft capsule.

[0087] Comparative Example 1

[0088] The difference from Example 1 is that the soft capsule shell of the present comparative example is only one layer, and the component of the shell is sodium alginate.

[0089] The present comparative example provides a method for preparing a soft capsule, comprising the following steps:

[0090] S1: The washed Litsea cubeba root block was dried at 60°C, cut into 0.1 cm thin slices, 1 kg of the Litsea cubeba root slices were weighed and placed in 12 L of water, heated in a water bath at 100°C for 2 h, filtered to remove the residue, and the filtrate was concentrated to 0.12 L under reduced pressure at 65°C to prepare a Litsea cubeba root extract, which was stored at 20°C for later use;

[0091] S2: 0.9 g of sodium alginate was dissolved in 60 mL of water, stirred at a rotation speed of 700 rpm for 2 h to dissolve it, to obtain a sodium alginate solution, which was prepared for later use;

[0092] S3: 20 mL of the Litsea cubeba root extract of step S1 was dispersed in 80 mL of the sodium alginate of step S2, stirred at a rotation speed of 500 rpm at 60°C for 2 h to prepare a mixed solution;

[0093] S4: The mixed solution of step S3 is added dropwise into a calcium chloride solution with a concentration of 1% w / v, left to stand for 30 min, filtered, and washed with deionized water to obtain the soft capsules.

[0094] Comparative Example 2

[0095] The difference from Example 1 is that the soft capsules of the present comparative example only have one layer of capsule skin, and the components of the capsule skin are sodium alginate, high-acyl-konjac gum, and shellac.

[0096] The present comparative example provides a method for preparing soft capsules, comprising the following steps:

[0097] S1: Cleaned Litsea cubeba root pieces are dried at 60°C, cut into 0.1 cm thin slices, 1 kg of Litsea cubeba root thin slices are weighed and placed in 12 L of water, heated in a water bath at 100°C for 2 h, filtered to remove residues, and the filtrate is concentrated to 0.12 L under reduced pressure at 65°C to prepare a Litsea cubeba root extract, which is stored at 20°C for later use;

[0098] S2: 0.9 g of sodium alginate and 0.3 g of high-acyl-konjac gum are dissolved in 60 mL of water, stirred at a speed of 700 rpm for 2 h to dissolve them, to obtain a sodium alginate-high-acyl-konjac gum solution, which is stored for later use;

[0099] S3: 6 g of shellac is added to 30 mL of anhydrous ethanol, stirred at a speed of 700 rpm for 1 h to dissolve it, to obtain a shellac solution, which is stored for later use;

[0100] S4: 60 mL of the sodium alginate-high-acyl-konjac gum solution of step S2 is mixed with 20 mL of the shellac solution of step S3, stirred at a speed of 500 rpm for 30 min, and the pH is adjusted to 7.5 with a NaOH solution to obtain a sodium alginate-high-acyl-konjac gum-shellac solution;

[0101] S5: 20 mL of the Litsea cubeba root extract of step S1 is dispersed in 80 mL of the sodium alginate-high-acyl-konjac gum-shellac solution of step S4, stirred at a speed of 500 rpm for 2 h at 60°C to prepare a mixed solution;

[0102] S6: The mixed solution of step S5 is added dropwise into a calcium chloride solution with a concentration of 1% w / v, left to stand for 30 min, filtered, and washed with deionized water to obtain the soft capsules.

[0103] Comparative Example 3

[0104] The difference from Example 1 is that the soft capsules of the present comparative example include soft capsule contents and capsule skin, the soft capsule contents are Litsea cubeba root extract, the capsule skin includes an inner layer and an outer layer, the components of the inner layer are sodium alginate, high-acyl-konjac gum, and shellac, and the components of the outer layer are chitosan hydrochloride.

[0105] The present comparative example provides a method for preparing a soft capsule, comprising the following steps:

[0106] S1: The washed Litsea cubeba root pieces were dried at 60°C, cut into 0.1 cm slices, and 1 kg of the Litsea cubeba root slices were placed in 12 L of water and heated in a water bath at 100°C for 2 h. The residue was removed by filtration, and the filtrate was concentrated to 0.12 L under reduced pressure at 65°C to obtain a Litsea cubeba root extract, which was stored at 20°C for later use;

[0107] S2: 0.9 g of sodium alginate and 0.3 g of high-acyl gellan gum were dissolved in 60 mL of water by stirring at a speed of 700 rpm for 2 h to obtain a sodium alginate-high-acyl gellan gum solution, which was stored for later use;

[0108] S3: 6 g of shellac was dissolved in 30 mL of anhydrous ethanol by stirring at a speed of 700 rpm for 1 h to obtain a shellac solution, which was stored for later use;

[0109] S4: 60 mL of the sodium alginate-high-acyl gellan gum solution of step S2 was mixed with 20 mL of the shellac solution of step S3, and stirred at a speed of 500 rpm for 30 min. The pH was adjusted to 7.5 with a NaOH solution to obtain a sodium alginate-high-acyl gellan gum-shellac solution;

[0110] S5: 20 mL of the Litsea cubeba root extract of step S1 was dispersed in 80 mL of the sodium alginate-high-acyl gellan gum-shellac solution of step S4, and stirred at a speed of 500 rpm for 2 h at 60°C to obtain a mixed solution;

[0111] S6: The mixed solution of step S5 was added dropwise to a calcium chloride solution with a concentration of 1% w / v, and allowed to stand for 30 min. The product was filtered and washed with deionized water to obtain a soft capsule with a single layer of encapsulation;

[0112] S7: The soft capsule with a single layer of encapsulation of step S6 was added to a chitosan hydrochloride solution with a concentration of 0.2% w / v, and stirred at a speed of 100 rpm for 20 min. The product was filtered and washed with deionized water to obtain the soft capsule.

[0113] Comparative Example 4

[0114] The difference between the present comparative example and Example 1 is that the soft capsule was prepared by a raw material mixing method.

[0115] The present comparative example provides a method for preparing a soft capsule, comprising the following steps:

[0116] S1: The washed Litsea cubeba root pieces were dried at 60°C, cut into 0.1 cm thin slices, and 1 kg of the Litsea cubeba root slices were placed in 12 L of water. The mixture was heated in a water bath at 100°C for 2 h, and the residue was removed by filtration. The filtrate was concentrated to 0.12 L at 65°C under reduced pressure to obtain a Litsea cubeba root extract, which was stored at 20°C for later use;

[0117] S2: 1.5% w / v sodium alginate, 0.5% w / v high acyl gellan gum, 20% w / v shellac, 0.2% w / v chitosan hydrochloride, and 0.2% w / v tremella polysaccharide were dissolved in water and stirred at a speed of 700 rpm for 2 h to obtain a fully mixed solution, which was stored for later use;

[0118] S3: 20 mL of the Litsea cubeba root extract of step S1 was dispersed in 80 mL of the fully mixed solution of step S2, and the mixture was stirred at a speed of 500 rpm at 60°C for 2 h to obtain a mixed solution;

[0119] S4: The mixed solution of step S3 was added dropwise to a 1% w / v calcium chloride solution, and the mixture was allowed to stand for 30 min. The mixture was filtered and washed with deionized water to obtain a soft capsule with a coating;

[0120] Evaluation of the implementation effect

[0121] The excellent effects achieved by the present application are further illustrated below by specific tests on the soft capsules prepared in Example 1 and Comparative Examples 1-4:

[0122] 0.2 g of the soft capsules was randomly taken from each of Example 1 and Comparative Examples 1-4. To simulate the digestion in the stomach, 0.2 g of the soft capsules was dispersed in distilled water to obtain a 2.5 mL dispersion. The dispersion was mixed with simulated gastric fluid (SGF), and the simulated gastric mixture was immediately incubated in a shaker at 100 rpm at 37°C for 4 hours. After 4 hours of gastric digestion, 5.5 mL of simulated intestinal fluid (SIF) was mixed with the simulated gastric mixture (10 mL), and the pH was adjusted to 7.0 with NaOH. Then, the simulated intestinal mixture was incubated in a shaker at 100 rpm at 37°C for 4 hours.

[0123] Figure 1 The schematic diagram of the soft capsules prepared in Example 1 and Comparative Examples 2-4 after being soaked in simulated gastric and intestinal fluids for 4 h is shown in FIG. 1. Figure 1 As can be seen from FIG. 1, the soft capsules prepared in Example 1 can protect the active ingredients in the Litsea cubeba root extract to the maximum extent, and target the release of the active substances to the intestine, preventing the degradation of the bioactive ingredients during digestion.

[0124] The in vitro drug release rate of the soft capsules prepared in Example 1 and Comparative Examples 1-4 was confirmed using a UV spectrum scanner, and the line graph of the measured data is shown in FIG. 2. Figure 2 As can be seen from FIG. 2, the soft capsules prepared in Example 1 have a slower drug release rate than the soft capsules prepared in Comparative Examples 1-4.Figure 2 As can be seen from Table 1, the soft capsules prepared in Example 1 can protect the active ingredients in the extract of Litsea cubeba root to the maximum extent, and target release of the active substances to the intestinal tract.

[0125] Figure 3 The encapsulation efficiency column chart of the soft capsules prepared in Example 1, and Comparative Examples 1-4 is shown in Table 2. Figure 3 As can be seen from Table 2, the soft capsules prepared in Example 1 have the highest encapsulation efficiency, which indicates that the present application can ensure effective delivery of the drug in the soft capsules, reduce waste of the dosage, and achieve the purpose of cost saving.

[0126] The above only describes the preferred embodiments of the present application, and it should be noted that, for those skilled in the art, without departing from the inventive concept, several modifications and improvements can be made, which are all within the protection scope of the present application.

Claims

1. A multi-layer gastroprotective soft capsule encapsulating a Litsea cubeba root extract, said soft capsule comprising a soft capsule content and a capsule shell, characterized in that, The soft capsule content is a root extract of Litsea cubeba, the capsule shell comprises an inner layer, a middle layer and an outer layer, the components of the inner layer are sodium alginate, high-acyl gellan gum and shellac, the component of the middle layer is chitosan hydrochloride, and the component of the outer layer is tremella polysaccharide; wherein the soft capsule content is arranged in the inner layer of the capsule shell, and the density of the root extract of Litsea cubeba is 8.333 g / mL.

2. The preparation method of the multi-layer encapsulated gastroprotective soft capsule of the root extract of Litsea cubeba according to claim 1, characterized in that, The method comprises the following steps: S1: drying washed Litsea cubeba root blocks, cutting into thin slices, placing the Litsea cubeba root slices in water for water bath heating, filtering out residues, taking the filtrate for vacuum concentration to prepare a root extract of Litsea cubeba, and placing it at 20℃ for standby; S2: dissolving sodium alginate and high-acyl gellan gum in water, stirring to dissolve, to obtain a sodium alginate-high-acyl gellan gum solution, and standby; S3: adding shellac to anhydrous ethanol, stirring to dissolve, to obtain a shellac solution, and standby; S4: mixing the sodium alginate-high-acyl gellan gum solution of step S2 and the shellac solution of step S3, stirring uniformly, and adjusting the pH to 7.5 with a NaOH solution to obtain a sodium alginate-high-acyl gellan gum-shellac solution; S5: dispersing the root extract of Litsea cubeba of step S1 in the sodium alginate-high-acyl gellan gum-shellac solution of step S4, stirring uniformly at 60-80℃ to prepare a mixed solution; S6: dropping the mixed solution of step S5 into a calcium chloride solution, standing for 30-60 min, filtering, and washing with deionized water to prepare a one-layer-encapsulated soft capsule; S7: adding the one-layer-encapsulated soft capsule of step S6 to chitosan hydrochloride, stirring, then filtering, and washing with deionized water to obtain a two-layer-encapsulated soft capsule; S8: adding the two-layer-encapsulated soft capsule of step S7 to tremella polysaccharide, stirring, then filtering, and washing with deionized water to finally obtain the multi-layer-encapsulated root extract of Litsea cubeba gastrointestinal protection soft capsule.

3. The preparation method of the multi-layer enteric-coated soft capsule of Litsea cubeba root extract according to claim 2, characterized in that, In step S1, the drying temperature is 55-65℃, the thickness of the dried Litsea cubeba root slices is 0.1 cm, the mass ratio of the Litsea cubeba root slices to water is 1:12, the water bath heating temperature is 100℃, and the time is 2 h, and the vacuum concentration temperature is 60-70℃.

4. The preparation method of the multi-layer coated gastroprotective soft capsule of the root extract of Litsea cubeba according to claim 2, characterized in that, In step S2, in the sodium alginate-high-acyl gellan gum solution, the concentration of sodium alginate is 1.5-15% w / v, the concentration of high-acyl gellan gum is 0.5-5% w / v, the mass ratio of sodium alginate to high-acyl gellan gum is 3:1, the stirring speed is 700-900 rpm, and the time is 1-2 h.

5. The preparation method of the multi-layer enteric-coated soft capsule of Litsea cubeba root extract according to claim 2, characterized in that, In step S3, the concentration of the shellac solution is 20% w / v, the stirring speed is 700-900 rpm, and the time is 1-2 h.

6. The preparation method of the multi-layer enteric-coated soft capsule of Litsea cubeba root extract according to claim 2, characterized in that, In step S4, in the sodium alginate-high-acyl gellan gum-shellac solution, the volume ratio of the sodium alginate-high-acyl gellan gum solution to the shellac solution is 3:1, the stirring speed is 500-600 rpm, and the time is 30-60 min.

7. The preparation method of the multi-layer enteric-coated soft capsule of Litsea cubeba root extract according to claim 2, characterized in that, In step S5, the volume ratio of the mixture of the extract of Litsea cubeba root and the sodium alginate-high acyl gellan gum- shellac solution is 1:4, the stirring speed is 500-600 rpm, and the stirring time is 1-2 h.

8. The preparation method of the multi-layer enteric-coated soft capsule of Litsea cubeba root extract according to claim 2, characterized in that, In step S6, the concentration of the calcium chloride solution is 1-3% w / v.

9. The preparation method of the multi-layer enteric-coated soft capsule of Litsea cubeba root extract according to claim 2, characterized in that, In step S7, the concentration of the chitosan hydrochloride is 0.2-2% w / v, the stirring speed is 100 rpm, and the stirring time is 20-60 min.

10. The preparation method of the multi-layer enteric-coated soft capsule of the gut-protective cinnamomum pedunculatum root extract according to claim 2, characterized in that, In step S8, the concentration of the tremella polysaccharide is 0.2-2% w / v, the stirring speed is 100 rpm, and the stirring time is 20-60 min.

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