Propolis soft capsule and production process thereof

Abstract

The invention provides a propolis soft capsule which comprises a soft capsule shell and a content wrapped in the soft capsule shell, and the content comprises 400-750 g of propolis extract, 2000-2400 g of vegetable oil, 1000-1400 g of modified starch, 75-100 g of tea seed oil, 50-100 g of natural antioxidant and 75-125 g of cellulose on the basis of 10000 propolis soft capsules. One of the purposes of the invention is to provide the propolis soft capsule and the production process thereof, and by optimizing the formula and the production process of the propolis soft capsule, the purposes of improving the bioavailability, enhancing the stability of the product, improving the mouth feel, improving the safety of the product and improving the environmental friendliness of the product can be achieved on the premise of not influencing the active ingredients of the propolis.

Description

Technical Field

[0001] The invention mainly relates to the technical field of propolis application, in particular to a propolis soft capsule and a production process thereof. Background Art

[0002] Propolis is a natural substance made from resin collected by bees from plant spores or wounds and mixed with bee saliva and other secretions. It contains a variety of bioactive ingredients such as flavonoids, phenolic acids, aromatic acids and amino acids, and is widely used in health foods and medicines. However, there are some problems with the direct use of propolis, such as low bioavailability, poor stability and poor taste.

[0003] In the prior art, propolis is usually available in the form of alcohol extract or direct powder, but these all have certain limitations. Alcohol extract may be affected by the alcohol content when used, while powder form has solubility and mouthfeel problems. In addition, propolis is easily oxidized when directly exposed to air, affecting its stability and effectiveness.

[0004] After searching, relevant patent documents have been disclosed in the prior art for the application of propolis, such as Chinese patent document: A propolis soft capsule and a preparation method thereof, whose application number is: 201310116947.4, and Chinese patent document: A propolis astragalus soft capsule and a preparation method thereof, whose application number is 201210308329.5. The above two patent documents are both aimed at the application of propolis, but there is still room for improvement in terms of bioavailability, overall efficacy and stability of the product, and shelf life.

[0005] In order to better meet the needs of the market and consumers, the inventors of this application have developed a propolis soft capsule after years of research, which has obvious advantages in improving bioavailability, enhancing stability, improving taste, improving safety and environmental friendliness. Summary of the invention

[0006] To solve the above technical problems, one of the objects of the present invention is to provide a propolis soft capsule and a production process thereof. By optimizing the formula and production process of the propolis soft capsule, the bioavailability can be improved, the stability of the product can be enhanced, the taste can be improved, and the product safety and environmental friendliness can be improved without affecting the effective ingredients of propolis.

[0007] In order to solve the above technical problems, the technical solution adopted by the present invention is as follows: In a first aspect, the present invention provides a propolis soft capsule, comprising a soft capsule shell and contents wrapped in the soft capsule shell, wherein, based on 10,000 propolis soft capsules, the contents comprise 400-750 g of propolis extract, 2,000-2,400 g of vegetable oil, 1,000-1,400 g of modified starch, 100-150 g of tea seed oil, 50-100 g of natural antioxidant and 75-125 g of cellulose; Based on 10,000 propolis soft capsules, the soft capsule shell comprises 450-500 g of modified starch, 260-350 g of gelatin, 200-280 g of glycerol, 50-75 g of sorbitol and 300-380 g of water.

[0008] Propolis is the core ingredient of soft capsules and has multiple biological activities, such as anti-oxidation, anti-bacterial, anti-inflammatory, and immunity enhancement. Its content within a certain range ensures that the product can play an effective health or medicinal function. Too low a content may not achieve the expected effect, while too high a content may increase costs and may cause unnecessary burdens or side effects on the human body.

[0009] The active ingredients in propolis extract can be well dissolved in vegetable oil, which as a solvent helps the dispersion and absorption of propolis. At the same time, auxiliary materials such as modified starch can help stabilize the distribution of propolis in the contents and prevent it from precipitation or aggregation.

[0010] As a solvent, vegetable oil can dissolve propolis extract and other fat-soluble ingredients such as tea seed oil, so that the contents form a uniform system; on the other hand, vegetable oil itself has certain nutrients, such as unsaturated fatty acids, which are beneficial to human health. The amount used should be able to fully dissolve propolis and other ingredients, while taking into account the total volume and content requirements of the soft capsule.

[0011] Tea seed oil itself is rich in various nutrients, such as unsaturated fatty acids (mainly oleic acid, linoleic acid, etc.). Unsaturated fatty acids are beneficial to human health. For example, oleic acid can lower blood cholesterol and help maintain cardiovascular health.

[0012] In the contents of propolis soft capsules, rapeseed oil and vegetable oil dissolve in each other and serve as carriers of the contents together, optimizing the carrier performance of the single contents, and can better encapsulate and disperse the propolis extract, making the distribution of the propolis extract in the contents more uniform. It can help dissolve the propolis extract and other fat-soluble ingredients, so that the contents form a uniform system. This uniform system contributes to the stability of the product and prevents the stratification and precipitation of the ingredients.

[0013] Natural antioxidants mainly act on easily oxidizable ingredients such as vegetable oils and propolis extracts to protect them from oxidation and deterioration. Cellulose acts as a filler and disintegrant. It can adjust the volume and density of the contents, and helps the soft capsule to disintegrate quickly in the human gastrointestinal tract, so that the contents can be released and absorbed in time. In addition, it works together with modified starch to enhance the structural stability of the contents. In the gastrointestinal tract, the disintegration of cellulose may promote the release and absorption of other ingredients. In an achievable manner of the first aspect, the modified starch in the content is hydroxypropyl starch; And / or, starch is modified by using propylene oxide to obtain hydroxypropyl starch.

[0014] Hydroxypropyl starch has good thickening and stabilizing effects. In the contents, it can increase the viscosity of the system, prevent the precipitation and stratification of ingredients such as propolis extract, and ensure the stability of the product during storage and transportation. At the same time, its hydrophilicity and structural characteristics may help regulate the release and absorption of the contents in the gastrointestinal tract.

[0015] Hydroxypropyl starch interacts with propolis extract and vegetable oil to form a stable dispersion system. Cellulose may work together with modified starch to further enhance the stability and structural integrity of the contents.

[0016] In an achievable manner of the first aspect, the modified starch in the soft capsule shell is cross-linked starch; And / or, a bifunctional or multifunctional cross-linking agent reacts with starch molecules to form chemical bonds between starch molecular chains, thereby obtaining cross-linked starch after modification.

[0017] Cross-linked starch can improve the mechanical properties of soft capsule shells and enhance their strength and toughness. In soft capsule shells, it works with other ingredients such as gelatin to improve the stability of the capsule shell, prevent rupture, and ensure the sealing of the contents. At the same time, the modified starch has good biocompatibility and meets the material requirements of soft capsule shells.

[0018] Cross-linked starch interacts with gelatin to form a more stable capsule shell structure. Gelatin provides basic film-forming properties and flexibility, while cross-linked starch enhances its strength. Plasticizers such as glycerol and sorbitol can be inserted between the starch and gelatin molecular chains to further adjust the properties of the capsule shell.

[0019] Sorbitol can also improve the taste of the capsule shell to a certain extent (if the capsule shell is likely to be chewed during oral administration). It works together with glycerol on gelatin and modified starch to adjust the properties of the capsule shell and help maintain the stability of the capsule shell under different storage conditions.

[0020] In a second aspect, the present invention provides a production process of propolis soft capsules, which is used to prepare the above-mentioned propolis soft capsules, and the production process comprises the following steps: (1) Add the soaked and swollen gelatin solution into a sol tank according to the raw material ratio of the soft capsule shell, start stirring, then slowly add the mixed glycerol and sorbitol solution, then add the modified starch, continue stirring, and obtain a gelatin solution; (2) Add vegetable oil into a mixer according to the ratio of the raw materials in the above contents, start stirring, and then add propolis extract, hydroxypropyl starch, tea seed oil, natural antioxidant and cellulose in sequence to ensure that the ingredients are fully mixed to obtain a liquid material; (3) The glue solution obtained in step (1) and the content material solution obtained in step (2) are dripped or pressed to obtain propolis soft capsules.

[0021] In an achievable manner of the second aspect, the propolis extract in step (2) is pretreated, and the pretreatment includes microencapsulation treatment, and the microencapsulation treatment includes the following steps: A1: dissolving the wall material in acetone to prepare a wall material solution, wherein the ratio of propolis extract to wall material is 1:4; In practice, gelatin or some plant glue or PLGA can be used as wall materials. PLGA (polylactic acid-co-glycolic acid) is selected as the wall material, which has good biocompatibility and degradability. The ratio of propolis extract to wall material is 1:4, which ensures that enough wall material can wrap the propolis extract to form a stable microcapsule structure. PLGA is dissolved in acetone. Acetone is a good solvent that can fully dissolve PLGA, laying the foundation for the subsequent formation of a uniform wall material solution.

[0022] A2: Mix the propolis extract with a nonionic surfactant and add an appropriate amount of water to prepare a core material solution; Propolis extract is mixed with non-ionic surfactants, such as Span80 (sorbitan monooleate) and Tween80 (polysorbate 80). Span80 is an oil-in-water emulsifier, and Tween80 is an oil-in-water emulsifier. Together, they can form a stable emulsion of propolis extract in the aqueous phase. An appropriate amount of water is added to prepare the core material solution to provide an aqueous phase environment for the subsequent emulsification process.

[0023] A3: Slowly add the wall material solution to the core material solution, and use high-speed shear stirring at the same time. The stirring speed is controlled at 1000-3000rpm, the temperature is controlled at 40-45℃, and the pH value is controlled at 4.0-5.0 to form a stable emulsion; this condition is conducive to the activity of the emulsifier and the stability of the emulsion, and prevents the propolis extract from deteriorating or becoming unstable during the emulsification process.

[0024] A4: Dry the emulsified emulsion at a temperature of 40-45°C, which can ensure rapid evaporation of water without damaging the propolis extract and microcapsule structure. The drying time is adjusted according to the specific situation until dry microcapsule powder is obtained; A5: The dried microcapsule powder is washed with deionized water to remove residual solvents and emulsifiers, further improving the purity and safety of the product. It is then freeze-dried, which can avoid the influence of high temperature on the activity of propolis extract while maintaining the structural integrity of the microcapsules to obtain the final microencapsulated propolis extract.

[0025] Microencapsulation can improve the stability of propolis extracts and prevent them from being degraded or inactivated by external factors during storage and processing. At the same time, the microencapsulated propolis extracts can control their release rate, improve their bioavailability, and slowly release them in the gastrointestinal tract to increase their absorption effect.

[0026] In an achievable manner of the second aspect, the pretreatment further comprises enzymatic hydrolysis, wherein the microencapsulated propolis extract is mixed with papain and bromelain, the enzymatic hydrolysis time is 2 to 3 hours, and the temperature is maintained at 35 to 38° C.; And / or, after enzymatic hydrolysis is completed, ultrafiltration combined with heat inactivation is used to remove excess enzyme.

[0027] In a method that can be implemented in the second aspect, in step (1), gelatin is added to an appropriate amount of water, and the mass ratio of gelatin to water is 1:1 to 1:1.2, and the mixture is soaked at 40 to 50° C. for 1 to 2 hours to allow the mixture to fully swell and form a uniform gelatin solution; Gelatin needs to fully absorb water in water to swell and form a uniform solution. Water with a mass ratio of 1:1-1:1.2 can provide enough water for gelatin to fully swell without making the solution too diluted. The temperature range of 40-50℃ is conducive to the movement and water absorption of gelatin molecules, accelerating the swelling process. At this temperature, the structure of gelatin will not be destroyed and its good film-forming properties can be maintained. Soaking for 1-2 hours ensures that the gelatin is fully swollen and forms a uniform gelatin solution, providing a good foundation for subsequent sol preparation.

[0028] Glycerol and sorbitol are uniformly mixed in a certain proportion and then slowly added into the soaked and swollen gelatin solution, wherein the mass ratio of glycerol to sorbitol is 4:1-6:1.

[0029] In an achievable manner of the second aspect, the method for modifying the modified starch in the soft capsule shell comprises the following steps: Disperse the starch in an aqueous solution containing an appropriate amount of sodium hydroxide to prepare starch milk, with the concentration controlled at 20% to 30%, then add a bifunctional or multifunctional cross-linking agent and react at a temperature of 40 to 60°C for 2 to 4 hours; And / or, after the reaction is completed, unreacted cross-linking agent and alkali are removed by washing, filtering and the like, and finally drying is performed to obtain cross-linked starch; And / or, the drying may be performed by hot air drying or vacuum drying, and the drying temperature is controlled at 50-70°C.

[0030] In an achievable manner of the second aspect, the method for modifying the modified starch in the content comprises the following steps: Disperse starch in an aqueous solution containing sodium hydroxide to make starch milk, with the concentration controlled at 30%-40%. Slowly add propylene oxide at 40-50°C, and continue the reaction for 3-5 hours. and / or, after the reaction is completed, the alkali in the system is neutralized with an acid, the pH value of the mixed emulsion is adjusted to a range of 6 to 7, and the mixed emulsion is subjected to post-treatment steps of washing, filtering and drying to obtain hydroxypropyl starch; And / or, the drying may be performed by vacuum drying, and the drying temperature is controlled at 60-80°C.

[0031] In a method that can be implemented in the second aspect, the glue prepared in step (1) is placed in a vacuum degasser, the vacuum degree is controlled in the range of -0.06MPa to -0.08MPa, and the degassing time is 10 to 20 minutes to remove bubbles in the glue and ensure the quality of the soft capsule shell.

[0032] During the preparation of soft capsule shells, air bubbles may be mixed into the glue. If these bubbles are not removed, defects will occur in the capsule shell during the soft capsule molding process, such as bubble cavities and uneven thickness, affecting the quality and sealing of the capsule shell. Through vacuum degassing, the volume of air bubbles will expand rapidly and escape from the surface of the glue at a vacuum degree of -0.06MPa to -0.08MPa. The degassing time is 10-20min, which is enough to discharge most of the bubbles without having too much impact on the properties of the glue, ensuring the quality and stability of the glue, thereby improving the quality of the soft capsule shell.

[0033] In the implementation of the second aspect, a soft capsule machine is used to transport the prepared and degassed glue liquid to the vicinity of the spray body or the mold through a pipeline system. The glue liquid needs to maintain a suitable temperature (generally 50-60° C.) and fluidity to ensure that subsequent molding operations proceed smoothly. The contents are also transported to the corresponding position, and their temperature must be controlled within an appropriate range to match the temperature of the glue solution so that the two have good synergy when combined, preparing for the subsequent dripping or pressing process.

[0034] The prepared capsules are dried, wherein the drying temperature is controlled at 20-30°C, the relative humidity is controlled at 30%-50%, and the drying time is 12-24 hours. The drying temperature is controlled at 20~30℃, which is a relatively low temperature range. It can prevent the soft capsule shell from deforming, cracking or causing the contents to deteriorate due to excessive temperature during the drying process. At the same time, the lower temperature is also conducive to maintaining the structural integrity of the soft capsule shell and the stability of the ingredients. The relative humidity is controlled at 30%~50%. Within this humidity range, the soft capsule shell can gradually lose moisture to achieve the purpose of drying, and will not become brittle or crack due to excessive drying due to low humidity, nor will it extend the drying time or cause microbial growth due to excessive humidity. The drying time is 12~24 hours, which is enough time for the moisture in the soft capsule shell to fully evaporate, reach the appropriate degree of drying, and ensure the quality and stability of the soft capsule. During the drying process, the soft capsule should be checked regularly to ensure uniform drying effect and no adhesion and deformation on the surface of the soft capsule.

[0035] In the present invention, the propolis extract is processed by microencapsulation to control its release rate so that it is slowly released in the gastrointestinal tract, thereby increasing the absorption effect and improving the bioavailability.

[0036] Reasonable formula and production process ensure the quality and stability of soft capsules, reduce the loss of active ingredients during production and storage, and thus help improve bioavailability.

[0037] (1) Compared with the direct use of propolis extract or powder, the present invention utilizes microencapsulation technology, whereby the propolis extract is encapsulated in a wall material to protect it from being destroyed by gastric acid and digestive enzymes, thereby improving its release and absorption in the intestine. Enzymatic hydrolysis further converts macromolecules in propolis into small molecules, thereby improving its bioavailability.

[0038] (2) Hydroxypropyl starch has good thickening and stabilizing effects. In the contents, it can increase the viscosity of the system, prevent the precipitation and stratification of ingredients such as propolis extract, and ensure the stability of the product during storage and transportation. At the same time, its hydrophilicity and structural characteristics may help regulate the release and absorption of the contents in the gastrointestinal tract.

[0039] (3) Hydroxypropyl starch interacts with propolis extract and vegetable oil to form a stable dispersion system. Cellulose may work together with modified starch to further enhance the stability and structural integrity of the contents.

[0040] (4) Cross-linked starch can improve the mechanical properties of soft capsule shells and enhance their strength and toughness. In the soft capsule shell, it is combined with other ingredients such as gelatin to improve the stability of the capsule shell, prevent rupture, and ensure the sealing of the contents. At the same time, the modified starch has good biocompatibility and meets the material requirements of the soft capsule shell.

[0041] (5) In the present invention, the addition of cellulose improves the fluidity and filling efficiency of the capsule contents.

[0042] In summary, the optimized propolis soft capsule formula and production process have obvious advantages in improving bioavailability, enhancing stability, improving taste, improving safety and environmental friendliness. Compared with existing technologies, they can better meet the needs of the market and consumers.

[0043] The present invention will be explained in detail below with reference to the accompanying drawings and specific embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Figure 1 It is an overall flow chart of an embodiment of the present invention. DETAILED DESCRIPTION

[0045] To facilitate understanding of the present invention, the present invention will be described more comprehensively below with reference to the relevant drawings. Several embodiments of the present invention are given in the drawings, but the present invention can be implemented in different forms and is not limited to the embodiments described in the text. On the contrary, these embodiments are provided to make the content disclosed in the present invention more thorough and comprehensive.

[0046] Example 1: On the one hand, the embodiment of the present invention provides a propolis soft capsule, including a soft capsule shell and contents wrapped in the soft capsule shell. Based on 10,000 propolis soft capsules, the contents include the following raw material components by weight: 400g propolis extract, 2000g vegetable oil, 1000g hydroxypropyl starch, 100g tea seed oil, 50g natural antioxidant, and 75g cellulose.

[0047] The soft capsule shell comprises the following raw material components by weight: 450 g of cross-linked starch, 260 g of gelatin, 200 g of glycerol, 50 g of sorbitol, and 300 g of water.

[0048] In a second aspect, an embodiment of the present invention further provides a production process of propolis soft capsules, which is used to prepare the above-mentioned propolis soft capsules. The production process comprises the following steps: (1) Add the soaked and swollen gelatin solution into a sol tank according to the raw material ratio of the soft capsule shell, start stirring, then slowly add the mixed glycerol and sorbitol solution, then add the modified starch, continue stirring, and obtain a gelatin solution; Add gelatin to an appropriate amount of water with a mass ratio of gelatin to water of 1:1, and soak at 40°C for 1 hour to allow it to fully swell and form a uniform gelatin solution; Glycerol and sorbitol are uniformly mixed in a certain proportion and then slowly added into the soaked and swollen gelatin solution, wherein the mass ratio of glycerol to sorbitol is 4:1-6:1.

[0049] The prepared glue solution in step (1) is placed in a vacuum degasser with the vacuum degree controlled at -0.06 MPa for 10 min to remove bubbles in the glue solution and ensure the quality of the soft capsule shell. (2) Add vegetable oil into a mixer according to the ratio of the raw materials in the above contents, start stirring, and then add propolis extract, hydroxypropyl starch, tea seed oil, natural antioxidant, and cellulose in sequence to ensure that all ingredients are fully mixed to obtain a content material liquid.

[0050] The propolis extract in step (2) is pretreated, wherein the pretreatment includes microencapsulation treatment, and the microencapsulation treatment includes the following steps: A1: PLGA was used as the wall material, the ratio of propolis extract to the wall material was 1:4, PLGA was dissolved in acetone to prepare a wall material solution; A2: Mix the propolis extract with Span80 and Tween80, and add an appropriate amount of water to prepare a core material solution; A3: Slowly add the wall material solution to the core material solution while using high-speed shear stirring at a stirring speed of 1000 rpm, a temperature of 40°C, and a pH value of 4.0 to form a stable emulsion; A4: Dry the emulsified emulsion at a temperature of 40° C. and adjust the drying time according to the specific situation until dry microcapsule powder is obtained; A5: The dried microcapsule powder is washed with deionized water to remove the residual solvent and emulsifier, and then freeze-dried to obtain the final microencapsulated propolis extract.

[0051] The pretreatment also includes enzymatic treatment, wherein the microencapsulated propolis extract is mixed with papain and bromelain, the enzymatic treatment time is 2 hours, and the temperature is maintained at 38°C; After enzymatic hydrolysis, the excess enzyme was removed by ultrafiltration combined with heat inactivation.

[0052] (3) The glue solution obtained in step (1) and the content material solution obtained in step (2) are dripped or pressed to obtain propolis soft capsules.

[0053] The prepared and degassed glue liquid is transported to the spray body or the vicinity of the mold through the pipeline system using a soft capsule machine. The glue liquid needs to maintain a suitable temperature (50° C. in this embodiment) and fluidity to ensure that the subsequent molding operation proceeds smoothly; The contents are also transported to the corresponding position, and their temperature also needs to be controlled in an appropriate range (35°C in this embodiment) to match the temperature of the glue solution, so that the two have good synergy when combined, preparing for the subsequent dripping or pressing process. The produced capsules were dried at a temperature of 20°C, a relative humidity of 30%, and a drying time of 12 h.

[0054] Example 2: The propolis soft capsules and the production process in this example are basically the same as those in Example 1, except that the propolis soft capsules in this example include a soft capsule shell and contents wrapped in the soft capsule shell. Based on 10,000 propolis soft capsules, the contents include the following raw material components by weight: 500 g propolis extract, 2200 g vegetable oil, 1100 g hydroxypropyl starch, 110 g tea seed oil, 60 g natural antioxidant, and 80 g cellulose.

[0055] The soft capsule shell comprises the following raw material components by weight: 460 g of cross-linked starch, 280 g of gelatin, 220 g of glycerol, 55 g of sorbitol, and 320 g of water.

[0056] In the production process of this embodiment, gelatin is dissolved in acetone as a wall material in the microencapsulation process, the ratio of propolis extract to wall material is 1:4, the stirring speed is 1500 rpm, the temperature is 42°C, the pH value is 4.2, and the drying temperature is 42°C.

[0057] In the production process of this embodiment, during the gelatin soaking and swelling process, the mass ratio of gelatin to water is 1:1.1, and the soaking is at 42°C for 1.2 hours; the sol stirring time is 1.2 hours, the temperature is 65°C; the degassing vacuum degree is -0.065MPa, and the time is 12min.

[0058] During the soft capsule forming process: the gel temperature is 52°C, the content temperature is 37°C, and the dripping method is adopted.

[0059] The produced capsules were dried at a temperature of 22°C, a relative humidity of 35%, and a drying time of 14 hours.

[0060] Example 3: The propolis soft capsules and the production process in this example are basically the same as those in Example 1, except that the propolis soft capsules in this example include a soft capsule shell and contents wrapped in the soft capsule shell. Based on 10,000 propolis soft capsules, the contents include the following raw material components by weight: 600 g of propolis extract, 2300 g of vegetable oil, 1200 g of hydroxypropyl starch, 120 g of tea seed oil, 70 g of natural antioxidants, and 90 g of cellulose.

[0061] The soft capsule shell comprises the following raw material components by weight: 470 g of cross-linked starch, 300 g of gelatin, 240 g of glycerol, 60 g of sorbitol and 340 g of water.

[0062] In the production process of this embodiment, in the microencapsulation process, PLGA is dissolved in acetone, the ratio of propolis extract to wall material is 1:4, the stirring speed is 2000 rpm, the temperature is 43°C, the pH value is 4.5, and the drying temperature is 43°C.

[0063] In the production process of this embodiment, during the gelatin soaking and swelling process, the mass ratio of gelatin to water is 1:1.1, and the soaking is at 45°C for 1.5 hours; the sol stirring time is 1.5 hours, the temperature is 70°C; the degassing vacuum degree is -0.07MPa, and the time is 15min.

[0064] During the soft capsule forming process: the gel temperature is 55°C, the content temperature is 38°C, and the dripping method is adopted.

[0065] The produced capsules were dried at a temperature of 25°C, a relative humidity of 40%, and a drying time of 16 hours.

[0066] Example 4: The propolis soft capsule and the production process in this example are basically the same as those in Example 1, except that the propolis soft capsule in this example includes a soft capsule shell and contents wrapped in the soft capsule shell. Based on 10,000 propolis soft capsules, the contents include the following raw material components by weight: 650 g of propolis extract, 2350 g of vegetable oil, 1300 g of hydroxypropyl starch, 130 g of tea seed oil, 80 g of natural antioxidant, and 100 g of cellulose.

[0067] The soft capsule shell comprises the following raw material components by weight: 480 g of cross-linked starch, 320 g of gelatin, 260 g of glycerol, 65 g of sorbitol, and 360 g of water.

[0068] In the production process of this embodiment, in the microencapsulation process, PLGA is dissolved in acetone, the ratio of propolis extract to wall material is 1:4, the stirring speed is 2500 rpm, the temperature is 44°C, the pH value is 4.8, and the drying temperature is 44°C.

[0069] In the production process of this embodiment, during the gelatin soaking and swelling process, the mass ratio of gelatin to water is 1:1.2, and the soaking is at 48°C for 1.8 hours; the sol stirring time is 1.5 hours, the temperature is 70°C; the degassing vacuum degree is -0.075MPa, and the time is 18min.

[0070] During the soft capsule forming process: the gel temperature is 58°C, the content temperature is 40°C, and the dripping method is adopted.

[0071] The produced capsules were dried at a temperature of 28°C, a relative humidity of 45%, and a drying time of 18 hours.

[0072] Example 5: The propolis soft capsules and the production process in this example are basically the same as those in Example 1, except that the propolis soft capsules in this example include a soft capsule shell and contents wrapped in the soft capsule shell. Based on 10,000 propolis soft capsules, the contents include the following raw material components by weight: 700 g of propolis extract, 2400 g of vegetable oil, 1350 g of hydroxypropyl starch, 140 g of tea seed oil, 90 g of natural antioxidants, and 110 g of cellulose.

[0073] The soft capsule shell comprises the following raw material components by weight: 490 g of cross-linked starch, 340 g of gelatin, 270 g of glycerol, 70 g of sorbitol and 370 g of water.

[0074] In the production process of this embodiment, in the microencapsulation process, PLGA is dissolved in acetone, the ratio of propolis extract to wall material is 1:4, the stirring speed is 2800 rpm, the temperature is 45°C, the pH value is 5.0, and the drying temperature is 45°C.

[0075] In the production process of this embodiment, during the gelatin soaking and swelling process, the mass ratio of gelatin to water is 1:1.2, and the sol is soaked at 50°C for 2 hours; the sol is stirred for 2 hours at a temperature of 80°C; the degassing vacuum degree is -0.08MPa, and the time is 20min.

[0076] During the soft capsule forming process: the gel temperature is 60°C, the content temperature is 42°C, and the dripping method is adopted.

[0077] The produced capsules were dried at a temperature of 30°C, a relative humidity of 50%, and a drying time of 20 hours.

[0078] Example 6: The propolis soft capsules and the production process in this example are basically the same as those in Example 3, except that the propolis soft capsules in this example include a soft capsule shell and contents wrapped in the soft capsule shell. Based on 10,000 propolis soft capsules, the contents include the following raw material components by weight: 750 g of propolis extract, 2300 g of vegetable oil, 1200 g of hydroxypropyl starch, 150 g of tea seed oil, 55 g of natural antioxidants, and 75 g of cellulose.

[0079] The soft capsule shell comprises the following raw material components by weight: 470 g of cross-linked starch, 300 g of gelatin, 240 g of glycerol, 60 g of sorbitol and 340 g of water.

[0080] The production process parameters in this embodiment are the same as those in Example 3.

[0081] Example 7: The propolis soft capsules and the production process in this example are basically the same as those in Example 3, except that the propolis soft capsules in this example include a soft capsule shell and contents wrapped in the soft capsule shell. Based on 10,000 propolis soft capsules, the contents include the following raw material components by weight: 600 g of propolis extract, 2300 g of vegetable oil, 1200 g of hydroxypropyl starch, 120 g of tea seed oil, 70 g of natural antioxidants, and 90 g of cellulose.

[0082] The soft capsule shell comprises the following raw material components by weight: 470 g of cross-linked starch, 350 g of gelatin, 240 g of glycerol, 60 g of sorbitol and 340 g of water.

[0083] The production process parameters in this example are the same as those in the microencapsulation process in Example 3, the stirring speed is 1000 rpm, and the other parameters are the same as those in Example 3.

[0084] Example 8: The propolis soft capsule and the production process in this example are basically the same as those in Example 3, except that the stirring speed in the microencapsulation process of the production process in this example is 1000 rpm, and the other parameters are the same as those in Example 3.

[0085] The formula of the propolis soft capsule in this embodiment is consistent with that in Example 3.

[0086] Example 9: The propolis soft capsule and production process in this example are basically the same as those in Example 3, except that, in the microencapsulation process of this example, the stirring time when the contents are mixed is 40 minutes, the temperature is 30°C, and the other parameters are the same as those in Example 3.

[0087] The formula of the propolis soft capsule in this embodiment is consistent with that in Example 3.

[0088] Example 10: The propolis soft capsule and production process in this example are basically the same as those in Example 3, except that, during the preparation of the soft capsule shell, the degassing vacuum degree is -0.05MPa, and the other parameters are the same as those in Example 3.

[0089] The formula of the propolis soft capsule in this embodiment is consistent with that in Example 3.

[0090] Comparative Example 1: The propolis soft capsule in this comparative example includes a soft capsule shell and contents wrapped in the soft capsule shell. Calculated based on 10,000 propolis soft capsules, the contents include the following raw material components by weight: 400g propolis extract, 2000g vegetable oil, 1000g ordinary starch (non-modified), 100g tea seed oil, 50g natural antioxidant, and 75g cellulose.

[0091] The soft capsule shell comprises the following raw material components by weight: 300 g of gelatin, 200 g of glycerol and 300 g of water.

[0092] The production process of this comparative example adopts a conventional production process without microencapsulation and enzymatic treatment steps.

[0093] Comparative Example 2: The propolis soft capsule in this comparative example includes a soft capsule shell and contents wrapped in the soft capsule shell. Calculated based on 10,000 propolis soft capsules, the contents include the following raw material components by weight: 400g propolis extract, 2000g vegetable oil, 1000g hydroxypropyl starch, 75g tea seed oil, 50g natural antioxidant, 25g, and 75g cellulose.

[0094] The soft capsule shell includes the following raw material components by weight: 450 g of common starch (unmodified), 260 g of gelatin, 150 g of glycerol, 50 g of sorbitol, and 300 g of water.

[0095] The production process parameters in this comparative example are basically the same as those in Example 1.

[0096] Comparative Example 3: The propolis soft capsule and the production process in this comparative example are basically the same as those in Example 1, except that there is no enzymatic hydrolysis step, and the other process step parameters are basically the same as those in Example 1, and the stirring speed during the microencapsulation process is 500 rpm.

[0097] The formula of the propolis soft capsule in this comparative example is consistent with that in Example 1.

[0098] Comparative Example 4: The propolis soft capsule and the production process in this comparative example are basically the same as those in Example 1, except that there is no microencapsulation step, and the other process step parameters are basically the same as those in Example 1.

[0099] The formula of the propolis soft capsule in this comparative example is consistent with that in Example 1.

[0100] Comparative Example 5: The propolis soft capsule and the production process in this comparative example are basically the same as those in Example 1, except that no vacuum degassing treatment is performed during the preparation of the soft capsule shell, and the other process step parameters are basically the same as those in Example 1. The formula of the propolis soft capsule in this comparative example is consistent with that in Example 1.

[0101] Table 1 is a performance comparison table of the capsules prepared in Examples 1-10 and Comparative Examples 1-5 Performance Indicators Appearance (uniform color) Content uniformity (propolis active ingredients) Disintegration time (min) Bioavailability (relative value) Stability (accelerated test, active ingredient retention rate, 6 months) Example 1 excellent excellent 15 85% 95% Example 2 excellent excellent 14 86% 96% Example 3 excellent excellent 13 87% 97% Example 4 excellent excellent 12 88% 97% Example 5 excellent excellent 11 89% 98% Example 6 excellent excellent 10 90% 98% Example 7 excellent excellent 13 87% 97% Example 8 excellent excellent 14 86% 96% Example 9 excellent excellent 15 85% 95% Example 10 excellent excellent 14 86% 96% Comparative Example 1 good good 25 70% 80% Comparative Example 2 excellent excellent 18 80% 80% Comparative Example 3 good good 20 75% 85% Comparative Example 4 good good 22 72% 82% Comparative Example 5 good good 19 78% 88% From the analysis of Table 1 above, we can see that: 1. Appearance: Examples 1-10 have good overall performance, uniform color, high transparency and smooth surface, which is due to the optimized formula and fine production process. Among Comparative Examples 1-5, except for Comparative Example 2, which has excellent appearance, the other Comparative Examples are slightly inferior to the Examples to varying degrees. For example, the use of ordinary starch in Comparative Example 1 may result in the capsule surface being not smooth and uniform.

[0102] 2. Content uniformity: The propolis active ingredient content uniformity in Examples 1-10 is high, ensuring the consistency of product quality. The propolis active ingredient content uniformity in Comparative Example 1-5 is significantly inferior to that in Examples 1-10.

[0103] 3. Disintegration time: Examples 1-10 have a shorter disintegration time of 10-15 minutes, which is conducive to the rapid release and absorption of the drug in the body. Comparative Examples 1-5 have a longer disintegration time, especially Comparative Example 1, which uses ordinary starch without microencapsulation, and has a disintegration performance that is significantly inferior to that of the examples, reaching 25 minutes; Comparative Examples 3-5 also have a relatively long disintegration time due to unreasonable process parameters.

[0104] 4. Bioavailability: The bioavailability of Examples 1-10 is relatively high, because the process optimization such as microencapsulation treatment improves the absorption effect of propolis. The bioavailability of the comparative examples is significantly lower than that of the examples. Comparative Example 1 is not microencapsulated and the starch is not modified, and the bioavailability is only 70%; Comparative Examples 2-5 also have different degrees of reduction in bioavailability due to defects in formulation or process.

[0105] 5. Stability: Examples 1-10 have high active ingredient retention rates after 6 months of accelerated testing, indicating that the products have good stability. Comparative Example 1 has the worst stability, with an active ingredient retention rate of only 80%, which is due to its inadequate formula and process; Comparative Example 2 has a reduced amount of glycerol, Comparative Example 3 has improper microencapsulation, Comparative Example 4 has insufficient content mixing, and Comparative Example 5 has incomplete degassing, all of which lead to a decrease in stability relative to the Examples.

[0106] In summary, the formula and production process of Examples 1-10 are significantly better than those of Comparative Examples 1-5 in multiple performance indicators. The quality, bioavailability and stability of propolis soft capsules are improved by optimizing the raw materials (such as modified starch, tea seed oil, etc.) and proportions in the formula, using microencapsulation to treat propolis extracts, and accurately controlling production process parameters. However, the comparative examples have defects in different aspects, resulting in product performance that is inferior to that of the examples.

[0107] The above is an exemplary description of the present invention in combination with the accompanying drawings. It is obvious that the specific implementation of the present invention is not limited to the above-mentioned method. As long as such non-substantial improvements are made by adopting the method concept and technical solution of the present invention, or the concept and technical solution of the present invention are directly applied to other occasions without improvement, they are all within the protection scope of the present invention.

Claims

1. A propolis soft capsule, comprising a soft capsule shell and contents wrapped in the soft capsule shell, characterized in that: Based on 10,000 propolis soft capsules, the contents include the following raw material components by weight: 400-750 g of propolis extract, 2000-2400 g of vegetable oil, 1000-1400 g of modified starch, 100-150 g of tea seed oil, 50-100 g of natural antioxidant and 75-125 g of cellulose.

2. The propolis soft capsule according to claim 1, characterized in that Based on 10,000 propolis soft capsules, the soft capsule shell includes the following raw material components by weight: 450-500 g of modified starch, 260-350 g of gelatin, 200-280 g of glycerol, 50-75 g of sorbitol and 300-380 g of water.

3. The propolis soft capsule according to claim 1, characterized in that The modified starch in the content is hydroxypropyl starch; And / or, starch is modified by using propylene oxide to obtain hydroxypropyl starch.

4. The propolis soft capsule according to any one of claims 1 to 3, characterized in that: The modified starch in the soft capsule shell is cross-linked starch; And / or, a bifunctional or multifunctional cross-linking agent reacts with starch molecules to form chemical bonds between starch molecular chains, thereby obtaining cross-linked starch after modification.

5. A production process of propolis soft capsules, characterized in that: For preparing the propolis soft capsule according to any one of claims 1 to 4, the production process comprises the following steps: (1) Add the soaked and swollen gelatin solution into a sol tank according to the raw material ratio of the soft capsule shell, start stirring, then slowly add the mixed glycerol and sorbitol solution, then add the modified starch, continue stirring, and obtain a gelatin solution; (2) Add vegetable oil into a mixer according to the ratio of the raw materials in the above contents, start stirring, and then add propolis extract, hydroxypropyl starch, tea seed oil, natural antioxidant and cellulose in sequence to ensure that the ingredients are fully mixed to obtain a liquid material; (3) The glue solution obtained in step (1) and the content material solution obtained in step (2) are dripped or pressed to obtain propolis soft capsules.

6. The production process of the propolis soft capsule according to claim 5, characterized in that: The propolis extract in step (2) is pretreated, wherein the pretreatment includes microencapsulation treatment, and the microencapsulation treatment includes the following steps: A1: dissolving the wall material in acetone to prepare a wall material solution, wherein the ratio of propolis extract to wall material is 1:4; A2: Mix the propolis extract with a nonionic surfactant and add an appropriate amount of water to prepare a core material solution; A3: Slowly add the wall material solution to the core material solution while using high-speed shear stirring. The stirring speed is controlled at 1000-3000 rpm, the temperature is controlled at 40-45°C, and the pH value is controlled at 4.0-5.0 to form a stable emulsion. A4: Dry the emulsified emulsion at a temperature of 40-45°C and adjust the drying time according to the specific situation until dry microcapsule powder is obtained; A5: The dried microcapsule powder is washed with deionized water to remove the residual solvent and emulsifier, and then freeze-dried to obtain the final microencapsulated propolis extract.

7. The production process of the propolis soft capsule according to claim 6, characterized in that: The pretreatment also includes enzymatic treatment, mixing the microencapsulated propolis extract with papain and bromelain, the enzymatic treatment time is 2-3 hours, and the temperature is maintained at 35-38°C; And / or, after enzymatic hydrolysis is completed, ultrafiltration combined with heat inactivation is used to remove excess enzyme.

8. The production process of the propolis soft capsule according to claim 5, characterized in that: In step (1), gelatin is added to an appropriate amount of water, with a mass ratio of gelatin to water of 1:1 to 1:1.2, and the mixture is soaked at 40 to 50° C. for 1 to 2 hours to allow the mixture to fully swell and form a uniform gelatin solution; Glycerol and sorbitol are uniformly mixed in a certain proportion and then slowly added into the soaked and swollen gelatin solution, wherein the mass ratio of glycerol to sorbitol is 4:1-6:

1.

9. The production process of the propolis soft capsule according to claim 5, characterized in that: The modification method of the modified starch in the soft capsule shell comprises the following steps: Disperse the starch in an aqueous solution containing an appropriate amount of sodium hydroxide to prepare starch milk, with the concentration controlled at 20% to 30%, then add a bifunctional or multifunctional cross-linking agent and react at a temperature of 40 to 60°C for 2 to 4 hours; And / or, after the reaction is completed, unreacted cross-linking agent and alkali are removed by washing, filtering and the like, and finally drying is performed to obtain cross-linked starch; And / or, the drying may be performed by hot air drying or vacuum drying, and the drying temperature is controlled at 50-70°C.

10. The production process of the propolis soft capsule according to claim 5, characterized in that: The modification method of the modified starch in the content comprises the following steps: Disperse starch in an aqueous solution containing sodium hydroxide to make starch milk, with the concentration controlled at 30%-40%. Slowly add propylene oxide at 40-50°C, and continue the reaction for 3-5 hours. and / or, after the reaction is completed, the alkali in the system is neutralized with an acid, the pH value of the mixed emulsion is adjusted to a range of 6 to 7, and the mixed emulsion is subjected to post-treatment steps of washing, filtering and drying to obtain hydroxypropyl starch; And / or, the drying may be performed by vacuum drying, and the drying temperature is controlled at 60-80°C.

11. The production process of the propolis soft capsule according to any one of claims 5 to 10, characterized in that: The prepared glue solution in step (1) is placed in a vacuum degasser, and the vacuum degree is controlled in the range of -0.06MPa to -0.08MPa. The degassing time is 10 to 20 minutes to remove bubbles in the glue solution and ensure the quality of the soft capsule shell.

12. The production process of the propolis soft capsule according to claim 11, characterized in that: The soft capsule machine is used to transport the prepared and degassed glue liquid to the spray body or near the mold through the pipeline system. The glue liquid needs to maintain a suitable temperature and fluidity to ensure the subsequent molding operation goes smoothly; The contents are also transported to the corresponding position, and their temperature must be controlled within an appropriate range to match the temperature of the glue solution so that the two have good synergy when combined, preparing for the subsequent dripping or pressing process.

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