Multi-layer encapsulated litsea cubeba root extract gastrointestinal protection soft capsule and preparation method thereof

Abstract

The invention discloses a multi-layer encapsulated litsea cubeba root extract gastrointestinal protection soft capsule, the soft capsule 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 inner layer comprises sodium alginate, high acyl gellan gum and shellac, and the middle layer comprises 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 on the inner layer of the capsule skin, and the density of the litsea cubeba root extract is 8.333 g / mL. Sodium alginate, high acyl gellan gum and shellac are adopted as a composite inner layer of the soft capsule shell, chitosan hydrochloride is adopted as a middle layer material of the soft capsule shell, so that the soft capsule shell is digested in intestinal juice to achieve the purpose of protecting intestines, tremella polysaccharide is adopted as an outer layer material of the soft capsule shell, so that the soft capsule shell is digested in gastric juice to achieve the purpose of protecting intestines. And finally, active ingredients in the litsea cubeba root extract in the soft capsule content are released in the intestinal tract.

Description

Technical Field

[0001] The invention belongs to the technical field of medicine, and particularly relates to a multi-layer encapsulated soft capsule for protecting the gastrointestinal tract of a litsea cubeba root extract and a preparation method thereof. Background Art

[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 effects of dispelling wind, dispersing cold and removing dampness, warming the middle and regulating qi to relieve pain, and is often used for colds, headaches, cold pain in the heart and stomach, abdominal pain, vomiting and diarrhea. However, the extract of Litsea cubeba root is unstable and easily affected by external conditions, which inactivates some active substances in it, restricting its application. At present, making drugs into multi-layer encapsulated gastrointestinal protection soft capsules is one of the main methods to achieve the purpose of drug sustained release. Soft capsules are often used as effective delivery systems for irritating drugs, easily oxidized drugs, volatile drugs, hydrophobic drugs and various health oils because of their advantages such as high bioavailability, ability to cover up bad odors, and preventing drugs from contacting air. They are widely used in the pharmaceutical, cosmetic, health care products and other industries. Among them, the selection of soft capsule wall materials has a great influence on the overall performance of soft capsules. Traditional methods often use gelatin and agar as soft capsule wall materials, but they are easy to disintegrate in an acidic environment and are not suitable for use as wall materials for enteric-coated capsules.

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

[0004] The Chinese patent application number CN201511023661.7 discloses a plant-type enteric soft capsule and a preparation method thereof, which involves preparing a gelatin with sodium alginate and gelatin, and then adding fillers, pressing soft capsules and drying to prepare soft capsules. However, the soft capsules of the invention focus on providing plant-type enteric soft capsules with good transparency and simple preparation process, and the preparation method cannot produce soft capsules that are digested in different digestive juices. The Chinese patent application number CN201580023702.4 discloses an enteric soft capsule and a preparation method thereof, using gelatin and low methoxy pectin with an amidation degree of 5-25% as the shell of the enteric capsule, and encapsulating the contents by punching, but the soft capsule focuses on providing soft capsules with enteric solubility and excellent preparation properties, and does not use multi-layer encapsulation technology. The Chinese patent application with application number CN202310357775.3 discloses a probiotic enteric soft capsule and its preparation method and application, which uses sodium alginate as a film-forming material and acid-resistant component, carrageenan and gellan gum as gelling agents, water as a solvent, and glycerol, maltitol, etc. as plasticizers to prepare plant capsule skin. The soft capsule provided by the invention focuses on isolating the outside air and water to extend the shelf life of probiotics, but it cannot make the capsule have the effect of resisting the harsh environment in the stomach. Therefore, it is urgent to develop a soft capsule that can prevent the bioactive ingredients from being degraded during the digestion process and efficiently transport them to the intestine for absorption. Summary of the invention

[0005] In order to solve the above problems, the present invention provides a multi-layer encapsulated litsea cubeba root extract gastrointestinal protection soft capsule and a preparation method thereof.

[0006] The technical solution of the present invention is as follows:

[0007] One of the purposes of the present invention is to provide a multi-layer encapsulated litsea cubeba root extract gastrointestinal protection soft capsule, the soft capsule comprises soft capsule content and a capsule skin, the soft capsule content is 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 components of the middle layer are chitosan hydrochloride, and the components of the outer layer are 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.

[0008] The second object of the present invention is to provide a method for preparing a multi-layer encapsulated soft capsule of Litsea cubeba root extract for gastrointestinal protection, comprising the following steps:

[0009] S1: drying the washed litsea cubeba root block, cutting it into thin slices, placing the litsea cubeba root slices in water for water bath heating, filtering to remove residues, taking the filtrate for vacuum concentration to obtain the litsea cubeba root extract, and placing it at 20° C. for later use;

[0010] S2: dissolving sodium alginate and high acyl gellan gum in water, stirring to dissolve, and obtaining a sodium alginate-high acyl gellan gum solution for later use;

[0011] S3: adding shellac to anhydrous ethanol and stirring to dissolve it to obtain a shellac solution for later use;

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

[0013] S5: dispersing the Litsea cubeba root extract of step S1 in the sodium alginate-high acyl gellan gum-shellac solution of step S4, stirring evenly at 60-80° C. to prepare a mixed solution;

[0014] S6: adding the mixed solution of step S5 dropwise to the calcium chloride solution, allowing to stand for 30-60 minutes, filtering, and washing with deionized water to obtain a single-layer encapsulated soft capsule;

[0015] S7: adding the one-layer encapsulated soft capsule of step S6 into chitosan hydrochloride, stirring, filtering, and washing with deionized water to obtain a two-layer encapsulated soft capsule;

[0016] S8: adding the two-layer encapsulated soft capsules of step S7 into Tremella fuciformis polysaccharide, stirring, filtering, and washing with deionized water to finally obtain the multi-layer encapsulated Litsea cubeba root extract gastrointestinal protection soft capsules.

[0017] Furthermore, in step S1, the drying temperature is 55-65°C, the thickness of the elm tree root slices is 0.1 cm, the mass ratio of the elm tree root slices to water is 1:12, the water bath heating temperature is 100°C, the time is 2h, and the reduced pressure concentration temperature is 60-70°C.

[0018] Furthermore, 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 1-2h.

[0019] Furthermore, 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] Furthermore, 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 rotation speed of the stirring process is 500-600 rpm, and the time is 30-60 min.

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

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

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

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

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

[0026] 1. The present invention provides a multi-layer encapsulated soft capsule for gastrointestinal protection of Litsea cubeba root extract, which uses sodium alginate, high acyl gellan gum and shellac as the inner layer of the soft capsule skin, uses chitosan hydrochloride as the middle layer material of the soft capsule skin, so that it can be digested in the intestinal fluid to achieve the purpose of protecting the intestine, and uses Tremella polysaccharide as the outer layer material of the soft capsule skin, so that it can be digested in the gastric juice to achieve the purpose of protecting the stomach, and finally releases the active ingredients in the Litsea cubeba root extract in the soft capsule content in the intestine. Among them, the combination of sodium alginate and high acyl gellan gum significantly improves the swelling index, helps the Litsea cubeba root extract to be uniformly and continuously released in the intestine, and improves the solubility and absorption rate of the Litsea cubeba root extract in the intestine, and enhances the gastrointestinal protection effect. At the same time, the sodium alginate-shellac soft capsule has a low porosity, which can effectively protect the Litsea cubeba root extract from the gastrointestinal environment, thereby significantly improving the storage stability of the active ingredients. The present invention adopts cationic polysaccharide chitosan hydrochloride as the middle layer material of the soft capsule skin. Due to its excellent water solubility, it can expand rapidly in a wet environment, solves the problem of high fragility of the traditional soft capsule film, and due to the good stability given by the protonation of its amino group, chitosan hydrochloride will not be easily degraded or hydrolyzed in an acidic environment, so the soft capsule can effectively resist gastric acid erosion, and ensure the continuous targeted release of active substances in the capsule in the intestinal environment. The present invention also adopts anionic polysaccharide Tremella polysaccharide as the outer layer material of the soft capsule skin. Tremella polysaccharide itself has the functions of anti-inflammatory, anti-tumor and regulating gastrointestinal flora. It can be decomposed in gastric juice to expose the chitosan hydrochloride layer. The intestinal juice performs preliminary digestion on the chitosan hydrochloride layer, and further digests the sodium alginate-high acyl gellan gum-shellac layer, thereby protecting the active ingredients in the Litsea cubeba root extract to the maximum extent, and making the active substances targeted to the intestinal tract. As a delivery system for bioactive substances, the soft capsule can effectively prevent the bioactive ingredients from being degraded during the digestion process and efficiently transport them to the intestine for absorption, ensuring the continuous and directional release of the Litsea cubeba root extract.

[0027] 2. The present invention provides a method for preparing a multi-layer encapsulated gastrointestinal protection soft capsule of Litsea cubeba root extract, which adopts an electrostatic self-assembly method to make anionic polysaccharide sodium alginate, high acyl gellan gum and shellac into a composite inner layer material of the soft capsule skin, and through electrostatic interaction, the cationic polysaccharide is adsorbed as the middle layer of the soft capsule skin, 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. In addition, the electrostatic self-assembly method can promote selective adsorption between different materials through charge interaction, accurately control the number of layers and thickness of the soft capsule and the arrangement and combination of materials, thereby giving the soft capsule the characteristics of uniformity, stability and controlled release. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1This is a schematic diagram of the soft capsules prepared in Example 1 and Comparative Examples 2-4 in the present invention after being immersed in simulated gastrointestinal fluid for 4 hours;

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

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

[0031] The present invention is further described below in conjunction with preferred embodiments. The endpoints and any values ​​of the ranges disclosed in the present invention are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values; for numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be regarded as specifically disclosed herein; the materials, reagents, etc. used in the following embodiments, unless otherwise specified, can be obtained from commercial channels; the experimental methods in the following embodiments, unless otherwise specified, are all conventional methods.

[0032] Example 1

[0033] The present embodiment provides a multi-layer encapsulated litsea cubeba root extract gastrointestinal protection soft capsule, the soft capsule comprising soft capsule content and a capsule skin, the soft capsule content is 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 components of the middle layer are chitosan hydrochloride, and the components of the outer layer are 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.

[0034] This embodiment also provides a method for preparing a multi-layer encapsulated soft capsule of Litsea cubeba root extract for gastrointestinal protection, comprising the following steps:

[0035] S1: Wash and dry the litsea cubeba root block at 60°C, cut it into 0.1 cm slices, weigh 1 kg of the litsea cubeba root slices and place them in 12 L of water, heat them in a water bath at 100°C for 2 h, filter and remove the residue, take the filtrate and concentrate it under reduced pressure at 65°C to 0.12 L, to obtain the litsea cubeba root extract, and place it at 20°C for later use;

[0036] S2: Dissolve 0.9 g of sodium alginate and 0.3 g of high acyl gellan gum in 60 mL of water, and stir at 700 rpm for 2 h to dissolve them to obtain a sodium alginate-high acyl gellan gum solution for later use;

[0037] S3: Add 6 g of shellac into 30 mL of anhydrous ethanol and stir at 700 rpm for 1 h to dissolve the shellac to obtain a shellac solution for later 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 500 rpm for 30 min, and adjusted the pH to 7.5 with a NaOH solution to obtain a sodium alginate-high acyl gellan gum-shellac solution;

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

[0040] S6: adding the mixed solution of step S5 dropwise to a calcium chloride solution having a concentration of 1% w / v, allowing to stand for 30 minutes, filtering, and washing with deionized water to obtain a single-layer encapsulated soft capsule;

[0041] S7: adding the one-layer encapsulated soft capsule of step S6 into chitosan hydrochloride with a concentration of 0.2% w / v, stirring at a speed of 100 rpm for 20 minutes, then filtering, and washing with deionized water to obtain a two-layer encapsulated soft capsule;

[0042] S8: adding the two-layer encapsulated soft capsules of step S7 into Tremella fuciformis polysaccharide with a concentration of 0.2% w / v, stirring at a rotation speed of 100 rpm for 20 minutes, then filtering, washing with deionized water, and finally obtaining the multi-layer encapsulated Litsea cubeba root extract gastrointestinal protection soft capsules.

[0043] Example 2

[0044] The present embodiment provides a multi-layer encapsulated litsea cubeba root extract gastrointestinal protection soft capsule, the soft capsule comprising soft capsule content and a capsule skin, the soft capsule content is 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 components of the middle layer are chitosan hydrochloride, and the components of the outer layer are 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] This embodiment also provides a method for preparing a multi-layer encapsulated soft capsule of Litsea cubeba root extract for gastrointestinal protection, comprising the following steps:

[0046] S1: Wash and dry the litsea cubeba root block at 55°C, cut it into 0.1 cm slices, weigh 1 kg of the litsea cubeba root slices and place them in 12 L of water, heat them in a water bath at 100°C for 2 h, filter and remove the residue, take the filtrate and concentrate it under reduced pressure at 70°C to 0.12 L, to obtain the litsea cubeba root extract, and place it at 20°C for later use;

[0047] S2: dissolving 9 g of sodium alginate and 3 g of high acyl gellan gum in 100 mL of water, stirring at 750 rpm for 2 h to dissolve the mixture, and obtaining a sodium alginate-high acyl gellan gum solution for later use;

[0048] S3: Add 6 g of shellac into 30 mL of anhydrous ethanol, and stir at 750 rpm for 1.5 h to dissolve the shellac to obtain a shellac solution for later use;

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

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

[0051] S6: adding the mixed solution of step S5 dropwise to a calcium chloride solution having a concentration of 1.5% w / v, allowing to stand for 60 minutes, filtering, and washing with deionized water to obtain a single-layer encapsulated soft capsule;

[0052] S7: adding the one-layer encapsulated soft capsule of step S6 into chitosan hydrochloride with a concentration of 0.6% w / v, stirring at a speed of 100 rpm for 30 minutes, then filtering, and washing with deionized water to obtain a two-layer encapsulated soft capsule;

[0053] S8: adding the two-layer encapsulated soft capsules of step S7 into Tremella fuciformis polysaccharide with a concentration of 0.6% w / v, stirring at a rotation speed of 100 rpm for 30 minutes, then filtering, washing with deionized water, and finally obtaining the multi-layer encapsulated Litsea cubeba root extract gastrointestinal protection soft capsules.

[0054] Example 3

[0055] The present embodiment provides a multi-layer encapsulated litsea cubeba root extract gastrointestinal protection soft capsule, the soft capsule comprising soft capsule content and a capsule skin, the soft capsule content is 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 components of the middle layer are chitosan hydrochloride, and the components of the outer layer are 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.

[0056] This embodiment also provides a method for preparing a multi-layer encapsulated soft capsule of Litsea cubeba root extract for gastrointestinal protection, comprising the following steps:

[0057] S1: Wash and dry the litsea cubeba root block at 65°C, cut it into 0.1 cm slices, weigh 1 kg of the litsea cubeba root slices and place them in 12 L of water, heat them in a water bath at 100°C for 2 h, filter and remove the residue, take the filtrate and concentrate it under reduced pressure at 60°C to 0.12 L, to obtain the litsea cubeba root extract, and place it at 20°C for later use;

[0058] S2: Dissolve 18 g of sodium alginate and 6 g of high acyl gellan gum in 120 mL of water, and stir at 800 rpm for 1.5 h to dissolve the mixture, thereby obtaining a sodium alginate-high acyl gellan gum solution for later use;

[0059] S3: Add 8 g of shellac into 40 mL of anhydrous ethanol, and stir at 800 rpm for 2 h to dissolve the shellac to obtain a shellac solution for later use;

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

[0061] S5: dispersing 40 mL of the Litsea cubeba root extract of step S1 in 160 mL of the sodium alginate-high acyl gellan gum-shellac solution of step S4, stirring at 70° C. and 600 rpm for 2 h to prepare a mixed solution;

[0062] S6: adding the mixed solution of step S5 dropwise to a 2% w / v calcium chloride solution, allowing to stand for 45 minutes, filtering, and washing with deionized water to obtain a single-layer encapsulated soft capsule;

[0063] S7: adding the one-layer encapsulated soft capsule of step S6 into chitosan hydrochloride with a concentration of 1.0% w / v, stirring at a speed of 100 rpm for 40 minutes, then filtering, and washing with deionized water to obtain a two-layer encapsulated soft capsule;

[0064] S8: adding the two-layer encapsulated soft capsules of step S7 into Tremella fuciformis polysaccharide with a concentration of 1.0% w / v, stirring at a speed of 100 rpm for 40 minutes, then filtering, washing with deionized water, and finally obtaining the multi-layer encapsulated Litsea cubeba root extract gastrointestinal protection soft capsules.

[0065] Example 4

[0066] The present embodiment provides a multi-layer encapsulated litsea cubeba root extract gastrointestinal protection soft capsule, the soft capsule comprising soft capsule content and a capsule skin, the soft capsule content is 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 components of the middle layer are chitosan hydrochloride, and the components of the outer layer are 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.

[0067] This embodiment also provides a method for preparing a multi-layer encapsulated soft capsule of Litsea cubeba root extract for gastrointestinal protection, comprising the following steps:

[0068] S1: Wash and dry the litsea cubeba root block at 60°C, cut it into 0.1 cm slices, weigh 1 kg of the litsea cubeba root slices and place them in 12 L of water, heat them in a water bath at 100°C for 2 h, filter and remove the residue, take the filtrate and concentrate it under reduced pressure at 65°C to 0.12 L, to obtain the litsea cubeba root extract, and place it at 20°C for later use;

[0069] S2: Dissolve 2.1 g of sodium alginate and 0.7 g of high acyl gellan gum in 140 mL of water, and stir at 850 rpm for 1 h to dissolve them to obtain a sodium alginate-high acyl gellan gum solution for later use;

[0070] S3: Add 10 g of shellac into 50 mL of anhydrous ethanol and stir at 850 rpm for 1 h to dissolve the shellac to obtain a shellac solution for later use;

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

[0072] S5: dispersing 50 mL of the Litsea cubeba root extract of step S1 in 200 mL of the sodium alginate-high acyl gellan gum-shellac solution of step S4, stirring at 75° C. and 500 rpm for 1 h to prepare a mixed solution;

[0073] S6: adding the mixed solution of step S5 dropwise to a calcium chloride solution having a concentration of 2.5% w / v, standing for 30 minutes, filtering, and washing with deionized water to obtain a single-layer encapsulated soft capsule;

[0074] S7: adding the one-layer encapsulated soft capsule of step S6 into chitosan hydrochloride with a concentration of 1.5% w / v, stirring at a speed of 100 rpm for 50 min, then filtering, and washing with deionized water to obtain a two-layer encapsulated soft capsule;

[0075] S8: adding the two-layer encapsulated soft capsules of step S7 into Tremella fuciformis polysaccharide with a concentration of 1.5% w / v, stirring at a speed of 100 rpm for 50 min, then filtering, washing with deionized water, and finally obtaining the multi-layer encapsulated Litsea cubeba root extract gastrointestinal protection soft capsules.

[0076] Example 5

[0077] The present embodiment provides a multi-layer encapsulated litsea cubeba root extract gastrointestinal protection soft capsule, the soft capsule comprising soft capsule content and a capsule skin, the soft capsule content is 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 components of the middle layer are chitosan hydrochloride, and the components of the outer layer are 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] This embodiment also provides a method for preparing a multi-layer encapsulated soft capsule of Litsea cubeba root extract for gastrointestinal protection, comprising the following steps:

[0079] S1: Wash and dry the litsea cubeba root block at 60°C, cut it into 0.1 cm slices, weigh 1 kg of the litsea cubeba root slices and place them in 12 L of water, heat them in a water bath at 100°C for 2 h, filter and remove the residue, take the filtrate and concentrate it under reduced pressure at 65°C to 0.12 L, to obtain the litsea cubeba root extract, and place it at 20°C for later use;

[0080] S2: Dissolve 2.4 g of sodium alginate and 0.8 g of high acyl gellan gum in 160 mL of water, and stir at 900 rpm for 2 h to dissolve them to obtain a sodium alginate-high acyl gellan gum solution for later use;

[0081] S3: Add 12 g of shellac into 60 mL of anhydrous ethanol, and stir at 900 rpm for 2 h to dissolve the shellac to obtain a shellac solution for later use;

[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 600 rpm for 60 min, and adjusted the pH to 7.5 with a NaOH solution to obtain a sodium alginate-high acyl gellan gum-shellac solution;

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

[0084] S6: adding the mixed solution of step S5 dropwise to a 3% w / v calcium chloride solution, leaving it to stand for 30 minutes, filtering it, and washing it with deionized water to obtain a single-layer encapsulated soft capsule;

[0085] S7: adding the one-layer encapsulated soft capsule of step S6 into chitosan hydrochloride with a concentration of 2% w / v, stirring at a speed of 100 rpm for 60 min, then filtering, and washing with deionized water to obtain a two-layer encapsulated soft capsule;

[0086] S8: adding the two-layer encapsulated soft capsules of step S7 into Tremella fuciformis polysaccharide with a concentration of 2.0% w / v, stirring at a speed of 100 rpm for 60 minutes, then filtering, washing with deionized water, and finally obtaining the multi-layer encapsulated Litsea cubeba root extract gastrointestinal protection soft capsules.

[0087] Comparative Example 1

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

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

[0090] S1: Wash and dry the litsea cubeba root block at 60°C, cut it into 0.1 cm slices, weigh 1 kg of the litsea cubeba root slices and place them in 12 L of water, heat them in a water bath at 100°C for 2 h, filter and remove the residue, take the filtrate and concentrate it under reduced pressure at 65°C to 0.12 L, to obtain the litsea cubeba root extract, and place it at 20°C for later use;

[0091] S2: Dissolve 0.9 g of sodium alginate in 60 mL of water, and stir at 700 rpm for 2 h to dissolve it, thereby obtaining a sodium alginate solution for later use;

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

[0093] S4: adding the mixed solution of step S3 dropwise into a calcium chloride solution with a concentration of 1% w / v, allowing to stand for 30 minutes, filtering, and washing with deionized water to obtain the soft capsule.

[0094] Comparative Example 2

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

[0096] This comparative example provides a method for preparing a soft capsule, comprising the following steps:

[0097] S1: Wash and dry the litsea cubeba root block at 60°C, cut it into 0.1 cm slices, weigh 1 kg of the litsea cubeba root slices and place them in 12 L of water, heat them in a water bath at 100°C for 2 h, filter and remove the residue, take the filtrate and concentrate it under reduced pressure at 65°C to 0.12 L, to obtain the litsea cubeba root extract, and place it at 20°C for later use;

[0098] S2: Dissolve 0.9 g of sodium alginate and 0.3 g of high acyl gellan gum in 60 mL of water, and stir at 700 rpm for 2 h to dissolve them to obtain a sodium alginate-high acyl gellan gum solution for later use;

[0099] S3: Add 6 g of shellac into 30 mL of anhydrous ethanol and stir at 700 rpm for 1 h to dissolve the shellac to obtain a shellac solution for later use;

[0100] 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 500 rpm for 30 min, and adjusted the pH to 7.5 with a NaOH solution to obtain a sodium alginate-high acyl gellan gum-shellac solution;

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

[0102] S6: adding the mixed solution of step S5 dropwise into a calcium chloride solution with a concentration of 1% w / v, allowing to stand for 30 minutes, filtering, and washing with deionized water to obtain the soft capsule.

[0103] Comparative Example 3

[0104] The difference from Example 1 is that the soft capsule of this comparative example includes soft capsule content and a capsule skin, the soft capsule content is the extract of the root of Litsea cubeba, the capsule skin includes an inner layer and an outer layer, the components of the inner layer are sodium alginate, high acyl gellan gum and shellac, and the component of the outer layer is chitosan hydrochloride.

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

[0106] S1: Wash and dry the litsea cubeba root block at 60°C, cut it into 0.1 cm slices, weigh 1 kg of the litsea cubeba root slices and place them in 12 L of water, heat them in a water bath at 100°C for 2 h, filter and remove the residue, take the filtrate and concentrate it under reduced pressure at 65°C to 0.12 L, to obtain the litsea cubeba root extract, and place it at 20°C for later use;

[0107] S2: Dissolve 0.9 g of sodium alginate and 0.3 g of high acyl gellan gum in 60 mL of water, and stir at 700 rpm for 2 h to dissolve them to obtain a sodium alginate-high acyl gellan gum solution for later use;

[0108] S3: Add 6 g of shellac into 30 mL of anhydrous ethanol and stir at 700 rpm for 1 h to dissolve the shellac to obtain a shellac solution 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, stirred at 500 rpm for 30 min, and adjusted the pH to 7.5 with a NaOH solution to obtain a sodium alginate-high acyl gellan gum-shellac solution;

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

[0111] S6: adding the mixed solution of step S5 dropwise to a 1% w / v calcium chloride solution, allowing to stand for 30 minutes, filtering, and washing with deionized water to obtain a single-layer encapsulated soft capsule;

[0112] S7: adding the one-layer encapsulated soft capsule of step S6 into chitosan hydrochloride with a concentration of 0.2% w / v, stirring at a rotation speed of 100 rpm for 20 minutes, then filtering, and washing with deionized water to obtain the soft capsule.

[0113] Comparative Example 4

[0114] The difference from Example 1 is that this comparative example adopts the raw material mixing method to prepare the soft capsule.

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

[0116] S1: Wash and dry the litsea cubeba root block at 60°C, cut it into 0.1 cm slices, weigh 1 kg of the litsea cubeba root slices and place them in 12 L of water, heat them in a water bath at 100°C for 2 h, filter and remove the residue, take the filtrate and concentrate it under reduced pressure at 65°C to 0.12 L, to obtain the litsea cubeba root extract, and place it at 20°C for later use;

[0117] S2: Dissolve 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 in water, stir at 700 rpm for 2 h to dissolve, and obtain a fully mixed solution for standby use;

[0118] S3: dispersing 20 mL of the Litsea cubeba root extract of step S1 in 80 mL of the whole mixed solution of step S2, stirring at 60° C. and 500 rpm for 2 h to prepare a mixed solution;

[0119] S4: adding the mixed solution of step S3 dropwise to a 1% w / v calcium chloride solution, allowing to stand for 30 minutes, filtering, and washing with deionized water to obtain a single-layer encapsulated soft capsule;

[0120] Implementation effect evaluation

[0121] The following is a specific test of the soft capsules prepared in Example 1 and Comparative Examples 1-4 to further illustrate the excellent effects achieved by the present invention:

[0122] 0.2 g of gastrointestinal protection soft capsules were randomly weighed from Example 1 and Comparative Examples 1-4. In order to simulate gastric digestion, 0.2 g of gastrointestinal protection soft capsules were dispersed in distilled water to obtain 2.5 mL of dispersion. The dispersion was mixed with simulated gastric fluid (SGF), and the simulated gastric mixture was immediately incubated at 37 ° C in a shaker at 100 rpm 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, and then the simulated intestinal mixture was incubated at 37 ° C in a shaker at 100 rpm for 4 hours.

[0123] Figure 1 Schematic diagram of the soft capsules prepared in Example 1 and Comparative Examples 2-4 after being immersed in simulated gastrointestinal fluid for 4 hours. Figure 1 It can be seen that the soft capsule prepared in Example 1 can protect the active ingredients in the extract of Litsea cubeba root to the greatest extent, release the active substances into the intestine in a targeted manner, and prevent the bioactive ingredients from being degraded during the digestion process.

[0124] The in vitro drug release rate of the soft capsules prepared in Example 1 and Comparative Examples 1-4 was confirmed by using an ultraviolet spectrum scanner. The line graph of the measured data is shown in FIG. Figure 2 As shown, from Figure 2 It can be seen that the soft capsule prepared in Example 1 can protect the active ingredients in the extract of Litsea cubeba root to the greatest extent and release the active substances into the intestine in a targeted manner.

[0125] Figure 3 The encapsulation efficiency bar graph of the soft capsules prepared in Example 1 and Comparative Examples 1-4 is shown in FIG. Figure 3 It can be seen that the encapsulation efficiency of the soft capsule prepared in Example 1 is the highest, indicating that the present invention can ensure the effective delivery of the drug in the soft capsule, reduce the waste of dosage and achieve the purpose of cost saving.

[0126] The above is only a preferred embodiment of the present invention. It should be pointed out that a person skilled in the art can make several modifications and improvements without departing from the inventive concept of the present invention, which all belong to the protection scope of the present invention.

Claims

1. A multi-layer encapsulated soft capsule for gastrointestinal protection of Litsea cubeba root extract, the soft capsule comprising soft capsule contents and capsule skin, characterized in that: The content of the soft capsule is a root extract of Litsea cubeba, and the capsule skin includes 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 components of the middle layer are chitosan hydrochloride, and the components of the outer layer are tremella polysaccharide; wherein the content of the soft capsule is arranged in the inner layer of the capsule skin, and the density of the root extract of Litsea cubeba is 8.333 g / mL.

2. The method for preparing a multi-layer encapsulated soft capsule for gastrointestinal protection of Litsea cubeba root extract according to claim 1, characterized in that: The following steps are involved: S1: drying the washed litsea cubeba root block, cutting it into thin slices, placing the litsea cubeba root slices in water for water bath heating, filtering to remove residues, taking the filtrate for vacuum concentration to obtain the litsea cubeba root extract, and placing it at 20° C. for later use; S2: dissolving sodium alginate and high acyl gellan gum in water, stirring to dissolve, and obtaining a sodium alginate-high acyl gellan gum solution for later use; S3: adding shellac to anhydrous ethanol and stirring to dissolve it to obtain a shellac solution for later use; S4: mixing the sodium alginate-high acyl gellan gum solution of step S2 with the shellac solution of step S3, stirring evenly, 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 Litsea cubeba root extract of step S1 in the sodium alginate-high acyl gellan gum-shellac solution of step S4, stirring evenly at 60-80° C. to prepare a mixed solution; S6: adding the mixed solution of step S5 dropwise to the calcium chloride solution, allowing to stand for 30-60 minutes, filtering, and washing with deionized water to obtain a single-layer encapsulated soft capsule; S7: adding the one-layer encapsulated soft capsule of step S6 into chitosan hydrochloride, stirring, filtering, and washing with deionized water to obtain a two-layer encapsulated soft capsule; S8: adding the two-layer encapsulated soft capsules of step S7 into Tremella fuciformis polysaccharide, stirring, filtering, and washing with deionized water to finally obtain the multi-layer encapsulated Litsea cubeba root extract gastrointestinal protection soft capsules.

3. The method for preparing a multi-layer encapsulated soft capsule for gastrointestinal protection of Litsea cubeba root extract according to claim 2, characterized in that: In step S1, the drying temperature is 55-65°C, the thickness of the elm tree root slices is 0.1 cm, the mass ratio of the elm tree root slices to water is 1:12, the water bath heating temperature is 100°C, the time is 2h, and the reduced pressure concentration temperature is 60-70°C.

4. The method for preparing a multi-layer encapsulated soft capsule for gastrointestinal protection of Litsea cubeba root extract 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 1-2h.

5. The method for preparing a multi-layer encapsulated soft capsule for gastrointestinal protection 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 hours.

6. The method for preparing a multi-layer encapsulated soft capsule of Litsea cubeba root extract for gastrointestinal protection 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 rotation speed of the stirring process is 500-600 rpm, and the time is 30-60 min.

7. The method for preparing a multi-layer encapsulated soft capsule of Litsea cubeba root extract for gastrointestinal protection according to claim 2, characterized in that: In step S5, in the mixed solution, the volume ratio of the extract from the root of Litsea cubeba to the sodium alginate-high acyl gellan gum-shellac solution is 1:4, the rotation speed of the stirring process is 500-600 rpm, and the time is 1-2 hours.

8. The method for preparing a multi-layer encapsulated soft capsule for gastrointestinal protection 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 method for preparing a multi-layer encapsulated soft capsule of Litsea cubeba root extract for gastrointestinal protection according to claim 2, characterized in that: In step S7, the concentration of chitosan hydrochloride is 0.2-2% w / v, the stirring speed is 100 rpm, and the stirring time is 20-60 min.

10. The method for preparing a multi-layer encapsulated soft capsule of Litsea cubeba root extract for gastrointestinal protection according to claim 2, characterized in that: In step S8, the concentration of Tremella polysaccharide is 0.2-2% w / v, the stirring speed is 100 rpm, and the time is 20-60 min.

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